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Combining encapsulated Co@C catalyst and H3PO4 aqueous solution, high value-added chemicals that are widely used in various fields can be obtained from renewable biomass materials.

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

Aim: To explore the association between TP53 mutation and atezolizumab in non-small-cell lung cancer (NSCLC) patients. Materials & methods: Patients with NSCLC from the POPLAR and OAK studies were included. Kaplan–Meier analysis was performed to detect progression-free survival (PFS) and overall survival (OS). PFS and OS were compared using multivariate Cox regression analysis. Results: OS was significantly longer with atezolizumab compared with docetaxel among TP53/KRAS co-mutant NSCLC patients (hazard ratio [HR]: 0.014; 95% CI: 0.000–0.721). There is no significant OS difference between atezolizumab versus docetaxel for TP53-mutant NSCLC patients (HR: 0.831; 95% CI: 0.473–1.458). There is no significant OS difference between atezolizumab versus docetaxel for KRAS-mutant NSCLC patients (HR: 1.354; 95% CI: 0.528–3.472). Conclusion: PD-L1 inhibitors may bring OS benefits for patients with NSCLC harbored TP53/KRAS co-mutation.

Background Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and is a major cause of mortality. Risk stratification for PM can optimize decision making in GC treatment. Methods A total of 25 GC patients (13 with synchronous, 6 with metachronous PM and 6 PM-free) were included in this study. Quantitative proteomics by high-depth tandem mass tags labeling and whole-exome sequencing were conducted in primary GC and PM samples. Proteomic signature and prognostic model were established by machine learning algorithms in PM and PM-free GC, then validated in two external cohorts. Tumor-infiltrating immune cells in GC were analyzed by CIBERSORT. Results Heterogeneity between paired primary and PM samples was observed at both genomic and proteomic levels. Compared to primary GC, proteome of PM samples was enriched in RNA binding and extracellular exosomes. 641 differently expressed proteins (DEPs) between primary GC of PM group and PM-free group were screened, which were enriched in extracellular exosome and cell adhesion pathways. Subsequently, a ten-protein signature was derived based on DEPs by machine learning. This signature was significantly associated with patient prognosis in internal cohort and two external proteomic datasets of diffuse and mixed type GC. Tumor-infiltrating immune cell analysis showed that the signature was associated with immune microenvironment of GC. Conclusions We characterized proteomic features that were informative for PM progression of GC. A protein signature associated with immune microenvironment and patient outcome was derived, and it could guide risk stratification and individualized treatment.

Objective: Esophageal carcinoma (ESCA) is a common malignancy characterized by high morbidity and mortality. Our work managed to dissect the modulatory mechanism of E2F1/miR-29c-3p/COL11A1 in the malignant progression and sensitivity of ESCA cells to sorafenib. Methods: Via bioinformatics approaches, we identified the target miRNA. Subsequently, CCK-8, cell cycle analysis, and flow cytometry were used to check the biological influences of miR-29c-3p on ESCA cells. TransmiR, mirDIP, miRPathDB, and miRDB databases were used as tools for the prediction of upstream transcription factors and downstream genes of miR-29c-3p. The targeting relationship of genes was detected via RNA immunoprecipitation and chromatin immunoprecipitation, which was further validated by dual-luciferase assay. Finally, in vitro experiments revealed the way E2F1/miR-29c-3p/COL11A1 affected sorafenib’s sensitivity, and in vivo experiments were used to verify the way E2F1 and sorafenib impacted ESCA tumor growth. Results: miR-29c-3p, downregulated in ESCA, could suppress ESCA cell viability, arrest the cell cycle in the G0/G1 phase, and impel apoptosis. E2F1 was found to be upregulated in ESCA and it could abate the transcriptional activity of miR-29c-3p. COL11A1 was found to be a downstream target of miR-29c-3p to enhance cell viability, induce cell cycle arrest in S phase, and constrain apoptosis. Cellular and animal experiments together demonstrated that E2F1 abated the sorafenib’s sensitivity of ESCA cells via miR-29c-3p/COL11A1. method: Via bioinformatics approaches, we identified the target miRNA. Subsequent CCK-8 and flow cytometry checked the biological influences of miR-29c-3p on ESCA cells. Bioinformatics approaches were tools for prediction of upstream transcription factors and downstream genes of miR-29c-3p. The targeting relationship of genes was detected via RNA Immunoprecipitation and chromatin immunoprecipitation, which was further validated by dual-luciferase assay. Finally, in vitro experiments revealed the way E2F1/miR-29c-3p/COL11A1 affected sorafenib sensitivity, and in vivo experiments were used to verify the way E2F1 and sorafenib impacted on ESCA tumor growth. Conclusion: E2F1 affected the viability, cell cycle, and apoptosis of ESCA cells by modulating miR-29c-3p/COL11A1, and it attenuated the sensitivity of ESCA cells to sorafenib, shedding new light on the treatment of ESCA. result: miR-29c-3p, downregulated in ESCA, could suppress ESCA cell viability, arrest the cell cycle in the G0/G1 phase, and impel apoptosis. E2F1 was upregulated in ESCA and could abate the transcriptional activity of miR-29c-3p. COL11A1 was a downstream target of miR-29c-3p to enhance cell viability, induced cell cycle arrest in S phase, and constrained apoptosis. Cellular and animal experiments together demonstrated that E2F1 abated the sorafenib sensitivity of ESCA cells via miR-29c-3p/COL11A1. conclusion: E2F1 affected the viability, cell cycle and apoptosis of ESCA cells by modulating miR-29c-3p/COL11A1, and it attenuated the sensitivity of ESCA cells to sorafenib, shedding new light on the treatment of ESCA. other: N/A

