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1.
Nucleic Acids Res ; 51(11): 5565-5583, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37140030

RESUMO

The single-stranded DNA (ssDNA) binding protein complex RPA plays a critical role in promoting DNA replication and multiple DNA repair pathways. However, how RPA is regulated to achieve its functions precisely in these processes remains elusive. Here, we found that proper acetylation and deacetylation of RPA are required to regulate RPA function in promoting high-fidelity DNA replication and repair. We show that yeast RPA is acetylated on multiple conserved lysines by the acetyltransferase NuA4 upon DNA damage. Mimicking constitutive RPA acetylation or blocking its acetylation causes spontaneous mutations with the signature of micro-homology-mediated large deletions or insertions. In parallel, improper RPA acetylation/deacetylation impairs DNA double-strand break (DSB) repair by the accurate gene conversion or break-induced replication while increasing the error-prone repair by single-strand annealing or alternative end joining. Mechanistically, we show that proper acetylation and deacetylation of RPA ensure its normal nuclear localization and ssDNA binding ability. Importantly, mutation of the equivalent residues in human RPA1 also impairs RPA binding on ssDNA, leading to attenuated RAD51 loading and homologous recombination repair. Thus, timely RPA acetylation and deacetylation likely represent a conserved mechanism promoting high-fidelity replication and repair while discriminating the error-prone repair mechanisms in eukaryotes.


Assuntos
Proteína de Replicação A , Proteínas de Saccharomyces cerevisiae , Humanos , Acetilação , Reparo do DNA , Replicação do DNA , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/genética , Histona Acetiltransferases/metabolismo , Rad51 Recombinase/metabolismo , Proteína de Replicação A/genética , Proteína de Replicação A/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Células HeLa
2.
Nano Lett ; 24(15): 4682-4690, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563501

RESUMO

Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined enzyme activity in vitro remains unexplored, primarily owing to limitations in precisely controlling the spatial topological configuration. Herein, we introduce a nanoscale 3D enzyme assembly using a tetrahedral DNA framework (TDF), enabling the replication of spatial topological configuration and maintenance of an identical edge-to-edge distance akin to natural enzymes. Our results demonstrate that 3D nanoscale enzyme assemblies in both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) and three-enzyme systems (amylglucosidase (AGO)/GOx/HRP) lead to enhanced cascade catalytic activity compared to the low-dimensional structure, resulting in ∼5.9- and ∼7.7-fold enhancements over homogeneous diffusional mixtures of free enzymes, respectively. Furthermore, we demonstrate the enzyme assemblies for the detection of the metabolism biomarkers creatinine and creatine, achieving a low limit of detection, high sensitivity, and broad detection range.


Assuntos
Enzimas Imobilizadas , Glucose Oxidase , Enzimas Imobilizadas/química , Peroxidase do Rábano Silvestre/química , Glucose Oxidase/química , DNA/química
3.
BMC Psychiatry ; 24(1): 357, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745124

RESUMO

BACKGROUND: Social anxiety among postoperative breast cancer patients is a prevalent concern, with its intensity fluctuating throughout the course of treatment. The study aims to describe the trajectory of social anxiety in postoperative breast cancer patients, explore the influencing factors, and provide theoretical support for the construction of future intervention programs. METHODS: This study was conducted from June 2022 to January 2023, encompassing 213 breast cancer patients from three first-class hospitals in China. Data collection occurred at four distinct time points. A growth mixture model was employed to identify latent categories representing the trajectories of social anxiety changes among patients. A multiple regression analysis was utilized to explore predictive factors associated with different latent trajectory categories. RESULTS: The trajectory of social anxiety changes in postoperative breast cancer patients includes five potential categories: maintaining mild social anxiety group, changing from mild to moderate social anxiety group, maintaining moderate social anxiety group, changing from moderate to severe social anxiety group, and maintaining severe social anxiety group. Cluster analysis results indicated three types: positive, negative, and low. Logistic regression analysis revealed that younger age, spouses concerned about postoperative appearance, chemotherapy with taxol-based drugs, opting for modified radical surgery or radical mastectomy surgical approaches, and breast cancer patients with negative rumination were factors that influenced patients' social anxiety (P < 0.05). CONCLUSION: The trajectory of social anxiety in postoperative breast cancer patients comprises five potential categories. In clinical practice, it is essential to strengthen the management of high-risk populations susceptible to experiencing social anxiety emotions, including younger age, spouses concerned about postoperative appearance, chemotherapy with taxol-based drugs, opting for modified radical surgery or radical mastectomy surgical approaches, and breast cancer patients with negative rumination.


