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1.
Sci Total Environ ; 932: 172872, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692322

RESUMO

The misuse of antitussives preparations is a continuing problem in the world, and imply that they might have potential new psychoactive substances (NPS) activity. However, few study focus on their ecological toxicity towards fish. In the present study, the machine learning (ML) methods gcForest and random forest (RF) were employed to predict NPS activity in 30 antitussives. The potential toxic target, mode of action (MOA), acute toxicity and chronic toxicity to fish were further investigated. The results showed that both gcForest and RF achieved optimal performance when utilizing combined features of molecular fingerprint (MF) and molecular descriptor (MD), with area under the curve (AUC) = 0.99, accuracy >0.94 and f1 score > 0.94, and were applied to screen the NPS activity in antitussives. A total of 15 antitussives exhibited potential NPS activity, including frequently-used substances like codeine and dextromethorphan. The binding affinity of these antitussives with zebrafish dopamine transporter (zDAT) was high, and even surpassing that of some traditional narcotics and NPS. Some antitussives formed hydrogen bonds or salt bridges with aspartate (Asp) 95, tyrosine (Tyr) 171 of zDAT. For the ecotoxicity, the MOA of these 15 antitussives in fish was predicted as narcosis. The prenoxdiazin, pholcodine, codeine, dextromethorphan and dextrorphan exhibited very toxic/toxic to fish. It was necessary to pay close attention to the ecotoxicity of these antitussives. In this study, the integration of ML, molecular docking and ECOSAR approaches are powerful tools for understanding the toxicity profiles and ecological hazards posed by new pollutants.

2.
Environ Res ; 252(Pt 3): 119043, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692422

RESUMO

It is of great significance to establish an effective method for removing Cr(VI) from wastewater. Herein, Fe-doped g-C3N4 (namely Fe-g-C3N4-2) was synthesized and then employed as photocatalyst to conduct the test of Cr(VI) reduction. Notably, the embedding of Fe ion in g-C3N4 can offer the Fe2+/Fe3+ redox couples, so reducing the interfacial resistance of charge transfer and suppressing the recombination of photogenerated electrons and holes. The impurity energy levels will form in g-C3N4 after the introduction of Fe ion, thereby boosting the light absorption capacity of catalyst. Thus, Fe-g-C3N4-2 showed good performance in photocatalytic Cr(VI) reduction, and the reduction efficiency of Cr(VI) can reach 39.9% within 40 min. Different with many previous studies, current work unexpectedly found that the addition of p-benzoquinone (BQ) can promote the Cr(VI) reduction, and the reduction efficiency of Cr(VI) over Fe-g-C3N4-2 was as high as 93.2% in the presence of BQ (1.5 mM). Further analyses showed that BQ can be reduced to hydroquinone (HQ) by photogenerated electrons, and UV light can also directly induce BQ to generate HQ by using H2O as the hydrogen donor. The HQ with reducing ability can accelerate the Cr(VI) reduction. In short, current work shared some novel insights into photocatalytic Cr(VI) reduction in the presence of BQ. Future research should consider possible reactions between photogenerated electrons and BQ. For the UV-induced photocatalysis, the suitability of BQ as the scavenger of O2•‒ must be given carefully consideration.

3.
Plant Cell Environ ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738504

RESUMO

Plants synthesise a vast array of volatile organic compounds (VOCs), which serve as chemical defence and communication agents in their interactions with insect herbivores. Although nitrogen (N) is a critical resource in the production of plant metabolites, its regulatory effects on defensive VOCs remain largely unknown. Here, we investigated the effect of N content in tomato (Solanum lycopersicum) on the tobacco cutworm (Spodoptera litura), a notorious agricultural pest, using biochemical and molecular experiments in combination with insect behavioural and performance analyses. We observed that on tomato leaves with different N contents, S. litura showed distinct feeding preference and growth and developmental performance. Particularly, metabolomics profiling revealed that limited N availability conferred resistance upon tomato plants to S. litura is likely associated with the biosynthesis and emission of the volatile metabolite α-humulene as a repellent. Moreover, exogenous application of α-humulene on tomato leaves elicited a significant repellent response against herbivores. Thus, our findings unravel the key factors involved in N-mediated plant defence against insect herbivores and pave the way for innovation of N management to improve the plant defence responses to facilitate pest control strategies within agroecosystems.

