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1.
Nat Immunol ; 21(9): 1107-1118, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32788748

RESUMEN

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.


Asunto(s)
Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Interferón Tipo I/metabolismo , Neumonía Viral/inmunología , Receptores Inmunológicos/metabolismo , Adolescente , Adulto , Anciano , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/metabolismo , Humanos , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/virología , RNA-Seq , Receptores Inmunológicos/genética , Receptores Inmunológicos/inmunología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Análisis de la Célula Individual
2.
Gastroenterology ; 164(3): 424-438, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36436593

RESUMEN

BACKGROUND & AIMS: In eukaryotes, the ubiquitin-proteasome system and the autophagy-lysosome pathway are essential for maintaining cellular proteostasis and associated with cancer progression. Our previous studies have demonstrated that phosphatase and tensin homolog (PTEN), one of the most frequently mutated genes in human cancers, limits proteasome abundance and determines chemosensitivity to proteasome inhibitors in cholangiocarcinoma (CCA). However, whether PTEN regulates the lysosome pathway remains unclear. METHODS: We tested the effects of PTEN on lysosome biogenesis and exosome secretion using loss- and gain-of-function strategies in CCA cell lines. Using in vitro dephosphorylation assays, we explored the regulatory mechanism between PTEN and the key regulator of lysosome biogenesis, transcription factor EB (TFEB). Using the migration assays, invasion assays, and trans-splenic liver metastasis mouse models, we evaluated the function of PTEN deficiency, TFEB-mediated lysosome biogenesis, and exosome secretion on tumor metastasis. Moreover, we investigated the clinical significance of PTEN expression and exosome secretion by retrospective analysis. RESULTS: PTEN facilitated lysosome biogenesis and acidification through its protein phosphatase activity to dephosphorylate TFEB at Ser211. Notably, PTEN deficiency increased exosome secretion by reducing lysosome-mediated degradation of multi-vesicular bodies, which further facilitated the proliferation and invasion of CCA. TFEB agonist curcumin analog C1 restrained the metastatic phenotype caused by PTEN deficiency in mouse models, and we highlighted the correlation between PTEN deficiency and exosome secretion in clinical cohorts. CONCLUSIONS: In CCA, PTEN deficiency impairs lysosome biogenesis to facilitate exosome secretion and cancer metastasis in a TFEB phosphorylation-dependent manner.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Colangiocarcinoma , Exosomas , Fosfohidrolasa PTEN , Animales , Humanos , Ratones , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Colangiocarcinoma/metabolismo , Modelos Animales de Enfermedad , Exosomas/metabolismo , Lisosomas/fisiología , Complejo de la Endopetidasa Proteasomal , Fosfohidrolasa PTEN/metabolismo , Estudios Retrospectivos
3.
Anal Chem ; 96(25): 10111-10115, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38869290

RESUMEN

The Si window is the most widely used internal reflection element (IRE) for electrochemical attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), yet local chemical etching on Si by concentrated OH- anions bottlenecks the reliable application of this method in strong alkaline electrolytes. In this report, atomic layer deposition of a 25 nm nonconductive TiO2 barrier layer on the reflecting plane of a Si prism is demonstrated to address this challenge. In situ ATR-SEIRAS measurement on a Au film electrode with the Si/TiO2 composite IRE in 1 M NaOH reveals reversible global spectral features without spectral distortion at 1000-1300 cm-1, in stark contrast to those obtained with a bare Si window. By applying this structured ATR-SEIRAS, ethanol electrooxidation on a Pt/C catalyst in 1 and 5 M NaOH is explored, manifesting that such high pH values prevent the adsorption of as-formed acetate in the C2 pathway but not that of CO intermediate in the C1 pathway.