Assuntos
Neoplasias da Mama , Mastectomia , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Adulto , Mastectomia/psicologia , Período Pós-Operatório , China , Ansiedade/psicologia , Idoso
4.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34140406

RESUMO

Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding. Here, we describe an important role of Rtt105 in high-fidelity DNA replication and recombination and demonstrate that these functions of Rtt105 primarily depend on its regulation of RPA. The deletion of RTT105 causes elevated spontaneous DNA mutations with large duplications or deletions mediated by microhomologies. Rtt105 is recruited to DNA double-stranded break (DSB) ends where it promotes RPA assembly and homologous recombination repair by gene conversion or break-induced replication. In contrast, Rtt105 attenuates DSB repair by the mutagenic single-strand annealing or alternative end joining pathway. Thus, Rtt105-mediated regulation of RPA promotes high-fidelity replication and recombination while suppressing repair by deleterious pathways. Finally, we show that the human RPA-interacting protein hRIP-α, a putative functional homolog of Rtt105, also stimulates RPA assembly on ssDNA, suggesting the conservation of an Rtt105-mediated mechanism.


Assuntos
Reparo do DNA , Replicação do DNA , Proteínas de Ligação a RNA/metabolismo , Proteína de Replicação A/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Transporte Ativo do Núcleo Celular , Proteínas de Transporte/metabolismo , Núcleo Celular/metabolismo , Quebras de DNA de Cadeia Dupla , DNA de Cadeia Simples/metabolismo , Conversão Gênica , Deleção de Genes , Duplicação Gênica , Humanos , Modelos Biológicos , Ligação Proteica , Rad51 Recombinase/metabolismo
5.
J Sci Food Agric ; 104(11): 6809-6820, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38572795

RESUMO

BACKGROUND: The present study aimed to investigate the effects of tremella polysaccharides on the gel properties and antioxidant activity of yak skin gelatin with a view to improving the quality of collagen jellies. The preparation of composite gels were performed by yak skin gelatin (66.7 mg mL-1) and tremella polysaccharides with different concentrations (0, 2, 4, 6, 8 mg mL-1), and finally the collagen jelly was prepared by composite gel (yak skin gelatin: 66.7 mg mL-1; tremella polysaccharides:6 mg mL-1) with the best performance. RESULTS: Tremella polysaccharides not only improved the hardness, springiness, gel strength, water holding capacity and melting temperature of yak skin gelatin, but also enhanced the composite gel's scavenging activity against ABTS radicals, DPPH radicals, O2 and OH radicals. The filling of tremella polysaccharides into the gelatin network increased the number of crosslinking sites inside the gel, which resulted in the gel network structure becoming dense and orderly. The gel particles became finer and more uniform, and the thermal stability was improved. Furthermore, the sensory score of commercially available gelatin jelly decreased more rapidly during storage compared to the composite gel jelly. CONCLUSION: The gel properties and antioxidant activity of yak skin gelatin were improved by adding tremella polysaccharides, and then the quality and storage properties of the jelly were improved, which also provided technical reference for the development of functional gel food. © 2024 Society of Chemical Industry.


Assuntos
Antioxidantes , Colágeno , Gelatina , Géis , Polissacarídeos , Pele , Gelatina/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Bovinos , Géis/química , Pele/química , Pele/efeitos dos fármacos , Colágeno/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Basidiomycota/química , Humanos
6.
Water Sci Technol ; 89(8): 2132-2148, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38678414

