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1.
Biotechnol Prog ; : e3268, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536540

RESUMO

Charge variants represent a critical quality attribute that must be controlled during the development and manufacturing of monoclonal antibodies (mAb). Previously, we reported the development of a cost-effective enzymatic treatment capable of removing the C-terminal lysine from a mAb produced by a Chinese hamster ovary (CHO) GS cell line. This treatment resulted in a significant decrease in basic charge variants and a corresponding improvement in the main peak, enabling a longer cell culture production duration for titer improvement. Here, we describe this enzymatic treatment protocol in detail and demonstrate its applicability to two additional mAbs produced by distinct industrial cell lines. The simple addition of carboxypeptidase B (CpB) at a ratio of 1:10,000 (w/w) to whole cell cultures significantly improved the main peaks for both mAbs without affecting other critical quality attributes, including size exclusion chromatography impurities and N-glycans. Our results demonstrate that this in vitro CpB treatment protocol can be used as a platform strategy to improve main peak for mAbs that exhibit high levels of basic variants attributable to C-terminal lysines. An in vitro enzymatic treatment in general may be another good addition to existing in vivo CHO cell culture strategies for titer improvement and control of critical quality attributes. This article is protected by copyright. All rights reserved.

2.
Cancer Med ; 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35526267

RESUMO

BACKGROUND: Isocitrate dehydrogenase (IDH) is an appealing target for anticancer therapy, and IDH (IDH1/2) inhibitors have been approved for targeted therapy of acute myeloid leukemia (AML) and Cholangiocarcinoma. The therapeutic potential of IDH inhibitors for non-small-cell lung cancer (NSCLC) patients is under active clinical investigation. Thus, it would be necessary and meaningful to study the molecular and clinical characteristics of IDH mutation in NSCLC patients, especially in the Chinese population. METHODS: A total of 17,978 Chinese patients with NSCLC who underwent next -generation sequencing (NGS) testing were retrospectively reviewed. RESULTS: We identified 161 unique IDH mutations in 361 of 17,978 patients (2.01%). Common active-site mutations, including IDH1R100 , IDH1R132 , IDH2R140 , and IDH2R172 , were detected in 154 patients (0.86%) and were associated with male sex (p = 0.004) and older age (p = 0.02). The IDH mutation spectra observed in NSCLC were quite different from those in glioma or AML. Patients with IDH active-site mutations exhibited significantly higher coalterations in KRAS (p. G12/13/61, 22.1% vs. 8.2%, p < 0.001) or BRAF (p. V600E, 6.5% vs. 1.0%, p < 0.001), but significantly lower coalterations in activating EGFR (e18-e20, 22.7 vs. 37.9%, p < 0.001) than IDH wild-type patients. Furthermore, we found that active-site IDH mutations were correlated with a short PFS (2-5.6 months) and short OS (2-9.5 months), which may arise as a resistance mechanism against common targeted drugs. In vitro, we experimentally observed that the combination of an IDH inhibitor and EGFR TKI could better inhibit lung cancer cell proliferation than an EGFR TKI alone. CONCLUSIONS: Taken together, this study reveals the molecular and clinical characteristics of IDH mutations in Chinese NSCLC patients and provides a theoretical basis for IDH-directed treatment. The potential of IDH mutations as response markers for targeted therapy warrants further investigation.

