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1.
BMC Med ; 22(1): 188, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715068

RESUMEN

BACKGROUND: Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. METHODS: Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. RESULTS: The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063-1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008-1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. CONCLUSIONS: Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.


Asunto(s)
Inundaciones , Humanos , Inundaciones/mortalidad , Estudios de Casos y Controles , Reino Unido/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Adulto , Causas de Muerte , Factores de Riesgo
2.
Abdom Radiol (NY) ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744700

RESUMEN

PURPOSE: This study aimed to determine the diagnostic efficacy of various indicators and models for the prediction of gastric cancer with liver metastasis. METHODS: Clinical and spectral computed tomography (CT) data from 80 patients with gastric adenocarcinoma who underwent surgical resection were retrospectively analyzed. Patients were divided into metastatic and non-metastatic groups based on whether or not to occur liver metastasis, and the region of interest (ROI) was measured manually on each phase iodine map at the largest level of the tumor. Iodine concentration (IC), normalized iodine concentration (nIC), and clinical data of the primary gastric lesions were analyzed. Logistic regression analysis was used to construct the clinical indicator (CI) and clinical indicator-spectral CT iodine concentration (CI-Spectral CT-IC) Models, which contained all of the parameters with statistically significant differences between the groups. Receiver operating characteristic (ROC) curves were constructed to evaluate the accuracy of the models. RESULTS: The metastatic group showed significantly higher levels of Cancer antigen125 (CA125), carcinoembryonic antigen (CEA), IC, and nIC in the arterial phase, venous phase, and delayed phase than the non-metastatic group (all p < 0.05). Normalized iodine concentration Venous Phase (nICVP) exhibited a favorable performance among all IC and nIC parameters for forecasting gastric cancer with liver metastasis (area under the curve (AUC), 0.846). The combination model of clinical data with significant differences and nICVP showed the best diagnostic accuracy for predicting liver metastasis from gastric cancer, with an AUC of 0.897. CONCLUSION: nICVP showed the best diagnostic efficacy for predicting gastric cancer with liver metastasis. Clinical Indicators-normalized ICVP model can improve the prediction accuracy for this condition.

3.
bioRxiv ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38746280

RESUMEN

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

4.
Curr Med Sci ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748369

RESUMEN

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

5.
Foods ; 13(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38731757

RESUMEN

The traditional fermentation process of soy sauce employs a hyperhaline model and has a long fermentation period. A hyperhaline model can improve fermentation speed, but easily leads to the contamination of miscellaneous bacteria and fermentation failure. In this study, after the conventional koji and moromi fermentation, the fermentation broth was pasteurized and diluted, and then inoculated with three selected microorganisms including Corynebacterium glutamicum, Corynebacterium ammoniagenes, and Lactiplantibacillus plantarum for secondary fermentation. During this ten-day fermentation, the pH, free amino acids, organic acids, nucleotide acids, fatty acids, and volatile compounds were analyzed. The fermentation group inoculated with C. glutamicum accumulated the high content of amino acid nitrogen of 0.92 g/100 mL and glutamic acid of 509.4 mg/100 mL. The C. ammoniagenes group and L. plantarum group were rich in nucleotide and organic acid, respectively. The fermentation group inoculated with three microorganisms exhibited the best sensory attributes, showing the potential to develop a suitable fermentation method. The brewing speed of the proposed process in this study was faster than that of the traditional method, and the umami substances could be significantly accumulated in this low-salt fermented model (7% w/v NaCl). This study provides a reference for the low-salt and rapid fermentation of seasoning.

6.
Discov Oncol ; 15(1): 157, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733530

RESUMEN

OBJECTIVE: To investigate the action of circPDK1 in paclitaxel (PTX) resistance in non-small cell lung cancer (NSCLC). METHODS: circPDK1, miR-4731-5p, and GIGYF1 levels were determined by RT-qPCR and Western blot. Cell proliferation was detected by CCK-8 and colony formation assay, apoptosis by flow cytometry, invasion by Transwell assay. The targeting relationship between miR-4731-5p and circPDK1 or GIGYF1 was confirmed by dual luciferase reporter gene and RIP assay. A xenograft tumor model was established to determine the role of circPDK1 in PTX resistance. RESULTS: circPDK1 was overexpressed in PTX-resistant NSCLC, and depleting circPDK1 hampered proliferation and invasion of PTX-resistant cells, activated apoptosis, and improved PTX sensitivity. circPDK1 bound to miR-4731-5p, and increasing miR-4731-5p expression salvaged the effect of circPDK1 depletion on PTX resistance. miR-4731-5p directly targeted GIGYF1, and upregulating GIGYF1 offset the promoting effect of circPDK1 knockdown on PTX sensitivity. NSCLC tumor growth was inhibited and PTX sensitivity improved when circPDK1 was suppressed. CONCLUSION: Depleting circPDK1 promotes PTX sensitivity of NSCLC cells via miR-4731-5p/GIGYF1 axis, thereby inhibiting NSCLC pregnancy.