RESUMO

Given the substantial environmental pollution from industrial expansion, environmental protection has become particularly important. Nowadays, anion exchange membranes (AEMs) are widely used in wastewater treatment. With the use of polyvinyl alcohol (PVA), ethylene-vinyl alcohol (EVOH) copolymer, and methyl iminodiacetic acid (MIDA), a series of cross-linked AEMs were successfully prepared using the solvent casting technique, and the network structure was formed in the membranes due to the cross-linking reaction between PVA/EVOH and MIDA. Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy were used to analyze the prepared membranes. At the same time, its comprehensive properties which include water uptake, linear expansion rate, ion exchange capacity, thermal stability, chemical stability, and mechanical stability were thoroughly researched. In addition, diffusion dialysis performance in practical applications was also studied in detail. The acid dialysis coefficient (UH+) ranged from 10.2 to 35.6 × 10-3 m/h. Separation factor (S) value ranged from 25 to 38, which were all larger than that of the commercial membrane DF-120 (UH+: 8.5 × 10-3 m/h, S: 18.5). The prepared membranes had potential application value in acid recovery.


Assuntos
Membranas Artificiais , Álcool de Polivinil , Álcool de Polivinil/química , Iminoácidos/química , Difusão , Purificação da Água/métodos , Diálise/métodos , Troca Iônica , Ânions/química , Polivinil/química
7.
Toxicol Appl Pharmacol ; 467: 116479, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36963520

RESUMO

Drug-induced organ injury is one of the key factors causing organ failure and death in the global public. Triptolide (TP) is the main immunosuppressive component of Tripterygium wilfordii Hook. f. (Leigongteng, LGT) for the first-line management of autoimmune conditions, but it can cause serious multi-organ injury. Lysimachia christinae (Jinqiancao, JQC) is a detoxifying Chinese medicine and could suppress LGT's toxicity. It contains many immune enhancement and organ protection components including chlorogenic acid (CA), rutin (Rut), and quercetin (Que). This study aimed to explore the protection of combined treatments of these organ-protective ingredients of JQC on TP-induced liver, kidney, and heart injury and initially explore the mechanisms. Molecular docking showed that CA, Rut, and Que bounded protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway-related molecules intimately and might competitively antagonize TP. Corresponding in vivo results showed that the combination activated TP-inhibited protein of AKT/mTOR pathway, and reversed TP-induced excessive ferroptosis (excessive Fe 2+ and lipid peroxidation malondialdehyde accumulation, decreased levels of antioxidant enzymes catalase, glutathione peroxidase, glutathione-s transferase, reduced glutathione, and superoxide dismutase, and down-regulated P62/nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway), and apoptosis (activated apoptotic factor Fas and Bax and inhibited Bcl-2) in the organ of mice to varying degrees. In conclusion, the combined treatments of CA, Rut, and Que from JQC inhibited TP-induced multi-organ injury in vivo, and the mechanism may largely involve immunomodulation and activation of the AKT/mTOR pathway-mediated cell death reduction including ferroptosis and apoptosis inhibition.


Assuntos
Diterpenos , Ferroptose , Fenantrenos , Camundongos , Animais , Quercetina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ácido Clorogênico , Lysimachia , Rutina/farmacologia , Simulação de Acoplamento Molecular , Estresse Oxidativo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Diterpenos/toxicidade , Fenantrenos/toxicidade , Apoptose , Compostos de Epóxi/toxicidade
8.
Eur J Nucl Med Mol Imaging ; 50(3): 727-741, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36409317

RESUMO

PURPOSE: This study aimed to develop deep learning (DL) models based on multicentre biparametric magnetic resonance imaging (bpMRI) for the diagnosis of clinically significant prostate cancer (csPCa) and compare the performance of these models with that of the Prostate Imaging and Reporting and Data System (PI-RADS) assessment by expert radiologists based on multiparametric MRI (mpMRI). METHODS: We included 1861 consecutive male patients who underwent radical prostatectomy or biopsy at seven hospitals with mpMRI. These patients were divided into the training (1216 patients in three hospitals) and external validation cohorts (645 patients in four hospitals). PI-RADS assessment was performed by expert radiologists. We developed DL models for the classification between benign and malignant lesions (DL-BM) and that between csPCa and non-csPCa (DL-CS). An integrated model combining PI-RADS and the DL-CS model, abbreviated as PIDL-CS, was developed. The performances of the DL models and PIDL-CS were compared with that of PI-RADS. RESULTS: In each external validation cohort, the area under the receiver operating characteristic curve (AUC) values of the DL-BM and DL-CS models were not significantly different from that of PI-RADS (P > 0.05), whereas the AUC of PIDL-CS was superior to that of PI-RADS (P < 0.05), except for one external validation cohort (P > 0.05). The specificity of PIDL-CS for the detection of csPCa was much higher than that of PI-RADS (P < 0.05). CONCLUSION: Our proposed DL models can be a potential non-invasive auxiliary tool for predicting csPCa. Furthermore, PIDL-CS greatly increased the specificity of csPCa detection compared with PI-RADS assessment by expert radiologists, greatly reducing unnecessary biopsies and helping radiologists achieve a precise diagnosis of csPCa.


