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The sensing of nitroaromatic compounds in aqueous solution is closely related to environmental sustainability and human health. In this study, a novel Cd(II) coordination polymer (Cd-HCIA-1) was designed and prepared, and its crystal structure, luminescence performance, detection of nitro pollutants in water, and fluorescence quenching mechanisms were studied. Cd-HCIA-1 exhibited a one-dimensional ladder-like chain based on a T-shape ligand of 5-((4-carboxybenzyl) oxy) isophthalic acid (5-H3CIA). The H-bonds and π-π stacking interactions were then used to construct the supramolecular skeleton in common. Luminescence studies revealed that Cd-HCIA-1 can detect nitrobenzene (NB) in aqueous solution with high sensitivity and selectivity, and the limit of detection was 3.03 × 10-9 mol L-1. The fluorescence quenching mechanism of the photo-induced electron transfer for NB by Cd-HCIA-1 was obtained through an investigation of the pore structure, density of states, excitation energy, orbital interactions, hole-electron analysis, charge transfer, and electron transfer spectra by using density functional theory (DFT) and time-dependent DFT methods. NB was absorbed in the pore, π-π stacking increased the orbital overlap, and the LUMO was mainly composed of NB fragments. The charge transfer between ligands was blocked, resulting in fluorescence quenching. This study on fluorescence quenching mechanisms can be used to develop efficient explosive sensors.
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Persistent human papillomavirus (HPV) infection has been associated with the development of cervical cancer. To reduce the incidence of cervical cancer and promote awareness of HPV, a government-sponsored epidemiological study was conducted from 2015 to 2018 in Zhengzhou City. A total of 184,092 women aged 25-64 years were included, of which 19,579 were infected with HPV, reflecting a prevalence of 10.64 percent (19,579/184,092). The HPV genotypes found were classified as high-risk (13 genotypes) and low-risk (8 genotypes). Single and multiple infections were detected in 13,787 (70.42 percent) and 5,792 (29.58 percent) women, respectively. The five most common high-risk genotypes detected, listed in descending order, were HPV52 (2.14 percent; 3,931/184,092), HPV16 (2.04 percent; 3,756/184,092), HPV58 (1.42 percent; 2,607/184,092), HPV56 (1.01 percent; 1,858/184,092), and HPV39 (0.81 percent; 1,491/184,092). Meanwhile, the most common low-risk genotype was HPV53 (0.88 percent; 1,625/184,092). The prevalence of HPV gradually increased with age, with the highest occurring in women aged 55-64 years. The prevalence of single-type HPV infection decreased with age, whereas that of multiple-type HPV infection increased with age. This study indicates a high burden of HPV infection in women in Zhengzhou City.
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Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/epidemiologia , Papillomavirus Humano , Infecções por Papillomavirus/epidemiologia , Genótipo , Papillomaviridae/genética , Prevalência , China/epidemiologiaRESUMO
OBJECTIVES: To analyse the characteristics and determinants of drug resistance mutations (DRMs) in HIV-infected children and adolescents on long-term ART in China. METHODS: An observational cohort study was conducted in five centres. All participants younger than 15 years at ART initiation were screened, and those identified as having virological failure (VF) with viral load (VL)â≥â400 copies/mL were included for genotypic resistance testing. Logistic regression analysis was performed and the accumulation of major mutations was analysed in a subgroup of resistant individuals with complete VL results since HIV diagnosis. RESULTS: Among 562 eligible participants, protease and RT regions were successfully amplified for 93 who failed treatment with a median of 10.0 years ART. Sixty-eight (73.1%) harboured ≥1 major mutations. NRTI, NNRTI and dual-class resistance accounted for 48.4%, 63.4% and 38.7%, respectively. Only 3.2% were resistant to PIs. Age at ART initiation [adjusted OR (aOR)â=â0.813, 95% CI 0.690-0.957], subtype B (aORâ=â4.378, 95% CI 1.414-13.560) and an initial NNRTI-based regimen (aORâ=â3.331, 95% CI 1.180-9.402) were independently associated with DRMs. Among 40 resistant participants with additional VL data, 55.0% had continued VF on a suboptimal regimen and the estimated duration of VF was positively correlated with the total number of major mutations (râ=â0.504, Pâ=â0.001). CONCLUSIONS: The development of DRMs was common in children and adolescents receiving long-term treatment, and continued VF was prevalent in those with resistance. Timely genotypic testing and new child-friendly formulations are therefore urgently required.