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1.
Environ Technol ; : 1-13, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773903

RESUMO

The increasing concentrations of heavy metals in livestock wastewater pose a serious threat to the environmental safety and human health, limiting its resource utilisation. In the present study, microalgae and nanoscale zero-valent iron were selected to construct a coupled system for copper-containing wastewater treatment. The addition of 50 mg·L-1 nanoscale zero-valent iron (50 nm) was the optimal value for the experiment, which could significantly increase the biomass of microalgae. In addition, nanoscale zero-valent iron stimulated microalgal secretion of extracellular polymeric substances, increasing the contents of binding sites, organic ligands, and functional groups on the microalgal surfaces and ultimately promoting the settling of microalgae and binding of heavy metals. The coupled system could quickly adapt to copper-containing wastewater of 10 mg·L-1, and the copper removal rate reached 94.99%. Adsorption and uptake by organisms, together with the contribution of zero-valent iron nanoparticles, are the major copper removal pathways. Overall, this work offers a novel technical solution for enhanced treatment of copper-containing livestock wastewater, which will help improve the efficiency and quality of wastewater treatment.

2.
J Fluoresc ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722498

RESUMO

In this study, we present a novel near-infrared (NIR) fluorescent probe Nile-ONO designed for the selective and sensitive detection of ONOO-. The probe Nile-ONO employed Nile red as the fluorophore, with diphenylphosphinate serving as the reaction site. In the presence of ONOO-, the probe Nile-ONO exhibits remarkable fluorescence enhancement at 659 nm, with a response time of less than 20 min and a low detection limit of 0.32 µM. Importantly, MTT assays demonstrate low cytotoxicity in living cells. Furthermore, Nile-ONO has excellent imaging capabilities for endogenous ONOO-. Overall, this work introduces a valuable new method for the rapid detection of ONOO- in biological systems.

3.
Food Chem ; 452: 139522, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38723568

RESUMO

ß-lactoglobulin (ß-Lg) is a major food allergen, there is an urgent need to develop a rapid method for detecting ß-Lg in order to avoid contact or ingestion by allergic patients. Peptide aptamers have high affinity, specificity, and stability, and have broad prospects in the field of rapid detection. Using ß-Lg as the target, this study screened 11 peptides (P1-11) from a phage display library. Using molecular docking technology to predict binding energy and binding mode of proteins and peptides. Select the peptides with the best binding ability to ß-Lg (P5, P7, P8) through ELISA. Combining them with whey protein, casein, and bovine serum protein, it was found that P7 has the best specificity for ß-Lg, with an inhibition rate of 87.99%. Verified by molecular dynamics that P7 binds well with ß-Lg. Therefore, this peptide can be used for the recognition of ß-Lg, becoming a new recognition element for detecting ß-Lg.

4.
Biochem Biophys Res Commun ; 720: 150105, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38754163

RESUMO

BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. METHODS: Ryanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2R2474S/+ mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. RESULTS: DEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2R2474S/+ mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD80) and calcium transient duration (CaTD80) in both RyR2R2474S/+ and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2R2474S/+ hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. CONCLUSION: DEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca2+. DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.

5.
Zool Res ; 45(3): 551-566, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38757223

RESUMO

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Proteínas Proto-Oncogênicas p21(ras) , Animais , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Carcinoma Hepatocelular/patologia , Camundongos , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Humanos
6.
Front Med (Lausanne) ; 11: 1390878, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737762

RESUMO

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

7.
J Agric Food Chem ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748811

RESUMO

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

8.
Cell Biochem Funct ; 42(4): e4039, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751189

RESUMO

Platelet hyperreactivity contributes to the pathogenesis of COVID-19, which is associated with a hypercoagulability state and thrombosis disorder. It has been demonstrated that Vitamin D deficiency is associated with the severity of COVID-19 infection. Vitamin D supplement is widely used as a dietary supplement due to its safety and health benefits. In this study, we investigated the direct effects and underlying mechanisms of 1,25(OH)2D3 on platelet hyperreactivity induced by SRAS-CoV-2 spike protein via Western blot and platelet functional studies in vitro. Firstly, we found that 1,25(OH)2D3 attenuated platelet aggregation and Src-mediated signaling. We further observed that 1,25(OH)2D3 attenuated spike protein-potentiated platelet aggregation in vitro. Mechanistically, 1,25(OH)2D3 attenuated spike protein upregulated-integrin αIIbß3 outside-in signaling such as platelet spreading and the phosphorylation of ß3, c-Src and Syk. Moreover, using PP2, the Src family kinase inhibitor to abolish spike protein-stimulated platelet aggregation and integrin αIIbß3 outside-in signaling, the combination of PP2 and 1,25(OH)2D3 did not show additive inhibitory effects on spike protein-potentiated platelet aggregation and the phosphorylation of ß3, c-Src and Syk. Thus, our data suggest that 1,25(OH)2D3 attenuates platelet aggregation potentiated by spike protein via downregulating integrin αIIbß3 outside-in signaling.


