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1.
J Food Sci ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720581

RESUMO

In response to the challenges of low automation and a lack of a continuous processing system for Taiping Houkui tea, this study proposed a design scheme for a continuous processing line and built a continuous processing prototype for testing by combining the production requirements of Taiping Houkui tea, the characteristics of withered leaves, and the existing relevant production equipment. First, the physical properties of Taiping Houkui tea were determined. A simulation was performed using the Hertz-Mindlin model, and the motion states of the tea leaves were obtained under different conditions to define the parameter design range of the experimental platform and verify its structural rationality. Then, the response surface methodology was used to optimize the working parameter ranges and obtain the best working parameters for the feeding and kneading mechanisms. Finally, a continuous production prototype was constructed for further production verification. The experimental results show that the success rate of continuous production on this platform was 70.68%, with an average output of approximately 0.4 kg/h for Taiping Houkui dry tea on a single slide track, and the produced tea was similar to manually made tea. This demonstrates that the continuous production technique has high feasibility and provides a reference for continuous production of Taiping Houkui tea.

2.
Exp Biol Med (Maywood) ; 249: 10112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715976

RESUMO

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2Mφs, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1Mφs), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2Mφs and improved myocardial fibrosis, but interestingly, both M1Mφs and M2Mφs were increased in the peritoneal cavity of SHRs, the number of M2Mφs remained lower than M1Mφs. In vitro, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca2+ ([Ca2+]i) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1Mφs. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1Mφs and increasing M2Mφs.


Assuntos
Macrófagos , Ratos Endogâmicos SHR , Receptores de Detecção de Cálcio , Animais , Receptores de Detecção de Cálcio/metabolismo , Macrófagos/metabolismo , Ratos , Masculino , Remodelação Ventricular/fisiologia , Miocárdio/patologia , Miocárdio/metabolismo , Fibrose/metabolismo , Pressão Sanguínea , Camundongos , Hipertensão/metabolismo , Hipertensão/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
4.
BMC Plant Biol ; 24(1): 385, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724918

RESUMO

Waterlogging stress is one of the major abiotic stresses affecting the productivity and quality of many crops worldwide. However, the mechanisms of waterlogging tolerance are still elusive in barley. In this study, we identify key differentially expressed genes (DEGs) and differential metabolites (DM) that mediate distinct waterlogging tolerance strategies in leaf and root of two barley varieties with contrasting waterlogging tolerance under different waterlogging treatments. Transcriptome profiling revealed that the response of roots was more distinct than that of leaves in both varieties, in which the number of downregulated genes in roots was 7.41-fold higher than that in leaves of waterlogging sensitive variety after 72 h of waterlogging stress. We also found the number of waterlogging stress-induced upregulated DEGs in the waterlogging tolerant variety was higher than that of the waterlogging sensitive variety in both leaves and roots in 1 h and 72 h treatment. This suggested the waterlogging tolerant variety may respond more quickly to waterlogging stress. Meanwhile, phenylpropanoid biosynthesis pathway was identified to play critical roles in waterlogging tolerant variety by improving cell wall biogenesis and peroxidase activity through DEGs such as Peroxidase (PERs) and Cinnamoyl-CoA reductases (CCRs) to improve resistance to waterlogging. Based on metabolomic and transcriptomic analysis, we found the waterlogging tolerant variety can better alleviate the energy deficiency via higher sugar content, reduced lactate accumulation, and improved ethanol fermentation activity compared to the waterlogging sensitive variety. In summary, our results provide waterlogging tolerance strategies in barley to guide the development of elite genetic resources towards waterlogging-tolerant crop varieties.


Assuntos
Perfilação da Expressão Gênica , Hordeum , Metaboloma , Estresse Fisiológico , Transcriptoma , Hordeum/genética , Hordeum/fisiologia , Hordeum/metabolismo , Estresse Fisiológico/genética , Água/metabolismo , Folhas de Planta/genética , Folhas de Planta/fisiologia , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
5.
Med Sci Monit ; 30: e942509, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561932

