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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124988, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39163772

RESUMEN

Two quinoxaline dyes utilized in copper-electrolyte-based dye-sensitized solar cells (Cu-DSSCs) are theoretically investigated to analyze the impact of alkyl chains on dye performance. The investigation shows that ZS4, known for its record efficiency of up to 13.2 %, exhibits higher electron coupling and fewer binding sites for dye-[Cu(tmby)2]2+ interaction compared to ZS5. Contrary to common belief, alkyl chains are found to not only provide shielding but also hinder the interaction between dye and [Cu(tmby)2]2+ by influencing the optimal conformation of dyes, thereby impeding the charge recombination process. It is crucial to consider the influence of alkyl chains on dye conformation when discussing the relationship between dye structure and performance, rather than oversimplifying it as often done traditionally. Building on these findings, eight dyes are strategically designed by adjusting the position of the alkyl chain to further decrease charge recombination compared to ZS4. Theoretical evaluation of these dyes reveals that changing the alkyl chain on the nitrogen atom from 2-ethylhexyl (ZS4) to 1-hexylheptyl (D3-2) not only reduces the charge recombination rate but also enhances light harvesting ability. Therefore, D3-2 shows potential as a candidate for experimental synthesis of high-performance Cu-DSSCs with improved efficiency.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39361459

RESUMEN

Optical flow is an indispensable building block for various important computer vision tasks, including motion estimation, object tracking, and disparity measurement. To date, the dominant methods are CNN-based, leaving plenty of room for improvement. In this work, we propose TransFlow, a transformer architecture for optical flow estimation. Compared to dominant CNN-based methods, TransFlow demonstrates three advantages. First, it provides more accurate correlation and trustworthy matching in flow estimation by utilizing spatial self-attention and cross-attention mechanisms between adjacent frames to effectively capture global dependencies; Second, it recovers more compromised information (e.g. occlusion and motion blur) in flow estimation through long-range temporal association in dynamic scenes; Third, it introduces a concise self-learning paradigm, eliminating the need for complex and laborious multi-stage pre-training procedures. The versatility and superiority of TransFlow extend seamlessly to 3D scene motion, yielding competitive outcomes in 3D scene flow estimation. Our approach attains state-of-the-art results on benchmark datasets such as Sintel and KITTI-15, while also exhibiting exceptional performance on downstream tasks, including video object detection using the ImageNet VID dataset, video frame interpolation using the GoPro dataset, and video stabilization using the DeepStab dataset. We believe that the effectiveness of TransFlow positions it as a flexible baseline for both optical flow and scene flow estimation, offering promising avenues for future research and development.

3.
Am J Clin Nutr ; 120(4): 988-990, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39362733

Asunto(s)
Humanos
4.
Ther Adv Endocrinol Metab ; 15: 20420188241274350, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39350947

RESUMEN

The term metabolic-associated fatty liver disease (MAFLD), with a global prevalence estimated at 38.77%, has gradually replaced the traditional concept of non-alcoholic fatty liver disease (NAFLD). Compared to the general population, the incidence of MAFLD is notably higher among pregnant women, posing potential risks to both maternal and neonatal health. This review summarizes the latest research on MAFLD, focusing on its association with pregnancy complications. Additionally, it provides a comparative analysis with previous studies on NAFLD, presenting a comprehensive perspective for clinical management. Findings suggest that pregnant women with MAFLD face a higher risk of gestational hypertension and cesarean delivery compared to those with NAFLD, while the risk for gestational diabetes mellitus remains similar between the two conditions. Additionally, MAFLD is associated with an increased likelihood of delivering large-for-gestational-age infants and heightened risks of preterm birth and low birth weight. Current treatment strategies for MAFLD focus on lifestyle modifications, such as dietary adjustments and increased physical activity. However, there is an urgent need for the development of safe and effective pharmacological treatments, particularly tailored toward pregnant women. Future research should delve deeper into the causal relationships between MAFLD and pregnancy complications and explore optimal therapeutic approaches to improve outcomes for mothers and their infants.