Assuntos
Agregação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , COVID-19/metabolismo , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Calcitriol/farmacologia , Quinases da Família src/metabolismo , Quinases da Família src/antagonistas & inibidores , Quinase Syk/metabolismo , Quinase Syk/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
9.
Res Sq ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38746402

RESUMO

Background X-linked Dystonia-Parkinsonism(XDP) is an adult-onset neurodegenerative disorder that results in the loss of striatal medium spiny neurons (MSNs). XDP is associated with disease-specific mutations in and around the TAF1 gene. This study highlights the utility of directly reprogrammed MSNs from fibroblasts of affected XDP individuals as a platform that captures cellular and epigenetic phenotypes associated with XDP-related neurodegeneration. In addition, the current study demonstrates the neuroprotective effect of SAK3 currently tested in other neurodegenerative diseases. Methods XDP fibroblasts from three independent patients as well as age- and sex-matched control fibroblasts were used to generate MSNs by direct neuronal reprogramming using miRNA-9/9*-124 and thetranscription factors CTIP2 , DLX1 -P2A- DLX2 , and MYT1L . Neuronal death, DNA damage, and mitochondrial health assays were carried out to assess the neurodegenerative state of directly reprogrammed MSNs from XDP patients (XDP-MSNs). RNA sequencing and ATAC sequencing were performed to infer changes in the transcriptomic and chromatin landscapesof XDP-MSNs compared to those of control MSNs (Ctrl-MSNs). Results Our results show that XDP patient fibroblasts can be successfully reprogrammed into MSNs and XDP-MSNs display several degenerative phenotypes, including neuronal death, DNA damage, and mitochondrial dysfunction, compared to Ctrl-MSNs reprogrammed from age- and sex-matched control individuals' fibroblasts. In addition, XDP-MSNs showed increased vulnerability to TNFα -toxicity compared to Ctrl-MSNs. To dissect the altered cellular state in XDP-MSNs, we conducted transcriptomic and chromatin accessibility analyses using RNA- and ATAC-seq. Our results indicate that pathways related to neuronal function, calcium signaling, and genes related to other neurodegenerative diseases are commonly altered in XDP-MSNs from multiple patients. Interestingly, we found that SAK3, a T-type calcium channel activator, that may have therapeutic values in other neurodegenerative disorders, protected XDP-MSNs from neuronal death. Notably, we found that SAK3-mediated alleviation of neurodegeneration in XDP-MSNs was accompanied by gene expression changes toward Ctrl-MSNs.

10.
Front Endocrinol (Lausanne) ; 15: 1369600, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711979

RESUMO

Background: The Metabolic Score for Insulin Resistance (METS-IR) offers a promising and reliable non-insulin-based approach to assess insulin resistance and evaluate cardiometabolic risk. However, evidence for the association between METS-IR and hypertension was still limited. Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2016 were selected for weighted multivariable regression analyses, subgroup analyses and restricted cubic spline (RCS) modeling to assess the association between the METS-IR and hypertension, as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP). Results: This study enrolled 7,721 adults aged ≥20 years, 2,926 (34.03%) of whom was diagnosed as hypertension. After adjusting for all potential covariates, an increased METS-IR (log2 conversion, denoted as log2METS-IR) was independently associated with a higher prevalence of hypertension (odd ratio [OR] 3.99, 95% confidence interval [CI] 3.19~5.01). The OR for hypertension in subjects with the highest quartile of METS-IR was 3.89-fold (OR 3.89, 95% CI 3.06~4.94) higher than that in those with the lowest quartile of METS-IR. This positive correlation became more significant as METS-IR increased (p for trend < 0.001). Log2METS-IR was significantly correlated with increase in SBP (ß 6.75, 95% CI 5.65~7.85) and DBP (ß 5.59, 95% CI 4.75~6.43) in a fully adjusted model. Consistent results were obtained in subgroup analyses. Hypertension, SBP and DBP all exhibited a non-linear increase with the rise in METS-IR. The minimal threshold for the beneficial association of METS-IR with hypertension, SBP and DBP were all identified to be 46.88. Conclusion: The findings of this study revealed a significant positive association between METS-IR and hypertension among US adults, suggesting METS-IR as a potential tool for assessing hypertension risk.