RESUMO

BACKGROUND Diabetic peripheral neuropathy (DPN) is a prevalent complication affecting over 60% of type 2 diabetes patients. Early diagnosis is challenging, leading to irreversible impacts on quality of life. This study explores the predictive value of combining HbA1c and Neutrophil-to-Lymphocyte Ratio (NLR) for early DPN detection. MATERIAL AND METHODS An observational study was conducted at the First People's Hospital of Linping District, Hangzhou spanning from May 2019 to July 2020. Data on sex, age, biochemical measurements were collected from electronic medical records and analyzed. Employing multivariate logistic regression analysis, we sought to comprehend the factors influencing the development of DPN. To assess the predictive value of individual and combined testing for DPN, a receiver operating characteristic (ROC) curve was plotted. The data analysis was executed using R software (Version: 4.1.0). RESULTS The univariate and multivariate logistic regression analysis identified the level of glycated hemoglobin (HbA1C) (OR=1.94, 95% CI: 1.27-3.14) and neutrophil-to-lymphocyte ratio (NLR) (OR=4.60, 95% CI: 1.15-22.62, P=0.04) as significant risk factors for the development of DPN. Receiver operating characteristic (ROC) curve analysis demonstrated that HbA1c, NLR, and their combined detection exhibited high sensitivity in predicting the development of DPN (71.60%, 90.00%, and 97.2%, respectively), with moderate specificity (63.8%, 45.00%, and 50.00%, respectively). The area under the curve (AUC) for these predictors was 0.703, 0.661, and 0.733, respectively. CONCLUSIONS HbA1c and NLR emerge as noteworthy risk indicators associated with the manifestation of DPN in patients with type 2 diabetes. The combined detection of HbA1c and NLR exhibits a heightened predictive value for the development of DPN.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/etiologia , Hemoglobinas Glicadas , Linfócitos , Neutrófilos , Qualidade de Vida , Curva ROC , Masculino , Feminino
6.
Chemistry ; : e202400714, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622057

RESUMO

Quantum chemical calculations using ab initio methods at the MRCI+Q(8,9)/def2-QZVPPD and CCSD(T)/def2-QZVPPD levels as well as density functional theory are reported for the diatomic molecules AeN- (Ae = Ca, Sr, Ba). The nature of the bonds is analyzed with a variety of methods. The anions CaN- and SrN- have electronic triplet (3Π) ground states with nearly identical bond dissociation energies De ~57 kcal/mol calculated at the MRCI+Q(8,9)/def2-QZVPPD level of theory. In contrast, the heavier homologue BaN- has a singlet (1Σ+) ground state, which is only 1.1 kcal/mol below the triplet (3Σ-) state. The computed bond dissociation energy of (1Σ+) BaN- is 68.4 kcal/mol. The calculations at the CCSD(T)-full/def2-QZVPPD and BP86-D3(BJ)/def2-QZVPPD levels of theory are in reasonable agreement with the MRCI+Q(8,9)/def2-QZVPPD data except for the singlet (1Σ+) state, which has a large multireference character. The calculated atomic partial charges given by the CM5, Voronoi and Hirshfeld methods suggest small to medium-sized charge donation toward Ae atom Ae←N- for most electronic states. In contrast, the NBO method predicts for all species medium to large electronic charge donation toward nitrogen Ae→N-, which is due to the neglect of the (n)p AOs of Ae atoms as genuine valence orbitals.

7.
New Phytol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622763

RESUMO

Climate change-induced drought is a major threat to agriculture. C4 crops have a higher water use efficiency (WUE) and better adaptability to drought than C3 crops due to their smaller stomatal morphology and faster response. However, our understanding of stomatal behaviours in both C3 and C4 Poaceae crops is limited by knowledge gaps in physical traits of guard cell (GC) and subsidiary cell (SC). We employed infrared gas exchange analysis and a stomatal assay to explore the relationship between GC/SC sizes and stomatal kinetics across diverse drought conditions in two C3 (wheat and barley) and three C4 (maize, sorghum and foxtail millet) upland Poaceae crops. Through statistical analyses, we proposed a GCSC-τ model to demonstrate how morphological differences affect stomatal kinetics in C4 Poaceae crops. Our findings reveal that morphological variations specifically correlate with stomatal kinetics in C4 Poaceae crops, but not in C3 ones. Subsequent modelling and experimental validation provide further evidence that GC/SC sizes significantly impact stomatal kinetics, which affects stomatal responses to different drought conditions and thereby WUE in C4 Poaceae crops. These findings emphasize the crucial advantage of GC/SC morphological characteristics and stomatal kinetics for the drought adaptability of C4 Poaceae crops, highlighting their potential as future climate-resilient crops.

8.
J Clin Invest ; 134(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618952

RESUMO

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.


