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1.
Molecules ; 29(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39125045

RESUMO

In order to improve dispersibility, polymerization characteristics, chemical stability, and magnetic flocculation performance, magnetic Fe3O4 is often assembled with multifarious polymers to realize a functionalization process. Herein, a typical three-dimensional configuration of hyperbranched amino acid polymer (HAAP) was employed to assemble it with Fe3O4, in which we obtained three-dimensional hyperbranched magnetic amino acid composites (Fe3O4@HAAP). The characterization of the Fe3O4@HAAP composites was analyzed, for instance, their size, morphology, structure, configuration, chemical composition, charged characteristics, and magnetic properties. The magnetic flocculation of kaolin suspensions was conducted under different Fe3O4@HAAP dosages, pHs, and kaolin concentrations. The embedded assembly of HAAP with Fe3O4 was constructed by the N-O bond according to an X-ray photoelectron energy spectrum (XPS) analysis. The characteristic peaks of -OH (3420 cm-1), C=O (1728 cm-1), Fe-O (563 cm-1), and N-H (1622 cm-1) were observed in the Fourier transform infrared spectrometer (FTIR) spectra of Fe3O4@HAAP successfully. In a field emission scanning electron microscope (FE-SEM) observation, Fe3O4@HAAP exhibited a lotus-leaf-like morphological structure. A vibrating sample magnetometer (VSM) showed that Fe3O4@HAAP had a relatively low magnetization (Ms) and magnetic induction (Mr); nevertheless, the ferromagnetic Fe3O4@HAAP could also quickly respond to an external magnetic field. The isoelectric point of Fe3O4@HAAP was at 8.5. Fe3O4@HAAP could not only achieve a 98.5% removal efficiency of kaolin suspensions, but could also overcome the obstacles induced by high-concentration suspensions (4500 NTU), high pHs, and low fields. The results showed that the magnetic flocculation of kaolin with Fe3O4@HAAP was a rapid process with a 91.96% removal efficiency at 0.25 h. In an interaction energy analysis, both the UDLVO and UEDLVO showed electrostatic repulsion between the kaolin particles in the condition of a flocculation distance of <30 nm, and this changed to electrostatic attraction when the separation distance was >30 nm. As Fe3O4@ HAAP was employed, kaolin particles could cross the energy barrier more easily; thus, the fine flocs and particles were destabilized and aggregated further. Rapid magnetic separation was realized under the action of an external magnetic field.

2.
Chem Commun (Camb) ; 60(58): 7499-7502, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38946539

RESUMO

Designing electrocatalysts for seawater splitting remains challenging. A Ru-Co alloy supported by an N-doped carbon substrate catalyst has been designed using etching and a low-temperature treatment method. Studies show that the superior performance of this catalyst is related to the hollow-structured N-doped carbon frame and surface reconstruction of the Ru-Co alloy.

3.
Small ; : e2401730, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39036843

RESUMO

Stable, efficient, and economical bifunctional electrocatalysts for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are needed for rechargeable Zn-air batteries. In this study, a directional electron transfer pathway is exploited in a spatial heterojunction of CoyNix@Fe─N─C heterogeneous catalyst for effective bifunctional electrolysis (OER/ORR). Thereinto, the Co/Ni alloy is strongly coupled to the Fe─N─C support through Co/Ni─N bonds. DFT calculations and experimental findings confirm that Co/Ni─N bonds play a bridging role in the directional electron transfer from Co/Ni alloy to the Fe─N─C support, increasing the content of pyridinic nitrogen in the ORR-active support. In addition, the discovered directional electron transfer mechanism enhances both the ORR/OER activity and the durability of the catalyst. The Co0.66Ni0.34@Fe─N─C with the optimal Ni/Co ratio exhibits satisfying bifunctional electrocatalytic performance, requiring an ORR half-wave potential of 0.90 V and an OER overpotential of 317 mV at 10 mA cm-2 in alkaline electrolytes. The assembled rechargeable zinc-air batteries (ZABs) incorporating Co0.66Ni0.34@Fe─N─C cathode exhibits a charge-discharge voltage gap comparable to the Pt/C||IrO2 assembly and high robustness for over 60 h at 20 mA cm-2.