Assuntos
Hipertensão , Resistência à Insulina , Inquéritos Nutricionais , Humanos , Hipertensão/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Estados Unidos/epidemiologia , Estudos Transversais , Prevalência , Pressão Sanguínea/fisiologia , Adulto Jovem , Idoso , Fatores de Risco
11.
Small ; : e2401457, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733086

RESUMO

The separator is an important component in batteries, with the primary function of separating the positive and negative electrodes and allowing the free passage of ions. Porous organic framework materials have a stable connection structure, large specific surface area, and ordered pores, which are natural places to store electrolytes. And these materials with specific functions can be designed according to the needs of researchers. The performance of porous organic framework-based separators used in rechargeable lithium metal batteries is much better than that of polyethylene/propylene separators. In this paper, the three most classic organic framework materials (MOF, COF, and HOF) are analyzed and summarized. The applications of MOF, COF, and HOF separators in lithium-sulfur batteries, lithium metal anode, and solid electrolytes are reviewed. Meanwhile, the research progress of these three materials in different fields is discussed based on time. Finally, in the conclusion, the problems encountered by MOF, COF, and HOF in different fields as well as their future research priorities are presented. This review will provide theoretical guidance for the design of porous framework materials with specific functions and further stimulate researchers to conduct research on porous framework materials.

12.
Heliyon ; 10(9): e30505, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726194

RESUMO

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

13.
Metabolism ; : 155933, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729601

RESUMO

AIMS/HYPOTHESIS: cGAS (cyclic GMP-AMP synthase) has been implicated in various cellular processes, but its role in ß-cell proliferation and diabetes is not fully understood. This study investigates the impact of cGAS on ß-cell proliferation, particularly in the context of diabetes. METHODS: Utilizing mouse models, including cGAS and STING (stimulator of interferon genes) knockout mice, we explored the role of cGAS in ß-cell function. This involved ß-cell-specific cGAS knockout (cGASßKO) mice, created by breeding cGAS floxed mice with transgenic mice expressing Cre recombinase under the insulin II promoter. We analyzed cGAS expression in diabetic mouse models, evaluated the effects of cGAS deficiency on glucose tolerance, and investigated the molecular mechanisms underlying these effects through RNA sequencing. RESULTS: cGAS expression is upregulated in the islets of diabetic mice and by high glucose treatment in MIN6 cells. Both global cGAS deficiency and ß-cell-specific cGAS knockout mice lead to improved glucose tolerance by promoting ß-cell mass. Interestingly, STING knockout did not affect pancreatic ß-cell mass, suggesting a STING-independent mechanism for cGAS's role in ß-cells. Further analyses revealed that cGAS- but not STING-deficiency leads to reduced expression of CEBPß, a known suppressor of ß-cell proliferation, concurrently with increased ß-cell proliferation. Moreover, overexpression of CEBPß reverses the upregulation of Cyclin D1 and D2 induced by cGAS deficiency, thereby regulating ß-cell proliferation. These results confirm that cGAS regulation of ß-cell proliferation via a CEBPß-dependent but STING-independent mechanism. CONCLUSIONS/INTERPRETATION: Our findings highlight the pivotal role of cGAS in promoting ß-cell proliferation and maintaining glucose homeostasis, potentially by regulating CEBPß expression in a STING-independent manner. This study uncovers the significance of cGAS in controlling ß-cell mass and identifies a potential therapeutic target for enhancing ß-cell proliferation in the treatment of diabetes.

14.
Sci Rep ; 14(1): 10126, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698088

RESUMO

In a battery pack, several lithium-ion batteries (LiBs) are connected in series and parallel so that sufficient voltage, current and power can be provided for applications. To ensure safe operation, when one of the LiB cells in a pack has its SoH below 80%, the entire pack will have to be discarded. Thus, ensuring all the LiB cells degrade similarly in a pack is crucial to maximize the potential of all the cells in a pack. There are several methods to perform screening on the LiB cells for such purpose, but there exist many practical challenges for estimating and predicting the degradation rate of the cells before they are chosen to be put in a pack which will be described in this work. This work provides solutions to some of these challenges and shows through experiments that one can screen the weak cells from production batch with just the first discharge cycle, and one can also predict the statistical distribution of the degradation rates of LiB cells in a production batch. On-line in-situ determination of the SoH of each cell connected in a pack is also made possible with a solution presented in this work, and this method is verified over many different types of LiB from various manufacturers.

