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1.
Water Sci Technol ; 89(7): 1665-1681, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619896

RESUMO

By integrating the successful case of the European Union emissions trading system, this study proposes a water emissions trading system, a novel method of reducing water pollution. Assuming that upstream governments allocate initial quotas to upstream businesses as the compensation standard, this approach defines the foundational principles of market trading mechanisms and establishes a robust watershed ecological compensation model to address challenges in water pollution prevention. To be specific, the government establishes a reasonable initial quota for upstream enterprises, which can be used to limit the emissions of upstream pollution. When enterprises exceed their allocated emissions quota, they face financial penalties. Conversely, these emissions rights can be transformed into profitable assets by participating in the trading market as a form of ecological compensation. Numerical simulations demonstrate that various pollutant emissions from upstream businesses will have various effects on the profits of other businesses. Businesses in the upstream region received reimbursement from the assigned emission rights through the market mechanism, demonstrating that ecological compensation for the watershed can be achieved through the market mechanism. This novel market trading system aims at controlling emissions management from the perspectives of individual enterprises and ultimately optimizing the aquatic environment.


Assuntos
Poluentes Ambientais , Rios , Poluição da Água/análise , Modelos Teóricos , China
2.
PLoS One ; 19(4): e0299982, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564602

RESUMO

The wing is one of the most important parts of a bird's locomotor system and is the inspiration origination for bionic wing design. During wing motions, the wing shape is closely related to the rotation angles of wing bones. Therefore, the research on the law of bone movement in the process of wing movement can be good guidance for the design of the bionic morphing wing. In this paper, the skeletal posture of the peregrine falcon wing during the extension/flexion is studied to obtain critical data on skeletal posture. Since an elbow joint and a wrist joint rotate correlatively to drive a wing to flex/extend, the wing skeleton is simplified as a four-bar mechanism in this paper. The degree of reproduction of wing skeleton postures was quantitatively analyzed using the four-bar mechanism model, and the bionic wing skeleton was designed. It is found that the wing motions have been reproduced with high precision.


Assuntos
Falconiformes , Aves Predatórias , Animais , Biônica , Asas de Animais , Osso e Ossos
3.
Biochem Biophys Rep ; 38: 101709, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38638675

RESUMO

B-cell Chronic Lymphocytic Leukemia (B-CLL) is a malignancy caused by the clonal expansion of mature B lymphocytes bearing a CD5+CD19+ (B1) phenotype. However, the origin of B-CLL remains controversial. We showed previously that STYK1/NOK transgenic mice develop a CLL-like disease. Using this model system in this study, we attempt to define the stage of CLL initiation. Here, we show that the phenotype of STYK1/NOK-induced B-CLL is heterogeneous. The expanded B1 lymphocyte pool was detected within peripheral lymphoid organs and was frequently associated with the expansions of memory B cells. Despite this immunophenotypic heterogeneity, suppression of B cell development at an early stage consistently occurred within the bone marrow (BM) of STYK1/NOK-tg mice. Overall, we suggest that enforced expression of STYK1/NOK in transgenic mice might significantly predispose BM hematopoietic stem cells (HSCs) towards the development of B-CLL.

4.
Foods ; 13(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38611377

RESUMO

Beekeeping directly depends on the floral biodiversity available to honey bees. In tropical regions, where nectar and pollen resources are numerous, the botanical origin of some honey is still under discussion. A precise knowledge of plants foraged by honey bees is useful to understand and certify the botanical origin of honey. In this study, attention was paid to honey samples from the French Guiana Atlantic coast where beekeepers generally place their hives in four types of biotopes: seaside vegetation, mangrove, savannah, and secondary forest. Pollen analysis of 87 honey samples enabled the identification of major plants visited by Africanized honey bees during the dry season (approximately from July to January). Through melissopalynologic analysis, 51 pollen types were identified and classified according to their relative presence. Frequently observed pollens (with relative presence > 50%) in French Guiana kinds of honey were those from Mimosa pudica, Cocos sp., Rhyncospora sp., Avicennia germinans, Paspalum sp., Spermacoce verticillata, Tapirira guianensis, Cecropia sp., Myrtaceae sp., Mauritia flexuosa sp., Solanum sp., and Protium sp. In many honeys, only M. pudica was over-represented (relative frequency > 90%). Color and electrical conductivity in French Guiana honeys exhibit significant variations, with color ranging from 27 mm to 110 mm Pfund, and electrical conductivity ranging from 0.35 to 1.22 mS/cm.