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adolescente , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Falha de TratamentoRESUMO
Norovirus (NoV) infection is a leading cause of non-bacterial gastroenteritis worldwide and there are currently no effective therapeutics available to target the virus. The norovirus major capsid protein VP1 is a potential candidate for the development of vaccines due to the similar morphology and immunogenicity of its assembled virus-like particles (VLPs) compared to native virions. In this study, we explored the effects of N- and C-terminal sequence additions to the VP1 of a GII.4 NoV during its assembly into VLPs. A series of sequences of different lengths derived from the minor capsid protein VP2 of the GII.4 NoV were added to the N- and C-terminus of VP1. The fusion proteins were expressed using a recombinant baculovirus expression system and the assembly of the expressed fusion proteins was subsequently observed under electron microscopy (EM). Our results indicated that all constructed fusion proteins were successfully expressed with different degrees of enzyme cleavage at the N-terminus. Electron microscopy revealed the successful assembly of VLPs of different sizes for all fusion proteins. An in vitro binding assay for VLP-histo-blood group antigens (HBGAs) indicated that all fusion proteins exhibited similar binding patterns compared with their wild-type VP1. Our results demonstrate that (Xi et al., 1990) [1] NoV VP1 can tolerate foreign sequences at its N- or C-terminus without affecting its ability to assemble into VLPs, and (Jiang et al., 1992) [2] that the cleavage pattern and effects of foreign sequences on the sizes of assembled VLPs observed in this study might represent important experimental data that can be used to elucidate VP1 self-assembly.
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Infecções por Caliciviridae , Gastroenterite , Norovirus , Proteínas do Capsídeo , Genótipo , Humanos , Norovirus/genética , Ligação Proteica , Proteínas Recombinantes/metabolismoRESUMO
The surface-exposed loop regions of the protruding domain of the norovirus (NoV) major capsid protein VP1 can tolerate the insertion of foreign antigens without affecting its assembly into subviral particles. In this study, we investigated the tolerance of the surface-exposed loop region of the GII.4 NoV VP1 by replacing it with homologous or heterologous sequences. We designed a panel of constructs in which the amino acid sequence from position 298-305 of the GII.4 NoV VP1 was replaced by sequences derived from the same region of GI.3, GII.3, GII.6, and GII.17 NoVs as well as neutralizing epitopes of enterovirus type 71 and varicella-zoster virus. The constructs were synthesized and expressed using a recombinant baculovirus expression system. The expression of target proteins was measured by indirect enzyme-linked immunosorbent assay (ELISA), and the assembly of virus-like particles (VLPs) was confirmed by electron microscopy. Our results showed that all of the constructs expressed high levels of target chimeric proteins, and all of the chimeric proteins successfully assembled into VLPs or subviral particles. An in vitro VLP-histo-blood group antigen (HBGA) binding assay revealed that chimeric-protein-containing VLPs did not bind or showed reduced binding to salivary HBGAs, a ligand for NoV particles. The results of an in vitro VLP-HBGA binding blockade assay indicated that the predicted surface-exposed loop region of the GII.6 NoV VP1 may comprise a blockade epitope. In summary, the surface-exposed loop region of the GII.4 NoV VP1 can be replaced by foreign sequences of a certain length. Using this strategy, we found that the predicted surface-exposed loop region of GII.6 NoV VP1 might contain a blockade epitope.