4.
FASEB J ; 38(13): e23802, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38979944

RESUMO

Intercellular adhesion molecule 1 (ICAM1) is a cell surface adhesion glycoprotein in the immunoglobulin supergene family. It is associated with several epithelial tumorigenesis processes, as well as with inflammation. However, the function of ICAM1 in the prognosis of tumor immunity is still unclear. This study aimed to examine the immune function of ICAM1 in 33 tumor types and to investigate the prognostic value of tumors. Using datasets from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Cancer Cell Lines Encyclopedia (CCLE), Human Protein Atlas (HPA), and cBioPortal, we investigated the role of ICAM1 in tumors. We explored the potential correlation between ICAM1 expression and tumor prognosis, gene mutations, microsatellite instability, and tumor immune cell levels in various cancers. We observed that ICAM1 is highly expressed in multiple malignant tumors. Furthermore, ICAM1 is negatively or positively associated with different malignant tumor prognoses. The expression levels of ICAM1 were correlated with the tumor mutation burden (TMB) in 11 tumors and with MSI in eight tumors. ICAM1 is a gene associated with immune infiltrating cells, such as M1 macrophages and CD8+ T cells in gastric and colon cancer. Meanwhile, the expression of ICAM1 is associated with several immune-related functions and immune-regulation-related signaling pathways, such as the chemokine signaling pathway. Our study shows that ICAM1 can be used as a prognostic biomarker in many cancer types because of its function in tumorigenesis and malignant tumor immunity.


Assuntos
Biomarcadores Tumorais , Molécula 1 de Adesão Intercelular , Neoplasias , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/metabolismo , Mutação , Regulação Neoplásica da Expressão Gênica , Instabilidade de Microssatélites , Microambiente Tumoral/imunologia
5.
J Nat Prod ; 87(7): 1735-1745, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38976838

RESUMO

Heterologous expression of an atr terpenoid gene cluster derived from Streptomyces atratus Gö66 in S. albus J1074 led to the discovery of three novel labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A-C (1-3), along with a known compound, labdanmycin A. Compounds 1-3 were identified through extensive spectroscopic analysis, including NMR calculations with DP4+ probability analysis, and a comparative assessment of experimental and theoretical electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for these compounds was proposed. Compounds 1-3 exhibited inhibitory activity against the human neurotropic coxsackievirus B3 (CVB3); 1 was the most potent, surpassing the positive control ribavirin with a higher therapeutic index.


Assuntos
Antivirais , Microbiologia do Solo , Streptomyces , Streptomyces/química , Streptomyces/genética , Antivirais/farmacologia , Antivirais/química , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/química , Humanos , Enterovirus Humano B/efeitos dos fármacos , Família Multigênica
6.
Clin Immunol ; 266: 110331, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067675