5.
Neural Netw ; 175: 106312, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38642415

RESUMO

In recent years, there has been a significant advancement in memristor-based neural networks, positioning them as a pivotal processing-in-memory deployment architecture for a wide array of deep learning applications. Within this realm of progress, the emerging parallel analog memristive platforms are prominent for their ability to generate multiple feature maps in a single processing cycle. However, a notable limitation is that they are specifically tailored for neural networks with fixed structures. As an orthogonal direction, recent research reveals that neural architecture should be specialized for tasks and deployment platforms. Building upon this, the neural architecture search (NAS) methods effectively explore promising architectures in a large design space. However, these NAS-based architectures are generally heterogeneous and diversified, making it challenging for deployment on current single-prototype, customized, parallel analog memristive hardware circuits. Therefore, investigating memristive analog deployment that overrides the full search space is a promising and challenging problem. Inspired by this, and beginning with the DARTS search space, we study the memristive hardware design of primitive operations and propose the memristive all-inclusive hypernetwork that covers 2×1025 network architectures. Our computational simulation results on 3 representative architectures (DARTS-V1, DARTS-V2, PDARTS) show that our memristive all-inclusive hypernetwork achieves promising results on the CIFAR10 dataset (89.2% of PDARTS with 8-bit quantization precision), and is compatible with all architectures in the DARTS full-space. The hardware performance simulation indicates that the memristive all-inclusive hypernetwork costs slightly more resource consumption (nearly the same in power, 22%∼25% increase in Latency, 1.5× in Area) relative to the individual deployment, which is reasonable and may reach a tolerable trade-off deployment scheme for industrial scenarios.

7.
Food Chem ; 447: 138992, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38503066

RESUMO

The low solubility limits the utilization of other functional characteristics of wheat gluten (WG). This study effectively improved the solubility of WG through protease modification and explored the potential mechanism of protease modification to enhance the solubility of WG, further stimulating the potential application of WG in the food industry. Solubility of WG modified with alkaline protease, complex protease, and neutral protease was enhanced by 98.99%, 54.59%, and 51.68%, respectively. Notably, the content of ß-sheet was reduced while the combined effect of hydrogen bond and ionic bond were increased after protease modification. Meanwhile, the reduced molecular size and viscoelasticity as well as the elevated surface hydrophobicity, thermostability, water absorption capacity, and crystallinity were observed in modified WG. Moreover, molecular docking indicated that protease was specifically bound to the amino acid residues of WG through hydrogen bonding, hydrophobic interaction, and salt bridge.


Assuntos
Peptídeo Hidrolases , Triticum , Peptídeo Hidrolases/metabolismo , Triticum/química , Simulação de Acoplamento Molecular , Glutens/química , Aminoácidos/metabolismo
8.
Front Microbiol ; 15: 1288051, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529182

