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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 193-203, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38686715

RESUMEN

Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.


Asunto(s)
Población Rural , Población Urbana , Humanos , Anciano , China , Masculino , Femenino , Persona de Mediana Edad , Encuestas y Cuestionarios , Servicios de Salud para Ancianos/estadística & datos numéricos , Anciano de 80 o más Años , Necesidades y Demandas de Servicios de Salud
2.
Bioresour Technol ; 401: 130730, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38657825

RESUMEN

Achieving partial denitrification (PD) by using fermentation products extracted from waste activated sludge (WAS) rather than commercial organic matters is a promising approach for providing nitrite for anammox, while sludge reduction could also be realized by WAS reutilization. This study proposed an In-situ Sludge Fermentation coupled with Partial Denitrification (ISFPD) system and explored its performance under different conditions, including initial pH, nitrate concentrations, and organic matters. Results showed that nitrite production increased with the elevation of initial pH (from 6 to 9), and the highest nitrate-to-nitrite transformation ratio (NTR) reached 77% at initial pH 9. The PD rates and NTR were observed to be minimally influenced by initial nitrate concentrations. Acetate was preferred by denitrifying bacteria, while macromolecules such as proteins necessitated be hydrolyzed to be suitable for further utilization. The insights gained through this study paved the way for efficient nitrite production and sustainable WAS reutilization in harmony.

3.
Food Chem ; 449: 139191, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38583396

RESUMEN

This study discusses interaction differences between three phenols (protocatechuic acid, naringin and tannic acid) and starch helix, investigates influences of phenols at different doses on properties of maize starch, and further determines their effects on quality and function of maize-starchy foods. Simulated results indicate variations of phenolic structure (phenolic hydroxyl group amount, glycoside structure and steric hindrance) and dose induce phenols form different complexes with starch helix. Formation of different starch-phenols complexes alters gelatinization (1.65-5.63 J/g), pasting form, water binding capacity (8.83-12.69 g/g) and particle size distribution of starch. Meanwhile, differences in starch-phenols complexes are reflected in fingerprint area (R1045/1022: 0.920 to 1.047), crystallinity (8.3% to 17.0%), rheology and gel structure of starch. Additionally, phenols change texture and color of cold maize cake, giving them different antioxidant capacity and lower digestibility. Findings are beneficial for understanding interaction between starch and different phenols and their potential application.


Asunto(s)
Fenoles , Almidón , Zea mays , Zea mays/química , Almidón/química , Fenoles/química , Calidad de los Alimentos , Reología , Antioxidantes/química , Tamaño de la Partícula
4.
Dalton Trans ; 53(13): 6120-6127, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38482711

RESUMEN

A new hydrazone Schiff base ligand was condensed from 2-hydroxy-3-methoxybenzaldehyde and pyrimidine-4-carbohydrazide {H2L = (E)-N'-(2-hydroxy-3-methoxybenzylidene)pyrimidine-4-carbohydrazide}, which was used to assemble two new Dy2 complexes Dy2L2(DMF)2(NO3)2 (1) and Dy2L2(DMF)2(AcO)2 (2). Notably, the coordinated anions have a subtle effect on the coordination configurations of the Dy3+ ions and the magnetic properties of the two Dy2 complexes. The Dy3+ ions in 1 and 2 have the same N2O5 coordination environment but show the triangular dodecahedron and the biaugmented trigonal prism coordination configurations, respectively. Magnetic measurements revealed that both 1 and 2 have intramolecular ferromagnetic interactions between the Dy3+ ions and show single-molecule magnet behaviors at 0 Oe, with Ueff/k values of 58.2 K for 1 and 59.9 K for 2. These magnetic properties may be explained by theoretical calculations.

