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While the industry has produced sugar-derived ethanol from the conventional method of fermentation for hundreds of years, other effective routes involving the direct transformation of carbohydrates still remain extremely rare. Very recently, an innovative chemo-catalytic method driven by the aqueous-phase catalysis was created for the synthesis of cellulosic ethanol, making a great breakthrough in the common ways as it can theoretically utilize all of the carbon atoms in sugars with faster kinetics; up to now, results from the relevant studies have been accumulated to a certain extent, but the periodic conclusions in this field are unfortunately absent. For this reason, this work tries to offer an overview of the cellulosic ethanol produced by chemo-catalytic routes, highlighting the present knowledge in relation to the technical efficiency, catalytic mechanisms as well as practical applications. At first, the advanced progress on the increasing efficiency from a varied type of catalytic systems are extensively discussed, which involves the specific functions of hybrid components from different strategies; meanwhile, the general influences of processing conditions, such as the hydrothermal severity and aqueous environments, are also identified. Subsequently, possible mechanisms behind the chemo-catalytic processes are widely elaborated by analyzing a number of experimental cases associated with the reaction network and its kinetic models. After that, the actual effects of this technique on the real biomass are collected to identify the positive/negative interactions between multiple components, together with the potential solutions on the semi-continuous processes of pilot scale application. The techno-economic analysis (TEA) is also calculated and compared with other similar methods, such as fermentation and gasification. Finally, several proposals aimed at upgrading the whole chain of chemo-catalytic processes are clearly provided, which may function as a guideline for future studies on the production of bio-ethanol from lignocellulosic materials.

Abstract Background There is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC. Methods The data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC. Results We have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB

Abstract Hydroxide exchange membrane fuel cells (HEMFCs) have the advantages of using cost-effective materials, but hindered by the sluggish anodic hydrogen oxidation reaction (HOR) kinetics. Here, we report an atomically dispersed Ir on Mo2C nanoparticles supported on carbon (IrSA-Mo2C/C) as highly active and stable HOR catalysts. The specific exchange current density of IrSA-Mo2C/C is 4.1 mA cm−2 ECSA, which is 10 times that of Ir/C. Negligible decay is observed after 30,000-cycle accelerated stability test. Theoretical calculations suggest the high HOR activity is attributed to the unique Mo2C substrate, which makes the Ir sites with optimized H binding and also provides enhanced OH binding sites. By using a low loading (0.05 mgIr cm−2) of IrSA-Mo2C/C as anode, the fabricated HEMFC can deliver a high peak power density of 1.64 W cm−2. This work illustrates that atomically dispersed precious metal on carbides may be a promising strategy for high performance HEMFCs.

Background: Neutrophil extracellular trap (NET) is associated with host response, tumorigenesis, and immune dysfunction. However, the link between NET and the tumor microenvironment (TME) of gastric cancer (GC) remains unclear. Our study aims to characterize the expression patterns of NET-related genes and their relationships with clinicopathological characteristics, prognosis, TME features, and immunotherapy efficacy in GC cohorts. Methods: Transcriptomic and single-cell RNA sequencing profiles of GC with annotated clinicopathological data were obtained from TCGA-STAD (n = 415), GSE62254 (n = 300), GSE15459 (n = 192), and GSE183904 (n = 26). The consensus cluster algorithm was used to classify tumor samples into different NET-related clusters. A NET-related signature was constructed using LASSO regression and verified in four immunotherapy cohorts. ROC and Kaplan-Meier analyses were conducted to evaluate the predictive and prognostic value of the model for immunotherapy efficacy. Results: This study identified two NET-related clusters with distinct clinicopathological features, prognosis, and TME landscapes. The high NET-related cluster, characterized by increased NET-related gene expression, exhibited more aggressive behavior and a worse prognosis (HR = 1.63, P = 0.004) than the low NET-related cluster. DEGs were primarily involved in the chemokine/cytokine-associated pathways. Moreover, the high NET-related cluster had significantly higher levels of TME scores, immune infiltration, and immune effectors (all P

Background: Gastric cancer (GC) is one of the most common malignant tumors in the world. It has become increasingly difficult to meet the needs of precision therapy using the existing molecular typing system. Therefore, developing a more effective molecular typing system for GC is urgent. Methods: In this study, 100 Chinese GC patients were included. Whole-exome sequencing (WES) and metabolomics analysis were performed to reveal the characteristics of genomic and metabolic changes. Results: In WES, nonsynonymous mutations accounted for the majority. Based on metabolomics, GC has been divided into three subtypes with distinct metabolic features. Importantly, we ultimately divided GC into four subtypes with different metabolic characteristics, genomic alterations, and clinical prognoses by incorporating biomics analysis. Conclusions: Integrating biological features, we constructed a novel molecular system for GC that was closely related to genetics and metabolism, providing new insights for further understanding the heterogeneity and formulating precise treatment strategies.

Abstract High-performance platinum-group-metal-free alkaline hydrogen oxidation reaction catalysts are essential for the hydroxide exchange membrane fuel cells, which generally require high Pt loadings on the anode. Herein, we report a highly active hydrogen oxidation reaction catalyst, NiCuCr, indicated by the hydroxide exchange membrane fuel cell with a high peak power density of 577 mW cm−2 (18 times as high as the Ni/C anode) and a stability of more than 150 h (a degradation rate slower by 7 times than the Ni/C anode). The spectroscopies demonstrate that the alloy effect from Cu weakens the hydrogen binding, and the surface Cr2O3 species enhance the interfacial water binding. Both effects bring an optimized apparent hydrogen binding energy and thus lead to the high hydrogen oxidation reaction performance of NiCuCr. These results suggest that the apparent hydrogen binding energy determines the hydrogen oxidation reaction performance and that its tuning is beneficial toward high electrocatalytic performance.

