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1.
Ecotoxicol Environ Saf ; 277: 116371, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663196

RESUMO

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.

2.
Huan Jing Ke Xue ; 45(5): 2507-2515, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629516

RESUMO

To study the long-term variation in ozone (O3) pollution in Sichuan Basin,the spatiaotemporal distribution of O3 concentrations during 2017 to 2020 was analyzed using ground-level O3 concentration data and meteorological observation data from 18 cities in the basin. The dominant meteorological factors affecting the variation in O3 concentration were screened out,and a prediction model between meteorological factors and O3 concentration was constructed based on a random forest model. Finally,a prediction analysis of O3 pollution in the Sichuan Basin urban agglomeration during 2020 was carried out. The results showed that:① O3 concentrations displayed a fluctuating trend during the period from 2017 to 2020,with a downward trend in 2019 and a rebound in 2020. ② The fluctuating trend of O3 concentration was significantly influenced by relative humidity,daily maximum temperature,and sunshine hours,whereas wind speed,air pressure,and precipitation had less impact. The linear relationships between meteorological factors were different. Air pressure was negatively correlated with other meteorological factors,whereas the remaining meteorological factors had a positive correlation. ③ The goodness of fit statistics (R2) between the predicted and actual values of the O3 prediction model constructed based on random forest demonstrated a strong predictive performance and ability to accurately forecast the long-term daily variations in O3 concentration. The random forest O3 prediction model exhibited excellent stability and generalization capability. ④ The prediction analysis of O3 concentrations in 18 cities in the basin showed that the explanation rate of variables in the prediction model reached over 80% in all cities (except Ya'an),indicating that the random forest model predicted the trend of O3 concentration accurately.

3.
Chem Sci ; 15(12): 4349-4357, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516075

RESUMO

Metallenes, intermetallic compounds, and porous nanocrystals are the three types of most promising advanced nanomaterials for practical fuel cell devices, but how to integrate the three structural features into a single nanocrystal remains a huge challenge. Herein, we report an efficient one-step method to construct freestanding mesoporous Mo-doped PtBi intermetallic metallene superstructures (denoted M-PtBiMo IMSs) as highly active and stable ethylene glycol oxidation reaction (EGOR) catalysts. The materials retained their catalytic performance, even in complex direct ethylene glycol fuel cells (DEGFCs). The M-PtBiMo IMSs showed EGOR mass and specific activities of 24.0 A mgPt-1 and 61.1 mA cm-2, respectively, which were both dramatically higher than those of benchmark Pt black and Pt/C. In situ infrared spectra showed that ethylene glycol underwent complete oxidation via a 10-electron CO-free pathway over the M-PtBiMo IMSs. Impressively, M-PtBiMo IMSs demonstrated a much higher power density (173.6 mW cm-2) and stability than Pt/C in DEGFCs. Density functional theory calculations revealed that oxophilic Mo species promoted the EGOR kinetics. This work provides new possibilities for designing advanced Pt-based nanomaterials to improve DEGFC performance.

4.
Front Pharmacol ; 15: 1324892, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487164

RESUMO

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD.

5.
Harmful Algae ; 133: 102586, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38485436

RESUMO

The red Noctiluca scintillans (RNS) blooms often break out near Pingtan Island, in the northern Taiwan Strait from April to June. It is essential to gain insights into their formation mechanism to predict and provide early warnings for these blooms. Previous studies and observations showed that RNS blooms are the most likely to occur when winds are weak and shifting in direction. To explore this phenomenon further, we employed a high-resolution coastal model to investigate the hydrodynamics influencing RNS blooms around Pingtan Island from April to June 2022. The model results revealed that seawater exhibited weak circulation but strong stratification during RNS blooms. Residence time were examined through numerical experiments by releasing passive neutrally buoyant particles in three bays of Pingtan Island. The results showed a significantly longer residence time during RNS blooms, indicating reduced flushing capabilities within the bays, which could give RNS a stable environment to multiply and aggregate. This hydrodynamic condition provided a favorable basis for RNS blooms breakout near Pingtan Island. The shifts and weakening of the prevailing northeast wind contributed substantially to weakening the flow field around Pingtan Island and played a crucial role in creating the hydrodynamics conducive to RNS blooms. Our study offers fresh insights into the mechanisms underpinning RNS blooms formation near Pingtan Island, providing a vital framework for forecasting RNS blooms in this region.


