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1.
Nat Immunol ; 22(9): 1127-1139, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34413521

RESUMEN

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.


Asunto(s)
Ferroptosis/fisiología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Selenio/farmacología , Células T Auxiliares Foliculares/fisiología , Adolescente , Adulto , Animales , Supervivencia Celular/inmunología , Niño , Femenino , Centro Germinal/citología , Centro Germinal/inmunología , Homeostasis/efectos de los fármacos , Homeostasis/genética , Humanos , Inmunidad Humoral/inmunología , Vacunas contra la Influenza/inmunología , Peroxidación de Lípido/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/fisiología , Ovalbúmina , Células T Auxiliares Foliculares/inmunología , Vacunación , Adulto Joven
3.
Nature ; 618(7963): 193-200, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37225986

RESUMEN

Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors1,2 (TAARs). TAARs emerged following the divergence of jawed and jawless fish, and comprise a large monophyletic family of receptors that recognize volatile amine odorants to elicit both intraspecific and interspecific innate behaviours such as attraction and aversion3-5. Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9-Gs or mTAAR9-Golf trimers in complex with ß-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved D3.32W6.48Y7.43 motif, which is essential for amine odorant recognition. In the mTAAR9 structure, a unique disulfide bond connecting the N terminus to ECL2 is required for agonist-induced receptor activation. We identify key structural motifs of TAAR family members for detecting monoamines and polyamines and the shared sequence of different TAAR members that are responsible for recognition of the same odour chemical. We elucidate the molecular basis of mTAAR9 coupling to Gs and Golf by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and Golf coupling of an amine olfactory receptor.


Asunto(s)
Aminas Biogénicas , Odorantes , Percepción Olfatoria , Poliaminas , Receptores Odorantes , Animales , Ratones , Aminas Biogénicas/análisis , Aminas Biogénicas/química , Aminas Biogénicas/metabolismo , Microscopía por Crioelectrón , Subunidades alfa de la Proteína de Unión al GTP Gs/química , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/ultraestructura , Odorantes/análisis , Percepción Olfatoria/fisiología , Poliaminas/análisis , Poliaminas/química , Poliaminas/metabolismo , Receptores de Amina Biogénica/química , Receptores de Amina Biogénica/genética , Receptores de Amina Biogénica/metabolismo , Receptores de Amina Biogénica/ultraestructura , Receptores Odorantes/química , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/ultraestructura , Olfato/fisiología , Espermidina/análisis , Espermidina/química , Espermidina/metabolismo
5.
Nano Lett ; 24(15): 4537-4545, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38568783

RESUMEN

An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of ∼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of ∼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.

6.
J Exp Bot ; 75(3): 979-1003, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-37877811

RESUMEN

High temperatures impair plant growth and reduce agricultural yields, but the underlying mechanisms remain elusive. The unicellular green alga Chlamydomonas reinhardtii is an excellent model to study heat responses in photosynthetic cells due to its fast growth rate, many similarities in cellular processes to land plants, simple and sequenced genome, and ample genetic and genomics resources. Chlamydomonas grows in light by photosynthesis and with externally supplied acetate as an organic carbon source. Understanding how organic carbon sources affect heat responses is important for the algal industry but remains understudied. We cultivated wild-type Chlamydomonas under highly controlled conditions in photobioreactors at 25 °C (control), 35 °C (moderate high temperature), or 40 °C (acute high temperature) with or without constant acetate supply for 1 or 4 day. Treatment at 35 °C increased algal growth with constant acetate supply but reduced algal growth without sufficient acetate. The overlooked and dynamic effects of 35 °C could be explained by induced acetate uptake and metabolism. Heat treatment at 40 °C for more than 2 day was lethal to algal cultures with or without constant acetate supply. Our findings provide insights to understand algal heat responses and help improve thermotolerance in photosynthetic cells.


Asunto(s)
Chlamydomonas reinhardtii , Chlamydomonas , Chlamydomonas reinhardtii/metabolismo , Temperatura , Carbono/metabolismo , Fotosíntesis , Acetatos/metabolismo
7.
Soft Matter ; 20(5): 1089-1099, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38221881

RESUMEN

An exciting result is reported in this study where a polypropylene (PP) foam with a high open-cell content was achieved by constructing a thermally conductive network for the first time. PP and nano-graphite particles were used as substrate and filler, respectively, to prepare the PP-graphite (PP-G) composite foam by twin-screw blending, hot pressing, and supercritical CO2 foaming. The nano-graphite particles can effectively adjust the microstructure of the PP-G foam and achieve a high porosity. When the amount of nano-graphite is 10.0 wt%, the PP-G foam exhibits optimal sound absorption performance, compression resistance, heat insulation, and hydrophobic properties. In the human-sensitive frequency range of 1000-6000 Hz, the corresponding average SAC is above 0.9, and the internal tortuosity is 5.27. After 50 cycles of compression, the compressive stress is 980 kPa and the SAC loss is only 7.8%. This study also innovatively proposed a new strategy to achieve the simple and rapid preparation of open-cell PP foams by increasing the thermal conductivity of the foaming substrate.