With the increasing use of cloud backup methods for storing important files, the demand for privacy protection has also grown.Reversible data hiding in encrypted images (RDHEI) is an important technology in the field of information security that allows embedding secret information in encrypted images while ensuring error-free extraction of the secret information and lossless recovery of the original plaintext image.This technology not only enhances image security but also enables efficient transmission of sensitive information over networks.Its application in cloud environments for user privacy protection has attracted significant attention from researchers.A reversible data hiding method in encrypted images based on prediction error and bitplane coding was proposed to improve the embedding rate of existing RDHEI algorithms.Different encoding methods were employed by the algorithm depending on the distribution of the bitplanes, resulting in the creation of additional space in the image.The image was rearranged to allocate the freed-up space to the lower-order planes.Following this, a random matrix was generated using a key to encrypt the image, ensuring image security.Finally, the information was embedded into the reserved space.The information can be extracted and the image recovered by the receiver using different keys.The proposed algorithm achieves a higher embedding rate compared to five state-of-the-art RDHEI algorithms.The average embedding rates on BOWS-2, BOSSBase, and UCID datasets are 3.769 bit/pixel, 3.874 bit/pixel, and 3.148 bit/pixel respectively, which represent an improvement of 12.5%, 6.9% and 8.6% compared to the best-performing algorithms in the same category.Experimental results demonstrate that the proposed algorithm effectively utilizes the redundancy of images and significantly improves the embedding rate.

The role of fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) demethylase, in non-small cell lung cancer (NSCLC) has recently received widespread attention. However the underlying mechanisms of FTO-mediated autophagy regulation in NSCLC progression remain elusive. In this study, we found that FTO was significantly upregulated in NSCLC, and downregulation of FTO suppressed the growth, invasion and migration of NSCLC cells by inducing autophagy. FTO knockdown resulted in elevated m6A levels in NSCLC cells. Methylated RNA immunoprecipitation sequencing showed that sestrin 2 (SESN2) was involved in m6A regulation during autophagy in NSCLC cells. Interestingly, m6A modifications in exon 9 of SESN2 regulated its stability. FTO deficiency promoted the binding of insulin-like growth factor 2 mRNA-binding protein 1 to SESN2 mRNA, enhancing its stability and elevating its protein expression. FTO inhibited autophagic flux by downregulating SESN2, thereby promoting the growth, invasion and migration of NSCLC cells. Besides, the mechanism by which FTO blocked SESN2-mediated autophagy activation was associated with the AMPK-mTOR signaling pathway. Taken together, these findings uncover an essential role of the FTO–autophagy–SESN2 axis in NSCLC progression.

Abstract Small cell lung cancer (SCLC) is a recalcitrant malignancy with elusive mechanism of pathogenesis and dismal prognosis. Over the past decades, platinum-based chemotherapy has been the backbone treatment for SCLC. However, subsequent chemoresistance after initial effectiveness urges researchers to explore novel therapeutic targets of SCLC. Recent years have witnessed significant improvements in targeted therapy in SCLC. New molecular candidates such as Ataxia telangiectasia and RAD3-related protein (ATR), WEE1, checkpoint kinase 1 (CHK1) and poly-ADP-ribose polymerase (PARP) have shown promising therapeutic utility in SCLC. While immune checkpoint inhibitor (ICI) has emerged as an indispensable treatment modality for SCLC, approaches to boost efficacy and reduce toxicity as well as selection of reliable biomarkers for ICI in SCLC have remained elusive and warrants our further investigation. Given the increasing importance of precision medicine in SCLC, optimal subtyping of SCLC using multi-omics have gradually applied into clinical practice, which may identify more drug targets and better tailor treatment strategies to each individual patient. The present review summarizes recent progress and future directions in SCLC. In addition to the emerging new therapeutics, we also focus on the establishment of predictive model for early detection of SCLC. More importantly, we also propose a multi-dimensional model in the prognosis of SCLC to ultimately attain the goal of accurate treatment of SCLC.

Abstract Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live SARS-COV-2 infection, S-BiTE treated mice showed significantly less viral load than neutralization only treated group. The S-BiTE strategy may have broad applications in combating other coronavirus infections.

ABSTRACT Purpose: Esophageal squamous cell carcinoma (ESCC) is characterized by early metastasis and late diagnosis. miR-29c-3p is confirmed to repress angiogenesis in multiple tumor types. Yet, the functions of miR-29c-3p in the mechanism of ESCC angiogenesis, which were not sufficiently explored previously, were exactly what we investigated here at the molecular level. Methods: The mRNA level of miR-29c-3p and Serpin peptidase inhibitor clade H member 1 (SERPINH1) in ESCC tissues were assessed via bioinformatics analysis. Thereafter, miR-29c-3p and SERPINH1 (HSP47) mRNA level in ESCC cell lines was evaluated via quantitative real-time polymerase chain reaction. The effects of abnormal miR-29c-3p and SERPINH1 expression on ESCC cell viability, proliferation, migration, invasion, and HUVEC angiogenesis were examined via CCK8, colony formation, transwell, and angiogenesis assays, respectively. The protein levels of SERPINH1, vascular endothelial growth factor-A (VEGFA), Wnt-1, ?-catenin, and p-?-catenin were evaluated via Western blot. Expression of VEGFA secreted by ESCC cells was measured via enzyme-linked immunosorbent assay. Treatment with the Wnt activator BML-284 further revealed the way miR-29c-3p mediated the Wnt signaling pathway and its effects on angiogenesis. Results: Herein, we revealed a decrease of miR-29c-3p expression in ESCC tissues and cells, while the overexpressed miR-29c-3p could remarkably suppress ESCC cell progression, as well as HUVEC angiogenesis. Meanwhile, overexpressed miR-29c-3p notably downregulated VEGFA and repressed the Wnt signaling pathway. Treatment with the Wnt activator BML-284 could reverse the inhibition of HUVEC angiogenesis caused by miR-29c-3p. SERPINH1 was a downstream target of miR-29c-3p. SERPINH1 knockdown suppressed the malignant phenotypes of ESCC cells and impeded the Wnt signaling activation, while such suppression was reversed through miR-29c-3p inhibitor. Conclusions: We confirmed the mechanism that miR-29c-3p targeted SERPINH1, thus regulating angiogenesis in ESCC through the Wnt signaling pathway. It improves the understanding of angiogenesis in ESCC and offers new ideas for the research of ESCC treatment strategies in the future.

