Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.

Algal Extracellular Organic Matter Induced Photochemical Oxidation of Mn(II) to Solid Mn Oxide: Role of Mn(III)-EOM Complex and Its Ability to Remove 17α-Ethinylestradiol.

Photosensitizer-mediated abiotic oxidation of Mn(II) can yield soluble reactive Mn(III) and solid Mn oxides. In eutrophic water systems, the ubiquitous algal extracellular organic matter (EOM) is a potential photosensitizer and may have a substantial impact on the oxidation of Mn(II). Herein, we focused on investigating the photochemical oxidation process from Mn(II) to solid Mn oxide driven by EOM. The results of irradiation experiments demonstrated that the generation of Mn(III) intermediate was crucial for the successful photo oxidization of Mn(II) to solid Mn oxide mediated by EOM. EOM can serve as both a photosensitizer and a ligand, facilitating the formation of the Mn(III)-EOM complex. The complex exhibited excellent efficiency in removing 17α-ethinylestradiol. Furthermore, the complex underwent decomposition as a result of reactions with reactive intermediates, forming a solid Mn oxide. The presence of nitrate can enhance the photochemical oxidation process, facilitating the conversion of Mn(II) to Mn(III) and then to solid Mn oxide. This study deepens our grasp of Mn(II) geochemical processes in eutrophic water and its impact on organic micropollutant fate.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

The changes and correlation of IL-6 and oxidative stress levels in RAW264.7 macrophage cells induced by PAHs in PM2.5.

The objective of this study was to investigate the effects of anthracene (Ant) with 3 rings, benzo[a]anthracene (BaA) with 4 rings and benzo[b]fluoranthene (BbF) with 5 rings in fine particulate matter (PM2.5) at different exposure times (4 h and 24 h) and low exposure levels (0 pg/mL, 0.1 pg/mL, 1 pg/mL, 100 pg/mL and 10,000 pg/mL) on RAW264.7 cells. The changes of interleukin-6 (IL-6) and oxidative stress levels in RAW264.7 cells were investigated by methyl-thiazolyl-tetrazolium (MTT) and enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to analyze the correlation between variables. Ant, BaA and BbF induced the secretion of IL-6 and the occurrence of oxidative stress in RAW264.7 cells. The inflammatory effect and oxidative damage were exacerbated with prolonged exposure time, increasing exposure concentration and increasing number of PAH rings. At the same time, IL-6 was found to have a certain correlation with the levels of ROS, MDA and SOD. Exposure to atmospheric PAHs at low concentrations can also produce toxic effects on cells, IL-6 and oxidative stress work together in cell damage. The study is expected to provide a theoretical and experimental basis for air pollution control and human health promotion.

Dissolved organic matter accelerates microbial degradation of 17 alpha-ethinylestradiol in the presence of iron mineral.

Dissolved organic matter (DOM) and iron minerals widely existing in the natural aquatic environment can mediate the migration and transformation of organic pollutants. However, the mechanism of interaction between DOM and iron minerals in the microbial degradation of pollutants deserves further investigation. In this study, the mechanism of 17 alpha-ethinylestradiol (EE2) biodegradation mediated by humic acid (HA) and three kinds of iron minerals (goethite, magnetite, and pyrite) was investigated. The results found that HA and iron minerals significantly accelerated the biodegradation process of EE2, and the highest degradation efficiency of EE2 (48%) was observed in the HA-mediated microbial system with pyrite under aerobic conditions. Furthermore, it had been demonstrated that hydroxyl radicals (HO•) was the main active substance responsible for the microbial degradation of EE2. HO• is primarily generated through the reaction between hydrogen peroxide secreted by microorganisms and Fe(II), with aerobic conditions being more conducive. The presence of iron minerals and HA could change the microbial communities in the EE2 biodegradation system. These findings provide new information for exploring the migration and transformation of pollutants by microorganisms in iron-rich environments.

Expression patterns and DNA methylation profile of GTL2 gene in goats.

