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Cyanobacteria have great potential in CO2-based bio-manufacturing and synthetic biological studies. The filamentous cyanobacterium, Leptolyngbya sp. strain BL0902, is comparable to Arthrospira (Spirulina) platensis in commercial-scale cultivation while proving to be more genetically tractable. Here, we report the analyses of the whole genome sequence, gene inactivation/overexpression in the chromosome and deletion of non-essential chromosomal regions in this strain. The genetic manipulations were performed via homologous double recombination using either an antibiotic resistance marker or the CRISPR/Cpf1 editing system for positive selection. A desD-overexpressing strain produced γ-linolenic acid in an open raceway photobioreactor with the productivity of 0.36 g·m-2·d-1. Deletion mutants of predicted patX and hetR, two genes with opposite effects on cell differentiation in heterocyst-forming species, were used to demonstrate an analysis of the relationship between regulatory genes in the non-heterocystous species. Furthermore, a 50.8-kb chromosomal region was successfully deleted in BL0902 with the Cpf1 system. These results supported that BL0902 can be developed into a stable photosynthetic cell factory for synthesizing high value-added products, or used as a model strain for investigating the functions of genes that are unique to filamentous cyanobacteria, and could be systematically modified into a genome-streamlined chassis for synthetic biological purposes.
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Mercury ion (Hg2+), a highly toxic metal pollutant, is widely found in the environment and can enter the human body through the food chain, causing various health issues. Sensitive and accurate methods for monitoring Hg2+ are highly desirable for ensuring food safety. Herein, we propose a self-sustainable multiple amplification system (MAS) for Hg2+ determination through the reciprocal activation between catalytic hairpin assembly (CHA) and rolling circle amplification (RCA). The thymine-encoded recognition element specifically recognizes Hg2+, triggering the exposure of the initiator. The initiator then motivates the mutual activation of CHA and RCA to accelerate the production of an exponentially amplified signal. The MAS method achieved a low detection limit of 11 pM. Due to its reliable target recognition and robust amplification efficiency, the MAS circuit facilitated the highly efficient and accurate analysis of low-abundance Hg2+ in milk and snakehead samples, thus providing a potentially new tool for food safety control.
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Background: The tumor microenvironment (TME) plays an important role in tumor progression and immunotherapy responses in non-small cell lung cancer (NSCLC). The programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) checkpoint is a central mediator of immunosuppression in the TME. However, there is still a need to identify additional biomarkers that could reflect the difference in TME and PD-L1 expression in NSCLC patients. To this end, we focused on the expression of G-protein-coupled receptor family C group 5 type A (GPRC5A) in NSCLC. GPRC5A, is a retinoic acid-inducible gene that plays multiple roles in NSCLC. However, little is known about the role of GPRC5A in regulating the TME and PD-L1. Our objective was to describe the critical role of GPRC5A expression in NSCLC in the setting of immune cell infiltration. Methods: We identified the relationship between GPRC5A expression and the clinicopathologic characteristics of NSCLC patients in the Fudan University Shanghai Cancer Center (FUSCC) cohort. Furthermore, we validated GPRC5A as a predictive biomarker by using public databases to reveal the relationship between GPRC5A expression and immune cell infiltration. To correlate the expression of GPRC5A with the spatial distribution of PD-L1 in NSCLC samples, we performed multiplex immunohistochemistry (mIHC). Results: Low GPRC5A expression is associated with earlier pathological stage (pStage). Analysis of immune cell infiltration indicates there is a relationship between low GPRC5A expression and increased infiltration of CD8+ T cells, activated CD4+ T cells, and M1 macrophages within the TME. Furthermore, low GPRC5A expression is associated with an increased immunophenotype score (IPS) in NSCLC. Additionally, analysis of mIHC reveals there is a correlation between low GPRC5A expression and spatial distribution of tumoral PD-L1 expression. Conclusions: Our study revealed the relationship between low expression of GPRC5A and earlier pStage in NSCLC. Furthermore, we observed that low expression of GPRC5A is associated with increased infiltration of immune cells, higher IPS, and spatial distribution of PD-L1-positive tumor cells. Therefore, we speculate that low expression of GPRC5A is associated with immunotherapy, but further validation is still required.
