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1.
Med Image Anal ; 98: 103311, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39217674

RESUMEN

Optical Coherence Tomography Angiography (OCTA) is a crucial tool in the clinical screening of retinal diseases, allowing for accurate 3D imaging of blood vessels through non-invasive scanning. However, the hardware-based approach for acquiring OCTA images presents challenges due to the need for specialized sensors and expensive devices. In this paper, we introduce a novel method called TransPro, which can translate the readily available 3D Optical Coherence Tomography (OCT) images into 3D OCTA images without requiring any additional hardware modifications. Our TransPro method is primarily driven by two novel ideas that have been overlooked by prior work. The first idea is derived from a critical observation that the OCTA projection map is generated by averaging pixel values from its corresponding B-scans along the Z-axis. Hence, we introduce a hybrid architecture incorporating a 3D adversarial generative network and a novel Heuristic Contextual Guidance (HCG) module, which effectively maintains the consistency of the generated OCTA images between 3D volumes and projection maps. The second idea is to improve the vessel quality in the translated OCTA projection maps. As a result, we propose a novel Vessel Promoted Guidance (VPG) module to enhance the attention of network on retinal vessels. Experimental results on two datasets demonstrate that our TransPro outperforms state-of-the-art approaches, with relative improvements around 11.4% in MAE, 2.7% in PSNR, 2% in SSIM, 40% in VDE, and 9.1% in VDC compared to the baseline method. The code is available at: https://github.com/ustlsh/TransPro.


Asunto(s)
Imagenología Tridimensional , Vasos Retinianos , Tomografía de Coherencia Óptica , Tomografía de Coherencia Óptica/métodos , Humanos , Vasos Retinianos/diagnóstico por imagen , Imagenología Tridimensional/métodos , Heurística , Enfermedades de la Retina/diagnóstico por imagen , Algoritmos , Angiografía/métodos
2.
Int J Biol Macromol ; 280(Pt 1): 135630, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278445

RESUMEN

Conductive hydrogels as ideal candidate materials for flexible sensors have exhibited many promising applications. However, complex application environments, such as low temperatures or underwater conditions, have introduced new requirements for hydrogel sensors. Herein, a high-performance conductive hydrogel based on carboxymethyl cellulose-polyaniline (CMC-PANI) submicron spheres, poly (vinyl alcohol) (PVA) and phytic acid (PA) was designed and fabricated via a dual design strategy. CMC-PANI particles were introduced to not only empower the good electromechanical performance to the hydrogels, but also enhance the mechanical properties. The obtained hydrogel exhibited good mechanical property, anti-freezing, anti-swellable behavior and recyclable performance. Resistive-type strain sensors assembled by the prepared hydrogels exhibited high pressure sensitivity (34.17×10-2 kPa-1) and fast response time (100 ms), which can clearly detect the pulse beats. Moreover, the hydrogel sensors can achieve long-term stability, high sensitivity and fatigue resistance as an underwater sensor. Based on these favorable performances, the conductive polymer hydrogels may open up an enticing avenue for functional soft materials in health diagnostic and electronic components.

3.
Immunol Invest ; : 1-16, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291775

RESUMEN

OBJECTIVES: The mitochondrial function in anti-MDA5 and TIF1-γ-positive dermatomyositis (DM) is relatively unknown. This study attempted to explore mitochondrial mass within the peripheral lymphocyte subsets of anti-MDA5 and TIF1-γ-positive DM. METHODS: This cross-sectional study enrolled 109 DM patients and 32 healthy controls (HCs). The mitochondrial mass of peripheral lymphocyte subsets was analyzed via flow cytometry using median fluorescence intensity assessment. RESULTS: Compared with HCs, there was an abnormal change in peripheral lymphocyte subsets in anti-MDA5 and anti-TIF1-γ-positive DM patients. Anti-MDA5 and anti-TIF1-γ-positive DM patients also exhibited a significantly elevated mitochondrial mass in peripheral lymphocyte subsets. Furthermore, anti-MDA5 antibody levels were positively associated with the mitochondrial mass of most lymphocyte subsets in anti-MDA5-positive DM patients. Univariate logistic regression analysis indicated that the increased mitochondrial mass in some peripheral lymphocyte subsets was related to the occurrence of anti-MDA5-positive DM and presence of anti-MDA5 antibodies. Similar results were obtained in anti-TIF1-γ-positive DM patients. CONCLUSIONS: Abnormal lymphocyte subset counts and percentages as well as altered mitochondrial mass in anti-MDA5 and TIF1-γ-positive DM patients were associated with anti-MDA5 and TIF1-γ antibodies. We believe that these results may provide novel mitochondria-based insights into DM pathogenesis.

