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1.
J Acoust Soc Am ; 156(2): 891-897, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39120871

RESUMEN

Unconsolidated porous media are distinct from consolidated porous rocks in the negligible bulk and shear moduli. This paper is motivated by resolving the control mechanism of P-wave attenuation in the media (represented by Toyoura sands and glass beads) saturated with water. The first model is Biot theory in which longitudinal friction (arising from velocity difference between the two phases) is quantified using dynamic permeability as a function of frequency. The first model simulates phase velocity (Vp) and the ultrasonically measured quality factor (Qp) well. A second model is the transverse squirt model in which squirt is induced by pressure differential between contact of grains (COG) and the main pore space. The second model outputs unrealistic Vp and Qp. The results reveal that P-wave attenuation in unconsolidated porous media (saturated with water) is governed by longitudinal friction rather than intrapore squirt. Remarkably, low-frequency dynamic permeability is much smaller than Darcy permeability, indicating that ultrasonic P-wave is surprisingly capable of indirectly detecting the very narrow gap at COG.

2.
Nat Prod Res ; : 1-9, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39105448

RESUMEN

To reveal the potential mechanism of the effect of Chinese Herbal Medicine Fuzi on Aplastic anaemia (AA) according to the network pharmacology approach and molecular docking. According to Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS/MS), 146 chemical ingredients of Fuzi were obtained. By SwissADME online system analysis, a total of 55 compounds such as Magnoflorine, Scutellarein, Luteolin and Gingerol may be the main active components of Fuzi and 145 common targets related to AA were predicted. 17 targets such as MAPK1, AKT1 and GRB2 were considered as hub targets. KEGG and GO enrichment analysis obtained 122 signalling pathways and 950 remarkable results. These results suggested that Fuzi exerted pharmacological effects on AA mainly by regulating PI3K-Akt, MAPK and JAK-STAT signalling pathways and epithelial cell proliferation, cell differentiation, regulate energy production and other biological processes. Meanwhile, molecular docking results showed that the hub targets had good binding ability with the main active ingredients.

3.
Proc Natl Acad Sci U S A ; 121(28): e2402407121, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38959045

RESUMEN

Trade-offs between evolutionary gain and loss are prevalent in nature, yet their genetic basis is not well resolved. The evolution of insect resistance to insecticide is often associated with strong fitness costs; however, how the fitness trade-offs operates remains poorly understood. Here, we show that the mitogen-activated protein kinase (MAPK) pathway and its upstream and downstream actors underlie the fitness trade-offs associated with insecticide resistance in the whitefly Bemisia tabaci. Specifically, we find a key cytochrome P450 gene CYP6CM1, that confers neonicotinoids resistance to in B. tabaci, is regulated by the MAPKs p38 and ERK through their activation of the transcription factor cAMP-response element binding protein. However, phosphorylation of p38 and ERK also leads to the activation of the transcription repressor Cap "n" collar isoform C (CncC) that negatively regulates exuperantia (Ex), vasa (Va), and benign gonial cell neoplasm (Bg), key genes involved in oogenesis, leading to abnormal ovary growth and a reduction in female fecundity. We further demonstrate that the transmembrane G protein-coupled receptor (GPCR) neuropeptide FF receptor 2 (NPFF2) triggers the p38 and ERK pathways via phosphorylation. Additionally, a positive feedback loop between p38 and NPFF2 leads to the continuous activation of the MAPK pathways, thereby constitutively promoting neonicotinoids resistance but with a significant reproductive cost. Collectively, these findings provide fundamental insights into the role of cis-trans regulatory networks incurred by GPCR-MAPK signaling pathways in evolutionary trade-offs and applied knowledge that can inform the development of strategies for the sustainable pest control.


Asunto(s)
Hemípteros , Proteínas de Insectos , Resistencia a los Insecticidas , Sistema de Señalización de MAP Quinasas , Receptores Acoplados a Proteínas G , Animales , Hemípteros/genética , Hemípteros/metabolismo , Resistencia a los Insecticidas/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Femenino , Insecticidas/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética
4.
Nat Commun ; 15(1): 6418, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080296

RESUMEN

Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.