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BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.
Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.
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The present study investigated the difference in transmittance of light carrying opposite spin angular momentum (SAM) and orbital angular momentum (OAM) through chlorella algal fluid with varying concentrations and thicknesses. Our results indicate that, under specific conditions, right-handed light sources exhibit higher transmittance in the algal fluid compared to left-handed light sources. Furthermore, we observed that light with OAM also demonstrated higher transmittance than other types of light sources, leading to faster cell density growth of Chlorella. Interestingly, we also discovered that light with OAM stimulates Chlorella to synthesize more proteins. These findings provide different insights for selecting appropriate light sources for large-scale algae cultivation, and may facilitate the realization of carbon peaking and carbon neutrality in the future.
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Chlorella , Proliferación Celular , Carbono , Ciclo Celular , ManoRESUMEN
BACKGROUND: Optimal antihypertensive medication for chronic type B aortic dissection (AD) remains undecided. This study compared the efficacy and safety of sacubitril/valsartan with valsartan to determine suitable antihypertensive drug combinations. METHODS: In this single-center, open-label, randomized, controlled trial, patients with chronic Stanford type B AD and mild hypertension were randomized to receive sacubitril/valsartan 100/200 mg or valsartan 80/160 mg. The primary endpoint was the reduction in mean sitting systolic blood pressure (msSBP) at week 8 in patients with sacubitril/valsartan vs. valsartan. Key secondary endpoints included changes in (i) mean sitting diastolic blood pressure (msDBP); (ii) pulse pressure (PP); and (iii) mean ambulatory blood pressure (BP) for 24-hour, daytime, and nighttime. Safety assessments included adverse events (AEs) and serious AEs. This trial was registered with the Chinese Clinical Trial Registry, identifier: ChiCTR2300073399. RESULTS: A total of 315 patients completed the study. Sacubitril/valsartan provided a significantly greater reduction in msSBP than valsartan at week 8 (between-treatment difference: -5.1 mm Hg [95% confidence interval -5.8 to -4.5], Pâ <â 0.001). Reductions in msSBP, msDBP, and PP as well as the mean ambulatory BP for 24-hour, daytime, and nighttime, were significantly greater in sacubitril/valsartan compared with valsartan (all Pâ <â 0.001). No excessive episodes of AEs occurred in the sacubitril/valsartan group. CONCLUSIONS: Sacubitril/valsartan and valsartan reduced BP compared with baseline values. However, sacubitril/valsartan improved BP control to a greater extent than valsartan. It may offer a new treatment option for patients with mild hypertension and chronic type B AD.
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Aminobutiratos , Antihipertensivos , Disección Aórtica , Compuestos de Bifenilo , Presión Sanguínea , Combinación de Medicamentos , Hipertensión , Valsartán , Humanos , Valsartán/uso terapéutico , Aminobutiratos/uso terapéutico , Aminobutiratos/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/diagnóstico , Disección Aórtica/fisiopatología , Disección Aórtica/tratamiento farmacológico , Resultado del Tratamiento , Anciano , Presión Sanguínea/efectos de los fármacos , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Enfermedad Crónica , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Tetrazoles/uso terapéutico , Tetrazoles/efectos adversos , Aneurisma de la Aorta/tratamiento farmacológico , China/epidemiología , Factores de Tiempo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversosRESUMEN
Inappropriate use of veterinary drugs can result in the presence of antibiotic residues in animal-derived foods, which is a threat to human health. A simple yet efficient antibiotic-sensing method is highly desirable. Programmable DNA amplification circuits have supplemented robust toolkits for food contaminants monitoring. However, they currently face limitations in terms of their intricate design and low signal gain. Herein, we have engineered a robust reciprocal catalytic DNA (RCD) circuit for highly efficient bioanalysis. The trigger initiates the cascade hybridization reaction (CHR) to yield plenty of repeated initiators for activating the rolling circle amplification (RCA) circuit. Then the RCA-generated numerous reconstituted triggers can reversely stimulate the CHR circuit. This results in a self-sufficient supply of numerous initiators and triggers for the successive cross-invasion of CHR and RCA amplifiers, thus leading to exponential signal amplification for the highly efficient detection of analytes. With its flexible programmability and modular features, the RCD amplifier can serve as a universal toolbox for the high-performance and accurate sensing of kanamycin in buffer and food samples including milk, honey, and fish, highlighting its enormous promise for low-abundance contaminant analysis in foodstuffs.
