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SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.
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COVID-19 , Senescência Celular , Células Gigantes , Insuficiência Cardíaca , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/virologia , Animais , Células Gigantes/virologia , Células Gigantes/metabolismo , Células Gigantes/patologia , COVID-19/metabolismo , COVID-19/complicações , COVID-19/virologia , COVID-19/patologia , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Camundongos , Vesículas Extracelulares/metabolismoRESUMO
Using myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46â C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H-1,2,4-triazole-3-thiol and 1-(4-hydroxyphenyl)-1H-pyrrole-2,5-dione. The engineered proteins, termed F46C-triazole Mb and F46C-phenol Mb, respectively, were characterized by X-ray crystallography, spectroscopic and stopped-flow kinetic studies. The results showed that both the heme coordination state and the protein function such as H2 O2 activation and peroxidase activity could be efficiently regulated, which suggests that this approach might be generally applied to the design of functional heme proteins.
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Heme , Mioglobina , Mioglobina/química , Mioglobina/genética , Mioglobina/metabolismo , Domínio Catalítico , Heme/química , Cinética , Conformação Proteica , Compostos de SulfidrilaRESUMO
Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.
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OBJECTIVES: Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. METHODS: The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. RESULTS: The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. CONCLUSIONS: The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. CLINICAL RELEVANCE STATEMENT: Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. KEY POINTS: ⢠In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. ⢠In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. ⢠For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/genética , Biópsia por Agulha Fina/métodos , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Estudos Prospectivos , Inteligência ArtificialRESUMO
The development of photocatalytic systems with an electron tandem transport channel represents a promising avenue for improving the utilization of photogenerated electrons and holes despite encountering significant challenges. In this study, ZnIn2S4 (Sv-ZIS) with sulfur vacancies was fabricated using a solvothermal technique to create defect energy levels. Subsequently, Cu3P nanoparticles were coupled onto the surface of Sv-ZIS, forming a Cu3P/Sv-ZIS p-n heterojunction with an electron tandem transport channel. Experimental findings demonstrated that this tandem transport channel enhanced the carrier lifetime and separation efficiency. In addition, mechanistic investigations unveiled the formation of a robust built-in electric field (BEF) at the interface between Cu3P and Sv-ZIS, providing a driving force for electron migration. The combined consequences of the transport channel, the strong BEF, and photothermal effect led to a surface carrier separation efficiency of 65.85%. Consequently, Cu3P/Sv-ZIS achieved simultaneous H2 yield and benzaldehyde production rates of 18,101.4 and 15,012.6 µmol·g-1·h-1, which were 2.31 and 2.62 times higher than those of ZnIn2S4, respectively. This work exemplifies the design of the p-n heterojunction for the efficient utilization of photogenerated electrons and holes.
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Three novel phragmalin-type limonoids, swieteliacates S-U (1-3), were isolated from Swietenia macrophylla leaves, alongside four previously identified limonoids (4-7). The structures, encompassing absolute configurations, were delineated through 1D and 2D NMR analyses, high-resolution mass spectrometry (HR-MS), and NMR and ECD calculations. Swieteliacate S (1) is a distinctive cryptate comprising a tricyclo[4.2.110,30.11,4]decane fragment and an additional five-membered oxygen ring. Compounds 3 and 5 exhibited inhibition rates of 26.08 ± 2.26% and 15.42 ± 3.66%, respectively, on triglyceride (TG) production in Hep G2 cells at 40 µM.
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Limoninas , Meliaceae , Limoninas/química , Limoninas/farmacologia , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Meliaceae/químicaRESUMO
BACKGROUND: Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years. CASE PRESENTATION: A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND. CONCLUSION: The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.
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Agenesia do Corpo Caloso , Anormalidades Craniofaciais , Face , Hidrocefalia , Imageamento Tridimensional , Deformidades Congênitas dos Membros , Ultrassonografia Pré-Natal , Humanos , Feminino , Adulto , Gravidez , Anormalidades Craniofaciais/diagnóstico por imagem , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/genética , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/genética , Face/anormalidades , Face/diagnóstico por imagem , Hidrocefalia/diagnóstico por imagem , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genéticaRESUMO
The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5â¯g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0â¯g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in "photosynthesis" and "photosynthesis, light reaction" in Sedum alfredii Hance leaves. Moreover, the "plant hormone signal transduction" pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants.
