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We have utilized reversible covalent bonding to expand the accessible states of a molecular switch. Introducing a hydroxyl group onto the donor moiety of a donor-acceptor Stenhouse adduct (DASA) imparts an acidity response by forming an oxazolidine ring through intramolecular nucleophilic addition. Furthermore, we observed distinct color changes under cryogenic conditions, extending the thermal responsiveness beyond the cyclization equilibrium observed at elevated temperatures. These unique responses present promising prospects for diverse applications compared to traditional photoinduced binary isomerization.
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Background: Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent. Methods and results: Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline. Conclusion: This work provides a meaningful insight for the mechanism of AAΙ renal injury.
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Household animal fat has been linked to increased incidence of cancers compared with vegetable fat. However, few epidemiological studies have associated these two cooking oil types with precancerous genotoxic effects, such as occurrence of micronuclei (MN). This study aimed to explore the association between oral MN frequency and household cooking oil type and whether the association can be attributed to polycyclic aromatic hydrocarbons (PAHs). We collected information about individual cooking oil use, measured genotoxic effects by MN tests and urinary PAHs metabolites (OHPAHs) in 245 nonsmokers. The associations between household cooking oil type and MN frequency and OHPAHs were analyzed using generalized linear models (GLMs) and logistic regression models, evaluating odds ratios and coefficient (95% confidence intervals) (ORs, 95% Cls; ß, 95% Cls). The odds of animal fat consumers, rather than vegetable fat consumers, was positively associated with higher MN frequency (OR = 1.94, P < 0.05). The associations were discovered in participants only using kitchen ventilation (OR = 2.04, P < 0.05). Animal fat consumers had higher total OHPAHs than vegetable fat consumers (1.58 ± 0.22 mg/mol, Cr vs 1.20 ± 0.12 mg/mol, Cr; P = 0.028). Significant correlations were observed between total OHPAHs quartiles and increased MN frequency (ß = 0.38, P-trend = 0.026). After stratifying by household cooking oil type, sensitivity analyses showed that the positive association between total OHPAHs quartiles and increased MN frequency was only observed in animal fat consumers (ß = 0.61, P-trend = 0.030). In conclusion, usage of household animal fat was associated with an increased odds of oral MN frequency in Chinese nonsmokers and the odds correlated with increased PAHs exposure. This finding supplemented evidence associating cooking oil type with genotoxic effects and explained its association with PAHs exposure.
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não Fumantes , Hidrocarbonetos Policíclicos Aromáticos , China , Culinária , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , VentilaçãoRESUMO
As a traditional Chinese medicine (TCM), Millettia speciosa Champ (MSC), exerts a wide range of pharmacological activities. Our research group previously found that MSC has antidepressant effects, but the specific antidepressant mechanisms remain unclear. Therefore, in this study, urine metabolomics based on ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) combined with pharmacodynamics was used to explore the pathogenesis of depression and the antidepressant effects of MSC. The results showed that MSC treatment could significantly improve chronic unpredictable mild stress (CUMS)-induced depression. Urine metabolic showed that the profiles of the CUMS model group were significantly separated from the control group, while the drug-treated groups were closer to the control group, especially the MSC group treated with a 14 g/kg dose of MSC. Furthermore, 9 metabolites, including glutaric acid, L-isoleucine, L-Dopa, sebacic acid, 3-methylhistidine, allantoin, caprylic acid, tryptophol, and 2-phenylethanol glucuronide, were identified as potential biomarkers of depression. Metabolic pathway analysis showed that these potential biomarkers were mainly involved in valine, leucine, and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine degradation, tyrosine metabolism, histidine metabolism, fatty acid biosynthesis, and pentose and glucuronate interconversions. Through Receiver operating characteristic (ROC) analysis and Pearson correlation analysis, the combination of L-isoleucine, sebacic acid, and allantoin, were further screened out as potential pharmacodynamic biomarkers associated with the efficacy of MSC. This study suggests that the integration of metabolomics with pharmacodynamics helps to further understand the pathogenesis of depression and provides novel insight into the efficacy of TCM.