Assuntos
Aprendizado Profundo , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Próstata/patologia
9.
J Magn Reson Imaging ; 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37602942

RESUMO

BACKGROUND: Accurately detecting adverse pathology (AP) presence in prostate cancer patients is important for personalized clinical decision-making. Radiologists' assessment based on clinical characteristics showed poor performance for detecting AP presence. PURPOSE: To develop deep learning models for detecting AP presence, and to compare the performance of these models with those of a clinical model (CM) and radiologists' interpretation (RI). STUDY TYPE: Retrospective. POPULATION: Totally, 616 men from six institutions who underwent radical prostatectomy, were divided into a training cohort (508 patients from five institutions) and an external validation cohort (108 patients from one institution). FIELD STRENGTH/SEQUENCES: T2-weighted imaging with a turbo spin echo sequence and diffusion-weighted imaging with a single-shot echo plane-imaging sequence at 3.0 T. ASSESSMENT: The reference standard for AP was histopathological extracapsular extension, seminal vesicle invasion, or positive surgical margins. A deep learning model based on the Swin-Transformer network (TransNet) was developed for detecting AP. An integrated model was also developed, which combined TransNet signature with clinical characteristics (TransCL). The clinical characteristics included biopsy Gleason grade group, Prostate Imaging Reporting and Data System scores, prostate-specific antigen, ADC value, and the lesion maximum cross-sectional diameter. STATISTICAL TESTS: Model and radiologists' performance were assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The Delong test was used to evaluate difference in AUC. P < 0.05 was considered significant. RESULTS: The AUC of TransCL for detecting AP presence was 0.813 (95% CI, 0.726-0.882), which was higher than that of TransNet (0.791 [95% CI, 0.702-0.863], P = 0.429), and significantly higher than those of CM (0.749 [95% CI, 0.656-0.827]) and RI (0.664 [95% CI, 0.566-0.752]). DATA CONCLUSION: TransNet and TransCL have potential to aid in detecting the presence of AP and some single adverse pathologic features. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 4.

10.
BMC Psychiatry ; 23(1): 814, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940898

RESUMO

BACKGROUND: Smartphone game addiction has emerged as a major public health problem in China and worldwide. In November 2019 and August 2021, the National Press and Publication Administration of China implemented two increasingly strict policies, as a means of preventing smartphone game addiction in adolescents aged 18 or below. This study aimed to analyze the effect of the policies on smartphone game play time, addiction, and emotion among rural adolescents in China. METHODS: We sent the questionnaire to rural adolescents through the online survey tool Questionnaire Star, a professional online survey evaluation platform. The questionnaire included demographic data, smartphone use survey, smartphone game addiction and emotion evaluation scales. The Smartphone Addiction Scale-Short Version (SAS-SV) measured adolescents' smartphone game addiction. The Short Version of UPPS-P Impulsive Behavior Scale (SUPPS-P) and Social Anxiety Scale for Children (SASC) measured emotion. According to SAS-SV score, the enrolled rural adolescents were divided into addiction group and non-addiction group. The t-test, Chi-square test, and repeated measure ANOVA assessed the effect of the policies on adolescents' smartphone game addiction and emotion. RESULTS: Among enrolled 459 rural adolescents with a mean age of 14.36 ± 1.37years, 151 (32.90%) were in the addiction group and 308 (67.10%) were in the non-addiction group. Adolescents in the addiction group were older, more male, and higher grade. There were time and group effects between the two groups in playtime. After a year of policies implementation, the weekly game time dropped from 3.52 ± 1.89 h to 2.63 ± 1.93 h in the addiction group and from 2.71 ± 1.75 h to 2.36 ± 1.73 h in the non-addiction group. There were also time and group effects in SAS-SV and SASC scores, but not for SUPPS-P score. In the addiction group, the SAS-SV score dropped from 41.44 ± 7.45 to 29.58 ± 12.43, which was below the cut-off value for addiction, and the level of social anxiety was consistently higher than non-addiction group. CONCLUSIONS: The playtime of rural adolescents spent on smartphone games has decreased significantly due to the restriction of the policies rather than the lack of addiction or social anxiety. The policies had practically significant effects in reducing smartphone game play time for rural adolescents in China.