Gene trap locus 2 (GTL2), a long non-coding paternal imprinting gene, participates in various biological processes, including cell proliferation, differentiation, and apoptosis, by regulating the transcription of target mRNA, which is tightly related to the growth of the organic and maintenance of function. In this study, DNA methylation patterns of CpG islands (CGI) of GTL2 were explored, and its expression level was quantified in six tissues, rumen epithelium cells, and skeletal muscle cells in goats. GTL2 expression levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and the methylation model was confirmed by bisulfite-sequencing PCR (BSP). CGI methylation of GTL2 indicated a moderate methylation (ranging from 81.42 to 86.83%) in the brain, heart, liver, kidney, lung, and longissimus dorsi. GTL2 is most highly expressed in brain tissues, but there is no significant difference in the other five tissues. In addition, in the rumen epithelium cell proliferation, GTL2 expression was highest at 60 h, followed by 72 h, and almost unchanged at 12-48 h. In the skeletal muscle cell differentiation, GTL2 expression was highest at 0 and 24 h, significantly decreasing at 72 and 128 h. Pearson correlation analysis did not indicate a clear relationship between methylation and GTL2 expression levels, suggesting that other regulatory factors may modulate GTL2 expression. This study will provide a better understanding of the expression regulation mechanism of genes in the delta-like homolog 1 gene (DLK1)-GTL2 domain.

Sunlight-induced degradation of COVID-19 antivirals arbidol in natural aquatic environments: Mechanisms, pathways and toxicity.

Insights into COVID-19 antivirals' environmental fate and ecological risk are urgently required due to their increasing concentrations in aquatic environments, which have rarely been studied. Herein, we first investigated the photochemical transformation and the resulting alterations in toxicity of arbidol, an antiviral drug with relatively higher toxicity. The photolysis of arbidol was rapid with a rate constant of 0.106 min-1 due to its superior ultraviolet light absorption, in which the direct photolysis was predominated with a contribution of 91.5%. Despite its substantial photolysis, only 14.45% of arbidol was mineralized after 100 min, implying that arbidol and its products might have a long-term impact on aquatic environment. It was inferred that arbidol was photolyzed mainly via the loss of thiophenol, bromine, and alkylamine, based on twelve photolytic products identified. Notably, the experimental results demonstrated that the photolysis process increased the acute toxicity of arbidol, and the toxicity prediction indicated that the ecotoxicity of two photolytic products was very high with LC50 values below 0.1 mg/L. Due to the co-effect of multiple constituents, the photolytic rate observed in wastewater treatment plant effluent and in river water was comparable to that in ultra-pure water, while it was slightly enhanced in lake water. The presence of dissolved organic matter suppressed arbidol photolysis, while NO3- exhibited a promotion effect. These results would be of great significance to assess the fate and risk of COVID-19 antivirals in natural aquatic environments.

Clinical predictors for nondiabetic kidney diseases in patients with type 2 diabetes mellitus: a retrospective study from 2017 to 2021.

BACKGROUND: Nondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy. METHODS: This is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD. RESULTS: A total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118/244), 45.9% (112/244) and 5.74% (14/244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio [OR] = 4.476; 95% confidence interval [CI]: 2.257-8.877; P < 0.001), an absence of diabetic retinopathy (OR = 4.174; 95% CI: 2.049-8.502; P < 0.001), a high RBC count (OR = 1.901; 95% CI: 1.251-2.889; P = 0.003), and a negative of urinary glucose excretion test result (OR = 2.985; 95% CI: 1.474-6.044; P = 0.002).. CONCLUSIONS: A DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.

Characterization of a lipid droplet and endoplasmic reticulum stress related gene risk signature to evaluate the clinical and biological value in hepatocellular carcinoma.

INTRODUCTION: Lipid metabolism and endoplasmic reticulum (ER) stress play an important role in the progression and metastasis of hepatocellular carcinoma (HCC). We aimed to establish lipid droplet (LD)-associated and ER stress-related gene risk signature as prognostic indicators. MATERIALS AND METHODS: Literature searches for LD-associated proteins was screened and validated in The Cancer Genome Atlas (TCGA) and International Cancer Genome Collaboratory (ICGC) databases. A total of 371 samples were enrolled from the TCGA RNA-seq dataset (training cohort) and 240 samples from IGGC RNA-seq dataset (validation cohort). A 10-gene risk signature was established by the last absolute shrinkage and selection operator (LASSO) regression analysis. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan-Meier and ROC Curve analyses. Biological features associated with LD and ER stress-related factors were explored by functional analysis and in vitro experiment. RESULTS: Based on the medical literatures, 124 lipid droplet-associated proteins were retrieved, and three genes failed to establish a valid prognostic model. ER stress was considered as an important component by functional analysis. A 10-gene risk signature compared the clinicopathology characteristics, immunosuppressive events and a nomogram in HCC patients. CONCLUSION: LD-associated and ER stress-related gene risk signatures highlighted poor prognosis for clinicopathological features, positively correlate with macrophages and T cell immunoglobulin and mucin-3 (TIM-3) expression in the tumor microenvironment, and might act as independent prognostic factors.

