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1.
J Am Chem Soc ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39106438

RESUMO

The vinylene-linked covalent organic frameworks (viCOFs) have been generally synthesized in the presence of homogeneous catalysts such as KOH or trifluoroacetic acid. However, highly ordered viCOFs cannot always be obtained due to the uncommitted growth of viCOF layers in the homogeneous system with ubiquitous catalysts. Here, we propose a scalable protocol to restrict the growth of viCOFs along the two-dimensional (2D) plane by introducing a heterogeneous catalyst, polyoxometalates (POMs). With the unique Brønsted alkalinity and catalytic surface, POMs induce the growth of 2D viCOF layers along the surface of the catalytic substrate and restrain the generation of out-of-plane branches. Based on this protocol, six typical 2D viCOFs with high crystallinity and porosity were synthesized within a shorter reaction time as compared with the reported works using the common homogeneous catalysts for viCOF synthesis. On the basis of the density functional theory calculations and experimental results, a bottom intercalation growth pattern of viCOFs was revealed during the heterogeneous reaction. The unique growth pattern greatly promotes the orderly assembly of monomers, thus shortening the reaction time and improving the crystallinity of viCOFs. Furthermore, this heterogeneous catalysis strategy is suitable for the gram-scale preparation of 2D viCOFs. These results provide a novel avenue for the synthesis of high-quality viCOFs and may bring new insights into the synthetic methodology of COFs.

2.
Opt Lett ; 49(15): 4326-4329, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090927

RESUMO

We present what we believe is the first report on a polarization-insensitive 3 × 3 silicon star-crossing utilizing a composite subwavelength metamaterial waveguide structure. Two different types of subwavelength grating metamaterials (nanohole grating and fan-shaped bent subwavelength grating) are respectively used to address diffraction issues in the crossing region and mode interference issues caused by a compact non-adiabatic design. This approach results in a device with an ultra-compact footprint of 12.68 × 10.98 µm2 on a standard 220 nm silicon-on-insulator (SOI) platform. Simulation results show low insertion loss (IL) values of <0.2 dB/0.3 dB and suppressed cross talk (CT) levels of <-27.2 dB/-23.6 dB for TE/TM polarizations across a wavelength range of 100 nm (1500-1600 nm). Experimental measurements of the fabricated devices confirm outstanding performance, with IL values of <0.35 dB/0.4 dB and CT levels of <-31.5 dB/-28.6 dB for TE/TM polarization in the C-band.

3.
Exp Eye Res ; 247: 110030, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39127236

RESUMO

PURPOSE: Benzalkonium chloride (BAC) is commonly used as a preservative in ophthalmic medications, despite its potential to induce chemical injury. Extensive research has demonstrated that BAC can lead to adverse effects, including injuries to the ocular surface. Our study aimed to elucidate the underlying mechanism of necroptosis induced by BAC. METHODS: Human corneal epithelial (HCE) cells and mouse corneas were subjected to chemical injury, and the necrostatin-1 (Nec1) group was compared to the dimethylsulfoxide (DMSO) group. The extent of damage to HCE cells was assessed using CCK-8 and flow cytometry. Hematoxylin and eosin staining, as well as fluorescein sodium staining, were used to detect and characterize corneal injury. The activation of inflammatory cytokines and necroptosis-related proteins and genes was evaluated using Western blotting, immunofluorescence staining, and quantitative RT‒PCR. RESULTS: In our study, the induction of necroptosis by a hypertonic solution was not observed. However, necroptosis was observed in HCE cells exposed to NaOH and BAC, which activated the receptor-interacting protein kinase 1 (RIPK1) - receptor-interacting protein kinase 3 (RIPK3) - mixed lineage kinase domain-like protein (MLKL) signaling pathway. In mouse corneal tissues, BAC could induce necroptosis and inflammation. The administration of Nec1 mitigated the inflammatory response and ocular surface damage caused by BAC-induced necroptosis in our experimental models. Furthermore, our in vivo experiments revealed that the severity of necroptosis was greater in the 3-day group than in the 7-day group. CONCLUSIONS: Necroptosis plays a role in the pathological development of ocular surface injury caused by exposure to BAC. Furthermore, our study demonstrated that the administration of Nec1 could mitigate the pathological effects of necroptosis induced by BAC in clinical settings.