Abstract Immunotherapy has greatly improved outcomes for patients with advanced melanoma, but good predictive biomarkers remain lacking in clinical practice. Although increasing evidence has revealed a vital role of pyroptosis in the tumor microenvironment (TME), it remains unclear for pyroptosis as a predictive biomarker for immunotherapy in melanoma. RNA sequencing data and annotated clinical information of melanoma patients were obtained from four published immunotherapy datasets. LASSO regression analysis was conducted to develop a pyroptosis‐based model for quantifying a pyroptosis score in each tumor. Based on four clinical cohorts, we evaluated the predictive capability of the model using multiple immunotherapeutic outcomes, including clinical benefits, overall survival (OS), and progression‐free survival (PFS). Furthermore, we depicted the distinctive TME features associated with pyroptosis. Compared with the group with low pyroptosis scores, the group with high pyroptosis scores consistently achieved better durable clinical benefits in four independent cohorts and the meta‐cohort. ROC analysis validated that the pyroptosis‐based model was a reliable biomarker for predicting clinical benefits from immunotherapy in melanoma. Survival analyses showed that the group with high pyroptosis scores harbored more favorable OS and PFS than those with low pyroptosis scores. Molecular analysis revealed that tumors with high pyroptosis scores displayed a typical immune‐inflamed phenotype in TME, including enrichment of immunostimulatory pathways, increased level of tumor‐infiltrating lymphocytes, upregulation of immune effectors, and activation of the antitumor immune response. Our findings suggested that the pyroptosis‐related model associated with multiple immune‐inflamed characteristics might be a reliable tool for predicting clinical benefit and survival outcomes from immunotherapy in melanoma.

JPEG Reversible Data Hiding (RDH) is a method designed to extract hidden data from a marked image and perfectly restore the image to its original JPEG form. However, while existing RDH methods adaptively manage the visual distortion caused by embedded data, they often neglect the concurrent increase in file size. In rectifying this oversight, we have designed a new JPEG RDH scheme that addresses all influential metrics during the embedding phase and a dynamic frequency selection strategy with recoverable frequency order after data embedding. The process initiates with a pre-processing phase of blocks and the subsequent selection of frequencies. Utilizing a two-dimensional (2D) mapping strategy, we then compute the visual distortion and file size increment (FSI) for each image block by examining non-zero alternating current (AC) coefficient pairs (NZACPs) and their corresponding run lengths. Finally, we select appropriate block groups based on the influential metrics of each block group and proceed with data embedding by 2D histogram shifting (HS). Extensive experimentation demonstrates how our method’s efficiently and consistently outperformed existing techniques with a superior peak signal-to-noise Ratio (PSNR) and optimized FSI.

Abstract The majority of patients with human epidermal growth factor receptor 2 (Her2)‐positive gastric cancer develop refractory to Her2‐targeted therapy, where upregulation of immune checkpoints plays an essential role. Herein, a recombinant fully human IgG1 bispecific antibody IBI315 targeting both PD‐1 and Her2 is developed and its antitumor efficacy as well as the underlying mechanism is investigated. IBI315 crosslinks the physical interaction between Her2‐positive tumor cells and PD‐1‐positive T cells, resulting in significantly enhanced antitumor effects compared to each parent antibody or their combination, both in vitro and in vivo mouse tumor models reconstituted with human immune cells using patient‐derived xenografts and organoids. Moreover, IBI315 treatment also induces the recruitment and activation of immune cells in tumors. Mechanistically, IBI315 triggers gasdermin B (GSDMB)‐mediated pyroptosis in tumor cells, leading to the activation and recruiments of T cells. The activated T cells secret IFNγ, enhancing GSDMB expression and establishing a positive feedback loop of T cell activation and tumor cell killing. Notably, GSDMB is found to be elevated in Her2‐positive gastric cancer cells, providing a rationale for IBI315's efficacy. IBI315 is supported here as a promising bispecific antibody‐based immunotherapy approach for Her2‐positive gastric cancer in preclinical studies, broadening the therapeutic landscape of this patient population.

Abstract Background The aim of the study was to investigate predictive value of gene mutation for atezolizumab treatment response from OAK and POPLAR cohorts. Methods Several public databases were used for analyzing gene mutation type of EPHA5 and association with alterations of other genes. Survival analysis was performed for patients receiving atezolizumab from OAK and POPLAR cohorts. Results EPHA5 mutation have high frequency to harbor TP53 and KEAP1 mutations. The bTMB value has significant difference between EPHA5 mutant and wild-type cases. Patients with EPHA5 mutation got worse survival compared to those without gene mutations receiving atezolizumab (P = 0.0186). Conclusions EPHA5 mutant NSCLC may represent a subpopulation which showed worse response after treatment of atezolizumab compared to wild-type ones.

Immunotherapy is a type of treatment that uses our own immune system to fight cancer. Studies have shown that traditional Chinese medicine (TCM) has antitumor activity and can enhance host immunity. This article briefly describes the immunomodulatory and escape mechanisms in tumors, as well as highlights and summarizes the antitumor immunomodulatory activities of some representative active ingredients of TCM. Finally, this article puts forward some opinions on the future research and clinical application of TCM, aiming to promote the clinical applications of TCM in tumor immunotherapy and to provide new ideas for the research of tumor immunotherapy using TCM.

Nowadays, 2-methylfuran is urgently needed especially in pharmaceutical manufacture. However, the direct synthesis of 2-methylfuran via the efficient dehydration and hydrogenation of xylose usually requires a multistep reaction. Herein, a route of tandem conversion xylose to 2-methylfuran was developed. The xylose was firstly converted into furfural by Hβ zeolite, followed by the catalysis of furfural to 2-methylfuran over 0.5NiCu/C. Compared with two-step reaction, cascade strategy applied xylose conversion improved the 2-methylfuran yield rate by 41.5%. In general, this work expanded the application of tandem method for the enhancement of xylose effective conversion and provided a new biomass utilization technology.

