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Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1-deficient cNK cells and liver ILC1s. Single-cell RNA sequencing (scRNA-seq) data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s, and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.
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Neoplasias Hepáticas , Camundongos Knockout , Fator 1 de Ligação ao Domínio I Regulador Positivo , Animais , Camundongos , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Células Matadoras Naturais/imunologia , Interferon gama/metabolismo , Imunidade Inata , Linfócitos/imunologia , Vigilância Imunológica , Granzimas/metabolismo , Granzimas/genética , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/genética , Perforina/metabolismo , Perforina/genética , Fígado/imunologia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Microambiente Tumoral/imunologia , Antígenos LyRESUMO
PURPOSE: Concurrent chemoradiotherapy is the current non-surgical standard of care for locally advanced non-small cell lung cancer (NSCLC). However, this is a difficult regimen to tolerate especially for those who are elderly, have multiple comorbidities or poor performance status. Alternative treatment regimens are needed for this vulnerable population. We report initial results of concurrent durvalumab, an immune checkpoint inhibitor, and hypofractionated, dose-escalating, proton external beam radiotherapy (EBRT). PATIENTS AND METHODS: This phase I, pilot dose-escalation trial enrolled seven patients with newly diagnosed stage IIIA-IIIC NSCLC who were unable or unwilling to undergo concurrent chemoradiotherapy. Patients previously treated with immunotherapy were excluded. Five patients in the initial phase of this 3+3 study design received a fixed dose of durvalumab each 28-day cycle plus hypofractionated proton EBRT 60 Gy in 20 fractions while two patients received the escalation dose of 69 Gy in 23 fractions. The primary objective assessed safety while secondary objectives assessed feasibility and adverse events. RESULTS: All patients experienced treatment-related adverse events, primarily grades 1-2. Pneumonitis and anemia were the most common. Only one dose limiting toxicity occurred, in arm one, which was a grade 3 pneumonitis leading to grade 5 pneumonia. Additionally, two delayed-onset grade 5 tracheal necrosis events occurred > 13 months after treatment initiation. CONCLUSIONS: Concurrent durvalumab plus hypofractionated proton EBRT was well tolerated in the short term. However, three treatment-related deaths, including two delayed-onset grade 5 tracheal necroses negatively impacted overall safety. A dose de-escalation protocol of proton-based radiotherapy plus durvalumab is warranted.
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Faba bean wilt disease is a key factor limiting its production. Intercropping of faba bean with wheat has been adopted as a prevalent strategy to mitigate this disease. Nitrogen fertilizer improves faba bean yield, yet wilt disease imposes limitations. However, faba bean-wheat intercropping is effective in controlling wilt disease. To investigate the effect of intercropping under varying nitrogen levels on the incidence of faba bean wilt disease, nutrient uptake, and biochemical resistance in faba bean. Field and pot experiments were conducted in two cropping systems: faba bean monocropping (M) and faba bean-wheat intercropping (I). At four nitrogen levels, we assessed the incidence rate of wilt disease, quantified nutrient uptake, and evaluated biochemical resistance indices of plants. The application of N decreased the incidence rate of wilt disease, with the lowest reduction observed in intercropping at the N2 level. N application at levels N1, N2, and N3 enhanced the content of N, P, K, Fe, and Mn as well as superoxide dismutase (SOD), phenylalanine ammonia lyase (PAL), and polyphenol oxidase (PPO) activities and defense gene expression in monocultured plants. Additionally, these levels increased the contents of total phenols, flavonoids, soluble sugars, and soluble proteins, and all reached their maximum in intercropping at the N2 level. The application of intercropping and N effectively controlled the occurrence of faba bean wilt disease by promoting nutrient absorption, alleviating peroxidation stress, and enhancing resistance in plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01466-1.
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Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.