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Técnicas Biosensibles , ADN Catalítico , Animales , Humanos , Kanamicina/análisis , Antibacterianos/análisis , Hibridación de Ácido Nucleico/métodos , Peces/metabolismo , Técnicas Biosensibles/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Límite de DetecciónRESUMEN
Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance. We evaluate intratumoral (IT) vaccination with CXCL9- and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a strategy to overcome resistance. IT CXCL9/10-DC leads to enhanced T cell infiltration and activation in the TME and tumor inhibition in murine NSCLC models. The antitumor efficacy of IT CXCL9/10-DC is dependent on CD4+ and CD8+ T cells, as well as CXCR3-dependent T cell trafficking from the lymph node. IT CXCL9/10-DC, in combination with ICB, overcomes resistance and establishes systemic tumor-specific immunity in murine models. These studies provide a mechanistic understanding of CXCL9/10-DC-mediated host immune activation and support clinical translation of IT CXCL9/10-DC to augment ICB efficacy in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Ratones , Animales , Linfocitos T CD8-positivos , Inhibidores de Puntos de Control Inmunológico , Células Dendríticas , Microambiente Tumoral , Quimiocina CXCL9RESUMEN
The Tup1-Cyc8 complex is a highly conserved transcriptional corepressor that regulates intricate genetic network associated with various biological processes in fungi. Here, we report the role and mechanism of FonTup1 in regulating physiological processes and pathogenicity in watermelon Fusarium wilt fungus, Fusarium oxysporum f. sp. niveum (Fon). FonTup1 deletion impairs mycelial growth, asexual reproduction, and macroconidia morphology, but not macroconidial germination in Fon. The ΔFontup1 mutant exhibits altered tolerance to cell wall perturbing agent (congo red) and osmotic stressors (sorbitol or NaCl), but unchanged sensitivity to paraquat. The deletion of FonTup1 significantly decreases the pathogenicity of Fon toward watermelon plants through attenuating the ability to colonize and grow within the host. Transcriptome analysis revealed that FonTup1 regulates primary metabolic pathways, including the tricarboxylic acid (TCA) cycle, via altering the expression of corresponding genes. Downregulation of three malate dehydrogenase genes, FonMDH1-3, occurs in ΔFontup1, and disruption of FonMDH2 causes significant abnormalities in mycelial growth, conidiation, and virulence of Fon. These findings demonstrate that FonTup1, as a global transcriptional corepressor, plays crucial roles in different biological processes and pathogenicity of Fon through regulating various primary metabolic processes, including the TCA cycle. This study highlights the importance and molecular mechanism of the Tup1-Cyc8 complex in multiple basic biological processes and pathogenicity of phytopathogenic fungi.