Assuntos
Comportamento Aditivo , Smartphone , Criança , Humanos , Masculino , Adolescente , China , Emoções , Comportamento Aditivo/psicologia , Inquéritos e Questionários
11.
Int J Med Sci ; 20(1): 114-124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36619221

RESUMO

Background: Interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) promotes peritoneal angiogenesis by stimulating SP4-mediated vascular endothelial growth factor (VEGF) production in peritoneal dialysis (PD). Moreover, histone methyltransferase enhancer of zeste homologue 2 (EZH2) is involved in IL-6/sIL-6R signalling via the acceleration of vascular endothelial growth factor (VEGF)-induced angiogenesis. However, the molecular mechanism underlying how EZH2 epigenetically activates VFGF expression in IL-6/sIL-6R signalling during PD is still unclear. Methods and Results: In this study, we measured the expression of EZH2, DNMT3B and SP4 in human peritoneal mesothelial cells (HPMCs) treated with IL-6/sIL-6R stimulation and/or EZH2 overexpression, silencing or inhibition. Methylation of the CpG site in the SP4 promoter region and VEGF production were measured under these treatments in HPMCs. Moreover, tube formation in human umbilical vein endothelial cells (HUVECs) was detected following treatment with conditioned media from these stimulated HPMCs. The 5/6 nephrectomy (5/6Nx) rat model was established, and the rats were injected with peritoneal dialysate. EZH2, DNMT3B and SP4 expression and microvessels were analysed in 5/6Nx + PD rats treated with IL-6/sIL-6R and EZH2 overexpression. The results showed that IL-6/sIL-6R and EZH2 overexpression enhanced the expression of EZH2, DNMT3B and SP4, but EZH2 silencing/inhibition reduced these expression levels. The results for VEGF production and tube formation in vitro followed the same trend. IL-6/sIL-6R and EZH2 overexpression increased the methylation percentage of the -170 bp CpG site in the SP4 promoter region in HPMCs. Moreover, IL-6/sIL-6R and EZH2 overexpression stimulated EZH2, DNMT3B and SP4 expression and promoted angiogenesis in 5/6Nx + PD rats. Conclusions: Thus, this study indicated that EZH2 is involved in IL-6/sIL-6R signalling and epigenetically regulates SP4 expression, thereby stimulating VEGF production and angiogenesis in PD. Targeting EZH2 is expected to be a novel therapeutic approach for end-stage renal disease (ESRD) patients with PD treatment.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste , Interleucina-6 , Diálise Peritoneal , Receptores de Interleucina-6 , Fator de Transcrição Sp4 , Animais , Humanos , Ratos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células Endoteliais da Veia Umbilical Humana , Interleucina-6/metabolismo , Diálise Peritoneal/efeitos adversos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptores de Interleucina-6/metabolismo , Fator de Transcrição Sp4/metabolismo , Epigênese Genética
12.
J Sep Sci ; 46(16): e2300250, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37357157