Assuntos
Dinoflagelados , Monitoramento Ambiental , Taiwan , Monitoramento Ambiental/métodos , Estações do Ano , Surtos de Doenças
6.
J Colloid Interface Sci ; 662: 208-217, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38350344

RESUMO

Exploring low-cost, high-activity, and structurally stable nonprecious metal electrocatalysts for sluggish oxygen evolution reaction (OER) is paramount for water electrolysis. Herein, we successfully prepare a novel Fe,Co-CeO2/CeF3@MXene heterostructure with Fe-Co dual active sites and oxygen vacancies for alkaline OER using an energy-free consumption co-deposition method. Impressively, Fe,Co-CeO2/CeF3@MXene achieves an ultralow overpotential of 192 mV and a long-term stability of 110 h at 10 mA cm-2 without structural changes, thereby outperforming the commercial IrO2 (345 mV). In addition, Fe,Co-CeO2/CeF3@MXene exhibits much superior activity (271 mV) and durability to IrO2 (385 mV) in the real seawater OER. Wind- and solar energy-assisted water electrolysis devices show their promising prospects for sustainable green hydrogen production. Characterization techniques and theoretical calculations reveal that the Fe,Co co-implanted CeO2/CeF3 heterostructure effectively degrades the energy barrier of the OER and optimizes the adsorption strength of *OH, *O, and *OOH intermediates. It exhibits the dual coupling mechanism of the adsorbed evolution and lattice oxygen mechanisms, which synergistically improves the OER performance. This work provides a facile and efficacious strategy for synthesizing a new class of heterostructures to achieve significant enhancement in the activity and stability of OER catalysts.

7.
J Mol Model ; 30(3): 75, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376546

RESUMO

CONTEXT: To lessen the impact of the dangerous metal Cr, this paper applies the first principles to investigate the adsorption behavior and photoelectric properties of GaS on Cr. The effects of doped GaS on Cr adsorption behavior are investigated with four GaS systems, which are pure, boron (B)-doped, nitrogen (N)-doped, and oxygen (O)-doped, in order to maximize the characteristics of GaS for use in novel sectors, to obtain understanding of the impact of doping on the electronic structure and optical properties of GaS adsorption of Cr, as well as to promote the development of the material. Four GaS adsorbed Cr systems, pure, B-doped, N-doped, and O-doped, are optimized, and the optimized results show that the stable adsorption position of Cr on both pure and doped GaS is the top position of Ga atoms, whereas doped elements B, N, and O can promote the adsorption of Cr on GaS, and the order of the strength of this promotion is B > N > O. METHOD: In this paper, molecular simulation calculations and analyses using the CASTEP module in the software Materials Studio are performed to simulate the structure optimization of GaS-adsorbed Cr materials doped with B, N, and O atoms by using the generalized gradient approximation (GGA) plane-wave pseudopotential approach [1] and the Perdew-Burke-Ernzerhof (PBE) generalized function [2]. From the convergence test, it is reasonable to set the K-point network to 4 × 4 × 1 and the truncation energy to 500 eV [3]. In this paper, a 3 × 3 × 1 supercell structure with 18 S atoms and 18 Ga atoms is selected. The convergence value of the iterative accuracy is 1.0e - 5 eV/atom, and all the atomic forces are less than 0.02 eV/Å. A vacuum layer of 16 Å is also set in the C direction to avoid interlayer interactions of GaS. First, we optimize the geometry of the model and then analyze the nature of the adsorption energy and electronic structure corresponding to the model.