Chenyue Zhang,1,* Zhenxiang Li,2,* Yanxiang Zhang,3 Chenglong Zhao,4 Hui Wang,5 Jiamao Lin,6 Cuicui Liu,7 Xiaohui Wang,8 Haiyong Wang9 1Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, 200032, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3Berry Oncology Corporation, Beijing, 102206, People’s Republic of China; 4Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, 250013, People’s Republic of China; 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 6Department of Traditional Chinese Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 7Department of Oncology, Linyi People’s Hospital, Linyi, 276000, People’s Republic of China; 8Research Service Office, Shandong Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 9Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyong Wang, Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Tel +86 0531 67626332, Fax +86 0531 67626332, Email wanghaiyong6688@126.comBackground: Pulmonary sarcomatoid carcinoma (PSC) is a rare and distinct subtype of lung cancer characterized by its aggressiveness and dismal prognosis. However, genomic landscape and immune contexture have not been fully elucidated among PSC patients.Methods: In the present study, whole-exome-sequencing (WES) analyses were performed to depict genomic landscape of 38 independent PSC samples. Tumor mutation burden (TMB) was calculated with the total number of non-synonymous SNVs and indel variants per megabase of coding regions. PD-L1 expression and CD8+ T cell density were evaluated by immunohistochemistry in PSC samples. Their associations with genomic mutation were further assessed in genes with most frequent mutation. Overall survival (OS) of PSC patients with top mutated genes and high and low TMB, PD-L1 and CD8+ TIL expressions were further compared. Subgroup analyses of OS stratified by morphology and pathological type were conducted. Their correlation with TMB, PD-L1 and CD8+ T cell were further assessed.Results: We identified a cohort of genomic and somatic mutation in PSC patients. Subgroup patients with distinct clinicopathological features were found to harbor different genomic mutations and immunologic features. Besides, genomic profiles influenced outcomes, with SARS mutation associated with worsened prognosis.Conclusion: Through the mapping of genetic and immunologic landscape, we find the heterogeneity among the subgroups of PSC. Our findings may provide opportunities for therapeutic susceptibility among Chinese PSC patients.Keywords: pulmonary sarcomatoid carcinoma, mutational landscape, tumor mutational burden, programmed death ligand-1, CD8+ T cell

To achieve autonomous all-day flight by high-altitude long-endurance unmanned aerial vehicle (HALE UAV), a new navigation method with deep integration of strapdown inertial measurement unit (SIMU) and triple star sensors based on atmospheric refraction correction is proposed. By analysing the atmospheric refraction model, the stellar azimuth coordinate system is introduced and the coupling relationship between attitude and position is established. Based on the geometric relationship whereby all the stellar azimuth planes intersect on the common zenith direction, the sole celestial navigation system (CNS) method by stellar refraction with triple narrow fields of view (FOVs) is studied and a loss function is built to evaluate the navigation accuracy. Finally, the new SIMU/triple star sensors deep integrated navigation method with refraction correction upgraded from the traditional inertial navigation system (INS)/CNS integrated method can be established. The results of simulations show that the proposed method can effectively restrain navigation error of a HALE UAV in 24 h steady-state cruising in the stratosphere.

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

The encapsulated Co@C catalyst was firstly applied for the direct production of ethylene glycol (EG) from cellulose hydrogenolysis. The multi-step reaction can be well-balanced by regulating the synergy between Co@C and tungstic acid (TA).