Metabolic-associated fatty liver disease and pregnancy complications Metabolic-associated fatty liver disease (MAFLD) is a new term for what used to be called non-alcoholic fatty liver disease, affecting nearly two-fifths of people worldwide. It's especially concerning for pregnant women, as it can cause serious problems for both the mother and the baby. This summary looks at the latest studies on how MAFLD affects pregnant women and how it compares to the older diagnosis of NAFLD. The findings show that pregnant women with MAFLD are more likely to have high blood pressure during pregnancy and need a cesarean section. However, the chance of getting gestational diabetes is about the same for both MAFLD and NAFLD. MAFLD also increases the risk of having a baby that is too large for its gestational age, as well as the risks of preterm birth and low birth weight. Right now, the main way to treat MAFLD is through healthy lifestyle changes like diet and exercise. But there's a big need for new medicines that are safe for pregnant women. Future studies should look more into how MAFLD causes complications during pregnancy and find the best ways to treat it to help mothers and their babies.

5.
Angew Chem Int Ed Engl ; : e202414209, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39384542

RESUMEN

Photoelectrochemical water splitting offers a promising approach for carbon neutrality, but its commercial prospects are still hampered by a lack of efficient and stable photoelectrodes with earth-abundant materials. Here, we report a strategy to construct an efficient photoanode with a coaxial nanobelt structure, comprising a buried-ZrS3/ZrOS n-p junction, for photoelectrochemical water splitting. The p-type ZrOS layer, formed on the surface of the n-type ZrS3 nanobelt through a pulsed-ozone-treatment method, acts as a hole collection layer for hole extraction and a protective layer to shield the photoanode from photocorrosion. The resulting ZrS3/ZrOS photoanode exhibits light harvesting with good photo-to-current efficiencies across the whole visible region to over 650 nm. By further employing NiOOH/FeOOH as the oxygen evolution reaction cocatalyst, the ZrS3/ZrOS/NiOOH/FeOOH photoanode yields a photocurrent density of ~9.3 mA cm-2 at 1.23 V versus the reversible hydrogen electrode with an applied bias photon-to-current efficiency of ~3.2% under simulated sunlight irradiation in an alkaline solution (pH = 13.6). The conformal ZrOS layer enables ZrS3/ZrOS/NiOOH/FeOOH photoanode operation over 1000 hours in an alkaline solution without obvious performance degradation. This study, offering a promising approach to fabricate efficient and durable photoelectrodes with earth-abundant materials, advances the frontiers of photoelectrochemical water splitting.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39401936

RESUMEN

In this work, we designed two nitrogen-bridged fluorene-based heptacyclic FNT and nonacyclic FNTT ladder-type structures, which were constructed by one-pot palladium-catalyzed Buchwald-Hartwig amination. FNT and FNTT were further end-capped by FIC acceptors to form two FNT-FIC and FNTT-FIC non-fullerene acceptors (NFAs), respectively. The two NFAs exhibit more red-shifted absorption and higher crystallinity compared to those of the corresponding carbon-bridged FCT-FIC and FCTT-FIC counterparts. Grazing incidence wide-angle X-ray scattering (GIWAXS) measurements reveal that the 2-butyloctyl groups on the nitrogen in the convex region of FNT-FIC interdigitate with the dioctyl groups on the fluorene in the concave region of another FNT-FIC, resulting in a lamellar packing structure with a d spacing of 13.27 Å. As a consequence, the PM6:FNT-FIC (1:1 wt %) device achieved a power conversion efficiency (PCE) of only 6.60%, primarily due to the highly crystalline nature of FNT-FIC, which induced significant phase separation between PM6 and FNT-FIC in the blended film. However, FNTT-FIC, featuring 2-butyloctyl groups positioned on the nitrogen within the concave region of its curved skeleton, exhibits improved donor-acceptor miscibility, thereby promoting a more favorable morphology. As a result, the PM6:FNTT-FIC (1:1.2 wt %) device exhibited a higher PCE of 12.15% with an exceptional Voc of 0.96 V. This research demonstrates that placing alkylamino moieties within the concave region of curved A-D-A NFAs leads to a better molecular design.