Abstract Background Constrictive pericarditis is more common in adults and has a low incidence in children. Here is a case of coxsackie virus induced myocarditis in children, resulting in constrictive pericarditis. Conclusion Chronic inflammation of viral myocarditis can cause inflammatory changes of pericarditis and cause constrictive pericarditis.

Abstract Background Immune checkpoint inhibitors (ICIs) have shown numerous clinical benefits in multiple cancer types, but good predictive biomarkers are severely lacking. Although increasing evidence has linked Hedgehog (Hh) signaling pathway with tumor development, a systematic investigation for its potential as a biomarker remains elusive. Methods We collected and analyzed the transcriptional data and clinical outcomes of diverse cancers from the Cancer Genome Atlas and four published ICI datasets. Hh activity was estimated by conducting a single‐sample gene‐set enrichment analysis (ssGSEA) for the Hh‐related genes and calculating the ssGSEA score in each tumor sample. Results Our findings suggest that tumors with high Hh activity displayed multiple immunosuppressive characteristics, including lack of anti‐tumor response pathways, downregulation of immune effectors, enrichment of immunosuppressive cells and chemokines, and activation of immunosuppressive signaling. Notably, patients in the non‐response group had enriched Hh activity and showed worse overall survival (OS; pooled HR = 1.50, 95% CI = 1.02–2.21, p = 0.039). In the subgroup of high programmed cell death ligand 1 (PD‐L1) expression, patients who harbored high Hh activity displayed a dramatically lower response rate to ICIs and a strikingly worse OS (pooled HR = 2.89, 95% CI = 1.53–5.49, p

Abstract Cancer immunotherapy has made remarkable progress in the past decade. Bispecific antibodies (BsAbs) have acquired much attention as the next generation strategy of antibody-target cancer immunotherapy, which overwhelmingly focus on T cell recruitment and dual receptors blockade. So far, BsAb drugs have been proved clinically effective and approved for the treatment of hematologic malignancies, but no BsAb have been approved in solid tumors. Numerous designed BsAb drugs for solid tumors are now undergoing evaluation in clinical trials. In this review, we will introduce the formats of bispecific antibodies, and then update the latest preclinical studies and clinical trials in solid tumors of BsAbs targeting EpCAM, CEA, PMSA, ErbB family, and so on. Finally, we discuss the BsAb-related adverse effects and the alternative strategy for future study.

BackgroundAs a rare subtype of primary lung adenocarcinoma (LUAD), mucinous pulmonary adenocarcinoma (MPA) was considered a distinctive entity with unfavorable outcomes. Therefore, there is a great need for a better understanding of the genomic and immunological landscape of this rare tumor type, which would inform improved therapeutic strategies.MethodsA total of 96 patients histologically confirmed with MPA were recruited from Shandong Cancer Hospital and Institute (SCH). Single nucleotide variation (SNV), copy number variation (CNV), genomic instability, and immunological landscape insights into 96 MPA patients were identified using WES.ResultsWe demonstrated that MPAs had marked different genomic alterations and were more complex in genomic profiles than LUADs. Mutations in Tumor Protein 53 (TP53) and CYP7A Promoter-Binding Factor (CPF) pathways significantly shortened survival whereas mutations in Notch and Wnt pathways significantly prolonged survival in MPA. Besides, we demonstrated that mutations in immune-related genes influenced outcomes, with mutations in TP53, Ataxia Telangiectasia Mutated (ATM), Polymerase (DNA) Delta 1 (POLD1), and Epidermal Growth Factor Receptor (EGFR) correlated with worsened survival.ConclusionsWe not only depicted the genetic and immunologic landscape of Chinese MPA but also reveal its distinction from LUAD in genomic and immune context. Our findings may provide opportunities for therapeutic susceptibility among Chinese MPA patients.

Metalloproteinases (MPs) is a large family of proteinases with metal ions in their active centers. According to the different domains metalloproteinases can be divided into a variety of subtypes mainly including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteases (ADAMs) and ADAMs with Thrombospondin Motifs (ADAMTS). They have various functions such as protein hydrolysis, cell adhesion and remodeling of extracellular matrix. Metalloproteinases expressed in multiple types of cancers and participate in many pathological processes involving tumor genesis and development, invasion and metastasis by regulating signal transduction and tumor microenvironment. In this review, based on the current research progress, we summarized the structure of MPs, their expression and especially immunomodulatory role and mechanisms in cancers. Additionally, a relevant and timely update of recent advances and future directions were provided for the diagnosis and immunotherapy targeting MPs in cancers.

Gastric cancer (GC) is one of the main causes of cancer incidence rate and mortality worldwide. As the main breakthrough direction, the application of immune checkpoint inhibitors makes patients with GC have better prognosis, where PD-L1/PD-1 inhibitors in immunotherapy have good anti-tumor immune efficacy. Further understanding of the regulatory mechanism of PD-L1 in GC may bring substantial progress to the immunotherapy. In this review, we provide information on the endogenous and exogenous regulatory mechanisms of PD-L1 and its biological functions combined with current clinical trials of PD-L1/PD-1 inhibitors in GC. The malignant biological phenotypes caused by PD-L1 and the corresponding clinical combined treatment scheme have been reported. Identifying the biomarkers of the potential efficacy of immunotherapy and specifying the clinical immunotherapy scheme in combination with molecular characteristics of patients may maximize clinical benefits and better prognosis.

