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1.
Clin Lung Cancer ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38945800

RESUMO

BACKGROUND: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significant antitumor activity to advanced non-small-cell lung cancer (NSCLC) patients with classic EGFR mutations. However, EGFR-TKI monotherapy shows poor efficacy in patients whose circulating tumor cell DNA (ctDNA) of EGFR mutations cannot be rapidly cleared. MATERIALS AND METHODS: As a third-generation TKI, furmonertinib has shown superior antitumor activity and minor toxicity. The FOCUS-C study is a prospective, multicenter, randomized controlled trial (NCT05334277) to explore the efficacy and safety of furmonertinib plus pemetrexed-platinum doublet chemotherapy with or without bevacizumab versus furmonertinib monotherapy in untreated advanced EGFR mutant NSCLC patients without EGFR clearance after the induction therapy of furmonertinib. Patients with EGFR clearance will still receive furmonertinib as Arm A. Patients without ctDNA clearance will be randomized in a 2:2:1 ratio as Arm B1 (furmonertinib), Arm B2 (furmonertinib combined with carboplatin and pemetrexed for 4 cycles, and then furmonertinib and pemetrexed as maintenance therapy) and Arm B3 (Arm B2 regimen plus bevacizumab). The primary endpoint is progression-free survival (PFS) in Arm B2/B1. Secondary endpoints include PFS in Arm B3/B1, PFS in Arm A/B1, PFS in Arm B3/B2, objective response and disease control rate, overall survival and safety in all Arms. Exploratory endpoints are focused on the efficacy based on plasma NGS at different timepoints. CONCLUSION: This study will evaluate the efficacy and tolerability of furmonertinib plus carboplatin and pemetrexed with or without bevacizumab verses furmonertinib alone in untreated patients with advanced EGFR mutant NSCLC without EGFR clearance.

2.
Lung Cancer ; 192: 107818, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763102

RESUMO

INTRODUCTIONS: The 2021 WHO Classification of Thoracic Tumors recognized SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) as a distinct entity that shows a striking overlap in demographic and molecular profiles with SMARCA4-deficient non-small lung cancer (SMARCA4-dNSCLC). The implications of SMARCA4 deficiency based on immunohistochemistry remain unclear. We aimed to investigate molecular characteristics of SMARCA4-deficient thoracic tumors (SDTT) and explore optimal therapeutics. METHODS: From June.15, 2018, to Nov.15, 2023, a large cohort including patients diagnosed with SMARCA4-deficient (N = 196) and SMARCA4-intact (N = 438) thoracic tumors confirmed by immunohistochemistry at SYSUCC were screened. Clinicopathologic and molecular characteristics were identified and compared. External SRRSH cohort (N = 34) was combined into a pooled cohort to compare clinical outcome of first-line therapy efficacy. RESULTS: SDTT is male predominance with smoking history, high tumor burden, and adrenal metastases. The relationship between SMARCA4 mutation and protein expression is not completely parallel. The majority of SMARCA4-deficient patients harbor truncating (Class-I) SMARCA4 mutations, whereas class-II alterations and wild-type also exist. Compared with SMARCA4-intact thoracic tumors, patients with SDTT displayed a higher tumor mutation burden (TMB) and associated with a shorter median OS (16.8 months vs. Not reached; P < 0.001). Notably, SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in these differences. SDTT is generally resistant to chemotherapy, while sensitive to chemoimmunotherapy (median PFS: 7.5 vs. 3.5 months, P < 0.001). In particular, patients with SMARCA4 deficient thoracic tumors treated with paclitaxel-based chemoimmunotherapy achieved a longer median PFS than those with pemetrexed-based chemoimmunotherapy (10.0 vs. 7.3 months, P = 0.028). CONCLUSIONS: SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in its characteristics of higher TMB and poor prognosis. Chemoimmunotherapy serves as the optimal option in the current treatment regimen. Paclitaxel-based chemoimmunotherapy performed better than those with pemetrexed-based chemoimmunotherapy.