8.
Drug Metab Dispos ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302428

RESUMO

The mammalian gut microbiota plays diverse and essential roles in modulating host physiology. Key mediators determining the outcome of the microbiota-host interactions are the small molecule metabolites produced by the gut microbiota. The liver is the organ massively exposed to gut microbial metabolites, and it serves as the nexus, maintaining healthy interactions between the gut microbiota and host. At the same time, the liver is the primary target of harmful gut microbial metabolites. This review provides an up-to-date list of gut microbial metabolites identified to increase or decrease host susceptibility to APAP-induced liver injury. Signaling pathways and molecular factors involved in the progression of APAP-induced hepatotoxicity are well-established, and we propose that the mouse model of APAP-induced hepatotoxicity serves as an excellent system for uncovering gut microbial metabolites of previously unknown function. Moreover, we envision that gut microbial metabolites identified to alter APAP-induced hepatotoxicity likely have broader implications in other liver diseases. Significance Statement This review provides an overview of recent discoveries from investigating whether and how the gut microbiota modulates the host susceptibility to APAP-induced liver injury. It focuses on the roles of gut bacterial small molecule metabolites as mediators of the interaction between the gut microbiota and the liver. It also illustrates the utility of APAP-induced liver injury as a model to identify gut microbial metabolites with biological function.

10.
medRxiv ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38405849

RESUMO

Background: Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and end-organ damage such as proteinuria. PE poses a significant threat to women's long-term health, including an increased risk of cardiovascular and renal diseases. Most previous studies have been hypothesis-based, potentially overlooking certain significant complications. This study conducts a comprehensive, non-hypothesis-based analysis of PE-complicated diagnoses after pregnancies using multiple large-scale electronic health records (EHR) datasets. Method: From the University of Michigan (UM) Healthcare System, we collected 4,348 PE patients for the cases and 27,377 patients with pregnancies not complicated by PE or related conditions for the controls. We first conducted a non-hypothesis-based analysis to identify any long-term adverse health conditions associated with PE using logistic regression with adjustments to demographics, social history, and medical history. We confirmed the identified complications with UK Biobank data which contain 443 PE cases and 14,870 non-PE controls. We then conducted a survival analysis on complications that exhibited significance in more than 5 consecutive years post-PE. We further examined the potential racial disparities of identified complications between Caucasian and African American patients. Findings: Uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity exhibited significantly increased risks whereas hypothyroidism showed decreased risks, in 5 consecutive years after PE in the UM discovery data. UK Biobank data confirmed the increased risks of uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity. Further survival analysis using UM data indicated significantly increased risks in uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity, and significantly decreased risks in hypothyroidism. There exist racial differences in the risks of developing hypertension and hypothyroidism after PE. PE protects against hypothyroidism in African American postpartum women but not Cacausians; it also increases the risks of uncomplicated hypertension but less severely in African American postpartum women as compared to Cacausians. Interpretation: This study addresses the lack of a comprehensive examination of PE's long-term effects utilizing large-scale EHR and advanced statistical methods. Our findings underscore the need for long-term monitoring and interventions for women with a history of PE, emphasizing the importance of personalized postpartum care. Notably, the racial disparities observed in the impact of PE on hypertension and hypothyroidism highlight the necessity of tailored aftercare based on race.

11.
Science ; 383(6685): eadj2609, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38305684

RESUMO

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Açúcares , Percepção Gustatória , Paladar , Animais , Paladar/fisiologia , Percepção Gustatória/fisiologia , Drosophila melanogaster/fisiologia , Proteínas de Drosophila/química , Conformação Proteica
12.
ACS Nano ; 18(4): 3234-3250, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38214975