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Líquidos Corporais , Medicamentos de Ervas Chinesas , Millettia , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Isoleucina , Metabolômica , RatosRESUMO
PURPOSE: The objective of this retrospective study was to determine whether patients undergoing in vitro fertilization (IVF) benefit from reducing the gamete co-incubation time. METHODS: Patients (n = 570) were enrolled, including 281 patients in the reduced incubation time group (2-h incubation) and 289 patients in the standard IVF group (18-h incubation). RESULTS: The observed outcomes, including the clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), and miscarriage rate (MR), were similar between the two groups. When the data were divided into two subgroups based on the maternal age (≤30 and >30 years), the rates of top-quality embryos (30.83 vs. 25.89 %; p = 0.028), CPR (66.67 vs. 42.11 %; p = 0.013), and IR (41.90 vs. 31.25 %, p = 0.019) of the 2-h incubation group were significantly higher in the younger subgroup. However, for older patients, only a lower MR (7.59 vs. 20.83 %; p = 0.019) was achieved. Reducing the time of incubation still improved the CPR (OR = 1.993, 95 % CI 1.141-3.480) and MR (OR = 3.173, 95 % CI 1.013-9.936) in the younger and older subgroups, respectively, after it was adjusted for potential confounders. CONCLUSIONS: Reducing incubation time improves the clinical results of IVF, although the LBR is not statistically different between the 2- and 18-h incubation time groups. And the specific clinical outcomes of reducing incubation time varied between the >30-year-old and the ≤30-year-old.
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Fertilização in vitro , Células Germinativas/crescimento & desenvolvimento , Idade Materna , Taxa de Gravidez , Aborto Espontâneo/epidemiologia , Adulto , Implantação do Embrião , Transferência Embrionária/métodos , Feminino , Humanos , Nascido Vivo/epidemiologia , GravidezRESUMO
PURPOSE: To explore the optimal timing for hCG triggering by investigating the impact of different proportion of dominant follicles on the oocyte developmental competence. METHODS: One hundred ninety-eight infertile women were divided into three groups according to the proportion of dominant follicles on hCG day: (1) low: <15% (n = 66); (2) middle: 15-27% (n = 66); (3) high: >27% (n = 66). The grouping criteria were the bottom and top tertiles of the proportion of dominant follicles. RESULTS: The gonadotropin dosage, duration and maximum follicle diameter in the low proportion group were lower than those in the middle and high proportion groups. Oocyte maturation and the abnormal fertilization rate in the low proportion group were lower than those in the middle and high proportion groups. The normal fertilization rate did not differ among the three groups. The cleavage rate and number of transferable embryos in the low proportion group were significantly higher than those in the high proportion group. The high-quality embryo rate, implantation rate, and pregnancy rate in the low proportion group were significantly higher than those in the middle and high proportion groups. CONCLUSIONS: A high proportion of dominant follicles are closely associated with impaired oocyte developmental competence and low pregnancy rate. These findings suggest that follicular overgrowth induced by delayed hCG triggering may undermine oocyte developmental competence and the proportion of dominant follicles may be a potential parameters for hCG triggering.