3.
J Exp Clin Cancer Res ; 41(1): 171, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538499

RESUMO

BACKGROUND: RNA-binding proteins (RBPs) and circular RNAs (circRNAs) play important roles in glioblastoma multiforme (GBM). Aerobic glycolysis is a metabolic characteristic of GBM. However, the roles of RBPs and circRNAs in aerobic glycolysis in GBM remain unclear. The aim of this study is to explore the mechanisms by which RBPs and circRNAs regulate aerobic glycolysis in GBM cells. METHODS: RNA sequencing and circRNA microarray analysis were performed to identify RBPs and circRNAs for further study. Mass spectrometry validated the encoded protein and its interacting proteins. Quantitative reverse transcription PCR and western blot assays were used to determine the mRNA and protein expression, respectively. Furthermore, immunofluorescence and fluorescence in situ hybridization assays were used to determine the protein and RNA localization, respectively. Glucose and lactate measurement assays, Seahorse XF glycolysis stress assays and cell viability assays were conducted to investigate the effects on glycolysis and proliferation in GBM cells. RESULTS: We selected zinc finger CCHC-type and RNA-binding motif 1 (ZCRB1) and circRNA HEAT repeat containing 5B (circHEATR5B) as candidates for this study. These genes were expressed at low levels in GBM tissues and cells. Both ZCRB1 and circHEATR5B overexpression suppressed aerobic glycolysis and proliferation in GBM cells. ZCRB1 overexpression promoted the Alu element-mediated formation of circHEATR5B. In addition, circHEATR5B encoded a novel protein HEATR5B-881aa which interacted directly with Jumonji C-domain-containing 5 (JMJD5) and reduced its stability by phosphorylating S361. JMJD5 knockdown increased pyruvate kinase M2 (PKM2) enzymatic activity and suppressed glycolysis and proliferation in GBM cells. Finally, ZCRB1, circHEATR5B and HEATR5B-881aa overexpression inhibited GBM xenograft growth and prolonged the survival time of nude mice. CONCLUSIONS: This study reveals a novel mechanism of regulating aerobic glycolysis and proliferation in GBM cells through the ZCRB1/circHEATR5B/HEATR5B-881aa/JMJD5/PKM2 pathway, which can provide novel strategies and potential targets for GBM therapy.

4.
Allergol Immunopathol (Madr) ; 50(3): 24-37, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35527653

RESUMO

BACKGROUND: The purpose of this meta-analysis is to systematically evaluate the efficacy of probiotics on allergic rhinitis (AR). METHODS: Collecting randomized controlled trials (RCTs) with probiotics as intervention measures for AR, two researchers independently screened the literature, extracted the data and evaluated the methodological quality of the included studies, and used RevMan 5.3 software for meta-analysis to observe the effects of probiotics on Rhinitis Quality of Life (RQLQ) scores, Rhinitis Total Symptom Scores (RTSS), blood eosinophil count, total and antigen-specific serum immunoglobulin E (IgE) levels by using the fixed- or the random-effects model to calculate the pooled risk for significant heterogeneity. RESULTS: A total of 2708 patients were included in 30 RCTs. Meta-analysis results showed that the RQLQ global scores (mean difference [MD] = -9.43; P < 0.00001), RQLQ nasal scores (MD = -1.52; P = 0.03), and RTSS nasal scores (MD = -1.96; P = 0.02) significantly improved in the probiotic group when compared with those in the placebo group. There was no significant difference in blood eosinophil count (MD = -0.09; P=0.82), RQLQ eye scores (MD = -1.45; P = 0.07), RTSS global scores (MD = -2.24; P = 0.26), RTSS eye scores (MD = -0.39; P = 0.31), total and antigen-specific serum IgE levels (MD = -0.04; P = 0.7 and MD = -0.08; P = 0.81) between the probiotic and the placebo group. CONCLUSION: Compared with the placebo group, the quality of life and symptoms of patients with AR significantly improved in the probiotic group, thus providing a new potential method for the application of probiotics in AR. However, because of the limited evidence for the current study outcomes, the heterogeneity of research, and the differences in research results, more high-quality studies are needed to in the future.


Assuntos
Probióticos , Rinite Alérgica , Rinite , Humanos , Imunoglobulina E , Probióticos/uso terapêutico , Qualidade de Vida , Rinite Alérgica/tratamento farmacológico
5.
J Environ Radioact ; 248: 106884, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35398758

