Search

Abstract A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57–0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring.

Abstract Triplophysa bombifrons, a species of bony fish localized in China, has largely been understudied genetically, with limited data available beyond its mitochondrial genome. This study introduces a chromosome-level genome assembly for T. bombifrons, achieved through the integration of PacBio long-read sequencing and Hi-C chromatin interaction mapping. The assembly reveals a genome structure comprising 25 chromosomes and an overall size of 655.95 Mb. The quality of this assembly is demonstrated by a scaffold N50 length of 24.25 Mb, and a genome completeness evaluation via BUSCO, which shows that 97.4% of the Vertebrata Benchmarking Universal Single-Copy Orthologs are present. Gene prediction methods including de novo, homology-based, and transcript-based, identified 34,211 genes, with 34,151 being functionally annotated. These findings may provide valuable resources in conservation, functional genomics, and molecular breeding of T. bombifrons, as well as the molecular phylogenetics and evolutionary patterns in Triplophysa.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Background Overcoming resistance to Osimertinib in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is clinically challenging because the underlying mechanisms are not fully understood. The murine double minute 2 (MDM2) has been extensively described as a tumor promotor in various malignancies, mainly through a negative regulatory machinery on the p53 tumor suppressor. However, the significance of MDM2 on the sensitivity to Osimertinib has not been described. Methods Osimertinib resistant cells were generated by standard dose escalation strategy and individual resistant clones were isolated for MDM2 testing. The MDM2 and its mutant constructs (ΔPBD, ΔRING, C464A) were introduced into PC-9, HCC827 and H1975 cells and evaluated for the sensitivity to Osimertinib by MTT assay, colony formation, EdU assay and TUNEL assay. MDM2 expression in resistant cells was manipulated by pharmacological and molecular approaches, respectively. Proteins that were implicated in PI3K/Akt, MAPK/Erk and apoptosis signaling were measured by Western blot analysis. Candidate proteins that interacted with MDM2 were captured by immunoprecipitation and probed with indicated antibodies. Results In comparison with parental PC-9 cells, the PC-9 OR resistant cells expressed high level of MDM2. Ectopic expression of MDM2 in PC-9, HCC827 and H1975 sensitive cells generated an Osimertinib resistant phenotype, regardless of p53 status. MDM2 promoted resistance to Osimertinib through a PI3K/Akt and MAPK/Erk-independent machinery, in contrast, MDM2 selectively stabilized MCL-1 protein to arrest Osimertinib-induced cancer cell apoptosis. Mechanistically, MDM2 acted as a E3 ligase to ubiquitinate FBW7, a well-established E3 ligase for MCL-1, at Lys412 residue, which resulted in FBW7 destruction and MCL-1 stabilization. Targeting MDM2 to augment MCL-1 protein breakdown overcame resistance to Osimertinib in vitro and in vivo. Finally, the clinical relevance of MDM2-FBW7-MCL-1 regulatory axis was validated in mouse xenograft tumor model and in NSCLC specimen. Conclusion Overexpression of MDM2 is a novel resistant mechanism to Osimertinib in EGFR mutant NSCLC. MDM2 utilizes its E3 ligase activity to provoke FBW7 destruction and sequentially leads to MCL-1 stabilization. Cancer cells with aberrant MDM2 state are refractory to apoptosis induction and elicit a resistant phenotype to Osimertinib. Therefore, targeting MDM2 would be a feasible approach to overcome resistance to Osimertinib in EGFR mutant NSCLC.

Succinylation represents an emerging class of post-translational modifications (PTMs), characterized by the enzymatic or non-enzymatic transfer of a negatively charged four-carbon succinyl group to the ϵ-amino group of lysine residues, mediated by succinyl-coenzyme A. Recent studies have highlighted the involvement of succinylation in various diseases, particularly cancer progression. Sirtuin 5 (SIRT5), a member of the sirtuin family, has been extensively studied for its robust desuccinylase activity, alongside its deacetylase function. To date, only a limited number of SIRT5 substrates have been identified. These substrates mediate diverse physiological processes such as glucose oxidation, fatty acid oxidation, ammonia detoxification, reactive oxygen species scavenging, anti-apoptosis, and inflammatory responses. The regulation of these activities can occur through either the same enzymatic activity acting on different substrates or distinct enzymatic activities targeting the same substrate. Aberrant expression of SIRT5 has been closely linked to tumorigenesis and disease progression; however, its role remains controversial. SIRT5 exhibits dual functionalities: it can promote tumor proliferation, metastasis, drug resistance, and metabolic reprogramming, thereby acting as an oncogene; conversely, it can also inhibit tumor cell growth and induce apoptosis, functioning as a tumor suppressor gene. This review aims to provide a comprehensive overview of the current research status of SIRT5. We discuss its structural characteristics and regulatory mechanisms, compare its functions with other sirtuin family members, and elucidate the mechanisms regulating SIRT5 activity. Specifically, we focus on the role of succinylation modification mediated by SIRT5 in tumor progression, highlighting how desuccinylation by SIRT5 modulates tumor development and delineating the underlying mechanisms involved.