7.
Cancer Med ; 13(18): e70256, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39358989

RESUMEN

PURPOSE: To compare the efficacy of first-line regimens based on programmed cell death (or ligand) [PD-(L)1] blockade in extensive-stage small-cell lung cancer (ES-SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. METHODS: Network meta-analysis of randomized controlled trials (RCTs) comparing chemo-immunotherapy (CIT) and chemotherapy (CT) in ES-SCLC patients stratified by LM. Overall survival (OS) and progression-free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Seven RCTs involving 3658 ES-SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti-PD-1 + CT (HR, 0.67; 95% CI, 0.54%-0.82%; p < 0.001) and anti-PD-L1 + CT + anti-angiogenesis (HR, 0.84; 95% CI, 0.71%-0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti-PD-1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti-angiogenesis + anti-PD-L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. CONCLUSIONS: CIT is effective for ES-SCLC patients regardless of LM status. For patients with LM, PD-1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti-angiogenesis, PD-L1 blockade, and CT.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hepáticas , Neoplasias Pulmonares , Metaanálisis en Red , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estadificación de Neoplasias , Supervivencia sin Progresión
8.
Dig Liver Dis ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39227295
9.
Nucleic Acids Res ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39329270

RESUMEN

Various post-translational modifications (PTMs) participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently associated with human diseases. Here, we present a comprehensive database of PTMs associated with diseases (PTMD 2.0), including 342 624 PTM-disease associations (PDAs) in 15 105 proteins for 93 types of PTMs and 2083 diseases. Based on the distinct PTM states in diseases, we classified all PDAs into six categories: upregulation (U) or downregulation (D) of PTM levels, absence (A) or presence (P) of PTMs, and creation (C) or disruption (N) of PTM sites. We provided detailed annotations for each PDA and carefully annotated disease-associated proteins by integrating the knowledge from 101 additional resources that covered 13 aspects, including disease-associated information, variation and mutation, protein-protein interaction, protein functional annotation, DNA and RNA element, protein structure, chemical-target relationship, mRNA expression, protein expression/proteomics, subcellular localization, biological pathway annotation, functional domain annotation and physicochemical property. With a data volume of ∼8 GB, we anticipate that PTMD 2.0 will serve as a fundamental resource for further analysing the relationships between PTMs and diseases. The online service of PTMD 2.0 is freely available at https://ptmd.biocuckoo.cn/.

10.
J Dent Sci ; 19(4): 1961-1971, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39347062

RESUMEN

Background/purpose: The use of computed tomography (CT) for craniofacial measurements is common in medical imaging, but concerns about accuracy and reliability persist, especially with different CT technologies. This study assessed the accuracy of twenty-six common measurements on consecutive CT images from the same patients, using multidetector CT (MDCT) and cone-beam CT (CBCT) with two software programs (Amira and Dolphin). Materials and methods: Ten adult subjects with consecutive CBCT scans within one year were randomly selected. Another ten subjects with consecutive MDCT scans were paired with the CBCT group based on age, gender, race, occlusion, and craniofacial pattern. All digital imaging and communications in medicine (DICOM) files were randomly coded and analyzed using the two software programs. Intra-examiner reliability was assessed using the intraclass correlation coefficient. Successive measurement errors from consecutive scans for both imaging modalities and software programs were compared. Results: For most skeletal linear and angular measurements, Dolphin showed greater successive measurement errors compared to Amira. Eight of the 26 common measurements had errors greater than one unit (millimeter or degree). Despite almost perfect intra-examiner reliability for upper airway analysis, average successive measurement errors were notably high, particularly for intraoral and oropharyngeal airway volumes. The successive Dolphin measurement error for oropharyngeal airway volume on CBCT images was over three times that on MDCT images. Conclusion: Given the substantial successive measurement errors observed during consecutive CT scanning for the upper airway, this study does not support the quantitative use of CT for analyzing changes in airway dimensions for research purposes.

