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1.
Cell ; 187(11): 2717-2734.e33, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653239

RESUMEN

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.


Asunto(s)
Akkermansia , Bacteroides , Ácidos y Sales Biliares , Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Simbiosis , Animales , Humanos , Masculino , Ratones , Akkermansia/metabolismo , Bacteroides/metabolismo , beta-Lactamasas/metabolismo , Ácidos y Sales Biliares/metabolismo , Vías Biosintéticas/genética , Hígado Graso/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BL , Verrucomicrobia/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/microbiología
2.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33657410

RESUMEN

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Asunto(s)
COVID-19/inmunología , Megacariocitos/inmunología , Monocitos/inmunología , ARN Viral , SARS-CoV-2/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , China , Estudios de Cohortes , Citocinas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ARN Viral/aislamiento & purificación , Análisis de la Célula Individual , Transcriptoma/inmunología , Adulto Joven
4.
Nature ; 616(7955): 77-83, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37020008

RESUMEN

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.

5.
Nature ; 601(7892): 257-262, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34937940

RESUMEN

The methanogenic degradation of oil hydrocarbons can proceed through syntrophic partnerships of hydrocarbon-degrading bacteria and methanogenic archaea1-3. However, recent culture-independent studies have suggested that the archaeon 'Candidatus Methanoliparum' alone can combine the degradation of long-chain alkanes with methanogenesis4,5. Here we cultured Ca. Methanoliparum from a subsurface oil reservoir. Molecular analyses revealed that Ca. Methanoliparum contains and overexpresses genes encoding alkyl-coenzyme M reductases and methyl-coenzyme M reductases, the marker genes for archaeal multicarbon alkane and methane metabolism. Incubation experiments with different substrates and mass spectrometric detection of coenzyme-M-bound intermediates confirm that Ca. Methanoliparum thrives not only on a variety of long-chain alkanes, but also on n-alkylcyclohexanes and n-alkylbenzenes with long n-alkyl (C≥13) moieties. By contrast, short-chain alkanes (such as ethane to octane) or aromatics with short alkyl chains (C≤12) were not consumed. The wide distribution of Ca. Methanoliparum4-6 in oil-rich environments indicates that this alkylotrophic methanogen may have a crucial role in the transformation of hydrocarbons into methane.


Asunto(s)
Euryarchaeota , Hidrocarburos , Metano , Alcanos/metabolismo , Biodegradación Ambiental , Euryarchaeota/enzimología , Euryarchaeota/genética , Hidrocarburos/metabolismo , Metano/metabolismo , Oxidorreductasas/metabolismo , Filogenia
6.
Nature ; 610(7932): 562-568, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36261549

RESUMEN

Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD)1-5, but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression.


Asunto(s)
Bacterias , Intestinos , Nicotina , Enfermedad del Hígado Graso no Alcohólico , Fumar Tabaco , Animales , Humanos , Ratones , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Ceramidas/biosíntesis , Nicotina/efectos adversos , Nicotina/metabolismo , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/microbiología , Esfingomielina Fosfodiesterasa/metabolismo , Fumar Tabaco/efectos adversos , Fumar Tabaco/metabolismo , Intestinos/efectos de los fármacos , Intestinos/microbiología , Proteínas Quinasas Activadas por AMP/metabolismo , Progresión de la Enfermedad
7.
Nat Methods ; 19(6): 662-670, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35577954

RESUMEN

Spatial transcriptomics approaches have substantially advanced our capacity to detect the spatial distribution of RNA transcripts in tissues, yet it remains challenging to characterize whole-transcriptome-level data for single cells in space. Addressing this need, researchers have developed integration methods to combine spatial transcriptomic data with single-cell RNA-seq data to predict the spatial distribution of undetected transcripts and/or perform cell type deconvolution of spots in histological sections. However, to date, no independent studies have comparatively analyzed these integration methods to benchmark their performance. Here we present benchmarking of 16 integration methods using 45 paired datasets (comprising both spatial transcriptomics and scRNA-seq data) and 32 simulated datasets. We found that Tangram, gimVI, and SpaGE outperformed other integration methods for predicting the spatial distribution of RNA transcripts, whereas Cell2location, SpatialDWLS, and RCTD are the top-performing methods for the cell type deconvolution of spots. We provide a benchmark pipeline to help researchers select optimal integration methods to process their datasets.