An Experimental Study Reveals the Protective Effect of Autophagy against Realgar-Induced Liver Injury via Suppressing ROS-Mediated NLRP3 Inflammasome Pathway.

Realgar, a poisonous traditional Chinese medicine, has been shown to cause liver injury when used for long periods or overdoses. However, the underlying molecular mechanisms and therapeutic targets have not been fully elucidated. The aim of this study is to explore the role of autophagy in sub-chronic realgar exposure-induced liver injury. Here, the liver injury model was established by continuously administrating mice with 1.35 g/kg realgar for 8 weeks. 3-methyladenine (3-MA) and rapamycin (RAPA) were used to regulate autophagy. The results showed that realgar induced abnormal changes in liver function, pathological morphology, expression of inflammatory cytokines, and upregulated NLRP3 inflammasome pathway in mouse livers. RAPA treatment (an inducer of autophagy) significantly improved realgar-induced liver injury and NLRP3 inflammasome activation, while 3-MA (an inhibitor of autophagy) aggravated the realgar-induced liver injury and NLRP3 inflammasome activation. Furthermore, we found that realgar-induced NLRP3 inflammasome activation in mouse livers is mediated by ROS. RAPA eliminates excessive ROS, inhibits NF-κB nuclear translocation and down-regulates the TXNIP/NLRP3 axis, consequently suppressing ROS-mediated NLRP3 inflammasome activation, which may be the underlying mechanism of the protective effect of autophagy on realgar-induced liver injury. In conclusion, the results of this study suggest that autophagy alleviates realgar-induced liver injury by inhibiting ROS-mediated NLRP3 inflammasome activation. Autophagy may represent a therapeutic target in modulating realgar-induced liver injury.

Effective degradation of COVID-19 related drugs by biochar-supported red mud catalyst activated persulfate process: Mechanism and pathway.

With the global spread of the COVID-19 pandemic, the water pollution caused by extensive production and application of COVID-19 related drugs has aroused growing attention. Herein, a novel biochar-supported red mud catalyst (RM-BC) containing abundant free hydroxyl groups was synthesized. The RM-BC activated persulfate process was firstly put forward to degrade COVID-19 related drugs, including arbidol (ARB), chloroquine phosphate, hydroxychloroquine sulfate, and acyclovir. Highly effective removal of these pharmaceuticals was achieved and even 100% of ARB was removed within 12 min at optimum conditions. Mechanism study indicated that SO4 •- and HO• were the predominant radicals, and these radicals were responsible for the formation of DMPOX in electron spin resonance experiments. Fe species (Fe0 and Fe3O4) and oxygen-containing functional groups in RM-BC played crucial roles in the elimination of ARB. Effects of degradation conditions and several common water matrices were also investigated. Finally, the degradation products of ARB were identified by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and possible degradation pathways were proposed. This study demonstrated that RM-BC/PS system would have great potential for the removal of COVID-19 related drug residues in water by the catalyst synthesized from the solid waste.

Identification of YAP1 as a novel downstream effector of the FGF2/STAT3 pathway in the pathogenesis of renal tubulointerstitial fibrosis.

Chronic kidney disease is a global health problem and eventually develops into an end-stage renal disease (ESRD). It is now widely believed that renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of ESRD. Renal tubular epithelial-mesenchymal transition (EMT) is an important cause of TIF. Studies have shown that FGF2 is highly expressed in fibrotic renal tissue, although the mechanism remains unclear. We found that FGF2 can activate STAT3 and induce EMT in renal tubular epithelial cells. STAT3, an important transcription factor, was predicted by the JASPAR biological database to bind to the promoter region of YAP1. In this study, STAT3 was shown to promote the expression of the downstream target gene YAP1 through transcription, promote EMT of renal tubular epithelial cells, and mediate the occurrence of renal TIF. This study provides a theoretical basis for the involvement of the FGF2/STAT3/YAP1 signaling pathway in the process of renal interstitial fibrosis and provides a potential target for the treatment of renal fibrosis.

Ordering of colloidal hard spheres under gravity: from monolayer to multilayer.