RESUMO

A brain-targeting nanodelivery system has been a hot topic and has undergone rapid progression. However, due to various obstacles such as the intestinal epithelial barrier (IEB) and the blood-brain barrier (BBB), few nanocarriers can achieve brain-targeting through oral administration. Herein, an intelligent oral brain-targeting nanoparticle (FTY@Man NP) constructed from a PLGA-PEG skeleton loaded with fingolimod (FTY) and externally modified with mannose was designed in combination with a glucose control strategy for the multitarget treatment of Alzheimer's disease (AD). The hydrophilic and electronegative properties of the nanoparticle facilitated its facile penetration through the mucus barrier, while the mannose ligand conferred IEB targeting abilities to the nanoparticle. Subsequently, glycemic control allowed the mannose-integrated nanoparticle to hitchhike the glucose transporter 1 (GLUT1) circulation across the BBB. Finally, the released FTY modulated the polarity of microglia from pro-inflammatory M1 to anti-inflammatory M2 and normalized the activated astrocyte, enhancing the clearance of toxic protein Amyloid-ß (Aß) while alleviating oxidative stress and neuroinflammation. Notably, both in vitro and in vivo results have consistently demonstrated that the oral administration of FTY@Man NP could effectively traverse the multiple barriers, thereby exerting significant therapeutic effects. This breakthrough holds the promise of realizing a highly effective orally administered treatment for AD.


Assuntos
Doença de Alzheimer , Nanopartículas , Humanos , Doença de Alzheimer/tratamento farmacológico , Transportador de Glucose Tipo 1/metabolismo , Manose , Barreira Hematoencefálica/metabolismo , Peptídeos beta-Amiloides/metabolismo
13.
Eye (Lond) ; 38(1): 132-137, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37380787

RESUMO

PURPOSE: To compare the performance of Barrett toric calculator incorporated with measured posterior corneal astigmatism (PCA) derived from IOL Master 700 and Pentacam HR versus predicted PCA. METHODS: The predicted residual astigmatism using Barrett toric IOL calculator with predicted PCA, measured PCA from IOL Master 700 and measured PCA from Pentacam were calculated with the preoperative keratometry and intended IOL axis with modification. The vector analysis was performed to calculate the mean absolute prediction error (MAE), the centroid of the prediction error and the percentage of eyes with a prediction error within ±0.50 D, ±0.75 D, and ±1.00 D. RESULTS: In 57 eyes of 57 patients with mean age of 70.42 ± 10.75 years, the MAE among the three calculation methods were 0.59 ± 0.38 D (Predicted PCA), 0.60 ± 0.38 D (Measured PCA from IOL Master 700) and 0.60 ± 0.36 D (Measured PCA from Pentacam) with no significant difference, either in the whole sample, the WTR eyes and the ATR eyes (F = 0.078, 0.306 and 0.083, p = 0.925, 0.739 and 0.920, respectively). Measured PCA obtained from IOL Master 700 resulted in one level reduction (from Tn to Tn-1) in 49.12% eyes in cylindrical model selection, while measured PCA obtained from Pentacam resulted in one level reduction of toric model selection in 18.18% eyes. CONCLUSION: The present study suggested that the incorporation of measured PCA values derived from IOL Master 700 and Pentacam produce comparable clinical outcome with the predicted PCA mode in Barrett toric calculator.


Assuntos
Astigmatismo , Doenças da Córnea , Lentes Intraoculares , Facoemulsificação , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Implante de Lente Intraocular/métodos , Refração Ocular , Acuidade Visual , Astigmatismo/diagnóstico , Astigmatismo/cirurgia , Tomografia de Coerência Óptica , Biometria/métodos , Córnea , Doenças da Córnea/cirurgia , Estudos Retrospectivos
14.
J Craniofac Surg ; 35(1): e102-e103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37983056

RESUMO

It is rare that cavernous sinus complications are caused by maxillary sinus lesions because the locations of these lesions are some distant from each other. The authors describe an unusual presentation that the primary lesion was located in the maxillary sinus and triggered cavernous sinus syndrome and optic nerve symptoms. The most likely possibility was that the infection traveled retrograde along the vascular plexus. Removal of maxillary sinus lesions and establishment ventilation may achieve source control.


