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This study investigates the effects of orientation and strain rate on the hydrogen-enhanced localized plasticity mechanism during shear deformation of interstitial free steel. The stress-orientation correlation of hydrogen embrittlement is related to atomic-scale mechanisms, as evidenced through in situ electron backscatter diffraction, slow-strain-rate shear testing, electron microscopic characterization, and molecular dynamics simulations. The dislocation density increment after hydrogen charging was 59.25% higher along the [100] crystallographic zone axis than along the [11‾1‾] crystallographic zone axis, which is mainly attributed to the combined effect of strain-induced transport and interstitial diffusion of hydrogen atoms. The strain rate correlation of hydrogen embrittlement is also affected by the interstitial diffusion during the strain-induced transport of H. Interstitial diffused hydrogen induce dislocation forest emissions that promote local plasticity, which ultimately leads to the orientation and strain rate correlation of hydrogen embrittlement.

Abstract Nanotechnology shows potential to promote sustainable and productive agriculture and address the growing population and food demand worldwide. However, the applications of nanotechnology are hindered by the lack of knowledge on nanoparticle (NP) transformations and the interactions between NPs and macromolecules within crops. In this Review, we discuss the beneficial and toxicity-relieving transformation products of NPs that provide agricultural benefits and the toxic and physiology-disturbing transformations that induce phytotoxicities. Based on knowledge related to the management of NP transformations and their long-term effects, we propose feasible design suggestions to attain nano-enabled efficient and sustainable agricultural applications.

Melanoma is a highly malignant skin tumor characterized by high metastasis and poor prognosis. Recent studies have highlighted the pivotal role of melanoma stem cells (MSCs)—a subpopulation of cancer stem cells (CSCs)—in driving tumor growth, metastasis, therapeutic resistance, and recurrence. Similar to CSCs in other cancers, MSCs possess unique characteristics, including specific surface markers, dysregulated signaling pathways, and the ability to thrive within complex tumor microenvironment (TME). This review explored the current landscape of MSC research, discussing the identification of MSC-specific surface markers, the role of key signaling pathways such as Wnt/β-catenin, Notch, and Hedgehog (Hh), and how interactions within the TME, including hypoxia and immune cells, contribute to MSC-mediated drug resistance and metastatic behavior. Furthermore, we also investigated the latest therapeutic strategies targeting MSCs, such as small-molecule inhibitors, immune-based approaches, and novel vaccine developments, with an emphasis on their potential to overcome melanoma progression and improve clinical outcomes. This review aims to provide valuable insights into the complex roles of MSCs in melanoma biology and offers perspectives for future research and therapeutic advances against this challenging disease.

Abstract Background The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first‐line immunotherapy and chemotherapy in patients with extensive‐stage small cell lung cancer (ES‐SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first‐line immunotherapy and chemotherapy. Methods Our retrospective study included patients with ES‐SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first‐line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment‐related toxicities across both cohorts were compared using the Chi‐squared test. Results A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow‐up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P

Abstract Background Circulating tumor cells (CTCs) play a crucial role in the early diagnosis and prognosis of lung cancer. Identification of a more suitable sample source could be a breakthrough towards enhancing CTC detectability in early‐stage lung cancer. We investigated the differences in detectable CTCs between peripheral arterial and venous blood in early‐ and mid‐stage lung cancer patients undergoing surgery and analyzed the association between clinicopathological factors and detectable CTCs in peripheral arterial and venous blood. Methods Peripheral arterial and venous blood was collected in 5‐mL samples from 56 patients with surgically resected and pathologically clear at early‐ or mid‐stage lung cancer. Blood specimens were enriched for CTCs based on isolation by size of epithelial tumor cells. The CTCs were identified using Swiss Giemsa staining and immunohistochemistry for CD45/CD31. Results In stage I lung cancer, CTC‐positive rate was significantly higher in peripheral arterial than in venous blood (45.45% vs. 17.39%). There was no significant difference in the number of detectable CTCs between peripheral arterial and venous blood. A low degree of differentiation was associated with a high positive rate of CTCs in peripheral venous blood. The number of circulating tumor microemboli was significantly higher in patients with tumor size >3 cm compared with ≤3 cm. Conclusion CTC levels in peripheral arterial and venous blood differed little in lung cancer patients.Compared to peripheral venous blood, peripheral arterial blood had a higher CTC positivity rate in early‐stage lung cancer.This study was favorable for early detection and monitoring of lung cancer.