The phase behaviour of hard spheres confined by a gravitational potential to a thin layer (up to several monolayers) near a hard, flat surface is investigated using grand canonical Monte Carlo simulation. Depending on the strength of the gravitational field, the bottom monolayer of spheres may adopt uniform hexagonal order before, during, or after the growth of the second layer of particles. The crossover from ordering with a sparsely populated overlayer to ordering with almost one-third of the system's particles forming a second layer is observed upon decreasing the dimensionless Péclet number Pe = mgσ/kBT from 18 to 16. The particular sensitivity of the nature of the transition to particle size in this range is interpreted in terms of competing influences on the base layer structure by particles in the overlayer: promotion of order through increased pressure, versus stabilization of defects through occupation of low-lying sites on top of them. Simulations of grain boundaries between 2-D ordered domains of different orientation are used to correlate the degree of overlayer coverage to its effects on grain boundary stiffness as an indicator of defect free energy. Finally, we examine the structure of the ordered phases at coexistence over a range of gravitational strengths and find that orientational ordering of the second monolayer occurs along with first-order transition of the base layer at Pe = 8 but not at Pe = 10.

Competing factors in grain boundary loop shrinkage: Two-dimensional hard sphere colloidal crystals.

A grain boundary (GB) loop in a two-dimensional solid is the boundary of a domain or grain whose lattice orientation is mismatched with its uniform surroundings. Understanding the factors that influence the rate at which the interior of a GB loop relaxes to the orientation of its surroundings is an important step toward control and predictability of grain coarsening in general. Recent computational and experimental studies looking at the rate of GB loop shrinkage in two-dimensional colloidal hard sphere solids have uncovered contradictory trends: in experiments, GB loops with low misorientation angles shrank the fastest, while in simulations, they persisted the longest. In this study, the computational system's behavior is brought into qualitative agreement with the experimental results through increasing the lateral packing pressure, decreasing the domain size, and mimicking the experimental protocol used to form the GB loop. Small GB loops with the same misorientation, but displaying either a hexagonal or starlike grain shape depending on the orientation of their six dislocations, are shown to differ in their rates of shrinkage by two orders of magnitude. The evidence suggests that both the barrier to generating new dislocations as well as the pattern of dislocations formed by different GB loop preparation methods will determine which trend is observed.

Partitioning of Size-Mismatched Impurities to Grain Boundaries in 2d Solid Hard-Sphere Monolayers.

Computational studies have been carried out to investigate the equilibrium partitioning of size-mismatched impurities between the bulk solid and grain boundary (GB) environments in 2d hard-sphere monolayers. The solvent repacking Monte Carlo method and a new variation were used to exchange varying numbers and types of particles under conditions of fixed particle fugacities, allowing efficient sampling of impurity particle distributions even within the bulk solid. Measurements of GB stiffness depression arising from the impurities were made via the capillary fluctuation method and found to agree with calculations based on the Gibbs adsorption isotherm, providing a test of the internal consistency of the results. The dependence of the excess concentration at the GB on factors, including impurity size (diameter ratios λ = 0.5-4 times the majority host particle diameter), impurity concentration, grain misorientation angle, and packing pressure, was studied. In general, the affinity of impurity particles for GB increased with the difference between their size and the host particles, and varied with grain misorientation angle with a dependence reflecting the excess free area at the GB. Impurities with λ = 4 were exceptions to both these trends, due to their ability to substitute efficiently for six-coordinate host particles within the bulk and for five-coordinate host particles at dislocations in the grain boundaries. Comparison with results from an experimental study of mixed colloidal monolayers raises questions about how kinetic effects during grain coarsening might produce less impurity segregation to the GB than equilibrium exchange.

Simulations of grain boundaries between ordered hard sphere monolayer domains: Orientation-dependent stiffness and its correlation with grain coarsening dynamics.

The properties of grain boundaries (GBs) between ordered 2-d domains of a hard-sphere monolayer have been investigated using grand canonical Monte Carlo simulations. The capillary fluctuation method was used to determine the GB stiffness over a range of pressures, misorientations, and inclinations. Stiffness was found to be sensitive to misorientation (mismatch in the orientation angle of neighboring grains) but not to depend on inclination (angle between the boundary and the grain orientation). Excess area per GB length was observed to follow the same trend as stiffness with respect to grain misorientation and GB inclination angles. Dynamical studies of the evolution of bicrystalline or multicrystalline monolayers with simple geometries show that the calculated angle-dependent stiffnesses correlate well with the rate at which the evolving grain structure decreases the lengths of various GBs, in agreement with recent experimental results on monolayers of colloidal microspheres.

