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1.
Small ; : e2402655, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949408

RESUMO

Solution Gated Graphene Field-Effect Transistors (SGGT) are eagerly anticipated as an amplification platform for fabricating advanced ultra-sensitive sensors, allowing significant modulation of the drain current with minimal gate voltage. However, few studies have focused on light-matter interplay gating control for SGGT. Herein, this challenge is addressed by creating an innovative photoelectrochemical solution-gated graphene field-effect transistor (PEC-SGGT) functionalized with enzyme cascade reactions (ECR) for Organophosphorus (OPs) detection. The ECR system, consisting of acetylcholinesterase (AChE) and CuBTC nanomimetic enzymes, selectively recognizes OPs and forms o-phenylenediamine (oPD) oligomers sediment on the PEC electrode, with layer thickness related to the OPs concentration, demonstrating time-integrated amplification. Under light stimulation, the additional photovoltage generated on the PEC gate electrode is influenced by the oPD oligomers sediment layer, creating a differentiated voltage distribution along the gate path. PEC-SGGT, inherently equipped with built-in amplification circuits, sensitively captures gate voltage changes and delivers output with an impressive thousandfold current gain. The seamless integration of these three amplification modes in this advanced sensor allows a good linear range and highly sensitive detection of OPs, with a detection limit as low as 0.05 pm. This work provides a proof-of-concept for the feasibility of light-assisted functionalized gate-controlled PEC-SGGT for small molecule detection.

2.
J Am Chem Soc ; 146(28): 18899-18904, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38975975

RESUMO

In recent years, dysprosium macrocycle single-molecule magnets (SMMs) have received increasing attention due to their excellent air/thermal stability, strong magnetic anisotropy, and rigid molecular skeleton. However, they usually display fast zero-field quantum tunneling of the magnetization (QTM) rate, severely hindering their data storage applications. Herein, we report the design, synthesis, and characterization of an air-stable monodecker didysprosium macrocycle integrating strong single-ion anisotropy, near-perfect local crystal field (CF) symmetry, and efficient exchange bias. These indispensable features enable clear-cut elucidation of the crucial role of very weak antiferromagnetic coupling on magnetization dynamics, creating a prominent SMM with a large effective energy barrier (Ueff) of 670 cm-1, open hysteresis loops at zero field up to 14.9 K, and a record relaxation time of QTM (τQTM), 24281 s, for all known nonradical-bridged lanthanide SMMs.

3.
Cell Res ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898113

RESUMO

The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.

4.
Sci Total Environ ; 945: 174126, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38909799

RESUMO

Differences in electrical properties of media are the basis for determining the type and extent of contamination using geophysical methods. However, differences in heavy metals and organic matter complicate the electrical properties of compound-contaminated media, and existing geophysical methods cannot independently identify compound contamination. Therefore, this study proposes a geophysical detection system that combines electrical resistance tomography (ERT) and induced polarization methods and establishes a solid theory as the basis for the system application through laboratory experiments, model analysis, and site applications. The study reveals that as the organics volume proportion increases, the resistivity and normalized chargeability of contaminated media increased slowly, followed by a rapid increase, and finally reached a stable state. The specific type of compound significantly influences the electrical properties, while the resistivity of different kinds of compound-contaminated media reaches the same maximum value as the organics volume proportion increases. The medium type determines the contaminated media's lower resistivity limit and upper normalized chargeability limit. Additionally, the interplay between heavy metal type, content, and medium complicates the electrical properties of the media, with the compound type exerting a significant impact on resistivity. Archie's law and random forest modeling reveal that the inflection point for resistivity change occurs at 40 % and 80 % organics volume proportions, while the inflection point for normalized chargeability change occurs at 30 % and 70 % organics volume proportions in compound-contaminated media. These inflection points depend on the types of compounds, compositions, proportions, and media, and their importance for the electrical properties of the media changes with the increasing organics volume proportion. Based on the changing patterns of resistivity and normalized chargeability in heavy metal-organic compound contaminated media, the modified geophysical detection system can effectively identify the pollution type and intensity, which provides accurate pollution information to develop effective treatment strategies.