4.
Health Inf Sci Syst ; 12(1): 30, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38617016

RESUMO

The prediction of drug-target interactions (DTI) is a crucial preliminary stage in drug discovery and development, given the substantial risk of failure and the prolonged validation period associated with in vitro and in vivo experiments. In the contemporary landscape, various machine learning-based methods have emerged as indispensable tools for DTI prediction. This paper begins by placing emphasis on the data representation employed by these methods, delineating five representations for drugs and four for proteins. The methods are then categorized into traditional machine learning-based approaches and deep learning-based ones, with a discussion of representative approaches in each category and the introduction of a novel taxonomy for deep neural network models in DTI prediction. Additionally, we present a synthesis of commonly used datasets and evaluation metrics to facilitate practical implementation. In conclusion, we address current challenges and outline potential future directions in this research field.

5.
medRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38585741

RESUMO

A common feature of human aging is the acquisition of somatic mutations, and mitochondria are particularly prone to mutation due to their inefficient DNA repair and close proximity to reactive oxygen species, leading to a state of mitochondrial DNA heteroplasmy1,2. Cross-sectional studies have demonstrated that detection of heteroplasmy increases with participant age3, a phenomenon that has been attributed to genetic drift4-7. In this first large-scale longitudinal study, we measured heteroplasmy in two prospective cohorts (combined n=1405) at two timepoints (mean time between visits, 8.6 years), demonstrating that deleterious heteroplasmies were more likely to increase in variant allele fraction (VAF). We further demonstrated that increase in VAF was associated with increased risk of overall mortality. These results challenge the claim that somatic mtDNA mutations arise mainly due to genetic drift, instead demonstrating positive selection for predicted deleterious mutations at the cellular level, despite an negative impact on overall mortality.

6.
Angew Chem Int Ed Engl ; : e202402374, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655601

RESUMO

The construction of secondary building units (SBUs) in versatile metal-organic frameworks (MOFs) represents a promising method for developing multi-functional materials, especially for improving their sensitizing ability. Herein, we developed a dual small molecules auxiliary strategy to construct a high-nuclear transition-metal-based UiO-architecture Co16-MOF-BDC with visible-light-absorbing capacity. Remarkably, the N3- molecule in hexadecameric cobalt azide SBU offers novel modification sites to precise bonding of strong visible-light-absorbing chromophores via click reaction. The resulting Bodipy@Co16-MOF-BDC exhibits extremely high performance for oxidative coupling benzylamine (~100% yield) via both energy and electron transfer processes, which is much superior to that of Co16-MOF-BDC (31.5%) and Carboxyl Bodipy@Co16-MOF-BDC (37.5%). Systematic investigations reveal that the advantages of Bodipy@Co16-MOF-BDC in dual light-absorbing channels, robust bonding between Bodipy/Co16 clusters and efficient electron-hole separation can greatly boost photosynthesis. This work provides an ideal molecular platform for synergy between photosensitizing MOFs and chromophores by constructing high-nuclear transition-metal-based SBUs with surface-modifiable small molecules.

7.
J Transl Med ; 22(1): 358, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627718

RESUMO

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Inibidores da Angiogênese/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/tratamento farmacológico , Injeções Intravítreas , Aprendizado de Máquina , Edema Macular/complicações , Edema Macular/diagnóstico por imagem , Edema Macular/tratamento farmacológico , Radiômica , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Fatores de Crescimento do Endotélio Vascular
8.
Sci Transl Med ; 16(743): eadk5395, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630847

RESUMO

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.


Assuntos
Aprendizado Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Pessoa de Meia-Idade , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Lesões Pré-Cancerosas/patologia
9.
Int J Ophthalmol ; 17(4): 616-624, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638265