11.
Sci Total Environ ; 954: 176337, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39304154

RESUMEN

Dark microbial fixation of CO2 is an indispensable process for soil carbon sequestration. However, the whole genetic information involved in dark CO2 fixation and its influence on dark CO2 fixation rates under diversified fertilization regimes were largely unclear. Here, revealed by 13C-CO2 labeling, dark CO2 fixation rates in upland red soils ranged from 0.029 mg kg-1 d-1 to 0.092 mg kg-1 d-1, and it was 75.49 % higher (P < 0.05) in organic manure (OM) soil but 44.2 % decline (P < 0.05) in chemical nitrogen fertilizer (N) soil compared to unfertilized (CK) soil. In addition, the normalized abundance and Chao1 index of dark CO2 fixation genes (KO level) were significantly different between OM and N soils, showing the highest and lowest, respectively. And they were positively (P < 0.05) correlated with dark CO2 fixation rate. Besides, among the identified CO2 fixation pathways in this study, the DC/4-HB cycle (M00374) was enriched in OM soil, yet the 3-HP cycle (M00376) was enriched in N soil, and their relative abundances were positively and negatively correlated (P < 0.05) with dark CO2 fixation rate, respectively. The PLS-SEM analysis revealed that dark CO2 fixation-related functional traits (i.e. normalized abundance, Chao1 index and gene composition) were directly and positively associated with dark CO2 fixation rate, and organic manure could exert a positive effect on soil dark CO2 fixation rate through enhancing soil properties (e.g., pH and soil organic carbon) and further altering associated microbial functional traits. These results have implications for explaining and predicting the soil CO2 fixation process from the perspective of microbial functional potential.

12.
bioRxiv ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39345558

RESUMEN

The emergence of drug-resistant strains exacerbates the global challenge of tuberculosis caused by Mycobacterium tuberculosis (Mtb). Central to the pathogenicity of Mtb is its complex cell envelope, which serves as a barrier against both immune system and pharmacological attacks. Two key components of this envelope, arabinogalactan (AG) and lipoarabinomannan (LAM) are complex polysaccharides that contain integral arabinan domains important for cell wall structural and functional integrity. The arabinofuranosyltransferase AftB terminates the synthesis of these arabinan domains by catalyzing the addition of the addition of ß-(1→2)-linked terminal arabinofuranose residues. Here, we present the cryo-EM structures of Mycobacterium chubuense AftB in its apo and donor substrate analog-bound form, determined to 2.9 Å and 3.4 Å resolution, respectively. Our structures reveal that AftB has a GT-C fold transmembrane (TM) domain comprised of eleven TM helices and a periplasmic cap domain. AftB has an irregular tube-shaped cavity that bridges the two proposed substrate binding sites. By integrating structural analysis, biochemical assays, and molecular dynamics simulations, we elucidate the molecular basis of the reaction mechanism of AftB and propose a model for catalysis.

13.
Ecology ; 105(10): e4418, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39252134

RESUMEN

Common mycorrhizal networks (CMNs) can link multiple plants and distribute nutrients among them. However, how parasitic plants regulate the carbon and nutrient exchange between CMNs and the linked plants is unknown. Thus, we conducted a container experiment with two Trifolium pratense grown in two plastic cores and connected only by CMNs using a 25-µm nylon fabric in each container. Host T. pratense was parasitized or not parasitized by Cuscuta gronovii. CMNs were left intact or broken by rotating the cores with the host or neighboring T. pratense. The dual 15N and 13C labeling method was used to evaluate the N distributed by CMNs to the host and neighboring T. pratense and the recently fixed C from the host and neighboring T. pratense to CMNs. The results showed that CMNs distributed more 15N to unparasitized neighboring T. pratense than the parasitized host T. pratense. Moreover, the unparasitized neighboring T. pratense provides more recently fixed C to CMNs than the parasitized host T. pratense. These results revealed that the parasite regulated C and nutrient exchange between CMNs and the linked plants following the reciprocal rewards rule. Moreover, this study highlights the importance of parasitic plants in the regulation of mutualistic interactions in ecological webs.


Asunto(s)
Carbono , Micorrizas , Nitrógeno , Trifolium , Micorrizas/fisiología , Trifolium/microbiología , Trifolium/fisiología , Nitrógeno/metabolismo , Carbono/metabolismo , Cuscuta/fisiología
14.
Exp Eye Res ; 248: 110110, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39326773

RESUMEN

The intricate interaction network necessary for essential physiological functions underscores the interdependence among eukaryotic cells. Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs), specialized junctions between mitochondria and the ER, were recently discovered. These junctions participate in various cellular processes, including calcium level regulation, lipid metabolism, mitochondrial integrity maintenance, autophagy, and inflammatory responses via modulating the structure and molecular composition of various cellular components. Therefore, MAMs contribute to the pathophysiology of numerous ocular disorders, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and glaucoma. In addition to providing a concise overview of the architectural and functional aspects of MAMs, this review explores the key pathogenetic pathways involving MAMs in the development of several ocular disorders.