4.
Front Psychol ; 15: 1465841, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220393

RESUMEN

[This corrects the article DOI: 10.3389/fpsyg.2023.1139373.].

5.
Bioresour Technol ; 410: 131278, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151572

RESUMEN

The efficient utilization of residual sludge and the rapid cultivation of aerobic granular sludge in continuous-flow engineering applications present significant challenges. In this study, aerobic granular cultivation was fostered in a continuous-flow system using Ca(ClO)2-sludge carbon (Ca-SC). Ca-SC retained the original sludge properties, contributing to granular growth in an A/O bioreactor. By day 40, the granule diameters increased to 0.8 mm with the SVI30 decreased by 2.7 times. Moreover, Ca-SC facilitated protein secretion, reaching 98.06 mg/g VSS and enhanced the hydrophobicity to 68.4 %. The continuous-flow aerobic granular sludge exhibited a nutrient removal rate above 90 %. Furthermore, Tessaracoccus and Nitrospira were enriched to promote granular formation and nitrogen removal. The residual sludge was carbonized and reused in the traditional wastewater treatment process to culture granular sludge in situ, aiming to achieve "self-production and self-consumption" of sludge and promote the innovative model of "treating waste with waste" in urban sewage environmental restoration.


Asunto(s)
Reactores Biológicos , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , Aerobiosis , Nitrógeno , Eliminación de Residuos Líquidos/métodos , Purificación del Agua/métodos , Cloruro de Calcio/farmacología
6.
ACS Appl Mater Interfaces ; 16(34): 45704-45712, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39199021

RESUMEN

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a promising hole-transporting material for perovskite light-emitting diodes (PeLEDs). However, intrinsic luminance quenching at the PEDOT:PSS/perovskite interface causes deterioration of performance. Here, we develop a facile and effective strategy to passivate the interface defects via the modification of PEDOT:PSS by l-norvaline. As a pre-buried additive, l-norvaline not only reacts with PEDOT:PSS, but also forms the coordination and hydrogen bond with perovskite. We demonstrated that the generation of buried defects at the PEDOT:PSS/perovskite interface originates from the crystallization process of the perovskite film during annealing by in-situ photoluminescence measurements. The surface of l-norvaline-modified PEDOT:PSS can passivate the interfacial defects and inhibit exciton quenching. As a result, the PeLED shows a good device performance with a luminance of 80089 cd m-2 at 509 nm and an external quantum efficiency of 13.04%.

7.
Environ Sci Pollut Res Int ; 31(38): 50952-50966, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39103584

RESUMEN

Antibiotic resistance genes (ARG) are widespread across various regions. While several studies have investigated the distribution of antibiotic resistance in natural environments, the occurrence and diversity of ARGs in the Three Gorges Reservoir have not been fully elucidated. In this study, we employed metagenomic sequencing techniques to investigate the abundance, diversity, and influencing factors of ARGs in the ecosystem of the Three Gorges Reservoir. A total of 874 ARGs, 20 antibiotic classes, and 6 resistance mechanisms were detected. The dominant ARG is the macB, the dominant antibiotic class is multidrug resistance (MDR), and the dominant resistance mechanism is antibiotic efflux. The microorganisms with the highest contribution to ARGs are Betaproteobacteria and Gammaproteobacteria. In this region, pH and NH4+ concentration were significantly negatively correlated with the relative abundance of most ARGs, while NO3- concentration and TN were significantly positively correlated with the relative abundance of most ARGs. The results indicate that the Three Gorges Reservoir constitutes a significant reservoir of ARGs. By studying the distribution of ARGs in the sediments of the Three Gorges Reservoir Area and the relationship between environmental factors and ARGs, we can more comprehensively understand the pollution status of ARGs in this area, and provide theoretical support for subsequent treatment.