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BACKGROUND: Left-right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left-right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. METHODS: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). RESULTS: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. CONCLUSION: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.
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Dineínas do Axonema , Sequenciamento do Exoma , Cardiopatias Congênitas , Mutação , Humanos , Feminino , Gravidez , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/diagnóstico , Dineínas do Axonema/genética , Diagnóstico Pré-Natal/métodos , Heterozigoto , Situs Inversus/genética , Situs Inversus/diagnóstico , Situs Inversus/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único , Adulto , Síndrome de Heterotaxia/genética , Síndrome de Heterotaxia/diagnóstico por imagemRESUMO
Heavy metal pollution of agricultural soil is a major global concern, prompting the establishment of maximum allowable limits (MALs) to ensure food safety and protect human health. This study collected and compared MALs for six heavy metals (As, Cd, Hg, Pb, Zn, and Cu) in agricultural soils from representative countries and organizations (EU and WHO/FAO). The research evaluated the critical health risks and efficacy of these MALs under the hypothetical scenario of metals concentrations reaching the maximum allowable level. Safe thresholds for heavy metals were then derived based on maximum acceptable health risk levels. The comparative analysis revealed significant variations in the specific limit values and terms of MALs across countries and organizations, even for the same metal. This suggests that there is no consensus among countries and organizations regarding the level of metal-related health risks. Furthermore, the risk analysis of metal concentrations reaching the maximum level accentuated heightened risks associated with As, suggesting that the current risk of soil As exposure was underestimated, particularly for children. However, soil Cu, Cd, and Zn limits generally resulted in low health risks, implying that the current limits may overestimate their hazard. Overall, the results highlight that the current MALs for soil heavy metals may not fully safeguard human health. There is a critical need to optimize current soil MALs based on localized risks and the actual impact of these metals on human health. It is suggested to appropriately lower the limits of metals (such as As) whose impact on health risks is underestimated, and cautiously increase the limits of metals (such as Cu, Cd, and Zn) that currently pose minor health risks. This approach aims to reduce both over and insufficient protection problems of soil heavy metal MALs, emphasizing the importance of considering the locality in setting these limits.
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Metais Pesados , Poluentes do Solo , Solo , Metais Pesados/análise , Medição de Risco , Poluentes do Solo/análise , Humanos , Solo/química , Monitoramento AmbientalRESUMO
BACKGROUND: The prevention of unplanned endotracheal extubation (UEE) is significant for the critical care of intensive care unit (ICU) patients. AIM: To develop a questionnaire to assess the knowledge, attitude, and practice (KAP) of the nurses regarding of the prevention of UEE in ICU patients with transoral endotracheal intubation (TEI) and to test the validity and reliability of the questionnaire. STUDY DESIGN: Items relevant to KAP were prepared following a literature review, and then screened using a Delphi expert consultation, pre-test, and factor analysis. The nursing staffs in four tertiary hospitals in Qinghai, Jiangsu, Gansu, and Shandong provinces were surveyed to test the reliability and validity of the questionnaire. RESULTS: The questionnaire contained 76 items, including 10, 37, and 29 in the dimensions of knowledge, attitude, and practice, respectively. The scale-level content validity index (S-CVI) of the questionnaire was 0.96. The results of exploratory factor analysis (EFA) showed that the Kaiser-Meyer-Olkin value was 0.956, indicating that the sample was adequate and suitable for factor analysis. The result of the Bartlett spherical test was significant (p < .001), indicating that the questionnaire was suitable for further EFA. A total of six common factors were extracted by EFA with a cumulative variance interpretation rate of 85.52%, indicating that the questionnaire had good structural validity. The Cronbach's alpha was 0.981 for the whole questionnaire; and was 0.966, 0.996, and 0.981 for the dimensions of knowledge, attitude, and practice, respectively. The test-retest reliability for the questionnaire was 0.843. CONCLUSIONS: The developed questionnaire has good reliability and validity and can be used as a scientific tool for the nursing leaders to prevent UEE in ICU patients with TEI. RELEVANCE TO CLINICAL PRACTICE: The instrument provides a theoretical reference for establishing preventive strategies and management programs in clinical practice.