4.
Small ; : e2405118, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140191

RESUMEN

The development of polymer binders is necessary to meet the growing demands of modern energy storage technologies. While catechol-containing materials are proven successful in silicon anodes, their application in organic batteries remains unexplored. In this contribution, the synthesis of four polymers are described with nearly identical side chain composition but varying backbone structures. The materials are used to investigate the effect of polymer backbone structure on the binding abilities of catechol-containing materials. Comparative analysis with the commonly used polyvinylidene fluoride (PVDF) binder aims to address two critical questions: 1) Can catechol-rich polymers replace PVDF for use in organic cathodes? and 2) Does the choice of polymer backbone affect the performance of the battery?. The investigation reveals that supramolecular interactions, such as π-π stacking and coordination bonding, are pivotal features of catechol binders. Among the catechol-rich polymers, the polyacrylate binder stands out, likely attributed to its high flexibility. Additionally, introducing an oxygen atom into a catechol-rich polynorbornene enhances lithium-ion conductivity and rate performance. Overall, the findings highlight the viability of catechol-containing polymers as organic cathode binders, and that the choice of polymer backbone is a crucial factor for their use as lithium-ion battery binder materials.

5.
Metab Eng ; 82: 69-78, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38316239

RESUMEN

Microbial synthesis has emerged as a promising and sustainable alternative to traditional chemical synthesis and plant extraction. However, the competition between synthetic pathways and central metabolic pathways for cellular resources may impair final production efficiency. Moreover, when the synthesis of target product requires multiple precursors from the same node, the conflicts of carbon flux have further negative impacts on yields. In this study, a self-regulated network was developed to relieve the competition of precursors in complex synthetic pathways. Using 4-hydroxycoumarin (4-HC) synthetic pathway as a proof of concept, we employed an intermediate as a trigger to dynamically rewire the metabolic flux of pyruvate and control the expression levels of genes in 4-HC synthetic pathway, achieving self-regulation of multiple precursors and enhanced titer. Transcriptomic analysis results additionally demonstrated that the gene transcriptional levels of both pyruvate kinase PykF and synthetic pathway enzyme SdgA dynamically changed according to the intermediate concentrations. Overall, our work established a self-regulated network to dynamically balance the metabolic flux of two precursors in 4-HC biosynthesis, providing insight into balancing biosynthetic pathways where multiple precursors compete and interfere with each other.


Asunto(s)
Vías Biosintéticas , Ingeniería Metabólica , Vías Biosintéticas/genética , Ingeniería Metabólica/métodos , Redes y Vías Metabólicas
6.
Opt Lett ; 49(4): 838-841, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38359195

RESUMEN

We experimentally establish a 3 × 3 cross-shaped micro-ring resonator (MRR) array-based photonic multiplexing architecture relying on silicon photonics to achieve parallel edge extraction operations in images for photonic convolution neural networks. The main mathematical operations involved are convolution. Precisely, a faster convolutional calculation speed of up to four times is achieved by extracting four feature maps simultaneously with the same photonic hardware's structure and power consumption, where a maximum computility of 0.742 TOPS at an energy cost of 48.6 mW and a convolution accuracy of 95.1% is achieved in an MRR array chip. In particular, our experimental results reveal that this system using parallel edge extraction operators instead of universal operators can improve the imaging recognition accuracy for CIFAR-10 dataset by 6.2% within the same computing time, reaching a maximum of 78.7%. This work presents high scalability and efficiency of parallel edge extraction chips, furnishing a novel, to the best of our knowledge, approach to boost photonic computing speed.

7.
Opt Lett ; 49(13): 3556-3559, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950208

RESUMEN

Optical image encryption has long been an important concept in the fields of photonic network processing and communication. Here, we propose a convolution-like operation-based optical image encryption algorithm exploiting a silicon photonic multiplexing architecture to achieve content security. Particularly, the encryption process is completed in a 3 × 3 cross-shaped photonic micro-ring resonator (MRR) array on chip. For the first time, to the best of our knowledge, this algorithm encodes information in an integrated intensity modulation, effectively reducing the encoding difficulty. Moreover, the high reliability and scalability of optical encryption are ensured using both linear and nonlinear operations on photonic chips according to characteristics of MRRs. As the encryption and decryption experiments show, the image restoration accuracy of our optical encryption algorithm exceeds 99% under real system noise at the pixel level, indicating its noise-robust property. Meanwhile, the peak signal-to-noise ratios of the restored and encrypted images are >60 and <15 dB, respectively, revealing both the high accuracy of the restored image and the small correlation between the encrypted and original images. This work adds to the rapidly expanding field of optical image encryption on photonic chips.