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Fenómenos Biológicos , Citrullus , Fusarium , Virulencia/genética , Ciclo del Ácido Cítrico , Redes Reguladoras de Genes , Citrullus/genética , Citrullus/metabolismo , Citrullus/microbiología , Proteínas Co-Represoras/genética , Proteínas Co-Represoras/metabolismo , Enfermedades de las Plantas/microbiologíaRESUMEN
Adenosine triphosphate (ATP), the main carrier of chemical energy, plays a key role in various biochemical reactions such as cellular metabolism. Currently, ATP levels are considered important indicators of microbial content in food safety, and food freshness can be determined by detecting ATP content. Some ATP sensing strategies have been applied to evaluate food freshness. However, cumbersome nanomaterial preparation, low sensitivity, and low reliability hamper their widespread application. Herein, a simple, high-performance, and reliable dual-mode sensing system based on hemin-G-quadruplex (G4) DNAzyme was established to detect ATP and assess fish freshness. Two nucleic acid probes, including subunits of the hemin-G4 DNAzyme in inactive structures and anti-ATP aptamer, self-assemble upon the input of ATP into the active hemin-G4 DNAzyme unit. The generated DNAzyme acts as a biocatalyst for colorimetric or fluorescent readout of the sensing process. The colorimetric and fluorescent dual-mode sensing system enables highly sensitive and reliable analysis of target ATP with detection limits of 71 nM and 73 nM, respectively. Moreover, the biosensor exhibited good selectivity for differentiating ATP from other interfering analytes. The proposed system was used to detect ATP in perch samples, and a linear correlation between ATP level and microbial content was confirmed. The established ATP-sensing system reliably evaluated fish freshness. Notably, in comparison with microbiological counts, the proposed DNAzyme-based dual-mode strategy for freshness evaluation is facile, highly efficient, and cost-effective, thus providing a promising method for food safety and quality monitoring.
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Técnicas Biosensibles , ADN Catalítico , G-Cuádruplex , Animales , ADN Catalítico/química , Adenosina Trifosfato , Hemina/química , Reproducibilidad de los Resultados , Técnicas Biosensibles/métodosRESUMEN
Improper use of kanamycin can lead to trace kanamycin residues in animal-derived foods, which can pose a potential threat to public health. Isothermal enzyme-free DNA circuits have provided a versatile toolbox for detecting kanamycin residues in complicated food samples, yet they are always limited by low amplification efficiency and intricate design. Herein, we present a simple-yet-robust nonenzymatic self-driven hybridization chain reaction (SHCR) amplifier for kanamycin determination with 5800-fold sensitivity over that of the conventional HCR circuit. The analyte kanamycin-activated SHCR circuitry can generate numerous new initiators to promote the reaction and improve the amplification efficiency, thus achieving an exponential signal gain. With precise target recognition and multilayer amplification capability, our self-sustainable SHCR aptasensor facilitated the highly sensitive and reliable analysis of kanamycin in buffer, milk, and honey samples, thus holding great potential for the amplified detection of trace contaminants in liquid food matrices.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Animales , Kanamicina/análisis , Aptámeros de Nucleótidos/química , Límite de Detección , ADN/químicaRESUMEN
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in industrial and commercial products. It is generally believed that OPEs in street dust mainly originate from road traffic and anthropogenic activities. The influence of atmospheric deposition is still unknown. In this study, leaves were employed as a novel passive air sampler to collect particle matters (PM) in 12 cities in the central province of Henan, China. Similar compositional profiles of OPEs were found in street dust and PM samples. The concentrations of individual OPEs in PM were 1-4 times higher than in street dust. Chlorinated OPEs concentration in PM shows a moderate correlation (r2 = 0.538, p < 0.01) with that in street dust. The concentration of alkyl OPEs in PM has a high correlation (r2 = 0.843, p < 0.01) with that in street dust. No significant correlation (r2 = 0.133, p = 0.132) was found on the aryl OPEs concentrations between street dust and PM. Spearman correlation reveals that the emission sources of tricresyl phosphate (TCrP) and triethyl phosphate (TEP) may be different from other OPEs in dust and PM samples. Principle component analysis (PCA) provides an appropriate explanation that tris (2-chloroethyl) phosphate (TCEP), triphenyl phosphate (TPhP), tris (chloropropyl) phosphate (TCPP), tributyl phosphate (TnBP), and TEP in street dust and PM may be emitted from the same sources, suggesting that PM has a significant influence on the occurrence of OPEs in street dust. The estimated dry deposition fluxes of particle-bound OPEs show a significant correlation (R2 = 0.969, p < 0.01) with OPEs concentrations in street dust, revealing that the input of atmospheric deposition could be a major source of OPEs in street dust.
