RESUMO
The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 µg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 µg and 20 µg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.
RESUMO
BACKGROUND: The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH. METHODS: We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages. RESULTS: We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation. CONCLUSION: We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K-AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.
Assuntos
Polaridade Celular , Fator 4 de Crescimento de Fibroblastos , Hepatite Autoimune , Inflamação , Macrófagos , Camundongos Endogâmicos C57BL , Animais , Feminino , Humanos , Masculino , Camundongos , Polaridade Celular/efeitos dos fármacos , Modelos Animais de Doenças , Fator 4 de Crescimento de Fibroblastos/metabolismo , Hepatite Autoimune/patologia , Hepatite Autoimune/metabolismo , Inflamação/patologia , Fígado/patologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Antibiotic resistome has emerged as a global threat to public health. However, gestational antibiotic resistome and potential link with adverse pregnancy outcomes remains poorly understood. Our study reports for the first time an association between gut antibiotic resistome during early pregnancy and the risk of gestational diabetes mellitus (GDM) based on a prospective nested case-control cohort including 120 cases and 120 matched controls. A total of 214 antibiotic resistance gene (ARG) subtypes belonging to 17 ARG types were identified in > 10 % fecal samples collected during each trimester. The data revealed dynamic profiles of gut antibiotic resistome through pregnancy, and significant positive associations between selected features (i.e., ARG abundances and a GDM-ARG score which is a new feature characterizing the association between ARGs and GDM) of gut antibiotic resistome during early pregnancy and GDM risk as well as selected endogenous metabolites. The findings demonstrate ubiquitous presence of ARGs in pregnant women and suggest it could constitute an important risk factor for the development of GDM.
RESUMO
Urinary analysis of exogenous and endogenous molecules constitutes an efficient, noninvasive approach to evaluate human health status. However, the exposome characterization of urinary molecules remains extremely challenging with current techniques. Herein, we develop an ExpoNano strategy based on hyper-cross-linked polymers (HCPs) to achieve ultrahigh-throughput measurement of exo/endogenous molecules in urine. The strategy includes a simple trapping-detrapping procedure (15 min) with HCPs in enzymatically treated urine, followed by mass spectrometer determination. Molecules that can be determined by ExpoNano have a wide range of molecular weight (75-837 Da) and Log Kow (octanol-water partition coefficient; -9.86 to 10.56). The HCPs can be repeatedly used five times without decreasing the trapping efficiency. Application of ExpoNano in a biomonitoring study revealed a total of 63 environmental chemicals detected in >50% of the urine pools collected from Chinese adults living in 13 cities, with a median concentration of 0.026-47 ng/mL, while nontargeted analysis detected an additional 243 exogenous molecules. Targeted and nontargeted analysis also detected 926 endogenous molecules in pooled urine. Collectively, the ExpoNano strategy demonstrates unique advantages over traditional urine analysis approaches, including a wide range of analytes, satisfactory trapping efficiency, high simplicity and reusability, and extremely reduced time demand and financial cost.
Assuntos
Monitoramento Biológico , Polímeros , Humanos , Polímeros/química , Monitoramento Biológico/métodos , Expossoma , Monitoramento Ambiental/métodos , AdultoRESUMO
Due to the serious detrimental impact on human health, antibiotic pollution particularly tetracyclines residues has become a serious problem. Herein, a multiple response fluorescent probe consisted of dual-emission carbon dots and Eu3+ (D-CDs@Eu3+) is designed for the determination and discrimination of tetracyclines (TCs). Specifically, the carboxyl and amidogen group of dual-emission carbon dots (D-CDs) can coordinate with Eu3+ to form the D-CDs@Eu3+. Upon adding TCs, the fluorescence intensities of D-CDs at 405 nm and 495 nm are quenched due to inner filter effect (IFE) and the localization of fluorescence resonance energy transfer (L-FRET) between the D-CDs@Eu3+ and TC. Simultaneously, the D-CDs@Eu3+ may chelate with TCs to enhance the occurrence of antenna effect, while the characteristic peaks of Eu3+ at 590 nm and 615 nm are enhanced. On these bases, the TCs detection is achieved with low detection limits from 46.7 to 72.0 nM. Additionally, through the distinct efficiencies of L-FRET, the discrimination of TCs is achieved. Moreover, a novel centrifugated lateral flow assay strips (CLFASs) device is developed by integrating the D-CDs@Eu3+, lateral flow assay strips and smartphone using RGB variations for TCs detection, achieving remarkable recoveries (98.6-103.7 %) in real samples. Therefore, this CLFASs device provides a reliable approach for the TCs detection, demonstrating potential applications.