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Norovirus , Proteínas do Capsídeo , Epitopos/genética , Humanos , Norovirus/química , Norovirus/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismoRESUMO
BACKGROUND: Antiretroviral therapy (ART) regimens containing integrase strand transfer inhibitors (INSTIs) have become the recommended treatment for human immunodeficiency virus type 1 (HIV-1)-infected patients in the updated guidelines in China. In this study, we investigated the prevalence of acquired and transmitted INSTI-associated resistance of HIV-1 strains in the Henan Province (China) to provide guidance on the implementation of routine INSTI-associated HIV-1 genotypic resistance testing. METHODS: Serum samples from HIV-1-infected patients seeking treatment in our hospital from August 2018 to December 2020 were collected and the HIV-1 integrase gene coding sequence was amplified, sequenced and analyzed for INSTI resistance. RESULTS: We obtained integrase sequence data from a total of 999 HIV-1-infected patients, including 474 ART-naive patients, 438 ART-treated patients, and 87 patients with unknown treatment history. We detected INSTI resistance in 12 patients (1.2%, 12/999) of the study group, which included 9 ART-treated patients (2.05%, 9/438), with 6 being INSTI-treated (14.63%, 6/41) and 3 INSTI-naive (0.76%, 3/397) and 3 ART-naive (0.63%, 3/474) patients. The most common major resistance mutation was E138AK (0.5%, 5/999), while the most common accessory resistance mutation was E157Q (1.8%, 18/999). Phylogenetic analysis based on the HIV-1 integrase gene indicated that INSTI resistance was primarily detected in patients infected with HIV-1 subtype B. CONCLUSIONS: In conclusion, our study reveals that INSTI resistance is observed in INSTI-treated patients, as expected, and the prevalence of INSTI resistance in ART-naive patients in Henan Province is low. However, baseline INSTI resistance testing should be considered, as the prescription of INSTI-based regimens is anticipated to increase considerably in the near future.
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Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , China/epidemiologia , Farmacorresistência Viral/genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Integrase de HIV/genética , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , Humanos , Mutação , Filogenia , PrevalênciaRESUMO
The glycerol phosphate pathway produces more than 90% of the liver triacylglycerol (TAG). LysoPA, an intermediate in this pathway, is produced by glycerol-3-phosphate acyltransferase. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), whose gene was recently cloned, contains lysophospholipase D activity, which produces LysoPA from lysophospholipids. Whether human GDPD3 plays a role in hepatic TAG homeostasis is unknown. We hypothesized that human GDPD3 increases LysoPA production and availability in the glycerol phosphate pathway, promoting TAG biosynthesis. To test our hypothesis, we infected C57BL/6J mice with adeno-associated virus encoding a hepatocyte-specific albumin promoter that drives GFP (control) or FLAG-tagged human GDPD3 overexpression and fed the mice chow or a Western diet to induce hepatosteatosis. Hepatic human GDPD3 overexpression induced LysoPA production and increased FA uptake and incorporation into TAG in mouse hepatocytes and livers, ultimately exacerbating Western diet-induced liver steatosis. Our results also showed that individuals with hepatic steatosis have increased GDPD3 mRNA levels compared with individuals without steatosis. Collectively, these findings indicate that upregulation of GDPD3 expression may play a key role in hepatic TAG accumulation and may represent a molecular target for managing hepatic steatosis.
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Ácidos Graxos/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Lisofosfolipídeos/biossíntese , Diester Fosfórico Hidrolases/genética , Animais , Transporte Biológico/genética , Expressão Gênica , Humanos , CamundongosRESUMO
Human immunodeficiency virus type 1 (HIV-1) infection remains a severe public health problem worldwide. In this study, we investigated the distribution of HIV-1 subtypes and the prevalence of drug resistance mutations (DRMs) among patients with HIV-1 infection in Henan Province, China. HIV-1 strains in blood samples taken from inpatients and outpatients visiting the Sixth People's Hospital of Zhengzhou from August 2017 to July 2019 with a viral load (VL) greater than 1000 copies/ml were subjected to subtype and DRMs analysis. Out of a total of 769 samples, subtype and DRM data were obtained from 657 (85.43%) samples. Phylogenetic analysis based on partial pol gene sequences indicated that the most commonly found genotype was subtype B (45.51%, 299/657), followed by CRF01_AE (28.61%, 188/657), CRF07_BC (15.68%, 103/657), CRF08_BC (0.76%, 5/657), C (0.61%, 4/657), A (0.30%, 2/657), and others (8.52%, 56/657). Circulating recombinant forms (CRFs) were most commonly found in patients who were naïve to antiretroviral treatment (ART) (68.67%, 160/233). The percentage of patients with one or more major drug-resistance mutations was 50.99% (335/657), and it was 6.44% (15/233) in ART-naive patients that were primarily infected with subtype B (17.74%). Resistance mutations were most common at codons 65, 103, 106, 184, and 190 of the reverse transcriptase gene and codon 46 of the protease gene. Our study provides detailed information about the distribution of HIV-1 subtypes and the incidence of drug resistance mutations of different subtypes in ART-experienced and naïve patients. This can guide policymakers in making decisions about treatment strategies against HIV-1.