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Alterations in the composition of the gut microbiota may be causally associated with several brain diseases. Indole-3-propionic acid (IPrA) is a tryptophan-derived metabolite, which is produced by intestinal commensal microbes, rapidly enters the circulation, and crosses the blood-brain barrier. IPrA has neuroprotective properties, which have been attributed to its antioxidant and bioenergetic effects. Here, we evaluate an alternative and/or complementary mechanism, linking IPrA to kynurenic acid (KYNA), another neuroprotective tryptophan metabolite. Adult Sprague-Dawley rats received an oral dose of IPrA (200 mg/kg), and both IPrA and KYNA were measured in plasma and frontal cortex 90 minutes, 6 or 24 hours later. IPrA and KYNA levels increased after 90 minutes and 6 hours (brain IPrA: ~56- and ~7-fold; brain KYNA: ~4- and ~3-fold, respectively). In vivo microdialysis, performed in the medial prefrontal cortex and in the striatum, revealed increased KYNA levels (~2.5-fold) following the administration of IPrA (200 mg/kg, p.o), but IPrA failed to affect extracellular KYNA when applied locally. Finally, treatment with 100 or 350 mg IPrA, provided daily to the animals in the chow for a week, resulted in several-fold increases of IPrA and KYNA levels in both plasma and brain. These results suggest that exogenously supplied IPrA may provide a novel strategy to affect the function of KYNA in the mammalian brain.
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RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.
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Centrômero , DNA Topoisomerases Tipo I , DNA Satélite , RNA Polimerase II , Transcrição Gênica , Animais , DNA Satélite/genética , DNA Satélite/metabolismo , Humanos , Centrômero/metabolismo , Camundongos , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo I/genética , RNA Polimerase II/metabolismo , RNA Polimerase II/genética , Quebras de DNA de Cadeia Dupla , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Evolução MolecularRESUMO
Phenolic resins occupy an important position in industrial applications, but phenol, one of the raw materials for synthesis, is a non-renewable resource. Lignin, as a natural polymer containing phenolic hydroxyl groups, alcohol hydroxyl groups and other reactive groups, can replace some of the phenol in the synthesis of phenolic resins, which can reduce the amount of phenol, thus reducing the cost of phenolic resins, while effectively promoting the high value-added use of renewable biomass resources. Due to its low reactivity, alkaline lignin is usually discharged as production waste, unaware that lignin macromolecules can be modified. In this paper, the phenolic monomers were obtained by acid-catalyzed depolymerization of DES (choline chloride/p-toluenesulfonic acid or choline chloride/lactic acid) from waste alkaline lignin, and the recovery rate of the DES solution during the catalytic treatment was more than 85 %, in which the main monomer was 2-methoxy-4-(1-propyl) phenol. The degradation of alkaline lignin is still favorable after five times of DES solvent recovery. The depolymerized lignin monomer replaced phenol by 50 wt% and then ternary co-polymerized with phenol and formaldehyde to form a biomass phenol-based phenolic resin, providing a green route for phenolic resin production. The cost of resin preparation was economically calculated, and it was found that the cost of resin after accumulating 4 cycles of DES treatment was only 51.1 % of that of pure phenolic resin. The density functional theory (DFT) was used to simulate the possible radical reactions in the intermediate process of phenolic resin reaction, to explore the microscopic mechanism and competition, to provide theoretical reference for further experimental realization of resin structure control and optimization, and to improve the theoretical system of resin synthesis.
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Lignina , Fenóis , Polimerização , Lignina/química , Fenóis/química , Catálise , Fenol/química , Biomassa , Resinas Sintéticas/químicaRESUMO
Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.
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Beneficial fungi are well known for their contribution to insects' adaptation to diverse habitats. However, where insect-associated fungi reside and the underlying mechanisms of insect-fungi interaction are not well understood. Here, we show a pellet-like structure on the legs of mealybugs, a group of economically important insect pests. This at-leg pellet, formed by mealybugs feeding on tomato but not by those on cotton, potato, or eggplant, originates jointly from host secretions and mealybug waxy filaments. A fungal strain, Penicillium citrinum, is present in the pellets and it colonizes honeydew. P. citrinum can inhibit mealybug fungal pathogens and is highly competitive in honeydew. Compounds within the pellets also have inhibitory activity against mealybug pathogens. Further bioassays suggest that at-leg pellets can improve the survival rate of Phenacoccus solenopsis under pathogen pressure, increase their sucking frequency, and decrease the defense response of host plants. Our study presents evidences on how a fungi-associated at-leg pellet provides multiple protections for mealybugs through suppressing pathogens and host defense, providing new insights into complex insect × fungi × plant interactions and their coevolution.