RESUMO

Wasps play important roles as predators and pollinators in the ecosystem. The Jingpo minority residing in Yunnan Province, China, has a traditional practice of using wine infused with mature wasps as a customary remedy for managing rheumatoid arthritis. The larva of the wasp is also a tasteful folk dish that has created a tremendous market. There is a paucity of survival knowledge, which has greatly restricted their potential applications in food and healthcare. Recent research has highlighted the importance of gut microbiota in insect growth. Nevertheless, there is still a lack of understanding regarding the composition, changes, and functions of the gut microbiota in Vespa mandarinia during development. In this research, the gut microbiota were investigated across three growth stages of Vespa mandarinia using a metagenomic technology. The result revealed that there are significant variations in the proportion of main gut microbes during the metamorphosis of Vespa mandarinia. Tenericutes were found to dominate during the larval stage, while Proteobacteria emerged as the dominant group post-pupation. Through a comprehensive analysis of the gut microbiota metagenome, this study revealed functional differences in the wasp gut microbiota at various growth stages. During the larval stage, the gut microbiota plays a central role in promoting metabolism. Following pupation, the gut microbiota exhibited diversified functions, likely due to the complex environments and diverse food sources encountered after metamorphosis. These functions included amino acid metabolism, compound degradation, and defense mechanisms. This research provides an extensive dataset on the gut microbiota during the metamorphosis of Vespa mandarinia, contributing to a deeper understanding of the influence of gut microbiota on wasp growth. Furthermore, this study uncovers a unique microbial treasure within insect guts, which is important for advancing the application of wasps in the fields of food and medicine.

9.
Biol Reprod ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531779

RESUMO

Pigs serve as a robust animal model for the study of human diseases, notably in the context of disorders of sex development (DSD). This study aims to investigate the phenotypic characteristics and molecular mechanisms underlying the reproductive and developmental abnormalities of 38,XX ovotestis-DSD (OT-DSD) and 38,XX testis-DSD (T-DSD) in pigs. Clinical and transcriptome sequencing analyses were performed on DSD and normal female pigs. Cytogenetic and SRY analyses confirmed that OT/T-DSD pigs exhibited a 38,XX karyotype and lacked the SRY gene. The DSD pigs had higher levels of follicle-stimulating hormone, luteinizing hormone, and progesterone, but lower testosterone levels when compared with normal male pigs. The reproductive organs of OT/T-DSD pigs exhibit abnormal development, displaying both male and female characteristics, with an absence of germ cells in the seminiferous tubules. Sex determination and development-related differentially-expressed genes (DEGs) shared between DSD pigs were identified in the gonads, including WT1, DKK1, CTNNB1, WTN9B, SHOC, PTPN11, NRG1 and NXK3-1. DKK1 is proposed as a candidate gene for investigating the regulatory mechanisms underlying gonadal phenotypic differences between OT-DSD and T-DSD pigs. Consequently, our findings provide insights into the molecular pathogenesis of DSD pigs and present an animal model for studying into DSD in humans.

10.
BMC Cardiovasc Disord ; 24(1): 179, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528469

RESUMO

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Nomogramas , Estudos Retrospectivos , Infarto do Miocárdio/diagnóstico , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Hemorragia/epidemiologia
11.
J Mater Chem B ; 12(3): 730-741, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38165726

RESUMO

Melanoma, the most aggressive and life-threatening form of skin cancer, lacks innovative therapeutic approaches and deeper bioinformation. In this study, we developed a photothermal therapy (PTT) based on Mo2C nanosheets to eliminate melanoma while utilizing integrated metabolomics to investigate the metabolic shift of metabolome combined lipidome during PTT at the molecular level. Our results demonstrated that 1 mg ml-1 Mo2C nanosheets could efficiently convert laser energy into heat with a strong and stable photothermal effect (74 ± 0.9 °C within 7 cycles). Furthermore, Mo2C-based PTT led to a rapid decrease in melanoma volume (from 3.299 to 0 cm2) on the sixth day, indicating the effective elimination of melanoma. Subsequent integrated metabolomics analysis revealed significant changes in aqueous metabolites (including organic acids, amino acids, fatty acids, and amines) and lipid classes (including phospholipids, lysophospholipids, and sphingolipids), suggesting that melanoma caused substantial fluctuations in both metabolome and lipidome, while Mo2C-based PTT helped improve amino acid metabolism-related biological events (such as tryptophan metabolism) impaired by melanoma. These findings suggest that Mo2C nanosheets hold significant potential as an effective therapeutic agent for skin tumors, such as melanoma. Moreover, through exploring multidimensional bioinformation, integrated metabolomics technology provides novel insights for studying the metabolic effects of tumors, monitoring the correction of metabolic abnormalities by Mo2C nanosheet therapy, and evaluating the therapeutic effect on tumors.