4.
Eur Radiol ; 34(1): 579-587, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37528300

RESUMO

OBJECTIVES: This study was aimed to quantitatively assess hyperperfusion using arterial spin labeling (ASL) to predict hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. METHODS: This study enrolled 98 AIS patients with anterior circulation large vessel occlusion within 24 h of symptom onset. ASL was performed before mechanical endovascular therapy. On pre-treatment ASL maps, a region with relative cerebral blood flow (CBF) ≥ 1.4 was defined as an area of hyperperfusion. The maximum CBF (CBFmax) of hyperperfusion was calculated for each patient. A non-contrast CT scan was performed during the subacute phase for the evaluation of HT. Good clinical outcome was defined as a 90-day modified Rankin scale score of 0-2. RESULTS: The CBFmax of hyperperfusion (odds ratio, 1.023; 95% confidence interval [CI], 1.005-1.042; p = 0.012) was an independent risk factor for the status of HT. The CBFmax of hyperperfusion for HT showed an area under the curve of 0.735 (95% CI, 0.588-0.882) with optimal cutoff value, sensitivity, and specificity being 146.5 mL/100 g/min, 76.9%, and 69.6%, respectively. There was a statistically significant relationship between HT grades (from no HT to PH2) and CBFmax of hyperperfusion with a Spearman rank correlation of 0.446 (p = 0.001). In addition, low CBFmax of hyperperfusion were associated with good functional outcome (95% CI, 17.130-73.910; p = 0.002). CONCLUSIONS: High CBFmax of hyperperfusion was independently associated with subsequent HT and low CBFmax of hyperperfusion linked to good functional outcome. There was a positive correlation between HT grade and CBFmax. CLINICAL RELEVANCE STATEMENT: Arterial spin labeling is a noninvasive and contrast agent-independent technique, which is sensitive in detecting hyperperfusion. This study shows that the cerebral blood flow of hyperperfusion is associated with clinical prognosis, which will benefit more patients. KEY POINTS: • Quantitative assessment of hyperperfusion using pre-treatment arterial spin labeling to predict hemorrhagic transformation and prognosis in acute ischemic stroke patients. • The maximum cerebral blood flow of hyperperfusion was associated with hemorrhagic transformation and clinical prognosis and higher maximum cerebral blood flow of hyperperfusion was associated with higher grade hemorrhagic transformation. • The maximum cerebral blood flow of hyperperfusion can predict hemorrhagic transformation which enables timely intervention to prevent parenchymal hematoma.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , AVC Isquêmico/complicações , Marcadores de Spin , Artérias , Circulação Cerebrovascular/fisiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia
5.
Eur J Neurol ; 31(9): e16380, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38924331

RESUMO

BACKGROUND AND PURPOSE: This study aimed to investigate the effect of collateral circulation on the outcomes of thrombectomy versus medical management alone in basilar artery occlusion (BAO) patients with varying stroke severities. METHODS: Data from the ATTENTION cohort were used to perform a post-hoc analysis comparing the outcomes of thrombectomy with medical management in BAO patients with varying degrees of collateral circulation and stroke severity. Basilar Artery on Computed Tomography Angiography (BATMAN) scores were used to quantify the collateral circulation, and the effect was estimated through a primary outcome of 90-day functional independence (modified Rankin Scale score, mRS ≤2). Favorable versus unfavorable BATMAN scores were analyzed as both continuous and categorical variables, and an adjusted multivariate regression model was applied. RESULTS: Among 221 BAO patients, thrombectomy significantly improved functional independence compared to medical management in patients with favorable BATMAN scores (aOR 7.75, 95% CI 2.78-26.1), but not in those with unfavorable BATMAN scores (aOR 1.33, 95% CI 0.28-6.92; pinteraction = 0.028). When treated as a continuous variable, increased BATMAN score was found to be associated with a higher likelihood of functional independence in the thrombectomy group (aOR 1.97, 95% CI 1.44-2.81; pinteraction = 0.053). In severe stroke patients with higher BATMAN scores (National Institutes of Health Stroke Scale (NIHSS) ≥21), we identified a significant interaction for treatment effect with thrombectomy compared to medical management (pinteraction = 0.042). CONCLUSION: An increased BATMAN score was significantly associated with a higher probability of functional independence after thrombectomy than after medical management, particularly in patients with severe BAO.