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Conhecimentos, Atitudes e Prática em Saúde , Recursos Humanos de Enfermagem , Humanos , Reprodutibilidade dos Testes , Extubação , Inquéritos e Questionários , PsicometriaRESUMO
The design of functional metalloenzymes is attractive for the biosynthesis of biologically important compounds, such as phenoxazinones and phenazines catalyzed by native phenoxazinone synthase (PHS). To design functional heme enzymes, we used myoglobin (Mb) as a model protein and introduced an artificial CXXC motif into the heme distal pocket by F46C and L49C mutations, which forms a de novo disulfide bond, as confirmed by the X-ray crystal structure. We further introduced a catalytic Tyr43 into the heme distal pocket and found that the F43Y/F46C/L49C Mb triple mutant and the previously designed F43Y/F46S Mb exhibit PHS-like activity (80-98% yields in 5-15 min), with the catalytic efficiency exceeding those of natural metalloenzymes, including o-aminophenol oxidase, laccase, and dye-decolorizing peroxidase. Moreover, we showed that the oxidative coupling product of 1,6-disulfonic-2,7-diaminophenazine is a potential pH indicator, with the orange-magenta color change at pH 4-5 (pKa = 4.40). Therefore, this study indicates that functional heme enzymes can be rationally designed by structural modifications of Mb, exhibiting the functionality of the native PHS for green biosynthesis.
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Metaloproteínas , Mioglobina , Mioglobina/química , Heme/química , Oxazinas , Óxido Nítrico SintaseRESUMO
The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm2. H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Microambiente Tumoral , Fotoquimioterapia/métodos , Terapia Combinada , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Linhagem Celular Tumoral , Nanomedicina Teranóstica/métodosRESUMO
BACKGROUND: No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. METHODS: RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. RESULTS: Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p < 0.001; NRI = 0.122, IDI = 0.185, p < 0.01). CONCLUSION: Overall, we established a reliable, non-invasive, and objective detection method composed of circulating tumor-derived sEVs 4-miRNA plus CA-125 to preoperatively anticipate the high-risk AOC patients of residual disease to optimize clinical therapy.
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Vesículas Extracelulares , MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , MicroRNAs/genética , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Carcinoma Epitelial do Ovário , Terapia NeoadjuvanteRESUMO
It is desired to design and construct more efficient enzymes with better performance to catalyze carbene N-H insertions for the synthesis of bioactive molecules. To this end, we exploited and designed a series of human neuroglobin (Ngb) mutants. As shown in this study, a double mutant, A15C/H64G Ngb, with an additional disulfide bond and a modified heme active site, exhibited yields up to >99% and total turnover numbers up to 33000 in catalyzing the carbene N-H insertions for aromatic amine derivatives, including those with a large size such as 1-aminopyrene. Moreover, for o-phenylenediamine derivatives, they underwent two cycles of N-H insertions, followed by cyclization to form quinoxalinones, as confirmed by the X-ray crystal structures. This study suggests that Ngb can be designed into a functional carbene transferase for efficiently catalyzing carbene N-H insertion reactions with a range of substrates. It also represents the first example of the formation of quinoxalinones catalyzed by an engineered heme enzyme.
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Significant efforts have been made in the design of artificial metalloenzymes. Myoglobin (Mb), an O2 carrier, has been engineered to exhibit different functions. Herein, we applied a series of engineered Mb mutants with peroxidase activity for biosynthesis of clofazimine (CFZ), a potential drug with a broad-spectrum antiviral activity, by integration with chemical synthesis. Two of those mutants, F43Y Mb and F43Y/T67R Mb, have been shown to efficiently catalyze the oxidative coupling of 2-N-(4-chlorophenyl) benzene-1,2-diamine (N-4-CPBDA) in the presence of H2O2, with 97% yields. The overall catalytic efficiency (kcat/Km) is 46-fold and 82-fold higher than that of WT Mb, respectively. By further combination of this reaction with chemical synthesis, the production of CFZ was accomplished with an isolated yield of 72%. These results showed that engineered Mbs containing the Tyr-heme cross-link (F43Y Mb and F43Y/T67R Mb) exhibit enhanced activity in the oxidative coupling reaction. This study also indicates that the combination of biocatalysis and chemical synthesis avoids the need for the separation of intermediate products, which offers a convenient approach for the total synthesis of the biological compound CFZ.