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Gonadotropina Coriônica/administração & dosagem , Infertilidade Feminina/terapia , Oócitos/crescimento & desenvolvimento , Oogênese , Folículo Ovariano/crescimento & desenvolvimento , Adulto , Transferência Embrionária/métodos , Feminino , Fertilização in vitro , Humanos , Infertilidade Feminina/patologia , Indução da Ovulação/métodos , Gravidez , Taxa de GravidezRESUMO
BACKGROUND: Oocyte secreted factors (OSFs), including growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), play an important role in the process of follicular development and oocyte maturation. Since OSFs are expressed in oocytes and cumulus granulosa cells, the aim of the present study was to explore whether the expression levels of GDF9 and BMP15 mRNAs in cumulus granulosa cells can be used as molecular markers for predicting oocyte developmental potential. METHODS: Cumulus cells of 2426 cumulus-oocyte complexes were collected from 196 female patients who underwent intracytoplasmic sperm injection (ICSI) and were used for mRNA detection on the egg retrieval day. Pearson correlation analysis was used to analyze the correlation between OSF expression and general physiological parameters. Partial correlation analysis was used to analyze the correlation between OSF expression and oocyte developmental potential. Covariance analysis was used to compare OSF expression among different groups. Receiver operating characteristic curves were used to examine the diagnostic value of GDF9 and BMP15 mRNA for predicting pregnancy. RESULTS: The expression levels of GDF9 and BMP15 mRNAs were significantly associated with age, body mass index (BMI), oocyte maturation, normal fertilization, and cleavage rate (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the group with high-quality embryos were significantly higher than those in the group without high-quality embryos (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the pregnancy group were significantly higher than those in the nonpregnancy group (P < 0.05). The cut-off value of GDF9 mRNA for predicting pregnancy was 4.82, with a sensitivity of 82% and a specificity of 64%. The cut-off value of BMP15 mRNA for predicting pregnancy was 2.60, with a sensitivity of 78% and a specificity of 52%. CONCLUSIONS: The expression levels of GDF9 and BMP15 mRNAs were closely associated with oocyte maturation, fertilization, embryo quality, and pregnancy outcome; therefore, GDF9 and BMP15 mRNAs in cumulus granulosa cells may be considered as new molecular markers for predicting oocyte developmental potential.
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Proteína Morfogenética Óssea 15/metabolismo , Células do Cúmulo/metabolismo , Ectogênese , Fator 9 de Diferenciação de Crescimento/metabolismo , Oogênese , RNA Mensageiro/metabolismo , Regulação para Cima , Adulto , Biomarcadores/metabolismo , Proteína Morfogenética Óssea 15/genética , China/epidemiologia , Células do Cúmulo/citologia , Técnicas de Cultura Embrionária , Feminino , Fator 9 de Diferenciação de Crescimento/genética , Humanos , Técnicas de Maturação in Vitro de Oócitos , Infertilidade Masculina , Masculino , Gravidez , Taxa de Gravidez , Curva ROC , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas , CônjugesRESUMO
A series of tetrasubstituted fluoroalkene derivatives were synthesized by the reaction of α-fluoro-ß-carbonyl benzothiazol-2-yl sulfones with various nucleophiles in good yields with high stereoselectivities. The predominant cis configuration of fluorine and alkynyl groups was observed. A single isomer was obtained when a ketone, acetate or amide was used as the substrate in the presence of a base.
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Alcenos/química , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/química , Estrutura Molecular , Estereoisomerismo , Sulfonas/químicaRESUMO
OBJECTIVE: To compare the effects of Bushen Jiedu Recipe (BJR) and Jianpi Jiedu Recipe (JJR) containing plasma on dendritic cells (DCs) of chronic hepatitis B virus (HBV) infection patients under different immune states. METHODS: Recruited were 36 chronic HBV infection outpatients from First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from April 2010 to January 2011. They were assigned to the immune tolerance group (18 cases) and the immune clearance group (18 cases).Another 10 healthy subjects were recruited as the healthy control group. Their anticoagulated peripheral venous blood was respectively collected. The peripheral blood mononuclear cells (PBMCs) were isolated and further extracted for incubating DCs. The DCs were intervened by BJR and JJR containing plasma. The morphology of DCs was identified. The expressions of CD1alpha, CD80, CD86, and HLA-DR were detected. The level of interferon-alpha (IFN-alpha) in the supernatant was observed by ELISA. RESULTS: The CD80 expression level was lower in the immune clear group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, CD86, and HLA-DR were lower in the immune tolerance group than in the healthy control group before intervention (P < 0.05).The IFN-alpha expression level was lower in the immune tolerance group and the immune clearance group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, HLA-DR, and IFN-alpha were lower in the immune tolerance group than in the immune clearance group before intervention (P < 0.05). Compared with the same group before intervention, the CD80 expression significantly increased in each treatment group (P < 0.05). After intervention the expression levels of CD80 and HLA-DR were higher in the immune tolerance group than in the immune clearance group in the same time phase, and the CD86 expression level was higher in the BJR group than in the immune clearance group in the same time phase, showing statistical difference (P < 0.05). CONCLUSIONS: The middle dose BJR and the small dose JJR both could promote the recovery of DCs in chronic HBV infection patients. Besides, BJR showed more prominent effects on the function of DCs in chronic HBV infection patients in the immune tolerance stage.