RESUMO
Objectives: To determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR). Methods: Genetic variants significantly associated with lifestyle behaviours, abdominal obesity, generalized obesity and diabetic microvascular complications were extracted from the UK Biobank (UKB) and FinnGen. The inverse variance weighted (IVW) method was regarded as the primary method. The main results were presented in odds ratio (OR) per standard deviation (SD) increase, and a series of sensitivity analyses were also conducted to validate the stability of the results. Results: There was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04-1.30; p = 0.01). All of the indicators representing abdominal obesity had a statistically significant causal association with diabetic microvascular complications. Concerning generalized obesity, there were significant causal associations of body mass index (BMI) on diabetic nephropathy (OR = 1.92; 95%CI: 1.58-2.33; p < 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15-1.40; p < 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95-3.45; p < 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications. Conclusion: Our findings suggested that smoking has a genetically causal association with the development of diabetic retinopathy rather than diabetic nephropathy and diabetic neuropathy. In addition, both abdominal obesity and generalized obesity are risk factors for diabetic microvascular complications. To note, abdominal obesity represented by waist circumference (WC) is the most significant risk factor.
RESUMO
Continuous emission monitoring system is commonly employed to monitor NOx emissions in municipal solid waste incineration (MSWI) processes. However, it still encounters the challenges of regular maintenance and measurement lag. These issues significantly impact the accurate and stable control of NOx emissions. Therefore, developing a soft NOx emission sensor to complement hardware monitoring becomes imperative. Considering data noise, dynamic nonlinearity, time series characteristics and volatility in the MSWI process, this article introduces a soft sensor model for NOx emission prediction utilizing the complete ensemble empirical mode decomposition adaptive noise (CEEMDAN)-wavelet threshold (WT) method and bidirectional long short-term memory (Bi-LSTM). Firstly, the original data signal is decomposed into a group of intrinsic mode functions (IMFs) using the CEEMDAN. Subsequently, the WT processes the high-frequency IMFs that are noise-dominant. Then, all IMFs are reconstructed to obtain the denoized signal. Finally, the Bi-LSTM model is employed to predict NOx emissions. Compared to conventional modelling approaches, the model proposed in this article demonstrates the best predictive performance. The mean absolute percentage error, root-mean-squared error and average absolute error on the test set of the proposed model are 3.75%, 5.34 mg m-3 and 4.34 mg m-3, respectively. The proposed model provides a new method to soft sensing NOx emissions. It holds significant practical value for precise and stable monitoring of NOx emissions in MSWI processes and provides a reference for research on modelling key process parameters.
RESUMO
BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.
RESUMO
BACKGROUND: Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear. METHODS: This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed. RESULTS: Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively. CONCLUSIONS: The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02633358.
Assuntos
Colesterol , Ácido Láctico , Parada Cardíaca Extra-Hospitalar , Humanos , Masculino , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Colesterol/sangue , Prognóstico , Ácido Láctico/sangue , Idoso , Sobreviventes , Albumina Sérica/análise , Albumina Sérica/metabolismo , Biomarcadores/sangueRESUMO
Photon blockade (PB) is one of the effective methods to generate single-photon sources. In general, both the PB effect with the significant sub-Poissonian statistics and a large mean photon number are desired to guarantee the brightness and the purity of single-photon sources. Here, we propose to obtain the PB effect at the cavity dark-state polariton (DSP) using a cavity Λ-type electromagnetically induced transparency (EIT) system with and without the two-photon dissipation (TPD). In the Raman resonance case, the PB effect at the DSP could by realized by using the TPD process in the weak or intermediate coupling regime, which accompanies with near unity transmission, i.e., very high photon occupation. In the slightly detuned Raman resonance case, the excited state is induced into the components of the DSP, and the atomic dissipation path is added into the two-photon excitation paths. Thus, the PB effect at the DSP can be obtained due to the quantum destructive interference (QDI) in the strong coupling regime, which can be further enhanced using the TPD process. Due to the slight detuning, the PB effect still remains high photon occupation and has highly tunability. This work provides an alternative way to manipulate the photon statistics by the PB effect and has potential applications in generating single-photon sources with high brightness and purity.