The wall-associated kinase (WAK) gene family encodes functional cell wall-related proteins. These genes are widely presented in plants and serve as the receptors of plant cell membranes, which perceive the external environment changes and activate signaling pathways to participate in plant growth, development, defense, and stress response. However, the WAK gene family and the encoded proteins in soybean (Glycine max (L.) Merr) have not been systematically investigated. In this study, the soybean WAK genes (GmWAK) were identified based on genome-wide sequence information, the basic characteristics, chromosome location, gene replication, expression pattern, and responses to stress were comprehensively analyzed. A total of 74 GmWAK genes were identified and mapped to 19 different chromosomes in the soybean genome. Seventy-four GmWAK genes were divided into four groups, and GmWAK genes in the same group shared similar gene structures and conserved motifs. Thirty-seven duplicate pairs were identified in 74 GmWAK genes. Segmental duplication (SD) was critical in soybean WAK gene family expansion, and purification selection occurred during evolution. The promoter cis-element analysis displayed many hormone- and stress-related response elements in the promoter regions of GmWAK genes. GmWAK genes were diversely expressed in different organs and tissues, with most actively responding to cold, heat, salt, drought, and heavy metal stresses, suggesting that GmWAK genes could exhibit relevant roles in various bioprocesses.

Background Loss-of-function mutations of liver kinase B (LKB1, also termed as STK11 (serine/threonine kinase 11)) are frequently detected in patients with non-small cell lung cancer (NSCLC). The LKB1 mutant NSCLC was refractory to almost all the antitumor treatments, including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy. Unfortunately, mechanisms underlying resistance to immunotherapy are not fully understood. In this study, we deciphered how LKB1 regulated sensitivity to anti-PD-1/PD-L1 immunotherapy.Methods We investigated the mutational landscape of LKB1 mutant NSCLC in next generation sequencing (NGS) data sets. Expression of LKB1, PD-L1 and S-phase kinase-associated protein 2 (Skp2) in NSCLC samples were assessed by immunohistochemistry (IHC). The tumor microenvironment (TME) profiling of LKB1 wild type (WT) and mutant NSCLC was performed using fluorescent multiplex IHC. Mass spectrometry and enrichment analysis were used to identify LKB1 interacting proteins. Mechanistic pathways were explored by immunoblotting, ubiquitination assay, cycloheximide chase assay and immunoprecipitation assay.Results By using NGS data sets and histological approaches, we demonstrated that LKB1 status was positively associated with PD-L1 protein expression and conferred a T cell-enriched “hot” TME in NSCLC. Patients with good responses to anti-PD-1/PD-L1 immunotherapy possessed a high level of LKB1 and PD-L1. Skp2 emerged as the molecular hub connecting LKB1 and PD-L1, by which Skp2 catalyzed K63-linked polyubiquitination on K136 and K280 residues to stabilize PD-L1 protein. Inhibition of Skp2 expression by short hairpin RNA or its E3 ligase activity by compound #25 abrogated intact expression of PD-L1 in vitro and generated a T cell-excluded “cold” TME in vivo. Thus, the LKB1-Skp2-PD-L1 regulatory loop was crucial for retaining PD-L1 protein expression and manipulation of this pathway would be a feasible approach for TME remodeling.Conclusion LKB1 and Skp2 are required for intact PD-L1 protein expression and TME remodeling in NSCLC. Inhibition of Skp2 resulted in a conversion from “hot” TME to “cold” TME and abrogated therapeutic outcomes of immunotherapy. Screening LKB1 and Skp2 status would be helpful to select recipients who may benefit from anti-PD-1/PD-L1 immunotherapy.

This study aims to evaluate the effectiveness of various individual machine learning and their ensemble techniques such as Stacking, Voting and Meta-learning in landslide susceptibility assessment taking Poyang, Jiangxi, China as an example. Multi-source geo-environmental data including field surveys, Sentinel-2A/B satellite images, Digital Elevation Models (DEM), and geological and hydrological data were utilized to construct and validate landslide susceptibility models. Results show that the Stacking Classifier outperformed other models, achieving the highest F1 Score of 0.846 and AUC (Area Under ROC Curve) of 0.923, demonstrating its strong predictivity, followed by the Voting Classifier with the F1 Score of 0.829 and AUC of 0.922. Among the individual models, the Multi-Layer Perceptron (MLP) performed best with the F1 Score of 0.828 and AUC of 0.904. Furthermore, the explainable Artificial Intelligence (XAI) technique was applied to better understand the mechanism of classifiers in predicting landslide susceptibility and it suggests a significant correlation between land use, distance to fault, and landslide occurrences. In conclusion, Stacking and Voting hybrid learning models show clear advantages over the individual ones for landslide risk zoning. The results of study may provide technical support for disaster mitigation efforts and future urban planning in areas prone to landslides in Poyang.

Abstract Background Understanding the mechanisms that mediate the interaction between tumor and immune cells may provide therapeutic benefit to patients with cancer. The N6-methyladenosine (m6A) demethylase, ALKBH5 (alkB homolog 5), is overexpressed in non-small cell lung cancer. However, its role in the tumor microenvironment is unknown. Methods Datasets and tissue samples were used to determine the relationship between ALKBH5 expression and immunotherapy efficacy. Bioinformatic analysis, colorimetric assay to determine m6A RNA methylation, dual luciferase reporter assay, RNA/m6A-modified RNA immunoprecipitation, RNA stability assay, and RNA sequencing were used to investigate the regulatory mechanism of ALKBH5 in non-small cell lung cancer. In vitro and in vivo assays were performed to determine the contribution of ALKBH5 to the development of non-small cell lung cancer. Results ALKBH5 was upregulated in primary non-small cell lung cancer tissues. ALKBH5 was positively correlated with programmed death-ligand 1 expression and macrophage infiltration and was associated with immunotherapy response. JAK2 was identified as a target of ALKBH5-mediated m6A modification, which activates the JAK2/p-STAT3 pathway to promote non-small cell lung cancer progression. ALKBH5 was found to recruit programmed death-ligand 1-positive tumor-associated macrophages and promote M2 macrophage polarization by inducing the secretion of CCL2 and CXCL10. ALKBH5 and tumor-associated macrophage-secreted IL-6 showed a synergistic effect to activate the JAK2/p-STAT3 pathway in cancer cells. Conclusions ALKBH5 promotes non-small cell lung cancer progression by regulating cancer and tumor-associated macrophage behavior through the JAK2/p-STAT3 pathway and the expression of CCL2 and CXCL10, respectively. These findings suggest that targeting ALKBH5 is a promising strategy of enhancing the anti-tumor immune response in patients with NSCLC and that identifying ALKBH5 status could facilitate prediction of clinical response to anti-PD-L1 immunotherapy.