Assuntos
Adenina , Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Carcinogênese/genética , Carcinoma de Células Renais/genética , Transformação Celular Neoplásica , Expressão Gênica , Neoplasias Renais/genética , Metiltransferases/genética , Fosfatidilinositol 3-Quinases/genética
9.
Gigascience ; 132024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38608280

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomarkers for PDAC often suffer from replicability issues, arising from inherent limitations such as unmeasured confounding factors in conventional epidemiologic study designs. To circumvent these limitations, we use genetic instruments to identify proteins with genetically predicted levels to be associated with PDAC risk. Leveraging genome and plasma proteome data from the INTERVAL study, we established and validated models to predict protein levels using genetic variants. By examining 8,275 PDAC cases and 6,723 controls, we identified 40 associated proteins, of which 16 are novel. Functionally validating these candidates by focusing on 2 selected novel protein-encoding genes, GOLM1 and B4GALT1, we demonstrated their pivotal roles in driving PDAC cell proliferation, migration, and invasion. Furthermore, we also identified potential drug repurposing opportunities for treating PDAC. SIGNIFICANCE: PDAC is a notoriously difficult-to-treat malignancy, and our limited understanding of causal protein markers hampers progress in developing effective early detection strategies and treatments. Our study identifies novel causal proteins using genetic instruments and subsequently functionally validates selected novel proteins. This dual approach enhances our understanding of PDAC etiology and potentially opens new avenues for therapeutic interventions.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteoma , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Glicosiltransferases , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Biomarcadores , Proteínas de Membrana
10.
Front Mol Biosci ; 11: 1365760, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638689

RESUMO

The lungs are a key organ in the respiratory system. They are regulated by a complex network of nerves that control their development, structure, function, and response to various pathological stimuli. Accumulating evidence suggests the involvement of a neural mechanism in different pathophysiological conditions in the lungs and the development and progression of common respiratory diseases. Lung diseases are the chief source of death globally. For instance, lung cancer is the second most commonly diagnosed malignancy, after prostate cancer in men and breast cancer in women, and is the most lethal cancer worldwide. However, although airway nerves are accepted as a mechanistically and therapeutically important feature that demands appropriate emphasizing in the context of many respiratory diseases, significantly less is known about the role of the neuroglial cells in lung physiology and pathophysiology, including lung cancer. New data have uncovered some cellular and molecular mechanisms of how Schwann cells, as fundamental components of the peripheral nervous system, may regulate lung cancer cells' survival, spreading, and invasiveness in vitro and in vivo. Schwann cells control the formation and maintenance of the lung cancer microenvironment and support metastasis formation. It was also reported that the number of lung cancer-associated Schwann cells correlates with patients' survival. Different factors secreted by Schwann cells, including microRNA, are known to sharpen the lung cancer environment by regulating the tumor-neuro-immune axis. Further clinical and experimental studies are required to elucidate the detailed role of Schwann cells in creating and maintaining pulmonary tumor-neuro-immune axis, which will advance our understanding of the pathogenesis of lung cancer and may inform therapeutic hypotheses aiming neoplasms and metastases in the lung.

11.
Radiology ; 311(1): e230459, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563669

RESUMO

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.


Assuntos
Micro-Ondas , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Hospitalização , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia
12.
Materials (Basel) ; 17(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38591636

RESUMO

Surface features are crucial for assessing welding quality because they serve as an intuitive depiction of the quality of the joint and have a major influence on welding strength. According to the characteristics of the refill friction stir spot welding (RFSSW) process and an analysis of the surface-state and internal morphology of RFSSW joints, a method of predicting the mechanical properties of RFSSW joints based on surface-state characteristics was proposed. In this paper, a laser-ranging sensor was used to characterize the surface state of RFSSW joints, and parametric characterization methods of the surface-state features of RFSSW joints were proposed. On this basis, a support vector machine was used to predict and analyze the fracture mode of RFSSW joints. The accuracy of the analysis of the test samples reached 95.8%. This paper provides a more efficient and convenient new method for the quality evaluation of RFSSW joints.

13.
Heliyon ; 10(7): e28553, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596011

RESUMO

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS. Methods: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL). Results: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50-0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25-175.59] vs 116.44 [102.43-122.19]pg/ml, p < 0.0015). Conclusion: In this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS.