Alanine (Ala), regarded as the building block for protein synthesis, has been widely used in the field of food processing, pharmaceutical, and bio-based plastic industries. Containing plenty of oxygenic functional groups, biomass-derived chemicals are proper for Ala synthesis in an economic and green way

A GaN complementary field-effect transistor (FET) inverter monolithically integrated with power gate-injection high-electron-mobility transistors (HEMTs) was realized on a Si substrate. The GaN p-channel and n-channel logic devices and power devices were fabricated based on a p-GaN/AlGaN/GaN epi-structure. Through optimization of epi-layer thickness and doping, excellent low-level noise margin (NM $_{L}$ ) of 1.47 V and high-level noise margin (NM $_{H}$ ) of 0.98 V were achieved at a supply voltage $V_{DD}$ of 3 V at room temperature. A maximum current density ( $I_{D,max}$ ) of 0.36 mA/mm/220 mA/mm at $V_{DS}$ of -3 V/3 V and a threshold voltage $V_{TH}$ of -2.0 V/+2.3 V were achieved in the p-channel and n-channel FETs, respectively. A propagation delay of an inverter stage $τ_{pd}$ in a ring oscillator was measured to be 1.67 μs. The power gate-injection HEMT has an on-resistance $R_{{on}}$ of 18.7 Ω ·mm and a breakdown voltage (BV) of 900 V. These results show the great potential of the developed GaN complementary FET technology in the applications of GaN power modules.

Via hydrothermal synthesis of Sn-Al gels, mild dealumination and ion exchange, a bimetallic Sn-Ni-Beta catalyst was prepared which can convert glucose to methyl lactate (MLA) and methyl vinyl glycolate (MVG) in methanol at yields of 71.2 % and 10.2 %, respectively. Results from solid-state magic-angle spinning nuclear magnetic resonance, X-ray photoelectron spectroscopy, transmission electron microscopy, spectroscopic analysis, probe-temperature-programmed desorption, and density functional theory calculations conclusively reveal that the openness of the Sn sites, such as by the formation of [(SiO)

Small cell lung cancer (SCLC) is a heterogeneous malignancy with dismal prognosis. However, few studies have conducted on the metabolic heterogeneity in SCLC.We therefore identify SCLC classifications using untargeted metabolomics and lipidomics. We also compared their survival and the immunotherapy responses.Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis was performed in 191 SCLC serum samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to identify metabolic pathways. The Kaplan-Meier and log-rank test were used to analyze the survival curves. The univariate and multivariate Cox proportional hazards regression models were used to evaluate prognostic factors for OS in patients with SCLC.Distinct subtypes of SCLC were identified by consensus clustering algorithm using partioning around medoids (pam) based on untargeted metabolomics and lipidomics. Four distinct subtypes of SCLC were identified, with distinct metabolic pathways. Subgroup 2 had the longest survival whereas Subgroup 1 had the shortest. Subtype 2 benefited most from immunotherapy in OS, as in contrast to Subtype 3 with shortest survival.Our study revealed the metabolic heterogeneity in SCLC and identified four subtypes with distinct metabolic features. It indicates promising therapeutic and prognostic value that may guide treatment for SCLC. The subtype-specific clinical trials may be designed and would be instructive for drug development.

Non-small cell lung cancer (NSCLC) accounts for about 85% in all cases of lung cancer. In recent years, molecular targeting drugs for NSCLC have been developed rapidly. The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have changed the paradigm of cancer therapy from empirical cytotoxic chemotherapy to molecular-targeted cancer therapy. Currently, there are three generations of EGFR-TKIs, all of which have achieved good efficacy in clinical therapy. However, most patients developed drug resistance after 6-13 months EGFR-TKIs treatment. Therefore, a comprehensive understanding of EGFR-TKIs resistance mechanisms is of vital importance for clinical management of NSCLC.Relevant data and information about the topic were obtained by searching PubMed (Medline), Web of Science and Google Scholar using the subject headings, such as "NSCLC", "EGFR-TKIs resistance", "EGFR mutations", "human epidermal growth factor receptor-2 (HER2/erbB-2)", "hepatocyte growth factor (HGF)", "vascular endothelial growth factor (VEGF)", "insulin-like growth factor 1 (IGF-1)", "epithelial-mesenchymal transition (EMT)", "phosphatase and tensin homolog (PTEN)", "RAS mutation", "BRAF mutation", "signal transducer and activator of transcription 3 (STAT3)", and "tumor microenvironment", etc. RESULTS: The mechanisms for EGFR-TKIs resistance include EGFR mutations, upregulation of HER2, HGF/c-MET, VEGF IGF1, EMT and STAT3 pathways, mutations of PTEN, RAS and BRAF genes, and activation of other by-pass pathways. These mechanisms are interconnected and can be potential targets for the treatment of NSCLC.In this review, we discuss the mechanisms of EGFR-TKIs drug resistance and the clinical strategies to overcome drug resistance from the perspective of EGFR-TKIs combined treatment.