15.
J Ethnopharmacol ; 337(Pt 2): 118859, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39341266

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Dihuang Yinzi (DHYZ) is a classic prescription in traditional Chinese medicine. Its therapeutic effect on Alzheimer's disease (AD) has been widely validated. However, the underlying molecular mechanisms of DHYZ in AD treatment remain unclear and require further research. AIM OF THE STUDY: Elucidating DHYZ's promotion of mitochondrial biogenesis through the AMPK/SIRT1/PGC-1α pathway improves neuronal loss, mitochondrial damage, and memory deficits in AD. MATERIALS AND METHODS: Administering DHYZ by gavage to SAMP8 mice, after completing behavioral tests, the effects of DHYZ on hippocampal neuron loss and mitochondrial structural damage in AD model mice were assessed using Nissl staining and transmission electron microscopy. Western blot was used to detect the expression of mitochondrial biogenesis-related proteins PGC-1α, CREB, mitochondrial fusion protein MFN2, and mitochondrial fission proteins DRP1 and FIS1. At the same time, immunofluorescence (IF) was employed to measure the relative fluorescence intensity of mitochondrial fusion protein MFN1. After determining the optimal dose of DYHZ for treating AD, we conducted mechanistic studies. By intraperitoneally injecting SAMP8 mice with the AMPK inhibitor (Compound C) to inhibit AMPK protein expression and subsequently treating them with DHYZ, the impact of DHYZ on hippocampal neurons in AD model mice was evaluated using Nissl and hematoxylin-eosin staining. Western blot was used to detect the protein expression of AMPK, p-AMPK, SIRT1, PGC-1α, NRF1, and TFAM. In contrast, IF was used to measure the relative fluorescence intensity of PGC-1α, NRF1, and TFAM proteins in the hippocampal CA1 region. RESULTS: DHYZ significantly improved AD model mice's cognitive impairment and memory deficits and mitigated hippocampal neuron loss and degeneration. Additionally, it ameliorated mitochondrial morphological structures. DHYZ upregulated the protein expression of mitochondrial biogenesis-related proteins PGC-1α, CREB, and mitochondrial fusion proteins MFN1 and MFN2 while inhibiting the expression of mitochondrial fission proteins DRP1 and FIS1. Further studies revealed that DHYZ could upregulate the expression of the AMPK/SIRT1/PGC-1α pathway proteins and their downstream proteins NRF1 and TFAM. CONCLUSION: DHYZ promotes mitochondrial biogenesis by activating the AMPK/SIRT1/PGC-1α signaling pathway, thereby improving memory deficits, neuronal loss, and mitochondrial dysfunction in AD.

16.
Angle Orthod ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39317376

RESUMEN

OBJECTIVES: To compare the intra- and inter-examiner reliability of multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) using Amira and Dolphin software analyses for craniofacial/airway measurements by six examiners. MATERIALS AND METHODS: Five adults and one dry skull with CBCT and MDCT scan files were duplicated and randomly numbered. Six orthodontic residents imported these files into two software programs, oriented the images, set thresholds, and performed 26 measurements. Intra- and inter-examiner reliabilities were determined by using intraclass correlation coefficient (ICC) and presented with scatterplots. RESULTS: Variables including anterior nasal width, posterior nasal width, frontomaxillary suture right-to-left, inner nasal contour point right-to-left, and minimum cross-sectional area in the oropharynx showed "moderate" to "substantial" intra- or inter-examiner agreement. Amira provided relatively reliable airway assessment, while Dolphin showed standard deviations 10 to 30 times larger for volumetric airway measurements. MDCT scans significantly reduced airway volume/area measurements compared to CBCT, except for intraoral airway volume. CONCLUSIONS: Unreliable skeletal measurements and low reliability of Dolphin for airway analysis discourage using CT to quantitatively correlate changes in craniofacial structures with airway dimensions.