ObjectivesDifferences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations.Materials and methodsWe searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy. We also reviewed main conferences from January 1, 2021 to October 1, 2023. A trial-specific hazard ratio (HR) ratio for each subgroup was calculated, and these ratios were then pooled using the deft approach.ResultsA total of 9 RCTs with 4099 patients were finally included. The pooled ratios were 0.92 (95% CI = 0.77 to 1.09) for OS-HRs and 0.79 (95% CI = 0.55 to 1.13) for PFS-HRs in women versus men. The pooled ratios of OS-HRs and PFS-HRs in patients with positive versus negative PD-L1 expression were 1.26 (95% CI = 0.91 to 1.73) and 1.08 (95% CI = 0.77 to 1.52), respectively. The pooled ratios of OS-HRs and PFS-HRs in patients without versus with brain metastasis were 0.77 (95% CI = 0.59 to 1.01) and 0.71 (95% CI = 0.44 to 1.12). No statistically significant differences were also found in terms of subgroups for age, liver metastasis, smoking status, ECOG PS, LDH level, type of platinum salt and race.ConclusionWomen or patients with negative PD-L1 expression or with LDH ≤ ULN or without brain metastasis tend to benefit more from first-line chemoimmunotherapy in ES-SCLC. More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics.Systematic review registrationhttps://inplasy.com/inplasy-2023-3-0064/ identifier, INPLASY202330064.

Abstract Background The impact of lower urinary tract symptoms (LUTS) on the quality of life of patients with benign prostatic hyperplasia (BPH) has been rarely reported. Additionally, the challenges faced by these patients in seeking medical care have often been overlooked. In order to explore the personal struggles caused by LUTS and the difficulties or barriers experienced by Chinese patients with BPH when seeking help, we conducted a qualitative interview study. Methods Qualitative interviews were conducted among 46 patients with BPH who were hospitalized in three tertiary hospitals in China from July 2021 to November 2022. Grounded theory was adopted as the methodology for the qualitative study. After obtaining written informed consent from the study participants, semi-structured interviews were conducted according to the question guidelines. The interview process was audio-recorded; subsequently, the recordings were transcribed, coded, and thematically analyzed. Results The difficulties faced by Chinese patients with BPH were classified into seven main themes: (i) disturbed life, (ii) mental burden, (iii) disease cognition and communication, (iv) delayed treatment, (v) medication status, (vi) hospital visits barriers, and (vii) medical insurance issues. Further, each theme was subdivided into 2–5 sub-themes. Conclusions LUTS have a certain effect on the life and spirit of patients with BPH. These patients face different degrees of difficulties in treatment and hospital visits. Therefore, better healthcare systems and additional social support are crucial for improving the current plight of these patients.

Abstract Interactions of tumor cells with immune cells in the tumor microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited tumor development by suppressing proliferation of tumor cells in non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing role for tumor cell-derived GAS5 in regulating tumor microenvironment. GAS5 positively coordinated with the infiltration of macrophages and T cells in NSCLC clinically, and overexpression of GAS5 promoted macrophages and T cells recruitment both in vitro and in vivo. Mechanistically, GAS5 stabilized p53 by directly binding to MYBBP1A and facilitating MYBBP1A-p53 interaction, and enhanced p53-mediated transcription of IRF1, which activated type I interferon signaling and increased the production of downstream CXCL10 and CCL5. We also found that activation of type I interferon signaling was associated with better immunotherapy efficacy in NSCLC. Furthermore, the stability of GAS5 was regulated by NAT10, the key enzyme responsible for N4-acetylcytidine (ac4C) modification, which bound to GAS5 and mediated its ac4C modification. Collectively, tumor cell-derived GAS5 could activate type I interferon signaling via the MYBBP1A-p53/IRF1 axis, promoting immune cell infiltration and potentially correlating with immunotherapy efficacy, which suppressed NSCLC progression. Our results suggested GAS5 as a promising predictive marker and potential therapeutic target for combination therapy in NSCLC. A schematic diagram demonstrating the regulatory effect of GAS5 on immune cell infiltration by activating type I interferon signaling via MYBBP1A-p53/IRF1 axis in non-small cell lung cancer. IFN, interferon.