Asunto(s)
Benchmarking , Transcriptoma , ARN , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos
8.
Exp Cell Res ; 438(2): 114061, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38692345

RESUMEN

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease with high morbidity and mortality rates worldwide. Pyroptosis is an inflammatory form of programmed cell death that has been linked to various pathological conditions. However, its exact contribution to the onset and progression of heart injury in AMI has not yet fully elucidated. Herein, we established mouse AMI model by ligating the left anterior descending artery and performed transcriptome analysis during the early phase of AMI. Mouse HL-1 and human AC-16 cardiomyocytes were subjected to hypoxia to simulate ischemic injury in vitro. Our results revealed a significant activation of the inflammatory response at 3 h post-ligation, as confirmed by RNA sequencing. We identified the occurrence of NLRP3 inflammasome-mediated pyroptosis in the cardiac tissues of human cases with AMI, as well as in mouse models of AMI and hypoxia-induced cardiomyocytes, using immunohistochemistry staining and Western blotting assays. Concurrently, pharmacological inhibition of NLRP3 inflammasome-mediated pyroptosis with MCC950 and VX-765 effectively decreased hypoxia-induced cardiomyocytes injury, while mitigating myocardial oxidative stress, apoptosis and inflammation caused by hypoxia. Moreover, the circulating levels of gasdermin D (GSDMD), the pyroptosis executor, were remarkably elevated in the plasma of mice with early AMI and in the supernatant of hypoxia-exposed cardiomyocytes in a time-dependent manner using ELISA and Western blotting. Furthermore, the change in circulating GSDMD positively correlated with Creatine Kinase-MB (CK-MB) in the plasma of early-stage AMI mouse. In summary, these findings indicated a critical role for NLRP3 inflammasome-mediated pyroptosis in the progression of AMI, the administration of MCC950 and VX-765 may be attractive candidate therapeutic approaches for cardiac injury caused by acute hypoxia or even AMI. Additionally, the circulating GSDMD exhibits potential as a newly diagnostic biomarker for AMI.


Asunto(s)
Apoptosis , Furanos , Inflamación , Ratones Endogámicos C57BL , Infarto del Miocardio , Miocitos Cardíacos , Estrés Oxidativo , Piroptosis , Sulfonamidas , Piroptosis/efectos de los fármacos , Animales , Ratones , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sulfonamidas/farmacología , Humanos , Inflamación/metabolismo , Inflamación/patología , Inflamación/tratamiento farmacológico , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Masculino , Furanos/farmacología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/tratamiento farmacológico , Indenos/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , para-Aminobenzoatos/farmacología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Modelos Animales de Enfermedad , Miocardio/metabolismo , Miocardio/patología , Hipoxia/metabolismo , Hipoxia/complicaciones , Dipéptidos
9.
Nano Lett ; 24(15): 4408-4414, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38567928

RESUMEN

Tuning the interfacial Schottky barrier with van der Waals (vdW) contacts is an important solution for two-dimensional (2D) electronics. Here we report that the interlayer dipoles of 2D vdW superlattices (vdWSLs) can be used to engineer vdW contacts to 2D semiconductors. A bipolar WSe2 with Ba6Ta11S28 (BTS) vdW contact was employed to exhibit this strategy. Strong interlayer dipoles can be formed due to charge transfer between the Ba3TaS5 and TaS2 layers. Mechanical exfoliation breaks the superlattice and produces two distinguished surfaces with TaS2 and Ba3TaS5 terminations. The surfaces thus have opposite surface dipoles and consequently different work functions. Therefore, all the devices fall into two categories in accordance with the rectifying direction, which were verified by electrical measurements and scanning photocurrent microscopy. The growing vdWSL family along with the addition surface dipoles enables prospective vdW contact designs and have practical application in nanoelectronics and nano optoelectronics.