17.
Brain Res ; 1845: 149203, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39208968

RESUMEN

Neuroinflammation caused by the chronic periodontal pathogen Porphyromonas gingivalis is growing regarded as as a key factor in the pathogenesis of Alzheimer's disease (AD). Alantolactone (AL), a sesquiterpene lactone isolated from the root of Inula racemosa Hook. f, has been proven to provide various neuroprotective effects. However, whether AL can improve cognitive impairment caused by P. gingivalis infection remains unclear. In this research, a rat model of P. gingivalis infection was used to examine the neuroprotective benefits of AL. The results revealed that 6 weeks of AL treatment (50 and 100 mg/kg) shortened escape latency and increased the number of crossings over the platform location and time spent in the target quadrant of P. gingivalis-infected rats in the Morris water maze experiment. By activating the Nrf2/HO-1 pathway, AL suppressed malondialdehyde (MDA) levels and simultaneously increased the activity of total superoxide dismutase (T-SOD). Furthermore, AL lowered the presence of IL-6, IL-1ß, and TNFα in the hippocampal and cortical tissues of P. gingivalis-infected rats by inhibiting astrocyte and microglial activation and NF-κB phosphorylation. AL also significantly reduced Aß levels in the cortical and hippocampus tissues of rats infected with P. gingivalis. In conclusion, AL improved cognitive impairment in P. gingivalis-infected rats by inhibiting neuroinflammation, reducing Aß1-42 level, and exerting antioxidative stress effects.

18.
J Org Chem ; 89(17): 12716-12724, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39138971

RESUMEN

On the basis of a novel umpolung strategy, an efficient l-amino acid ester-mediated in situ reduction of 2-(2-oxoindolin-3-ylidene)malononitrile and sequential nucleophilic addition/cyclization cascade reaction is reported. Various densely substituted cyclopentene bispirooxindoles and dihydrofuran bispirooxindoles with two quaternary spirocenters were constructed in high yields (≤93%) with excellent diastereoselectivities (>20:1 dr). The method has advantages of readily available starting materials, mild reaction conditions, a one-pot process, a metal-free biomimetic reducing agent, a wide substrate scope, and operational simplicity (single filtration without column chromatography).

19.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39154193

RESUMEN

Cell segmentation is a fundamental task in analyzing biomedical images. Many computational methods have been developed for cell segmentation and instance segmentation, but their performances are not well understood in various scenarios. We systematically evaluated the performance of 18 segmentation methods to perform cell nuclei and whole cell segmentation using light microscopy and fluorescence staining images. We found that general-purpose methods incorporating the attention mechanism exhibit the best overall performance. We identified various factors influencing segmentation performances, including image channels, choice of training data, and cell morphology, and evaluated the generalizability of methods across image modalities. We also provide guidelines for choosing the optimal segmentation methods in various real application scenarios. We developed Seggal, an online resource for downloading segmentation models already pre-trained with various tissue and cell types, substantially reducing the time and effort for training cell segmentation models.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Biología Computacional/métodos , Algoritmos , Núcleo Celular
20.
Environ Pollut ; 360: 124764, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39154884

RESUMEN

Cigarette smoke (CS) is an important indoor air pollutant associated with an increased risk of ocular surface disease. As the eye's outermost layer, the cornea is highly sensitive to air pollutants like CS. However, the specific mechanisms linking CS exposure to corneal dysfunction have not been fully elucidated. In the present study, we found that CS exposure damages corneal epithelial cells, accompanied by increased iron (Fe2+) levels and lipid peroxidation, both hallmarks of ferroptosis. Ferroptosis inhibitors, including Ferrostatin-1 (Fer-1) and Deferoxamine mesylate (DFO), protect against CS-induced cell damage. To understand the underlying mechanisms, we investigated how CS affects iron and lipid metabolism. Our results showed that CS could upregulate intracellular iron levels by increasing TFRC expression and promote lipid peroxidation by increasing ACSL4 expression. Silencing ACSL4 or TFRC expression prevented CS-induced ferroptosis. Furthermore, we found that the upregulation of TFRC and ACSL4 was driven by increased YAP transcription. Pharmacological or genetic inhibition of YAP effectively prevented corneal epithelial cell ferroptosis under CS stimulation. Additionally, our results suggest that CS exposure could increase O-GlcNAc transferase activity, leading to YAP O-GlcNAcylation. This glycosylation of YAP interfered with its K48-linked ubiquitination, resulting in YAP stabilization. Collectively, we found that CS exposure induces corneal epithelial cell ferroptosis via the YAP O-GlcNAcylation, and provide evidence that CS exposure is a strong risk factor for ocular surface disease.


Asunto(s)
Células Epiteliales , Ferroptosis , Ferroptosis/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Animales , Ratones , Humanos , Hierro/metabolismo , Humo/efectos adversos , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/genética , Córnea/metabolismo , Peroxidación de Lípido/efectos de los fármacos
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