In order to clarify the basic properties of Golden Crown Bean starch, the Golden Crown Bean seed residues after extraction of salt soluble protein were used as raw materials, of which the starch was obtained by water extraction. The morphology of starch particles was observed, and the composition, particle size, physicochemical properties and in vitro anti-digestibility of the starch were determined. The results showed that the content of amylose and amylopectin in the starch of Golden Crown bean seeds was 47.39% and 52.07%, respectively. The morphology of the starch particles was similar to that of pea starch, with an oval or spherical shape. The surface of the particles was smooth and complete, with a particle size of 75.10 μm. The peak viscosity (212.20 RVU) and attenuation value (68.50 RVU) of Golden Crown Bean starch were lower, but the retrogradation value (96.80 RVU) was higher than that of corn starch; the starting temperature (T0), peak temperature (Tp) of starch gelatinization in Golden Crown Beans were significantly higher than those of pea starch (P

Abstract Pre-production quality defect inspection is a crucial step in industrial manufacturing, and many traditional inspection strategies suffer from inefficiency issues. This is especially true for tasks such as mechanical performance testing of steel products, which involve time-consuming processes like offline sampling, specimen preparation, and testing. The inspection volume significantly impacts the production cycle, inventory, yield, and labor costs. Constructing a data-driven model for predicting product quality and implementing proactive sampling inspection based on the prediction results is an appealing solution. However, the prediction uncertainty of data-driven models poses a challenging problem that needs to be addressed. This paper proposes an active quality inspection approach for steel products based on the uncertainty quantification in the predictive model for mechanical performance. The objective is to reduce both the sampling frequency and the omission rate on the production site. First, an ensemble model based on improved lower and upper bound estimation is established for interval prediction of mechanical performance. The uncertainty of the specific value prediction model is quantitatively estimated using interval probability distributions. Then, a predictive model for the mechanical performance failure probability is built based on the prediction interval size and probability distribution. By determining an appropriate probability threshold, the trade-off between prediction accuracy and defect detection accuracy (recall rate) is balanced, enabling the establishment of an active sampling strategy. Finally, this functionality is integrated into the manufacturing execution system of a steel factory, realizing a mechanical performance inspection approach based on proactive sampling. The proposed approach is validated using real production datasets. When the probability threshold is set to 30%, the prediction accuracy and recall rate for failure mechanical performance samples are 75% and 100%, respectively. Meanwhile, the sampling rate is only 5.33%, while controlling the risk of omission. This represents a 50% reduction in sampling rate compared to the inspection rules commonly used in actual production. The overall efficiency of product quality inspection is improved, and inspection costs are reduced.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Integrating RGB and Event (RGBE) multi-domain information obtained by high-dynamic-range and temporal-resolution event cameras has been considered an effective scheme for robust object tracking. However, existing RGBE tracking methods have overlooked the unique spatio-temporal features over different domains, leading to object tracking failure and inefficiency, especally for objects against complex backgrounds. To address this problem, we propose a novel tracker based on adaptive-time feature extraction hybrid networks, namely Siamese Event Frame Tracker (SiamEFT), which focuses on the effective representation and utilization of the diverse spatio-temporal features of RGBE. We first design an adaptive-time attention module to aggregate event data into frames based on adaptive-time weights to enhance information representation. Subsequently, the SiamEF module and cross-network fusion module combining artificial neural networks and spiking neural networks hybrid network are designed to effectively extract and fuse the spatio-temporal features of RGBE. Extensive experiments on two RGBE datasets (VisEvent and COESOT) show that the SiamEFT achieves a success rate of 0.456 and 0.574, outperforming the state-of-the-art competing methods and exhibiting a 2.3-fold enhancement in efficiency. These results validate the superior accuracy and efficiency of SiamEFT in diverse and challenging scenes.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract Background Over a dozen vaccines are in or have completed phase III trials at an unprecedented speed since the World Health Organization (WHO) declared COVID-19 a pandemic. In this review, we aimed to compare and rank these vaccines indirectly in terms of efficacy and safety using a network meta-analysis. Methods We searched Embase, MEDLINE, and the Cochrane Library for phase III randomized controlled trials (RCTs) from their inception to September 30, 2023. Two investigators independently selected articles, extracted data, and assessed the risk of bias. Outcomes included efficacy in preventing symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the incidence of serious adverse events (SAEs) according to vaccine type and individual vaccines in adults and elderly individuals. The risk ratio and mean differences were calculated with 95% confidence intervals using a Bayesian network meta-analysis. Results A total of 25 RCTs involving 22 vaccines were included in the study. None of vaccines had a higher incidence of SAEs than the placebo. Inactivated virus vaccines might be the safest, with a surface under the cumulative ranking curve (SUCRA) value of 0.16. BIV1-CovIran showed the highest safety index (SUCRA value: 0.13), followed by BBV152, Soberana, Gam-COVID-Vac, and ZF2001. There were no significant differences among the various types of vaccines regarding the efficacy in preventing symptomatic SARS-CoV-2 infection, although there was a trend toward higher efficacy of the mRNA vaccines (SUCRA value: 0.09). BNT162b2 showed the highest efficacy (SUCRA value: 0.02) among the individual vaccines, followed by mRNA-1273, Abdala, Gam-COVID-Vac, and NVX-CoV2373. BNT162b2 had the highest efficacy (SUCRA value: 0.08) in the elderly population, whereas CVnCoV, CoVLP + AS03, and CoronaVac were not significantly different from the placebo. Conclusions None of the different types of vaccines were significantly superior in terms of efficacy, while mRNA vaccines were significantly inferior in safety to other types. BNT162b2 had the highest efficacy in preventing symptomatic SARS-CoV-2 infection in adults and the elderly, whereas BIV1-CovIran had the lowest incidence of SAEs in adults.

Incorporating the current works in augmented large language models (LLM), a dual process theory based telecom augmented cognition architecture (TACA) was proposed.This architecture addressed challenges faced by LLM in the field of telecom, such as lack of domain-specific knowledge and limited reasoning capabilities.It aims to enhance cognitive reasoning, knowledge integration, tooling, and autonomous decision-execution capabilities for complex telco-scenarios.Technical application references for different telco-scenarios were provided, and the effectiveness and feasibility of the augmented cognition solution were preliminarily validated in addressing complex problems through experiments.The proposed TACA can serve as a future reference architecture for the application of LLMs in the telecom industry.