Background: We aim to investigate the prognostic value of different pathological patterns of non-adenocarcinoma prostate cancers (PCa) in radical prostatectomy (RP) and external beam radiation therapy (EBRT). Methods: Data of 470,258 localized PCa patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics of patients in different groups. Kaplan–Meier curves and Cox regression were used for survival analysis. Overall survival (OS) and cancer-specific survival (CSS) were set as endpoints. Results: Totally, 1044 patients with non-adenocarcinoma patterns of PCa were included. Patients with small cell neuroendocrine carcinoma (SCNC) and neuroendocrine differentiation (NED) harbored the worst prognosis in both RP and EBRT among all pathological groups. RP exhibited superior effects to EBRT for this group of cases. Ductal carcinoma (DA) was also related to poorer survival outcomes versus PAC in both local therapies. Yet, for men with DA, both RP and EBRT still improved patients' prognosis against no local therapy (NLT), with RP being the superior modality. Cases harboring mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) shared comparable clinical outcomes to men with PAC. However, for cases with MA, neither RP nor EBRT was related to better survival outcomes against NLT, while for patients with SRCC, both RP and EBRT prolonged patients’ survival with similar effects. Conclusions: Our study provided a comprehensive view of the treatment effect of RP and EBRT in non-adenocarcinoma PCa patients. These findings could facilitate clinicians in making therapeutic decision-making for non-adenocarcinoma patients.

Abstract Dermatological toxicities are well-recognized immune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) use. Corticosteroids are considered the first-line therapy for grade 3 or grade 4 skin irAEs, but long-term usage of corticosteroids may abolish the effect of ICIs. Multiple antitumor therapies might be an influencing factor in an increased incidence of skin irAEs. The safety and prognostic value in resuming ICIs after irAEs has been inconsistently reported, especially the severe skin irAE. We report a case of a 75-year-old man with non-small cell lung cancer (NSCLC) and prostate cancer with a Stevens-Johnson syndrome (SJS)-like eruption. The severe rash might have been induced by resuming pembrolizumab was successfully treated with a combination of corticosteroids, gamma globulin, and immunosuppressants. Early detection of dermatologic toxicity is crucial, especially for patients receiving multiple antitumor treatments. We should treat ICI resumption seriously after skin irAE.

Background: Human epidermal growth factor receptor 2 (HER2) overexpression is related to anti-HER2 therapy in many tumors. RC48- antibody-drug conjugate (ADC) has shown promising efficacy in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC). The characteristic expression and scoring systems of HER2 are nonexistent in UC. We aimed to explore HER2 status and its correlation with the efficacy of HER2-targeting ADC therapy in UC. Methods: A total of 137 and 43 patients were enrolled in cohort 1 and cohort 2, respectively, from March 2009 to December 2018. The patients in cohort 2 were enrolled in a phase II study of RC48-ADC. UC samples were tested for HER2 status using immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The 2018 ASCO/CAP HER2 scoring system was adopted and modified to score HER2 expression in UC. Results: The HER2-positive (IHC 2+ or 3+) rate was 24.1% (33/137). In HER2 IHC 2+ or 3+ patients, the HER2 gene amplification rate was 31% (13/42). The objective response rates (ORRs) in RC48-ADC-treated patients with IHC 3+, IHC 2+ and FISH+, IHC 2+ and FISH- were 58.8%, 66.7% and 40%, respectively. The ORR showed a trend toward a better benefit for RC48-ADC therapy in patients with HER2 amplification than in those without amplification (61.5% vs. 44.8%, P = 0.059). The heterogeneity of HER2 expression in the primary tumor was 55.5% (15/27), and the ORR was not significantly different between patients with tumor heterogeneity and homogeneity. Conclusions: IHC testing should be performed to assess the HER2 status before the initiation of HER2-ADC therapy. There was a trend toward a better benefit for patients with HER2 amplification, and tumor heterogeneity did not influence the drug efficacy.

Abstract Background Fumarate hydratase–deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear. Methods In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions. Results Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci. Conclusions Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

Abstract The mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1‐IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune‐hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)‐related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA‐based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.

Industrial parks in China have a large energy consumption with a noticeable peak valley difference between energy consumption and colossal carbon emission. This causes a significant contradiction between energy consumption and energy supply in the country. To solve the above-mentioned problems, an optimization method is proposed for the park integrated energy system based on integrated demand response. First, the energy supply model of the typical day integrated with the energy system in the industrial park during summer was constructed. Second, the price demand response model was established according to the substitution elasticity coefficient. Considering the dynamic characteristics of temperature, the equivalent thermal parameter model and the predicted mean vote (PMV) index model were used to select the adjustable demand response model. Then, aiming at the minimum operation cost and carbon emission, the adaptive chaotic drosophila melanogaster optimization algorithm with niche technology was used to solve this problem, whereby the Pareto optimal solution set was obtained. The VIKOR method was used to select the optimal result comprehensively. Finally, the integrated energy system of an north industrial park was analyzed, and the results were regarded as an example. The results showed that the method proposed by this paper improved the economy considerably and provided environmental protection effectively.