RESUMO
Limited proteolysis, CaCl2 and carboxymethyl cellulose (CMC) have individually demonstrated ability to increase the gel strength of laboratory-extracted plant proteins. However, the syneresis effects of their combination on the gelling capacity of commercial plant protein remains unclear. This was investigated by measuring the rheological property, microstructure and protein-protein interactions of gels formed from Alcalase hydrolyzed or intact pea proteins in the presence of 0.1 % CMC and 0-25 mM CaCl2. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed the molecular weight of pea protein in the mixture were < 15 kDa after hydrolysis. The hydrolysates showed higher intrinsic fluorescence intensity and lower surface hydrophobicity than the intact proteins. Rheology showed that the storage modulus (G') of hydrolyzed pea protein (PPH)-based gels sightly decreased compared to those of native proteins. 5-15 mM CaCl2 increased the G' for both PP and PPH-based gels and decreased the strain in the creep-recovery test. Scanning electron microscopy (SEM) showed the presence of smaller protein aggregates in the PPH-based gels compared to PP gels and the gel network became denser, and more compact and heterogenous in the presence of 15 and 25 mM CaCl2. The gel dissociation assay revealed that hydrophobic interactions and hydrogen bonds were the dominant forces to maintain the gel structure. In vitro digestion showed that the soluble protein content in PPH-based gels was 10 â¼ 30 % higher compared to those of the PP counterpart. CaCl2 addition reduced protein digestibility with a concentration dependent behavior. The results obtained show contrasting effects of limited proteolysis and CaCl2 on the gelling capacity and digestibility of commercial pea proteins. These findings offer practical guidelines for developing pea protein-based food products with a balanced texture and protein nutrition through formulation and enzymatic pre-treatment.
Assuntos
Cloreto de Cálcio , Carboximetilcelulose Sódica , Géis , Proteínas de Ervilha , Proteólise , Reologia , Cloreto de Cálcio/química , Proteínas de Ervilha/química , Carboximetilcelulose Sódica/química , Géis/química , Interações Hidrofóbicas e Hidrofílicas , Digestão , Pisum sativum/química , Microscopia Eletrônica de Varredura , Hidrólise , Eletroforese em Gel de PoliacrilamidaRESUMO
Photocatalysis is one of the most promising pathways to relieve the environmental contamination caused by the rapid development of modern technology. In this work, we demonstrate a green manufacturing process for the 3D/3D rod-shaped bamboo charcoal/Bi2WO6 photocatalyst (210BC-BWO) by controlled carbonization temperature. A series of morphology characterization and properties investigations (XRD, SEM, UV-vis DRS, transient photocurrent response, N2 absorption-desorption isotherms) indicate a 210BC-BWO photocatalyst with higher charge separation efficiency, larger surface area, and better adsorption capacity. The excellent photocatalytic performance was evaluated by degrading rhodamine B (RhB) (98.5%), tetracycline hydrochloride (TC-HCl) (77.1%), and H2 evolution (2833 µmol·g-1·h-1) coupled with furfuryl alcohol oxidation (3097 µmol·g-1·h-1) under visible light irradiation. In addition, the possible mechanisms for degradation of organic pollutants, H2 evolution, and furfuryl alcohol oxidation were schematically investigated, which make it possible to exert photocatalysis by increasing the active radical. This study shows that the combination of bamboo charcoal and bismuth tungstate can be a powerful photocatalyst that rationally combines H2 evolution coupled with furfuryl alcohol oxidation and degradation of pollutants.
RESUMO
OBJECTIVES: This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. METHODS: The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test. RESULTS: The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001). CONCLUSIONS: The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.
RESUMO
Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87⯵g/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30⯵g/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.