This study explored the differences in the chemical and elemental composition, anti-nutritional factors, and nitrate content of cassava tender shoots (CTS) pickled vegetables under various traditional processes, such as Kimchi (KIM), sprouts pickles (SPP), vegetable pickled in sauce (SP), olives pickles (OP), hot Kimchi (HK) and salted pickles (SAP), using sensory evaluation, the index of nutritional quality (INQ), and principal component analysis (PCA). The aim was to identify the optimal process for producing high-quality CTS pickled vegetables. Results indicated that different pickling processes significantly affect the quality of CTS pickled vegetables. SPP had the highest protein content at 35.29 g/100 g, while SAP had relatively lower chemical composition. The mineral content in the CTS pickled vegetables decreased to varying degrees, with SPP having the most significant decrease (71.91% in Mn content, 70.72% in Zn, 59.20% in K, and 60.84% in Mg). The cyanide content of CTS pickled vegetables ranged from 32.62 mg/kg to 82.41 mg/kg, while tannin content ranged from 1.07 g tannic acid/100 g to 2.33 g tannic acid/100 g, with nitrate content lower than the national standard at 0.37 mg/kg to 1.02 mg/kg. Sensory evaluation showed that KIM had satisfactory freshness, texture, and appearance, ranking the highest among all. INQ evaluation indicated that SAP, KIM, and HK had higher nutritional value. PCA analysis showed that the cumulative contribution rate of the first three principal components was 83.949%, and the overall score showed that KIM, OP and HK had higher quality. After comprehensive evaluation of sensory evaluation, INQ evaluation, and PCA analysis, KIM using the pickle-making process was determined to be the best method, followed by HK and SAP.

In the paper, we presented a data-driven optimal control method for the sub-satellite deployment of tethered satellite systems during the release phase, with the objective of reducing the libration angle fluctuation during system work. First, the dynamic equation of the tethered satellite system was established and processed dimensionless. Considering the presence of noise when sensors were put on the satellite to measure the libration angle, the corresponding state equation was derived. Next, we estimated the system state using an unscented Kalman filter and established a performance index and the Hamilton function. Based on the index, we designed an optimal control strategy and provided sufficient conditions for the asymptotic stability of the closed-loop system. We used critic-actor neural networks based on measurement data to implement the data-driven control algorithm to approximate the performance index function and the control policy, respectively. Finally, taking a tethered satellite system as an example, a simulation showed that the unscented Kalman filter can effectively estimate the system state and improve the impact of noise on the system, and the proposed optimal control strategy ensured that the tethered satellite system is stable, which shows the applicability and effectiveness of the control strategy in reducing the tether vibration of the disturbed system.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Lung cancer is the leading cause of cancer-related deaths worldwide. Bone is a common metastatic site of lung cancer, about 50% of bone metastatic patients will experience skeletal related events (SREs). SREs not only seriously impact the quality of life of patients, but also shorten their survival time. The treatment of bone metastasis requires multi-disciplinary therapy (MDT) and development of individualized treatment plan. In order to standardize the diagnosis and treatment of bone metastasis in lung cancer, the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

Artificial water bodies in Central Asia offer unique environments in which to study plankton diversity influenced by topographic barriers. However, the complexity of these ecosystems and limited comprehensive studies in the region challenge our understanding. In this study, we systematically investigated the water environment parameters and phytoplankton community structure by surveying 14 artificial waters on the southern side of the Altai Mountains and the northern and southern sides of the Tianshan Mountains in the Xinjiang region. The survey covered physical and nutrient indicators, and the results showed noticeable spatial differences between waters in different regions. The temperature, dissolved oxygen, total nitrogen, and total phosphorus of artificial water in the southern Altai Mountains vary greatly. In contrast, the waters in the northern Tianshan Mountains have more consistent physical indicators. The results of phytoplankton identification showed that the phytoplankton communities in different regions are somewhat different, with diatom species being the dominant taxon. The cluster analysis and the non-metric multidimensional scaling (NMDS) results also confirmed the variability of the phytoplankton communities in the areas. The variance partitioning analysis (VPA) results showed that climatic and environmental factors can explain some of the variability of the observed data. Nevertheless, the residual values indicated the presence of other unmeasured factors or the influence of stochasticity. This study provides a scientific basis for regional water resource management and environmental protection.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

In order to improve the processing and utilization value of the Northeast snap beans products by clarifying the saponin content, sites and influencing factors, this study extracted saponins from the seeds and pods of seven kinds of Northeast snap beans, including Golden Crown, Green Crown, and Sheng Crown within 10~40 d after blooming using ultrasonic-assisted methods. 0.4%~1.2% sodium chloride solution was used to conduct germination treatment under salt stress on the saponin content of Golden Crown and Mantangcai seed. Finally, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to identify the saponin species in the seeds of Golden Crown. The results showed that saponin existed mainly in the seeds, and the saponin content increased firstly but then decreased with the increase of growth time. The peak period of saponin content varied with the bean varieties. Compared with the other six varieties of snap beans, the saponin content in the full hall was the highest, with the highest saponin content of Mantangcai whole pods of 23.62±0.14 mg/g at 35 d. The change of saponin content was closely related to the sprouting time of bean seeds and bean varieties. Salt stress treatment could significantly increase the saponin content of Mantangcai seeds from (7.08±0.15) mg/g to (10.15±0.55) mg/g. The UHPLC-Q-TOF-MS analysis showed that there were seven saponins in the crude saponins of the Golden Crown bean, including saikosaponin F, adzuki saponin II and astragaloside IV. This study provides data support for the in-depth development of soybean saponins in Northeast China.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