7.
Nat Commun ; 15(1): 3891, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719858

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic, along with the implementation of public health and social measures (PHSMs), have markedly reshaped infectious disease transmission dynamics. We analysed the impact of PHSMs on 24 notifiable infectious diseases (NIDs) in the Chinese mainland, using time series models to forecast transmission trends without PHSMs or pandemic. Our findings revealed distinct seasonal patterns in NID incidence, with respiratory diseases showing the greatest response to PHSMs, while bloodborne and sexually transmitted diseases responded more moderately. 8 NIDs were identified as susceptible to PHSMs, including hand, foot, and mouth disease, dengue fever, rubella, scarlet fever, pertussis, mumps, malaria, and Japanese encephalitis. The termination of PHSMs did not cause NIDs resurgence immediately, except for pertussis, which experienced its highest peak in December 2023 since January 2008. Our findings highlight the varied impact of PHSMs on different NIDs and the importance of sustainable, long-term strategies, like vaccine development.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/prevención & control , China/epidemiología , Enfermedades Transmisibles/epidemiología , Pandemias/prevención & control , Incidencia , Estaciones del Año , Salud Pública , Control de Enfermedades Transmisibles/métodos
8.
Am J Cancer Res ; 14(4): 1609-1621, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38726282

RESUMEN

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings.

10.
BMC Anesthesiol ; 24(1): 176, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760677

RESUMEN

BACKGROUND: The role of mechanical power on pulmonary outcomes after thoracic surgery with one-lung ventilation was unclear. We investigated the association between mechanical power and postoperative pulmonary complications in patients undergoing thoracoscopic lung resection surgery. METHODS: In this single-center, prospective observational study, 622 patients scheduled for thoracoscopic lung resection surgery were included. Volume control mode with lung protective ventilation strategies were implemented in all participants. The primary endpoint was a composite of postoperative pulmonary complications during hospital stay. Multivariable logistic regression models were used to evaluate the association between mechanical power and outcomes. RESULTS: The incidence of pulmonary complications after surgery during hospital stay was 24.6% (150 of 609 patients). The multivariable analysis showed that there was no link between mechanical power and postoperative pulmonary complications. CONCLUSIONS: In patients undergoing thoracoscopic lung resection with standardized lung-protective ventilation, no association was found between mechanical power and postoperative pulmonary complications. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058528, date of registration: April 10, 2022.


Asunto(s)
Ventilación Unipulmonar , Complicaciones Posoperatorias , Humanos , Estudios Prospectivos , Masculino , Femenino , Ventilación Unipulmonar/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Persona de Mediana Edad , Anciano , Neumonectomía/efectos adversos , Neumonectomía/métodos , Toracoscopía/métodos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/epidemiología , Cirugía Torácica Asistida por Video/métodos , Cirugía Torácica Asistida por Video/efectos adversos
11.
Adv Sci (Weinh) ; : e2401263, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767182

RESUMEN

Single-cell multiomic and exosome analyses are potent tools in various fields, such as cancer research, immunology, neuroscience, microbiology, and drug development. They facilitate the in-depth exploration of biological systems, providing insights into disease mechanisms and aiding in treatment. Single-cell isolation, which is crucial for single-cell analysis, ensures reliable cell isolation and quality control for further downstream analyses. Microfluidic chips are small lightweight systems that facilitate efficient and high-throughput single-cell isolation and real-time single-cell analysis on- or off-chip. Therefore, most current single-cell isolation and analysis technologies are based on the single-cell microfluidic technology. This review offers comprehensive guidance to researchers across different fields on the selection of appropriate microfluidic chip technologies for single-cell isolation and analysis. This review describes the design principles, separation mechanisms, chip characteristics, and cellular effects of various microfluidic chips available for single-cell isolation. Moreover, this review highlights the implications of using this technology for subsequent analyses, including single-cell multiomic and exosome analyses. Finally, the current challenges and future prospects of microfluidic chip technology are outlined for multiplex single-cell isolation and multiomic and exosome analyses.

12.
Org Lett ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767212

RESUMEN

A catalytic-condition-controlled synthesis strategy was reported to build quinolizinone and indolizine derivatives from the easily available enamide and triazole substrates with high regioselectivity and good functional group tolerance. More especially, this transformation has successfully fulfilled a C-H bond activation of terminal olefin from enamides followed by a [3 + 3] and a [2 + 3] cyclization cascade under different catalytic conditions, respectively, to provide two kinds of potentially biologically active heterocyclic scaffolds with a ring-junction nitrogen atom. Mechanistically, the methoxyamine formyl group serves as either a traceless directing group (DG) or an oxidizing DG via the C-N and C-C cleavage in this protocol.