Asunto(s)
Farmacorresistencia Microbiana , Farmacorresistencia Microbiana/genética , China , Antibacterianos/análisis , Genes Bacterianos
8.
Mater Today Bio ; 27: 101152, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39104901

RESUMEN

Uniaxial cyclic stretching plays a pivotal role in the fields of tissue engineering and regenerative medicine, influencing cell behaviors and functionality based on physical properties, including matrix morphology and mechanical stimuli. This study delves into the response of endothelial cells to uniaxial cyclic strain within the geometric constraints of micro-nano fibers. Various structural scaffold forms of poly(l-lactide-co-caprolactone) (PLCL), such as flat membranes, randomly oriented fiber membranes, and aligned fiber membranes, were fabricated through solvent casting and electrospinning methods. Our investigation focuses on the morphological variation of endothelial cells under diverse geometric constraints and the mechanical-dependent release of nitric oxide (NO) on oriented fibrous membranes. Our results indicate that while uniaxial cyclic stretching promotes endothelial cell spreading, the anisotropy of the matrix morphology remains the primary driving factor for cell alignment. Additionally, uniaxial cyclic stretching significantly enhances NO release, with a notably stronger effect correlated to the increasing strain amplitude. Importantly, this study reveals that uniaxial cyclic stretching enhances the mRNA expression of key proteins, including talin, vinculin, rac, and nitric oxide synthase (eNOS).

9.
BMC Infect Dis ; 24(1): 809, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39123106

RESUMEN

OBJECTIVE: The current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred. METHOD: A cross-sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared. RESULT: Patients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO. CONCLUSION: This present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis.


Asunto(s)
COVID-19 , Enfermedad Crítica , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/epidemiología , Masculino , Femenino , China/epidemiología , SARS-CoV-2/inmunología , Persona de Mediana Edad , Estudios Transversales , Adulto , Anciano , Anticuerpos Antivirales/sangre , Citocinas/sangre , Citocinas/inmunología , Inflamación/inmunología
10.
J Mol Diagn ; 26(9): 832-842, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38972592

RESUMEN

Timely detection of Aspergillus infection is crucial given the high mortality rate of pulmonary aspergillosis (PA). Here, the diagnostic performances for PA of mycological culture, Aspergillus real-time PCR, and metagenomic next-generation sequencing (mNGS) assay from bronchoalveolar lavage fluid, were evaluated. In total, 139 patients with suspected fungal pneumonia were enrolled between December 2021 and July 2023, collecting 139 bronchoalveolar lavage fluid samples for real-time PCR and culture, with 87 undergoing mNGS assay. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve with 95% CIs of these assays for PA were as follows: 35.3% (14.2%-61.7%), 100.0% (94.0%-100.0%), 100.0% (54.1%-100.0%), 84.5% (79.3%-88.6%), and 0.676 (0.560-0.779), respectively, for culture; 82.4% (56.6%-96.2%), 98.3% (91.1%-100.0%), 93.3% (66.4%-99.0%), 95.2% (87.6%-98.2%), and 0.903 (0.815-0.959), respectively, for same diagnostic performance of real-time PCR and mNGS; and 94.1% (71.3%-99.9%), 96.7% (88.5%-99.6%), 88.9% (67.1%-96.9%), 98.3% (89.6%-99.7%), and 0.954 (0.880-0.989), respectively, for real-time PCR combining mNGS; real-time PCR, mNGS, and their combination significantly improved in area under the curve values over culture (P < 0.001), but real-time PCR testing and mNGS had no significant difference with each other and their combination. Overall, the performance of culture was limited by low sensitivity; both real-time PCR and mNGS assays as single diagnostic tests are promising compared with culture and combined tests.


Asunto(s)
Líquido del Lavado Bronquioalveolar , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Aspergilosis Pulmonar , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Humanos , Líquido del Lavado Bronquioalveolar/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Masculino , Persona de Mediana Edad , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/microbiología , Femenino , Metagenómica/métodos , Anciano , Adulto , Aspergillus/genética , Aspergillus/aislamiento & purificación
11.
J Inflamm Res ; 17: 4361-4372, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38983452