RESUMO

Co-activation signal that induces/sustains pleiotropic effector functions of antigen-specific γδ T cells remains unknown. Here, Mycobacteria tuberculosis (Mtb) tuberculin administration during tuberculosis (TB) skin test resulted in rapid expression of co-activation signal molecules CD137 and CD107a by fast-acting Vγ2Vδ2 T cells in TB-resistant subjects (Resisters), but not patients with active TB. And, anti-CD137 agonistic antibody treatment experiments showed that CD137 signaling enabled Vγ2Vδ2 T cells to produce more effector cytokines and inhibit intracellular Mtb growth in macrophages (Mɸ). Consistently, Mtb antigen (Ag) HMBPP stimulation induced sustainable high-level CD137 expression in fresh and activated Vγ2Vδ2 T cells from uninfected subjects, but not TB patients. CD137+Vγ2Vδ2 T-cell subtype predominantly displayed central memory phenotype and mounted better proliferative responses than CD137-Vγ2Vδ2 T-cells. In response to HMBPP, CD137+Vγ2Vδ2 T-cell subtype rapidly differentiated into greater numbers of pleiotropic effector cells producing anti-Mtb cytokines compared to CD137-Vγ2Vδ2 T subtype, with the non-canonical NF-κB pathway involved. CD137 expression in Vγ2Vδ2 T cells appeared to signal anti-Mtb effector functions leading to intracellular Mtb growth inhibition in Mɸ, and active TB disrupted such CD137-driven anti-Mtb effector functions. CD137+Vγ2Vδ2 T-cells subtype exhibited an epigenetic-driven high-level expression of GM-CSF and de novo production of GM-CSF critical for Vγ2Vδ2 T-cell controlling of Mtb growth in Mϕ. Concurrently, exosomes produced by CD137+Vγ2Vδ2 T cells potently inhibited intracellular mycobacterial growth. Furthermore, adoptive transfer of human CD137+Vγ2Vδ2 T cells to Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, our data suggest that CD137 expression/signaling drives pleiotropic γδ T-cell effector functions that inhibit intracellular Mtb growth.


Assuntos
Mycobacterium tuberculosis , Transdução de Sinais , Tuberculose , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Humanos , Mycobacterium tuberculosis/imunologia , Transdução de Sinais/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia , Camundongos , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Feminino , Animais , Macrófagos/imunologia , Masculino , Adulto , Antígenos de Bactérias/imunologia , Citocinas/metabolismo , Citocinas/imunologia , Ativação Linfocitária/imunologia , Camundongos SCID
7.
Sci Total Environ ; 947: 174567, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38981542

RESUMO

Coal spontaneous combustion (CSC) is disturbed by complex downhole conditions. However, current research by scholars mainly focuses on the impact of single conditional disturbances on CSC, which is difficult to comprehensively characterize the oxidation and spontaneous combustion characteristics of granular coal in a complex environment. For this reason, a temperature-programmed gas chromatographer (TP-GC) hyphenated instrument and a C600 high-precision microcalorimeter was used for analysis. The variation rules of derived gas and oxidizing thermodynamic parameters in the coal oxidizing and heating process under stress-heat-gas interaction were obtained. The intrinsic action mechanism of stress-heat-gas interaction to increase the risk of spontaneous combustion of granular coal is described. The results showed that as the level of air leakage (AL) rate increased, the concentration of derived gases in the coal sample showed a "˄"-shaped trend, and the heat release intensity and heat release varied in stages, both reaching their peak at a leakage rate of 150 mL/min. Under different stress conditions, the heat release intensity and heat release of coal also reach their maximum at 150 mL/min, indicating a higher risk of spontaneous combustion of coal at 150 mL/min. As the stress increases, the coal­oxygen reaction is inhibited, leading to a decrease in the concentration of derived gases and a reduction in the average heat release of the coal sample. This indicates that particulate coal is prone to spontaneous combustion when subjected to high air leakage rate and low stress conditions. The experimental results provide a theoretical basis for the prevention of CSC under complex conditions.