Abstract In this work, inspired by the definition of the photon surface given by Claudel, Virbhadra, and Ellis, we give an alternative quasi-local definition to study the circular orbits of single-pole particles. This definition does not only apply to photons but also to massive point particles. For the case of photons in spherically symmetric spacetime, it will give a photon surface equivalent to the result of Claudel, Virbhadra, and Ellis. Meanwhile, in general static and stationary spacetime, this definition can be regarded as a quasi-local form of the effective potential method. However, unlike the effective potential method which can not define the effective potential in dynamical spacetime, this definition can be applied to dynamical spacetime. Further, we generalize this definition directly to the case of pole–dipole particles. In static spherical symmetry spacetime, we verify the correctness of this generalization by comparing the results obtained by the effective potential method.

The intricate internal structure of fuel rods results in a non-uniform mass distribution, making it imperative to employ analytical methods for accurate assessment. The study utilizes Euler beam theory to derive the transverse vibration equation for beams with varying mass distribution. The approach involves transforming the non-uniform mass beam into a multi-segment beam with concentrated mass points. Modal function relationships between adjacent uniform segments are established based on continuous conditions at connection points. This transformation leads to the conversion of the variable coefficient differential equation into a nonlinear matrix equation. The Newton-Raphson method is then applied to calculate the characteristic equation and mode shapes, essential for determining natural frequencies. To validate precision, the results obtained are compared with those derived from the finite element method. Furthermore, the developed method is employed to assess the impact of gas plenum location and length on the natural frequency of fuel rods. The proposed methodology serves as a rapid design tool, particularly beneficial during the design phase of fuel rods with non-uniform mass distribution, aiding in configuring structural aspects effectively.

Abstract Background Malaria is a deadly disease caused by Plasmodium spp. Several blood phenotypes have been associated with malarial resistance, which suggests a genetic component to immune protection. Methods One hundred and eighty-seven single nucleotide polymorphisms (SNPs) in 37 candidate genes were genotyped and investigated for associations with clinical malaria in a longitudinal cohort of 349 infants from Manhiça, Mozambique, in a randomized controlled clinical trial (RCT) (AgeMal, NCT00231452). Malaria candidate genes were selected according to involvement in known malarial haemoglobinopathies, immune, and pathogenesis pathways. Results Statistically significant evidence was found for the association of TLR4 and related genes with the incidence of clinical malaria (p = 0.0005). These additional genes include ABO, CAT, CD14, CD36, CR1, G6PD, GCLM, HP, IFNG, IFNGR1, IL13, IL1A, IL1B, IL4R, IL4, IL6, IL13, MBL, MNSOD, and TLR2. Of specific interest, the previously identified TLR4 SNP rs4986790 and the novel finding of TRL4 SNP rs5030719 were associated with primary cases of clinical malaria. Conclusions These findings highlight a potential central role of TLR4 in clinical malarial pathogenesis. This supports the current literature and suggests that further research into the role of TLR4, as well as associated genes, in clinical malaria may provide insight into treatment and drug development.

Background and objective Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. Methods From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. Results (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. Conclusion Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.

Schizothoracinae species are the largest group of Cypriniformes that readily adapt to the natural conditions of the Qinghai-Tibet Plateau. This group has habitat characteristics and distribution patterns centered on the Qinghai-Tibet Plateau. To study the evolution of three Schizothoracinae species in Northwest China, the evolutionary characteristics of these species were explored based on differences in otolith morphology and skeletal morphology. From 2020 to 2022, 138 samples (63 Aspiorhynchus laticeps, 35 Diptychus maculatus and 40 Schizothorax pseudaksaiensis) were collected from the Tarim River and Ili River, 6 basic morphological parameters of otoliths were measured and converted into 6 morphological factors and 7 morphological indices. A total of 77 Fourier transform coefficients of each otolith were selected The first three principal components accounted for 92.834% of the total variation in 13 otolith morphological indices of the three Schizothoracinae species, and the overall discrimination rate was 94.20%. According to the principal component analysis of 77 Fourier harmonic values of otoliths, the first 20 principal components explained 97.233% of the total variation, and the overall discrimination rate was 100%. The results of the cluster analysis directly reflected the relationships between related species. The differences in the bone morphology of the three Schizothoracinae species were particularly reflected in the number of whiskers, pharyngeal teeth and vertebrae, and there were also significant differences in the shapes of the sphenotic (SP), pterotic (PTE), preoperculum (PO), branchiostegal ray (BRA) and basibranchial (BB) bones. Their unique morphological and skeletal characteristics are closely related to geological changes and water system evolutionary trends. This study contributes to the understanding of species identification and the evolutionary status of plateau fishes, provides a reference for further evolutionary classification and for assessing the evolutionary mechanisms of plateau fishes, and provides a scientific basis for phylogeny and germplasm resource protection.

Background: Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes. Methods: A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC. Results: In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months. Conclusions: EGFR-, ALK-, HER2-, RET- , and ROS1 -altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation, and MET amplification have better responses to immunotherapy, and more prospective studies are needed for further research.