5.
BMJ Open ; 14(6): e078687, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858136

RESUMO

OBJECTIVES: This study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid, and accurate diagnosis of sepsis in the intensive care unit (ICU). DESIGN: Clinical retrospective cross-sectional study. SETTING: A comprehensive teaching tertiary hospital in China. PARTICIPANTS: Adult patients (aged ≥18 years) who underwent HBP testing or whose blood samples were collected when admitted to the ICU. MAIN OUTCOME MEASURES: HBP, C reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), interleukin-6 (IL-6), lactate (LAC), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score were recorded. RESULTS: Between March 2019 and December 2021, 326 patients were enrolled in this study. The patients were categorised into a non-infection group (control group), infection group, sepsis group and septic shock group based on the final diagnosis. The HBP levels in the sepsis group and septic shock group were 45.7 and 69.0 ng/mL, respectively, which were significantly higher than those in the control group (18.0 ng/mL) and infection group (24.0 ng/mL) (p<0.001). The area under the curve (AUC) value of HBP for diagnosing sepsis was 0.733, which was lower than those corresponding to PCT, CRP and SOFA but higher than those of IL-6, LAC and APACHE II. Multivariate logistic regression analysis identified HBP, PCT, CRP, IL-6 and SOFA as valuable indicators for diagnosing sepsis. A sepsis diagnostic model was constructed based on these indicators, with an AUC of 0.901, a sensitivity of 79.7% and a specificity of 86.9%. CONCLUSIONS: HBP could serve as a biomarker for the diagnosis of sepsis in the ICU. Compared with single indicators, the sepsis diagnostic model constructed using HBP, PCT, CRP, IL-6 and SOFA further enhanced the diagnostic performance of sepsis.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Biomarcadores , Proteínas Sanguíneas , Proteína C-Reativa , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , Sepse , Humanos , Estudos Retrospectivos , Estudos Transversais , Feminino , Masculino , Biomarcadores/sangue , Pessoa de Meia-Idade , Sepse/diagnóstico , Sepse/sangue , China , Idoso , Proteínas Sanguíneas/análise , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Peptídeos Catiônicos Antimicrobianos/sangue , Pró-Calcitonina/sangue , APACHE , Interleucina-6/sangue , Adulto , Curva ROC , Ácido Láctico/sangue
6.
Nanotechnology ; 35(36)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38861963

RESUMO

Optimizing the width of depletion region is a key consideration in designing high performance photovoltaic photodetectors, as the electron-hole pairs generated outside the depletion region cannot be effectively separated, leading to a negligible contribution to the overall photocurrent. However, currently reported photovoltaic mid-infrared photodetectors based on two-dimensional heterostructures usually adopt a single pn junction configuration, where the depletion region width is not maximally optimized. Here, we demonstrate the construction of a high performance broadband mid-infrared photodetector based on a MoS2/b-AsP/MoS2npn van der Waals heterostructure. The npn heterojunction can be equivalently represented as two parallel-stacked pn junctions, effectively increasing the thickness of the depletion region. Consequently, the npn device shows a high detectivity of 1.3 × 1010cmHz1/2W-1at the mid-infrared wavelength, which is significantly improved compared with its single pn junction counterpart. Moreover, it exhibits a fast response speed of 12 µs, and a broadband detection capability ranging from visible to mid-infrared wavelengths.

8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(4): 353-357, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38813627