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Hemípteros , Penicillium , Penicillium/fisiologia , Animais , Hemípteros/microbiologia , Hemípteros/fisiologiaRESUMO
Continuous cropping of faba bean (Vicia faba L.) has led to a high incidence of wilt disease. The implementation of an intercropping system involving wheat and faba bean can effectively control the propagation of faba bean wilt disease. To investigate the mechanisms of wheat in mitigating faba bean wilt disease in a wheat-faba bean intercropping system. A comprehensive investigation was conducted to assess the temporal variations in Fusarium oxysporum f. sp. fabae (FOF) on the chemotaxis of benzoxazinoids (BXs) and wheat root through indoor culture tests. The effects of BXs on FOF mycelial growth, spore germination, spore production, and electrical conductivity were examined. The influence of BXs on the ultrastructure of FOF was investigated through transmission electron microscopy. Eukaryotic mRNA sequencing was utilized to analyze the differentially expressed genes in FOF upon treatment with BXs. FOF exhibited a significant positive chemotactic effect on BXs in wheat roots and root secretions. BXs possessed the potential to exert significant allelopathic effects on the mycelial growth, spore germination, and sporulation of FOF. In addition, BXs demonstrated a remarkable ability to disrupt the structural integrity and stability of the membrane and cell wall of the FOF mycelia. BXs possessed the capability of posing threats to the integrity and stability of the cell membrane and cell wall. This ultimately resulted in physiological dysfunction, effectively inhibiting the regular growth and developmental processes of the FOF.
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Benzoxazinas , Fusarium , Vicia faba , Parede Celular , Triticum , Crescimento e DesenvolvimentoRESUMO
KEY MESSAGE: The regulatory action of BXs secreted by wheat on the pathogenicity of FOF causing Fusarium wilt in faba bean were analyzed. DIMBOA and MBOA weakened the pathogenicity of FOF. A large number of pathogenic bacteria in continuous cropping soil infect faba bean plants, leading to the occurrence of wilt disease, which restricts their production. Faba bean-wheat intercropping is often used to alleviate this disease. This study investigates the effect of benzoxazinoids (BXs) secreted by wheat root on the pathogenicity of Fusarium oxysporum f. sp. Fabae (FOF) and underlying molecular mechanisms. The effects of DIMBOA(2,4-dihydroxy-7-methoxy-1,4-benzoxazine-4-one) and MBOA(6-methoxybenzoxazolin-2-one) on the activity of cell-wall-degrading enzymes in FOF(cellulase, pectinase, amylase, and protease), FOF Toxin (fusaric acid, FA) content were investigated through indoor culture experiments. The effect of BXs on the metabolic level of FOF was analyzed by metabonomics to explore the ecological function of benzoxazines intercropping control of Fusarium wilt in faba bean. The results show that the Exogenous addition of DIMBOA and MBOA decreased the activity of plant-cell-wall-degrading enzymes and fusaric acid content and significantly weakened the pathogenicity of FOF. DIMBOA and MBOA significantly inhibited the pathogenicity of FOF, and metabolome analysis showed that DIMBOA and MBOA reduced the pathogenicity of FOF by down-regulating related pathways such as nucleotide metabolism and linoleic acid metabolism, thus effectively controlling the occurrence of Fusarium wilt in faba bean.