Abstract Due to the similarity in the grain and difference in the market value among many rice varieties, deliberate mislabeling and adulteration has become a serious problem. To check the authenticity, we aimed to discriminate rice varieties based on their volatile organic compounds (VOCs) composition by headspace solid phase microextraction (HS-SPME) coupled with gas chromatography mass spectrometry (GC–MS). The VOC profiles of Wuyoudao 4 from nine sites in Wuchang were compared to 11 rice cultivar from other regions. Multivariate analysis and unsupervised clustering showed an unambiguous distinction between Wuchang rice and non-Wuchang rice. Partial least squares discriminant analysis (PLS-DA) demonstrated a goodness of fit of 0.90 and a goodness of prediction of 0.85. The discriminating ability of volatile compounds is also supported by Random forest analysis. Our data revealed eight biomarkers including 2-acetyl-1-pyrroline (2-AP) that can be used for variation identification. Taken together, the current method can readily distinguish Wuchang rice from other varieties which it holds great potential in checking the authenticity of rice.

Abstract Objectives Our research aimed to evaluate the effectiveness of first‐line immune checkpoint inhibitors (ICIs) with etoposide and platinum (EP) for extensive‐stage small cell lung cancer (ES‐SCLC) and identify prognostic factors, as real‐world outcomes and the inconsistency of PD‐1 and PD‐L1 inhibitors are uncertain. Methods We selected ES‐SCLC patients in three centers and conducted a propensity score‐matched analysis. The Kaplan–Meier method and Cox proportional hazards regression were conducted to compare the survival outcomes. We also performed univariate and multivariate Cox regression analyses to investigate predictors. Results Among 236 patients included, 83 pairs of cases were matched. The EP plus ICIs cohort had a longer median overall survival (OS) (17.3 months) than the EP cohort (13.4 months) (hazard ratio [HR], 0.61 [0.45, 0.83]; p = 0.001). The median progression‐free survival (PFS) was also longer in the EP plus ICIs cohort (8.3 months) than in the EP cohort (5.9 months) (HR, 0.44 [0.32, 0.60]; p

Abstract Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Abstract Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

Abstract In this paper, enlightened by the definition of the photon surface given by Claudel, Virbhadra and Ellis, we give a quasi-local definition of the particle surface. From this definition, one can study the evolution of the circular orbits in general spacetime. Especially, we pointed out that this definition can be used to get the spherical circular orbits in stationary spacetimes which cannot be got by the definition of Claudel, Virbhadra and Ellis. Further, we give a condition to exclude the particle surface in spacetime without gravity. Simultaneously, we give a quasi-local definition of the stability of the particle surface in general spacetime. From this definition, one can get the evolution equation of the innermost stable circular orbit (ISCO) in general spacetime. To verify the correctness of these definitions, we studied the circular orbits in some special cases and the results are all consistent with the previous results.

Background: The pathogenesis of hypertrophic scars (HS) is complex and unclear. It is of great importance to investigate the formation mechanism of HS at the gene level, find new targets for gene therapy, and establish effective prevention strategies for the formation of HS. Objectives: The study explored the expression pattern of HOX transcript antisense intergenic RNA (HOTAIR) and miR-30a-5p in scar tissues of HS patients and investigated their regulatory role in fibroblast function. Methods: Forty HS patients were recruited, and their scar tissues and adjacent normal skin tissues were collected. Fibroblasts were extracted from these tissues. The quantitative reverse transcription–polymerase chain reaction was used for the mRNA measurement. The CCK-8 and transwell assay were applied for cell proliferation and migration assessment. Luciferase reporter assay was done to verify the target gene of HOTAIR. Results: Elevated HOTAIR and decreased miR-30a-5p were measured in both scar tissues and scar fibroblasts, and their levels were negatively correlated. HOTAIR acted as the sponge of miR-30a-5p. HOTAIR knockdown inhibited fibroblast proliferation, migration, and the expression of collagen synthesis-related proteins (procollagen, alpha-smooth muscle actin, and collagen I), but these functions were abolished by miR-30a-5p downregulation. Conclusion: HS patients owned elevated HOTAIR and decreased miR-30a-5p. HOTAIR knockdown can inhibit the proliferation, migration, and collagen synthesis of scar fibroblasts by negatively regulating the expression of miR-30a-5p.

Based on dimensional memory mechanism and adaptive elite population, this paper proposes a satisfactory and efficient artificial bee colony algorithm (DMABC_elite) to solve optimization problems and train artificial neural networks (ANN). DMABC_elite proposes the concept of adaptive elite population that changes dynamically with the search process, and modifies the search equations for employed and onlooker bee phases on this basis. In addition, a dimensional memory mechanism has been introduced that allows multi-dimensional updates, which improves exploitation and speeds up convergence. Next, a new selection strategy and a Lévy flight-based solution-generating method are introduced in the scout bee phase to enhance the global search ability. Finally, the performance of DMABC_elite on two different problem groups is analyzed experimentally. On the one hand, DMABC_elite is evaluated using 22 classical benchmark functions with different dimensions and CEC 2013 test functions. Compared with basic ABC and nine state-of-the-art ABC variants, DMABC_elite achieved better results, ranking first in all 10-, 30- and 100-dimensional tests across 22 classical benchmark functions and 30-dimensional tests across CEC 2013 test functions. On the other hand, DMABC_elite is compared with traditional backpropagation-based algorithms and other ABC variants when training seven different ANNs. The results show that DMABC_elite is efficient and competitive in training ANNs.