BackgroundPatient-derived xenograft (PDX) models have shown a great efficiency in preclinical and translational applications. Gastrointestinal (GI) tumors have a strong heterogeneity, and the engraftment rate of PDX models remarkably vary. However, the clinicopathological and molecular characteristics affecting the engraftment rate still remain elusive.MethodsA total of 312 fresh tumor tissue samples from patients with GI cancer were implanted into immunodeficient mice. The median follow-up time of patients was 37 months. Patients’ characteristics were compared in terms of PDX growth and overall survival. PDX models of 3-6 generations were used for drug evaluation.ResultsIn total, 171 (54.8%, 171/312) PDX models were established, including 85 PDX models of colorectal cancer, 21 PDX models of esophageal cancer, and 65 PDX models of gastric cancer. Other than tumor site, histology, differentiation degree, and serum alpha-fetoprotein (AFP) level, no significant differences were found between transplantation of xenografts and patients’ characteristics. For patients who had undergone neoadjuvant therapy, the incidence of tumor formation was higher in those with progressive disease (PD) or stable disease (SD). In gastric cancer, the results showed a higher transplantation rate in deficient mismatch repair (dMMR) tumors, and Ki-67 could be an important factor affecting the engraftment rate. The gene mutation status of RAS and BRAF, two important molecular markers in colorectal cancer, showed a high degree of consistency between patients’ tumors and PDXs. However, no significant effects of these two mutations on PDX engraftment rate were observed. More importantly, in this study although KRAS mutations were detected in two clinical cases, evident tumor inhibition was still observed after cetuximab treatment in both PDX models and patients.ConclusionA large-scale PDX model including 171 cases was successfully established for GI tumors in our center. The relationship between clinicopathological and molecular features and engraftment rates were clarified. Furthermore, this resource provides us with profound insights into tumor heterogeneity, making these models valuable for PDX-guided treatment decisions, and offering the PDX model as a great tool for personalized treatment and translation research.

ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.

BackgroundThe clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC.MethodsAmong 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis.ResultsBorrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis.ConclusionsBorrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.

Abstract Objective A nomogram model based on clinical variables was conducted to predict the survival in patients with non‐small cell lung cancer (NSCLC) receiving second‐line atezolizumab. Methods Four hundred and twenty‐four patients with NSCLC receiving atezolizumab from OAK study were regarded as the training cohort. Next, a nomogram model based on clinical variables in the training cohort was established to predict the survival of patients receiving atezolizumab. The concordance index, area under curve (AUC), and calibration plots were used to assess the performance of the nomogram model. In addition, 144 patients with NSCLC receiving atezolizumab from POPLAR study were regarded as the test cohort to validate the nomogram model. Using Kaplan–Meier and log‐rank test, we compared the survival difference between the high‐ and low‐risk groups, atezolizumab and docetaxel treatment groups, respectively. Results We successfully constructed a nomogram model based on different variable scores for predicting the survival in NSCLC patients receiving atezolizumab using the training cohort. According to risk score, patients receiving atezolizumab were divided into the high‐ and low‐risk groups. Importantly, in the training cohort, patients had worse overall survival (OS) in high‐risk group compared with the low‐risk group (median survival: 252.3 vs. 556.9 days; p

In order to obtain the chemical composition characteristics and source apportionment of PM2.5 in a western industrial region of Jinan, manual sampling and analysis of PM2.5 in Pingyin County was conducted during 2019. The results showed that the total concentration of 29 species of PM2.5 was 53.8 μg·m−3. The NO3− concentration (14.6 ± 14.2 μg·m−3) was the highest, followed by OC (9.3 ± 5.5 μg·m−3), SO42− (9.1 ± 6.4 μg·m−3) and NH4+ (8.1 ± 6.8 μg·m−3). Concentrations of OC, NO3− and SO42− were highest in winter and lowest in summer. The concentration of NH4+ was highest in winter and lowest in spring. The annual SOR and NOR were 0.30 ± 0.14 and 0.21 ± 0.12, respectively. SO2 emission and conversion ratio was highest in winter, leading to the highest SO42− concentration. SO2 emission in summer was low, but the conversion ratio was high. NOR in winter and autumn were close and higher than spring and summer. The high NOR in autumn caused a higher NO3− concentration compared with that in spring and summer. The average concentration of SOC during 2019 was 2.8 ± 1.9 μg·m−3, accounting for 30% of OC. The PMF results showed that coal emission accounted for 36.5% of PM2.5 concentration, followed by mobile sources (32.6%), industry emission (17.4%), dust emission (7.1%) and other emissions (6.4%).

The emergence of the novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the pandemic of coronavirus disease 2019 (COVID-19), which has markedly affected global health and the economy. Both uncontrolled viral replication and a proinflammatory cytokine storm can cause severe tissue damage in patients with COVID-19. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as its entry receptor. In this study, we generated ACE2 extracellular domain-Fc and single-chain variable fragment-interleukin 6 (IL-6) single-chain variable fragment against IL-6 receptor (scFv-IL6R)-Fc fusion proteins to differentially neutralize viruses and ameliorate the cytokine storm. The human ACE2 (hACE2)1−740-Fc fusion protein showed a potent inhibitory effect on pseudo-typed SARS-CoV-2 entry and a good safety profile in mice. In addition, scFv-IL6R-Fc strongly blocked IL-6 signal activation. We also established a mesenchymal stromal cell (MSC)-based hACE21−740-Fc and scFv-IL6R-Fc delivery system, which could serve as a potential therapy strategy for urgent clinical needs of patients with COVID-19.

Alpha-fetoprotein producing gastric carcinomas (AFPGC) are rare and aggressive. Here, the authors profile AFPGC tumours using whole exome sequencing, and find amplifications in CCNE1 and ERBB2 that are associated with poor outcomes but are potential therapeutic targets, as shown in patient-derived xenografts.

Abstract Background The prognosis of patients with small cell lung cancer (SCLC) is poor, most of them are in the extensive stage at the time of diagnosis, and are prone to brain metastasis. In this study, we established a nomogram combined with some clinical parameters to predict the survival of SCLC patients with brain metastasis. Methods The 3522 eligible patients selected from the SEER database between 2010 and 2015 were randomly divided into training cohort and validation cohort. Univariate and multivariate Cox regression analysis were used to evaluate the ability of each parameter to predict OS. The regression coefficients obtained in multivariate analysis were visualized in the form of nomogram, thus a new nomogram and risk classification system were established. The calibration curves were used to verify the model. And ROC curves were used to evaluate the discrimination ability of the newly constructed nomogram. Survival curves were made by Kaplan-Meier method and compared by Log rank test. Results Univariate and multivariate analysis showed that age, race, sex, T stage, N stage and marital status were independent prognostic factors and were included in the predictive model. The calibration curves showed that the predicted value of the 1- and 3-year survival rate by the nomogram was in good agreement with the actual observed value of the 1- and 3-year survival rate. And, the ROC curves implied the good discrimination ability of the predictive model. In addition, the results showed that in the total cohort, training cohort, and validation cohort, the prognosis of the low-risk group was better than that of the high-risk group. Conclusions We established a nomogram and a corresponding risk classification system to predict OS in SCLC patients with brain metastasis. This model could help clinicians make clinical decisions and stratify treatment for patients.