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Células Dendríticas/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Adulto , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Estudos de Casos e Controles , Células Dendríticas/imunologia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Antígenos HLA-DR/metabolismo , Hepatite B Crônica/tratamento farmacológico , Humanos , Tolerância Imunológica/efeitos dos fármacos , Interferon-alfa/metabolismo , Masculino , Fitoterapia , Plasma , Adulto JovemRESUMO
OBJECTIVE: To analyze the outcomes of lung resection and off-pump coronary artery bypass grafting (OPCAB) synchronously for the patients with lung tumor and concurrent coronary heart disease. METHODS: Twenty-two patients with lung tumor and concurrent coronary heart disease underwent combined surgical interventions between January 2003 and December 2011. They included 20 males and 2 females with a mean age of (65 ± 4) years. The TNM stage of lung cancer was predominantly at stages I and II. A majority of them had two and three-vessel disease. The tests of cardiothoracic functions were normal. The biopsy of lung tumor was carried out initially through sternotomy approach. Then OPCAB was performed. Finally lung resection was carried out according to the pathological results of lung tumor. RESULTS: All patients survived. The average number of anastomosed coronary vessels was 2.3. After myocardial revascularization through a sternotomy approach, the procedures included lobectomy and partial lung resections through sternotomy only (n = 11), lobectomy through a lateral thoracotomy approach (n = 9) and lobectomy and bypass to left anterior descending (LAD) through left thoracotomy only (n = 2). Neither death nor new MI occurred during the perioperative period. The mean stay in-hospital was (17 ± 7) days and mean operative duration (233 ± 1) min. The diagnoses were non-small cell lung cancer (n = 18) and benign tumor (n = 4). The most frequent complications were cardiac arrhythmias, atelectasis and pulmonary infections. All of them were followed up for 10-60 months. Within this period, 4 patients died from cancer recurrence. CONCLUSION: The combined procedure of OPCABG grafting and pulmonary resection is a safe and effective treatment option for patients with lung cancer and concurrent coronary heart disease.
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Doença das Coronárias/cirurgia , Neoplasias Pulmonares/cirurgia , Idoso , Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença das Coronárias/complicações , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Resultado do TratamentoRESUMO
BACKGROUND: Surgical resection remains the treatment of choice for pulmonary arteriovenous malformation but removes some normal lung parenchyma. This study aimed to evaluate the effect and safety of the lung-saving procedure of fistulectomy as an alternative to lung resection. METHODS: From July 2003 to July 2008, 6 selected patients with pulmonary arteriovenous malformations underwent fistulectomies. Among them, 1 patient underwent emergency operation and 2 underwent bilateral operations. One patient received postoperative embolotherapy. RESULTS: No hospital deaths or postoperative morbidity occurred. PaO2 increased significantly after operation. All patients were free of symptoms and hypoxia during a follow-up for 9 months to 5 years. CONCLUSIONS: Fistulectomy is a safe and effective procedure for patients with pulmonary arteriovenous malformation and may be an alternative to lung resection.
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Malformações Arteriovenosas/cirurgia , Fístula/cirurgia , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Adolescente , Adulto , Idoso , Malformações Arteriovenosas/patologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PneumonectomiaRESUMO
OBJECTIVE: To summarize the experience in lung resection synchronous with off-pump coronary artery bypass grafting (OPCABG) in patients with lung tumor and coronary disease. METHODS: The clinical data of ten patients with coronary artery disease and lung tumor, 8 with peripheral malignant tumors and 2 with central benign tumors, all males, aged 56.2 (41 - 782), who underwent lung resection and OPCABG synchronously, were analyzed. RESULTS: There was no hospital death in this series. All patients regained their ideal cardiorespiratory function postoperatively. CONCLUSION: With experienced management, it is feasible and safe to perform lung resection and OPCABG synchronously for strictly selected patients.