RESUMEN

Purpose: This study investigated potential predictive models associated with natural killer (NK) cell mitochondrial membrane potential (MMP or ΔΨm) in predicting death among critically ill patients with COVID-19. Patients and Methods: We included 97 patients with COVID-19 of different severities attending Peking Union Medical College Hospital from December 2022 to January 2023. Patients were divided into three groups according to oxygen and mechanical ventilation use during specimen collection and were followed for survival and death at 3 months. The lymphocyte subpopulation MMP was detected via flow cytometry. We constructed a joint diagnostic model by integrating identified key indicators and generating receiver operating curves (ROCs) and evaluated its predictive performance for mortality risk in critically ill patients. Results: The NK-cell MMP median fluorescence intensity (MFI) was significantly lower in critically ill patients who died from COVID-19 (p<0.0001) and significantly and positively correlated with D-dimer content in critically ill patients (r=0.56, p=0.0023). The random forest model suggested that fibrinogen levels and NK-cell MMP MFI were the most important indicators. Integrating the above predictive models for the ROC yielded an area under the curve of 0.94. Conclusion: This study revealed the potential of combining NK-cell MMP with key clinical indicators (D-dimer and fibrinogen levels) to predict death among critically ill patients with COVID-19, which may help in early risk stratification of critically ill patients and improve patient care and clinical outcomes.

12.
Angew Chem Int Ed Engl ; : e202411474, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007514

RESUMEN

Owing to its prominent π-delocalization and stability, vinylene linkage holds great merits in the construction of covalent organic frameworks (COFs) with promising semiconducting properties. However, carbon-carbon double bond formation reaction always exhibits relatively low reversibility, unfavorable for the formation of high crystalline frameworks through self-error correction and assembling processes. In this work, we report a heteroatom-tuned strategy to build up a series of two-dimensional (2D) vinylene-linked COFs by Knoevenagel condensation of an electron-deficient methylthiazolyl-based monomer with different triformyl substituted (hetero-)aromatic derivatives. The resulting COFs show high-quality periodic mesoporous structures with high surface areas. Embedding heteroatoms into the backbones enables significantly improving their crystallinity, and finely tailoring their semiconducting structures. Upon visible light stimulation, one of the as-prepared COFs with donor-π-acceptor structure could deliver a nearly seven-fold increase in the catalytic activity of hydrogen generation as compared with the other two. Meanwhile, in combination with high crystallinity and the matched conduction band energy level, such kind of COFs can be able to selectively generate singlet oxygen and superoxide radicals in a high ratio of up to 30:1, allowing for catalyzing aerobic thioanisole oxidation in distinctly tunable activities through the substituent electronic effect of the substrates.

13.
Heliyon ; 10(13): e33860, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39027572

RESUMEN

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that leads to reduced saliva production, primarily affecting women due to estrogen deficiency. The estrogen receptor α (ERα) plays a crucial role in mediating the expression of the aquaporin 5 (AQP5) gene through the estrogen response element-dependent signaling pathway, making ERα a key drug target for pSS. Several flavonoids have been reported to have the potential to treat pSS. This study aimed to screen and compare flavonoids binding to ERα using AutoDock, providing a basis for treating pSS with flavonoids. The estrogenic potential of six representative flavonoids was examined in this study. Molecular docking revealed that the binding energy of all six flavonoids to ERα was less than -5.6 kcal/mol. Apigenin, naringenin, and daidzein were the top three flavonoids with even lower binding energies of -7.8, -8.09, and -8.59 kcal/mol, respectively. Similar to the positive control estradiol, apigenin, naringenin, and daidzein showed hydrogen bond interactions with GLU353, GLY521, and HIS524 at the active site. The results of luciferase reporter assays demonstrated that apigenin, naringenin, and daidzein significantly enhanced the transcription of estrogen receptor element (ERE) in the PGL3/AQP5 promoter. Furthermore, molecular dynamics simulations using GROMACS for a time scale of 100 ns revealed relatively stable binding of apigenin-ERα, naringenin-ERα, and daidzein-ERα. Mechanistically, homology modeling indicated that GLU353, GLY521, and HIS524 were the key residues of ERα exerting an estrogenic effect. The therapeutic effect of apigenin on dry mouth in pSS models was further validated. In conclusion, these results indicate the estrogenic and pSS therapeutic potential of apigenin, naringenin, and daidzein.

14.
BMC Pulm Med ; 24(1): 312, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961438

RESUMEN

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidad , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Anciano , Factores de Riesgo , Hospitalización/estadística & datos numéricos , Adulto , Pronóstico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Factores de Edad , Modelos Logísticos , Neutrófilos , Nitrógeno de la Urea Sanguínea , L-Lactato Deshidrogenasa/sangre
15.
Environ Int ; 190: 108863, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38959566

RESUMEN

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.