The poor survival rate of small cell lung cancer (SCLC) is mainly related to the condition that patients with SCLC often have good responses to first-line chemotherapy initially, but later on, most of these patients relapse rapidly due to resistance to further treatment. In this study, we attempted to analyze whole-exome sequencing data based on the largest sample size to date, to develop a classifier to predict whether a patient will be chemorefractory or chemosensitive and to explicate the risk of recurrence that affects the prognosis of patients. We showed the different characteristics of somatic mutational signatures, somatic mutation genes, and distinct genome instability between chemorefractory and chemosensitive SCLC patients. Amplified mutations in the chemosensitive group inhibited the regulation of the cell cycle process, transcription factor binding, and B-cell differentiation. Analysis of deletion mutation also suggested that detection of the chromosomal-level variation might influence our treatment decisions. Higher PD-L1 expressions (based on TPS methods) were mostly present among chemosensitive patients (p = 0.026), while there were no differences in PD-L1 expressions (based on CPS methods) and CD8+ TILs between the two groups. According to the model determined by logistic regression, each sample was endowed with a predictive probability value (PV). The samples were divided into a high-risk group (>0.55) and a low-risk group (≤0.55), and the survival analysis showed obvious differences between the two groups. This study provides a reference basis to translate this knowledge into practice, such as formulating personalized treatment plans, which may benefit Chinese patients with SCLC.

The formation of dark-colored solids, as known as humins, was observed during acid-catalyzed dehydration of certain biomass platform molecules like fructose, glucose and 5-hydroxymethylfurfural (HMF). Humins structures were found to be precipitated as microspheres in the liquid phase and/or on the surfaces of solid catalyst and reactor walls. Humins formation begins with random and uncontrollable condensation of key intermediate molecules, namely, glucose, HMF, 1,2,4-Trihydroxybenzene (TB), 2,5-dioxo-6-hydroxyhexanal (DHH), etc. Further, mechanism network of humins formation also contains polymerization of soluble oligomers, growth of primary particles, physical absorption to soluble molecules and aggregation of particle groups. Humins formation retards the economy, safety and efficiency of cellulosic carbon conversion including wasting the substrates, blocking the reactor, causing deactivation of catalyst and absorbing the high-value molecules products. This necessitates the systematic elucidation of humins, including its formation mechanism network, characterization techniques and high-value utilization. This review organized significant studies of humins formation, including (i) background information of humins during different conversion process, (ii) different analytical techniques for humins characterization, (iii) the properties and formation mechanism of humins, (iv) prevention methods of humins formation and (v) exploration of high-value humins utilization.

A reverse-blocking AlGaN/GaN metal-insulator-semiconductor high electron mobility transistor (RB-MISHEMT) is proposed and fabricated. Compared with the conventional MISHEMT with ohmic drain, the proposed device features a hybrid Schottky-ohmic drain with a low work function Tungsten (W), based on which the state-of-the-art ultralow turn-on voltage ( ${V} _{\mathrm{ on}}$ ) of 0.25 V could be realized without degradation in on-state characteristics. In addition, the fabricated RB-MISHEMT exhibits the excellent reverse blocking voltage of −1332 V (at ${V} _{\mathrm{ GS}}= 0$ V) and forward blocking voltage of 1315 V (at ${V} _{\mathrm{ GS}} = -15$ V) with a specific on-resistance ( ${R} _{\mathrm{ on,sp}}$ ) of 3.5 $\text{m}\Omega $ cm2, leading in the highest power figure-of-merit (FOM) of > 494 MW/cm2. The good thermal stability could also be observed in fabricated RB-MISHEMT. The corresponding operation mechanism of RB-MISHEMT are also revealed by Silvaco ATLAS simulations. These results demonstrate the great potential in power electronics applications.

Response characteristics of key strata during the periodic weighting process in Dongjiahe coal mine were investigated using micro-seismic (MS) monitoring. Fracture types of key strata were identified through the moment tensor inversion. Finally, fracture mechanism of roof key strata was revealed from a microscopic viewpoint. The results show that there are three concentrations of MS events distributed along the dip direction. And two MS event clusters were formed in “pairs” before and behind the working face. Along the strike direction, tensile and shear factures occur in front of the working face with a dip angle of 54°, while the micro-fractures are mainly mixed and partial shear types behind the working face. By contrast, the rock fracture usually occurs behind the working face along the dip direction. The micro-fractures are mainly tensile and mixed types before fracturing compared to mainly mixed and shear fractures with slight tensile ones after fracturing. The fracture pattern basically conforms to the “O-X” type. The X-shaped fracture extends outward with an angle of 46° with the due north. The findings in this paper provide a theoretical reference for strata behaviours and hazard risk assessment under similar conditions.