This study presents a novel event-triggered relearning framework for neural network modeling, designed to improve prediction precision in dynamic stochastic complex industrial systems under non-stationary and variable conditions. Firstly, a sliding window algorithm combined with entropy is applied to divide the input and output datasets across different operational conditions, establishing clear data boundaries. Following this, the prediction errors derived from the neural network under different operational states are harnessed to define a set of event-triggered relearning criteria. Once these conditions are triggered, the relevant dataset is used to recalibrate the model to the specific operational condition and predict the data under this operating condition. When the predicted data fall within the training input range of a pre-trained model, we switch to that model for immediate prediction. Compared with the conventional BP neural network model and random vector functional-link network, the proposed model can produce a better estimation accuracy and reduce computation costs. Finally, the effectiveness of our proposed method is validated through numerical simulation tests using nonlinear Hammerstein models with Gaussian noise, reflecting complex stochastic industrial processes.

The rapid development of the global economy and society relies on continuous energy demand, while the severe impact of carbon emissions on the ecological environment has garnered significant international attention. Accurately forecasting carbon emission trends is crucial for developing effective reduction strategies and ensuring sustainable green economic development. In this paper, we propose a Metabolic Neural Network Prediction Model (MNPM) for carbon emissions. This model comprehensively considers the impact of various carbon emission-related factors across different regions in China. By employing one-hot encoding, we address the difficulties traditional classifiers face when handling categorical data, enabling predictions under more realistic conditions. To optimize the nonlinear characteristics of the data and overcome the limitations of grey models, we utilize dynamic iterative time series training to address errors due to data inaccuracies effectively. Experimental results demonstrate that our approach outperforms other methods in filtering out irrelevant data, achieving an average relative residual of 0.055 and an average ratio bias of 0.049, translating to more precise prediction accuracy.

The effects of deacidification, decolorization and deodorization at different temperatures on the content of squalene, sterols and volatile organic compounds in pressed camellia oil were investigated. The results showed that the content of squalene in crude camellia oil was 127.46 mg/kg, and after deacidification decolorization, and deodorization at 150 oC, content of squalene was decreased to 105.82, 89.52 and 79.79 mg/kg, respectively. Meanwhile, content of squalene was decreased with the increase of deodorization temperature (150~240 ℃). When the deodorization temperature was increased to 210 ℃, content of squalene was decreased by 53.70%. Subsequently, content of squalene was not change significantly after deodorization temperature was elevated to 240 ℃. The content of total sterols in crude camellia oil was 3074.24 mg/kg. After deacidification, content of total sterols was decreased (14.2%), but it was increased after decolorization (13.2%). With the increasing of refining degree, δ-7-oat sterol was disappeared, and β-sitosterol was formed. In addition, the content of δ-5,23-soybean sterol was substantially changed. Deodorization process and the increasing of deodorization temperature evidently reduced the types of volatile organic compounds in camellia oil, and the quantity and relative percentage content of acids, alcohols and esters were greatly decreased.

TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare subtype of kidney cancer with no standard treatment options for the advanced disease. Here, the authors perform genomic and transcriptomic profiling of 63 untreated primary TFE3-tRCC tumours and reveal potential therapeutic targets.

Background: Pyroptosis is an important component of the tumor microenvironment and associated with the occurrence and progression of cancer. As the expression of pyroptosis-related genes and its impact on the prognosis of colon cancer (CC) remains unclear, we constructed and validated a pyroptosis-related genes signature to predict the prognosis of patients with CC.Methods: Microarray datasets and the follow-up clinical information of CC patients were obtained from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Candidate genes were screened out for further analysis. Various methods were combined to construct a robust pyroptosis-related genes signature for predicting the prognosis of patients with CC. Based on the gene signature and clinical features, a decision tree and nomogram were developed to improve risk stratification and quantify risk assessment for individual patients.Results: The pyroptosis-related genes signature successfully discriminated CC patients with high-risk in the training cohorts. The prognostic value of this signature was further confirmed in independent validation cohort. Multivariable Cox regression and stratified survival analysis revealed this signature was an independent prognostic factor for CC patients. The decision tree identified risk subgroups powerfully, and the nomogram incorporating the gene signature and clinical risk factors performed well in the calibration plots.Conclusion: Pyroptosis-related genes signature was an independent prognostic factor, and can be used to predict the prognosis of patients with CC.