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Clofazimina , Mioglobina , Mioglobina/genética , Mioglobina/química , Peróxido de Hidrogênio/química , Modelos Moleculares , Heme/químicaRESUMO
It aimed to discuss the adoption of nanoparticle micro-infusion valves in the totally implantable venous access port (TIVAP) of tumor patients and analyze the self-care of patients after surgery. A total of 189 tumor patients who received TIVAP chemotherapy were selected from the day chemotherapy outpatient department of the Second People's Hospital of Lianyungang City from June to October 2021. The questionnaire survey was conducted to collect and analyze the general information about the patients and the patient's self-care ability. All the surveys and analyses were performed using a general information questionnaire, self-care competence scale, self-management efficacy scale, social support scale, and self-rating anxiety scale. Moreover, the nanoparticle micro-infusion valve was prepared, and its characterization, in vitro drug release, and cytotoxicity were studied. The self-management ability of patients was concentrated in the middle and high levels. Marital status, education level, and economic status all had a great impact on the patient's self-care ability. The infusion of dithiothreitol (DTT) increased the drug release of the nanoparticle micro-infusion valve. When pH=5.0, the drug-loaded nanoparticle micro-infusion valve release amount was greater than when pH=7.4. When pH=5.0 and pH=7.4, the cell survival rates under the drug-loaded nanoparticle micro-infusion valve were both lower than that without drug loading. Nanoparticle micro-infusion valves can specifically identify tumor cells, and have good adoption prospects in TIVAP implantation in tumor patients. Gender, marital status, education level, etc. all affected the self-care ability of patients.
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Neoplasias , Autocuidado , Humanos , Catéteres , Neoplasias/tratamento farmacológico , Ditiotreitol , Liberação Controlada de FármacosRESUMO
The paper aimed to explore the influence factors of corneal edema after phacoemulsification for diabetic cataracts. For this aim, 80 patients (80 eyes) with senile cataracts who underwent phacoemulsification implantation in our hospital from August 2021 to January 2022 were included in this study, including 39 males (48.75%) and 41 females (51.25%), with an average age of 70.35±5.22 years. The OCT system during ophthalmology was used to capture corneal OCT images in the center of the cornea in real time before the phacoemulsification (the phacoemulsification probe just entered the anterior chamber after the balanced saline left the separated nucleus), at the end of phacoemulsification (when the phacoemulsification ultrasound probe was still in the anterior chamber and the perfusion pressure did not change compared with that in the previous step), at the end of perfusion aspiration (after the perfusion aspiration probe left the anterior chamber), and after surgery (after the watertight incision is closed). The corneal thickness was measured at each time point using Photoshop software. AL, curvature and ACD were measured using IOL-Master bio-measurement technology, and ACD referred to the distance between the front surface of the cornea and the front surface of the lens. Endothelial cell density was measured using CIM-530 non-contact mirror microscope. A handheld rebound tonometer was used to measure intraocular pressure and optical coherence tomography was used to assess the macular area of the fundus. Fundus photography was performed with a non-diffuse fundus camera. The results indicated that the preoperative corneal thickness was 514.35±29.62 µm, and the average corneal thickness at the end of the operation was 535.26±30.29µm, which was increased by 20.91±1.67 µm compared with that before operation (P<0.05), and the increase rate of corneal thickness was 4.07%. The corneal thickness of patients tended to increase with the increase in operation time and intraocular operation time (P<0.05). The distribution of corneal edema-related features showed that 42.50% of patients had persistent edema at the time of cataract surgery. The median onset time of corneal edema in the remaining patients was 5.44 years (1.96-21.35 years for 90% CR). The higher the nuclear hardness, the more severe the cataract, and the higher APT, EPT, APE, and TST (P<0.05). The older the patient, the higher the grade of cataract nucleus, and the higher EPT, APE, and TST, the greater the intraoperative corneal thickening (P<0.05). The higher the maximum area of endothelial cells, the greater the intraoperative corneal thickness increase, the lower the corneal endothelial cell density and the greater the intraoperative corneal thickness increase (P<0.05). It was concluded that postoperative corneal edema in phacoemulsification surgery for diabetic cataracts is closely related to intraocular perfusion pressure, nuclear hardness of lens, the density of corneal endothelial cells, the energy of phacoemulsification and duration.