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Benzoxazinas , Fusarium , Triticum , Benzoxazinas/farmacologia , Ácido Linoleico , Virulência , Ácido Fusárico , NucleotídeosRESUMO
The direct ink writing technique used in 3D printing technology is generally applied to designing biomedical hydrogels. Herein, we proposed a strategy for preparing all-chitin-based inks for wound dressing via direct ink writing technique. The ß-chitin nanofibers (MACNF) with a high aspect ratio were applied as a nanofiller to modulate the rheological properties of the alkaline dissolved chitin solution. The printing fidelity significantly depends on the MACNF introduction amount to the composite ink. 5-10 wt% MACNF ratio showed superior printing performance. The printed scaffold showed a uniform micron-sized pore structure and a woven network of nanofibers. Due to the good biocompatibility of chitin and the stereoscopic spatial skeleton, this scaffold showed excellent performance as a wound dressing, which can promote cell proliferation, collagen deposition and the angiogenesis of wounds, demonstrating its potential in biomedical applications. This approach successfully balanced the chitinous printability and biofunctions.
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Quitina , Hidrogéis , Quitina/química , Hidrogéis/farmacologia , Hidrogéis/química , Bandagens , Colágeno , Impressão TridimensionalRESUMO
Silicon is a promising anode material for lithium-ion batteries with its superior capacity. However, the volume change of the silicon anode seriously affects the electrode integrity and cycle stability. The waterborne guar gum (GG) binder has been regarded as one of the most promising binders for Si anodes. Here, a unique steric molecular combing approach based on guar gum, glycerol, and citric acid is proposed to develop a self-healing binder GGC, which would boost the structural stability of electrode materials. The GGC binder is mainly designed to weaken van der Waals' forces between polymers through the plasticizing effect of glycerol, combing and straightening the guar molecular chain of GG, and exposing the guar hydroxyl sites of GG and the carboxyl groups of citric acid. The condensation reaction between the hydroxyl sites of GG and the carboxyl groups of citric acid forms stronger hydrogen bonds, which can help achieve self-healing effect to cope with the severe volume expansion effect of silicone-based materials. Silicon electrode lithium-ion batteries prepared with GGC binders exhibit outstanding electrochemical performance, with a discharge capacity of up to 1579 mAh/g for 1200 cycles at 1 A/g, providing a high capacity retention rate of 96%. This paper demostrates the great potential of GGC binders in realizing electrochemical performance enhancement of silicon anode.
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Mutations leading to a reduced or loss of function in genes of the leptin-melanocortin system confer a risk for monogenic forms of obesity. Yet, gain of function variants in the melanocortin-4-receptor (MC4R) gene predispose to a lower BMI. In individuals with reduced body weight, we thus expected mutations leading to an enhanced function in the respective genes, like leptin (LEP) and MC4R. Therefore, we have Sanger sequenced the coding regions of LEP and MC4R in 462 female patients with anorexia nervosa (AN), and 445 healthy-lean controls. In total, we have observed four and eight variants in LEP and MC4R, respectively. Previous studies showed different functional in vitro effects for the detected frameshift and non-synonymous variants: (1) LEP: reduced/loss of function (p.Val94Met), (2) MC4R: gain of function (p.Val103Ile, p.Ile251Leu), reduced or loss of function (p.Thr112Met, p.Ser127Leu, p.Leu211fsX) and without functional in vitro data (p.Val50Leut). In LEP, the variant p.Val94Met was detected in one patient with AN. For MC4R variants, one patient with AN carried the frameshift variant p.Leu211fsX. One patient with AN was heterozygous for two variants at the MC4R (p.Val103Ile and p.Ser127Leu). All other functionally relevant variants were detected in similar frequencies in patients with AN and lean individuals.