15.
Nat Commun ; 15(1): 3685, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693116

RESUMO

Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships and underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.2-13.8% of Drosophila genes known to regulate the 3 behaviors. We develop an instrument for simultaneous video tracking of multiple moving objects, and conduct a genome-wide screen. We have identified 758 fly genes that regulate sleep and activities, including mre11 which regulates sleep only in the presence of conspecifics, and NELF-B which regulates sleep regardless of whether conspecifics are present. Based on LLM-reasoning, an educated signal web is modeled for understanding of potential relationships between its components, presenting comprehensive molecular signatures that control sleep, locomotor and social activities. This LLM-aided strategy may also be helpful for addressing other complex scientific questions.


Assuntos
Comportamento Animal , Drosophila melanogaster , Locomoção , Sono , Animais , Sono/fisiologia , Sono/genética , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Locomoção/fisiologia , Locomoção/genética , Comportamento Animal/fisiologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Comportamento Social , Masculino
16.
Clin Respir J ; 18(5): e13761, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693705

RESUMO

BACKGROUND: In order to improve survival outcomes in resectable non-small cell lung cancer (NSCLC), strategies for neoadjuvant therapy need to be revisited. We evaluated and compared the efficacy of different neoadjuvant therapeutic modalities in a real-world setting. METHODS: A total of 258 patients with clinical stage IIA to IIIB NSCLC was included. All the patients underwent surgical resection after one to four cycles of neoadjuvant treatment consisting of chemotherapy (83), immunotherapy (23), and immunotherapy plus chemotherapy (152). RESULTS: The radiologic response rate in the combined immunochemotherapy group was 67.8%, higher than that of 48.2% in the chemotherapy group and 4.3% in the immunotherapy group (p < 0.001). An improved major pathological response (MPR) was also achieved in the combined therapy group compared with the chemotherapy group and the immunotherapy group (53.9% vs. 10.8% vs. 8.7%, p < 0.001). Patients in the combined therapy group had a significant trend toward longer disease-free survival than those in the chemotherapy alone group (3-year disease-free survival [DFS] of 68.79% vs. 50.81%; hazard ratio [HR] for progression or death, 0.477; p = 0.003). Multivariate Cox analysis identified radical surgery (HR, 0.328; p = 0.033), ypN0-1 stage (HR, 0.591; p = 0.038) and MPR result (HR, 0.362; p = 0.007) to be independent prognostic factors for DFS. CONCLUSIONS: Neoadjuvant treatment with a combination of immunotherapy plus chemotherapy appears to achieve higher radiological and pathological responses than monotherapy for IIA-IIIB NSCLC. Log-rank analysis showed that a better outcome could be expected in patients with the addition of immunotherapy to neoadjuvant chemotherapy if compared with patients with chemotherapy alone in terms of DFS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Terapia Neoadjuvante/métodos , Masculino , Feminino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Imunoterapia/métodos , Estadiamento de Neoplasias , Resultado do Tratamento , Estudos Retrospectivos , Pneumonectomia/métodos , Intervalo Livre de Doença , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
17.
Front Nutr ; 11: 1349876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699544

RESUMO

Malnutrition persists as one of the most severe symptoms in patients with chronic kidney disease (CKD) globally. It is a critical risk factor for cardiovascular and all-cause mortality in patients with CKD. Readily available objective indicators are used to calculate composite objective nutritional assessment indexes, including the geriatric nutritional risk index, prognostic nutritional index, and controlling nutritional status score. These indexes offer a straightforward and effective method for evaluating nutritional status and predicting clinical outcomes in patients with CKD. This review presents supporting evidence on the significance of composite nutritional indexes.

18.
Int J Biol Macromol ; 269(Pt 2): 131959, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38692548

RESUMO

Polyphenol-protein complexes delivery systems are gaining attention for their potential health benefits and food industry development. However, creating an ideal delivery system requires extensive wet-lab experimentation. To address this, we collected 525 ligand-protein interaction data pairs and established an interaction prediction model using Bilinear Attention Networks. We utilized 10-fold cross validation to address potential overfitting issues in the model, resulting in showed higher average AUROC (0.8443), AUPRC (0.7872), and F1 (0.8164). The optimal threshold (0.3739) was selected for the model to be used for subsequent analysis. Based on the model prediction results and optimal threshold, by verifying experimental analysis, the interaction of paeonol with the following proteins was obtained, including bovine serum albumin (lgKa = 6.2759), bovine ß-lactoglobulin (lgKa = 6.7479), egg ovalbumin (lgKa = 5.1806), zein (lgKa = 6.0122), bovine α-lactalbumin (lgKa = 3.9170), bovine lactoferrin (lgKa = 4.5380), the first four proteins are consistent with the predicted results of the model, with lgKa >5. The established model can accurately and rapidly predict the interaction of polyphenol-protein complexes. This study is the first to combine open ligand-protein interaction experiments with Deep Learning algorithms in the food industry, greatly improving research efficiency and providing a novel perspective for future complex delivery system construction.