Assuntos
Molibdênio , Molibdênio/urina , Molibdênio/toxicidade , Molibdênio/análise , Humanos , China/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/análise , Cistatina C , Medição de Risco , Poluentes Ambientais/urina , Poluentes Ambientais/análise , Adulto Jovem , Teorema de Bayes , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/induzido quimicamente , Idoso , Indústria Química , Rim/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacosRESUMO
Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.
Assuntos
Alcaloides , Corydalis , Metabolômica , Raízes de Plantas , Corydalis/genética , Corydalis/metabolismo , Metabolômica/métodos , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Alcaloides/biossíntese , Alcaloides/metabolismo , Transcriptoma , Benzilisoquinolinas/metabolismo , Regulação da Expressão Gênica de Plantas , Vias Biossintéticas/genética , Perfilação da Expressão Gênica , Alcaloides de Berberina/metabolismo , MetabolomaRESUMO
A smarter city should be a safer city. Nighttime safety in metropolitan areas has long been a global concern, particularly for large cities with diverse demographics and intricate urban forms, whose citizens are often threatened by higher street-level crime rates. However, due to the lack of night-time urban appearance data, prior studies based on street view imagery (SVI) rarely addressed the perceived night-time safety issue, which can generate important implications for crime prevention. This study hypothesizes that night-time SVI can be effectively generated from widely existing daytime SVIs using generative AI (GenAI). To test the hypothesis, this study first collects pairwise day-and-night SVIs across four cities diverged in urban landscapes to construct a comprehensive day-and-night SVI dataset. It then trains and validates a day-to-night (D2N) model with fine-tuned brightness adjustment, effectively transforming daytime SVIs to nighttime ones for distinct urban forms tailored for urban scene perception studies. Our findings indicate that: (1) the performance of D2N transformation varies significantly by urban-scape variations related to urban density; (2) the proportion of building and sky views are important determinants of transformation accuracy; (3) within prevailed models, CycleGAN maintains the consistency of D2N scene conversion, but requires abundant data. Pix2Pix achieves considerable accuracy when pairwise day-and-night-night SVIs are available and are sensitive to data quality. StableDiffusion yields high-quality images with expensive training costs. Therefore, CycleGAN is most effective in balancing the accuracy, data requirement, and cost. This study contributes to urban scene studies by constructing a first-of-its-kind D2N dataset consisting of pairwise day-and-night SVIs across various urban forms. The D2N generator will provide a cornerstone for future urban studies that heavily utilize SVIs to audit urban environments.
RESUMO
Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.
Assuntos
Poliestirenos , Reprodução , Triclosan , Poluentes Químicos da Água , Peixe-Zebra , Animais , Triclosan/toxicidade , Poliestirenos/toxicidade , Feminino , Masculino , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Fatores SexuaisRESUMO
The induction of viable but nonculturable (VBNC) bacteria with cellular integrity and low metabolic activity by chemical disinfection causes a significant underestimation of potential microbiological risks in drinking water. Herein, a physical Co3O4 nanowire-assisted electroporation (NW-EP) was developed to induce cell damage via the locally enhanced electric field over nanowire tips, potentially achieving effective inhibition of VBNC cells as compared with chemical chlorination (Cl2). NW-EP enabled over 5-log removal of culturable cell for various G+/G- bacteria under voltage of 1.0 V and hydraulic retention time of 180 s, and with â¼3-6 times lower energy consumption than Cl2. NW-EP also achieved much higher removals (â¼84.6 % and 89.5 %) of viable Bacillus cereus (G+) and Acinetobacter schindleri (G-) via generating unrecoverable pores on cell wall and reversible/irreversible pores on cell membrane than Cl2 (â¼28.6 % and 41.1 %) with insignificant cell damage. The residual VBNC bacteria with cell wall damage and membrane pore resealing exhibited gradual inactivation by osmotic stress, leading to â¼99.8 % cell inactivation after 24 h storage (â¼59.4 % for Cl2). Characterizations of cell membrane integrity and cell morphology revealed that osmotic stress promoted cell membrane damage for the gradual inactivation of VBNC cells during storage. The excellent adaptability of NW-EP for controlling VBNC cells in DI, tap and lake waters suggested its promising application potentials for drinking water, such as design of an external device on household taps.