Glioblastoma (GBM), a highly aggressive form of brain tumor, responds poorly to current conventional therapies, including surgery, radiation therapy, and systemic chemotherapy. The reason is that the delicate location of the primary tumor and the existence of the blood-brain barrier limit the effectiveness of traditional local and systemic therapies. The immunosuppressive status and multiple carcinogenic pathways in the complex GBM microenvironment also pose challenges for immunotherapy and single-targeted therapy. With an improving understanding of the GBM microenvironment, it has become possible to consider the immunosuppressive and highly angiogenic GBM microenvironment as an excellent opportunity to improve the existing therapeutic efficacy. Oncolytic virus therapy can exert antitumor effects on various components of the GBM microenvironment. In this review, we have focused on the current status of oncolytic virus therapy for GBM and the related literature on antitumor mechanisms. Moreover, the limitations of oncolytic virus therapy as a monotherapy and future directions that may enhance the field have also been discussed.

BackgroundIncreasing evidence has emerged to reveal the correlation between genomic instability and long non-coding RNAs (lncRNAs). The genomic instability-derived lncRNA landscape of prostate cancer (PCa) and its critical clinical implications remain to be understood.MethodsPatients diagnosed with PCa were recruited from The Cancer Genome Atlas (TCGA) program. Genomic instability-associated lncRNAs were identified by a mutator hypothesis-originated calculative approach. A signature (GILncSig) was derived from genomic instability-associated lncRNAs to classify PCa patients into high-risk and low-risk groups. The biochemical recurrence (BCR) model of a genomic instability-derived lncRNA signature (GILncSig) was established by Cox regression and stratified analysis in the train set. Then its prognostic value and association with clinical features were verified by Kaplan–Meier (K-M) analysis and receiver operating characteristic (ROC) curve in the test set and the total patient set. The regulatory network of transcription factors (TFs) and lncRNAs was established to evaluate TF–lncRNA interactions.ResultsA total of 95 genomic instability-associated lncRNAs of PCa were identified. We constructed the GILncSig based on 10 lncRNAs with independent prognostic value. GILncSig separated patients into the high-risk (n = 121) group and the low-risk (n = 121) group in the train set. Patients with high GILncSig score suffered from more frequent BCR than those with low GILncSig score. The results were further validated in the test set, the whole TCGA cohort, and different subgroups stratified by age and Gleason score (GS). A high GILncSig risk score was significantly associated with a high mutation burden and a low critical gene expression (PTEN and CDK12) in PCa. The predictive performance of our BCR model based on GILncSig outperformed other existing BCR models of PCa based on lncRNAs. The GILncSig also showed a remarkable ability to predict BCR in the subgroup of patients with TP53 mutation or wild type. Transcription factors, such as FOXA1, JUND, and SRF, were found to participate in the regulation of lncRNAs with prognostic value.ConclusionIn summary, we developed a prognostic signature of BCR based on genomic instability-associated lncRNAs for PCa, which may provide new insights into the epigenetic mechanism of BCR.

Background: Pancreatic squamous cell carcinoma (PSCC) is a rare pancreatic malignancy compared to most common pancreatic adenocarcinoma (PAC). Aims: To analyze the prognostics factors of PSCC and compare PAC with PSCC in demographic patterns, clinicopathologic characteristics and treatment modalities. Methods: Data of PSCC and PAC patients from January 1, 2004 to December 31, 2015 were extracted from Surveillance, Epidemiology and End Results (SEER) database for case-control study. Kaplan-Meier method and Cox proportional hazards analysis were used in survival analysis. A 1:3 propensity-score matching (PSM) was performed to compare the overall survival (OS) and cancer specific survival (CSS) between PAC and PSCC in each variable. Results: PAC patients (n = 38 968) and PSCC patients (n = 124) were analyzed. After PSM, 372 PAC patients and 124 PSCC patients were obtained. PSCC tends to happen to elders, white and female with a predilection site of pancreatic head, followed by tail, then body. PSCC have a higher proportion to be poorly differentiated and metastatic when diagnosed. The prognosis of PSCC patients was significantly worse than PAC patients in both univariate and multivariate analyses. Surgery and chemotherapy were independent prognostic factors for PSCC. Conclusions: PSCC patients were identified associated with a worse prognosis than PAC patients. PSCC tend to be poorly differentiated and more easily to be metastatic. Surgery and chemotherapy may be effective therapies to improve the OS of PSCC significantly.