Assuntos
Seio Cavernoso , Sinusite Maxilar , Micoses , Sinusite , Humanos , Sinusite Maxilar/diagnóstico por imagem , Sinusite Maxilar/cirurgia , Sinusite/complicações , Sinusite/diagnóstico por imagem , Sinusite/terapia , Micoses/complicações , Seio Cavernoso/diagnóstico por imagem , Seio Cavernoso/patologia , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia
15.
Stem Cells Transl Med ; 13(3): 255-267, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38159248

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have been widely studied to alleviate acute lung injury (ALI) due to their paracrine function. However, the microenvironment of inflammatory outbreaks significantly restricted the factors secreted from MSCs like keratinocyte growth factor (KGF). KGF is a growth factor with tissue-repaired ability. Is there a better therapeutic prospect for MSCs in combination with compounds that promote their paracrine function? Through compound screening, we screened out isoxazole-9 (ISX-9) to promote MSCs derived KGF secretion and investigated the underlying mechanisms of action. METHODS: Compounds that promote KGF secretion were screened by a dual-luciferase reporter gene assay. The TMT isotope labeling quantitative technique was used to detect the differential proteins upon ISX-9 administrated to MSCs. The expressions of NGFR, ERK, TAU, and ß-catenin were detected by Western blot. In the ALI model, we measured the inflammatory changes by HE staining, SOD content detection, RT-qPCR, immunofluorescence, etc. The influence of ISX-9 on the residence time of MSCs transplantation was explored by optical in vivo imaging. RESULTS: We found out that ISX-9 can promote the expression of KGF in MSCs. ISX-9 acted on the membrane receptor protein NGFR, upregulated phosphorylation of downstream signaling proteins ERK and TAU, downregulated phosphorylation of ß-catenin, and accelerated ß-catenin into the nucleus to further increase the expression of KGF. In the ALI model, combined ISX-9 with MSCs treatments upgraded the expression of KGF in the lung, and enhanced the effect of MSCs in reducing inflammation and repairing lung damage compared with MSCs alone. CONCLUSIONS: ISX-9 facilitated the secretion of KGF from MSCs both in vivo and in vitro. The combination of ISX-9 with MSCs enhanced the paracrine function and anti-inflammatory effect of MSCs compared with MSCs applied alone in ALI. ISX-9 played a contributive role in the transplantation of MSCs for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , Isoxazóis , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Tiofenos , Humanos , beta Catenina/metabolismo , beta Catenina/farmacologia , Fator 7 de Crescimento de Fibroblastos/metabolismo , Fator 7 de Crescimento de Fibroblastos/farmacologia , Lesão Pulmonar Aguda/terapia , Células-Tronco Mesenquimais/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo
16.
Food Chem ; 440: 138214, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150903

RESUMO

Pesticide residue poses a significant global public health concern, necessitating improved detection methods. Here, a novel platform was introduced based on surface-enhanced Raman spectroscopy (SERS) to detect ten distinct types of pesticides. Notably, the sensitivity of this approach is exemplified by detecting trace amounts of 50 pM (10 ppt) thiabendazole. The correlation between the characteristic peak intensity of coexisting pesticides and their concentrations displays an exceptional linear relationship (R2 = 0.9999), underscoring its utility for quantitative mixed pesticide detection. Additionally, qualitative analysis of five mixed pesticides was conducted leveraging distinctive peak labeling. Harnessing machine learning techniques, a model for classifying and predicting pesticides on pericarps was developed. Remarkably, the convolutional neural network achieved classification accuracy of 100 % and prediction accuracy of 99.62 %. This innovative approach accurately identifies and quantifies diverse pesticides, thus offering a feasible scheme for in-situ detection of pesticide residues. Ultimately, this strategy contributes to ensuring food safety and public health.