13.
Adv Healthc Mater ; : e2400343, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738846

RESUMEN

Stem cell transplantation has been proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel was proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protected BMSCs from shear force and mechanical stress before and after injection but also repaired the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD. This article is protected by copyright. All rights reserved.

14.
Food Funct ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38727519

RESUMEN

In order to explore the in vivo anti-food allergy activity of Lactobacillus sakei subsp. sakei-fermented Eucheuma spinosum polysaccharides F1-ESP-3, an ovalbumin (OVA)-induced food allergy mouse model was established by ascites immunization and gavage. The weight, temperature, incidence of diarrhea, levels of allergic mediators and inflammatory factors in the serum of mice were analyzed. We analyzed the differentiation of mouse spleen lymphocytes and the proportion of sensitized mast cells by flow cytometry. The intestinal barrier status of mice was analyzed by intestinal pathological tissue sections and microbiota sequencing. The results showed that F1-ESP-3 could alleviate the food allergy symptoms of mice, such as hypothermia and loose stool; levels of OVA-specific immunoglobulin E, mast cell protease and histamine in the serum of sensitized mice and the proportion of dendritic cells and mast cells in mouse spleen were significantly reduced; in addition, F1-ESP-3 may protect the intestinal barrier and further improve the intestinal microenvironment of food-allergic mice by regulating the abundance of Bacteroidetes and Firmicutes. F1-ESP-3 can further improve the intestinal microenvironment of food-allergic mice by upregulating the levels of Lachnospiraceae, and may affect the signal pathways such as NOD-like receptor, MAPK, I kappa B and antigen processing and presentation.

15.
Sci Rep ; 14(1): 10646, 2024 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724530

RESUMEN

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.


Asunto(s)
Imagen por Resonancia Magnética , Nanomedicina Teranóstica , Imagen por Resonancia Magnética/métodos , Nanomedicina Teranóstica/métodos , Animales , Ratones , Humanos , Doxorrubicina/química , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Línea Celular Tumoral , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Succímero/química , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología
16.
Int J Biol Macromol ; 269(Pt 2): 132215, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38729482

RESUMEN

Food allergy has a significant impact on the health and well-being of individuals, affecting both their physical and mental states. Research on natural bioactive compounds, such as polysaccharides extracted from seaweeds, holds great promise in the treatment of food allergies. In this study, fermented Gracilaria lemaneiformis polysaccharides (F-GLSP) were prepared using probiotic fermentation. Probiotic fermentation of Gracilaria lemaneiformis reduces the particle size of polysaccharides. To compare the anti-allergic activity of F-GLSP with unfermented Gracilaria lemaneiformis polysaccharides (UF-GLSP), an OVA-induced mouse food allergy model was established. F-GLSP exhibited a significant reduction in OVA-specific IgE and mMCP levels in allergic mice. Moreover, it significantly inhibited Th2 differentiation and IL-4 production and significantly promoted Treg differentiation and IL-10 production in allergic mice. In contrast, UF-GLSP only reduced OVA-specific IgE and mMCP in the serum of allergic mice. Furthermore, F-GLSP demonstrated a more pronounced regulation of intestinal flora abundance compared to UF-GLSP, significantly influencing the populations of Firmicutes, Bacteroidetes, Lactobacillus, and Clostridiales in the intestines of mice with food allergy. These findings suggest that F-GLSP may regulate food allergies in mice through multiple pathways. In summary, this study has promoted further development of functional foods with anti-allergic properties based on red algae polysaccharides.