Asunto(s)
Blastocisto , Proteína p300 Asociada a E1A , Desarrollo Embrionario , Regulación del Desarrollo de la Expresión Génica , Histonas , Lisina , Histonas/metabolismo , Animales , Desarrollo Embrionario/genética , Femenino , Ratones , Proteína p300 Asociada a E1A/metabolismo , Proteína p300 Asociada a E1A/genética , Blastocisto/metabolismo , Lisina/metabolismo , Humanos , Procesamiento Proteico-Postraduccional , Regiones Promotoras Genéticas , Epigénesis Genética , Masculino
7.
Sci Rep ; 14(1): 17086, 2024 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048697

RESUMEN

We conducted a retrospective study to investigate risk factors for tuberculosis care-seeking delay and diagnostic delays among pediatric pulmonary tuberculosis cases in Zhejiang Province from 2013 to 2022. Among 1274 cases, 49.61% experienced tuberculosis care-seeking delays (> 14 days from symptom onset to first hospital visit) and 14.91% faced diagnostic delays (> 14 days from initial consultation to diagnosis). The proportion of care-seeking delays ranged from 37.42 to 64.89%, while diagnostic delay fluctuated from 6.11 to 21.02%. Urban residence (OR = 0.78, 95% CI 0.62-0.98, P = 0.030), first visiting a municipal-level hospital (OR = 0.57, 95% CI 0.45-0.72, P < 0.001), and diagnostic method (OR = 0.66, 95%CI 0.52-0.84, P < 0.001) were associated with tuberculosis care-seeking delay, whereas first visiting a municipal-level hospital (OR = 2.05, 95% CI 1.49-2.80, P < 0.001) was linked to diagnostic delay. Further analysis using a 28-day cutoff point revealed that children aged 0-4 years, those from migrant populations, laboratory-confirmed patients, and those who first visited a county-level hospital were more likely to experience delays in seeking tuberculosis care. Thus, society should pay more attention to the health of rural, migrant, and 0-4-year-old children, as they are at higher risk of experiencing tuberculosis care-seeking delays.


Asunto(s)
Diagnóstico Tardío , Aceptación de la Atención de Salud , Tuberculosis Pulmonar , Humanos , China/epidemiología , Femenino , Masculino , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Estudios Retrospectivos , Diagnóstico Tardío/estadística & datos numéricos , Niño , Preescolar , Aceptación de la Atención de Salud/estadística & datos numéricos , Factores de Riesgo , Lactante , Adolescente
8.
Opt Express ; 32(11): 19495-19507, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859083

RESUMEN

We propose two schemes for estimating the separation of two thermal sources via double homodyne and double array homodyne detection considering the joint measurement of conjugate quadratures of the image plane field.By using the Cramér-Rao bound, we demonstrate that the two schemes can estimate the separation well below the Rayleigh limit and have an advantage over direct imaging when the average photon number per source exceeds five.For arbitrary source strengths, double homodyne detection is superior to homodyne detection when the separation is above 25/4 σ/N s , σ is the beam width, Ns is the average photon number per source.A larger separation can be estimated better via double array homodyne detection with the superiority of flexible operation compared with other schemes. High-speed and high-efficiency detection enables the measurement schemes with potential practical applications in fluorescence microscopy, astronomy and quantum imaging.

9.
Am J Cancer Res ; 14(5): 2584-2607, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859838

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) has been characterized by a low therapeutic response and poor prognosis. Currently, there are no reliable predictive models for HNSCC progression and therapeutic efficacy. This study explores the role of diverse patterns of cell death in tumor development, positing them as predictive factors of HNSCC prognosis. We utilized bulk transcriptome and single-cell transcriptome, align with clinical information from TCGA and GEO database, to analyze genes associated with 15 types of cell death and construct a cell death index (CDI) signature. The associations of CDI with tumor-infiltrating immune cells and immunotherapy-related biomarkers were also evaluated using various algorithms. The CDI signature emerged as a robust prognosis biomarker that could identify patients who can benefit potentially from immunotherapy, thus improving diagnostic accuracy and optimizing clinical decisions in HNSCC management. Notably, we discovered that CAAP1 deficiency not only induced apoptosis but also enhanced anti-tumor immunity, suggesting its potential as a target for clinical drug development.