8.
BMC Cancer ; 24(1): 510, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654281

RESUMEN

BACKGROUND: To develop a deep learning(DL) model utilizing ultrasound images, and evaluate its efficacy in distinguishing between benign and malignant parotid tumors (PTs), as well as its practicality in assisting clinicians with accurate diagnosis. METHODS: A total of 2211 ultrasound images of 980 pathologically confirmed PTs (Training set: n = 721; Validation set: n = 82; Internal-test set: n = 89; External-test set: n = 88) from 907 patients were retrospectively included in this study. The optimal model was selected and the diagnostic performance evaluation is conducted by utilizing the area under curve (AUC) of the receiver-operating characteristic(ROC) based on five different DL networks constructed at varying depths. Furthermore, a comparison of different seniority radiologists was made in the presence of the optimal auxiliary diagnosis model. Additionally, the diagnostic confusion matrix of the optimal model was calculated, and an analysis and summary of misjudged cases' characteristics were conducted. RESULTS: The Resnet18 demonstrated superior diagnostic performance, with an AUC value of 0.947, accuracy of 88.5%, sensitivity of 78.2%, and specificity of 92.7% in internal-test set, and with an AUC value of 0.925, accuracy of 89.8%, sensitivity of 83.3%, and specificity of 90.6% in external-test set. The PTs were subjectively assessed twice by six radiologists, both with and without the assisted of the model. With the assisted of the model, both junior and senior radiologists demonstrated enhanced diagnostic performance. In the internal-test set, there was an increase in AUC values by 0.062 and 0.082 for junior radiologists respectively, while senior radiologists experienced an improvement of 0.066 and 0.106 in their respective AUC values. CONCLUSIONS: The DL model based on ultrasound images demonstrates exceptional capability in distinguishing between benign and malignant PTs, thereby assisting radiologists of varying expertise levels to achieve heightened diagnostic performance, and serve as a noninvasive imaging adjunct diagnostic method for clinical purposes.


Asunto(s)
Aprendizaje Profundo , Neoplasias de la Parótida , Ultrasonografía , Humanos , Estudios Retrospectivos , Ultrasonografía/métodos , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano , Adulto Joven , Curva ROC , Diagnóstico Diferencial , Adolescente , Anciano de 80 o más Años , Sensibilidad y Especificidad , Niño
9.
Cell Commun Signal ; 22(1): 395, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39123188

RESUMEN

Esophageal cancer is common worldwide, with ESCC being the most frequent tumor in East Asia. Tumor-associated macrophages are an important component of the ESCC microenvironment. SUMOylation is a post-translational modification of proteins, and SUMO-specific proteases (SENPs) play an important role in de-SUMOylation. In human patients, we discovered that the levels of SENP3 were upregulated in the tumor-associated macrophages. Furthermore, the loss of SENP3 enhanced the alternative activation of macrophages in the 4-NQO-induced ESCC mice model. This is the first study to identify SENP3-mediated macrophage polarization via the de-SUMOylation of interferon regulatory factor 4 (IRF4) at the K349 site. Alternative activation of macrophages increases the migration and invasion potential of ESCC cells and promotes their progression in vivo. Moreover, patients with relatively low SENP3 expression in macrophages exhibit higher primary PET SUVmax value and lymph node metastasis rates. In summary, this study revealed that SENP3-mediated IRF4 de-SUMOylation is crucial for the alternative activation of macrophages and influences the progression of ESCC.