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Farmacorresistência Viral/genética , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirretrovirais/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Filogeografia , Carga Viral , Adulto JovemRESUMO
OBJECTIVES: To analyze the clinical characteristics of 71 patients with coronavirus disease 2019 (COVID-19). METHODS: The general data, epidemiological data, laboratory tests, imaging examinations, and treatment of 71 patients with COVID-19 admitted to the Sixth People's Hospital of Zhengzhou from January 19, 2020 to March 3, 2020 were retrospectively analyzed. RESULTS: Of the 71 COVID-19 patients, the ages were 4-84 (41.29±15.21) years, 38 (53.5%) patients were male, 33 (46.5%) were female, and 52 (73.2%) were in 22 clusters. The main clinical manifestations were fever (78.9%), cough (64.8%), and sputum (38.0%). The fever was mainly low and moderate, with 49 patients (69.0%) at 37.3-39.0 â. Most of the leukocytes, neutrophils, and lymphocytes were normal, accounting for 47 (66.2%), 51 (71.8%), and 51 (71.8%) patients, respectively; a few of them were decreased, accounting for 21 (29.6%), 16 (22.5%), and 20 (28.2%) patients, respectively. There were 38 (53.5%) and 31 (43.7%) patients with the decreased CD4+ and CD8+ T cell counts, respectively. There were 41 (57.7%), 38 (53.5%), 32 (45.1%), 26(36.6%), 22 (31.0%), 20 (28.2%), 14 (19.7%), 14 (19.7%), and 9 (12.7%) patients with the increased levels of C-reactive protein, erythrocyte sedimentation rate, procalcitonin, fibrinogen,interleukin 6, lactate dehydrogenase,D-dimer,alanine aminotransferase, and aspartate aminotransferase, respectively. Of the 71 patients, the lung was involved in 60 (84.5%) patients, the double lung was involved in 47 (66.2%) patients, and the single lung was involved in 13 (18.3%) patients. The course of the disease was long, and the time from symptom onset to the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid negative transformation was (17.22±6.34) days.There were no significant differences in the incubation period (t=-0.453, P>0.05), the complicates (χ2=0.042, P>0.05), and the time from symptom onset to diagnosis (t=-1.330, P>0.05) in patients between the non-severe group and the severe group. The onset age, gender, SARS-CoV-2 nucleic acid negative time, lymphocyte count, D-dimer, C-reactive protein, total bilirubin, direct bilirubin, lactate dehydrogenase, calcium ion, CD4+ T cell count, CD8+ T cell count, calcitonin, procalcitonin, and troponin were significantly different between the severe group and the non-severe group (all P<0.05). Among the 71 patients, 4 (5.6%) patients were mild, 59 (83.1%) were normal, and 8 (11.3%) were severe or critical. CONCLUSIONS: The aggregation phenomenon of COVID-19 is obvious. Fever and cough are the main clinical manifestations. White blood cells, neutrophils, and lymphocytes in the most patients in the early onset are normal. Most COVID-19 patients are light and ordinary type, with good prognosis.