Abstract The outbreak of coronavirus disease 2019 (COVID-19) triggered by the new member of the coronaviridae family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented challenge for global health. In addition to mild to moderate clinical manifestations such as fever, cough, and fatigue, severe cases often developed lethal complications including acute respiratory distress syndrome (ARDS) and acute lung injury. Given the alarming rate of infection and increasing trend of mortality, the development of underlying therapeutic and preventive treatment, as well as the verification of its effectiveness, are the top priorities. Current research mainly referred to and evaluated the application of the empirical treatment based on two precedents, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), including antiviral drugs targeting different stages of virus replication, immunotherapy modulating the overactivated inflammation response, and other therapies such as herbal medicine and mesenchymal stem cells. Besides, the ongoing development of inventing prophylactic interventions such as various vaccines by companies and institutions worldwide is crucial to decline morbidity and mortality. This review mainly focused on promising candidates for the treatment of COVID-19 and collected recently updated evidence relevant to its feasibility in clinical practice in the near future.

Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of multiple malignancies, especially in non-small cell lung cancer (NSCLC). With the extensive application of ICIs in clinical practice, clinicians have to manage their toxicities, which are often termed immune-related adverse events (irAEs). Several ICIs, such as nivolumab, pembrolizumab, atezolizumab, and durvalumab, have been approved by the US Food and Drug Administration (FDA) to treat advanced NSCLC, accompanied by a broad spectrum of toxicity reactions. However, ICIs-associated neurological toxicities, regarding polyneuropathy, Bell palsy, encephalopathy, and myasthenia gravis, as uncommon emerging toxicities have not been well recognized, present a challenge for clinicians to improve awareness of supervision, recognition, and management before death from them. Herein, we have summarized the incidence, diagnosis, clinical manifestations, potential mechanisms, treatments, and outcomes of ICIs-related neurotoxicity and optimized the management approach for NSCLC patients. Prompt recognition and proper management are indispensable to reduce the morbidity of these patients with immune-related neurological toxicities.

The outer surface of the tube is worn under the interaction between the velocity difference and rolling pressure, in the process of rolling the circular tube into a rectangular tube. In order to predict the wear depth, according to the characteristics of roll forming, the causes of wear in the forming process are analyzed. The finite element model of rolling forming was established based on Archard theory, and the 40 mm × 27.5 mm × 3 mm SUS304 stainless steel rectangular tube was simulated. The simulated results were compared with a test rolling of the steel tubes of the same size material, and the wear areas were found to be highly consistent, which verified the accuracy of the finite element model. The effects of the friction coefficient and the flat roller angular velocity on the simulation results which wear depth were analyzed, and the regression model of wear depth was established by response surface method. The results showed that the flat roller angular velocity had the greatest effect on wear depth; moreover, the flat roller friction coefficient was the second, and the vertical roller friction coefficient was the lowest. The minimum value of the regression model was optimized, the simulation value of the optimization scheme was compared with the optimized value, and the error of the two values was less than 5%, which verified the correctness of the regression model. The wear depth of the rectangular tube after optimization was reduced by 64.69% compared with that before optimization, which verified the effectiveness of the optimization results.

Somatic mutation-derived neoantigens, expressed only on tumor cells, may elicit antitumor T-cell responses in cancer immunotherapies with minimal immune tolerance. Neoantigens can be identified by multiple bioinformatics technologies, mainly based on whole-exome sequencing. Personalized cancer vaccines and adoptive T cell therapies are two primary treatment modalities targeting neoantigens, and both of them have shown promising therapeutic effects. This review, summarizes the history of neoantigen-related tumor control, introduces recent neoantigen screening and identification methods, and discusses the role of neoantigen in cancer immunotherapies. Moreover, we propose the challenges of targeting neoantigens for cancer treatment.

The hydrogen embrittlement problem of alloy steel heavy forgings not only has the common properties of general hydrogen embrittlement, but also has the characteristics brought by its scale characteristics. The research of hydrogen embrittlement, combined with its characteristics and commonness, is of vital importance for the service safety of engineering structures. The temperature field and microstructure distribution in the machining process were investigated through the simulation of a finite element. On this basis, the physical simulation experiments were carried out to obtain the microstructure of heavy forgings in radial directions. The hydrogen embrittlement sensitivity was characterized by electrochemical hydrogen charging and slow strain rate tests (SSRT). The microstructure and fracture morphology of the samples were characterized to explore the law and mechanism of hydrogen embrittlement sensitivity gradient distribution along the axial direction. It is helpful to understand the hydrogen embrittlement of heavy forgings in order to guide engineering practice.