RESUMO

OBJECTIVE: To investigate the predictive value of left ventricular global longitudinal peak strain (GLPS) for the prognosis of septic patients. METHODS: A prospective cohort study was conducted. Patients diagnosed with sepsis and admitted to the intensive care unit (ICU) of the First Affiliated Hospital, Sun Yat-sen University from December 2018 to November 2019 were enrolled. The patient characteristics, cardiac ultrasound parameters [left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), four-dimensional ejection fraction (4DEF), GLPS] and cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT)] within 24 hours of ICU admission, organ support therapies, severity of illness, and prognostic indicators were documented. The differences in clinical parameters between patients with varying outcomes during ICU hospitalization were assessed. Pearson correlation analysis was employed to explore the correlation between GLPS and other cardiac systolic parameters, as well as the associations between various cardiac systolic parameters and sequential organ failure assessment (SOFA) score. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive capacity of cardiac ultrasound parameters and cardiac biomarkers for death during ICU hospitalization in septic patients. RESULTS: A total of 50 septic patients were enrolled, with 40 surviving and 10 dying during ICU hospitalization, resulting in a mortality of 20.0%. All patients in the death group were male. Compared with the survival group, the patients in the death group were older, had a higher prevalence of diabetes mellitus, and received continuous renal replacement therapy (CRRT) more frequently, additionally, they exhibited more severe illness and had longer length of ICU stay. The levels of GLPS and cTnT in the death group were significantly elevated as compared with the survival group [GLPS: -7.1% (-8.5%, -7.0%) vs. -12.1% (-15.5%, -10.4%), cTnT (µg/L): 0.07 (0.05, 0.08) vs. 0.03 (0.02, 0.13), both P < 0.05]. However, no statistically significant difference was found in other cardiac ultrasound parameters or cardiac biomarkers between the two groups. Pearson correlation analysis revealed a negative correlation between GLPS and LVEF (r = -0.377, P = 0.014) and 4DEF (r = -0.697, P = 0.000), while no correlation was found with RVEF (r = -0.451, P = 0.069). GLPS demonstrated a positive correlation with SOFA score (r = 0.306, P = 0.033), while LVEF (r = 0.112, P = 0.481), RVEF (r = -0.134, P = 0.595), and 4DEF (r = -0.251, P = 0.259) showed no significant correlation with SOFA score. ROC curve analysis indicated that the area under the ROC curve (AUC) of GLPS for predicting death during ICU hospitalization in septic patients was higher than other cardiac systolic parameters, including LVEF, RVEF, and 4DEF, as well as cardiac biomarkers NT-proBNP and cTnT (0.737 vs. 0.628, 0.556, 0.659, 0.580 and 0.724). With an optimal cut-off value of -14.9% for GLPS, the sensitivity and negative predictive value reached to 100%. CONCLUSIONS: GLPS < -14.9% within 24 hours of ICU admission in septic patients indicated a reduced risk of death risk during ICU hospitalization, while also correlating with the severity of organ dysfunction in this patient population.


Assuntos
Unidades de Terapia Intensiva , Sepse , Humanos , Estudos Prospectivos , Prognóstico , Sepse/diagnóstico , Sepse/mortalidade , Sepse/fisiopatologia , Troponina T/sangue , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Biomarcadores/sangue , Ecocardiografia , Função Ventricular Esquerda , Volume Sistólico , Masculino , Feminino , Peptídeo Natriurético Encefálico/sangue , Curva ROC , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Pessoa de Meia-Idade
9.
J Am Chem Soc ; 146(21): 14528-14538, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38742912

RESUMO

Composite oxides have been widely applied in the hydrogenation of CO/CO2 to methanol or as the component of bifunctional oxide-zeolite for the synthesis of hydrocarbon chemicals. However, it is still challenging to disentangle the stepwise formation mechanism of CH3OH at working conditions and selectively convert CO2 to hydrocarbon chemicals with narrow distribution. Here, we investigate the reaction network of the hydrogenation of CO2 to methanol over a series of spinel oxides (AB2O4), among which the Zn-based nanostructures offer superior performance in methanol synthesis. Through a series of (quasi) in situ spectroscopic characterizations, we evidence that the dissociation of H2 tends to follow a heterolytic pathway and that hydrogenation ability can be regulated by the combination of Zn with Ga or Al. The coordinatively unsaturated metal sites over ZnAl2Ox and ZnGa2Ox originating from oxygen vacancies (OVs) are evidenced to be responsible for the dissociative adsorption and activation of CO2. The evolution of the reaction intermediates, including both carbonaceous and hydrogen species at high temperatures and pressures over the spinel oxides, has been experimentally elaborated at the atomic level. With the integration of a series of zeolites or zeotypes, high selectivities of hydrocarbon chemicals with narrow distributions can be directly produced from CO2 and H2, offering a promising route for CO2 utilization.