5.
Int J Cardiol ; 402: 131851, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38360099

RESUMEN

BACKGROUND: Based solely on pre-ablation characteristics, previous risk scores have demonstrated variable predictive performance. This study aimed to predict the recurrence of AF after catheter ablation by using artificial intelligence (AI)-enabled pre-ablation computed tomography (PVCT) images and pre-ablation clinical data. METHODS: A total of 638 drug-refractory paroxysmal atrial fibrillation (AF) patients undergone ablation were recruited. For model training, we used left atria (LA) acquired from pre-ablation PVCT slices (126,288 images). A total of 29 clinical variables were collected before ablation, including baseline characteristics, medical histories, laboratory results, transthoracic echocardiographic parameters, and 3D reconstructed LA volumes. The I-Score was applied to select variables for model training. For the prediction of one-year AF recurrence, PVCT deep-learning and clinical variable machine-learning models were developed. We then applied machine learning to ensemble the PVCT and clinical variable models. RESULTS: The PVCT model achieved an AUC of 0.63 in the test set. Various combinations of clinical variables selected by I-Score can yield an AUC of 0.72, which is significantly better than all variables or features selected by nonparametric statistics (AUCs of 0.66 to 0.69). The ensemble model (PVCT images and clinical variables) significantly improved predictive performance up to an AUC of 0.76 (sensitivity of 86.7% and specificity of 51.0%). CONCLUSIONS: Before ablation, AI-enabled PVCT combined with I-Score features was applicable in predicting recurrence in paroxysmal AF patients. Based on all possible predictors, the I-Score is capable of identifying the most influential combination.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Inteligencia Artificial , Resultado del Tratamiento , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Ablación por Catéter/métodos , Recurrencia , Valor Predictivo de las Pruebas
6.
Sci Bull (Beijing) ; 69(6): 803-822, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38320897

RESUMEN

Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily result in adequate infiltration of CD8+ T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8+ T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle. By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors, we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8+ T cell infiltration. Using pretreatment RNA-seq data from 13 ICI-treated cohorts, we validated the use of MOTIF in predicting CD8+ T cell infiltration and ICI efficacy. Among the components of MOTIF, we identified EMC3 as a negative regulator of CD8+ T cell infiltration, which was validated via in vivo studies. Additionally, MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8+ T cell infiltration and improve ICI efficacy.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias , Humanos , Mutación , Neoplasias/tratamiento farmacológico , Terapia Combinada , Inmunoterapia
7.
Int J Biol Macromol ; 260(Pt 1): 129446, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38409770

RESUMEN

Effects of Epiphyllum oxypetalum (DC.) Haw polysaccharide (EP) on physicochemical/digestive properties of tapioca starch (TS) were investigated, and its effects on final quality of TS-based foods were further determined. Results showed EP significantly decreased gelatinization enthalpy (3.92 to 2.11 J/g) and increased breakdown (302 to 382 cp), thereby inducing the gelatinization of TS. Meanwhile, EP decreased setback viscosity (324 to 258 cp), suggesting the retrogradation of TS paste was inhibited. Rheological determination results suggested EP had an impact on the viscoelasticity of TS paste. Moreover, particle size distribution showed EP increased size of TS by cross-linking. Additionally, the suitable addition of EP ameliorated the microstructure and decreased the crystal diffraction peak area of TS gel. Infrared spectroscopy results revealed EP modified the above properties of TS by hydrogen bonds and non-covalent forces. Furthermore, EP inhibited the in vitro digestion of TS paste. Using taro balls as TS-based food model, appropriate addition of EP (0.10 %) improved texture properties, frozen storage stability and color of samples. The present results can not only facilitate the understanding of the modification mechanism of EP on the properties of TS, but also induce the burgeoning of starchy products and the possible application of EP in foods.


Asunto(s)
Manihot , Manihot/química , Almidón/química , Viscosidad , Alimentos , Termodinámica
8.
Cell Metab ; 36(2): 408-421.e5, 2024 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-38325336

RESUMEN

Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus Clostridium in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of Clostridium sp. and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the Clostridium sp.-bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.