Assuntos
Circulação Colateral , Trombectomia , Insuficiência Vertebrobasilar , Humanos , Trombectomia/métodos , Masculino , Circulação Colateral/fisiologia , Feminino , Idoso , Pessoa de Meia-Idade , Insuficiência Vertebrobasilar/cirurgia , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/fisiopatologia , Resultado do Tratamento , Índice de Gravidade de Doença , Recuperação de Função Fisiológica/fisiologia , Idoso de 80 Anos ou mais , Estado Funcional , Angiografia por Tomografia Computadorizada , Artéria Basilar/cirurgia , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/fisiopatologia
6.
Dig Dis Sci ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020183

RESUMO

OBJECTIVE: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear. METHOD: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells. RESULTS: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used. CONCLUSION: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function.

7.
Appl Opt ; 63(11): 2854-2862, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856381

RESUMO

A new microwave photonic structure for measuring the frequency of an RF signal, to the best of our knowledge, is presented. The frequency of an unknown RF signal can be determined by simply measuring the system output optical powers. The proposed frequency measurement system can be designed so that the ratio of the two system output optical powers as a function of the RF signal frequency or the amplitude comparison function (ACF) has a steep linear slope over a wide frequency range. This enables the RF signal frequency to be measured in high resolution and high accuracy. The proposed frequency measurement system has a simple and compact structure, and is free of high-speed photodetectors as well as RF components and instruments. It also has a fast response time compared to many reported photonics-based frequency measurement systems. A proof-of-concept experiment is carried out. Experimental results show a linear ACF with a slope of more than 4.4 dB/GHz over a frequency measurement range of 5-26 GHz and a frequency measurement accuracy of better than ±0.1G H z.

8.
Biol Res ; 57(1): 43, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915069

RESUMO

BACKGROUND: Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. METHODS: In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. RESULTS: Our results indicate that 3-4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. CONCLUSIONS: Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.


Assuntos
Modelos Animais de Doenças , Hidrogênio , Neuroglia , Oxigênio , Neovascularização Retiniana , Retinopatia da Prematuridade , Animais , Hidrogênio/farmacologia , Neovascularização Retiniana/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Camundongos , Retinopatia da Prematuridade/tratamento farmacológico , Camundongos Endogâmicos C57BL , Retina/efeitos dos fármacos , Animais Recém-Nascidos , Regeneração/efeitos dos fármacos , Imuno-Histoquímica , Vasos Retinianos/efeitos dos fármacos
9.
Adv Exp Med Biol ; 1445: 47-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38967749

RESUMO

Traditionally, immunoglobulin (Ig) expression has been attributed solely to B cells/plasma cells with well-documented and accepted regulatory mechanisms governing Ig expression in B cells. Ig transcription is tightly controlled by a series of transcription factors. However, increasing evidence has recently demonstrated that Ig is not only produced by B cell lineages but also by various types of non-B cells (non-B-Ig). Under physiological conditions, non-B-Ig not only exhibits antibody activity but also regulates cellular biological activities (such as promoting cell proliferation, adhesion, and cytoskeleton protein activity). In pathological conditions, non-B-Ig is implicated in the development of various diseases including tumour, kidney disease, and other immune-related disorders. The mechanisms underline Ig gene rearrangement and transcriptional regulation of Ig genes in non-B cells are not fully understood. However, existing evidence suggests that these mechanisms in non-B cells differ from those in B cells. For instance, non-B-Ig gene rearrangement occurs in an RAG-independent manner; and Oct-1 and Oct-4, rather than Oct-2, are required for the transcriptional regulation of non-B derived Igs. In this chapter, we will describe and compare the mechanisms of gene rearrangement and expression regulation between B-Ig and non-B-Ig.


Assuntos
Regulação da Expressão Gênica , Imunoglobulinas , Transcrição Gênica , Humanos , Animais , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Rearranjo Gênico , Linfócitos B/metabolismo , Linfócitos B/imunologia
10.
Ecotoxicol Environ Saf ; 278: 116381, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38676963

RESUMO

Bioaerosols produced during animal production have potential adverse effects on the health of workers and animals. Our objective was to investigate characteristics, antibiotic-resistance genes (ARGs), and health risks of bioaerosols in various animal barns. Poultry and swine barns had high concentrations of airborne bacteria (11156 and 10917 CFU/m3, respectively). Acinetobacter, Clostridium sensu stricto, Corynebacterium, Pseudomonas, Psychrobacter, Streptococcus, and Staphylococcus were dominant pathogenic bacteria in animal barns, with Firmicutes being the most abundant bacterial phylum. Based on linear discriminant analysis effect size (LEfSe), there were more discriminative biomarkers in cattle barns than in poultry or swine barns, although the latter had the highest abundance of bacterial pathogens and high abundances of ARGs (including tetM, tetO, tetQ, tetW sul1, sul2, ermA, ermB) and intI1). Based on network analyses, there were higher co-occurrence patterns between bacteria and ARGs in bioaerosol from swine barns. Furthermore, in these barns, relative abundance of bacteria in bioaerosol samples was greatly affected by environmental factors, mainly temperature, relative humidity, and concentrations of CO2, NH3, and PM2.5. This study provided novel data regarding airborne bio-contaminants in animal enclosures and an impetus to improve management to reduce potential health impacts on humans and animals.