RESUMO

This paper reviews the current knowledge on plutonium (Pu) isotopic composition (the atom or activity ratios) and activity concentrations of 238Pu, 239Pu, 240Pu, and 241Pu resulting from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011. In this critical review, we document the characteristic values of Pu atom or activity ratios (fingerprints) and present their spatial distributions around the FDNPP site. Based on multiple Pu fingerprints (238Pu/239+240Pu activity ratio, 240Pu/239Pu atom ratio, and 241Pu/239Pu atom ratio), we clarify that Pu contamination from the FDNPP accident occurred in a restricted terrestrial area, while Pu in the Northwest Pacific Ocean is still predominately sourced from the Pacific Proving Grounds (PPG) and global fallout. Using a simple two end-member mixing model, we calculate average contributions of Pu from the FDNPP accident of 13 ± 20% (n = 180) in soil samples, 55 ± 32% (n = 38) in leaf litter samples, and 67 ± 26% (n = 129) in air dust/black substances. In the marine environment, the PPG source average contributions are 45 ± 15% (n = 76) in seawater and 42 ± 12% (n = 48) in sediments. The spatial distributions of Pu atom or activity ratios based on existing studies suggest that: 1) in the terrestrial region investigated 80 km northwest of the FDNPP site, the Pu contamination is mainly observed in an area within a 50 km distance, and 2) in the terrestrial region investigated 60 km southwest of the FDNPP site, the Pu contamination is mainly observed in an area within a 30 km distance. Studies of Cs-bearing radioactive particles indicate that Pu occurs as Pu oxide, and the fuel fragments containing Pu that were released from the reactors to the surrounding environment are associated with micron-scale Cs-bearing radioactive particles. We note that the fractionation between Pu and other radionuclides occurred after release. These new findings about the Pu fingerprints around the FDNPP site will help researchers to establish a reference background database for future environmental risk assessment and geochemical study there.


Assuntos
Acidente Nuclear de Fukushima , Plutônio , Monitoramento de Radiação , Poluentes Radioativos da Água , Japão , Centrais Nucleares , Plutônio/análise , Poluentes Radioativos da Água/análise
6.
Sci Rep ; 12(1): 5462, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361855

RESUMO

The aim of this study was to evaluate the effectiveness and safety of AngioJet rheolytic thrombectomy among patients with high thrombus burden. Routine manual thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) does not improve clinical outcomes and was associated with an increased rate of stroke. However, the safety of mechanical thrombus aspiration is still unknown. This was a retrospective, single-center study involving 621 patients with Thrombolysis In Myocardial Infarction thrombus grade 5. The primary outcome was the composite of major adverse cardiovascular events (MACE) within 12 months. The safety outcome was stroke within 1-year. Propensity matching score was calculated due to the significant baseline differences between the AngioJet rhelytic thrombectomy group and the routine treatment group. AngioJet rheolytic thrombectomy was performed in 117 patients. After propensity-score matching, there was no significant difference both in the incidence of MACE (11.1% vs 17.9%, hazard ratio, 1.641; 95% confidence interval [CI] 0.822 to 3.277, p = 0.161) and the incidences of stroke (1.7% vs 2.6%, hazard ratio 1.522; 95% confidence interval [CI] 0.254 to 9.107, p = 0.646) between two groups at 1-year follow-up. In patients with Thrombolysis In Myocardial Infarction thrombus grade 5, AngioJet rheolytic thrombectomy did not improve clinical outcomes at 1 year. However, AngioJet rheolytic thrombectomy did not increase the risk of stroke in patients with high thrombus burden.


Assuntos
Angioplastia Coronária com Balão , Trombose Coronária , Infarto do Miocárdio , Angiografia Coronária , Trombose Coronária/etiologia , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Estudos Retrospectivos , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos
8.
Transl Res ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489692

RESUMO

Multiple SARS-CoV-2 variants are identified with higher rates of transmissibility or greater disease severity. Particularly, recent emergence of Omicron variant with rapid human-to-human transmission posts new challenges to the current prevention strategies. In this study, following vaccination with an mRNA vaccine encoding SARS-CoV-2 receptor-binding domain (RBD-mRNA), we detected serum antibodies that neutralized pseudoviruses expressing spike (S) protein harboring single or multiple mutations, as well as authentic SARS-CoV-2 variants, and evaluated its protection against SARS-CoV-2 infection. The vaccine induced durable antibodies that potently neutralized prototypic strain and B.1.1.7 lineage variant pseudoviruses containing N501Y or D614G mutations alone or in combination with a N439K mutation (B.1.258 lineage), with a L452R mutation (B.1.427 or B.1.429 lineage), or a L452R-E484Q double mutation (B.1.617.1 variant), although neutralizing activity against B.1.1.7 lineage variant containing 10 amino acid changes in the S protein was slightly reduced. The RBD-mRNA-induced antibodies exerted moderate neutralization against authentic B.1.617.2 and B.1.1.529 variants, and pseudotyped B.1.351 and P.1 lineage variants containing K417N/T, E484K, and N501Y mutations, the B.1.617.2 lineage variant harboring L452R, T478K, and P681R mutations, and the B.1.1.529 lineage variant containing 38 mutations in the S protein. Particularly, RBD-mRNA vaccine completely protected mice from challenge with a virulent mouse-adapted SARS-CoV-2 variant. Among these lineages, B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529 belong to Alpha, Beta, Gamma, Delta, and Omicron variants, respectively. Our observations reveal that RBD-mRNA vaccine is promising and highlights the need to design novel vaccines with improved neutralization against current and future pandemic SARS-CoV-2 variants.