A novel nitrogen-containing alkylphosphinate salt—aluminium β-(p-nitrobenzamide) ethyl methyl phosphinate (AlNP) was synthesized and used to flame retard acrylonitrile–butadiene–styrene copolymer (ABS). The Fourier transform infrared spectrometry, 1H, 13C and 31P nuclear magnetic resonance and X-ray fluorescent spectroscopy (XRF) were applied to characterize the structure and composition of products. The flame retardancy performance, thermal properties and mechanical strength of the ABS/AlNP with respect to AlNP loading were investigated. AlNP was stable before 330°C and decomposed very slowly with residues high up to 56.1% at 700°C. Adding 25–30 wt% of AlNP alone can make ABS to pass V0 rating in the vertical burning tests (UL 94). The results according to the micro combustion calorimeter, thermogravimetric analysis showed that AlNP can depress the heating release and retard the thermal degradation of the ABS. Scanning electron microscopy observation of the residues from LOI test indicated that AlNP formed the condensed and tough residues layer during combustion; XRF analysis showed that the residues contained phosphorus and aluminium element and nitrogen element was not detected. The compact phosphorus/aluminium-rich substance acted as a barrier to enhance flame-retardant properties of the ABS.

The structural analogs, 2,4-dibromophenol (2,4-DBP) and 2,4-dibromoanisole (2,4-DBA), have both natural and artificial sources and are frequently detected in environmental matrices. Their environmental fates, especially volatilization, including both direct volatilization from cultivation solution and phytovolatilization through rice plants were evaluated using hydroponic exposure experiments. Results showed that 2,4-DBA displayed stronger volatilization tendency and more bioaccumulation in aboveground rice tissues. Total volatilized 2,4-DBA accounted for 4.74% of its initial mass and was 3.43 times greater than 2,4-DBP. Phytovolatilization of 2,4-DBA and 2,4-DBP contributed to 6.78% and 41.7% of their total volatilization, enhancing the emission of these two contaminants from hydroponic solution into atmosphere. In this study, the interconversion processes between 2,4-DBP and 2,4-DBA were first characterized in rice plants. The demethylation ratio of 2,4-DBA was 12.0%, 32.0 times higher than methylation of 2,4-DBP. Formation of corresponding metabolites through methylation and demethylation processes also contributed to the volatilization of 2,4-DBP and 2,4-DBA from hydroponic solution into the air phase. Methylation and demethylation processes increased phytovolatilization by 12.1% and 36.9% for 2,4-DBP and 2,4-DBA. Results indicate that phytovolatilization and interconversion processes in rice plants serve as important pathways for the global cycles of bromophenols and bromoanisoles.

The contactless electric–field accomplishes particles alignment in solution allowing free solvent evaporation without electrochemical decomposition. Herein the nanoparticle Li1+xAlxGe2-x(PO4)3(LAGP) Z-direction (out-of-plane) alignment was driven by a contactless electric field within a cross-linked solid electrolyte of poly(ethylene oxide)/poly(ethylene glycol) diacrylate/lithium bis(trifluoromethylsulfonyl)imide (PEO/PEGDA/LiTFSI). The alignment and chain formation of nanoparticles was verified by scanning electron microscope combining with energy dispersive X-ray spectrometry. Benefiting from this Z-direction alignment, LAGP/PEO/PEGDA/LiTFSI membrane possesses enhanced ionic conductivity and improved flexibility. With 20 wt% LAGP loading, 2.7 times ionic conductivity was achieved in the Z- direction and 1.6 times elongation at breaking was obtained along the membrane surface after alignment. This contactless electrical field method is a new strategy to prepare polymer composite membrane with anisotropic property from solvent-containing system.

Introduction: Sequential therapy with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) is effective in some patients with metastatic renal cell carcinoma (mRCC) progressed from or were intolerant to a prior TKIs. Anlotinib is a multi-kinase inhibitor targeting VEGFR1/2/3, PDGFR and FGFR, which has demonstrated efficacy and safety in first-line treatment of mRCC. This study assessed the potential of anloitnib as second-line treatment for patients with mRCC after prior one VEGFR-TKI.Methods: This is a single-arm, open-label, phase 2 study. Patients progressed after or were intolerant to sorafenib or sunitinib were enrolled. Anlotinib was administrated orally 12 mg once daily for 14 days every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), safety and quality of life (QoL).Results: Forty three patients were enrolled and 42 received anlotinib, of whom 32 progressed after and 10 were intolerant to sorafenib or sunitinib. Median PFS were 14.0 months (95% CI 8.3–20.3) and 8.5 months (95% CI 5.6–16.6) for overall population and patients progressed after a previous VEGFR-TKI, respectively. Median OS was 21.4 months (95% CI 16.0–34.5), confirmed ORR and DCR were 16.7 and 83.3% in overall population. The most common adverse events included diarrhea (47.6%), hypertension (45.2%), hand and foot syndrome (42.9%), and fatigue (40.5%). Grade 3 hematological adverse events occurred in four cases, while no grade 4 hematological adverse events was observed.Conclusions: Anlotinib showed promising efficacy as well as favorable safety as second-line treatment for patients with mRCC.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02072044.