Assuntos
Resíduos de Praguicidas , Praguicidas , Resíduos de Praguicidas/análise , Análise Espectral Raman/métodos , Praguicidas/análise , Inocuidade dos Alimentos , Tiabendazol/análise
17.
Dev Cell ; 58(23): 2761-2775.e5, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37922908

RESUMO

Endoplasmic reticulum (ER)-phagy is crucial to regulate the function and homeostasis of the ER via lysosomal degradation, but how it is initiated is unclear. Here we discover that Z-AAT, a disease-causing mutant of α1-antitrypsin, induces noncanonical ER-phagy at ER exit sites (ERESs). Accumulation of misfolded Z-AAT at the ERESs impairs coat protein complex II (COPII)-mediated ER-to-Golgi transport and retains V0 subunits that further assemble V-ATPase at the arrested ERESs. V-ATPase subsequently recruits ATG16L1 onto ERESs to mediate in situ lipidation of LC3C. FAM134B-II is then recruited by LC3C via its LIR motif and elicits ER-phagy leading to efficient lysosomal degradation of Z-AAT. Activation of this ER-phagy mediated by the V-ATPase-ATG16L1-LC3C axis (EVAC) is also triggered by blocking ER export. Our findings identify a pathway which switches COPII-mediated transport to lysosomal degradation for ER quality control.


Assuntos
Adenosina Trifosfatases , Lisossomos , Adenosina Trifosfatases/metabolismo , Lisossomos/metabolismo , Transporte Proteico/fisiologia , Complexo de Golgi/metabolismo , Retículo Endoplasmático/metabolismo , Autofagia
18.
medRxiv ; 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37693517

RESUMO

Epigenome-wide DNA methylation analysis (EWAS) is an important approach to identify biomarkers for early disease detection and prognosis prediction, yet its results could be confounded by other factors such as cell-type heterogeneity and patient characteristics. In this study, we address the importance of confounding adjustment by examining DNA methylation patterns in cord blood exposed to severe preeclampsia (PE), a prevalent and potentially fatal pregnancy complication. Without such adjustment, a misleading global hypomethylation pattern is obtained. However, after adjusting cell type proportions and patient clinical characteristics, most of the so-called significant CpG methylation changes associated with severe PE disappear. Rather, the major effect of PE on cord blood is through the proportion changes in different cell types. These results are validated using a previously published cord blood DNA methylation dataset, where global hypomethylation pattern was also wrongfully obtained without confounding adjustment. Additionally, several cell types significantly change as gestation progress (eg. granulocyte, nRBC, CD4T, and B cells), further confirming the importance of cell type adjustment in EWAS study of cord blood tissues. Our study urges the community to perform confounding adjustments in EWAS studies, based on cell type heterogeneity and other patient characteristics.

20.
Leg Med (Tokyo) ; 65: 102304, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37562072

RESUMO

The method proposed by Suchey-Brooks for adult age estimation based on the surface morphology of the pubic symphysis has been widely accepted. The applicability of the method varies considerably in different populations. The present study established a virtual reference sample and aimed to develop population-specific criteria that can be used for age estimation in different skeletal samples. First, The dry bone specimens from 100 individuals were compared with their corresponding three-dimensional (3D) reconstruction model and showed high inter-method agreement (k = 0.743-0.811), suggesting that the virtual bone model and physical bone specimens have comparable performances in describing the surface morphology of the pubic symphysis. We retrospectively collected clinical computed tomography (CT) data from 895 Chinese patients to create a virtual reference sample of the pubic symphysis. Based on the original Suchey-Brooks method, each of the 895 reference samples was assigned a phase, for each sex and phase, data on the mean age, standard deviation, and 95% age range of the corresponding sample were obtained, which was then used as the "method modified for Chinese" (modified method) and compared to the "SB method". Compared to the SB method, modified method had a lower inaccuracy in dry bones for males over 35 years and females over 45 years, in dry bone CT test sample for males over 55 years and females over 45 years, and in postmortem CT test sample for males over 35 years and females over 55 years. The modified method can improve the accuracy of age estimation for older samples over 40 years. It has shown considerable reliability when applied as a population-specific criterion, but its accuracy is still not sufficient, and caution is needed when using it.


Assuntos
População do Leste Asiático , Sínfise Pubiana , Adulto , Feminino , Humanos , Masculino , Determinação da Idade pelo Esqueleto/métodos , Antropologia Forense/métodos , Imageamento Tridimensional/métodos , Sínfise Pubiana/anatomia & histologia , Sínfise Pubiana/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Pessoa de Meia-Idade
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