10.
Comput Biol Med ; 146: 105545, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35477048

RESUMO

Accurate skin lesion segmentation plays a fundamental role in computer-aided melanoma analysis. Recently, some FCN-based methods have been proposed and achieved promising results in lesion segmentation tasks. However, due to the variable shapes, different scales, noise interference, and ambiguous boundaries of skin lesions, the capabilities of lesion location and boundary delineation of these works are still insufficient. To overcome the above challenges, in this paper, we propose a novel Neighborhood Context Refinement Network (NCRNet) by using the coarse-to-fine strategy to achieve accurate skin lesion segmentation. The proposed NCRNet contains a shared encoder and two different but closely related decoders for locating the skin lesions and refining the lesion boundaries. Specifically, we first design the Parallel Attention Decoder (PAD), which can effectively extract and fuse the local detail information and global semantic information on multiple levels to locate skin lesions of different sizes and shapes. Then, based on the initial lesion location, we further design the Neighborhood Context Refinement Decoder (NCRD), aiming at leveraging the fine-grained multi-stage neighborhood context cues to refine the lesion boundaries continuously. Furthermore, the neighborhood-based deep supervision used in the NCRD can make the shared encoder pay more attention to the lesion boundary areas and promote convergence of the segmentation network. The public skin lesion segmentation dataset ISIC2017 is adopted to validate the effectiveness of the proposed NCRNet. Comprehensive experiments prove that the proposed NCRNet reaches the state-of-the-art performance than the other nine competitive methods and gets 78.62%, 86.55%, and 94.01% on Jaccard, Dice, and Accuracy, respectively.

11.
Bioengineering (Basel) ; 9(4)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35447688

RESUMO

Fed-batch process intensification with a significantly shorter culture duration or higher titer for monoclonal antibody (mAb) production by Chinese hamster ovary (CHO) cells can be achieved by implementing perfusion operation at the N-1 stage for biomanufacturing. N-1 perfusion seed with much higher final viable cell density (VCD) than a conventional N-1 batch seed can be used to significantly increase the inoculation VCD for the subsequent fed-batch production (referred as N stage), which results in a shorter cell growth phase, higher peak VCD, or higher titer. In this report, we incorporated a process analytical technology (PAT) tool into our N-1 perfusion platform, using an in-line capacitance probe to automatically adjust the perfusion rate based on real-time VCD measurements. The capacitance measurements correlated linearly with the offline VCD at all cell densities tested (i.e., up to 130 × 106 cells/mL). Online control of the perfusion rate via the cell-specific perfusion rate (CSPR) decreased media usage by approximately 25% when compared with a platform volume-specific perfusion rate approach and did not lead to any detrimental effects on cell growth. This PAT tool was applied to six mAbs, and a platform CSPR of 0.04 nL/cell/day was selected, which enabled rapid growth and maintenance of high viabilities for four of six cell lines. In addition, small-scale capacitance data were used in the scaling-up of N-1 perfusion processes in the pilot plant and in the GMP manufacturing suite. Implementing a platform approach based on capacitance measurements to control perfusion rates led to efficient process development of perfusion N-1 for supporting high-density CHO cell cultures for the fed-batch process intensification.