19.
Invest Ophthalmol Vis Sci ; 65(5): 7, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38700875

RESUMO

Purpose: This study aimed to explore the underlying mechanisms of the observed visuomotor deficit in amblyopia. Methods: Twenty-four amblyopic (25.8 ± 3.8 years; 15 males) and 22 normal participants (25.8 ± 2.1 years; 8 males) took part in the study. The participants were instructed to continuously track a randomly moving Gaussian target on a computer screen using a mouse. In experiment 1, the participants performed the tracking task at six different target sizes. In experiments 2 and 3, they were asked to track a target with the contrast adjusted to individual's threshold. The tracking performance was represented by the kernel function calculated as the cross-correlation between the target and mouse displacements. The peak, latency, and width of the kernel were extracted and compared between the two groups. Results: In experiment 1, target size had a significant effect on the kernel peak (F(1.649, 46.170) = 200.958, P = 4.420 × 10-22). At the smallest target size, the peak in the amblyopic group was significantly lower than that in the normal group (0.089 ± 0.023 vs. 0.107 ± 0.020, t(28) = -2.390, P = 0.024) and correlated with the contrast sensitivity function (r = 0.739, P = 0.002) in the amblyopic eyes. In experiments 2 and 3, with equally visible stimuli, there were still differences in the kernel between the two groups (all Ps < 0.05). Conclusions: When stimulus visibility was compensated, amblyopic participants still showed significantly poorer tracking performance.


Assuntos
Ambliopia , Acuidade Visual , Humanos , Ambliopia/fisiopatologia , Masculino , Feminino , Adulto , Adulto Jovem , Acuidade Visual/fisiologia , Psicofísica/métodos , Percepção de Movimento/fisiologia , Sensibilidades de Contraste/fisiologia , Movimentos Oculares/fisiologia
20.
Magn Reson Imaging ; 111: 120-130, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38703971

RESUMO

OBJECTIVE: To construct a user-friendly nomogram with MRI and clinicopathological parameters for the prediction of pathological complete response (pCR) after neoadjuvant therapy (NAT) in patients with breast cancer (BC). METHODS: We retrospectively enrolled consecutive female patients pathologically confirmed with breast cancer who received NAT followed by surgery between January 2018 and December 2022 as the development cohort. Additionally, we prospectively collected eligible candidates between January 2023 and December 2023 as an external validation group at our institution. Pretreatment MRI features and clinicopathological variables were collected, and the pre- and post-treatment background parenchymal enhancement (BPE) and the changes in BPE on two MRIs were compared between patients who achieved pCR and those who did not. Multivariable logistic regression analysis was used to identify independent variables associated with pCR in the development cohort. These independent variables were combined into a predictive nomogram for which performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, decision curve analysis, and external validation. RESULTS: In the development cohort, there were a total of 276 female patients with a mean age of 48.3 ± 8.7 years, while in the validation cohort, there were 87 female patients with a mean age of 49.0 ± 9.5 years. Independent prognostic factors of pCR included small tumor size, HER2(+), high Ki-67 index,high signal enhancement ratio (SER), low minimum value of apparent diffusion coefficient (ADCmin), and significantly decreased BPE after NAT(change of BPE). The nomogram, which incorporates the above parameters, demonstrated excellent predictive performance in both the development and external validation cohorts, with AUC values of 0.900 and 0.850, respectively. Additionally, the nomogram showed excellent calibration capacities, as indicated by Hosmer-Lemeshow test p values of 0.508 and 0.423 in the two cohorts. Furthermore, the nomogram provided greater net benefits compared to the default simple schemes in both cohorts. CONCLUSION: A nomogram constructed using tumor size, HER2 status, Ki-67 index, SER, ADCmin, and changes in pre- and post-NAT BPE demonstrated strong predictive performance, calibration ability, and greater net benefits for predicting pCR in patients with BC after NAT. This suggests that the user-friendly nomogram could be a valuable imaging biomarker for identifying suitable candidates for NAT.

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