10.
Lancet Oncol ; 25(7): 843-852, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38852601

RESUMEN

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Inestabilidad de Microsatélites , Terapia Neoadyuvante , Piridinas , Humanos , Persona de Mediana Edad , Femenino , Masculino , Terapia Neoadyuvante/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto Joven , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Adolescente
11.
Br J Cancer ; 130(7): 1176-1186, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38280969

RESUMEN

BACKGROUND: Nasopharyngeal carcinoma (NPC) treatment is largely based on a 'one-drug-fits-all' strategy in patients with similar pathological characteristics. However, given its biological heterogeneity, patients at the same clinical stage or similar therapies exhibit significant clinical differences. Thus, novel molecular subgroups based on these characteristics may better therapeutic outcomes. METHODS: Herein, 192 treatment-naïve NPC samples with corresponding clinicopathological information were obtained from Fujian Cancer Hospital between January 2015 and January 2018. The gene expression profiles of the samples were obtained by RNA sequencing. Molecular subtypes were identified by consensus clustering. External NPC cohorts were used as the validation sets. RESULTS: Patients with NPC were classified into immune, metabolic, and proliferative molecular subtypes with distinct clinical features. Additionally, this classification was repeatable and predictable as validated by the external NPC cohorts. Metabolomics has shown that arachidonic acid metabolites were associated with NPC malignancy. We also identified several key genes in each subtype using a weighted correlation network analysis. Furthermore, a prognostic risk model based on these key genes was developed and was significantly associated with disease-free survival (hazard ratio, 1.11; 95% CI, 1.07-1.16; P < 0.0001), which was further validated by an external NPC cohort (hazard ratio, 7.71; 95% CI, 1.39-42.73; P < 0.0001). Moreover, the 1-, 3-, and 5-year areas under the curve were 0.84 (95% CI, 0.74-0.94), 0.81 (95% CI, 0.73-0.89), and 0.82 (95% CI, 0.73-0.90), respectively, demonstrating a high predictive value. CONCLUSIONS: Overall, we defined a novel classification of nasopharyngeal carcinoma (immune, metabolism, and proliferation subtypes). Among these subtypes, metabolism and proliferation subtypes were associated with advanced stage and poor prognosis of NPC patients, whereas the immune subtype was linked to early stage and favorable prognosis.


Asunto(s)
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Análisis por Conglomerados
12.
Expert Rev Mol Med ; 26: e7, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602081

RESUMEN

Trauma is a significant health issue that not only leads to immediate death in many cases but also causes severe complications, such as sepsis, thrombosis, haemorrhage, acute respiratory distress syndrome and traumatic brain injury, among trauma patients. Target protein identification technology is a vital technique in the field of biomedical research, enabling the study of biomolecular interactions, drug discovery and disease treatment. It plays a crucial role in identifying key protein targets associated with specific diseases or biological processes, facilitating further research, drug design and the development of treatment strategies. The application of target protein technology in biomarker detection enables the timely identification of newly emerging infections and complications in trauma patients, facilitating expeditious medical interventions and leading to reduced post-trauma mortality rates and improved patient prognoses. This review provides an overview of the current applications of target protein identification technology in trauma-related complications and provides a brief overview of the current target protein identification technology, with the aim of reducing post-trauma mortality, improving diagnostic efficiency and prognostic outcomes for patients.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Humanos , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Hemorragia
13.
Small ; : e2401650, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712474

RESUMEN

Piezoelectric catalysis is a novel catalytic technology that has developed rapidly in recent years and has attracted extensive interest among researchers in the field of tumor therapy for its acoustic-sensitizing properties. Nevertheless, researchers are still controversial about the key technical difficulties in the modulation of piezoelectric sonosensitizers for tumor therapy applications, which is undoubtedly a major obstacle to the performance modulation of piezoelectric sonosensitizers. Clarification of this challenge will be beneficial to the design and optimization of piezoelectric sonosensitizers in the future. Here, the authors start from the mechanism of piezoelectric catalysis and elaborate the mechanism and methods of defect engineering and phase engineering for the performance modulation of piezoelectric sonosensitizers based on the energy band theory. The combined therapeutic strategy of piezoelectric sonosensitizers with enzyme catalysis and immunotherapy is introduced. Finally, the challenges and prospects of piezoelectric sonosensitizers are highlighted. Hopefully, the explorations can guide researchers toward the optimization of piezoelectric sonosensitizers and can be applied in their own research.