Asunto(s)
Contaminantes Atmosféricos , Material Particulado , Proto-Oncogenes Mas , Humanos , Material Particulado/toxicidad , Femenino , Masculino , Contaminantes Atmosféricos/toxicidad , Bases de Datos Factuales , Enfermedades Respiratorias/inducido químicamente , Enfermedades del Sistema Endocrino/inducido químicamente
16.
Cell Metab ; 36(8): 1745-1763.e6, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38851189

RESUMEN

Impaired self-renewal of Kupffer cells (KCs) leads to inflammation in metabolic dysfunction-associated steatohepatitis (MASH). Here, we identify neutrophil cytosolic factor 1 (NCF1) as a critical regulator of iron homeostasis in KCs. NCF1 is upregulated in liver macrophages and dendritic cells in humans with metabolic dysfunction-associated steatotic liver disease and in MASH mice. Macrophage NCF1, but not dendritic cell NCF1, triggers KC iron overload, ferroptosis, and monocyte-derived macrophage infiltration, thus aggravating MASH progression. Mechanistically, elevated oxidized phospholipids induced by macrophage NCF1 promote Toll-like receptor (TLR4)-dependent hepatocyte hepcidin production, leading to increased KC iron deposition and subsequent KC ferroptosis. Importantly, the human low-functional polymorphic variant NCF190H alleviates KC ferroptosis and MASH in mice. In conclusion, macrophage NCF1 impairs iron homeostasis in KCs by oxidizing phospholipids, triggering hepatocyte hepcidin release and KC ferroptosis in MASH, highlighting NCF1 as a therapeutic target for improving KC fate and limiting MASH progression.


Asunto(s)
Ferroptosis , Macrófagos del Hígado , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno , Ferroptosis/genética , Macrófagos del Hígado/metabolismo , Animales , Humanos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Masculino , Hierro/metabolismo , NADPH Oxidasas/metabolismo , Macrófagos/metabolismo , Hepcidinas/metabolismo , Hepcidinas/genética
17.
Angew Chem Int Ed Engl ; 63(34): e202402446, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-38859748

RESUMEN

In this study, we successfully developed two novel vinylene-linked covalent organic frameworks (COFs) using 2-connected 3,6-dimethylpyridazine through Knoevenagel condensation. These COFs featured finely tailored micro-/nano-scale pore sizes, high surface areas and stable non-polar vinylene linkages. Finely resolved powder X-ray diffraction patterns demonstrated highly crystalline structures with a hexagonal lattice in the AA layer stacking. The resulting one-dimensional channels possess strong hydrogen-bond accepting sites arising from the decorated cis-azo/azine units with two pairs of fully exposed lone pair electrons, endowing the as-prepared COFs with exceptional water absorption properties. The g-DZPH-COF exhibited successive steep water uptake steps starting from low relative pressures (P/PSTA=0.1), with the remarkable water uptake capacity of 0.26 g/g at P/PSTA=0.2 (25 °C), which is the optimal value recorded among the reported COFs. Dynamic vapour sorption measurements revealed the fast kinetics of these COFs, even in the cluster formation process. Water uptake and release cycling tests demonstrated their outstanding hydrolytic stability, durability, and adsorption-desorption retention ability.