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Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , Criança , Pré-Escolar , China , Tosse/virologia , Feminino , Febre/virologia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Adulto JovemAssuntos
Fabaceae , Microbiota , Bálsamos , Nitrogênio , Raízes de Plantas , Rizosfera , Solo , Glycine maxRESUMO
OBJECTIVE: To explore whether thioredoin-2 (Trx-2) is involved in the development of cataract and to study the effect of Trx-2 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells.â© Methods: A total of 10 volunteers (removing the lens due totraumatism) and 30 patients received phacoemulsification (age more than 60 years) were selected. The expression of Trx-2 protein in lens epithelial cells from cataract patients and volunteers were detected by the immunohistochemical streptavidin-peroxidase (SP) method. SRA01/04 cells were cultured and were divided into six groups according to different treatment: a control group, H2O2-treated groups at 20, 50 or 100 µmol/L, a negative control group (transfected with pCMV6 plasmid plus 100 µmol/L H2O2), and a Trx-2 overexpression group (transfected with pCMV6-Trx-2 plasmid plus 100 µmol/L H2O2). Methyl thiazolyltetrazolium (MTT) assay and flow cytometry was performed to measure the cell viability and apoptosis for SRA01/04 cells, respectively. The activities of superoxide dismutase (SOD) and catalase (CAT), the content of glutathione (GSH) and malondialdehyde (MDA) in human lens epithelial cells were measured via chemical chromatometry. Western blot was used to measure the protein levels of Trx-2, B-cell lymphoma 2 protein (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3.â© Results: Compared with the volunteers, the expression of Trx-2 was significantly decreased in lens epithelial cells in patients with cataract (P<0.05). Compared with the control group, the expression of Trx-2 protein in the 20, 50 or 100 µmol/L H2O2 groups was decreased (all P<0.05). Compared with the control group, the cell survival rates were decreased in the 100 µmol/L H2O2 group and the negative control group (both P<0.05), along with enhanced apoptotic rates, inhibited cellular SOD activities and CAT activities, reduced GSH contents, augmented MDA contents, down-regulated Trx-2 and Bcl-2 expression and up-regulated Bax and caspase-3 expression (all P<0.05). Compared with the negative control group, the cell survival rate was increased in the Trx-2 overexpression group (P<0.05), along with suppressed apoptosis, increased SOD activities and CAT activities, elevated GSH contents, decreased MDA content, up-regulated Trx-2 and Bcl-2 expression and down-regulated Bax and caspase-3 expression (P<0.05).â© Conclusion: Trx-2 might be involved in the apoptosis of lens epithelial cells in patients with cataract. The overexpression of Trx-2 obviously attenuated H2O2-induced injury of human lens epithelial cells, which might be associated with the inhibition of H2O2-mediated oxidative stress.
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Catarata/metabolismo , Sobrevivência Celular , Células Epiteliais/metabolismo , Cristalino/citologia , Proteínas Mitocondriais/metabolismo , Estresse Oxidativo , Tiorredoxinas/metabolismo , Apoptose , Catarata/etiologia , Células Epiteliais/efeitos dos fármacos , Humanos , Peróxido de HidrogênioRESUMO
Although alcohol is an established breast cancer risk factor, the underlying mechanisms remain unclear. Previous studies examined the general association between alcohol consumption and breast cancer risk; however, the risk for different breast cancer subtypes has been rarely reported. Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking hormone receptors and HER2 expression, and having poor prognosis. Understanding the molecular mechanisms of TNBC etiology remains a significant challenge. In this study, we investigated cellular responses to alcohol in two TNBC cell lines, MDA-MB-231 and MDA-MB-468. Our results showed that alcohol at low concentrations (0.025-0.1% v/v) induced cell proliferation, migration, and invasion in 1% FBS-containing medium. Molecular analysis indicated that these phenotypic changes were associated with alcohol-induced reactive oxygen species production and increased p38 and JNK phosphorylation. Likewise, p38 or JNK inhibition attenuated alcohol-induced cell migration and invasion. We revealed that alcohol treatment activated/phosphorylated NF-κB regulators and increased transcription of NF-κB-targeted genes. While examining the role of acetaldehyde, the major alcohol metabolite, in alcohol-associated responses in TNBC cells, we saw that acetaldehyde induced cell migration, invasion, and increased phospho-p38, phospho-JNK, and phospho-IκBα in a pattern similar to alcohol treatment. Taken together, we established that alcohol promotes TNBC cell proliferation, migration, and invasion in vitro. The underlying mechanisms involve the induction of oxidative stress and the activation of NF-κB signaling. In particular, the activation of p38 and JNK plays a pivotal role in alcohol-induced cellular responses. These results will advance our understanding of alcohol-mediated development and promotion of TNBC. © 2016 Wiley Periodicals, Inc.