Asunto(s)
Intolerancia a la Glucosa , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Resistencia a la Insulina , Microbiota , Humanos , Animales , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Péptido 1 Similar al Glucagón , Intolerancia a la Glucosa/tratamiento farmacológico , Ácidos y Sales Biliares , Ácido Ursodesoxicólico/farmacología , Ácido Ursodesoxicólico/uso terapéutico
9.
Opt Express ; 32(1): 857-870, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38175105

RESUMEN

Charge migration initiated by the coherent superposition of several electronic states is a basic process in intense laser-matter interactions. Observing this process on its intrinsic timescale is one of the central goals of attosecond science. Here, using forward-scattering photoelectron holography we theoretically demonstrate a scheme to probe the charge migration in molecules. In our scheme, by solving the time-dependent Schrödinger equation, the photoelectron momentum distributions (PEMDs) for strong-field tunneling ionization of the molecule are obtained. For a superposition state, it is shown that an intriguing shift of the holographic interference appears in the PEMDs, when the molecule is aligned perpendicularly to the linearly polarized laser field. With the quantum-orbit analysis, we demonstrate that this shift of the interference fringes is caused by the time evolution of the non-stationary superposition state. By analyzing the dependence of the shift on the final parallel momentum of the electrons, the relative phase and the expansion coefficient ratio of the two electronic states involved in the superposition state are determined accurately. Our study provides an efficient method for probing the charge migration in molecules. It will facilitate the application of the forward-scattering photoelectron holography to survey the electronic dynamics in more complex molecules.

10.
Adv Mater ; 36(15): e2311073, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38199249

RESUMEN

Despite the first observations that the perforin can punch holes in target cells for live/dead cycles in the human immune system over 110 years ago, emulating this behavior in materials science remains challenging. Here, a perforin-mimicking molecular drilling strategy is employed to engineer macroporous hollow lignin spheres as performance-configurable catalysts, adhesives, and gels. Using a toolbox of over 20 molecular compounds, the local curvature of amphiphilic lignin is modulated to generate macroporous spheres with hole sizes ranging from 0 to 100 nm. Multiscale control is precisely achieved through noncovalent assembly directing catalysis, synthesis, and polymerization. Exceptional performance mutations correlate with the changes in hole size, including an increase in catalytic efficiency from 50% to 100%, transition from nonstick synthetics to ultrastrong adhesives (adhesion ≈18.3 MPa, exceeding that of classic epoxies), and transformation of viscous sols to tough nanogels. Thus, this study provides a robust and versatile noncovalent route for mimicking perforin-induced structural variations in cells, representing a significant stride toward the exquisite orchestration of assemblies over multiple length scales.

11.
J Transl Med ; 22(1): 6, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167440

RESUMEN

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.


Asunto(s)
Neoplasias de la Mama , Animales , Ratones , Humanos , Femenino , Neoplasias de la Mama/patología , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Ácidos Grasos , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica
12.
Anal Chem ; 96(5): 2264-2272, 2024 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-38266388

RESUMEN

Lipid metabolism diseases have become a tremendous risk worldwide, along with the development of productivity and particular attention to public health. It has been an urgent necessity to exploit reliable imaging strategies for lipids and thus to monitor fatty liver diseases. Herein, by converting the NIR-I signal to the NIR-II signal with IR1061 for the monitoring of lipid, the in vivo imaging of fatty liver disease was promoted on the contrast and visual effect. The main advantages of the imaging promotion in this work included a long emission wavelength, rapid response, and high signal-background-ratio (SBR) value. After promoting the NIR-I signal to NIR-II signal, IR1061 achieved higher SBR value and exhibited a dose-dependent fluorescence intensity at 1100 nm along with the increase of the EtOH proportion as well as steady and selective optical responses toward liposomes. IR1061 was further applied in the in vivo imaging of lipid in fatty liver diseases. In spite of the differences in body weight gain and TC level between healthy mice and fatty liver diseases two models, IR1061 achieved high-resolution imaging in the liver region to monitor the fatty liver disease status. This work might be informatic for the clinical diagnosis and therapeutical treatments of fatty liver diseases.