Asunto(s)
Cisteína Endopeptidasas , Factores Reguladores del Interferón , Activación de Macrófagos , Sumoilación , Animales , Femenino , Humanos , Masculino , Ratones , Línea Celular Tumoral , Movimiento Celular , Cisteína Endopeptidasas/metabolismo , Cisteína Endopeptidasas/genética , Progresión de la Enfermedad , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Factores Reguladores del Interferón/metabolismo , Factores Reguladores del Interferón/genética , Macrófagos/metabolismo , Macrófagos Asociados a Tumores/metabolismo
10.
J Vasc Interv Radiol ; 35(7): 1004-1011, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38537738

RESUMEN

PURPOSE: To investigate the feasibility, safety, and clinical outcomes of image-guided thermal ablation in patients with hepatic epithelioid hemangioendothelioma (HEHE). MATERIALS AND METHODS: This was a multicenter retrospective investigation of 18 patients (43.9 years [SD ± 14.8]; 6 men) who underwent image-guided thermal ablation for HEHE between January 2013 and February 2023. A total of 31 ablation sessions (24 involving microwave ablation and 7 involving radiofrequency ablation) were evaluated. The rates of technical success, adverse events, and outcomes were assessed. The Kaplan‒Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) rates. The risk factors affecting PFS were investigated using Cox proportional hazard regression analysis. RESULTS: The technical success rate was 93.5% (29/31). No major adverse events occurred. Local tumor progression occurred after 2 sessions (6.5%, 2/31), and intrahepatic distant metastasis occurred after 16 sessions (51.6%, 16/31). During the medium follow-up time of 37.2 months (range, 3-117 months), the OS and PFS rates were 87.6% and 62.2%, respectively, at 1 year; 75.5% and 37.4%, respectively, at 3 years; and 75.5% and 37.4%, respectively, at 5 years. The median OS and PFS were 90.5 months (95% CI: 68.1-112.8) and 23.8 months (95% CI: 15.4-32.2), respectively. According to the multivariate analysis, a larger tumor size (P = .026) was associated with shorter PFS. CONCLUSIONS: Image-guided thermal ablation is a feasible and safe treatment option for patients with HEHE that resulted in local tumor control and a favorable long-term prognosis.


Asunto(s)
Estudios de Factibilidad , Hemangioendotelioma Epitelioide , Neoplasias Hepáticas , Supervivencia sin Progresión , Humanos , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Hemangioendotelioma Epitelioide/cirugía , Hemangioendotelioma Epitelioide/patología , Hemangioendotelioma Epitelioide/mortalidad , Hemangioendotelioma Epitelioide/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Factores de Riesgo , Factores de Tiempo , Ablación por Radiofrecuencia/efectos adversos , Ablación por Radiofrecuencia/mortalidad , Microondas/uso terapéutico , Microondas/efectos adversos , Progresión de la Enfermedad , Adulto Joven , Anciano , China , Resultado del Tratamiento
11.
BMC Infect Dis ; 24(1): 457, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689228

RESUMEN

BACKGROUND: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. METHODS: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). RESULTS: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. CONCLUSIONS: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.


Asunto(s)
Coinfección , Infecciones por VIH , Puntaje de Propensión , Tuberculosis , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Femenino , Masculino , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Adulto , China/epidemiología , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , Persona de Mediana Edad , Resultado del Tratamiento , Antituberculosos/uso terapéutico , Tiempo de Tratamiento/estadística & datos numéricos , Diagnóstico Tardío
12.
BMC Psychiatry ; 24(1): 466, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914977

RESUMEN

BACKGROUND: Non-suicidal self-injury (NSSI) has exhibited an increasing trend in recent years and is now globally recognized as a major public health problem among adolescents and young adults. Negative life events (NLEs) are positively associated with NSSI. We sought to explore (1) whether sex plays a role in the risk of NLEs leading to NSSI and (2) the role played by mental health (MH). METHODS: We adopted a multi-stage cluster sampling method to select college students across four grades from May to June 2022. Generalized linear models were used to evaluate the relationships between NLEs, sex, MH and NSSI, presented as incidence-rate ratios (RRs) with 95% confidence intervals (CIs). We examined the complex relationship between these variables using the PROCESS method for moderation analysis. RESULTS: Following the exclusion of data that did not meet the study requirements, data from 3,578 students (mean age: 20.53 [± 1.65] years) were included. Poisson regression results indicate that high-level NLEs (RR = 0.110, 95%CI: 0.047-0.173) are associated with increased NSSI. Furthermore, interaction effects were observed among sex, NLEs and NSSI. MH and sex moderated the relationship between NLEs and NSSI. CONCLUSION: Identifying risk factors for NSSI is also important when exploring the interaction between NLEs and MH given the potential for NSSI to significantly increase the risk of later psychopathological symptoms and substance abuse problems. In addition, the significance of sex differences in risk factors for NSSI should be determined. This study evaluated how the impact of NLEs on NSSI can be reduced among adolescents from multiple perspectives.