Size-asymmetrical Lennard-Jones solid solutions: Interstitials and substitutions.

We present simulation studies of solid solutions formed upon compression of mixtures of Lennard-Jones particles with diameter ratios 2:1 and 3:1. Grand canonical Monte Carlo (GCMC) and Gibbs-Duhem integration were used to determine the compositions of coexisting solid and liquid phases at several pressures and fixed temperature. Concentrations of small particles dissolved in interstitial sites of the large-particle lattice, under liquid-solid coexistence conditions, were determined directly from GCMC simulations. Indirect methods were used to calculate levels of small particles dissolved substitutionally, either singly or in plural, with the average number of small solutes occupying a lattice site vacated by a large particle increasing with higher pressure. In the cases studied, the fraction of small solutes occupying these substitutional sites was found to be small (2% or lower, depending on the mixture and conditions), but to stay roughly constant with increasing pressure. Structural and dynamic characteristics of the solid solutions are described and compared with reported characteristics of the related interstitial solid solution formed by hard spheres.

Stepwise construction of discrete heterometallic coordination cages based on self-sorting strategy.

A chelation-directed self-sorting synthesis of a series of cationic heterometallic coordination cages (HCCs) with tunable sizes is described. Two complexation modes were found in the cage-forming process. Metal-anchoring host-guest behavior and size-selective in-cage catalytic activities were found for the HCCs.

Design of smart citrus picking model based on Mask RCNN and adaptive threshold segmentation.

Smart agriculture is steadily progressing towards automation and heightened efficacy. The rapid ascent of deep learning technology provides a robust foundation for this trajectory. Leveraging computer vision and the depths of deep learning techniques enables real-time monitoring and management within agriculture, facilitating swift detection of plant growth and autonomous assessment of ripeness. In response to the demands of smart agriculture, this exposition delves into automated citrus harvesting, presenting an ATT-MRCNN target detection model that seamlessly integrates channel attention and spatial attention mechanisms for discerning and identifying citrus images. This framework commences by subjecting diverse citrus image classifications to Mask Region-based CNN's (Mask RCNN's) discerning scrutiny, enhancing the model's efficacy through the incorporation of attention mechanisms. During the model's training phase, transfer learning is utilized to expand data performance and optimize training efficiency, culminating in parameter initialization. Empirical results notably demonstrate that this method achieves a recognition rate surpassing the 95% threshold across the three sensory recognition tasks. This provides invaluable algorithmic support and essential guidance for the imminent era of intelligent harvesting.

Non-tumor-related prognostic factors for immunotherapy-chemotherapy or immunotherapy alone as first-line in advanced non-small cell lung cancer (NSCLC).

Besides programmed death ligand 1 (PD-L1) expression, rapid, cost-effective and validated scores or models are critical for the prognosis and prediction of patients received immune checkpoint inhibitors (ICIs). In this retrospective study, 182 patients with NSCLC receiving ICIs from 2015 to 2022 were divided 1:1 into a training cohort and a validation cohort. We identified a score established by three factors and analyzed the prognostic implications by Kaplan-Meier approach (Log rank test) and time-dependent receiver operating characteristic (ROC) analyses. A non-tumor-related score (NTRS) was established that could be used as a prognostic factor (HR 2.260, 95% CI 1.559-3.276, P < 0.001 in training cohort; HR 2.114, 95% CI 1.493-2.994, P < 0.001 in validation cohort) and had a high time-dependent ROC for overall survival (OS) (AUC 0.670-0.782 in training cohort; AUC 0.682-0.841 in validation cohort). PD-L1 (1-49%) and NTRS (score = 0, 1, 2, 3) combination significantly improved the assessment of patients' OS and progress-free survival (PFS), which was statistically different in training cohorts (P < 0.001 for OS, 0.012 for PFS) and validation cohorts (P = 0.01 for OS, < 0.001 for PFS). The NTRS provided a better assessment of durable clinical benefit (DCB) compared to PD-L1 expression (P = 0.009 vs. 0.232 in training cohort; P = 0.004 vs. 0.434 in validation cohort). NTRS may help improve prognosis stratification of patients receiving ICIs in first-line NSCLC and may be combined with tumor-related parameters.