10.
Front Pharmacol ; 15: 1383831, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863976

RESUMEN

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

11.
BMC Med Educ ; 24(1): 680, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902673

RESUMEN

BACKGROUND: Blended learning comprised with flipped classroom (FC) and "internet plus" is a new learning strategy that reverses the position of teacher and students in class, and provides abundant learning resources before and after class. This study aimed to assess the impact of blended learning on learning outcomes in evidence-based medicine course, and compare with traditional learning method. METHODS: The participants of the two groups were from two difference cohorts in Air force medical university in China. The two groups toke the same pre-test before class and then were given the teaching of same chapters of evidence-based medicine with two different learning strategy. In the blended learning group, the participants were required to create a debriefing slide about their learning outcomes and the answers of questions given in advance after study the learning material sent by teacher a week before class, and the teacher gave a detailed summary based on the common problems, and distributed multimedia resources for review. After the experiment was carried out, learning outcomes including mastering knowledge, learning satisfaction, and self-evaluation were compared. RESULTS: 37 and 39 participants were enrolled to blended learning and traditional learning groups, respectively, and no statistically significant difference were found in baseline information and pre-test grades. Statistically significant differences were found in learning outcomes including post-test score (t = 2.90, p = 0.005), changes of scores between pre-test and post-test (t = 2.49, p = 0.022), learning satisfaction (t = 12.41, p = 0.001), and self-evaluation of the two groups (t = 7.82, p = 0.001). Especially, the changes of scores between pre-test and post-test of blended learning and traditional learning groups were 4.05 (4.26), and 2.00 (2.85), respectively. CONCLUSIONS: This study showed that compared with traditional learning strategy, blended learning can effectively enhanced participants' acquisition of knowledge, learning satisfaction, and self-evaluation in evidence-based medicine. Using blended learning method including "internet plus" and flipped classroom is recommended in the teaching of evidence-based medicine course.


Asunto(s)
Evaluación Educacional , Medicina Basada en la Evidencia , Humanos , Medicina Basada en la Evidencia/educación , China , Curriculum , Femenino , Masculino , Aprendizaje Basado en Problemas/métodos , Estudiantes de Medicina/psicología , Enseñanza , Aprendizaje , Educación de Pregrado en Medicina/métodos
12.
Ambio ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38727941

RESUMEN

Considering both ecological and social dimensions in the assessment of ecosystem services (ESs) can facilitate acceptable and inclusive management strategies, especially in peri-urban areas characterized by intricate human-ecosystem interactions. A limited body of research, however, has mapped the plural values of ESs and their different types of trade-offs in such areas. This research aimed to execute an interdisciplinary analysis of the biophysical and social values of ESs in peri-urban Shanghai, China, through a social-ecological approach that integrates spatial biophysical assessment with participatory mapping. Trade-off analysis in both ES types and ES valuations were then conducted, and multicriteria decision-making was applied for conservation. Our results reveal that trade-off intensities were lower within the social values compared to the biophysical values. Within both value dimensions, relatively stronger trade-offs were found between food production and other ESs. Areas with both high biophysical and social values were infrequently observed across ESs. Based on the characteristics of diverse values, our study identified priority conservation areas and provided management implications. We argue that adopting the integrated social-ecological perspective in sustainable environmental management contributes to the realization of harmonious coexistence between people and nature in peri-urban areas.

13.
Front Pharmacol ; 15: 1380939, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38799157

RESUMEN

Introduction: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in patients with no obvious signs of infection, early antibiotic treatment seems to clinically improve the disease, but more studies are needed to determine the prognostic impact of antibiotic treatment in AECOPD patients with no obvious signs of infection. Purpose: To clarify the impact of antibiotic treatment on the short-term and long-term prognoses of AECOPD patients without obvious signs of infection. Methods: The impact of the two treatment methods on the prognosis of patients was compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, parallel-controlled clinical trial was conducted in a department of respiratory and critical care medicine in Central China. All patients met the inclusion criteria for AECOPD, and the patients were randomly assigned to the antibiotic group or the nonantibiotic group at a 1:1 ratio. Patients in the antibiotic group were given moxifloxacin 400 mg/day intravenously for 7 days. Patients in the nonantibiotic group were intravenously injected with the same amount of normal saline as the amount of moxifloxacin given to those in the antibiotic group for 7 days. Results: There were 406 patients in the antibiotic group and 410 patients in the nonantibiotic group. During the short-term and long-term follow-ups, the acute exacerbation frequency, intensive care unit (ICU) treatment rate, mortality, and mMRC and CAT scores were not significantly different between the two groups (p > 0.05). At the 180- and 360-day follow-ups, the forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (p > 0.05). The 30-day readmission rate was significantly lower in the antibiotic group than in the nonantibiotic group (p < 0.05). The time from discharge to the first acute exacerbation was not significantly different between the two groups (p > 0.05). The length of the first hospital stay after discharge was significantly lower in the antibiotic group (5.84 days) than in the nonantibiotic group (6.75 days) (p < 0.05). At the 30-day follow-up, the acute exacerbation frequency, age, C-reactive protein (CRP) level, and sputum viscosity were significantly greater in the nonantibiotic group than in the antibiotic group (p < 0.05). In addition, according to the receiver operating characteristic (ROC) analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly greater in COPD patients aged >62.5 years, with a CRP level >12.56 mg/L or with a sputum viscosity >III, in the nonantibiotic group than in those in the antibiotic group, suggesting that the short-term prognosis was poor. Conclusion: Patients who are >62.5 years of age, have a CRP concentration >12.56 mg/L, or have a sputum viscosity >III without obvious signs of infection should be treated with antibiotics to improve their short-term prognosis. Clinical Trial Registration: (https://www.chictr.org.cn), (ChiCTR1800018921).