Assuntos
Aerossóis , Microbiologia do Ar , Bactérias , Animais , Aerossóis/análise , Suínos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Bovinos , Monitoramento Ambiental , Criação de Animais Domésticos , Aves Domésticas , Abrigo para Animais , Humanos , Material Particulado/análise , Resistência Microbiana a Medicamentos/genética , Poluição do Ar em Ambientes Fechados/análise
11.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1956-1965, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812208

RESUMO

The latent structure model and association rules analysis were employed to explore the compatibility rules of prescriptions for heart failure of dilated cardiomyopathy, with a view to providing theoretical support for the clinical treatment of this disease based on syndrome differentiation and the formulation of guidelines. The articles about the treatment of heart failure of dilated cardiomyopathy were retrieved from CNKI, Wanfang, VIP, and SinoMed. The database was established in Microsoft Excel 2019. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of Chinese medicine with the frequency greater than 4.00%. Furthermore, the frequency structure model was used to mine the rules of prescriptions for heart failure of dilated cardiomyopathy. The study included 175 traditional Chinese medicine(TCM) prescriptions, involving 128 Chinese medicines, with the cumulative frequency of 1 847. High-frequency medicines included Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, with the main effects of tonifying, activating blood, resolving stasis, and releasing exterior. A total of 17 hidden variables, 34 hidden categories, and 6 comprehensive cluster models, along with 15 core prescriptions, were obtained. According to the prescriptions, the patients mainly had the syndromes of heart-Yang and Qi deficiency, Qi deficiency and blood stasis, heart-kidney Yang deficiency or Qi-Yin deficiency. Fifty-four strong association rules were obtained through association rule analysis. The highest degree of support was observed for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix, while the highest degree of confidence was found for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Cinnamomi Ramulus-Ophiopogonis Radix-Astragali Radix. The heart failure of dilated cardiomyopathy, characterized by internal deficiency and excess manifestations, is attributed to deficiency, stasis, and water. These factors are closely associated with the heart, lung, and spleen. The treatment should follow the principle of invigorating Qi and warming Yang, and meanwhile the method of activating blood and resolve stasis or moving Qi and promoting urination can be adopted according to the specific syndrome of patients.


Assuntos
Cardiomiopatia Dilatada , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/fisiopatologia , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Medicina Tradicional Chinesa , Prescrições de Medicamentos/estatística & dados numéricos
12.
J Med Virol ; 95(1): e28150, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36112136

RESUMO

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; -log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs = 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17-3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14-4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20-0.44), and 0.44 (95% CI: 0.19-0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.


Assuntos
COVID-19 , Ácido Glutâmico , Humanos , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Metabolômica , Biomarcadores
13.
Microb Cell Fact ; 22(1): 116, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370116

RESUMO

BACKGROUND: 17ß-estradiol (E2) residues exhibit harmful effects both for human and animals and have got global attention of the scientific community. Microbial enzymes are considered as one of the effective strategies having great potential for removal E2 residues from the environment. However, limited literature is available on the removal of E2 from wastewater using short-chain dehydrogenase. RESULTS: In this study, 17ß-estradiol degrading enzyme (17ß-HSD-0095) was expressed and purified from Microbacterium sp. MZT7. The optimal pH and temperature for reaction was 7 and 40 °C, respectively. Molecular docking studies have shown that the ARG215 residue form a hydrogen bond with oxygen atom of the substrate E2. Likewise, the point mutation results have revealed that the ARG215 residue play an important role in the E2 degradation by 17ß-HSD-0095. In addition, 17ß-HSD-0095 could remediate E2 contamination in synthetic livestock wastewater. CONCLUSIONS: These findings offer some fresh perspectives on the molecular process of E2 degradation and the creation of enzyme preparations that can degrade E2.