12.
Bioengineering (Basel) ; 9(4)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35447733

RESUMO

Improving productivity to reduce the cost of biologics manufacturing and ensure that therapeutics can reach more patients remains a major challenge faced by the biopharmaceutical industry. Chinese hamster ovary (CHO) cell lines are commonly prepared for biomanufacturing by single cell cloning post-transfection and recovery, followed by lead clone screening, generation of a research cell bank (RCB), cell culture process development, and manufacturing of a master cell bank (MCB) to be used in early phase clinical manufacturing. In this study, it was found that an additional round of cloning and clone selection from an established monoclonal RCB or MCB (i.e., re-cloning) significantly improved titer for multiple late phase monoclonal antibody upstream processes. Quality attributes remained comparable between the processes using the parental clones and the re-clones. For two CHO cells expressing different antibodies, the re-clone performance was successfully scaled up at 500-L or at 2000-L bioreactor scales, demonstrating for the first time that the re-clone is suitable for late phase and commercial manufacturing processes for improvement of titer while maintaining comparable product quality to the early phase process.

13.
Front Oncol ; 12: 872033, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463310

RESUMO

Purpose: Long noncoding RNAs (LncRNAs) play complex but important roles in the progression of various tumors. This study aimed to elucidate the functional mechanisms of the HLA complex group 11 (HCG11) in nasopharyngeal carcinoma (NPC). Patients and Methods: HCG11 levels in NPC specimens were determined by fluorescence in situ hybridization (FISH) and qPCR. Proliferation, apoptosis, and metastasis of NPC cells were determined using CCK8, colony formation, annexin V-PI, and transwell assays. A murine tumor xenograft model was used to investigate the regulatory function of HCG11 in NPC in vivo, and immunohistochemical staining was used to determine the Ki-67 level in tumors. The target relationships between HCG11, microRNA miR-490-3p, and MAPK kinase kinase 9 (MAP3K9) were detected using bioinformatics, qPCR, western blotting, and luciferase reporter assays. Results: HCG11 was highly expressed in NPC tissues and was positively associated with tumor stage, lymphatic metastasis, and poor prognosis. Functionally, HCG11 knockdown inhibited proliferation and migration and induced apoptosis of NPC cells. Mechanistically, miR-490-3p is a direct target of HCG11, oncogenic functions of HCG11 in NPC cell proliferation and migration can be partially reversed by the miR-490-3p inhibitor. HCG11 significantly increased mitogen-activated protein kinase MAPK kinase 9 (MAP3K9) levels by inhibiting miR-490-3p. Conclusion: HCG11 facilitates NPC progression via MAP3K9 signaling by sponging miRNA-490-3p, which may contribute to new prognostic markers and promising therapeutic targets.

14.
Front Oncol ; 12: 846775, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359387

RESUMO

Purpose: To compare the performances of deep learning (DL) to radiomics analysis (RA) in predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) based on pretreatment dynamic contrast-enhanced MRI (DCE-MRI) in breast cancer. Materials and Methods: This retrospective study included 356 breast cancer patients who underwent DCE-MRI before NAC and underwent surgery after NAC. Image features and kinetic parameters of tumors were derived from DCE-MRI. Molecular information was assessed based on immunohistochemistry results. The image-based RA and DL models were constructed by adding kinetic parameters or molecular information to image-only linear discriminant analysis (LDA) and convolutional neural network (CNN) models. The predictive performances of developed models were assessed by receiver operating characteristic (ROC) curve analysis and compared with the DeLong method. Results: The overall pCR rate was 23.3% (83/356). The area under the ROC (AUROC) of the image-kinetic-molecular RA model was 0.781 [95% confidence interval (CI): 0.735, 0.828], which was higher than that of the image-kinetic RA model (0.629, 95% CI: 0.595, 0.663; P < 0.001) and comparable to that of the image-molecular RA model (0.755, 95% CI: 0.708, 0.802; P = 0.133). The AUROC of the image-kinetic-molecular DL model was 0.83 (95% CI: 0.816, 0.847), which was higher than that of the image-kinetic and image-molecular DL models (0.707, 95% CI: 0.654, 0.761; 0.79, 95% CI: 0.768, 0.812; P < 0.001) and higher than that of the image-kinetic-molecular RA model (0.778, 95% CI: 0.735, 0.828; P < 0.001). Conclusions: The pretreatment DCE-MRI-based DL model is superior to the RA model in predicting pCR to NAC in breast cancer patients. The image-kinetic-molecular DL model has the best prediction performance.