RESUMO

Efficient enrichment is a challenging and indispensable step in the quantification of polar synthetic auxins in complex samples. In the current study, a new magnetic adsorbent based on polymeric ionic liquid/aminated carbon nanotube composite was fabricated with a one-pot precipitation copolymerization strategy and employed as the extraction phase of magnetic solid phase extraction of synthetic auxins. Various characterization techniques were utilized to inspect the morphology, structure, magnetic property, and functional groups of the prepared adsorbent. Under the optimal conditions, the obtained adsorbent displayed satisfactory capture performance towards studied auxins through multiple interactions. Adsorption studies evidenced that the adsorption procedure of the developed method towards analytes was fit for the Freundlich adsorption model and pseudo-second-order kinetics. Combining with high-performance liquid chromatography, sensitive and reliable method for the identification and quantification of trace synthetic auxins in environmental water and fruit juice samples was developed. The obtained limits of detection for water and fruit juice samples located in the ranges of 0.0059-0.013 and 0.018-0.031 µg/L, respectively. Recoveries in actual samples with different fortified contents varied from 82.2% to 117%, with satisfactory reproducibility. The results will evidence that the introduced extraction technique is a useful alternative for the entrapment of trace synthetic auxins from complex samples.


Assuntos
Líquidos Iônicos , Nanotubos de Carbono , Líquidos Iônicos/química , Ácidos Indolacéticos/análise , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Água/química , Adsorção , Polímeros/química , Cromatografia Líquida de Alta Pressão , Fenômenos Magnéticos , Limite de Detecção
13.
Lett Appl Microbiol ; 76(1)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688784

RESUMO

2,5-Pyridinedicarboxylic acid (2,5-PDA), a natural N-heterocyclic compound and a substitute for production in plastics, was widely distributed in industrial wastewater. However, the biodegradation of 2,5-PDA has been rarely reported. In this study, strain YJ-5, which could utilize 2,5-PDA as the sole carbon source for growth was isolated from pesticide-contaminated soil. Based on the comparative analysis of the 16S rRNA gene sequence, strain YJ-5 was identified as Agrobacterium sp. 2,5-PDA was completely degraded within 7 d and the optimal growth conditions of temperature, pH, and substrate concentration were 30°C, 7.0, and 0.6 mmol-1, respectively. A new intermediate 6-hydroxy-2,5-PDA was determined by UV/VIS spectroscopy and liquid chromatograph coupled time of flight mass spectrometry. When the electron acceptor (2,6-dichlorophenolindophenol) was employed, the 2,5-PDA could be converted by cell extracts of strain YJ-5 cells into 6-hydroxy-2,5-PDA. These results provided new insights for biodegradation on pyridine dicarboxylate.


Assuntos
Agrobacterium , Piridinas , Agrobacterium/genética , RNA Ribossômico 16S/genética , Biodegradação Ambiental , Filogenia , Microbiologia do Solo
14.
Ren Fail ; 45(1): 2159431, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36632821

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of kidney failure worldwide. Anxiety has been associated with disease progression in non-diabetes patients. We aimed to examine the prospective association between anxiety and progression of DKD in type 2 diabetes. METHODS: We conducted a prospective cohort study of 2040 participants with type 2 diabetes at the Diabetes Center of Shanghai General Hospital between May 2017 and June 2020. Anxiety disorders at baseline were diagnosed by a structured clinical interview based on the 10th Revision of International Classification of Disease (ICD). Progression of DKD was identified as the transition from one urinary albumin excretion rate (AER) stage to the next or the development of kidney failure during the follow-up period. RESULTS: At baseline, 403 (19.8%) had a diagnosis of anxiety disorders, of whom 107 (26.6%) also received a depression diagnosis. During a median follow-up time of 3.2 years, deterioration of the kidney status occurred in 340 (16.7%) individuals. After adjustment for potential confounders including depression or an anxiety × depression interaction term, anxiety disorders were independently related to an increased risk of progression of DKD (HR 1.539, 95% CI 1.130-2.095, p = 0.006; HR 1.536, 95% CI 1.111-2.122, p = 0.009, respectively). CONCLUSIONS: Anxiety disorders at baseline, independent of possible confounders, were associated with the progression of DKD in type 2 diabetes. Whether therapeutic interventions for anxiety reduce the risk needs to be investigated.