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Catarata , Edema da Córnea , Diabetes Mellitus , Hominidae , Facoemulsificação , Masculino , Feminino , Humanos , Animais , Idoso , Facoemulsificação/efeitos adversos , Facoemulsificação/métodos , Edema da Córnea/etiologia , Células Endoteliais , Implante de Lente Intraocular , Catarata/complicaçõesRESUMO
OBJECTIVE: This study aimed to investigate the value of left ventricular (LV) press-strain loop (PSL) in evaluating global and regional myocardial work (MW) in hypertrophic cardiomyopathy (HCM) patients. METHODS: A total of 30 HCM patients with interventricular septum hypertrophy (HCM group) and 35 healthy subjects (control group) were selected from First Hospital of Qinhuangdao. The general clinical data and conventional ultrasound parameters of two groups were acquired. The MW parameters were analyzed using LV PSL. The regional MW parameters in the HCM group were compared between ventricular septum and the free walls of left ventricle. RESULTS: The epicardial adipose tissue thickness of the HCM group was significantly greater than that of the control group (P < 0.05). Global work efficiency was significantly reduced, while global wasted work was increased in patients with HCM compared with controls (all P < 0.05). The HCM group was compared in the group, to be specific, in the HCM group, the work index, the work efficiency, and the longitudinal strain on the interventricular septum were lower than those on the free wall (all P < 0.05). CONCLUSION: PSL is more effective than LVEF in assessing left ventricular systolic function in HCM and is able to quantify regional myocardial work in the ventricular septum in HCM patients with preserved LVEF, suggesting a novel idea for clinical diagnosis and assessment.
Assuntos
Cardiomiopatia Hipertrófica , Humanos , Pressão Ventricular , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Miocárdio , Sístole , Função Ventricular EsquerdaRESUMO
BACKGROUND: Diabetes is the leading cause of chronic kidney disease (CKD) and contributes to an elevated incidence of diastolic dysfunction in the early stages of CKD. Intracardiac vortex is a novel hemodynamic index for perceiving cardiac status. Here, we visualized left ventricular (LV) vortex characteristics using vector flow mapping (VFM) in type 2 diabetic patients with early CKD. METHODS: This cross-sectional study included 67 controls and 89 type 2 diabetic patients with stages 2-3a CKD. All subjects underwent transthoracic echocardiographic examination. LV anterior vortex during early diastole (E-vortex), atrial contraction (A-vortex) and systole (S-vortex) were assessed using VFM in the apical long-axis view. Its relation to glycemia or LV filling echocardiographic parameters were further analyzed using correlation analysis. RESULTS: Type 2 diabetic patients with early CKD had a small area (439.94 ± 132.37 mm2 vs. 381.66 ± 136.85 mm2, P = 0.008) and weak circulation (0.0226 ± 0.0079 m2/s vs. 0.0195 ± 0.0070 m2/s, P = 0.013) of E-vortex, but a large area (281.52 ± 137.27 mm2 vs. 514.83 ± 160.33 mm2, P Ë 0.001) and intense circulation (0.0149 ± 0.0069 m2/s vs. 0.0250 ± 0.0067 m2/s, P < 0.001) of A-vortex compared to controls. CKD patients with poorly controlled hyperglycemia had stronger A-vortex (area: 479.06 ± 146.78 mm2 vs. 559.96 ± 159.27 mm2, P = 0.015; circulation: 0.0221 ± 0.0058 m2/s vs. 0.0275 ± 0.0064 m2/s, P < 0.001) and S-vortex (area: 524.21 ± 165.52 mm2 vs. 607.87 ± 185.33 mm2, P = 0.029; circulation: 0.0174 ± 0.0072 m2/s vs. 0.0213 ± 0.0074 m2/s, P = 0.015), and a longer relative duration of S-vortex (0.7436 ± 0.0772 vs. 0.7845 ± 0.0752, P = 0.013) than those who had well-controlled hyperglycemia. Glycemia, and E/A (a LV filling parameter) were respectively found to had close correlation to the features of A-vortex and S-vortex (all P < 0.05). CONCLUSIONS: Abnormal LV vortices were detected in type 2 diabetic patients with early CKD using VFM, especially in those who neglected hyperglycemic control. LV vortex might be a promising parameter to slow or halt the hyperglycemia-induced diastolic dysfunction in early CKD.