Assuntos
DNA Helicases , Neoplasias Pulmonares , Proteínas Nucleares , Neoplasias Torácicas , Fatores de Transcrição , Humanos , DNA Helicases/genética , DNA Helicases/deficiência , Fatores de Transcrição/genética , Masculino , Feminino , Neoplasias Torácicas/genética , Neoplasias Torácicas/patologia , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/terapia , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Nucleares/deficiência , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Idoso , Mutação , Prognóstico , Adulto , Biomarcadores Tumorais/genética
3.
Cell Chem Biol ; 31(5): 932-943.e8, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38759619

RESUMO

Nucleotides perform important metabolic functions, carrying energy and feeding nucleic acid synthesis. Here, we use isotope tracing-mass spectrometry to quantitate contributions to purine nucleotides from salvage versus de novo synthesis. We further explore the impact of augmenting a key precursor for purine synthesis, one-carbon (1C) units. We show that tumors and tumor-infiltrating T cells (relative to splenic or lymph node T cells) synthesize purines de novo. Shortage of 1C units for T cell purine synthesis is accordingly a potential bottleneck for anti-tumor immunity. Supplementing 1C units by infusing formate drives formate assimilation into purines in tumor-infiltrating T cells. Orally administered methanol functions as a formate pro-drug, with deuteration enabling kinetic control of formate production. Safe doses of methanol raise formate levels and augment anti-PD-1 checkpoint blockade in MC38 tumors, tripling durable regressions. Thus, 1C deficiency can gate antitumor immunity and this metabolic checkpoint can be overcome with pharmacological 1C supplementation.


Assuntos
Carbono , Camundongos Endogâmicos C57BL , Purinas , Animais , Camundongos , Purinas/química , Purinas/farmacologia , Carbono/química , Carbono/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Formiatos/química , Formiatos/metabolismo , Formiatos/farmacologia , Metanol/química , Metanol/farmacologia , Feminino , Humanos , Linhagem Celular Tumoral
4.
Cancer Med ; 13(7): e7175, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597130

RESUMO

BACKGROUND: Combination of chidamide and anti-PD-L1 inhibitor produce synergistic anti-tumor effect in advanced NSCLC patients resistant to anti-PD-1 treatment. However, the effect of chidamide plus envafolimab has not been reported. AIMS: This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti-PD-1 treatment. MATERIALS AND METHODS: Eligible advanced NSCLC patients after resistant to anti-PD-1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression-free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD-L1, and blood TMB (bTMB) was also analyzed. RESULTS: After a median follow-up of 8.1 (range: 7.6-9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9-5.5) months. Biomarker analysis revealed that patients with high-level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD-L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low-level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable. DISCUSSION: High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD-L1 and low-level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion. CONCLUSION: Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.


Assuntos
Aminopiridinas , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Benzamidas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores
5.
Cancer Med ; 13(7): e7135, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38549496

RESUMO

BACKGROUND: Inflammatory markers, including the product of neutrophil count, platelet count, and monocyte count divided by lymphocyte count (PIV) and the platelet-to-white blood cell ratio (PWR), have not been previously reported as prognostic factors in nasopharyngeal carcinoma (NPC) patients. In order to predict overall survival (OS) in NPC patients, our goal was to create and internally evaluate a nomogram based on inflammatory markers (PIV, PWR). METHODS: A retrospective study was done on patients who received an NPC diagnosis between January 2015 and December 2018. After identifying independent prognostic indicators linked to OS using Cox proportional hazards regression analysis, we created a nomogram with the factors we had chosen. RESULTS: A total of 630 NPC patients in all were split into training (n = 441) and validation sets (n = 189) after being enrolled in a population-based study in 2015-2018 and monitored for a median of 5.9 years. In the training set, the age, PIV, and PWR, selected as independent predictors for OS via multivariate Cox's regression model, were chosen to develop a nomogram. Both training and validation cohorts had C-indices of 0.850 (95% confidence interval [CI]: 0.768-0.849) and 0.851 (95% CI: 0.765-0.877). Furthermore, compared with traditional TNM staging, our nomogram demonstrated greater accuracy in predicting patient outcomes. The risk stratification model derived from our prediction model may facilitate personalized treatment strategies for NPC patients. CONCLUSION: Our findings confirmed the prognostic significance of the PWR and PIV in NPC. High PIV levels (>363.47) and low PWR (≤36.42) values are associated with worse OS in NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Nomogramas , Humanos , Carcinoma Nasofaríngeo/patologia , Estudos Retrospectivos , Prognóstico
6.
Nat Chem Biol ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448734