8.
J Insect Sci ; 24(4)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38989843

RESUMO

Cantharidin is a toxic defensive substance secreted by most blister beetles when attacked. It has been used to treat many complex diseases since ancient times and has recently regained popularity as an anticancer agent. However, the detailed mechanism of the cantharidin biosynthesis has not been completely addressed. In this study, we cloned McSTE24 (encoding STE24 endopeptidase) from terpenoid backbone pathway, McCYP305a1 (encoding cytochrome P450, family 305) and McJHEH [encoding subfamily A, polypeptide 1 and juvenile hormone (JH) epoxide hydrolase] associated to JH synthesis/degradation in the blister beetle Mylabris cichorii (Linnaeus, 1758, Coleoptera: Meloidae). Expression pattern analyses across developmental stages in adult males revealed that the expressions of 3 transcripts were closely linked to cantharidin titer exclusively during the peak period of cantharidin synthesis (20-25 days old). In contrast, at other stages, these genes may primarily regulate different biological processes. When RNA interference with double-stranded RNA suppressed the expressions of the 3 genes individually, significant reductions in cantharidin production were observed in males and also in females following McJHEH knockdown, indicating that these 3 genes might primarily contribute to cantharidin biosynthesis in males, but not in females, while females could self-synthesis a small amount of cantharidin. These findings support the previously hypothesized sexual dimorphism in cantharidin biosynthesis during the adult phase. McCYP305a1 collaborates with its upstream gene McSTE24 in cantharidin biosynthesis, while McJHEH independently regulates cantharidin biosynthesis in males.


Assuntos
Cantaridina , Besouros , Proteínas de Insetos , Animais , Cantaridina/metabolismo , Besouros/genética , Besouros/metabolismo , Masculino , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo
9.
J Fungi (Basel) ; 10(5)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38786704

RESUMO

Autophagy, a conserved cellular recycling process, plays a crucial role in maintaining homeostasis under stress conditions. It also regulates the development and virulence of numerous filamentous fungi. In this study, we investigated the specific function of ATG8, a reliable autophagic marker, in the opportunistic pathogen Aspergillus flavus. To investigate the role of atg8 in A. flavus, the deletion and complemented mutants of atg8 were generated according to the homologous recombination principle. Deletion of atg8 showed a significant decrease in conidiation, spore germination, and sclerotia formation compared to the WT and atg8C strains. Additionally, aflatoxin production was found severely impaired in the ∆atg8 mutant. The stress assays demonstrated that ATG8 was important for A. flavus response to oxidative stress. The fluorescence microscopy showed increased levels of reactive oxygen species in the ∆atg8 mutant cells, and the transcriptional result also indicated that genes related to the antioxidant system were significantly reduced in the ∆atg8 mutant. We further found that ATG8 participated in regulating the pathogenicity of A. flavus on crop seeds. These results revealed the biological role of ATG8 in A. flavus, which might provide a potential target for the control of A. flavus and AFB1 biosynthesis.

10.
Front Pharmacol ; 15: 1335786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774211

RESUMO

Background: Polygonatum sibiricum (PS) is a traditional Chinese medicine (TCM) first recorded in Mingyi Bielu. The book documents that PS can nourish five internal organs, be taken for a long time, relax the body and prolong lifespan. Presently, PS is widely used in TCM to prevent premature graying of hair. Based on TCM theory and clinical trials, the wine steaming processed product from PS provides a better effect. However, no published study has elucidated the anti-aging mechanism. Purpose: The study aim was to investigate the anti-aging mechanism of PS and its wine steaming processed product in mice, specifically focusing on the effect of D-galactose (D-gal) surrounding the intestinal flora and the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2-antioxidant response elements (Keap1/Nrf2/ARE) pathway. Methods: The chemical components in Raw PS (RPS) and Wine-steamed PS (WPS) were identified by ultra-performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). An aging model using Kunming mice was established through intraperitoneally injected D-gal. Concentrations of RPS and WPS at 5, 10, or 15 g/kg/day levels were administered intragastrically, respectively. The body weight, liver and spleen indexes, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) activities in serum and brain tissue were recorded. Hematoxylin and eosin (HE) stained brain tissue was histopathologically examined. The expressions of Keap1, Nrf2 and heme oxygenase 1 (HO-1) in the brain tissue at the mRNA and protein levels were respectively detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Moreover, an Illumina Hiseq platform was used for 16S ribosomal RNA (16S rRNA) high-throughput sequencing to evaluate the proportions of intestinal flora in aging mice. Results: The proportions of saccharides, flavonoids, and triterpene acids were different between RPS and WPS. In the aging model mice, WPS outperformed RPS in improving body weight and mental state by increasing the spleen index, SOD and GSH-PX activities, decreasing the liver index and MDA activities, and restoring the histopathological morphology in D-gal-induced aging mice. At the mRNA levels, RPS and WPS significantly reduced the expression of Keap1 and increased the expressions of Nrf2 and HO-1. The trend in protein expressions was similar to that of the mRNA results, and WPS had a stronger effect than RPS. Fecal microbiota analysis showed that RPS and WPS restored intestinal microbiota proportions to normal levels. Conclusion: The results demonstrated that PS and its WPS had a positive effect in relieving oxidative stress in aging mice. WPS outperformed RPS, which might be related to the activation of the Keap1/Nrf2/ARE pathway and regulation of intestinal flora.