14.
Small ; 20(3): e2305567, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37702141

RESUMEN

Mesoporous silica nanoparticles (MSNs) have been widely praised as nanoadjuvants in vaccine/tumor immunotherapy thanks to their excellent biocompatibility, easy-to-modify surface, adjustable particle size, and remarkable immuno-enhancing activity. However, the application of MSNs is still greatly limited by some severe challenges including the unclear and complicated relationships of structure and immune effect. Herein, three commonly used MSNs with different skeletons including MSN with tetrasulfide bonds (TMSN), MSN containing ethoxy framework (EMSN), and pure -Si-O-Si- framework of MSN (MSN) are comprehensively compared to study the impact of chemical construction on immune effect. The results fully demonstrate that the three MSNs have great promise in improving cellular immunity for tumor immunotherapy. Moreover, the TMSN performs better than the other two MSNs in antigen loading, cellular uptake, reactive oxygen species (ROS) generation, lymph node targeting, immune activation, and therapeutic efficiency. The findings provide a new paradigm for revealing the structure-function relationship of mesoporous silica nanoadjuvants, paving the way for their future clinical application.


Asunto(s)
Nanopartículas , Neoplasias , Nitrilos , Humanos , Porosidad , Dióxido de Silicio/química , Inmunoterapia , Nanopartículas/química , Neoplasias/terapia , Esqueleto
15.
J Transl Med ; 22(1): 568, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877591

RESUMEN

BACKGROUND: Metastasis renal cell carcinoma (RCC) patients have extremely high mortality rate. A predictive model for RCC micrometastasis based on pathomics could be beneficial for clinicians to make treatment decisions. METHODS: A total of 895 formalin-fixed and paraffin-embedded whole slide images (WSIs) derived from three cohorts, including Shanghai General Hospital (SGH), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Cancer Genome Atlas (TCGA) cohorts, and another 588 frozen section WSIs from TCGA dataset were involved in the study. The deep learning-based strategy for predicting lymphatic metastasis was developed based on WSIs through clustering-constrained-attention multiple-instance learning method and verified among the three cohorts. The performance of the model was further verified in frozen-pathological sections. In addition, the model was also tested the prognosis prediction of patients with RCC in multi-source patient cohorts. RESULTS: The AUC of the lymphatic metastasis prediction performance was 0.836, 0.865 and 0.812 in TCGA, SGH and CPTAC cohorts, respectively. The performance on frozen section WSIs was with the AUC of 0.801. Patients with high deep learning-based prediction of lymph node metastasis values showed worse prognosis. CONCLUSIONS: In this study, we developed and verified a deep learning-based strategy for predicting lymphatic metastasis from primary RCC WSIs, which could be applied in frozen-pathological sections and act as a prognostic factor for RCC to distinguished patients with worse survival outcomes.


Asunto(s)
Carcinoma de Células Renales , Aprendizaje Profundo , Neoplasias Renales , Metástasis Linfática , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Metástasis Linfática/patología , Persona de Mediana Edad , Masculino , Femenino , Pronóstico , Estudios de Cohortes , Procesamiento de Imagen Asistido por Computador/métodos , Anciano , Área Bajo la Curva
16.
Nat Mater ; 22(6): 725-730, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36894773

RESUMEN

The discovery of spin-transfer torque (STT) enabled the control of the magnetization direction in magnetic devices in nanoseconds using an electrical current. Ultrashort optical pulses have also been used to manipulate the magnetization of ferrimagnets at picosecond timescales by bringing the system out of equilibrium. So far, these methods of magnetization manipulation have mostly been developed independently within the fields of spintronics and ultrafast magnetism. Here we show optically induced ultrafast magnetization reversal taking place within less than a picosecond in rare-earth-free archetypal spin valves of [Pt/Co]/Cu/[Co/Pt] commonly used for current-induced STT switching. We find that the magnetization of the free layer can be switched from a parallel to an antiparallel alignment, as in STT, indicating the presence of an unexpected, intense and ultrafast source of opposite angular momentum in our structures. Our findings provide a route to ultrafast magnetization control by bridging concepts from spintronics and ultrafast magnetism.

17.
Ann Surg Oncol ; 31(7): 4250-4260, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38334847

RESUMEN

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.