10.
Environ Pollut ; 351: 124079, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38692390

RESUMO

With the application of engineered nanomaterials and antibiotics in the fields of medicine, aerospace, new energy and agriculture, the associated contamination is detected widely in soil-groundwater systems. It is of great scientific and practical significance to deeply explore the environmental interface process between nanoparticles and antibiotics for the scientific assessment of environmental fate and ecological environmental risks, as well as the development of new composite pollution control technologies. In this study, the co-transport behaviors of positively charged titanium dioxide nanoparticles (TiO2-NPs) and negatively charged levofloxacin (LEV) in quartz sand (QS) are investigated in this study. The results show that TiO2-NPs hardly flow out when transported alone in the column because of its positive charge, which creates a strong attraction with the negatively charged quartz sand on the surface. When TiO2-NPs co-migrate with LEV in porous media, the presence of LEV promotes the transport of TiO2-NPs, while the presence of TiO2-NPs inhibits LEV transport. Non-XDLVO interactions based on molecular dynamics (MD) simulations can help explain the observed promotion and inhibition phenomena as well as the correlation between TiO2-NPs and LEV. The results indicate that TiO2-LEV complexes or aggregates can be formed during the co-transportation process of TiO2-NPs and LEV in porous media. As flow velocity increases from 0.204 cm min-1 to 1.630 cm min-1, both the transport capacities of TiO2-NPs and LEV are enhanced significantly. Under the condition of high citric acid (CA) concentration (15 mmol L-1), the transport capacity of TiO2-NPs is slightly inhibited, while the transport capacity of LEV is enhanced. This study provides new insights into the transport of nanometallic oxides and antibiotics in porous media, which suggests that non-XDLVO interactions should be considered together when assessing the environmental risks and fate of nanometallic oxides and antibiotics in soil-groundwater systems.


Assuntos
Levofloxacino , Titânio , Titânio/química , Levofloxacino/química , Porosidade , Nanopartículas/química , Antibacterianos/química , Poluentes Químicos da Água/química , Poluentes do Solo/química , Nanopartículas Metálicas/química , Água Subterrânea/química , Simulação de Dinâmica Molecular
11.
Nat Prod Res ; : 1-10, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695089

RESUMO

Rubrolides are natural butyrolactones isolated from the tunicate Ritterella rubra, shows antibacterial, antiviral and plant photosynthesis inhibitory activities. In this study, a facile total synthetic method for preparing the rubrolides from benzaldehyde by a Darzens reaction, aldol reaction and vinylogous aldol condensation in five steps is presented. Three natural rubrolides (E, C and F) were synthesised in the total yields of 25-40%. The bioassay results indicate that rubrolides E, C and F exhibit some herbicidal inhibitory effect against rapeseed, in particular, rubrolide F shows the best herbicidal activities against rapeseed root with the growth inhibitory rate of 72.8%. At greenhouse treatment concentrations of 100 and 500 mg/L, rubrolide F show a positive dose-toxicity correlation towards abutilon plants. Collectively, facile total Synthesis strategy provided the base for further bioactivities study of rubrolides family. Rubrolide F may be act as inhibitor of photosynthesis, and this could be lead structure of new herbicide.

12.
Small ; : e2402000, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752453

RESUMO

This work reports on the preparation of uniform vesicle-structural carbon spheres doped with heteroatoms of N, P, and S, with the pore sizes strictly controlled by the hard templates of monodisperse submicron SiO2 spheres. The uniformly doped vesicular carbon microspheres are obtained in three steps: Stöber hydrolysis for the SiO2; in situ polymerization for the immobilization; and alkaline etching after carbonization. The size of the vesicles can be easily adjusted by regulating the particle size of the submicron SiO2 spheres, which has a significant effect on its electromagnetic wave (EMW) absorption performance. Compared with microspheres with pore sizes of 180 and 480 nm, when the vesicle aperture is 327 nm, with only 5.5 wt.% filling load and 1.9 mm thickness, the material shows the best EMW absorption behavior with the effective absorption bandwidth (EAB) covers the entire Ku band (6.32 GHz) and the minimum reflection loss (RLmin) of -36.10 dB, suggesting the optimized pore size of the microspheres can significantly improve the overall impedance matching of the material and achieve broadband wave absorption. This work paves the way for the enhancement of EMW absorption properties of porous material by optimizing the pore size of uniform apertures while maintaining their composition.