RESUMO

Metabolic efficiency profoundly influences organismal fitness. Nonphotosynthetic organisms, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. Although respiration is more energy efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (that is, faster). Through quantitative flux analysis and proteomics, we find, however, that mitochondrial respiration is actually more proteome efficient than aerobic glycolysis. This is shown across yeast strains, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which promotes hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth but outgrow respiratory cells during oxygen limitation. We accordingly propose that aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

7.
bioRxiv ; 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37961420

RESUMO

Nucleotides perform important metabolic functions, carrying energy and feeding nucleic acid synthesis. Here, we use isotope tracing-mass spectrometry to quantitate the contributions to purine nucleotides of salvage versus de novo synthesis. We further explore the impact of augmenting a key precursor for purine synthesis, one-carbon (1C) units. We show that tumors and tumor-infiltrating T cells (relative to splenic T cells) synthesize purines de novo. Purine synthesis requires two 1C units, which come from serine catabolism and circulating formate. Shortage of 1C units is a potential bottleneck for anti-tumor immunity. Elevating circulating formate drives its usage by tumor-infiltrating T cells. Orally administered methanol functions as a formate pro-drug, with deuteration enabling control of formate-production kinetics. In MC38 tumors, safe doses of methanol raise formate levels and augment anti-PD-1 checkpoint blockade, tripling durable regressions. Thus, 1C deficiency can gate antitumor immunity and this metabolic checkpoint can be overcome with pharmacological 1C supplementation.

8.
Ecol Evol ; 13(4): e9986, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37082323

RESUMO

Seed dormancy contributes greatly to successful establishment and community stability and shows large variation over a continuous status scale in mountain ecosystems. Although empirical studies have shown that seed dormancy status (SDS) is shaped by elevation and phylogenetic history in mountain ecosystems, few studies have quantified their combined effects on SDS. Here, we collected mature seeds from 51 populations of 11 Impatiens species (Balsaminaceae) along an elevational gradient in the Gaoligong Mountains of southwest China and estimated SDS using mean dormancy percentage of fresh seeds germinated at three constant temperatures (15, 20, and 25°C). We downloaded 19 bioclimatic variables from WorldClim v.2.1 for each Impatiens population and used internal transcribed spacer (ITS), atpB-rbcL, and trnL-F molecular sequences from the GenBank nucleotide database to construct a phylogenetic tree of the 11 species of Impatiens. Logistic regression model analysis was performed to quantify the effects of phylogeny and environment on SDS. Results identified a significant phylogenetic SDS signal in the Impatiens species. Furthermore, elevation and phylogeny accounted for 63.629% of the total variation in SDS among the Impatiens populations. The best logistic model indicated that temperature was the main factor influencing variation in SDS among the Impatiens species, and model residuals were significantly correlated with phylogeny, but not with elevation. Our results indicated that seed dormancy is phylogenetically conserved, and climate drives elevational patterns of SDS variation in mountain ecosystems. This study provides new insights into the response of seed plant diversity to climate change.

9.
Medicine (Baltimore) ; 102(7): e32924, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36800614

RESUMO

RATIONALE: Limited patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) have achieved complete response (CR) from induction chemotherapy (IC). Neoadjuvant immunotherapy combined with chemotherapy has marked therapeutic effects in some locoregionally advanced solid tumors. However, its efficacy and safety of NPC have not been reported so far. The rapid response of neoadjuvant tislelizumab combined with chemotherapy on LA-NPC may be associated with long-term survival benefit. PATIENT CONCERNS: A 57-year-old male patient presented with a 2-month history of bloody nasal discharge and right neck mass for 2 weeks. DIAGNOSIS: The patient was eventually diagnosed with nasopharyngeal nonkeratinizing undifferentiated cell carcinoma (stage IVA). INTERVENTIONS: The patient received tislelizumab combined with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) nab-paclitaxel plus cisplatin for 4 cycles, followed by cisplatin-based concurrent chemoradiotherapy (CCRT). OUTCOMES: A partial response (PR) was achieved after 2 cycles of tislelizumab and nab-paclitaxel plus cisplatin, and CR was achieved after 4 cycles of neoadjuvant treatment. The duration of response lasted 24 months, and the patient was still in CR as of November 2022. The patient had no serious adverse event (AEs) during the treatment. LESSONS: This case report showed that tislelizumab combined with cisplatin plus nab-paclitaxel followed CCRT for treatment of patients with LA-NPC may receive a fast and durable response with a manageable safety profile and long-term survival.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Nasofaríngeas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Cisplatino/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Fluoruracila/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimioterapia de Indução , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
10.
Nurs Open ; 10(3): 1526-1535, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36177862