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Polvo , Tritolilfosfatos , FosfatosRESUMEN
In this study, the impact of biochar on the degradation of organophosphate esters (OPEs) during the aerobic composting of sewage sludge was investigated. Three treatments were conducted with different percentages of biochar in the compost, including 5 %, 10 %, and 20 %. The treatment with 10 % of biochar showed the longest thermophilic phase compared to that of 5 % and 20 % of biochar, which greatly promoted the decomposition of organic matter. In addition, the degradation rate of the hard-to-degrade chlorinated-OPEs was significantly increased by 10 % biochar, reaching to 57.2 %. Correspondingly, approximately 43.6 % of the total concentration of OPEs (Σ6OPEs) was eliminated in the presence of 10 % of biochar, which was higher than the treatments with 5 % and 20 % of biochar. Biochar significantly influenced the microbial community structure of compost, but the previously reported organophosphorus-degrading bacteria did not play a major role in the degradation of OPEs. The redox ability of the increased oxygen-containing functional groups such as quinone on the surface of biochar and the biochar-mediated electron transfer ability may play an essential role in the degradation of OPEs during the composting process.
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Compostaje , Aguas del Alcantarillado/química , Organofosfatos , Oxígeno , Quinonas , Suelo/químicaRESUMEN
Recent years have seen a heated discussion on what influences employees' recognition of enterprise brand equity among the psychological community. Some empirical evidence suggests that the brand equity of consumers and brand equity of sales are two categories that should be studied. However, more recent discussions have focused more on the former. In contrast, this study discusses the factors influencing brand equity based on the employee level. Moreover, this paper examines whether FinTech can help companies get out of financing difficulties and thus improve employees' brand equity recognition. This research illustrates how FinTech has become an essential driver of brand equity value. Based on micro panel data on enterprises from 2011 to 2019, we analyze the transmission mechanism between the two factors and the mediating role of financing constraints. FinTech's development promotes employees' recognition of corporate brand equity, and financing constraints are an essential transmission path between the two factors. Furthermore, the impact of financing constraints on employee brand equity identity is characterized by cross-regional economic heterogeneity. In contrast, the development of FinTech characterizes the cross-enterprise heterogeneity in employees' recognition of brand equity value. Altogether, this study demonstrates the promising application of FinTech in influencing the mechanisms of employee brand equity.
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Photobiomodulation therapy (PBMT) is a non-invasive and pain-less treatment for hair loss. Researches on PBMT rarely considered the impact of different light structures. In this study, we irradiated shaven rats with both 650 nm, m = 32 vortex beams and ordinary Gaussian beams. The laser treatment was performed at 24-hour intervals for 20 days. The energy density was set to 4.25 J/cm2 . The results indicated that low-level vortex beam irradiation led to better stimulation of hair growth than the Gaussian beams, which might be related to deeper penetration. The underlying biological mechanisms are discussed in terms of the activation of Wnt/ß-catenin/sonic hedgehog pathway. Our results suggest that low-level vortex beam irradiation is advantageous to the treatment of hair loss because it is technically feasible, convenient and effective.