14.
Front Integr Neurosci ; 18: 1367593, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560577

RESUMO

[This corrects the article DOI: 10.3389/fnint.2023.1234471.].

15.
J Alzheimers Dis ; 98(4): 1415-1426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578889

RESUMO

Background: Amyloid-ß (Aß) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aß plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of Aß plaques. Objective: To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma Aß42/40 ratio. Methods: We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma Aß42/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results: Results from ADNI (mean age 72.6, Aß+ rate 49.5%) and BAI (mean age 66.2, Aß+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma Aß42/40 (0.73 and 0.81) predictors. CONCLUSIONS: Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to Aß plaques and structural MRI.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Placa Amiloide/diagnóstico por imagem , Peptídeos beta-Amiloides , Amiloide , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Proteínas tau
16.
Food Chem Toxicol ; 188: 114665, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641045

RESUMO

Amanita phalloides is one of the deadliest mushrooms worldwide, causing most fatal cases of mushroom poisoning. Among the poisonous substances of Amanita phalloides, amanitins are the most lethal toxins to humans. Currently, there are no specific antidotes available for managing amanitin poisoning and treatments are lack of efficacy. Amanitin mainly causes severe injuries to specific organs, such as the liver, stomach, and kidney, whereas the lung, heart, and brain are hardly affected. However, the molecular mechanism of this phenomenon remains not understood. To explore the possible mechanism of organ specificity of amanitin-induced toxicity, eight human cell lines derived from different organs were exposed to α, ß, and γ-amanitin at concentrations ranging from 0.3 to 100 µM. We found that the cytotoxicity of amanitin differs greatly in various cell lines, among which liver-derived HepG2, stomach-derived BGC-823, and kidney-derived HEK-293 cells are most sensitive. Further mechanistic study revealed that the variable cytotoxicity is mainly dependent on the different expression levels of the organic anion transporting polypeptide 1B3 (OATP1B3), which facilitates the internalization of amanitin into cells. Besides, knockdown of OATP1B3 in HepG2 cells prevented α-amanitin-induced cytotoxicity. These results indicated that OATP1B3 may be a crucial therapeutic target against amanitin-induced organ failure.


Assuntos
Amanitinas , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto , Humanos , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Amanitinas/toxicidade , Células HEK293 , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Alfa-Amanitina/toxicidade , Células Hep G2
17.
Cell Death Differ ; 31(5): 635-650, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493248

RESUMO

Diquat (DQ) poisoning is a severe medical condition associated with life-threatening implications and multiorgan dysfunction. Despite its clinical significance, the precise underlying mechanism remains inadequately understood. This study elucidates that DQ induces instability in the mitochondrial genome of endothelial cells, resulting in the accumulation of Z-form DNA. This process activates Z-DNA binding protein 1 (ZBP1), which then interacts with receptor-interacting protein kinase 3 (RIPK3), ultimately leading to RIPK3-dependent necroptotic and ferroptotic signaling cascades. Specific deletion of either Zbp1 or Ripk3 in endothelial cells simultaneously inhibits both necroptosis and ferroptosis. This dual inhibition significantly reduces organ damage and lowers mortality rate. Notably, our investigation reveals that RIPK3 has a dual role. It not only phosphorylates MLKL to induce necroptosis but also phosphorylates FSP1 to inhibit its enzymatic activity, promoting ferroptosis. The study further shows that deletion of mixed lineage kinase domain-like (Mlkl) and the augmentation of ferroptosis suppressor protein 1 (FSP1)-dependent non-canonical vitamin K cycling can provide partial protection against DQ-induced organ damage. Combining Mlkl deletion with vitamin K treatment demonstrates a heightened efficacy in ameliorating multiorgan damage and lethality induced by DQ. Taken together, this study identifies ZBP1 as a crucial sensor for DQ-induced mitochondrial Z-form DNA, initiating RIPK3-dependent necroptosis and ferroptosis. These findings suggest that targeting the ZBP1/RIPK3-dependent necroptotic and ferroptotic pathways could be a promising approach for drug interventions aimed at mitigating the adverse consequences of DQ poisoning.