15.
Ann Surg Oncol ; 2022 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-35366706

RESUMO

BACKGROUND: Liver metastasis (LM) after pancreatic ductal adenocarcinoma (PDAC) resection is common but difficult to predict and has grave prognosis. We combined preoperative clinicopathological variables and quantitative analysis of computed tomography (CT) imaging to predict early LM. METHODS: We retrospectively evaluated patients with PDAC submitted to resection between 2005 and 2014 and identified clinicopathological variables associated with early LM. We performed liver radiomic analysis on preoperative contrast-enhanced CT scans and developed a logistic regression classifier to predict early LM (< 6 months). RESULTS: In 688 resected PDAC patients, there were 516 recurrences (75%). The cumulative incidence of LM at 5 years was 41%, and patients who developed LM first (n = 194) had the lowest 1-year overall survival (OS) (34%), compared with 322 patients who developed extrahepatic recurrence first (61%). Independent predictors of time to LM included poor tumor differentiation (hazard ratio (HR) = 2.30; P < 0.001), large tumor size (HR = 1.17 per 2-cm increase; P = 0.048), lymphovascular invasion (HR = 1.50; P = 0.015), and liver Fibrosis-4 score (HR = 0.89 per 1-unit increase; P = 0.029) on multivariate analysis. A model using radiomic variables that reflect hepatic parenchymal heterogeneity identified patients at risk for early LM with an area under the receiver operating characteristic curve (AUC) of 0.71; the performance of the model was improved by incorporating preoperative clinicopathological variables (tumor size and differentiation status; AUC = 0.74, negative predictive value (NPV) = 0.86). CONCLUSIONS: We confirm the adverse survival impact of early LM after resection of PDAC. We further show that a model using radiomic data from preoperative imaging combined with tumor-related variables has great potential for identifying patients at high risk for LM and may help guide treatment selection.

16.
Br J Cancer ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388140

RESUMO

BACKGROUND: The potential of using magnetic resonance image tumour-regression grading (MRI-TRG) system to predict pathological TRG is debatable for locally advanced rectal cancer treated by neoadjuvant radiochemotherapy. METHODS: Referring to the American Joint Committee on Cancer/College of American Pathologists (AJCC/CAP) TRG classification scheme, a new four-category MRI-TRG system based on the volumetric analysis of the residual tumour and radiochemotherapy induced anorectal fibrosis was established. The agreement between them was evaluated by Kendall's tau-b test, while Kaplan-Meier analysis was used to calculate survival outcomes. RESULTS: In total, 1033 patients were included. Good agreement between MRI-TRG and AJCC/CAP TRG classifications was observed (k = 0.671). Particularly, as compared with other pairs, MRI-TRG 0 displayed the highest sensitivity [90.1% (95% CI: 84.3-93.9)] and specificity [92.8% (95% CI: 90.4-94.7)] in identifying AJCC/CAP TRG 0 category patients. Except for the survival ratios that were comparable between the MRI-TRG 0 and MRI-TRG 1 categories, any two of the four categories had distinguished 3-year prognosis (all P < 0.05). Cox regression analysis further proved that the MRI-TRG system was an independent prognostic factor (all P < 0.05). CONCLUSION: The new MRI-TRG system might be a surrogate for AJCC/CAP TRG classification scheme. Importantly, the system is a reliable and non-invasive way to identify patients with complete pathological responses.

17.
Comput Intell Neurosci ; 2022: 8699322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371225

RESUMO

Considering that collision accidents happen sometimes, it is necessary to predict the collision risk to ensure navigation safety. With the information construction in maritime and the popularity of automatic identification system application, it is more convenient to obtain ship navigation dynamics. How to obtain ship encounter dynamic parameters through automatic identification system information, assess ship collision risk, find out dangerous target ships, and give early warning and guarantee for ship navigation safety, is a problem that scholars have been studying. As an index to measure the degree of ship collision risk, CRI, namely, collision risk index, is usually obtained by calculating ship encounter parameters and comprehensive analysis. There are many factors that affect CRI, and the values of many parameters depend on expert judgment. The corresponding CRI has nonlinear and complex characteristics, which is highly correlated with the time sequence. In order to enhance the prediction accuracy and efficiency, PSO-LSTM neural network is applied in the paper to predict CRI. Experiments show that PSO-LSTM neural network can effectively predict collision risk and provide a reference for navigation safety.