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Proteínas Hedgehog , Terapia por Luz de Baja Intensidad , Animales , Ratas , Cabello , Alopecia , Terapia por Luz de Baja Intensidad/métodosRESUMEN
BACKGROUND: Artificial intelligence (AI) analysis may serve as a scoring tool for programmed cell death ligand-1 (PD-L1) expression. In this study, a new AI-assisted scoring system for pathologists was tested for PD-L1 expression assessment in non-small cell lung cancer (NSCLC). METHODS: PD-L1 expression was evaluated using the tumor proportion score (TPS) categorized into three levels: negative (TPS < 1%), low expression (TPS 1-49%), and high expression (TPS ≥ 50%). In order to train, validate, and test the Aitrox AI segmentation model at the whole slide image (WSI) level, 54, 53, and 115 cases were used as training, validation, and test datasets, respectively. TPS reading results from five experienced pathologists, six inexperienced and the Aitrox AI model were analyzed on 115 PD-L1 stained WSIs. The Gold Standard for TPS was derived from the review of three expert pathologists. Spearman's correlation coefficient was calculated and compared between the results. RESULTS: Aitrox AI Model correlated strongly with the TPS Gold Standard and was comparable with the results of three of the five experienced pathologists. In contrast, the results of four of the six inexperienced pathologists correlated only moderately with the TPS Gold Standard. Aitrox AI Model performed better than the inexperienced pathologists and was comparable to experienced pathologists in both negative and low TPS groups. Despite the fact that the low TPS group showed 5.09% of cases with large fluctuations, the Aitrox AI Model still showed a higher correlation than the inexperienced pathologists. However, the AI model showed unsatisfactory performance in the high TPS groups, especially lower values than the Gold Standard in images with large regions of false-positive cells. CONCLUSION: The Aitrox AI Model demonstrates potential in assisting routine diagnosis of NSCLC by pathologists through scoring of PD-L1 expression.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Inteligencia Artificial , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/diagnósticoRESUMEN
In this study, the gas-phase retention volume behavior of four highly volatile organophosphate esters (OPEs) on polyurethane foam (PUF) was studied using a frontal chromatogram. The breakthrough volumes (VB) of trimethyl phosphate (TMP), triethyl phosphate (TEP), tripropyl phosphate (TPrP), and tri-n-butyl phosphate (TnBP) were 0.33, 0.59, 10.5, and 32.4 m3, respectively. A significant negative correlation was found between the logarithm value of VB and the subcooled liquid vapor pressure (PL) with an r2 of 0.905, indicating that the vapor penetration depends on both the volatility and total air volume. The enthalpy of desorption and vaporization (ΔHS-ΔHV) showed a significant difference between the tested OPEs and polycyclic aromatic hydrocarbons (PAHs), revealing that the strength of the sorption interaction of the tested OPEs vapor on PUF should be different from that of PAHs. The PUF-air partition coefficients (KPUF-air) of the tested OPEs ranged from 4.3 to 8.1, which were lower than those of three-to four-ring PAHs (7.02-10.2) and organochlorines (8.01-9.72), revealing that the partition of highly volatile OPEs on PUF is lower than that of low-volatile compounds. The PUF/XAD cartridge improved the absorption efficiency of the tested OPEs; however, its sorptive capacity was still limited.
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Retardadores de Llama , Hidrocarburos Policíclicos Aromáticos , China , Monitoreo del Ambiente , Ésteres , Retardadores de Llama/análisis , Gases , Organofosfatos , PoliuretanosRESUMEN
BACKGROUND: The combined positive score (CPS) of the programmed death ligand-1 (PD-L1) 22C3 assay is a predictive marker of pembrolizumab monotherapy for advanced esophageal cancer (EC) patients. However, little is known about the association of the PD-L1 22C3 CPS with the clinicopathological features and heterogeneity of PD-L1 expression in EC in the Chinese population in a real-world setting. METHODS: We examined the association of the PD-L1 22C3 CPS with clinicopathological characteristics in 533 EC specimens. Further, we compared 37 cases' different blocks of the same specimen and 50 paired primary/metastatic lymph node lesions to investigate the heterogeneity of PD-L1 expression. RESULTS: PD-L1 positive expression was observed in 45.0% of 533 EC patients, including 46.8% with squamous cell carcinoma, 15.4% with adenocarcinoma, 28.6% with basaloid squamous carcinoma, 42.9% with spindle cell carcinoma, and 33.3% with neuroendocrine tumors. PD-L1 positive expression was positively associated with lymph node metastasis (59.2% chance, p = 0.021) and venous/lymphatic invasion (66.3% chance, p = 0.029). PD-L1 expression was highly consistent in different paraffin blocks of the same surgically resected specimen (concordance rate: 86.5%, p = 0.000016) and a moderate consistency (concordance rate: 78.0%, p = 0.000373) for the primary and metastatic lymph node lesion comparison. CONCLUSIONS: This is a novel study which demonstrated a positive correlation between a high PD-L1 22C3 CPS and invasion/metastasis risk in EC surgical specimens. Both paired blocks and paired primary/metastatic lymph node lesions showed significant concordance. PD-L1 heterogeneity was inferred to be mainly related to positive mononuclear inflammatory cells (MICs), which might have substantial implications for clinical practice.