Asunto(s)
Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Femenino , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Persona de Mediana Edad , Masculino , Tasa de Supervivencia , Anciano , Pronóstico , Estudios de Seguimiento , Neumonectomía/mortalidad , Estudios de Cohortes
18.
Chemistry ; : e202401389, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38779789

RESUMEN

Transition metal-catalyzed epoxidation of carbonyl compounds through carbonyl ylides represents a highly effective method for synthesizing a diverse range of valuable epoxides. This review offers an in-depth overview of the latest developments in inter- and intramolecular epoxidation reactions involving metal carbenes and carbonyl compounds, encompassing both racemic to enantioselective transformations. These catalytic epoxidations are reviewed by highlighting their product selectivity, diversity and applicability, and the related mechanistic rationale is showcased where possible.

19.
J Magn Reson Imaging ; 59(5): 1832-1840, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37681476

RESUMEN

BACKGROUND: Cardiac MRI feature-tracking (FT) with breath-holding (BH) cine balanced steady state free precession (bSSFP) imaging is well established. It is unclear whether FT-strain measurements can be reliably derived from free-breathing (FB) compressed sensing (CS) bSSFP imaging. PURPOSE: To compare left ventricular (LV) strain analysis and image quality of an FB CS bSSFP cine sequence with that of a conventional BH bSSFP sequence in children. STUDY TYPE: Prospective. SUBJECTS: 40 children able to perform BHs (cohort 1 [12.1 ± 2.2 years]) and 17 children unable to perform BHs (cohort 2 [5.2 ± 1.8 years]). FIELD STRENGTH/SEQUENCE: 3T, bSSFP sequence with and without CS. ASSESSMENT: Acquisition times and image quality were assessed. LV myocardial deformation parameters were compared between BH cine and FB CS cine studies in cohort 1. Strain indices and image quality of FB CS cine studies were also assessed in cohort 2. Intraobserver and interobserver variability of strain parameters was determined. STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient (ICC), and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: In cohort 1, the mean acquisition time of the FB CS cine study was significantly lower than for conventional BH cine study (15.6 s vs. 209.4 s). No significant difference were found in global circumferential strain rate (P = 0.089), global longitudinal strain rate (P = 0.366) and EuroCMR image quality scores (P = 0.128) between BH and FB sequences in cohort 1. The overall image quality score of FB CS cine in cohort 2 was 3.5 ± 0.5 with acquisition time of 14.7 ± 2.1 s. Interobserver and intraobserver variabilities were good to excellent (ICC = 0.810 to 0.943). DATA CONCLUSION: FB CS cine imaging may be a promising alternative technique for strain assessment in pediatric patients with poor BH ability. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.


Asunto(s)
Corazón , Función Ventricular Izquierda , Humanos , Niño , Estudios Prospectivos , Ventrículos Cardíacos/diagnóstico por imagen , Imagen por Resonancia Magnética , Imagen por Resonancia Cinemagnética/métodos , Reproducibilidad de los Resultados
20.
J Biomed Sci ; 31(1): 25, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408962

RESUMEN

Breast cancer is one of the most common malignancies that pose a serious threat to women's health. Reprogramming of energy metabolism is a major feature of the malignant transformation of breast cancer. Compared to normal cells, tumor cells reprogram metabolic processes more efficiently, converting nutrient supplies into glucose, amino acid and lipid required for malignant proliferation and progression. Non-coding RNAs(ncRNAs) are a class of functional RNA molecules that are not translated into proteins but regulate the expression of target genes. NcRNAs have been demonstrated to be involved in various aspects of energy metabolism, including glycolysis, glutaminolysis, and fatty acid synthesis. This review focuses on the metabolic regulatory mechanisms and clinical applications of metabolism-regulating ncRNAs involved in breast cancer. We summarize the vital roles played by metabolism-regulating ncRNAs for endocrine therapy, targeted therapy, chemotherapy, immunotherapy, and radiotherapy resistance in breast cancer, as well as their potential as therapeutic targets and biomarkers. Difficulties and perspectives of current targeted metabolism and non-coding RNA therapeutic strategies are discussed.


Asunto(s)
Neoplasias de la Mama , ARN Largo no Codificante , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , Transformación Celular Neoplásica
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