Asunto(s)
Conducta Autodestructiva , Humanos , Conducta Autodestructiva/psicología , Conducta Autodestructiva/epidemiología , Masculino , Femenino , Adulto Joven , Adolescente , Factores Sexuales , Estudiantes/psicología , Adulto , Acontecimientos que Cambian la Vida , Factores de Riesgo , Salud Mental
13.
J Plant Res ; 137(4): 589-604, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38739241

RESUMEN

Reevesia is an eastern Asian-eastern North American disjunction genus in the family Malvaceae s.l. and comprises approximately 25 species. The relationships within the genus are not well understood. Here, 15 plastomes representing 12 Reevesia species were compared, with the aim of better understanding the species circumscription and phylogenetic relationships within the genus and among genera in the family Malvaceae s.l. The 11 newly sequenced plastomes range between 161,532 and 161, 945 bp in length. The genomes contain 114 unique genes, 18 of which are duplicated in the inverted repeats (IRs). Gene content of these plastomes is nearly identical. All the protein-coding genes are under purifying selection in the Reevesia plastomes compared. The top ten hypervariable regions, SSRs, and the long repeats identified are potential molecular markers for future population genetic and phylogenetic studies. Phylogenetic analysis based on the whole plastomes confirmed the monophyly of Reevesia and a close relationship with Durio (traditional Bombacaceae) in subfamily Helicteroideae, but not with the morphologically similar genera Pterospermum and Sterculia (both of traditional Sterculiaceae). Phylogenetic relationships within Reevesia suggested that two species, R. pubescens and R. thyrsoidea, as newly defined, are not monophyletic. Six taxa, R. membranacea, R. xuefengensis, R. botingensis, R. lofouensis, R. longipetiolata and R. pycnantha, are suggested to be recognized.


Asunto(s)
Evolución Molecular , Filogenia , Plastidios , Plastidios/genética , Genoma de Plastidios/genética , Genes de Plantas , Análisis de Secuencia de ADN
14.
Drug Resist Updat ; 68: 100953, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36841133

RESUMEN

Due to the frequent international and intercontinental transmission of multidrug-resistant bacteria, it is imperative to understand the epidemiology, phylogeography, and population structure of carbapenem-resistant Salmonella enterica (CRSE) across the globe. During the period of 2015-2022, two blaNDM-carrying S. enterica strains were recovered from 3695 Salmonella strains in four hospitals in China. The global phylogenetic framework and geographical distribution of CRSE were defined by our recently updated bacterial whole genome sequence typing and source tracking database BacWGSTdb 2.0 to measure the diversity and evolutionary relatedness in context with epidemiological metadata. Phylogeny for all carbapenemase gene-harboring plasmids in S. enterica based on the pairwise Mash differences was also constructed to evaluate the potential transmission of these plasmids in a global context. A large-scale phylogenetic analysis grouped global CRSE into nine distinct clades. The small genetic distance (< 20 SNPs) between 198 pairs of CRSE suggested the presence of clonal transmission. Global CRSE have significant geographical variations, which was associated with the clonal lineages and carbapenemase genes. Carbapenemase gene-carrying plasmids with a high degree of similarity have surfaced in various hosts and countries. The widespread of multiple-replicon plasmids that offer a great capacity to accommodate multiple antimicrobial resistance genes is continuously enhancing the potential risk of CRSE isolates to propagate globally. Both clonal spread of strains and horizontal transfer of carbapenemase gene-harboring plasmids contribute to the global dissemination of CRSE. Our findings on the worldwide spread and transmission dynamics of this emerging bacterium has increased the knowledge of its global epidemics. Continued epidemiological surveillance is necessary to prevent global outbreak of multidrug-resistant Salmonella infections.