Assuntos
Melanoma , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Lipidômica , Terapia Fototérmica , Metaboloma , Homeostase
12.
Cell Transplant ; 33: 9636897231223293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38193390

RESUMO

The objective of this study was to evaluate the feasibility, safety, and effectiveness of intravenous stem cell delivery utilizing ultrasound-targeted microbubble destruction (UTMD) in a rat model of middle cerebral artery occlusion (MCAO), while investigating the underlying mechanisms. Acute cerebral infarction (ACI) was induced surgically in adult rats to create the MCAO rat model. Intravenous injection of SonoVue microbubbles and bone marrow-derived mesenchymal stem cells (BMSC) was performed concurrently, with or without ultrasound targeting the stroke. The animals were divided into four groups: sham-operated group, ACI-MCAO rats treated with phosphate-buffered saline (ACI+PBS), rats receiving intravenous delivery of BMSC expressing green fluorescent protein (GFP-BMSC; ACI+BMSC), and rats receiving intravenous GFP-BMSC with simultaneous UTMD exposure (ACI+BMSC+UTMD). The efficacy of the treatments was assessed by evaluating the animals' neurological function using the Longa score and examining histopathological changes such as cerebral infarct volume, cerebral edema, and cell apoptosis. A rat cytokine array was utilized to identify the potential cytokines that may be responsible for the therapeutic effect of UTMD-mediated BMSC treatment. Optimal UTMD parameters resulted in an increase in blood-brain barrier (BBB) permeability after 30 min, which returned to baseline 72 h later without causing any residual injury. UTMD application significantly increased the homing of intravenously delivered BMSC, resulting in a 2.2-fold increase in GFP-BMSC cell count on day 3 and a 2.6-fold increase on day 7 compared with intravenous delivery alone. This effect persisted for up to 6 weeks after injection. Intravenous BMSC delivery significantly reduced the volume of cerebral infarct and decreased cerebral edema, leading to a lower Longa score. Furthermore, this effect was further enhanced by UTMD. Acute cerebral infarction induced by MCAO led to elevated matrix metalloproteinase 8 (MMP8) levels in the cerebrospinal fluid, which were significantly reduced following UTMD-mediated BMSC treatment. Ultrasound-targeted microbubble destruction facilitates the migration and homing of BMSC into the brain, possibly by transiently increasing blood-brain barrier (BBB) permeability, thereby improving therapeutic outcomes in an ACI rat model. The observed effect may be partly attributed to modulation of MMP8 levels.Advances in knowledge: UTMD-mediated intravenously delivered BMSC transplantation led to a significant increase in cell homing and reduction of MMP8 levels, resulting in increased therapeutic effect in an acute ischemic cerebral infarction model.


Assuntos
Edema Encefálico , Isquemia Encefálica , Acidente Vascular Cerebral , Animais , Ratos , Barreira Hematoencefálica , Metaloproteinase 8 da Matriz , Microbolhas , Acidente Vascular Cerebral/terapia , Infarto Cerebral , Células-Tronco
13.
Atherosclerosis ; 388: 117396, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38086281