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Anorexia Nervosa , Leptina , Receptor Tipo 4 de Melanocortina , Feminino , Humanos , Anorexia Nervosa/genética , Leptina/genética , Melanocortinas/genética , Mutação , Obesidade/genética , Receptor Tipo 4 de Melanocortina/genéticaRESUMO
Cancer vaccines provide a potential strategy to cure patients. Their clinical utilization and efficacy is, however, limited by incomplete coverage of tumor neoantigens and unspecific and restricted activation of dendritic cells (DCs). Tumor cell lysates (TCLs) containing a broad spectrum of neoantigens, while are considered ideal in formulating personalized vaccines, induce generally poor antigen presentation and transient antitumor immune response. Here, intelligent polymersomal nanovaccines (PNVs) that quantitatively coload, efficiently codeliver, and responsively corelease TCL and CpG adjuvant to lymph node (LN) DCs are developed to boost antigen presentation and to induce specific and robust antitumor immunity. PNVs carrying CpG and ovalbumin (OVA) markedly enhance the maturation, antigen presentation, and downstream T cell activation ability of bone-marrow-derived dendritic cells and induce strong systemic immune response after tail base injection. Remarkably, PNVs carrying CpG and TCL cure 85% of B16-F10 melanoma-bearing mice and generate long-lasting anticancer immune memory at a low dose, protecting all cured mice from tumor rechallenge. These LN-directed PNVs being highly versatile and straightforward opens a new door for personalized cancer vaccines.
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Vacinas Anticâncer , Células Dendríticas , Imunoterapia , Linfonodos , Camundongos Endogâmicos C57BL , Animais , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Células Dendríticas/imunologia , Linfonodos/imunologia , Camundongos , Adjuvantes Imunológicos/administração & dosagem , Melanoma Experimental/terapia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Ovalbumina/imunologia , Ovalbumina/administração & dosagem , Ovalbumina/química , Linhagem Celular Tumoral , Feminino , Nanopartículas/químicaRESUMO
INTRODUCTION: Stereotactic body radiation therapy (SBRT) is an effective treatment for medically inoperable early-stage non-small cell lung cancer (NSCLC). The prognostic value of invasive nodal staging (INS) for patients undergoing SRBT has not been studied extensively. Herein, we report the impact of INS in addition to 18F-FDG-PET on treatment outcome for patients with NSCLC undergoing SBRT. MATERIALS AND METHODS: Patients with stage I/ II NSCLC who underwent SBRT were included with IRB approval. Clinical, dosimetric, and radiological data were obtained. Overall survival (OS), regional recurrence free survival (RRFS), local recurrence free survival (LRFS), and distant recurrence free survival (DRFS) were analyzed using Kaplan Meyer method. Univariable analysis (UVA) and multivariable analysis (MVA) were performed to assess the relationship between the variables and the outcomes. RESULTS: A total of 376 patients were included in the analysis. Median follow up was 43 months (IQ 32.6-45.8). Median OS, LRFS, RRFS, DRFS were 40, 32, 32, 33 months, respectively. The 5-year local, regional, and distant failure rates were 13.4%, 23.5% and 25.3%, respectively. The 1-year, 3-year and 5-year OS were 83.8%, 55.6%, and 36.3%, respectively. On MVA, INS was not a predictor of either improved overall or any recurrence free survival endpoints while larger tumor size, age, and adjusted Charleston co-morbidity index (aCCI) were significant for inferior LRFS, RRFS, and DRFS. CONCLUSION: Invasive nodal staging did not improve overall or recurrence free survival among patients with early-stage NSCLC treated with SBRT whereas older age, aCCI, and larger tumor size were significant predictors of LRFS, RRFS, and DRFS.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Radiocirurgia/métodos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Seguimentos , Estudos Retrospectivos , Prognóstico , Resultado do Tratamento , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Metástase Linfática , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Adulto , Recidiva Local de Neoplasia/patologia , Endossonografia/métodos , Taxa de SobrevidaRESUMO
Purpose: Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Methods and Materials: Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n = 163) and follow-up FDG-PET/CT at 3 or 6 months (n = 71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Results: Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P = .006), >12.3 for PFS (aHR, 2.80, P = .011), and >12.6 for OS (aHR, 3.00, P = .003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P = .018), and 53% at 6 months (aHR, 0.12, P = .046) were associated with improved local failure-free survival. Conclusions: Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.