RESUMO

AIM: To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus (A. fumigatus) keratitis in mice and the role of innate and adaptive immunity in it. METHODS: Mice models of A. fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching. Subconjunctival injections of natamycin, wedelolactone, LOX-1 inhibitor (poly I) or Dectin-1 inhibitor (laminarin) were used to treat mice with A. fumigatus keratitis. Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε. We observed the corneal infection of mice under the slit lamp microscope and made a clinical score. The protein expression of CD3ε and interleukin-10 (IL-10) was determined by Western blotting. RESULTS: With the disease progresses, the degree of corneal opacity and edema augmented. In the intra-stromal injection models, CD3ε protein expression began to increase significantly on the 2nd day. However, in the scraping epithelial method models, CD3ε only began to increase on the 3rd day. After natamycin treatment, the degree of corneal inflammation in mice was significantly attenuated on the 3rd day. After wedelolactone treatment, the severity of keratitis worsened. And the amount of CD3ε protein was also reduced, compared with the control group. By inhibiting LOX-1 and Dectin-1, there was no significant difference in CD3ε production compared with the control group. After inhibiting CD3ε, corneal ulcer area and clinical score increased, and IL-10 expression was downregulated. CONCLUSION: As a pan T cell marker, CD3ε participate in the adaptive immunity of A. fumigatus keratitis in mice. In our mice models, the corneas will enter the adaptive immune stage faster. By regulating IL-10, CD3ε exerts anti-inflammatory and repairs effects in the adaptive immune stage.

10.
World J Cardiol ; 16(3): 161-167, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38576523

RESUMO

BACKGROUND: Patients with tetralogy of Fallot (TOF) often have arrhythmias, commonly being atrial fibrillation (AF). Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative hypoxemia, but the risk of complications may increase in patients with conditions such as TOF. CASE SUMMARY: We report a young male patient with a history of TOF repair who developed severe hypoxemia after radiofrequency ablation for AF and was ultimately confirmed to have a new right-to-left shunt. The patient subsequently underwent atrial septal occlusion and eventually recovered. CONCLUSION: Radiofrequency ablation may cause iatrogenic atrial septal injury; thus possible complications should be predicted in order to ensure successful treatment and patient safety.

11.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 343-349, 2024 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-38660897

RESUMO

OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.


Assuntos
Permeabilidade do Canal Arterial , Hemodinâmica , Ibuprofeno , Recém-Nascido Prematuro , Falha de Tratamento , Humanos , Ibuprofeno/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Permeabilidade do Canal Arterial/fisiopatologia , Recém-Nascido , Feminino , Fatores de Risco , Masculino , Estudos Retrospectivos , Hemodinâmica/efeitos dos fármacos , Modelos Logísticos
12.
J Colloid Interface Sci ; 667: 700-712, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38670013

RESUMO

Aqueous zinc-ion capacitors (AZICs) are considered potential energy storage devices thanks to their ultrahigh power density, high safety, and extended cycling life. Carbon-based materials widely used as cathodes in AZICs face challenges, such as inappropriate pore sizes, poor electrolyte-electrode wettability, and insufficient vacancy defects and active sites. These limitations hinder efficient energy storage capacity and long-term stability. To address these issues, the B and F co-doped hierarchical porous carbon cathode materials (BFPC) are constructed through a facile annealing treatment process. The BFPC-2//Zn device exhibited high capacities of 222.4 and 118.3 mAh g-1 at current densities of 0.2 and 10 A g-1, respectively. Notably, the BFPC-2//Zn device demonstrated long-term cycling stability with a high capacity retention of 96.9 % after 20,000 cycles at 10 A g-1. Additionally, the assembled BFPC-2 based AZICs displayed a maximum energy density of 175.8 Wh kg-1 and an ultrahigh power density of 17.3 kW kg-1. Mechanism studies revealed that the exceptional energy storage ability and charge-transfer process of the BFPC cathode are attributed to the synergistic effect of B and F heteroatoms and the coupling effect between vacancy defects and pore size. This work presents a novel design strategy by incorporating B and F active sites into hierarchical porous carbon materials, providing enhanced energy storage capabilities for practical application in AZICs.