Assuntos
Microbacterium , Águas Residuárias , Animais , Humanos , Microbacterium/metabolismo , Simulação de Acoplamento Molecular , Estradiol/metabolismo
14.
Cell Biol Toxicol ; 39(3): 813-825, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-34524571

RESUMO

Chemotherapy resistance is an important problem for clinical therapy of osteosarcoma (OS). The potential effects of histone deacetylases (HDACs) on OS chemoresistance are studied. The expression of HDACs in OS cells resistance to doxorubicin (Dox) and cisplatin (CDDP) is checked. Among 11 members of HDACs, levels of HDAC6 are significantly upregulated in OS cells resistance to Dox and CDDP. Inhibition of HDAC6 via its specific inhibitor ACY1215 restores chemosensitivity of OS-resistant cells. Further, HDAC6 directly binds with estrogen-related receptors alpha (ERRα) to regulate its acetylation and protein stability. Inhibition of ERRα further strengthens ACY1215-increased chemosensitivity of OS-resistant cells. Mechanistically, K129 acetylation is the key residue for HDAC6-regulated protein levels of ERRα. Collectively, we find that ERRα contributes to HDAC6-induced chemoresistance of OS cells. Inhibition of HDAC6/ERRα axis might be a potential approach to overcome chemoresistance and improve therapy efficiency for OS treatment. 1. HDAC6 was significantly upregulated in Dox and CDDP resistant OS cells; 2. Inhibition of HDAC6 can restore chemosensitivity of OS cells; 3. HDAC6 binds with ERRα at K129 to decrease its acetylation and increase protein stability; 4. ERRα contributes to HDAC6-induced chemoresistance of OS cells.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Resistencia a Medicamentos Antineoplásicos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Linhagem Celular Tumoral , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Desacetilase 6 de Histona/metabolismo , Desacetilase 6 de Histona/farmacologia , Desacetilase 6 de Histona/uso terapêutico , Receptor ERRalfa Relacionado ao Estrogênio
15.
Environ Res ; 217: 114963, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36471558

RESUMO

17ß-estradiol (E2) pollution has attracted much attention, and the existence of E2 poses certain risks to the environment and human health. However, the mechanism of microbial degradation of E2 remains unclear. In this study, the location of E2-degrading enzymes was investigated, and transcriptome analysis of Microbacterium resistens MZT7 (M. resistens MZT7) exposed to E2. The degradation of E2 by M. resistens MZT7 was via the biological action of E2-induced intracellular enzymes. With the RNA sequencing, we found 1109 differentially expressed genes (DEGs). Among them, 773 genes were up-regulated and 336 genes were down-regulated. The results of the RNA sequencing indicated the DEGs were related to transport, metabolism, and stress response. Genes for transport, transmembrane transport, oxidoreductase activity, ATPase activity, transporter activity and quorum sensing were up-regulated. Genes for the tricarboxylic acid cycle, ribosome, oxidative phosphorylation and carbon metabolism were down-regulated. In addition, heterologous expression of one enzymes efficiently degraded E2. These findings provide some new insights into the molecular mechanism of biotransformation of E2 by M. resistens MZT7.


Assuntos
Estradiol , Perfilação da Expressão Gênica , Humanos , Biotransformação , Fosforilação Oxidativa , Transcriptoma
16.
BMC Anesthesiol ; 23(1): 116, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024806

RESUMO

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by the infection-related host response disorder. Adequate mean arterial pressure is an important prerequisite of tissue and organ perfusion, which runs through the treatment of sepsis patients, and an appropriate mean arterial pressure titration in the early-stage correlates to the positive outcome of the treatment. Therefore, in the present study, we aimed to elucidate the relationship between early mean arterial pressure levels and short-term mortality in sepsis patients. METHODS: We included all suspected sepsis patients from MIMIC-III database with average mean arterial pressure ≥ 60 mmHg on the first day of intensive care unit stay. Those patients were then divided into a permissive low-mean arterial pressure group (60-65 mmHg) and a high-mean arterial pressure group (> 65 mmHg). Multivariate Cox regression analysis was conducted to analyze the relationship between MAP level and 30-day, 60-day, and 100-day mortality of suspected sepsis patients in the two groups. Propensity score matching, inverse probability of treatment weighing, standardized mortality ratio weighting, PA weighting, overlap weighting, and doubly robust analysis were used to verify our results. RESULTS: A total of 14,031 suspected sepsis patients were eligible for inclusion in our study, among which 1305 (9.3%) had an average first-day mean arterial pressure of 60-65 mmHg, and the remaining 12,726 patients had an average first-day mean arterial pressure of more than 65 mmHg. The risk of 30-day mortality was reduced in the high mean arterial pressure group compared with the permissive low-mean arterial pressure group (HR 0.67 (95% CI 0.60-0.75; p < 0.001)). The higher mean arterial pressure was also associated with lower 60-day and 100-day in-hospital mortality as well as with shorter duration of intensive care unit stay. Patients in the high-mean arterial pressure group also had more urine output on the first and second days of intensive care unit admission. CONCLUSIONS: After risk adjustment, the initial mean arterial pressure of above 65 mmHg was associated with reduced short-term mortality, shorter intensive care unit stay, and higher urine volume in the first two days among patients with sepsis.