Asunto(s)
Carbapenémicos , Salmonella enterica , Humanos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Salmonella enterica/genética , Filogenia , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Genómica , Pruebas de Sensibilidad Microbiana
15.
J Ultrasound Med ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152758

RESUMEN

OBJECTIVES: Pancreatic steatosis (PS) and pancreatic fibrosis (PF) both show increased pancreatic echogenicity on conventional B-mode ultrasound. In this study, we assessed the applicability of two-dimensional shear-wave elastography (2D-SWE) for their discrimination. METHODS: We gathered data from 120 adults with valid 2D-SWE measurements, comprising 40 healthy individuals, 55 individuals diagnosed with PS via non-enhanced computed tomography (CT), and 25 patients clinically diagnosed with non-calcific chronic pancreatitis. The participants were divided into three groups: normal pancreas (NP), PS, and PF. pancreatic echogenicity, pancreatic stiffness, and CT values between groups were analyzed. RESULTS: The 2D-SWE and CT values among the NP, PS, and PF groups all showed significant differences (P < .001). For the diagnosis of PS and PF using 2D-SWE, the area under the curve (AUC) values were 0.9100 and 0.9940, respectively, with optimal cut-off values of 5.7 kPa for predicting PS and 8.2 kPa for predicting PF. CONCLUSIONS: The 2D-SWE technique enabled rapid and quantitative assessment of the hardness of hyperechoic pancreas visualized on conventional B-mode ultrasound, which holds certain value in distinguishing PS from PF.

16.
Int J Mol Sci ; 25(11)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38891826

RESUMEN

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.


Asunto(s)
Senescencia Celular , Complejo de la Endopetidasa Proteasomal , Proteolisis , Complejo de la Endopetidasa Proteasomal/metabolismo , Humanos , Animales , Histonas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas Nucleares
17.
Angew Chem Int Ed Engl ; 63(13): e202317740, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38318927

RESUMEN

Plasmon-mediated electrocatalysis that rests on the ability of coupling localized surface plasmon resonance (LSPR) and electrochemical activation, emerges as an intriguing and booming area. However, its development seriously suffers from the entanglement between the photoelectronic and photothermal effects induced by the decay of plasmons, especially under the influence of applied potential. Herein, using LSPR-mediated CO2 reduction on Ag electrocatalyst as a model system, we quantitatively uncover the dominant photoelectronic effect on CO2 reduction reaction over a wide potential window, in contrast to the leading photothermal effect on H2 evolution reaction at relatively negative potentials. The excitation of LSPR selectively enhances the CO faradaic efficiency (17-fold at -0.6 VRHE ) and partial current density (100-fold at -0.6 VRHE ), suppressing the undesired H2 faradaic efficiency. Furthermore, in situ attenuated total reflection-surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) reveals a plasmon-promoted formation of the bridge-bonded CO on Ag surface via a carbonyl-containing C1 intermediate. The present work demonstrates a deep mechanistic understanding of selective regulation of interfacial reactions by coupling plasmons and electrochemistry.

18.
J Am Chem Soc ; 145(45): 24499-24505, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38104268

RESUMEN

The transition metal-catalyzed enantioselective C-H functionalization strategy has revolutionized the logic of natural product synthesis. However, previous applications have heavily relied on the use of noble metal catalysts such as rhodium and palladium. Herein, we report the efficient synthesis of C1-chiral 1,2-dihydroisoquinolines (DHIQs) via enantioselective C-H/N-H annulation of picolinamides with alkynes catalyzed by a more sustainable and cheaper 3d metal catalyst, cobalt(II) acetate tetrahydrate. A wide range of enantiomerically enriched DHIQs were obtained in good yields with excellent enantioselectivities (up to 98% yield and >99% ee). The robustness and synthetic potential of this method were demonstrated by the modular and asymmetric syntheses of several tetrahydroisoquinoline alkaloids, including (S)-norlaudanosine, (S)-laudanosine, (S)-xylopinine, (S)-sebiferine, and (S)-cryptostyline II, and the asymmetric syntheses of key intermediates of (+)-solifenacin, FR115427, and (+)-NPS R-568.