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Rational design of hierarchical porous architecture with abundant pseudocapacitive sites is highly desirable for carbon electrode materials. However, the lengthy production process and high economic input limit its broader application. Herein, we successfully prepared N, O co-doped hierarchical porous carbon (NOHC) through hydrothermal carbonization (HTC) of chitin biomass with the assist of NH4Cl and subsequent carbonization with NaNH2. The optimal NOHC600 exhibits a remarkable hierarchical porous structure and an ultrahigh specific surface area (SSA) of 2555 m2 g-1. Furthermore, it showcases a significant content of N, O co-doping, thereby providing abundant defects and additional active sites for ion adsorption. The aforementioned characteristics ensure outstanding capacitance performance of NOHC600. In the three-electrode system, NOHC600 exhibits a remarkable specific capacitance of up to 455 F g-1 at a current density of 0.5 A g-1. The symmetric supercapacitors (SCs) based on NOHC600 achieve an impressive energy density of 30.4 Wh kg-1 at a power density of 180 W kg-1. Moreover, the all-solid-state NOHC600 microsupercapacitors (MSCs) demonstrate an exceptional areal capacitance of 78.2 mF cm-2 and an areal energy density of up to 10.8 µWh cm-2. Accordingly, this facile and scalable strategy shows a great potential for producing high-heteroatom-doped porous carbon materials from chitin biomass, which can be applied in practical energy-related applications.
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Continuous cropping severely affects faba bean growth, mainly due to pathogen and autotoxic substance accumulation. Here, we used faba bean monocropping (M) and intercropping with wheat (I), with stress treatments of Fusarium oxysporum f. sp. fabae (FOF) alone (F) and combined with cinnamic acid (F + C), to analyze seedling growth, defense-related enzymes, levels of resistance-associated substances, and protein expression profiles in roots. The results showed that intercropping mitigated the inhibitory effects of FOF and cinnamic acid. FOF resulted in increased activities of defense-related enzymes as well as levels of resistance-associated substances. Proteomic analysis showed that 22 proteins were upregulated following FOF inoculation (M + F), and 6 proteins were downregulated after the addition of cinnamic acid (M + F + C) in monocropping plants; these proteins were mainly involved in pathways associated with carbohydrate metabolism, energy, and the cytoplasm. Comparison of monocropping and intercropping indicated that the upregulated proteins were mostly associated with stress and defense, carbohydrate transport and metabolism, maintenance of cellular homeostasis, and protein synthesis. KEGG analysis revealed that intercropping increased enrichment in pathways associated with metabolism, ribosomes, biosynthesis of secondary metabolites, proteasomes, pyruvate metabolism, and pentose and glucuronate interconversions. The results indicated that intercropping mitigated growth inhibition by FOF and cinnamic acid by increasing energy production, maintaining normal cellular functions, and promoting the synthesis of defense-associated secondary metabolites. These findings provide a basis for further investigation into the molecular mechanisms underlying the effects of intercropping in controlling resistance to Fusarium wilt in the faba bean.
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Fusarium , Vicia faba , Triticum , Plântula , ProteômicaRESUMO
Allelopathy is the main reason for disease control in intercropping systems. The effects of different extracts, root secretions and phenolic acids of wheat and faba bean on Fusarium oxysporum f. fabae (FOF) growth were studied to explore the allelopathy mechanism of wheat in disease control of faba bean. Various extracts and root exudate of faba bean were promoted but those of wheat inhibited the growth and reproduction of FOF. High-performance liquid chromatography revealed significant differences in the contents of phenolic acids in the various extracts and root exudate of wheat and faba bean. The total content of syringic acid (SA) was much higher, but that of other five phenolic acids were lower in wheat than in faba bean. The in vitro addition of these phenolic acids revealed that cinnamic acid (CA), p-hydroxybenzoic acid (PHBA), benzoic acid (BA), vanillic acid (VA) and ferulic acid (FA) exhibited significant promoting effects and SA exhibited strong inhibitory effects on the growth of FOF. These results suggest that the inhibitory effect of various extracts and root exudates from wheat on FOF growth may be due to differences in phenolic acid content and high levels of SA.