Assuntos
DNA Mitocondrial , Ferroptose , Necroptose , Proteínas de Ligação a RNA , Proteína Serina-Treonina Quinases de Interação com Receptores , Animais , Humanos , Masculino , Camundongos , DNA Mitocondrial/metabolismo , DNA Mitocondrial/genética , Ferroptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Necroptose/efeitos dos fármacos , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Diquat/toxicidade
18.
Sci Total Environ ; 925: 171740, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38494017

RESUMO

Seawater intrusion (SI) has become a global issue exacerbated by intense anthropogenic activities and climate change. It is imperative to seek a synergistic strategy to reconcile environmental and economic benefits in the coastal regions. However, the intricate SI process and data scarcity present formidable challenges in dynamically assessing the coastal groundwater vulnerability. To address the challenge, this study proposed a novel framework that integrates the existing vulnerability assessment method (GALDIT) and variable-density groundwater model (SEAWAT). The future scenarios from 2019 to 2050 were investigated monthly under climate change (SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5) and human activities (80 % and 50 % of current groundwater abstraction) in Longkou city, China, a typical coastal region subject to extensive SI, compared with the status quo in 2018. Results indicated that by 2050, the high vulnerability area, is in a narrow buffer within 1.2 km from the shoreline and exhibits minor changes while the salt concentration here increased by about 2700 mg/L compared with the current situation. The moderate vulnerability zone expands by about 30 km2, and the low vulnerable area decreases proportionally. The groundwater over-abstraction is identified as a more critical factor compared to the regional precipitation under climate change. When groundwater abstraction is reduced to 80 % of the current scale, the expansion rate of the moderate-vulnerable area slows down significantly, with an expansion area of only 18 km2 by 2050. Further reducing groundwater abstraction to 50 % of the current scale shifts the evolution trend of the medium-vulnerable area from expansion to contraction, with the area shrinking by about 11 km2 by 2050. The integrated vulnerability assessment framework can be applied not only in the similar coastal regions but also provides insights into other natural hazards.

20.
Shock ; 61(3): 454-464, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38412105

RESUMO

ABSTRACT: Immunosuppression, commonly accompanied by persistent inflammation, is a key feature in the later phase of sepsis. However, the pathophysiological mechanisms underlying this phenomenon remain unclear. Dendritic cells (DCs), specifically tolerogenic DCs (tolDCs), play a crucial role in this process by regulating immune responses through inducing T cell anergy and releasing anti-inflammatory cytokines. Nevertheless, the existing cell models are inadequate for investigating tolDCs during the immunosuppressive phase of sepsis. Therefore, this study aimed to develop a novel in vitro model to generate tolDCs under chronic inflammatory conditions. We have successfully generated tolDCs by exposing them to sublethal lipopolysaccharide (LPS) for 72 h while preserving cell viability. Considering that IL-10-induced tolDCs (IL-10-tolDCs) are well-established models, we compared the immunological tolerance between LPS-tolDCs and IL-10-tolDCs. Our findings indicated that both LPS-tolDCs and IL-10-tolDCs exhibited reduced expression of maturation markers, whereas their levels of inhibitory markers were elevated. Furthermore, the immunoregulatory activities of LPS-tolDCs and IL-10-tolDCs were found to be comparable. These dysfunctions include impaired antigen presenting capacity and suppression of T cell activation, proliferation, and differentiation. Notably, compared with IL-10-tolDCs, LPS-tolDCs showed a reduced response in maturation and cytokine production upon stimulation, indicating their potential as a better model for research. Overall, in comparison with IL-10-tolDCs, our data suggest that the immunological dysfunctions shown in LPS-tolDCs could more effectively elucidate the increased susceptibility to secondary infections during sepsis. Consequently, LPS-tolDCs have emerged as promising therapeutic targets for ameliorating the immunosuppressed state in septic patients.


Assuntos
Interleucina-10 , Sepse , Humanos , Interleucina-10/metabolismo , Células Dendríticas/metabolismo , Lipopolissacarídeos/farmacologia , Tolerância Imunológica , Sepse/metabolismo , Inflamação/metabolismo
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