Asunto(s)
Boratos , Metabolismo de los Lípidos , Hepatopatías , Piranos , Animales , Ratones , Imagen Óptica/métodos , Colorantes Fluorescentes , Lípidos
13.
ACS Sens ; 9(2): 962-970, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38293708

RESUMEN

In this work, a photoacoustic (PA) probe, HDS-GGT, was developed for the in vivo imaging of cardiovascular diseases by monitoring the γ-glutamyl transferase (GGT) dynamics. HDS-GGT exhibited a stable PA signal with auxiliary absorbance and NIRF variation after the trigger by GGT. In all three modalities of absorbance, NIRF, and PA, HDS-GGT could quantitatively reflect the GGT level. In PA modality, HDS-GGT indicated the practical advantages including high sensitivity, high stability, and high specificity. In living oxidized low-density lipoprotein-induced RAW264.7 cells, HDS-GGT indicated proper capability for imaging the plaques by visualizing the GGT dynamics. Moreover, during imaging in living model mice, HDS-GGT was achieved to distinguish the plaques from healthy blood vessels via a multiview PA presentation. HDS-GGT could also suggest the severity of plaques in the extracted aorta from the model mice, which was consistent with the histological staining results. The information herein might be useful for future investigations on cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares , Animales , Ratones , Enfermedades Cardiovasculares/diagnóstico por imagen , gamma-Glutamiltransferasa , Análisis Espectral , Diagnóstico por Imagen
14.
JAMA Intern Med ; 184(3): 291-299, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38285562

RESUMEN

Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Chicles de Nicotina , Cese del Hábito de Fumar , Femenino , Humanos , Adulto , Masculino , Cese del Hábito de Fumar/métodos , Vareniclina/uso terapéutico , Agonistas Nicotínicos/efectos adversos , Dispositivos para Dejar de Fumar Tabaco , Fumar
15.
Small ; 20(13): e2309131, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37967324

RESUMEN

Sustainable long-lived room temperature phosphorescence (RTP) materials with color-tunable afterglows are attractive but rarely reported. Here, cellulose is reconstructed by directed redox to afford ample active hydroxyl groups and water-solubility; arylboronic acids with various π conjugations can be facilely anchored to reconstructed cellulose via click chemistry within 1 min in pure water, resulting in full-color tunable RTP cellulose. The rigid environment provided by the B─O covalent bonds and hydrogen bonds can stabilize the triplet excitons, thus the target cellulose displays outstanding RTP performances with the lifetime of 2.67 s, phosphorescence quantum yield of 9.37%, and absolute afterglow luminance of 348 mcd m-2. Furthermore, due to the formation of various emissive species, the smart RTP cellulose shows excitation- and time-dependent afterglows. Taking advantages of sustainability, ultralong lifetime, and full-color tunable afterglows, et al, the environmentally friendly RTP cellulose is successfully used for nontoxic afterglow inks, delay lighting, and afterglow display.

16.
Sci China Life Sci ; 67(3): 475-487, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37219765

RESUMEN

Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles (eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of eEVs after cardiopulmonary bypass, remains unclear. Plasma plasminogen-activated inhibitor-1 (PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice (C57BL/6, Toll-like receptor 4 knockout (TLR4-/-) and inducible nitric oxide synthase knockout (iNOS-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3 (JAK2/3)-signal transducer and activator of transcription 3 (STAT3)-interferon regulatory factor 1 (IRF-1) pathway, along with iNOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors (AG490 or S3I-201, respectively), and was relieved in TLR4-/- and iNOS-/- mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1 (FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.


Asunto(s)
Lesión Pulmonar Aguda , Vesículas Extracelulares , Proteínas Relacionadas con la Folistatina , Síndrome de Dificultad Respiratoria , Animales , Humanos , Ratones , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Células Endoteliales/metabolismo , Vesículas Extracelulares/metabolismo , Proteínas Relacionadas con la Folistatina/metabolismo , Proteínas Relacionadas con la Folistatina/uso terapéutico , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Pulmón/metabolismo , Ratones Endogámicos C57BL , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/uso terapéutico , Síndrome de Dificultad Respiratoria/etiología , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/uso terapéutico
17.
Photodiagnosis Photodyn Ther ; 45: 103954, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38145772

RESUMEN

Dermatophytosis is the most common fungal infectious disease in the world, which is commonly caused by Trichophyton rubrum in China. The traditional therapies for treating dermatophytosis include topical and oral antifungal agents like terbinafine, griseofulvin, and azole antifungal drugs. However, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) as a new alternative therapy avoids the side effects and drug resistance of traditional antifungal agents. We report two cases diagnosed as kerion and tinea faciei secondary to ulcers with CARD 9 deficiency, both of whom were infected by T.rubrum. They were both successfully treated by ALA-PDT combined with antifungal drugs, providing a feasible strategy for therapeutic choice for adult kerion and ulcer treatment.