19.
Emerg Infect Dis ; 29(11): 2246-2256, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37877525

RESUMEN

Prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has compromised antimicrobial efficacy against severe infections worldwide. To monitor global spread, we conducted a comprehensive genomic epidemiologic study comparing sequences from 21 blaOXA-232-carrying CRKP isolates from China with K. pneumoniae sequence type (ST) 15 strains from 68 countries available in GenBank. Phylogenetic and phylogeographic analyses revealed all blaOXA-232-carrying CRKP isolates belonged to ST15 lineage and exhibited multidrug resistance. Analysis grouped 330 global blaOXA-232-carrying ST15 CRKP strains into 5 clades, indicating clonal transmission with small genetic distances among multiple strains. The lineage originated in the United States, then spread to Europe, Asia, Oceania, and Africa. Most recent common ancestor was traced back to 2000; mutations averaged ≈1.7 per year per genome. Our research helps identify key forces driving global spread of blaOXA-232-carrying CRKP ST15 lineage and emphasizes the importance of ongoing surveillance of epidemic CRKP.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Humanos , Carbapenémicos/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Klebsiella pneumoniae , Filogeografía , Plásmidos , Filogenia , Genómica , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/tratamiento farmacológico , beta-Lactamasas/genética , Pruebas de Sensibilidad Microbiana
20.
Cancer ; 129(3): 356-366, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36401611

RESUMEN

BACKGROUND: Neoadjuvant chemotherapy (NAC) can downstage tumors and axillary lymph nodes in breast cancer (BC) patients. However, tumors and axillary response to NAC are not parallel and vary among patients. This study aims to explore the feasibility of deep learning radiomics nomogram (DLRN) for independently predicting the status of tumors and lymph node metastasis (LNM) after NAC. METHODS: In total, 484 BC patients who completed NAC from two hospitals (H1: 297 patients in the training cohort and 99 patients in the validation cohort; H2: 88 patients in the test cohort) were retrospectively enrolled. The authors developed two deep learning radiomics (DLR) models for personalized prediction of the tumor pathologic complete response (PCR) to NAC (DLR-PCR) and the LNM status (DLR-LNM) after NAC based on pre-NAC and after-NAC ultrasonography images. Furthermore, they proposed two DLRNs (DLRN-PCR and DLRN-LNM) for two different tasks based on the clinical characteristics and DLR scores, which were generated from both DLR-PCR and DLR-LNM. RESULTS: In the validation and test cohorts, DLRN-PCR exhibited areas under the receiver operating characteristic curves (AUCs) of 0.903 and 0.896 with sensitivities of 91.2% and 75.0%, respectively. DLRN-LNM achieved AUCs of 0.853 and 0.863, specificities of 82.0% and 81.8%, and negative predictive values of 81.3% and 87.2% in the validation and test cohorts, respectively. The two DLRN models achieved satisfactory predictive performance based on different BC subtypes. CONCLUSIONS: The proposed DLRN models have the potential to accurately predict the tumor PCR and LNM status after NAC. PLAIN LANGUAGE SUMMARY: In this study, we proposed two deep learning radiomics nomogram models based on pre-neoadjuvant chemotherapy (NAC) and preoperative ultrasonography images for independently predicting the status of tumor and axillary lymph node (ALN) after NAC. A more comprehensive assessment of the patient's condition after NAC can be achieved by predicting the status of the tumor and ALN separately. Our model can potentially provide a noninvasive and personalized method to offer decision support for organ preservation and avoidance of excessive surgery.


Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Estudios Retrospectivos , Terapia Neoadyuvante/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ultrasonografía , Metástasis Linfática/patología
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