High-strength aluminum alloys are widely used in industry. Hydrogen embrittlement greatly reduces the performance and service safety of aluminum alloys. The hydrogen traps in alumi-num profoundly affect the hydrogen embrittlement of aluminum. Here, we took a coinci-dence-site lattice (CSL) symmetrically tilted grain boundary (STGB) Σ5(120)[001] as an example to carry out molecular dynamics (MD) simulations of hydrogen diffusion in aluminum at dif-ferent temperatures, and to obtain results and rules consistent with the experiment. At 700 K, three groups of MD simulations with concentrations of 0.5, 2.5 and 5 atomic % hydrogen (at. % H) were carried out for STGB models at different angles. By analyzing the simulation results and the MSD curves of hydrogen atoms, we found that, in the low hydrogen concentration of STGB models, the grain boundaries captured hydrogen atoms and hindered their movement. In high-hydrogen-concentration models, the diffusion rate of hydrogen atoms was not affected by the grain boundaries. The analysis of the simulation results showed that the diffusion of hydro-gen atoms at the grain boundary is anisotropic.

The Titanium nitride was made by the carbamide and titanic chloride precursors. XRD results indicate that the precursor ratio N:Ti 3:1 leads to higher crystallinity. SEM and EDX demonstrated that Ti and N elements were distributed uniformly with the ratio of 1:1. The TiN used as the electrode material for supercapacitor was also studied. The specific capacities were changed from 407 F.g−1 to 385 F.g−1, 364 F.g−1 and 312 F.g−1, when the current densities were changed from 1 A.g−1 to 2 A.g−1, 5 A.g−1 and 10 A.g−1, respectively. Chronopotentiometry tests showed high coulombic efficiency. Cycling performance of the TiN electrode was evaluated by CV at a scanning rate of 50 mV.s−1 for 20,000 cycles and there was about 9.8% loss. These results indicate that TiN is a promising electrode material for the supercapacitors. Keywords: Energy storage, Nanomaterials, Anode, Titanium nitride, Supercapacitors

The quantum yield (QY) and lifetime are the important parameters for the photoluminescent materials. The data here report the changes of the QY and lifetime for the quantum dot (QD) nanocomposite after the UV curing of the urethane acrylate prepolymer. The data were collected based on the water soluble CdTe QDs and urethane acrylate prepolymer. Colloidal QDs were in various concentration from 0.5×10−3 molL−1 to 10×10−3 molL−1, and 1% (wt%) 1173 was the photoinitiator. The QY before the curing was 56.3%, 57.8% and 58.6% for the QDs 510 nm, 540 nm and 620 nm, respectively. The QY after the curing was changed to 8.9%, 9.6% and 13.4% for the QDs 510 nm, 540 nm and 620 nm, respectively. Lifetime data showed that the lifetime was changed from 23.71 ns, 24.55 ns, 23.52 ns to 1.29 ns, 2.74 ns, 2.45 ns for the QDs 510 nm, 540 nm and 620 nm, respectively.

Flame-retardant polyvinyl alcohol (PVA) membranes with high transparency and flexibility were prepared by mixing an aqueous solution of a phosphorus-containing acrylic acid (AOPA) with PVA. The reaction between AOPA and PVA, the transparency, the crystallinity and the flexibility of the membrane were investigated with Fourier transform infrared spectrometry (FTIR), UV–vis light transmittance, X-ray diffraction and tensile tests, respectively. The limited oxygen index (LOI) and vertical flame (UL 94 VTM), microscale combustion calorimetry, thermogravimetric analysis (TGA) and TGA-FTIR were employed to evaluate the flame retardancy as well as to reveal the corresponding mechanisms. Results showed that PVA containing 30 wt% of AOPA can reach the UL 94 VTM V0 rating with an LOI of 27.3% and retain 95% of the original transparency of pure PVA. Adding AOPA reduces crystallinity of PVA, while the flexibility is increased. AOPA depresses the thermal degradation of PVA and promotes char formation during combustion. The proposed decomposition mechanism indicates that AOPA acts mainly in the condensed phase.