Assuntos
Transtornos de Ansiedade , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal , Humanos , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/etiologia , China , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Progressão da Doença , Estudos Prospectivos , Insuficiência Renal/complicações
15.
Sensors (Basel) ; 23(8)2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37112144

RESUMO

Dragon fruit is one of the most popular fruits in China and Southeast Asia. It, however, is mainly picked manually, imposing high labor intensity on farmers. The hard branches and complex postures of dragon fruit make it difficult to achieve automated picking. For picking dragon fruits with diverse postures, this paper proposes a new dragon fruit detection method, not only to identify and locate the dragon fruit, but also to detect the endpoints that are at the head and root of the dragon fruit, which can provide more visual information for the dragon fruit picking robot. First, YOLOv7 is used to locate and classify the dragon fruit. Then, we propose a PSP-Ellipse method to further detect the endpoints of the dragon fruit, including dragon fruit segmentation via PSPNet, endpoints positioning via an ellipse fitting algorithm and endpoints classification via ResNet. To test the proposed method, some experiments are conducted. In dragon fruit detection, the precision, recall and average precision of YOLOv7 are 0.844, 0.924 and 0.932, respectively. YOLOv7 also performs better compared with some other models. In dragon fruit segmentation, the segmentation performance of PSPNet on dragon fruit is better than some other commonly used semantic segmentation models, with the segmentation precision, recall and mean intersection over union being 0.959, 0.943 and 0.906, respectively. In endpoints detection, the distance error and angle error of endpoints positioning based on ellipse fitting are 39.8 pixels and 4.3°, and the classification accuracy of endpoints based on ResNet is 0.92. The proposed PSP-Ellipse method makes a great improvement compared with two kinds of keypoint regression method based on ResNet and UNet. Orchard picking experiments verified that the method proposed in this paper is effective. The detection method proposed in this paper not only promotes the progress of the automatic picking of dragon fruit, but it also provides a reference for other fruit detection.


Assuntos
Algoritmos , Frutas , China
16.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834655

RESUMO

Cell morphology is an essential and phenotypic trait that can be easily tracked during adaptation and evolution to environmental changes. Thanks to the rapid development of quantitative analytical techniques for large populations of cells based on their optical properties, morphology can be easily determined and tracked during experimental evolution. Furthermore, the directed evolution of new culturable morphological phenotypes can find use in synthetic biology to refine fermentation processes. It remains unknown whether and how fast we can obtain a stable mutant with distinct morphologies using fluorescence-activated cell sorting (FACS)-directed experimental evolution. Taking advantage of FACS and imaging flow cytometry (IFC), we direct the experimental evolution of the E. coli population undergoing continuous passage of sorted cells with specific optical properties. After ten rounds of sorting and culturing, a lineage with large cells resulting from incomplete closure of the division ring was obtained. Genome sequencing highlighted a stop-gain mutation in amiC, leading to a dysfunctional AmiC division protein. The combination of FACS-based selection with IFC analysis to track the evolution of the bacteria population in real-time holds promise to rapidly select and culture new morphologies and association tendencies with many potential applications.


Assuntos
Bactérias , Escherichia coli , Citometria de Fluxo/métodos , Separação Celular , Fenótipo
17.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5326-5336, 2023 Oct.
Artigo em Zh | MEDLINE | ID: mdl-38114122

RESUMO

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Deficiência da Energia Yin , Masculino , Feminino , Camundongos , Animais , Fatores Sexuais , Ciclo-Oxigenase 2 , NF-kappa B , Antidepressivos/farmacologia
18.
Inflamm Res ; 71(1): 93-106, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34767031

RESUMO

INTRODUCTION: Cerebral ischemic injury is associated with long-term disability. Dexmedetomidine (Dex) can exert neuroprotective effects on cerebral ischemic/reperfusion injury. The present study explored the mechanism of Dex in cerebral ischemic injury. MATERIALS AND METHODS: To this end, the permanent middle cerebral artery occlusion (p-MCAO) mouse model was established and treated with Dex or/and Nrf2 inhibitor ML385. Subsequently, microglia were subjected to oxygen-glucose deprivation (OGD) in sugar-free environment and thereafter treated with Dex, Nrf2 inhibitor, and NLRP3 lentiviral overexpression vector, respectively. RESULTS: Dex alleviated the neurobehavioral deficit of p-MCAO mice, reduced brain water content, relieved pathological changes, and reduced cerebral infarction size. Dex promoted the polarization of microglia from M1 to M2, thus ameliorating oxidative stress and inflammatory responses. Our results showed that Dex promoted M2-polarization of microglia in vivo and in vitro by promoting HO-1 expression via Nrf2 nuclear import. Moreover, the Nrf2/HO-1 axis inhibited the activation of NLRP2 inflammasome and NLRP3 overexpression reversed the effect of Dex. CONCLUSION: In conclusion, Dex promoted M2-polarization of microglia and attenuated oxidative stress and inflammation, and thus protected against cerebral ischemic injury by activating the Nrf2/HO-1 pathway and inhibiting NLRP3 inflammasome.