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Álcoois/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Invasividade Neoplásica , FosforilaçãoRESUMO
BACKGROUND/AIMS: Elucidation of the molecular mechanisms governing osteoblast differentiation and angiogenesis are of great importance for improving the treatment of bone-related diseases. In this study, we examined the role of microRNA (miR)-10a in the differentiation of MC3T3-E1 cells and pro angiogenic activity of mouse umbilical vein endothelial cells (MUVECs). METHODS: The murine pre-osteoblast cell line MC3T3-E1 and MUVECs were used in the experiment. After transfected with miR-10a mimics or inhibitors, with or without LiCl pretreatment, the miR-10a, ALP, Runx2, Osx, OC and Dlx5 expression were assessed by RT-PCR. MC3T3-E1 cells were cultured with BMP2 to differentiate into bone cells, osteogenic differentiation of MC3T3-E1 cells were detected by ALP and ARS staining. Cell viability were analyzed by MTT and the protein expression of ß-catenin, LEF1, cyclinD1, MMP2, and VEGF were detected by Western blotting; VEGF and VE-cadherin release were assessed by ELISA, and the migration of MUVECs, as well as tube formation were also detected. RESULTS: MiR-10a expression was obviously down-regulated during osteogenic differentiation. Overexpression of miR-10a inhibited osteogenic differentiation of MC3T3-E1 cells, effectively decreasing MUVECs proliferation, migration, VEGF expression, VE-cadherin concentrations, and tube formation in vitro, whereas miR-10a silence enhanced those processes. Further mechanism assays demonstrated that overexpression of miR-10a reduced the ß-catenin at both protein and transcription level, while pretreatment with Wnt signaling activator Licl partially attenuated the suppression effects of miR-10a overexpression on osteoblast differentiation and angiogenesis. CONCLUSION: Our findings imply that miR-10a plays a suppressive role in osteoblast differentiation of MC3T3-E1 cells and pro angiogenic activity of MUVECs by regulating the ß-catenin expression, representing a novel and potential therapeutic target for the treatment of bone regeneration-related diseases.
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Diferenciação Celular/genética , MicroRNAs/fisiologia , Neovascularização Fisiológica/genética , Osteoblastos/citologia , beta Catenina/metabolismo , Células 3T3 , Animais , Regulação para Baixo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Camundongos , beta Catenina/genéticaRESUMO
BACKGROUND: Human leukocyte antigen (HLA)-B*5701 is strongly associated with developing a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*5701 prevalence in HIV-1-infected subjects in China. We investigated HLA-B*5701 prevalence in HIV-1-infected population including Han and non-Han ethnic groups. METHODS: A prospective multi-centre study was designed to determine status of HLA-B*5701 in HIV-1-infected adults at six sites across China. HLA-B*5701 was tested by the method of PCR-SSP. RESULTS: From six centers, 3,000 HIV-infected patients [2,452 (81.7%) Han, 548 (18.3%) Non-Han] were recruited with a mean age of 36.7 years old. The overall HLA-B*5701 prevalence was 0.86% [95% confidence interval (CI) 0.55-1.26%]. The prevalence of HLA-B*5701 among Han subjects was similar to that among non-Han subjects, which was 0.88% (95% CI 0.54-1.34%) and 0.76% (95% CI 0.19-1.93%), respectively (p value = 0.787). There were no differences in prevalence of HLA-B*5701 between subjects born in Henan, Yunnan, Shanxi, Guangdong, Hebei, Beijing and other provinces (p = 0.999). CONCLUSIONS: HLA-B*5701 prevalence is very low in HIV-infected Chinese subjects, both in the Han and Non-Han nationalities. And there are no differences among different birthplaces across China.
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Nitroaromatic compounds in aqueous undermine environmental sustainability and affect human health. The development of a fluorescent sensor capable of efficiently and selectively detecting trace amounts of nitroaromatic compounds presents a considerable challenge. This study introduced Zn/Cd isomeric coordination polymers (Zn-H2CIA-1/Cd-H2CIA-2), which are synthesized using 5-((4-carboxybenzyl)oxy)isophthalic acid (5-H3CIA) and 1,10-phenanthroline (Phen). The polymers have zero-dimensional discrete crystal structure with a six-coordinated scissor-like shape. The two coordination polymers can be used as fluorescent sensors for detecting nitrobenzene (NB) and demonstrated favorable sensitivity, with detection limits of 1.95 × 10-8 and 4.66 × 10-7 mol/L, respectively. Zn-H2CIA-1 exhibited stronger fluorescence and a more sensitive response to NB compared with Cd-H2CIA-2. To elucidate their fluorescence-quenching mechanisms, we analyzed Zn-H2CIA-1 by performing DFT and TD-DFT calculations. The pore structure, density of states, excitation energy, hole-electron distribution, and orbital composition were analyzed. The suitable size of pores in Zn-H2CIA-1 is the main reason for its high NB selectivity. Moreover, intermolecular π-π stacking interactions result in an orbital overlap between Zn-H2CIA-1 and NB, enabling the transfer of electrons from Zn-H2CIA-1 to NB. This electron transfer is identified as the fundamental cause of fluorescence quenching in Zn-H2CIA-1.