11.
FASEB J ; 38(10): e23665, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38780085

RESUMO

Chlorogenic acid improves diabetic symptoms, including inflammation, via the modulation of the gut microbiota. However, the mechanism by which the microbiota is regulated by chlorogenic acid remains unknown. In this study, we firstly explored the effects of chlorogenic acid on diabetic symptoms, colonic inflammation, microbiota composition, and microRNA (miRNA) expression in db/db mice. The results showed that chlorogenic acid decreased body weight, improved glucose tolerance and intestinal inflammation, altered gut microbiota composition, and upregulated the expression level of five miRNAs, including miRNA-668-3p, miRNA-467d-5p, miRNA-129-1-3p, miRNA-770-3p, and miRNA-666-5p in the colonic content. Interestingly, the levels of these five miRNAs were positively correlated with the abundance of Lactobacillus johnsonii. We then found that miRNA-129-1-3p and miRNA-666-5p promoted the growth of L. johnsonii. Importantly, miRNA-129-1-3p mimicked the effects of chlorogenic acid on diabetic symptoms and colonic inflammation in db/db mice. Furthermore, L. johnsonii exerted beneficial effects on db/db mice similar to those of chlorogenic acid. In conclusion, chlorogenic acid regulated the gut microbiota composition via affecting miRNA expression and ameliorated intestinal inflammation via the miRNA-microbe axis in db/db mice.


Assuntos
Ácido Clorogênico , Microbioma Gastrointestinal , Inflamação , MicroRNAs , Animais , Ácido Clorogênico/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo
12.
J Heart Lung Transplant ; 43(9): 1409-1421, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38759766

RESUMO

BACKGROUND: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated. METHODS: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed. RESULTS: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction. CONCLUSIONS: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.


Assuntos
Rejeição de Enxerto , Transplante de Coração , Sistema de Registros , Humanos , Transplante de Coração/efeitos adversos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Doença Aguda , Adulto , Incidência , Perfilação da Expressão Gênica , Biópsia , Ácidos Nucleicos Livres/sangue , Seguimentos , Estados Unidos/epidemiologia
13.
Front Pediatr ; 12: 1336583, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562140

RESUMO

Objective: Sepsis in pediatric patients can progress to severe sepsis, and identifying biomarkers of this progression may permit timely intervention to prevent it. This study aimed to investigate the ability of thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC) and tissue-type plasminogen activator-inhibitor complex (t-PAIC) to predict severe sepsis in pediatrics early. Methods: 148 eligible pediatric sepsis patients were enrolled in this study, and were then divided into those who progressed to severe sepsis (n = 50) or not (n = 98). Serum levels of TAT, PIC, and t-PAIC were analysed, and simplified pediatric critical illness score (PCIS) and DIC score were calculated on the day of pediatric sepsis diagnosis. Results: Compared with sepsis patients, severe sepsis patients had higher levels of TAT, PIC and t-PAIC. Correlation analysis revealed that TAT, PIC and t-PAIC were significantly correlated with simplified PCIS and DIC score. ROC curve analysis suggested that TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis with the AUC up to 0.862, 0.759 and 0.851, respectively. Stratified analysis demonstrated that the patients with increased levels of TAT, PIC and t-PAIC had worse illness severity and clinical outcome. Univariate logistic regression analysis revealed that TAT, PIC and t-PAIC were all risk factors for severe sepsis, yet only TAT and t-PAIC were independent risk factors in multivariate model. Conclusions: TAT, PIC and t-PAIC could serve as biomarkers for predicting severe sepsis, and correlated with illness severity in pediatrics, what's more, serum levels of TAT and t-PAIC may be independent risk factors for pediatric severe sepsis.