RESUMO

AIM: To examine the association between the hospitalization time and fall incidence. DESIGN: A secondary analysis using the Dryad Digital Repository public database. METHODS: Data were extracted from the Fukushima Medical University Hospital cohort study between August 2008 and September 2009. The final analytic sample included 8,598 participants, 156 of who fell. The risk of fall incidents according to hospitalization time was estimated using logistic proportional hazards models, and restricted cubic splines with four knots model were developed. RESULTS: The median hospitalization time was 9.00 (4.00, 17.00) days. The incidence of falls was 1.81% (N = 156). A U-shaped association between the hospitalization time and fall incidence, with an inflextion point of 8 days. We found a decreasing fall incidence as the hospitalization time increased from 0 to 8 days (OR 0.72 [0.62 ~ 0.83], p < .001); beyond 8 days, the fall incidence increased as the hospitalization time increased (OR 1.06 [1.04 ~ 1.09]).


Assuntos
Hospitalização , Pacientes Internados , Humanos , Estudos Transversais , Estudos de Coortes , Incidência , Japão/epidemiologia
11.
Emerg Med Int ; 2022: 6293816, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990372

RESUMO

Objective: To explore the clinical efficacy and safety of apatinib combined with paclitaxel in the first-line treatment of locally advanced nasopharyngeal carcinoma. Methods: From March 2016 to June 2018, 114 patients with locally advanced nasopharyngeal carcinoma who received first-line treatment in our hospital were selected as the patient group, and those who received apatinib combined with paclitaxel concurrent radiotherapy and chemotherapy were selected as the research group (n = 54), while those who received paclitaxel concurrent radiotherapy and chemotherapy were selected as the control group (n = 60). Sixty healthy individuals in our hospital were recruited in the same period as the healthy group. The clinical effective rate, adverse reactions, 2-year overall survival rate (OS), 2-year progression-free survival rate (PFS), and quality of life were compared between the two groups, and the expression of miR-655 in the serum of each group was tested by RT-qPCR. Results: The total clinical effective rate of the research group was higher than that of the control group, and the 2-year OS and PFS of the research group were also higher than those of the control group (P < 0.05). Both groups of patients could tolerate the treatment, but the incidence of hypertension and proteinuria in the research group was higher than that in the control group (P < 0.05). The expression of miR-655 in the serum of patients was lower than that of the healthy group (P < 0.05). After treatment, miR-655 in serum increased in both the groups and miR-655 in the research group was higher than that in the control group (P < 0.05). The 2-year survival rate of OS and PFS in patients with low expression of miR-655 was significantly lower than that in patients with high expression of miR-655 (P < 0.05). Conclusion: Apatinib combined with paclitaxel concurrent radiotherapy and chemotherapy is effective and well-tolerated in the treatment of locally advanced nasopharyngeal carcinoma, which improves the quality of life of patients and can be popularized in clinical practice. In addition, the increase of miR-655 may be a target for treating nasopharyngeal carcinoma.

12.
Reprod Biol ; 22(1): 100611, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35121558

RESUMO

Long non-coding RNAs (lncRNAs) have been elucidated to play vital roles in the phenotype of trophoblast cells. Nevertheless, the effect of SNHG1 has not been investigated on trophoblast cells in recurrent spontaneous abortion (RSA). We aim to investigate the effect of SNHG1 on the phenotype of trophoblast cells during RSA. The RSA mice were established by mating female CBA/J mice with male DBA/2 mice. Microarray analysis was applied in RSA mice, and SNHG1 was identified as a significantly downregulated lncRNA. SNHG1 improved pregnancy outcome and reduced embryo resorption in RSA mice. Trophoblast cell proliferation, apoptosis, migration, and invasion were investigated by CCK8, EdU, TUNEL, wound healing, and Transwell assays. SNHG1 promoted proliferation, migration, and invasion of trophoblast cells, and reduced apoptosis. Mechanistically, SNHG1 bound to miR-183-5p in trophoblast cells. Moreover, miR-183-5p directly targeted ZEB2. Rescue experiment showed that ZEB2 silencing reversed the ameliorative effect of SNHG1 on pregnancy outcome and the promotion of trophoblast activity in RSA mice by impaired the Wnt/ß-catenin pathway. In conclusion, we found that SNHG1 plays a critical role in the progression of RSA via miR-183-5p/ZEB2 and Wnt/ß-catenin signaling. It has potential to be a therapeutic marker of RSA.