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Adenocarcinoma , Neoplasias Esofágicas , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , HumanosRESUMEN
Programmed cell death ligend-1 (PD-L1) expression by immunohistochemistry (IHC) assays is a predictive marker of anti-PD-1/PD-L1 therapy response. With the popularity of anti-PD-1/PD-L1 inhibitor drugs, quantitative assessment of PD-L1 expression becomes a new labor for pathologists. Manually counting the PD-L1 positive stained tumor cells is an obviously subjective and time-consuming process. In this paper, we developed a new computer aided Automated Tumor Proportion Scoring System (ATPSS) to determine the comparability of image analysis with pathologist scores. A three-stage process was performed using both image processing and deep learning techniques to mimic the actual diagnostic flow of the pathologists. We conducted a multi-reader multi-case study to evaluate the agreement between pathologists and ATPSS. Fifty-one surgically resected lung squamous cell carcinoma were prepared and stained using the Dako PD-L1 (22C3) assay, and six pathologists with different experience levels were involved in this study. The TPS predicted by the proposed model had high and statistically significant correlation with sub-specialty pathologists' scores with Mean Absolute Error (MAE) of 8.65 (95% confidence interval (CI): 6.42-10.90) and Pearson Correlation Coefficient (PCC) of 0.9436 ([Formula: see text]), and the performance on PD-L1 positive cases achieved by our method surpassed that of non-subspecialty and trainee pathologists. Those experimental results indicate that the proposed automated system can be a powerful tool to improve the PD-L1 TPS assessment of pathologists.
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Antígeno B7-H1/genética , Carcinoma de Células Escamosas/diagnóstico , Perfilación de la Expresión Génica/métodos , Adulto , Anciano , Automatización de Laboratorios/métodos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Bioensayo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , China , Femenino , Expresión Génica/genética , Humanos , Inmunohistoquímica/métodos , Pulmón/patología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Transcriptoma/genéticaRESUMEN
INTRODUCTION: Lumbar disk herniation (LDH) is a common cause of low back pain and dysfunction. Studies have shown that electroacupuncture (EA) can achieve pain relief in patients with LDH. However, there is a lack of evidence regarding the effectiveness of deep EA with strong deqi and shallow EA with no deqi in patients with LDH. This study aims to evaluate the effectiveness of deep EA with strong deqi and shallow EA with no deqi in the treatment of LDH. METHODS AND ANALYSIS: In this randomised controlled trial, patients with LDH who have low back pain with or without radiculopathy for at least 12 weeks will be enrolled. In total, 44 patients will be recruited from the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China. Patients will be randomised into the deep EA group and the shallow EA group in a ratio of 1:1 and will be administered 12 sessions of EA treatment (three times a week for 4 weeks, 20 min for each session). The follow-up duration will be 4 weeks. Low back pain intensity and leg pain intensity (in patients with radicular pain) measured using the Visual Analogue Scale (VAS) will be assessed as the primary outcomes. Function (measured using the Roland-Morris Disability Questionnaire), quality of life (measured using the EuroQol Five-Dimensional Five-Level Questionnaire) and patient-evaluated therapeutic effect will be assessed as the secondary outcomes. Patients' expectations of EA, the success of the blinding method and safety will also be evaluated. Statistical analyses will be followed by the intention-to-treat analysis. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the Third Affiliated Hospital of Beijing University of Chinese Medicine (approval number: 2019-XS-ZB06). Study results will be disseminated through publication in an open access journal. TRIAL REGISTRATION NUMBER: ChiCTR-1900026518.