Assuntos
Hipotensão , Sepse , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Sepse/terapia , Pressão Arterial , Unidades de Terapia Intensiva
17.
BMC Med Inform Decis Mak ; 23(1): 32, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782168

RESUMO

BACKGROUND: The size and cost of outpatient capacity directly affect the operational efficiency of a whole hospital. Many scholars have faced the study of outpatient capacity planning from an operations management perspective. OBJECTIVE: The outpatient service is refined, and the quantity allocation problem of each type of outpatient service is modeled as an integer linear programming problem. Thus, doctors' work efficiency can be improved, patients' waiting time can be effectively reduced, and patients can be provided with more satisfactory medical services. METHODS: Outpatient service is divided into examination and diagnosis service according to lean thinking. CPLEX is used to solve the integer linear programming problem of outpatient service allocation, and the maximum working time is minimized by constraint solution. RESULTS: A variety of values are taken for the relevant parameters of the outpatient service, using CPLEX to obtain the minimum and maximum working time corresponding to each situation. Compared with no refinement stratification, the work efficiency of senior doctors has increased by an average of 25%. In comparison, the patient flow of associate senior doctors has increased by an average of 50%. CONCLUSION: In this paper, the method of outpatient capacity planning improves the work efficiency of senior doctors and provides outpatient services for more patients in need; At the same time, it indirectly reduces the waiting time of patients receiving outpatient services from senior doctors. And the patient flow of the associate senior doctors is improved, which helps to improve doctors' technical level and solve the problem of shortage of medical resources.


Assuntos
Pacientes Ambulatoriais , Médicos , Humanos , Assistência Ambulatorial , Hospitais , Programação Linear , Número de Leitos em Hospital
18.
Sheng Li Xue Bao ; 75(2): 231-240, 2023 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-37089097

RESUMO

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.


Assuntos
Hemorragia Encefálica Traumática , Encéfalo , AVC Isquêmico , Neurogênese , Adulto , Animais , Humanos , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Mamíferos/fisiologia , Neurogênese/fisiologia , Hemorragia Encefálica Traumática/fisiopatologia , Hemorragia Encefálica Traumática/terapia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/terapia , Recuperação de Função Fisiológica , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia
19.
Zhongguo Zhong Yao Za Zhi ; 48(22): 6225-6233, 2023 Nov.
Artigo em Zh | MEDLINE | ID: mdl-38114229

RESUMO

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Panax , Humanos , Síndrome do Nó Sinusal/tratamento farmacológico , Deficiência da Energia Yang/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Prescrições , Rizoma/química
20.
Angew Chem Int Ed Engl ; 62(36): e202308523, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37370248

RESUMO

Constructing a powerful photocatalytic system that can achieve the carbon dioxide (CO2 ) reduction half-reaction and the water (H2 O) oxidation half-reaction simultaneously is a very challenging but meaningful task. Herein, a porous material with a crystalline topological network, named viCOF-bpy-Re, was rationally synthesized by incorporating rhenium complexes as reductive sites and triazine ring structures as oxidative sites via robust -C=C- bond linkages. The charge-separation ability of viCOF-bpy-Re is promoted by low polarized π-bridges between rhenium complexes and triazine ring units, and the efficient charge-separation enables the photogenerated electron-hole pairs, followed by an intramolecular charge-transfer process, to form photogenerated electrons involved in CO2 reduction and photogenerated holes that participate in H2 O oxidation simultaneously. The viCOF-bpy-Re shows the highest catalytic photocatalytic carbon monoxide (CO) production rate (190.6 µmol g-1 h-1 with about 100 % selectivity) and oxygen (O2 ) evolution (90.2 µmol g-1 h-1 ) among all the porous catalysts in CO2 reduction with H2 O as sacrificial agents. Therefore, a powerful photocatalytic system was successfully achieved, and this catalytic system exhibited excellent stability in the catalysis process for 50 hours. The structure-function relationship was confirmed by femtosecond transient absorption spectroscopy and density functional theory calculations.

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