Assuntos
Aborto Habitual , MicroRNAs , RNA Longo não Codificante , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Aborto Habitual/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Masculino , Camundongos , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , MicroRNAs/genética , MicroRNAs/metabolismo , Gravidez , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
13.
Sci Total Environ ; 825: 153656, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35167893

RESUMO

The environmental pressures of major wastes in the circular economies can be abated leveraging the complementarity and optimal conditions of their co-combustion. The oxy-fuel co-combustion of phytoremediation biomass of Sedum alfredii Hance (SAH) and textile dyeing sludge (TDS) may be a promising choice for sustainable CO2 capture and a waste-to-energy conversion. This study characterized and quantified their co-combustion performances, kinetics, and interactions as a function of blend ratio, atmosphere type, and temperature. With a focus on the characteristic elements of SAH (Ca, K, Zn, and Cd) and TDS (Al and S), changes in the mineral phases and ash melting and slagging trends of K2O-Al2O3-SiO2 and CaO-Al2O3-SiO2 systems were quantified. The Zn and Cd residual rates of the co-combustion of 75% SAH and 25% TDS rose by 58.52% and 5.93%, respectively, in the oxy-fuel atmosphere at the 30% oxygen concentration, relative to the mono-combustion of SAH in the air atmosphere. The co-combustion in the oxy-fuel atmosphere at the 20% oxygen concentration delayed the release peaks of SO2, C2S, and H2S, while the Ca-rich SAH captured S in TDS through the formation of CaSO4. Our findings provide new and practical insights into the oxy-fuel co-combustion toward the enhanced co-circularity.


Assuntos
Cádmio , Esgotos , Biodegradação Ambiental , Biomassa , Oxigênio , Dióxido de Silício , Têxteis
14.
J Healthc Eng ; 2022: 6996444, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035852

RESUMO

Chest X-ray has become one of the most common ways in diagnostic radiology exams, and this technology assists expert radiologists with finding the patients at potential risk of cardiopathy and lung diseases. However, it is still a challenge for expert radiologists to assess thousands of cases in a short period so that deep learning methods are introduced to tackle this problem. Since the diseases have correlations with each other and have hierarchical features, the traditional classification scheme could not achieve a good performance. In order to extract the correlation features among the diseases, some GCN-based models are introduced to combine the features extracted from the images to make prediction. This scheme can work well with the high quality of image features, so backbone with high computation cost plays a vital role in this scheme. However, a fast prediction in diagnostic radiology is also needed especially in case of emergency or region with low computation facilities, so we proposed an efficient convolutional neural network with GCN, which is named SGGCN, to meet the need of efficient computation and considerable accuracy. SGGCN used SGNet-101 as backbone, which is built by ShuffleGhost Block (Huang et al., 2021) to extract features with a low computation cost. In order to make sufficient usage of the information in GCN, a new GCN architecture is designed to combine information from different layers together in GCNM module so that we can utilize various hierarchical features and meanwhile make the GCN scheme faster. The experiment on CheXPert datasets illustrated that SGGCN achieves a considerable performance. Compared with GCN and ResNet-101 (He et al., 2015) backbone (test AUC 0.8080, parameters 4.7M and FLOPs 16.0B), the SGGCN achieves 0.7831 (-3.08%) test AUC with parameters 1.2M (-73.73%) and FLOPs 3.1B (-80.82%), where GCN with MobileNet (Sandler and Howard, 2018) backbone achieves 0.7531 (-6.79%) test AUC with parameters 0.5M (-88.46%) and FLOPs 0.66B (-95.88%).