Methylated melamine grafted polyvinyl benzylchloride (mm-g-PvBCl) was prepared which was used as additive in poly(vinyl alcohol) (PVA) and graphene nanosheets (GNs) were used to reinforce the mechanical strength. Using casting method, antimicrobial nanocomposite films were prepared with the polymeric biocide loading lever of 1 wt%, 5 wt%, and 10 wt%. Thermogravimetric analysis (TGA) characterization revealed the 2.0 wt% of graphene content in resultant nanocomposites films. XRD showed that the resultant GNs 2 theta was changed from 16.6 degree to 23.3 degree. Using Japanese Industry Standard test methods, the antimicrobial efficiency for the loading lever of 1 wt%, 5 wt%, and 10 wt% was 92.0%, 95.8%, and 97.1%, respectively, against gram negative bacteria E. coli and 92.3%, 99.6%, and 99.7%, respectively, against the gram positive S. aureus. These results indicate the prepared nanocomposite films are the promising materials for the food and drink package applications.

BACKGROUND: It is very difficult to prevent pulmonary tuberculosis (TB) due to the lack of specific and diagnostic markers, which could lead to a high incidence of pulmonary TB. We screened the differentially expressed serum microRNAs (miRNAs) as potential biomarkers for the diagnosis of pulmonary TB. METHODS: In this study, serum miRNAs were screened using the Solexa sequencing method as the potential biomarkers for the diagnosis of pulmonary TB. The stem-loop quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was used to verify differentially expressed serum miRNAs. The receiver operating characteristic (ROC) curve and logistic regression model were used to analyze the sensitivity and specificity of the single miRNA and a combination of miRNAs for diagnosis, respectively. Using the predicted target genes, we constructed the regulatory networks of miRNAs and genes that were related to pulmonary TB. RESULTS: The Solexa sequencing data showed that 91 serum miRNAs were differentially expressed in pulmonary TB patients, compared to healthy controls. Following qRT-PCR confirmation, six serum miRNAs (hsa-miR-378, hsa-miR-483-5p, hsa-miR-22, hsa-miR-29c, hsa-miR-101 and hsa-miR-320b) showed significant difference among pulmonary TB patients, healthy controls (P

BACKGROUND: A large number of studies have investigated whether polymorphisms in the Toll-like receptor (TLR) genes are implicated in susceptibility to tuberculosis (TB) in different populations. However, the results are inconsistent and inconclusive. METHODS: A literature search was conducted using the PubMed, EMBASE, Medline (Ovid), ISI Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI). A meta-analysis on the associations between the TLR1 G1805T, TLR2 T597C, T1350C, G2258A, and TLR6 C745T polymorphisms and TB risk was carried out by comparison using different genetic models. RESULTS: In total, 16 studies from 14 articles were included in this review. In meta-analysis, significant associations were observed between the TLR2 2258AA (AA vs. AG+AG, OR 5.82, 95% CI 1.30-26.16, P = 0.02) and TLR6 745TT (TT vs. CT+CC, OR 0.61, 95% CI 0.39-0.97, P = 0.04) polymorphisms and TB risk. In the subgroup analysis by ethnicity, Africans and American Hispanic subjects with the TLR1 1805T allele had an increased susceptibility, whereas Asian and European subjects with the TLR2 2258A allele had an increased susceptibility to TB. CONCLUSIONS: The meta-analysis indicated that TLR2 G2258A is associated with increased TB risk, especially in Asians and Europeans. TLR1 G1805T is associated with increased TB in Africans and American Hispanics. TLR6 C745T is associated with decreased TB risk. Our systematic review and meta-analysis reported an interesting preliminary conclusion, but this must be validated by future large-scale and functional studies in different populations.

Developing highly efficient and low-cost photoelectrocatalyst for H2 evolution under visible-light irradiation is a key topic in the areas of energy and environment. In this work, we designed and deposited p-type semiconductor Cu3N onto 1D n-type rutile TiO2 nanorod array by the magnetron sputtering method. The formed TiO2/Cu3N p-n heterojunction not only exhibits a narrowed band gap from 3.09 eV for TiO2 to 2.01 eV for TiO2/Cu3N but also expands the light-response from UV to visiblelight region. In addition, the lifetime, separation and transfer of the photogenerated electron-hole pairs are efficiently prolonged and improved due to the build-in electric field at the interface of the TiO2/Cu3N p-n heterojunction. As a result, the photocurrent density under 4420 nm visible-light irradiation is enhanced for about 14.12 times, from 0.33 mA cm2 for TiO2 to 4.66 mA cm2 for TiO2/Cu3N at 0.97 V vs. RHE (reversible hydrogen electrode). Furthermore, the constructed TiO2/Cu3N heterojunction shows stable PEC H2 evolution performance, with the H2 production rate reaching 6.98 mmol cm2 h1 under 4420 nm visible-light irradiation. Our results suggest that the construction of nontoxic p-n heterojunction with suitable band gap should be a promising strategy to improve the photoelectrocatalytic performance of TiO2 and should be applied in other photoelectrocatalysts. [ABSTRACT FROM AUTHOR]