Abstract Background Treatment options for Chinese patients with locally advanced or metastatic squamous‐cell non‐small‐cell lung cancer (sqNSCLC) after failure of first‐line chemotherapy are limited. This study (ORIENT‐3) aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second‐line treatment in patients with locally advanced or metastatic sqNSCLC. Methods ORIENT‐3 was an open‐label, multicenter, randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first‐line platinum‐based chemotherapy. Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m2 of docetaxel intravenously every 3 weeks, stratified by the Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Results Between August 25, 2017, and November 7, 2018, 290 patients were randomized. For FAS, 10 patients from the docetaxel arm were excluded. The median OS was 11.79 (n = 145; 95% confidence interval [CI], 10.28‐15.57) months with sintilimab versus 8.25 (n = 135; 95% CI, 6.47‐9.82) months with docetaxel (hazard ratio [HR]: 0.74; 95% CI, 0.56‐0.96; P = 0.025). Sintilimab treatment significantly prolonged PFS (median 4.30 vs. 2.79 months; HR: 0.52; 95% CI, 0.39‐0.68; P < 0.001) and showed higher ORR (25.50% vs. 2.20%, P < 0.001) and DCR (65.50% vs. 37.80%, P < 0.001) than the docetaxel arm. The median DoR was 12.45 (95% CI, 4.86‐25.33) months in the sintilimab arm and 4.14 (95% CI, 1.41‐7.23) months in the docetaxel arm (P = 0.045). Treatment‐related adverse events of grade ≥ 3 were reported in 26 (18.1%) patients in the sintilimab arm and 47 (36.2%) patients in the docetaxel arm. Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors, including OVOL2 (HR: 0.35; P < 0.001) and CTCF (HR: 3.50; P < 0.001)，for sintilimab treatment. Conclusions Compared with docetaxel, sintilimab significantly improved the OS, PFS, and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.

Abstract Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in‐depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

The development of efficient, low-cost, and environmentally friendly catalysts has the potential to significantly enhance the persulfate-based advanced oxidation technology for wastewater treatment. In this study, chitosan gel was ultilized as the biomass to be pyrolyzed by two-step pyrolysis method at 600 °C and 800 °C to produce biochar (BC-800). Results from the SEM, TEM, BET, Raman, and XPS characterizations showed that the BC-800 had a surface area of 1748 m2/g and a hierarchical pore structure with co-existing macropores, mesopores, and micropores, as well as an obvious graphitic carbon, pyridinic N, and graphitic N configurations. The prepared biochar was found to activate persulfate (PS) for rapid degradation of 2,4-dichlorophenol, with 90% of pollutants removed in 5 min due to the excellent mass transfer facilitated by the abundant pores. Chemical quenching experiments, EPR detection, and electrochemical analysis indicated that the degradation process was triggered by a nonradical pathway, in which the biochar acted as an electron transfer shuttle between the oxidant and pollutant. This electron transfer mechanism not only enabled the degradation system have a wide pH range for application, but it also demonstrated high resistance to inorganic anions in the aquatic environment. This research is expected to enhance the preparation method of hierarchical porous biochar and provide effective technical support for the biochar-activated PS for water purification.

Spiking Neural Networks (SNNs) have shown great promise in processing spatio-temporal information compared to Artificial Neural Networks (ANNs). However, there remains a performance gap between SNNs and ANNs, which impedes the practical application of SNNs. With intrinsic event-triggered property and temporal dynamics, SNNs have the potential to effectively extract spatio-temporal features from event streams. To leverage the temporal potential of SNNs, we propose a self-attention-based temporal-channel joint attention SNN (STCA-SNN) with end-to-end training, which infers attention weights along both temporal and channel dimensions concurrently. It models global temporal and channel information correlations with self-attention, enabling the network to learn ‘what’ and ‘when’ to attend simultaneously. Our experimental results show that STCA-SNNs achieve better performance on N-MNIST (99.67%), CIFAR10-DVS (81.6%), and N-Caltech 101 (80.88%) compared with the state-of-the-art SNNs. Meanwhile, our ablation study demonstrates that STCA-SNNs improve the accuracy of event stream classification tasks.

Objectives: Several randomized controlled trials (RCTs) indicated that first-line programmed cell death protein-1/death-ligand 1 inhibitors plus chemotherapy (PD-1/PD-L1 + chemo) led to survival benefits in extensive-stage small-cell lung cancer (ES-SCLC) compared with platinum-based chemotherapy. This study aims to identify the optimal PD-1/PD-L1 + chemo combination strategy. Methods: We included RCTs comparing PD-1/ PD-L1 + chemo versus chemo alone in ES-SCLC. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ⩾3 treatment-related adverse events were considered. Odds ratios (ORs), hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted. Results: Six RCTs with 2600 patients were analyzed in this Bayesian network meta-analysis. Results showed that adding PD-1/PD-L1 inhibitors to chemotherapy led to significant benefits in OS (HR = 0.72, 95% CI: 0.66–0.79), PFS (HR = 0.69, 95% CI: 0.63–0.75), and ORR (OR = 1.32, 95% CI: 1.12–1.56), and no differences in toxicity were found (OR = 1.09, 95% CI: 0.92–1.30). Serplulimab plus chemotherapy was found to provide the best OS (HR = 0.63, 95% CI: 0.49–0.82), the best PFS (HR = 0.47, 95% CI: 0.38–0.59), and the best ORR (OR = 1.7, 95% CI: 1.15–2.53). Moreover, although there were no difference between PD-L1 + chemo and PD-1 + chemo regarding OS (HR = 0.99, 95% CI: 0.91–1.08) and ORR (OR = 1.27, 95% CI: 0.91–1.78), PD-1 + chemo showed a significant benefit in PFS (HR = 0.82, 95% CI: 0.68–0.98) compared with PD-L1 + chemo. Conclusions: Serplulimab plus chemotherapy seems to be superior first-line immunotherapy combination for patients with ES-SCLC. PD-1 + chemo seems to outperform PD-L1 + chemo in PFS.