13.
Lab Invest ; : 102069, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38670317

RESUMO

Tissue gene expression studies are impacted by biological and technical sources of variation, which can be broadly classified into wanted and unwanted variation. The latter, if not addressed, results in misleading biological conclusions. Methods have been proposed to reduce unwanted variation, such as normalization and batch correction. A more accurate understanding of all causes of variation could significantly improve the ability of these methods to remove unwanted variation while retaining variation corresponding to the biological question of interest. We used 17,282 samples from 49 human tissues in the Genotype Tissue Expression (GTEx) dataset (v8) to investigate patterns and causes of expression variation. Transcript expression was transformed to z-scores and only the most variable 2% of transcripts were evaluated and clustered based on co-expression patterns. Clustered gene sets were assigned to different biological or technical causes based on histologic appearances and metadata elements. We identified 522 variable transcript clusters (median 11 per tissue) among the samples. Of these, 63% were confidently explained, 16% were likely explained, 7% were low confidence explanations and 14% had no clear cause. Histologic analysis annotated 46 clusters. Other common causes of variability included sex, sequencing contamination, immunoglobulin diversity, and compositional tissue differences. Less common biological causes included death interval (Hardy score), disease status, and age. Technical causes included blood draw timing and harvesting differences. Many of the causes of variation in bulk tissue expression were identifiable in the Tabula Sapiens dataset of single cell expression. This is among the largest explorations of the underlying sources of tissue expression variation. It uncovered expected and unexpected causes of variable gene expression and demonstrated the utility of matched histologic specimens. It further demonstrated the value of acquiring meaningful tissue harvesting metadata elements to use for improved normalization, batch correction, and analysis of both bulk and single cell RNA-seq data.

14.
Proc Natl Acad Sci U S A ; 121(18): e2401060121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38648475

RESUMO

Electrochromic (EC) displays with electronically regulating the transmittance of solar radiation offer the opportunity to increase the energy efficiency of the building and electronic products and improve the comfort and lifestyle of people. Despite the unique merit and vast application potential of EC technologies, long-awaited EC windows and related visual content displays have not been fully commercialized due to unsatisfactory production cost, durability, color, and complex fabrication processes. Here we develop a unique EC strategy and system based on the natural host and guest interactions to address the above issues. A completely reusable and sustainable EC device has been fabricated with potential advantages of extremely low cost, ideal user-/environment friendly property, and excellent optical modulation, which is benefited from the extracted biomass EC materials and reusable transparent electrodes involved in the system. The as-prepared EC window and nonemissive transparent display also show comprehensively excellent properties: high transmittance change (>85%), broad spectra modulation covering Ultraviolet (UV), Visible (Vis) to Infrared (IR) ranges, high durability (no attenuation under UV radiation for more than 1.5 mo), low open voltage (0.9 V), excellent reusability (>1,200 cycles) of the device's key components and reversibility (>4,000 cycles) with a large transmittance change, and pleasant multicolor. It is anticipated that unconventional exploration and design principles of dynamic host-guest interactions can provide unique insight into different energy-saving and sustainable optoelectronic applications.

15.
Anal Chem ; 96(18): 7257-7264, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38664861

RESUMO

Confocal fluorescence imaging of fine structures of the cell membrane is important for understanding their biofunctions but is often neglected due to the lack of an effective method. Herein, we develop new amphiphilic rhodamine fluorescent probe RMGs in combination with basal imaging for this purpose. The probes show high signal-to-noise ratio and brightness and low internalization rate, making them suitable for imaging the fine substructures of the cell membrane. Using the representative probe RMG3, we not only observed the cell pseudopodia and intercellular nanotubes but also monitored the formation of migrasomes in real time. More importantly, in-depth imaging studies on more cell lines revealed for the first time that hepatocellular carcinoma cells secreted much more adherent extracellular vesicles than other cell lines, which might serve as a potential indicator of liver cells. We believe that RMGs may be useful for investigating the fine structures of the cell membrane.


Assuntos
Membrana Celular , Corantes Fluorescentes , Rodaminas , Corantes Fluorescentes/química , Rodaminas/química , Humanos , Membrana Celular/química , Imagem Óptica , Microscopia Confocal/métodos , Tensoativos/química
16.
J Nephrol ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512376

RESUMO

Vascular calcification is a common complication in patients with chronic kidney disease (CKD) and is strongly associated with an increased risk of cardiovascular events and all-cause mortality. Calciphylaxis is a specific and life-threatening manifestation of vascular calcifications that usually affects individuals with advanced kidney function impairment or those undergoing dialysis. Currently, the treatment of vascular calcification and calciphylaxis in CKD lacks approved treatments and focuses on controlling risk factors. SNF472, the intravenous formulation of myo-inositol hexaphosphate, is a novel vascular calcification inhibitor currently undergoing phase 3 clinical trials, demonstrating its ability to directly inhibit the formation of calcium and phosphorus crystals, thereby blocking the production and deposition of ectopic calcium. The efficacy and safety of SNF472 in inhibiting vascular calcification have been confirmed in recent clinical studies. This review summarizes the results of studies related to SNF472 to provide a comprehensive overview of its mechanism of action, efficacy, safety, and ongoing clinical studies.