14.
J Transl Med ; 22(1): 248, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454480

RESUMO

BACKGROUND: Acute ischemic stroke is a common neurological disease with a significant financial burden but lacks effective drugs. Hypoxia-inducible factor (HIF) and prolyl hydroxylases (PHDs) participate in the pathophysiological process of ischemia. However, whether FG4592, the first clinically approved PHDs inhibitor, can alleviate ischemic brain injury remains unclear. METHODS: The infarct volumes and behaviour tests were first analyzed in mice after ischemic stroke with systemic administration of FG4592. The knockdown of HIF-1α and pretreatments of HIF-1/2α inhibitors were then used to verify whether the neuroprotection of FG4592 is HIF-dependent. The targets predicting and molecular docking methods were applied to find other targets of FG4592. Molecular, cell biological and gene knockdown methods were finally conducted to explore the potential neuroprotective mechanisms of FG4592. RESULTS: We found that the systemic administration of FG4592 decreased infarct volume and improved neurological defects of mice after transient or permanent ischemia. Meanwhile, FG4592 also activated autophagy and inhibited apoptosis in peri-infarct tissue of mice brains. However, in vitro and in vivo results suggested that the neuroprotection of FG4592 was not classical HIF-dependent. 2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) was found to be a novel target of FG4592 and regulated the Pro-62 hydroxylation in the small ribosomal protein s23 (Rps23) with the help of target predicting and molecular docking methods. Subsequently, the knockdown of OGFOD1 protected the cell against ischemia/reperfusion injury and activated unfolded protein response (UPR) and autophagy. Moreover, FG4592 was also found to activate UPR and autophagic flux in HIF-1α independent manner. Blocking UPR attenuated the neuroprotection, pro-autophagy effect and anti-apoptosis ability of FG4592. CONCLUSION: This study demonstrated that FG4592 could be a candidate drug for treating ischemic stroke. The neuroprotection of FG4592 might be mediated by inhibiting alternative target OGFOD1, which activated the UPR and autophagy and inhibited apoptosis after ischemic injury. The inhibition of OGFOD1 is a novel therapy for ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Camundongos , Animais , Neuroproteção , Simulação de Acoplamento Molecular , Resposta a Proteínas não Dobradas , Isquemia , Autofagia , Infarto , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
15.
Heliyon ; 10(6): e27672, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38510033

RESUMO

The renovation of urban residential buildings in the context of urban renewal presents social challenges due to the involvement of diverse stakeholders and complex interest relations. This study identifies 28 critical success factors (CSFs) and 9 stakeholders, drawing insights from literature and on-site research of 45 old residential renewal projects in Jiangsu Province, China. Employing social network analysis, the intricate interplay between CSFs and stakeholders is explored, emphasizing the imperative for collaborative governance and elucidating governance mechanism principles. Focusing on stakeholders' resource contributions to transformation projects, the study devises a collaborative governance mechanism based on the specific types of resources required to support each CSF. This approach ensures that CSFs receive the necessary resources, enhancing project success. The paper concludes by outlining nine governance mechanisms and their implementation paths, anchored in the relationships between 13 CSFs and their respective stakeholders.