Asunto(s)
Arthrodermataceae , Fotoquimioterapia , Tiña del Cuero Cabelludo , Adulto , Humanos , Antifúngicos/uso terapéutico , Ácido Aminolevulínico/uso terapéutico , Úlcera , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico
18.
Cancer Commun (Lond) ; 44(1): 3-22, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38159059

RESUMEN

In recent years, remarkable breakthroughs have been reported on antibody-drug conjugates (ADCs), with 15 ADCs successfully entering the market over the past decade. This substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs, demonstrating their efficacy in treating a wide array of malignancies. Nonetheless, there is still an unmet clinical need for wider application, better efficacy, and fewer side effects of ADCs. An ADC generally comprises an antibody, a linker and a payload, and the combination has profound effects on drug structure, pharmacokinetic profile and efficacy. Hence, optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side effects. In this review, we comprehensively reviewed the current development and the prospects of ADC, provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China, highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies, and also discussed the new related technologies, possibility of next-generation ADCs and the directions of clinical research.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Neoplasias , Humanos , Inmunoconjugados/uso terapéutico , Inmunoconjugados/química , Inmunoconjugados/farmacología , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , China
19.
IEEE Trans Image Process ; 32: 6401-6412, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37976196

RESUMEN

This paper presents a Semantic Positioning System (SPS) to enhance the accuracy of mobile device geo-localization in outdoor urban environments. Although the traditional Global Positioning System (GPS) can offer a rough localization, it lacks the necessary accuracy for applications such as Augmented Reality (AR). Our SPS integrates Geographic Information System (GIS) data, GPS signals, and visual image information to estimate the 6 Degree-of-Freedom (DoF) pose through cross-view semantic matching. This approach has excellent scalability to support GIS context with Levels of Detail (LOD). The map data representation is Digital Elevation Model (DEM), a cost-effective aerial map that allows for fast deployment for large-scale areas. However, the DEM lacks geometric and texture details, making it challenging for traditional visual feature extraction to establish pixel/voxel level cross-view correspondences. To address this, we sample observation pixels from the query ground-view image using predicted semantic labels. We then propose an iterative homography estimation method with semantic correspondences. To improve the efficiency of the overall system, we further employ a heuristic search to speedup the matching process. The proposed method is robust, real-time, and automatic. Quantitative experiments on the challenging Bund dataset show that we achieve a positioning accuracy of 73.24%, surpassing the baseline skyline-based method by 20%. Compared with the state-of-the-art semantic-based approach on the Kitti dataset, we improve the positioning accuracy by an average of 5%.

20.
Opt Lett ; 48(21): 5547-5550, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37910699

RESUMEN

Fluorescence lifetime microscopy has been widely used in quantifying cellular interaction or histopathological identification of different stained tissues. A novel, to the best of our knowledge, approach for high-throughput multiplexed fluorescence lifetime imaging is presented. To establish a high-throughput fluorescence lifetime acquisition system, a uniformed illumination optical focus array was generated by a novel computer-generated hologram algorithm based on matrix triple product. This, in conjunction with an array detector and multichannel time-correlated single-photon counting, enables the full use of the acquisition ability of each detector. By utilizing interval segmentation of photon time detection, a high-throughput multiplexed fluorescence lifetime imaging is achieved. Experimental results demonstrate that this method achieves a fivefold increase in the collection throughput of fluorescence lifetime and is capable of simultaneous dual-target fluorescence lifetime measurement.

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