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Mercury ions (Hg(II)) in wastewater can accumulate and transform into the highly neurotoxic methylmercury (MeHg) in activated sludge. The release of MeHg can have severe environmental consequences, making the treatment of MeHg-contaminated sludge a pressing concern. In this study, we found that all the collected activated sludge samples, from different wastewater treatment plants in four cities, had the potential for Hg methylation. The Hg-methylating capacity reached a maximum level of 0.70-0.92 µg/g volatile suspended solids after 48 h of exposure to 5 µg/L Hg(II) and showed an average MeHg production rate of 4.8±0.5%. Accordingly, a sludge treatment method involving the addition of elemental sulfur (S0) for a short-term or long-term duration (3 or 180 days, respectively) was proposed. The results demonstrated that this treatment approach effectively mitigated and potentially eliminated MeHg formation by simultaneously reducing Hg bioavailability and Hg-methylating bioactivity. We found that bioavailable Hg(II) ions were converted to a secondary phase similar to insoluble HgS after S0 addition treatment, leading to a decrease in Hg bioavailability in sludge. The enhancement of Hg and extracellular polymeric substances (EPS) complexation via the increasing amount of thiol groups in EPS also reduced the Hg bioavailability after the long-term treatment. Furthermore, the long-term S0 addition significantly reduced the abundance of Hg-methylators with hgcA gene and promoted the growth of Hg-reducers with merA gene, which ensured the complete elimination of MeHg production potential of the excessive activated sludge. Our findings demonstrated that the proposed S0-addition sludge treatment is a promising and safe biotechnology for treating Hg-contaminated sludge. This approach has the potential to contribute significantly to the mitigation of MeHg pollution within environmental contexts.
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Mercúrio , Compostos de Metilmercúrio , Purificação da Água , Esgotos , Enxofre , ÍonsRESUMO
Background: Traditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV. Methods: We retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens. Results: This study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P<0.001). In addition, 11 patients showed consistent results between the two methods. Futhermore, mNGS showed excellent performance in identifying multi-infections in PLHIV, and 27 pathogens were detected in the BALF of 30 PLHIV by mNGS, among which 15 PLHIV were found to have multiple microbial infections (at least 3 pathogens). Pneumocystis jirovecii, human herpesvirus type 5, and human herpesvirus type 4 were the most common pathogen types. Conclusions: For PLHIV with suspected pulmonary infections, mNGS is capable of rapidly and accurately identifying the pathogen causing the pulmonary infection, which contributes to implement timely and accurate anti-infective treatment.