16.
Sci Transl Med ; 16(733): eadg1323, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324639

RESUMO

Neuroinflammation is acknowledged as a pivotal pathological event after cerebral ischemia. However, there is limited knowledge of the molecular and spatial characteristics of nonneuronal cells, as well as of the interactions between cell types in the ischemic brain. Here, we used spatial transcriptomics to study the ischemic hemisphere in mice after stroke and sequenced the transcriptomes of 19,777 spots, allowing us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of ischemia-associated gene expression in the peri-infarct area of the ischemic hemisphere. Analysis of ligand-receptor interactions in cell communication revealed galectin-9 to cell-surface glycoprotein CD44 (LGALS9-CD44) as a critical signaling pathway after ischemic injury and identified microglia and macrophages as the main source of galectins after stroke. Extracellular vesicle-mediated Lgals9 delivery improved the long-term functional recovery in photothrombotic stroke mice. Knockdown of Cd44 partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation and remyelination. In summary, our study provides a detailed molecular and cellular characterization of the peri-infact area in a murine stroke model and revealed Lgals9 as potential treatment target that warrants further investigation.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Camundongos , Animais , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Encéfalo/metabolismo , Microglia/metabolismo , Isquemia , Perfilação da Expressão Gênica
17.
Chem Commun (Camb) ; 60(16): 2176-2179, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38289337

RESUMO

d-π overlap, which represents overlap between metal-d and graphene-π orbitals to facilitate electron transfer, has rarely been reported. Ni/PtNi-G2 exhibits exceptional performance in seawater hydrogen evolution due to the electron-rich surface on Pt resulting from enhanced d-π overlap and subsequent electron transfer from graphene and Ni to Pt.

18.
Zhen Ci Yan Jiu ; 48(12): 1266-1273, 2023 Dec 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38146250

RESUMO

OBJECTIVES: To compare the effects of 2 Hz continuous wave and 2 Hz/100 Hz dilatational wave setting in electroacupuncture(EA) on ovulation frequency, hormone levels, body fat parameters, quality of life and depression-anxiety level in polycystic ovary syndrome (PCOS) patients with abdominal obesity. METHODS: PCOS patients with abdominal obesity were randomly divided into low-frequency group (n=29) and dilatational wave group (n=29). Patients in both groups were treated with "Tongtiaodaimai" (regulating Dai Meridian) acupuncture therapy, and EA was applied to bilateral Daimai (GB26), Tianshu (ST25), Shenshu (BL23) and Ciliao (BL32). The low-frequency group received EA using a continuous wave at a frequency of 2 Hz, while the dilatational wave group received dilatational wave at a frequency of 2 Hz/100 Hz. Both groups received treatment for 30 min each time, 3 times per week for 12 consecutive weeks. Ovulation frequency was calculated according to the ovulation cycle. The contents of serum anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG) were detected with electrochemiluminescence method. Body weight (BW) and waist circumference (WC) were measured, and body mass index (BMI) and waist-height ratio (WHtR) were calculated. PCOS questionnaire (Chi-PCOSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. RESULTS: Compared with before treatment, both the low-frequency group and the dilatational wave group showed an increase in ovulation frequency (P<0.01, P<0.05), and a decrease in BW, BMI, WC, WHtR, and SDS score (P<0.01, P<0.05);the dilatational wave group showed decreased serum AMH contents (P<0.05) and increased serum SHBG contents (P<0.05), the scores related to acne, fatigue, and dysmenorrhea in the Chi-PCOSQ increased (P<0.01, P<0.05). Compared with the low-frequency group, the dilatational wave group showed a reduction (P<0.05) in WC after treatment. CONCLUSIONS: 2 Hz/100 Hz dilatational wave EA is equally effective as 2 Hz low-frequency EA in improving ovulation frequency. In terms of reducing WC in abdominal obesity type PCOS patients, 2 Hz/100 Hz dilatational wave EA is superior to 2 Hz low-frequency EA. 2 Hz/100 Hz dilatational wave EA can decrease serum AMH, increase serum SHBG, and improve symptoms of acne, fatigue, and dysmenorrhea.