RESUMO

BACKGROUND AND AIMS: Lack of physical activity (PA) and sarcopenia is a known risk factors for ischemic heart disease (IHD). However, considering their coexistence in the middle-aged and elderly population, the interaction of these two factors remains uncertain. Here, we investigated the interactive effects of PA and sarcopenia on IHD. METHODS: We extracted 344,688 participants free of IHD at baseline from the UK Biobank. PA was classified into low, moderate, and high according to the International Physical Activity Questionnaire. Sarcopenia was identified in accordance with the European Working Group on Sarcopenia in Older People 2. Cox proportional hazard models were applied to estimate the effect of PA and sarcopenia on incident IHD and its subtypes. We also used objective PA data measured by wrist-worn devices to repeat these analyses. RESULTS: Over a median follow-up of 11.7 years, 24,809 (7.2%) participants developed incident IHD. Lack of PA was associated with a higher risk of IHD after adjusting for potential confounders. The hazard ratio (HR) was 1.09 (95% CI: 1.05-1.13) for individuals without sarcopenia and 1.29 (95% CI: 1.17-1.42) for those with sarcopenia. Regarding the joint effect, the combination of low PA and sarcopenia was associated with the highest risk of IHD, with an HR of 1.54 (95% CI: 1.44-1.66), and both additive and multiplicative interactions were significant (RERI 0.27, 95% CI: 0.14-0.39, p-interaction <0.01). For subtypes of IHD, the interaction was pronounced in acute myocardial infarction and chronic ischemic heart disease. CONCLUSIONS: These results suggest a synergistic interaction between lack of PA and sarcopenia on the risk of IHD. Findings from this study may help facilitate more effective primary prevention of IHD.


Assuntos
Isquemia Miocárdica , Sarcopenia , Pessoa de Meia-Idade , Humanos , Idoso , Estudos de Coortes , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/complicações , Incidência , Isquemia Miocárdica/epidemiologia , Fatores de Risco , Exercício Físico
14.
Ecotoxicol Environ Saf ; 269: 115792, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38064789

RESUMO

OBJECTIVE: We examined the relationships between infants' growth trajectories and prenatal exposure to air pollution, which is still under-investigated. METHODS: A birth cohort study was constructed using medical records of pregnant women and infants born between 2015 and 2019 in Foshan, China. Using satellite-based spatial-temporal models, prenatal exposure to air pollutants including particulate matter with an aerodynamic dimension of < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) was assessed at each woman's residence. Latent class growth modeling was used to identify trajectories of physical (body length and weight) growth and neurodevelopment, which were repeatedly measured within 1 year after birth. Logistic regression models were used to investigate the associations between prenatal exposure to air pollution and the risks of growth disorders, adjusting for an array of potential confounders. RESULTS: We identified two growth trajectories for body length [normal: 3829 (93%); retardation: 288 (7%)], three for weight [normal: 2475 (59.6%); retardation: 390 (9.4%); overgrowth: 1287 (31%)], and two for neurodevelopment [normal: 956 (66.1%); retardation: 491 (33.9%)]. For exposure over whole pregnancy, SO2 was associated with an increased risk of body length retardation (OR for per 1 µg/m3 increment: 1.09, 95%CI: 1.01-1.17); PM2.5 (OR: 1.05, 95%CI: 1.03-1.07), SO2 (OR: 1.15, 95%CI: 1.08-1.22), and NO2 (OR: 1.05, 95%CI: 1.03-1.07) were positively associated with neurodevelopmental retardation. Such associations appeared stronger for exposures over the first and second trimesters. No significant associations were detected for weight growth. CONCLUSIONS: Maternal exposure to air pollution during pregnancy was associated with higher risks of impairments in both physical growth, particularly body length, and neurodevelopment.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Efeitos Tardios da Exposição Pré-Natal , Lactente , Humanos , Feminino , Gravidez , Exposição Materna/efeitos adversos , Estudos de Coortes , Dióxido de Nitrogênio/análise , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/toxicidade
16.
Hypertension ; 81(2): 372-382, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38116660

RESUMO

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.


Assuntos
Doenças Cardiovasculares , Hipertensão Pulmonar , Humanos , Hematopoiese Clonal , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , Hematopoese/genética , Doenças Cardiovasculares/genética , Mutação
17.
Cancer Lett ; 582: 216569, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101608