17.
Org Lett ; 26(11): 2212-2217, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38452132

RESUMO

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.


Assuntos
Azidas , Benzeno , Ciclização , Aminas , DNA
18.
Sci Total Environ ; 923: 171475, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38453063

RESUMO

Climbazole is an azole biocide that has been widely used in formulations of personal care products. Climbazole can cause developmental toxicity and endocrine disruption as well as gut disturbance in aquatic organisms. However, the mechanisms behind gut toxicity induced by climbazole still remain largely unclear in fish. Here, we evaluate the gut effects by exposing grass carp (Ctenopharyngodon idella) to climbazole at levels ranging from 0.2 to 20 µg/L for 42 days by evaluating gene transcription and expression, biochemical analyses, correlation network analysis, and molecular docking. Results showed that climbazole exposure increased cyp1a mRNA expression and ROS level in the three treatment groups. Climbazole also inhibited Nrf2 and Keap1 transcripts as well as proteins, and suppressed the transcript levels of their subordinate antioxidant molecules (cat, sod, and ho-1), increasing oxidative stress. Additionally, climbazole enhanced NF-κB and iκBα transcripts and proteins, and the transcripts of NF-κB downstream pro-inflammatory factors (tnfα, and il-1ß/6/8), leading to inflammation. Climbazole increased pro-apoptosis-related genes (fadd, bad1, and caspase3), and decreased anti-apoptosis-associated genes (bcl2, and bcl-xl), suggesting a direct reaction to apoptosis. The molecular docking data showed that climbazole could form stable hydrogen bonds with CYP1A. Mechanistically, our findings suggested that climbazole can induce inflammation and oxidative stress through CYP450s/ROS/Nrf2/NF-κB pathways, resulting in cell apoptosis in the gut of grass carp.


Assuntos
Carpas , Suplementos Nutricionais , Imidazóis , Animais , Suplementos Nutricionais/análise , Dieta , NF-kappa B , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Imunidade Inata , Azóis/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Inflamação/induzido quimicamente , Inflamação/veterinária , Estresse Oxidativo , Apoptose , Carpas/metabolismo
19.
Bull Environ Contam Toxicol ; 112(4): 51, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556558

RESUMO

Esketamine (ESK) is the S-enantiomer of ketamine racemate (a new psychoactive substance) that can result in illusions, and alter hearing, vision, and proprioception in human and mouse. Up to now, the neurotoxicity caused by ESK at environmental level in fish is still unclear. This work studied the effects of ESK on behaviors and transcriptions of genes in dopamine and GABA pathways in zebrafish larvae at ranging from 12.4 ng L- 1 to 11141.1 ng L- 1 for 7 days post fertilization (dpf). The results showed that ESK at 12.4 ng L- 1 significantly reduced the touch response of the larvae at 48 hpf. ESK at 12.4 ng L- 1 also reduced the time and distance of larvae swimming at the outer zone during light period, which implied that ESK might potentially decrease the anxiety level of larvae. In addition, ESK increased the transcription of th, ddc, drd1a, drd3 and drd4a in dopamine pathway. Similarly, ESK raised the transcription of slc6a1b, slc6a13 and slc12a2 in GABA pathway. This study suggested that ESK could affect the heart rate and behaviors accompanying with transcriptional alterations of genes in DA and GABA pathways at early-staged zebrafish, which resulted in neurotoxicity in zebrafish larvae.


Assuntos
Dopamina , Ketamina , Humanos , Animais , Camundongos , Dopamina/metabolismo , Dopamina/farmacologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Ketamina/metabolismo , Ketamina/farmacologia , Larva , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia
20.
Hum Brain Mapp ; 45(5): e26672, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38549429

RESUMO

Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to explore how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child interbrain synchrony emerged primarily within the theta oscillations and the frontal lobe, which highly correlated with children's attachment to their mothers (self-reported by mothers). When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor's oscillations, which was related to the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how interbrain synchrony is established and dynamically changed during mother-child reciprocal interaction.


Assuntos
Encéfalo , Mães , Feminino , Humanos , Mães/psicologia , Encéfalo/diagnóstico por imagem , Lobo Frontal , Relações Mãe-Filho/psicologia , Diencéfalo
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