Abstract Background PD-L1 inhibitors is widely applied in lung adenocarcinoma patients. Tumor cells with high PD-L1 expression could trigger immune evasion. Cancer stem cells (CSCs) can evade from immunesurveillance due to their immunomodulating effects. However, the correlation between CSC and PD-L1 and some immune-related markers is seldom reported in patients with lung adenocarcinoma. Therefore, we aimed to ascertain their association in lung adenocarcinoma patients. Methods We assessed CD44 expression and its association with PD-L1 in lung adenocarcinoma, using Tumor Immune Estimation Resource (TIMER), which was further validated in our patient cohort. The immune cells infiltration was depicted by CIBERSORT using GEO database. The correlation between CD44 and immune cells was also analyzed. We further evaluated the prognostic role of CD44 in patients with lung adenocarcinoma both using Kaplan–Meier plotter and validated in our patient cohort. Results Positive association between CD44 and PD-L1 were found in lung adenocarcinoma patients. T cells CD4 memory resting cells and mast cells resting cells varied significantly between patients with CD44 high and those with CD44 low. Furthermore, positive association could be found between CD44 expression and immune cells. Arm-level depletion of CD44 was linked with B cell, CD4+ T cell, neutrophil and dendritic cell infiltration. Patients with higher CD44 levels had worsened overall survival (OS). Conclusions In summary, these results demonstrate that CD44 was associated with PD-L1 and infiltration of immune cells, and was a negative prognostic factor for predicting worsened OS in lung adenocarcinoma.

Abstract Several biomarkers such as tumor mutation burden (TMB), neoantigen load (NAL), programmed cell‐death receptor 1 ligand (PD‐L1) expression, and lactate dehydrogenase (LDH) have been developed for predicting response to immune checkpoint inhibitors (ICIs) in melanoma. However, some limitations including the undefined cut‐off value, poor uniformity of test platform, and weak reliability of prediction have restricted the broad application in clinical practice. In order to identify a clinically actionable biomarker and explore an effective strategy for prediction, we developed a genetic mutation model named as immunotherapy score (ITS) for predicting response to ICIs therapy in melanoma, based on whole‐exome sequencing data from previous studies. We observed that patients with high ITS had better durable clinical benefit and survival outcomes than patients with low ITS in three independent cohorts, as well as in the meta‐cohort. Notably, the prediction capability of ITS was more robust than that of TMB. Remarkably, ITS was not only an independent predictor of ICIs therapy, but also combined with TMB or LDH to better predict response to ICIs than any single biomarker. Moreover, patients with high ITS harbored the immunotherapy‐sensitive characteristics including high TMB and NAL, ultraviolet light damage, impaired DNA damage repair pathway, arrested cell cycle signaling, and frequent mutations in NF1 and SERPINB3/4. Overall, these findings deserve prospective investigation in the future and may help guide clinical decisions on ICIs therapy for patients with melanoma.

JMJD6 is a member of the Jumonji (JMJC) domain family of histone demethylases that contributes to catalyzing the demethylation of H3R2me2 and/or H4R3me2 and regulating the expression of specific genes. JMJD6-mediated demethylation modifications are involved in the regulation of transcription, chromatin structure, epigenetics, and genome integrity. The abnormal expression of JMJD6 is associated with the occurrence and development of a variety of tumors, including breast carcinoma, lung carcinoma, colon carcinoma, glioma, prostate carcinoma, melanoma, liver carcinoma, etc. Besides, JMJD6 regulates the innate immune response and affects many biological functions, as well as may play key roles in the regulation of immune response in tumors. Given the importance of epigenetic function in tumors, targeting JMJD6 gene by modulating the role of immune components in tumorigenesis and its development will contribute to the development of a promising strategy for cancer therapy. In this article, we introduce the structure and biological activities of JMJD6, followed by summarizing its roles in tumorigenesis and tumor development. Importantly, we highlight the potential functions of JMJD6 in the regulation of tumor immune response, as well as the development of JMJD6 targeted small-molecule inhibitors for cancer therapy.

Immune checkpoint inhibitors have greatly improved the prognoses of diverse advanced malignancies, including gastric and gastroesophageal junction (G/GEJ) cancer. However, the role of anti-programmed cell death protein-1 treatment in the neoadjuvant setting remains unclear. This phase 2 study aimed to evaluate sintilimab plus CapeOx as a neoadjuvant regimen in patients with advanced resectable G/GEJ adenocarcinoma. Eligible patients with resectable G/GEJ adenocarcinoma stage cT3-4NanyM0 were enrolled. Patients received neoadjuvant treatment with sintilimab (3 mg/kg for cases 1 patient) grade 3 treatment-related adverse events during neoadjuvant treatment were anemia and neutropenia (n=5 each, 13.9%). No serious adverse events (AEs) or grade 4–5 AEs were observed. Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with encouraging pCR rate and good safety profile in the neoadjuvant setting. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ adenocarcinoma. Trial registration; NCT04065282.

Here, we report two cases of advanced non‐small cell lung cancer (NSCLC) in patients with negative driver genes who received ICI treatment for less than two years but continued to benefit from their administration after drug withdrawal. The first patient was diagnosed with left lung adenocarcinoma, cT1cN3M1c, stage IVb, and after four cycles achieved a completed response (CR). After 10 cycles of camrelizumab treatment, immunotherapy was discontinued because of hepatotoxicity. When the drug was discontinued, the curative effect was evaluated as CR. At the last follow‐up, the drug withdrawal time had been more than 20 months, and the response was maintained at CR, with PFS of over 30 months. In the second case, the patient was diagnosed with left lung adenocarcinoma, cT1N3M1c, stage IVb. The patient was treated with sintilimab, and due to cardiac and skin toxicity, the patient withdrew from the trial after five cycles of immunotherapy. After drug withdrawal, the curative effect of the patients was maintained at PR. At the last follow‐up, the drug withdrawal time was more than three months, and the curative effect was evaluated as PR. The PFS was more than nine months. In conclusion, whether the drug can be discontinued in advance after immune checkpoint inhibitor (ICI) therapy has been effective remains a concern, and at present there is no final conclusion in the medical profession. However, the results of this study indicate that early withdrawal of immunotherapy due to adverse reactions might also benefit patients with advanced lung adenocarcinoma with negative driver genes who achieve an early response to immunotherapy.