Assuntos
Acne Vulgar , Eletroacupuntura , Síndrome do Ovário Policístico , Feminino , Humanos , Obesidade Abdominal/terapia , Qualidade de Vida , Síndrome do Ovário Policístico/terapia , Dismenorreia , Pontos de Acupuntura , Obesidade/terapia
19.
Artigo em Chinês | MEDLINE | ID: mdl-38114310

RESUMO

Objective:To analyze the clinical data of laryngeal airway diseases in infants and provide reference for the standardized diagnosis and treatment of the disease. Methods:From June 2022 to August 2023, analyze the clinical data of 4 cases of children with laryngeal airway diseases recently admitted to Department of Otolaryngology, Fuzhou Children's Hospital of Fujian Province, and summarize the experience and lessons of diagnosis and treatment by consulting relevant literature. Results:Three cases had symptoms such as laryngeal wheezing, dyspnea, backward growth and development, etc. After electronic laryngoscopy, the first case was diagnosed with laryngeal softening (severe, type Ⅱ), and the angular incision was performed. While cases 2, 3 diagnosed with case 2 and 3 were diagnosed with laryngeal cyst and underwent laryngeal cyst resection. All three cases underwent low-temperature plasma surgery under visual laryngoscope, and the symptoms were relieved after operation. Case 4 was laryngeal wheezing and dyspnea after extubation under general anesthesia. The electronic laryngoscopy showeded early stage of globetic stenosis, and endoscopic pseudomembrane clamping was performed, and the postoperative symptoms were relieved. Conclusion:Infants and young children with laryngeal airway diseases should pay attention to the early symptoms and be diagnosed by electronic laryngoscopy as soon as possible. With good curative effect and few complications, low-temperature plasma surgery under visual laryngoscope is recommended. The formation of pseudomembrane under the gluteal caused by tracheal intubation causes rapid onset and rapid development. The pseudomembrane extraction by clamping is convenient and fast, with good curative effect.


Assuntos
Cistos , Doenças da Laringe , Laringe , Lactente , Criança , Humanos , Pré-Escolar , Sons Respiratórios/etiologia , Doenças da Laringe/cirurgia , Laringoscopia , Intubação Intratraqueal/efeitos adversos , Dispneia/cirurgia , Cistos/cirurgia
20.
Artigo em Chinês | MEDLINE | ID: mdl-38114317

RESUMO

Congenital laryngomalacia is the most common disease causing laryngeal stridor in infants. The pathogenesis has not yet been clearly concluded. It may be related to abnormal development of laryngeal cartilage anatomical structure, neuromuscular dysfunction, gastroesophageal and laryngeal reflux disease, etc. The typical manifestations of the disease are inspiratory laryngeal stridor and feeding difficulties, which can be divided into mild, moderate and severe according to the severity of symptoms. The diagnosis is mainly based on clinical symptoms, signs and endoscopy, among which endoscopy is an important diagnostic basis. The treatment of laryngomalacia depends on the severity of symptoms. Mild and some moderate congenital laryngomalacia children can be relieved by conservative treatment, and severe and some moderate congenital laryngomalacia children should be treated by surgery. Supraglottic plasty is the main surgical method, which can effectively improve the symptoms of laryngeal stridor, dyspnea, feeding difficulties and growth retardation in most children, and the surgical effect is good.


Assuntos
Doenças da Laringe , Laringismo , Laringomalácia , Laringe , Lactente , Criança , Humanos , Laringomalácia/diagnóstico , Laringomalácia/terapia , Sons Respiratórios/diagnóstico , Sons Respiratórios/etiologia , Laringe/cirurgia , Doenças da Laringe/cirurgia , Endoscopia/efeitos adversos
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