14.
Environ Geochem Health ; 46(5): 162, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592579

RESUMO

Convenient transportation facilities not only bring the higher standard of living to big cities, but also bring some environmental pollution problems. In order to understand the presence and sources of methylated polycyclic aromatic hydrocarbons (Me-PAHs) in environmental samples and their association with total organic carbon (TOC), 49 Me-PAHs were analyzed in road dust, green belt soil and parking lot dust samples in Harbin. The results showed that the ranges of the total Me-PAHs (ΣMe-PAHs) content in road dust were 221-5826 ng/g in autumn and 697-7302 ng/g in spring, and those in green belt soil were 170-2509 ng/g and 155-9215 ng/g in autumn and spring, respectively. And ΣMe-PAHs content in parking lot dust ranged from 269 to 2515 ng/g in surface parking lots and from 778 to 10,052 ng/g in underground parking lots. In these samples, the composition profile of Me-PAHs was dominated by 4-ring Me-PAHs. The results of diagnostic ratios and principal component analysis (PCA) indicated that petrogenic and pyrogenic sources were the main sources of Me-PAHs in the samples. Spearman correlation analysis showed that there was no correlation for Me-PAHs in road dust and green belt soil on the same road. Furthermore, there was a significant positive relationship (0.12 ≤ R2 ≤ 0.67, P < 0.05) between Me-PAHs concentrations and the TOC content. This study demonstrated the presence of Me-PAHs with high concentrations in the road environment samples of Harbin.


Assuntos
Poeira , Hidrocarbonetos Policíclicos Aromáticos , Cidades , Poluição Ambiental , Solo
15.
Ultrasonics ; 141: 107331, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38685139

RESUMO

Different from the traditional frequency-mixing technique which employs a contacting transducer, the laser-induced acoustic nonlinear frequency-mixing detection technique utilizes a laser source to instigate crack motion and generate acoustic waves. Thus, apart from the temperature oscillation induced by the pump laser, the "basic temperature" originating from the probe laser can also influence the crack. This additional variable complicates the contact state of the crack, yielding a more diverse range of nonlinear acoustic signal attributes. In light of this, our study enhances the conventional opto-acoustic nonlinear frequency mixing experimental setup by integrating an independent heating laser beam. This modification isolates the impact of the "basic temperature" on crack width while also dialing down the probe laser power to mitigate its thermal effects. To amplify the sensitivity of crack detection, we deliberated on the optimal laser source parameters for this setup. Consequently, our revamped system, paired with fine-tuned parameters, captures nonlinear acoustic signals with an enriched feature set. This investigation can provide support for the non-contact opto-acoustic nonlinear frequency mixing technique in the detection and evaluation of micro-cracks.

16.
J Immunother Cancer ; 12(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38641349

RESUMO

BACKGROUND: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy. METHOD: 200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS<12 months). Serum samples were collected from all patients before treatment initiation for untargeted metabolomics analysis, with the goal of identifying and validating biomarkers that can predict the efficacy of immunotherapy plus chemotherapy. Additionally, the validated metabolites were grouped into high and low categories based on their medians, and their relationship with PFS was analyzed using Cox regression models in patients receiving combination therapy. RESULTS: After the impact of chemotherapy was accounted for, two significant differential metabolites were identified in both the Discovery and Validation sets: N-(3-Indolylacetyl)-L-alanine and methomyl (VIP>1 and p<0.05). Notably, upregulation of both metabolites was observed in the group with a poorer prognosis. In the univariate analysis of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were associated with longer PFS (HR=0.59, 95% CI, 0.41 to 0.84, p=0.003), and a prolonged PFS was also indicated by lower levels of methomyl (HR=0.67, 95% CI, 0.47 to 0.96, p=0.029). In multivariate analyses of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were significantly associated with a longer PFS (HR=0.60, 95% CI, 0.37 to 0.98, p=0.041). CONCLUSION: Improved outcomes were associated with lower levels of N-(3-Indolylacetyl)-L-alanine in patients with stage IIIB-IV NSCLC lacking driver gene mutations, who underwent first-line or second-line therapy with PD-1 inhibitors combined with chemotherapy. Further exploration of the potential predictive value of pretreatment detection of N-(3-Indolylacetyl)-L-alanine in peripheral blood for the efficacy of combination therapy is warranted. STATEMENT: The combination of ICIs and chemotherapy has established itself as the new standard of care for first-line or second-line treatment in patients with advanced NSCLC lacking oncogenic driver alterations. Therefore, identifying biomarkers that can predict the efficacy and prognosis of immunotherapy plus chemotherapy is of paramount importance. Currently, the only validated predictive biomarker is programmed cell death ligand-1 (PD-L1), but its predictive value is not absolute. Our study suggests that the detection of N-(3-Indolylacetyl)-L-alanine in patient serum with untargeted metabolomics prior to combined therapy may predict the efficacy of treatment. Compared with detecting PD-L1 expression, the advantage of our biomarker is that it is more convenient, more dynamic, and seems to work synergistically with PD-L1 expression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Metabolômica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
17.
Antioxidants (Basel) ; 13(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38671839