Abstract Immune checkpoint inhibitors (ICIs) have recently changed therapeutic paradigms for patients across multiple cancer types. However, current biomarkers cannot accurately predict responses to ICIs. Telomerase reverse transcriptase (TERT) mutations lead to an aberrant upregulation of TERT expression, and ultimately allow telomere maintenance, thus supporting immortalization of cancer cells. This study aimed to investigate whether the TERT mutation is a potential predictor of ICI treatment across all cancer types. TERT mutations positively correlated with a higher tumor mutational burden (TMB) value, neoantigen load, and tumor purity. Lymphocyte infiltration, macrophage regulation, interferon‐gamma (IFN‐γ) response, and transforming growth factor‐β (TGF‐β) response which was representative immune‐expression signatures, all had higher signature scores in the TERT mutation group. Activated CD4 T cell, naïve B cell, activated dendritic cell, M0 macrophage, M1 macrophage, neutrophil, resting NK cell, and plasma cells all had relatively higher immune scores in the TERT mutation group, whereas Th series cells, memory B cell, resting mast cells, monocytes, and activated NK cells had lower immune scores. Notably, in the subgroup analysis of monotherapy and combination ICI treatment, only in the anti‐cytotoxic‐T‐lymphocyte‐associated antigen 4 (anti‐CTLA4) group, patients with TERT mutations had a better prognosis, especially for melanoma. Therefore, TERT mutations were closely related to a higher TMB value and unique tumor microenvironment, which may be the reason that TERT mutations may be a potential biomarker for anti‐CTLA4 treatment.

Lung adenocarcinomas (LUADs) harbouring epidermal growth factor receptor (EGFR) mutations are generally unable to benefit from immune checkpoint inhibitors (ICIs) due to an immunosuppressive tumour microenvironment (TME) and a lower tumour mutation burden. Currently, no gene signature can comprehensively evaluate the TME and predict the prognosis of patients with EGFR-mutant LUAD. Using the Cancer Genome Atlas database of EGFR-mutant LUAD based on the immune score derived from the ESTIMATE algorithm, we divided 80 patients with EGFR-mutant LUAD samples into high and low immune score groups with different immune microenvironments. Subsequently, we screened 396 differentially expressed immune-related genes with prognostic value. The top Gene Ontology terms were significantly enriched in biological functions related to T cell differentiation, immune response, cell cycle, and cell proliferation, which are closely related to the immune microenvironment of tumours. In addition, the KEGG pathway enrichment analysis mainly focused on cell cycle, cell adhesion molecules, and cytokine-cytokine receptor interaction, which also had a relationship with the immune response. Subsequently, we identified a three-gene signature including BTLA, BUB1B, and CENPE using the LASSO Cox regression model. The three-gene signature could accurately identify patients at risk of EGFR-mutant LUAD in the training and validation sets and high-risk patients from both the sets exhibited significantly shorter overall survival (p=0.0053 and p=0.035, respectively). CIBERSORT was used to evaluate the abundance of immune cell infiltration in the EGFR-mutant LUAD microenvironment. The immune activity of B cells and macrophages was higher in the low-risk group, while the immune activity of natural killer cells and T cells was higher in the high-risk group. Thus, the three-gene signature closely related to immunosuppressive TME could predict the risk and prognosis in patients with EGFR-mutant LUAD.

BackgroundAt present, there is a lack of studies focusing on the survival prediction of patients with non-small cell lung cancer (NSCLC) receiving atezolizumab in light of gene mutation characteristic.MethodsPatients with NSCLC receiving atezolizumab from the OAK study were defined as the training group. LASSO Cox regressions were applied to establish the gene mutation signature model to predict the overall survival (OS) rate of the training group. NSCLC patients receiving atezolizumab from the POPLAR study were defined as the testing group to validate the gene mutation signature model. In addition, we compared the OS rate between patients receiving atezolizumab and docetaxel classified according to their risk score based on our gene mutation signature model.ResultsWe successfully established a 5-genomic mutation signature that included CREBBP, KEAP1, RAF1, STK11 and TP53 mutations. We found it was superior to the blood tumor mutation burden (bTMB) score and programmed death ligand 1 (PDL1) expression in the prediction of the OS rate for patients receiving atezolizumab. High-risk patients receiving atezolizumab had a worse OS rate compared with low-risk patients in the training (P = 0.0004) and testing (P = 0.0001) groups. In addition, low-risk patients using atezolizumab had a better OS rate compared with those in use of docetaxel for the training (P

Gastric cancer (GC) is one of the most prevalent digestive malignancies. A great number of patients at first visit or post curative resections are diagnosed with widespread metastasis within the peritoneal cavity. Overwhelming evidence has demonstrated that exosomes, a variety of biologically functional extracellular vesicles comprising active factors, mediate the progression and metastasis of GC. Although the regulatory mechanisms of exosomes remain fairly elusive, they are responsible for intercellular communication between tumor cells and normal stroma, cancer-related fibroblasts, immune cells within the primary tumor and metastatic niche. In this review, we provide new insight into the molecular signatures of GC-associated exosomes in reprogramming the tumor microenvironment and the subsequent promotion of peritoneal metastasis—including infiltration of the gastric wall, implantation of tumor cells onto the pre-metastatic peritoneum, and remodeling of the pre-metastatic niche. Based on this review, we hope to draw a more general conclusion for the functions of exosomes in the progression and peritoneal metastasis of GC and highlight the future perspective on strategies targeting exosomes in prognostic biomarkers and therapy for peritoneal metastasis.

Abstract Background This study aimed to evaluate the feasibility and prognostic accuracy of incorporating the number of positive lymph nodes (PLN) into the TNM staging system for non-small cell lung cancer (NSCLC) patients. Methods We screened a total of 9539 patients with resected stage IA-IIIB non-small cell cancer between 2010 and 2015 from SEER database. The chi-square test was used to compare patient baseline characteristics and the X-tile model was applied to determine cut-off values for the number of PLN (nN). The X-tile model was used to screen three different cut-off values including nN = 0, nN1–3 and nN4-. Univariate and multivariate Cox proportional hazards regression models were used to analyze the influence of different variables on overall survival (OS). Kaplan-Meier and log-rank test were used to compare survival differences. Results Based on the nN cutoffs, we conducted the univariate and multivariate Cox proportional hazards regression. The result showed that nN stage was a significant prognostic factor affecting patients' OS (all P