Assuntos
Aprendizado Profundo , Pneumopatias , Algoritmos , Humanos , Pneumopatias/diagnóstico por imagem , Redes Neurais de Computação
15.
J Hazard Mater ; 426: 128069, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34959215

RESUMO

Given the globally abundant availability of waste plastics and the negative environmental impacts of textile dyeing sludge (TDS), their co-combustion can effectively enhance the circular economies, energy recovery, and environmental pollution control. The (co-)combustion performances, gas emissions, and ashes of TDS and two plastics of polypropylene (PP) and polyethylene (PE) were quantified and characterized. The increased blend ratio of PP and PE improved the ignition, burnout, and comprehensive combustion indices. The two plastics interacted with TDS significantly in the range of 200-600 â„ƒ. TDS pre-ignited the combustion of the plastics which in turn promoted the combustion of TDS. The co-combustions released more CO2 but less CH4, C-H, and CO as CO2 was less persistent than the others in the atmosphere. The Ca-based minerals in the plastics enhanced S-fixation and reduced SO2 emission. The activation energy of the co-combustion fell from 126.78 to 111.85 kJ/mol and 133.71-79.91 kJ/mol when the PE and PP additions rose from 10% to 50%, respectively. The co-combustion reaction mechanism was best described by the model of f(α) = (1-α)n. The reaction order was reduced with the additions of the plastics. The co-combustion operation interactions were optimized via an artificial neural network so as to jointly meet the multiple objectives of maximum energy production and minimum emissions.


Assuntos
Plásticos , Esgotos , Inteligência Artificial , Atmosfera , Têxteis
16.
Sci Adv ; 7(47): eabk1023, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34788087

RESUMO

The KEAP1/NRF2 pathway promotes metabolic rewiring to support redox homeostasis. Activation of NRF2 occurs in many cancers, often due to KEAP1 mutations, and is associated with more aggressive disease and treatment resistance. To identify metabolic dependencies in cancers with NRF2 activation, we performed a metabolism-focused CRISPR screen. Glucose-6-phosphate dehydrogenase (G6PD), which was recently shown to be dispensable in Ras-driven tumors, was a top dependency. G6PD catalyzes the committed step of the oxidative pentose phosphate pathway that produces NADPH and nucleotide precursors, but neither antioxidants nor nucleosides rescued. Instead, G6PD loss triggered tricarboxylic acid (TCA) intermediate depletion because of up-regulation of the alternative NADPH-producing enzymes malic enzyme and isocitrate dehydrogenase. In vivo, G6PD impairment markedly suppressed KEAP1 mutant tumor growth, and this suppression was further augmented by TCA depletion by glutaminase inhibition. Thus, G6PD inhibition­induced TCA depletion is a therapeutic vulnerability of NRF2-activated cancer.

17.
J Hazard Mater ; 418: 126380, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34329026

RESUMO

In response to the global initiative for greenhouse gas emission reduction, the co-combustion of coal and spent pot lining (SPL) may cost-effectively minimize waste streams and environmental risks. This study aimed to quantify the emission-to-ash detoxification mechanisms of the co-combustion of SPL and pulverized coal (PC) and their kinetics, gas emission, fluorine-leaching toxicity, mineral phases, and migrations. The main reaction covered the ranges of 335-540 °C and 540-870 °C while the interactions occurred at 360-780 °C. The apparent activation energy minimized (66.99 kJ/mol) with 90% PC addition. The rising PC fraction weakened the peak intensity of NaF and strengthened that of Ca2F, NaAlSiO4, and NaAlSi2O6. The addition of PC enhanced the combustion efficiency of SPL and raised the melting temperature by capturing Na. PC exhibited a positive effect on solidifying water-soluble fluorine and stabilizing alkali and alkaline earth metals. The leaching fluorine concentrations of the co-combustion ashes were lower than did SPL mono-combustion. The main gases emitted were HF, NH3, NOx, CO, and CO2. HF was largely released at above 800 °C. Multivariate Gaussian process model-based optimization of the operational conditions also verified the gas emissions results. Our study synchronizes the utilization and detoxification of SPL though co-combustion and provides insights into an eco-friendlier life-cycle control on the waste-to-energy conversion.


Assuntos
Cinza de Carvão , Carvão Mineral , Flúor , Gases , Água
18.
RSC Adv ; 11(17): 10272-10284, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35423524