RESUMO

Progression occurs in approximately two-thirds of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving chemoradiation and consolidation immunotherapy. Molecular indicators for outcome prediction are under development. A novel metric, the ratio of mean to max variant allele frequency (mmVAF), was derived from 431 pre-treatment tissue biopsies from The Cancer Genome Atlas and evaluated in serial circulating tumor DNA (ctDNA) from 70 LA-NSCLC patients receiving definitive radiotherapy/chemoradiotherapy (RT/CRT) with/without immunotherapy. High mmVAFs in pre-treatment tissue biopsies, indicating clonal predominant tumors (P < 0.01), were associated with inferior overall survival [OS, hazard ratio (HR): 1.48, 95 % confidence interval (CI): 1.11-1.98]. Similar associations of mmVAF with clonality (P < 0.01) and OS (HR: 2.24, 95 % CI: 0.71-7.08) were observed in pre-treatment ctDNA. At 1-month post-RT, ctDNA mmVAF-high patients receiving consolidation immunotherapy exhibited improved progression-free survival (PFS) compared to those who did not (HR: 0.14, 95 % CI: 0.03-0.67). From the baseline to week 4 of RT and/or 1-month post-RT, survival benefits from consolidation immunotherapy were exclusively observed in ctDNA mmVAF-increased patients (PFS, HR: 0.39, 95 % CI: 0.14-1.15), especially in terms of distant metastasis (HR: 0.11, 95 % CI: 0.01-0.95). In summary, our longitudinal data demonstrated the applicability of ctDNA-defined clonality for prognostic stratification and immunotherapy benefit prediction in LA-NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Quimiorradioterapia , Imunoterapia
18.
Front Immunol ; 14: 1281888, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077319

RESUMO

Background: In the era of immunotherapy, the optimal combination of immune checkpoint inhibitors (ICIs) and chemoradiotherapy (CRT) for stage III non-small cell lung cancer (NSCLC) is not defined. The current study investigated the efficacy and safety of definitive CRT(dCRT) plus consolidation ICIs with or without induction ICIs in stage III NSCLC. Methods: 123 consecutive patients treated with dCRT followed by consolidation ICIs at our institution from 2018 to 2022 were retrospectively reviewed. Failure patterns, survival outcomes, and toxicity profiles were analyzed. Results: The 1- and 2- year PFS rates were 75.3% and 56.9%, respectively, and median PFS was 30.83 months from the start of treatment. In-field failure (18.7%) was the most common failure pattern. The most common adverse event (AE) was pneumonitis caused by ICIs or RT. The incidence of Grade 3-4 and Grade 5 pneumonitis was 5.7% and 1.6%, respectively. Further analysis showed that the induction plus consolidation ICIs group has significantly lower cumulative incidence of distant metastasis rates (HR: 0.30, 95%CI: 0.09-1.00, p=0.043) and higher incidence of pneumonitis (p=0.039) compared with patients in the consolidation ICIs group. Conclusions: Combined CRT and consolidation ICIs achieved encouraging efficacy and manageable toxicity in patients with stage III NSCLC in China. Induction plus consolidation ICIs might reduce distant metastasis and deserve further investigation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Quimiorradioterapia/efeitos adversos , Pneumonia/complicações
19.
Biochem Genet ; 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38108937

RESUMO

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.

20.
Sensors (Basel) ; 23(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37960615

RESUMO

The presence of speckle noise severely hampers the interpretability of synthetic aperture radar (SAR) images. While research on despeckling single-temporal SAR images is well-established, there remains a significant gap in the study of despeckling multi-temporal SAR images. Addressing the limitations in the acquisition of the "superimage" and the generation of ratio images within the RABASAR despeckling framework, this paper proposes an enhanced framework. This enhanced framework proposes a direction-based segmentation approach for multi-temporal SAR non-local means filtering (DSMT-NLM) to obtain the "superimage". The DSMT-NLM incorporates the concept of directional segmentation and extends the application of the non-local means (NLM) algorithm to multi-temporal images. Simultaneously, the enhanced framework employs a weighted averaging method based on wavelet transform (WAMWT) to generate superimposed images, thereby enhancing the generation process of ratio images. Experimental results demonstrate that compared to RABASAR, Frost, and NLM, the proposed method exhibits outstanding performance. It not only effectively removes speckle noise from multi-temporal SAR images and reduces the generation of false details, but also successfully achieves the fusion of multi-temporal information, aligning with experimental expectations.

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