14.
Sci Total Environ ; 935: 173335, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763194

RESUMEN

Maintaining and improving soil health (SH) is essential for the long-term sustainability and productivity of agriculture, notably in the face of climate change. This study addressed the challenge of selecting appropriate soil indicators, scoring methods, and indexing approaches for SH evaluation under no-till crop rotations. This study aimed to develop minimum datasets (MDS) and assess SH in six crop rotations (denoted as conventional, diversified, high-risk and high-reward, market-driven, pulse-oilseed intensified, and soil health-enhanced rotations) at three sites on the Canadian prairies. Fourteen soil indicators in the total dataset (TDS) were examined, encompassing both chemical (0-7.5 cm depth) and physical (5-10 cm depth) properties. Principal component analysis (PCA) identified MDSs from the TDS. Two scoring [linear (L) and non-linear (NL)] and two SH indexing approaches [additive (A) and weighted additive (WA)] were used to calculate the SH index (SHI). One-way ANOVA evaluated the SHI among crop rotations. The PCA revealed variations in the number of indicators in the MDS across sites, with soil organic carbon, bulk density, macroporosity, and plant-available water capacity as the common indicators for MDS across sites. Other indicators such as particulate organic matter carbon, aggregate stability, field capacity, and microporosity were found to be important, depending on the site. The non-linear weighted additive SH indexing (SHI.NLWA) proved to be the most sensitive and effective for differentiating among crop rotations in the short-term across study sites (R2 = 0.89-0.94, P < 0.05). Crop rotations significantly influenced SHI, with the diversified and high-risk and high-reward rotations having the highest SHI at Lethbridge and Scott, respectively. Overall, the diversified rotation at Lethbridge and Swift Current, along with the high-risk and high-reward rotation at Scott, exhibited better soil function than other rotations. Monitoring SHI over time and selecting crop rotations that improve SH can collectively enhance soil functions and agroecosystem productivity.


Asunto(s)
Agricultura , Monitoreo del Ambiente , Suelo , Suelo/química , Canadá , Agricultura/métodos , Monitoreo del Ambiente/métodos , Pradera , Productos Agrícolas , Cambio Climático
15.
Cell Rep Med ; 5(5): 101522, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38701781

RESUMEN

Neuroinflammation plays a significant role in ischemic injury, which can be promoted by oxidized mitochondrial DNA (Ox-mtDNA). Cytidine/uridine monophosphate kinase 2 (CMPK2) regulates mtDNA replication, but its role in neuroinflammation and ischemic injury remains unknown. Here, we report that CMPK2 expression is upregulated in monocytes/macrophages and microglia post-stroke in humans and mice, respectively. Microglia/macrophage CMPK2 knockdown using the Cre recombination-dependent adeno-associated virus suppresses the inflammatory responses in the brain, reduces infarcts, and improves neurological outcomes in ischemic CX3CR1Cre/ERT2 mice. Mechanistically, CMPK2 knockdown limits newly synthesized mtDNA and Ox-mtDNA formation and subsequently blocks NLRP3 inflammasome activation in microglia/macrophages. Nordihydroguaiaretic acid (NDGA), as a CMPK2 inhibitor, is discovered to reduce neuroinflammation and ischemic injury in mice and prevent the inflammatory responses in primary human monocytes from ischemic patients. Thus, these findings identify CMPK2 as a promising therapeutic target for ischemic stroke and other brain disorders associated with neuroinflammation.


Asunto(s)
Accidente Cerebrovascular Isquémico , Microglía , Enfermedades Neuroinflamatorias , Animales , Humanos , Masculino , Ratones , Lesiones Encefálicas/patología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/genética , Isquemia Encefálica/patología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Inflamasomas/metabolismo , Accidente Cerebrovascular Isquémico/patología , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/genética , Macrófagos/metabolismo , Macrófagos/patología , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/patología , Monocitos/metabolismo , Monocitos/efectos de los fármacos , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética
16.
J Hepatocell Carcinoma ; 11: 679-691, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585292

RESUMEN

Background: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA). Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems. Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.