RESUMO

Background: Grifola frondosa is a type of edible medicinal mushroom with abundant proteins. Selenium (Se) is an essential micronutrient for human. Many animal experiments and clinical studies had indicated that Se plays an important role in diverse physiologic actions. Most inorganic selenium compounds are toxic, and the lowest lethal dose is relatively small. Peptide-Se chelate can probably be dietary supplements in functional foods for humans with Se deficiency. Methods: In this study, a specific tripeptide Arg-Leu-Ala (RLA) with strong Se-chelating capacity was purified from Grifola frondosa through ultrafiltration, reversed-phase HPLC and gel filtration chromatography. The UV, SEM, XRD, 1H NMR spectra are shown to provide more information about characterization of RLA-Se chelates. The bioavailability of RLA-Se chelate in Caco-2 cell line was investigated by using human colon cancer Caco-2 cells as model. iTRAQ comparative proteomics approach were used to identify the differentially expressed proteins. Results: The Se binding capacity of RLA was 84.47 ± 1.21 mg g-1. The results of UV, X-ray diffraction (XRD), 1H NMR and SEM structure analysis showed that the binding of selenium in the hydrolysate of Grifola frondosa protein was successful, and the amino and carboxyl groups of RLA were involved in the coordination of Se, which was the main site of chelation. The results of absorption of RLA-Se chelate in Caco-2 cells showed that RLA-Se chelate could be used as selenium supplement source. Using iTRAQ comparative proteomics approach, 40 proteins found significant. RLA-Se treatment had been demonstrated to present a higher accumulation of Se compared with control treatment and show an effective absorption by Caco-2 with the result that E3 protein performed up regulation. RLA-Se may play roles in cell cycle and apoptosis as an essential micronutrient. To sum up, our research results show that Grifola polypeptide-Se chelate is a promising multifunctional organic selenium product, which can be used as a new functional supplement for selenium deficiency.

19.
J Hazard Mater ; 402: 123516, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739726

RESUMO

Given their non-biodegradable, space-consuming, and environmentally more benign nature, waste bicycle tires may be pyrolyzed for cleaner energies relative to the waste truck, car, and motorcycle tires. This study combined thermogravimetry (TG), TG-Fourier transform infrared spectroscopy (TG-FTIR), and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) analyses to dynamically characterize the pyrolysis behavior, gaseous products, and reaction mechanisms of both waste rubber (RT) and polyurethane tires (PUT) of bicycles. The main devolatilization process included the decompositions of the natural, styrene-butadiene, and butadiene rubbers for RT and of urethane groups in the hard segments, polyols in the soft segments, and regenerated isocyanates for PUT. The main TG-FTIR-detected functional groups included C-H, C=C, C=O, and C-O for both waste tires, and also, N-H and C-O-C for the PUT pyrolysis. The main Py-GC/MS-detected pyrolysis products in the decreasing order were isoprene and D-limonene for RT and 4, 4'-diaminodiphenylmethane and 2-hexene for PUT. The kinetic, thermodynamic, and comprehensive pyrolysis index data verified the easier decomposition of PUT than RT. The pyrolysis mechanism models for three sub-stages of the main devolatilization process were best described by two-dimensional diffusion and two second-order models for RT, and the three consecutive reaction-order (three-halves order, first-order, and second-order) models for PUT.

20.
Environ Pollut ; 266(Pt 3): 115420, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32829031

RESUMO

In this study, the detoxification mechanisms of water-soluble fluorine in the bottom ash and the distribution of fluorine during the spent potlining (SPL) incineration were characterized in response to four calcium compounds using an experimental tube furnace. CaSiO3, CaO, Ca(OH)2, and CaCO3-assisted SPL incineration converted NaF to low toxicity compounds in the bottom ash yielding a conversion range of 54.24-99.45% relative to the individual SPL incineration. The two main mechanisms of the fluorine transformation were the formations of CaF2 and Ca4Si2O7F2. The fluorine transformation efficiency was greater with CaSiO3 than CaO, Ca(OH)2, and CaCO3. Our simulations demonstrated that SiO2 enhanced the conversion of NaF. The fluorine leaching content of the bottom ash was estimated at 13.71 mg⋅L-1 after the SPL co-incineration with CaSiO3 (Ca:F = 1.2:1). The acid-alkali solutions had no significant effect on the fluorine leaching content of the bottom ash when 3 ≤ pH ≤ 12. Fluorine during the SPL co-incineration with CaSiO3 (Ca:F = 1.2:1) at 850 °C for 60 min was partitioned into 83.37, 13.90, and 2.72% in the bottom ash, fly ash, and flue gas, respectively. The transformation and detoxification mechanisms of water-soluble fluorine provide new insights into controls on fluorine emission from the SPL incineration.


Assuntos
Flúor , Incineração , Compostos de Cálcio , Cinza de Carvão , Dióxido de Silício , Água
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