18.
Wei Sheng Yan Jiu ; 53(3): 441-454, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38839586

RESUMEN

OBJECTIVE: To investigate the effects of long-term(7 days and 14 days) bisphenol S(BPS) exposure on the ERß-MAPK signaling pathway, hormone secretion phenotype and cell cycle in human normal ovarian epithelial cells IOSE 80 at actual human exposure level. METHODS: Physiologically based pharmacokinetic model combined with BPS levels in the serum of women along the Yangtze River in China was used to determine the dosing concentrations of BPS, and vehicle control and 17 ß-estradiol(E_2) control were used. Complete medium with corresponding concentrations(0, 6.79×10~(-6), 6.79×10~(-4), 6.79×10~(-2), 6.79 µmol/L BPS and 10 nmol/L E_2) was replaced every 2 days. mRNA expressions of estrogen receptor(ERß and GPR30), key genes in MAPK signaling pathway(P38/JNK/ERK signaling pathway) and gonadotropin-releasing hormone-related genes(GnRH-I, GnRH-II and GnRH-R) were measured by qPCR. The ERß-MAPK signaling pathway inhibitors were employed to detect the effect of long-term exposure to BPS on the cell cycle by flow cytometry. Dose-response relationship analysis was performed to calculate the benchmark does lower confidence limits. RESULTS: Compared to the vehicle control, after 7 days exposure to BPS, the ratio of G_2/M phase was significantly increased(P<0.05), and the mRNA expressions of GnRH-I, GnRH-II and GnRH-R were significantly decreased(P<0.05); after 14 days exposure to BPS, the mRNA expressions of ESR2, MAPK3, and MAPK9 were significantly increased(P<0.05), and the mRNA expressions of GnRH-II and GnRH-R were significantly decreased(P<0.05). The GnRH-II mRNA expression level of BPS treatment for 7 days; the G_0/G_1 phase ratio, MAPK3 and MAPK8 mRNA expression level of BPS exposure for 14 days; and the GnRH-I mRNA expression level after BPS treatment for 7 days and 14 days showed a good dose-response relationship but with poor fit. CONCLUSION: Long-term low-dose exposure to BPS may cause cell cycle arrest by activating the ERß-MAPK signaling pathway, and may lead to changes in the hormone secretion of IOSE 80 cells.


Asunto(s)
Células Epiteliales , Receptor beta de Estrógeno , Sistema de Señalización de MAP Quinasas , Ovario , Fenoles , Sulfonas , Humanos , Fenoles/toxicidad , Femenino , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Receptor beta de Estrógeno/metabolismo , Receptor beta de Estrógeno/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ovario/efectos de los fármacos , Ovario/metabolismo , Sulfonas/toxicidad , Línea Celular
19.
Biosens Bioelectron ; 260: 116427, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38823368

RESUMEN

The integrated smart electronics for real-time monitoring and personalized therapy of disease-related analytes have been gradually gaining tremendous attention. However, human tissue barriers, including the skin barrier and brain-blood barrier, pose significant challenges for effective biomarker detection and drug delivery. Microneedle (MN) electronics present a promising solution to overcome these tissue barriers due to their semi-invasive structures, enabling effective drug delivery and target-analyte detection without compromising the tissue configuration. Furthermore, MNs can be fabricated through solution processing, facilitating large-scale manufacturing. This review provides a comprehensive summary of the recent three-year advancements in smart MNs development, categorized as follows. First, the solution-processed technology for MNs is introduced, with a focus on various printing technologies. Subsequently, smart MNs designed for sensing, drug delivery, and integrated systems combining diagnosis and treatment are separately summarized. Finally, the prospective and promising applications of next-generation MNs within mediated diagnosis and treatment systems are discussed.


Asunto(s)
Técnicas Biosensibles , Sistemas de Liberación de Medicamentos , Diseño de Equipo , Agujas , Dispositivos Electrónicos Vestibles , Humanos , Técnicas Biosensibles/instrumentación , Sistemas de Liberación de Medicamentos/instrumentación , Electrónica/instrumentación
20.
Front Immunol ; 15: 1402862, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863706

RESUMEN

Ovarian cancer, ranking as the seventh most prevalent malignancy among women globally, faces significant challenges in diagnosis and therapeutic intervention. The difficulties in early detection are amplified by the limitations and inefficacies inherent in current screening methodologies, highlighting a pressing need for more efficacious diagnostic and treatment strategies. Phage display technology emerges as a pivotal innovation in this context, utilizing extensive phage-peptide libraries to identify ligands with specificity for cancer cell markers, thus enabling precision-targeted therapeutic strategies. This technology promises a paradigm shift in ovarian cancer management, concentrating on targeted drug delivery systems to improve treatment accuracy and efficacy while minimizing adverse effects. Through a meticulous review, this paper evaluates the revolutionary potential of phage display in enhancing ovarian cancer therapy, representing a significant advancement in combating this challenging disease. Phage display technology is heralded as an essential instrument for developing effective immunodiagnostic and therapeutic approaches in ovarian cancer, facilitating early detection, precision-targeted medication, and the implementation of customized treatment plans.


Asunto(s)
Técnicas de Visualización de Superficie Celular , Neoplasias Ováricas , Biblioteca de Péptidos , Femenino , Humanos , Neoplasias Ováricas/terapia , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/inmunología , Biomarcadores de Tumor , Animales , Inmunoterapia/métodos
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