Assuntos
Redes Neurais de Computação , Navios , Acidentes
18.
Bioact Mater ; 17: 496-505, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35415293

RESUMO

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 µm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

19.
Front Immunol ; 13: 845757, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401536

RESUMO

Background: Pyroptosis, as an inflammatory form of cell death, is involved in many physiological and pathological processes. Neuroblastoma is the most common extra-cranial solid tumor in children. In this study, the relationship between pyroptosis and tumor microenvironment in neuroblastoma was systematically studied. Methods: We integrated four datasets of neuroblastomas. Through robust clustering of the mRNA expression profiles of 24 pyroptosis-related genes, a total of three pyroptosis patterns were identified. We then constructed a novel scoring method named as pyroscore to quantify the level of pyroptosis in neuroblastoma. Multi-omics data and single-cell RNA sequencing were used to accurately and comprehensively evaluate the effectiveness of pyroscore. Clinical data sets were used to evaluate the use of pyroscore to predict the responsiveness of immune checkpoint treatment. Results: High pyroscore was associated with good prognosis, immune activation, and increased response to checkpoint blockade immunotherapy. Multivariate Cox analysis revealed that the pyroscore was an independent prognostic biomarker and could increase the accuracy of clinical prediction models. Etoposide, a drug picked up by our analysis, could increase the sensitivity of neuroblastoma cells to pyroptosis. External verification using four cohorts of patients who had received immunotherapy showed that high pyroscore was significantly associated with immunotherapy treatment benefit. Conclusions: Taken together, this study revealed that pyroptosis-related gene network could quantify the response of neuroblastoma to immune checkpoint blockade therapy and prognosis, and it may be helpful for clinical practitioners to choose treatment strategies for neuroblastoma patients.


Assuntos
Redes Reguladoras de Genes , Neuroblastoma , Criança , Humanos , Imunoterapia , Neuroblastoma/genética , Neuroblastoma/terapia , Prognóstico , Piroptose/genética , Microambiente Tumoral/genética
20.
BMC Plant Biol ; 22(1): 138, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35321648

RESUMO

BACKGROUND: Clematis species are attractive ornamental plants with a variety of flower colors and patterns. Heat stress is one of the main factors restricting the growth, development, and ornamental value of Clematis. Clematis lanuginosa and Clematis crassifolia are large-flowered and evergreen Clematis species, respectively, that show different tolerance to heat stress. We compared and analyzed the transcriptome of C. lanuginose and C. crassifolia under heat stress to determine the regulatory mechanism(s) of resistance. RESULTS: A total of 1720 and 6178 differentially expressed genes were identified from C. lanuginose and C. crassifolia, respectively. The photosynthesis and oxidation-reduction processes of C. crassifolia were more sensitive than C. lanuginose under heat stress. Glycine/serine/threonine metabolism, glyoxylic metabolism, and thiamine metabolism were important pathways in response to heat stress in C. lanuginose, and flavonoid biosynthesis, phenylalanine metabolism, and arginine/proline metabolism were the key pathways in C. crassifolia. Six sHSPs (c176964_g1, c200771_g1, c204924_g1, c199407_g2, c201522_g2, c192936_g1), POD1 (c200317_g1), POD3 (c210145_g2), DREB2 (c182557_g1), and HSFA2 (c206233_g2) may be key genes in the response to heat stress in C. lanuginose and C. crassifolia. CONCLUSIONS: We compared important metabolic pathways and differentially expressed genes in response to heat stress between C. lanuginose and C. crassifolia. The results increase our understanding of the response mechanism and candidate genes of Clematis under heat stress. These data may contribute to the development of new Clematis varieties with greater heat tolerance.


Assuntos
Clematis , Transcriptoma , Clematis/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico/genética
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