Background Combined small cell lung cancer (c-SCLC) distinguishes itself from small cell lung cancer (SCLC) due to its inclusion of both SCLC and non-small cell lung cancer (NSCLC) components. Few studies have compared clinicopathological characteristics, prognosis and factors affecting survival. We therefore addressed the issues in this study. Patients and Methods A total of 400 c-SCLC and 20,841 SCLC patients were enrolled using SEER database. Difference in clinicopathological characteristics of SCLC and c-SCLC patients was analyzed using chi-square. Kaplan–Meier was applied to compare their survival before and after propensity score matching (PSM). Cox regression model was adopted to assess the impact of different clinical variables on survival. Logistic regression was applied to identify risk factors for c-SCLC and SCLC patients. Results Differences in race, sex, T stage, N stage, surgery, bone, brain and liver metastasis were detected between c-SCLC and SCLC patients. c-SCLC patients had better overall survival (OS) than SCLC patients before PSM. Age, race, sex, T stage, N stage, surgery, bone, brain, liver and lung metastasis were prognostic factors affecting OS for c-SCLC and SCLC (P < 0.05). However, a significant OS benefit was not observed in c-SCLC after adjusting for clinicopathological variables (HR, 0.950; 95% CI, 0.842–1.073; P=0.411). No significant OS difference was found between c-SCLC and SCLC patients after PSM (P = 0.789). c-SCLC patients had lower risk of lymph node (OR: 0.555; 95% CI: 0.439–0.703; P < 0.001) and liver metastasis (OR: 0.591; 95% CI: 0.448–0.779; P < 0.001), whereas had no significant differences in bone and brain metastasis risks (P > 0.05) compared with SCLC patients. Conclusion The prognosis of c-SCLC did not significantly differ from that of SCLC if clinicopathological characteristics are controlled. Better prognosis for c-SCLC patients over SCLC patients may be ascribed to fewer liver and lymph node metastases upon diagnosis.

A monolithic bidirectional switch based on anti-paralleled two reverse blocking p-GaN HEMTs has been proposed and demonstrated in this work. The recessed Schottky drain technique is utilized to effectively reduce the on-state voltage and thus lowering the power loss of bidirectional switches. A significant reduction in parasitic elements and switch area is obtained by monolithic integration. The fabricated bidirectional switch exhibits a threshold voltage of ~1.85 V, on-state voltage of ~0.63 V, and the forward and reverse off-state breakdown voltages of ~650 V at ${I}_{{\text {S1}-\text {S2}}} = 1\,\,\mu \text{A}$ /mm. In addition, the function of proposed bidirectional switch as an AC power chopper has been successfully verified.

Small-cell lung cancer (SCLC) is an exceptionally lethal malignancy characterized by extremely high alteration rates and tumor heterogeneity, which limits therapeutic options. In contrast to non-small-cell lung cancer that develops rapidly with precision oncology, SCLC still remains outside the realm of precision medicine. No recurrent and actionable mutations have been detected. Additionally, a paucity of substantive tumor specimens has made it even more difficult to classify SCLC subtypes based on genetic background. We therefore carried out whole-exome sequencing (WES) on the largest available Chinese SCLC cohort. For the first time, we partitioned SCLC patients into three clusters with different genomic alteration profiles and clinical features based on their mutational signatures. We showed that these clusters presented differences in intratumor heterogeneity and genome instability. Moreover, a wide existence of mutually exclusive gene alterations, typically within similar biological functions, was detected and suggested a high SCLC intertumoral heterogeneity. Particularly, Cluster 1 presented the greatest potential to benefit from immunotherapy, and Cluster 3 constituted recalcitrant SCLC, warranting biomarker-directed drug development and targeted therapies in clinical trials. Our study would provide an in-depth insight into the genome characteristics of the Chinese SCLC cohort, defining distinct molecular subtypes as well as subtype-specific therapies and biomarkers. We propose tailoring differentiated therapies for distinct molecular subgroups, centering on a personalized precision chemotherapy strategy combined with immunization or targeted therapy for patients with SCLC.