17.
J Transl Med ; 22(1): 442, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730286

RESUMEN

INTRODUCTION: Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear. METHODS: Firstly, 277 advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy in Sun Yat-sen University Cancer Center were enrolled in the study. Pretreatment and the alteration of ChE after 2 courses of immunotherapy and survival outcomes were collected. Kaplan-Meier survival and cox regression analysis were performed, and nomogram was conducted to identify the prognostic and predicted values. Secondly, choline metabolism-related genes were screened using Cox regression, and a prognostic model was constructed. Functional enrichment analysis and immune microenvironment analysis were also conducted. Lastly, to gain further insights into potential mechanisms, single-cell analysis was performed. RESULTS: Firstly, baseline high level ChE and the elevation of ChE after immunotherapy were significantly associated with better survival outcomes for advanced NSCLC. Constructed nomogram based on the significant variables from the multivariate Cox analysis performed well in discrimination and calibration. Secondly, 4 choline metabolism-related genes (MTHFD1, PDGFB, PIK3R3, CHKB) were screened and developed a risk signature that was found to be related to a poorer prognosis. Further analysis revealed that the choline metabolism-related genes signature was associated with immunosuppressive tumor microenvironment, immune escape and metabolic reprogramming. scRNA-seq showed that MTHFD1 was specifically distributed in tumor-associated macrophages (TAMs), mediating the differentiation and immunosuppressive functions of macrophages, which may potentially impact endothelial cell proliferation and tumor angiogenesis. CONCLUSION: Our study highlights the discovery of ChE as a prognostic marker in advanced NSCLC, suggesting its potential for identifying patients who may benefit from immunotherapy. Additionally, we developed a prognostic signature based on choline metabolism-related genes, revealing the correlation with the immunosuppressive microenvironment and uncovering the role of MTHFD1 in macrophage differentiation and endothelial cell proliferation, providing insights into the intricate workings of choline metabolism in NSCLC pathogenesis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Colina , Células Endoteliales , Neoplasias Pulmonares , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Colina/metabolismo , Masculino , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Persona de Mediana Edad , Pronóstico , Inmunoterapia , Terapia de Inmunosupresión , Estimación de Kaplan-Meier , Nomogramas , Reprogramación Metabólica
18.
J Transl Med ; 22(1): 486, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773508

RESUMEN

BACKGROUND: Immunotherapy has brought about a paradigm shift in the treatment of cancer. However, the majority of patients exhibit resistance or become refractory to immunotherapy, and the underlying mechanisms remain to be explored. METHODS: Sing-cell RNA sequencing (scRNA­seq) datasets derived from 1 pretreatment and 1 posttreatment achieving pathological complete response (pCR) patient with lung adenocarcinoma (LUAD) who received neoadjuvant immunotherapy were collected, and pySCENIC was used to find the gene regulatory network (GRN) between cell types and immune checkpoint inhibitor (ICI) response. A regulon predicting ICI response was identified and validated using large­scale pan-cancer data, including a colorectal cancer scRNA­seq dataset, a breast cancer scRNA­seq dataset, The Cancer Genome Atlas (TCGA) pan-cancer cohort, and 5 ICI transcriptomic cohorts. Symphony reference mapping was performed to construct the myeloid cell map. RESULTS: Thirteen major cluster cell types were identified by comparing pretreatment and posttreatment patients, and the fraction of myeloid cells was higher in the posttreatment group (19.0% vs. 11.8%). A PPARG regulon (containing 23 target genes) was associated with ICI response, and its function was validated by a colorectal cancer scRNA­seq dataset, a breast cancer scRNA­seq dataset, TCGA pan-cancer cohort, and 5 ICI transcriptomic cohorts. Additionally, a myeloid cell map was developed, and cluster I, II, and III myeloid cells with high expression of PPARG were identified. Moreover, we constructed a website called PPARG ( https://pparg.online/PPARG/ or http://43.134.20.130:3838/PPARG/ ), which provides a powerful discovery tool and resource value for researchers. CONCLUSIONS: The PPARG regulon is a predictor of ICI response. The myeloid cell map enables the identification of PPARG subclusters in public scRNA-seq datasets and provides a powerful discovery tool and resource value.


Asunto(s)
Inmunoterapia , Células Mieloides , Terapia Neoadyuvante , Neoplasias , Regulón , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Humanos , Regulón/genética , Células Mieloides/metabolismo , Neoplasias/genética , Neoplasias/terapia , Neoplasias/inmunología , Resultado del Tratamiento , Redes Reguladoras de Genes , Femenino , Regulación Neoplásica de la Expresión Génica
19.
Adv Sci (Weinh) ; : e2309744, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773709

RESUMEN

Viral RNA detection is crucial in preventing and treating early infectious diseases. Traditional methods of RNA detection require a large amount of equipment and technical personnel. In this study, proposed a programmable controlled surface acoustic wave (SAW)-based RNA detecting device has been proposed. The proposed device can perform the entire viral RNA detection process, including cell lysis by cell-microparticle collision through SAW-induced liquid whirling, RNA capture by SAW-suspended magnetic beads, RNA elution through SAW-induced high streaming force, and PCR thermal cycling through SAW-generated heat. The device has completed all RNA detection steps in one mini chamber, requiring only 489 µl reagents for RNA extraction, much smaller than the amount used in manual RNA extraction (2065 µl). The experimental results have shown that PCR results from the device are comparable to those achieved via commercial qPCR instrumental detection. This work has demonstrated the potential of SAW-based lab-on-a-chip devices for point-of-care testing and provided a novel approach for rapidly detecting infectious diseases.

20.
Liver Int ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775078

RESUMEN

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

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