17.
J Nanobiotechnology ; 22(1): 159, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589859

RESUMEN

Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , Animales , Humanos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , ARN Interferente Pequeño/farmacología , Exosomas/metabolismo , Células HEK293 , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo
18.
Front Public Health ; 12: 1376404, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38651131

RESUMEN

Background: Tuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults. Methods: All notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China's TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored. Results: From January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05-1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28-2.26), passive case finding (AOR: 1.46, 95% CI: 1.07-1.98) and retreatment (AOR: 1.52, 95% CI: 1.11-2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53-0.90) and non-students (AOR: 0.83, 95% CI: 0.71-0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29-1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32-1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30-1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78-1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59-0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before. Conclusion: In general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.


Asunto(s)
COVID-19 , Tuberculosis Pulmonar , Humanos , Adolescente , Femenino , China/epidemiología , Masculino , Adulto Joven , COVID-19/epidemiología , Tuberculosis Pulmonar/epidemiología , Adulto , Tiempo de Tratamiento/estadística & datos numéricos , Diagnóstico Tardío/estadística & datos numéricos , Tuberculosis/epidemiología , Modelos Logísticos , SARS-CoV-2
19.
Sci Rep ; 14(1): 8877, 2024 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632368

RESUMEN

Aphanomyces euteiches causes root rot in pea, leading to significant yield losses. However, the metabolites involved in this pathosystem have not been thoroughly studied. This study aimed to fill this gap and explore mechanisms of bacterial suppression of A. euteiches via untargeted metabolomics using pea grown in a controlled environment. Chemical isotope labeling (CIL), followed by liquid chromatography-mass spectrometry (LC-MS), was used for metabolite separation and detection. Univariate and multivariate analyses showed clear separation of metabolites from pathogen-treated pea roots and roots from other treatments. A three-tier approach positively or putatively identified 5249 peak pairs or metabolites. Of these, 403 were positively identified in tier 1; 940 were putatively identified with high confidence in tier 2. There were substantial changes in amino acid pool, and fatty acid and phenylpropanoid pathway products. More metabolites, including salicylic and jasmonic acids, were upregulated than downregulated in A. euteiches-infected roots. 1-aminocyclopropane-1-carboxylic acid and 12-oxophytodienoic acid were upregulated in A. euteiches + bacterium-treated roots compared to A. euteiches-infected roots. A great number of metabolites were up- or down-regulated in response to A. euteiches infection compared with the control and A. euteiches + bacterium-treated plants. The results of this study could facilitate improved disease management.


Asunto(s)
Aphanomyces , Pisum sativum , Raíces de Plantas/metabolismo , Enfermedades de las Plantas/microbiología , Metabolómica
20.
J Am Chem Soc ; 146(11): 7779-7790, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38466142

RESUMEN

The electrochemical nitrate reduction reaction (NO3RR) holds promise for converting nitrogenous pollutants to valuable ammonia products. However, conventional electrocatalysis faces challenges in effectively driving the complex eight-electron and nine-proton transfer process of the NO3RR while also competing with the hydrogen evolution reaction. In this study, we present the thermally enhanced electrocatalysis of nitrate-to-ammonia conversion over nickel-modified copper oxide single-atom alloy oxide nanowires. The catalyst demonstrates improved ammonia production performance with a Faradaic efficiency of approximately 80% and a yield rate of 9.7 mg h-1 cm-2 at +0.1 V versus a reversible hydrogen electrode at elevated cell temperatures. In addition, this thermally enhanced electrocatalysis system displays impressive stability, interference resistance, and favorable energy consumption and greenhouse gas emissions for the simulated industrial wastewater treatment. Complementary in situ analyses confirm that the significantly superior relay of active hydrogen species formed at Ni sites facilitates the thermal-field-coupled electrocatalysis of Cu surface-adsorbed *NOx hydrogenation. Theoretical calculations further support the thermodynamic and kinetic feasibility of the relay catalysis mechanism for the NO3RR over the Ni1Cu model catalyst. This study introduces a conceptual thermal-electrochemistry approach for the synergistic regulation of complex catalytic processes, highlighting the potential of multifield-coupled catalysis to advance sustainable-energy-powered chemical synthesis technologies.

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