RESUMO

Extremely preterm infants are often treated with supraphysiological oxygen, which contributes to the development of bronchopulmonary dysplasia (BPD). These same infants exhibit compromised antioxidant capacities due in part to selenium (Se) deficiency. Se is essential for basal and inducible antioxidant responses. The present study utilized a perinatal Se deficiency (SeD) mouse model to identify the combined effects of newborn hyperoxia exposure and SeD on alveolarization and antioxidant responses, including the identification of affected developmental pathways. Se-sufficient (SeS) and SeD C3H/HeN breeding pairs were generated, and pups were exposed to room air or 85% O2 from birth to 14 d. Survival, antioxidant protein expression, and RNA seq analyses were performed. Greater than 40% mortality was observed in hyperoxia-exposed SeD pups. Surviving SeD pups had greater lung growth deficits than hyperoxia-exposed SeS pups. Gpx2 and 4 protein and Gpx activity were significantly decreased in SeD pups. Nrf2-regulated proteins, Nqo1 and Gclc were increased in SeD pups exposed to hyperoxia. RNA seq revealed significant decreases in the Wnt/ß-catenin and Notch pathways. Se is a biologically relevant modulator of perinatal lung development and antioxidant responses, especially in the context of hyperoxia exposure. The RNA seq analyses suggest pathways essential for normal lung development are dysregulated by Se deficiency.

18.
Chemphyschem ; : e202300816, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563655

RESUMO

The introduction of transition-metal doping has engendered a remarkable array of unprecedented boron motifs characterized by distinctive geometries and bonding, particularly those heretofore unobserved in pure boron clusters. In this study, we present a perfect (no defects) boron framework manifesting an inherently high-symmetry, bowl-like architecture, denoted as MB16 - (M=Sc, Y, La). In MB16 -, the B16 is coordinated to M atoms along the C5v-symmetry axis. The bowl-shaped MB16 - structure is predicted to be the lowest-energy structure with superior stability, owing to its concentric (2 π+10 π) dual π aromaticity. Notably, the C5v-symmetry bowl-like B16 - is profoundly stabilized through the doping of an M atom, facilitated by strong d-pπ interactions between M and boron motifs, in conjunction with additional electrostatic stabilization by an electron transfer from M to the boron motifs. This concerted interplay of covalent and electrostatic interactions between M and bowl-like B16 renders MB16 - a species of exceptional thermodynamic stability, thus making it a viable candidate for gas-phase experimental detection.

20.
Plant Physiol Biochem ; 210: 108626, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615443

RESUMO

Stomatal operation is crucial for optimising plant water and gas exchange and represents a major trait conferring abiotic stress tolerance in plants. About 56% of agricultural land around the globe is classified as acidic, and Al toxicity is a major limiting factor affecting plant performance in such soils. While most of the research work in the field discusses the impact of major abiotic stresses such as drought or salinity on stomatal operation, the impact of toxic metals and, specifically aluminium (Al) on stomatal operation receives much less attention. We aim to fill this knowledge gap by summarizing the current knowledge of the adverse effects of acid soils on plant stomatal development and operation. We summarised the knowledge of stomatal responses to both long-term and transient Al exposure, explored molecular mechanisms underlying plant adaptations to Al toxicity, and elucidated regulatory networks that alleviate Al toxicity. It is shown that Al-induced stomatal closure involves regulations of core stomatal signalling components, such as ROS, NO, and CO2 and key elements of ABA signalling. We also discuss possible targets and pathway to modify stomatal operation in plants grown in acid soils thus reducing the impact of Al toxicity on plant growth and yield.


Assuntos
Alumínio , Estômatos de Plantas , Solo , Alumínio/toxicidade , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/fisiologia , Solo/química , Produtos Agrícolas/metabolismo , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/crescimento & desenvolvimento , Adaptação Fisiológica/efeitos dos fármacos
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