Assuntos
Isquemia Encefálica , Dexmedetomidina , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas Reguladoras de Apoptose , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/prevenção & controle , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Heme Oxigenase-1 , Proteínas de Membrana , Camundongos , Microglia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais
19.
J Nanobiotechnology ; 20(1): 532, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517801

RESUMO

The increasing prevalence of antibiotic resistance by Pseudomonas aeruginosa (PA) raises an urgent need for an effective vaccine. The outer membrane proteins of PA, especially those that are upregulated during infection, are ideal vaccine targets. However, the strong hydrophobicity of these proteins hinders their application for this purpose. In this study, we selected eight outer membrane proteins from PA with the most significantly upregulated expression. Their extracellular loops were analyzed and screened by using sera from patients who had recovered from PA infection. As a result, a novel immunogenic epitope (Ep167-193) from PilY1 (PA4554) was found. Moreover, we constructed a macrophage membrane-coated PLGA (poly lactic-co-glycolic acid) nanoparticle vaccine carrying PilY1 Ep167-193 (PNPs@M-Ep167-193) that elicits a Th2 immune response and confers adequate protection in mice. Our data furnished the promising vaccine candidate PNPs@M-Ep167-193 while providing additional evidence for structure-based epitope identification and vaccine design.


Assuntos
Nanopartículas , Infecções por Pseudomonas , Camundongos , Animais , Pseudomonas aeruginosa , Epitopos , Infecções por Pseudomonas/prevenção & controle , Macrófagos , Proteínas de Membrana
20.
Pharmacology ; 107(5-6): 250-262, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35417907

RESUMO

INTRODUCTION: Mulberry (Morus alba L.) leaves are widely used in traditional Chinese medicine for their antioxidant, anti-inflammatory, antibacterial, anti-obesity, antidiabetic, antiatherosclerotic, and anticancer properties. The current study aimed to investigate the effect of mulberry leaf extract (MLE) on Staphylococcus aureus (S. aureus)-induced conjunctivitis (5 × 109 colony-forming units, 0.5 mL/eye) in a rabbit model. METHODS: Rabbits were treated with MLE (5 mL/kg·d-1 and 10 mL/kg·d-1), 0.9% saline, pearl bright eye (PBE) drops, or erythromycin eye ointment (EEO) group for 5 days. The ocular infection symptoms, bacterial negative conversion rate, and conjunctival histopathological changes of rabbits in each group were observed. The expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-18, IL-6, IL-1ß, TNFα, Keap1, and nuclear factor erythroid 2-related factor 2 (Nrf2) in conjunctival tissue of rabbits were detected by quantitative real-time reverse transcription PCR and/or Western blot analysis. RESULTS: The results showed that MLE treatment significantly reduced the clinical sign scores of conjunctivitis, alleviated clinical signs, and decreased bacterial load, and histological damage in a time- and dose-dependent manner was compared to that in the control group. The antibacterial and anti-inflammatory activities of MLE (10 mL/kg·d-1) were similar to those of the positive control drug PBE and EEO. In addition, MLE significantly decreased the levels of pro-inflammatory cytokines, downregulated the NLRP3 inflammasome, and upregulated the Nrf2 system. CONCLUSIONS: MLE is effective in alleviating S. aureus-induced conjunctivitis in rabbits, and this mechanism is associated with the inhibition of the NLRP3 inflammasome and activation of the Nrf2 system to regulate pro-inflammatory signaling.


Assuntos
Conjuntivite , Morus , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Conjuntivite/tratamento farmacológico , Citocinas/metabolismo , Regulação para Baixo , Inflamassomos , Interleucina-1beta/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Coelhos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/metabolismo , Regulação para Cima
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