8.
J Appl Clin Med Phys ; : e14483, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133901

RESUMEN

PURPOSE: In recent years, the use of deep learning for medical image segmentation has become a popular trend, but its development also faces some challenges. Firstly, due to the specialized nature of medical data, precise annotation is time-consuming and labor-intensive. Training neural networks effectively with limited labeled data is a significant challenge in medical image analysis. Secondly, convolutional neural networks commonly used for medical image segmentation research often focus on local features in images. However, the recognition of complex anatomical structures or irregular lesions often requires the assistance of both local and global information, which has led to a bottleneck in its development. Addressing these two issues, in this paper, we propose a novel network architecture. METHODS: We integrate a shift window mechanism to learn more comprehensive semantic information and employ a semi-supervised learning strategy by incorporating a flexible amount of unlabeled data. Specifically, a typical U-shaped encoder-decoder structure is applied to obtain rich feature maps. Each encoder is designed as a dual-branch structure, containing Swin modules equipped with windows of different size to capture features of multiple scales. To effectively utilize unlabeled data, a level set function is introduced to establish consistency between the function regression and pixel classification. RESULTS: We conducted experiments on the COVID-19 CT dataset and DRIVE dataset and compared our approach with various semi-supervised and fully supervised learning models. On the COVID-19 CT dataset, we achieved a segmentation accuracy of up to 74.56%. Our segmentation accuracy on the DRIVE dataset was 79.79%. CONCLUSIONS: The results demonstrate the outstanding performance of our method on several commonly used evaluation metrics. The high segmentation accuracy of our model demonstrates that utilizing Swin modules with different window sizes can enhance the feature extraction capability of the model, and the level set function can enable semi-supervised models to more effectively utilize unlabeled data. This provides meaningful insights for the application of deep learning in medical image segmentation. Our code will be released once the manuscript is accepted for publication.

9.
Aust Crit Care ; 37(5): 740-746, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38580485

RESUMEN

BACKGROUND: Intensive care unit (ICU) delirium is a common complication in older critically ill patients that has a significant impact. The Family Confusion Assessment Method (FAM-CAM) is a vital tool for assisting family members in identifying delirium; however, no study has yet been reported on the Chinese version of the scale. OBJECTIVES: The objective of this study was to translate the FAM-CAM into a Chinese version and to verify its effectiveness for delirium detection in an online patient visit setting. METHODS: This was a cross-sectional study. The FAM-CAM was translated to Chinese according to the International Society for Pharmacoeconomics and Outcomes Research guidelines. Patients and family members were recruited to participate in delirium assessments in three ICUs of one hospital. Family members then used the Chinese version of the FAM-CAM to assess for delirium via online visitation, and ICU nurses assessed patients for delirium using the Intensive Care Delirium Screening Checklist (ICDSC). Results were then compared between family members' and nurses' assessments. RESULTS: Overall, 190 critically ill patients and 190 family members were included, of whom 117 (61.6%) were assessed for delirium using the Intensive Care Delirium Screening Checklist. The Cohen's kappa coefficient between the Intensive Care Delirium Screening Checklist and FAM-CAM was 0.759 (P < 0.01). The sensitivity of the Chinese version of the FAM-CAM was 0.880, specificity was 0.890, positive predictive value was 0.928, negative predictive value was 0.823, and area under the receiver operating characteristic curve was 0.881 (95% confidence interval: 0.872-0.935, P < 0.01). CONCLUSION: The Chinese version of the FAM-CAM was shown to effectively help families detect delirium and was suggested as a crucial tool for assisting ICU nurses in the early identification of delirium. This tool may effectively be used to assess delirium during online visits.


Asunto(s)
Delirio , Unidades de Cuidados Intensivos , Humanos , Delirio/diagnóstico , Masculino , Femenino , Estudios Transversales , Anciano , Persona de Mediana Edad , Familia/psicología , China , Traducciones , Enfermedad Crítica , Comparación Transcultural , Internet
10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 444-448, 2024 Jun.
Artículo en Zh | MEDLINE | ID: mdl-38953269

RESUMEN

The incidence of urinary calculi in children has been increasing annually,and most of the cases are upper urinary tract stones.At present,surgery is the main way to treat upper urinary tract stones in children.With the gradual development of minimally invasive techniques in surgery,percutaneous nephrolithotomy,retrograde intrarenal surgery,and extracorporeal shock wave lithotripsy have become the main methods for treating upper urinary tract stones in children.We reviewed the current progress in surgical treatment of upper urinary tract stones in children and provided prospects for future treatment options.


Asunto(s)
Nefrolitotomía Percutánea , Humanos , Niño , Nefrolitotomía Percutánea/métodos , Litotricia/métodos , Cálculos Urinarios/cirugía , Cálculos Urinarios/terapia , Cálculos Renales/cirugía
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