Assuntos
Líquido da Lavagem Broncoalveolar , Infecções por HIV , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Masculino , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Estudos Retrospectivos , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/virologia , Adulto , Pessoa de Meia-Idade , China , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/virologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Infecções Respiratórias/microbiologiaRESUMO
BACKGROUND: Nitroaromatic compounds are inherently hazardous and explosive, so convenient and rapid detection strategies are needed for the sake of human health and the environment. There is an urgent demand for chemical sensing materials that offer high sensitivity, operational simplicity, and recognizability to effectively monitor nitroaromatic residues in industrial wastewater. Despite its importance, the mechanisms underlying fluorescence quenching or enhancement in fluorescent sensing materials have not been extensively researched. The design and synthesis of multiresponsive fluorescent sensing materials have been a great challenge until now. RESULTS: In this study, a one-dimensional Cd-based fluorescent porous coordination polymer (Cd-CIP-1) was synthesized using 5-(4-cyanobenzyl)isophthalic acid (5-H2CIP) and 4,4'-bis(1-imidazolyl)biphenyl (4,4'-bimp) and used for the selective detection of nitrobenzene in aqueous solution by fluorescence quenching, with a limit of detection of 1.38 × 10-8 mol L-1. The presence of aniline in the Cd-CIP-1 solution leads to the enhancement of fluorescence property. Density functional theory and time-dependent density functional theory calculations were carried out to elucidate the mechanisms of the fluorescence changes. This study revealed that the specific pore size of Cd-CIP-1 facilitates analyte screening and enhances host-guest electron coupling. Furthermore, π-π interactions and hydrogen bond between Cd-CIP-1 and the analytes result in intermolecular orbital overlap and thereby boosting electron transfer efficiency. The different electron flow directions in NB@Cd-CIP-1 and ANI@Cd-CIP-1 lead to fluorescence quenching and enhancement. SIGNIFICANCE AND NOVELTY: The multiresponsive coordination polymer (Cd-CIP-1) can selectively detect nitrobenzene and recognize aniline in aqueous solutions. The mechanism of fluorescence quenching and enhancement has been thoroughly elucidated through a combination of density functional theory and experimental approaches. This study presents a promising strategy for the practical implementation of a multiresponsive fluorescent chemical sensor.
RESUMO
The improper utilization of nitrobenzene (NB) and ornidazole (ORN) has resulted in irreversible effects on the environment. By combining experimental investigation, density functional theory (DFT) calculations, and machine learning, an effective green strategy for detecting NB and ORN in aqueous solutions can be developed. In this study, a one-dimensional Cd-based coordination polymer (Cd-HCIA-3) was designed and synthesized using 5-((4-carboxybenzyl)oxy)isophthalic acid and rigid 2,2'-bipyridine under solvothermal reaction conditions. Cd-HCIA-3 exhibits excellent fluorescence properties and stability in aqueous solutions. DFT calculations were performed to predict the fluorescence sensing performance of Cd-HCIA-3, revealing that photoinduced electron transfer is the key mechanism for inducing fluorescence quenching in the presence of NB and ORN, with weak molecular interactions promoting electron transfer. Fluorescence sensing experiments were conducted to verify the DFT results, showing that Cd-HCIA-3 can selectively detect NB and ORN in aqueous solutions with limits of detection of 7.22 × 10-8 and 1.31 × 10-7 mol/L, respectively. This study's findings provide valuable insights into the design and synthesis of fluorescent coordination polymers for target analytes.
RESUMO
OBJECTIVES: This study sought to examine the relationship between Toxoplasma gondii seropositivity and cognitive function in older adults. DESIGN: An observational cross-sectional study. SETTING: The National Health and Nutrition Examination Survey (NHANES) study took place at participants' homes and mobile examination centres. PARTICIPANTS: A total of 2956 older adults aged 60 and above from the NHANES from 2011 to 2014 were included in the study. Exposure of interest: participants had serum Toxoplasma gondii antibody analysed in the laboratory. A value>33 IU/mL was categorised as seropositive for Toxoplasma gondii infection; <27 IU/mL was categorised as seronegative for Toxoplasma gondii infection. PRIMARY AND SECONDARY OUTCOME MEASURES: Cognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD-WL) for immediate and delayed memory, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). RESULTS: About half of the 2956 participants (mean age 70.0) were female (51.0%), non-Hispanic White (48.3%), and completed some college or above (48.3%). A total of 703 participants were positive for Toxoplasma gondii infection (23.8%). Adjusted linear regression showed that compared with participants with negative Toxoplasma gondii infection, those with positive Toxoplasma gondii infection had lower CERAD-WL immediate memory (beta (ß) -0.16, 95% CI -0.25 to -0.07), CERAD-WL delayed memory (ß -0.15, 95% CI -0.24 to -0.06), AFT (ß -0.15, 95% CI -0.24 to -0.06), DSST (ß -0.34, 95% CI -0.43 to -0.26), and global cognition (ß -0.24, 95% CI -0.32 to -0.16) z-scores after controlling for the covariates. CONCLUSIONS: Toxoplasma gondii seropositivity is associated with worse immediate and delayed verbal learning, language proficiency, executive functioning, processing speed, sustained attention, working memory, as well as global cognition in older adults. Public health measures aiming at preventing Toxoplasma gondii infection may help preserve cognitive functioning in older adults.