Rice husk is considered as a waste product of farming. However, rice husk ash (RHA) has a good pozzolanic activity, which can be used in cement-based materials as a supplementary cementitious ...material (SCM), and it is also suitable for self-compacting concrete (SCC). This study reviews the physical and chemical properties of RHA and the properties of RHA–SCC mixtures such as fresh properties (crucial factors and evaluation methods of workability for fresh SCC), mechanical properties (compressive strength, splitting tensile strength, flexural strength, and modulus of elasticity), and durability (water absorption and sorptivity, acid resistance, chloride penetration resistance, electrical resistivity, and alkali silica reaction). It was observed that the workability of SCC decreases with an increase in the incorporation rate of RHA. An incorporation rate of RHA in the range of approximately 15–20% enhances the mechanical properties and durability of SCC. The incorporation of RHA into SCC can reduce the environmental burden of rice husk treatment, and promote sustainable development of cement industries and reduce the cost of SCC.
ROS1 rearrangements are validated drivers in lung cancer, which have been identified in a small subset (1-2%) of patients with non-small cell lung cancer (NSCLC). To date, 18 fusion genes of ROS1 ...have been identified in NSCLC. The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC. Next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers many fusion genes.
A 55-year-old female with EGFR mutation (L858R) was diagnosed with lung adenocarcinoma, who was responsive to first-generation EGFR-tyrosine kinase inhibitor (TKI). Afterwards, she developed acquired resistance accompanied with a ROS1 rearrangement. A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1-33 of ROS1 on chr6: q22.1 to exons of 2-26 of ADGRG6 on chr6: q24.2. The patient was obviously responsive to crizotinib.
We firstly identified ROS1-ADGRG6 fusion variant in NSCLC by NGS, which should be considered in further ROS1 detecting assays.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer. Finding prognostic biomarkers is helpful in stratifying LUAD patients with different prognosis.
Methods
We ...explored the correlation of LUAD prognosis and genes associated with chemotherapy in LUAD and obtained data of LUAD patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Drug sensitivity data were acquired from the Genomics of Drug Sensitivity in Cancer (GDSC) database. Differential and enrichment analyses were used to screen the target genes utilizing limma and “clusterProfiler” packages. Then univariate and LASSO Cox analyses were used to select the prognosis‐related genes. Survival analysis was used to estimate the overall survival (OS) of different groups.
Results
Twenty‐three differentially expressed genes (DEGs) were screened between LUAD samples and healthy samples, and BTK, FGFR2, PIM2, CHEK1, and CDK1 were selected to construct a prognostic signature. The OS of patients in the high‐risk group (risk score higher than 0.69) was worse than that in the low‐risk group (risk score lower than 0.69).
Conclusion
The risk score model constructed by five genes is a potential prognostic biomarker for LUAD patients.
The prognostic signature in LUAD was constructed according to BTK, FGFR2, PIM2, CHEK1, and CDK1. The LUAD patients in high‐risk group exhibited a poor prognosis. The risk score model was a potential prognostic biomarker for LUAD patients.
In this work, the mechanism of polyester polycondensation catalysed by titanium catalysts was investigated using density functional theory (DFT). Three polyester polycondensation reaction mechanisms, ...including the Lewis acid mechanism (M1), the coordination of the ester alkoxy oxygen mechanism (M2) and the coordination of the carboxy oxygen mechanism (M3), were investigated. Three reaction mechanisms for the polycondensation reaction of diethyl terephthalate (DET) were investigated using Ti(OEt)4 and cationic Ti(OEt)3+ as the catalyst. The results show that the polycondensation reaction of the Lewis acid mechanism exhibits similar energy barriers to the catalyst-free condition (42.6 kcal/mol vs. 47.6 kcal/mol). Mechanism M3 gives the lowest energy barrier of 17.5 kcal/mol, indicating that Ti(OEt)4 is the active centre for the polycondensation reaction. The catalytic efficiency of Ti(OEt)3+ is lower than that of Ti(OEt)4 catalysts due to its higher DET distortion energy (67.6 kcal/mol vs. 37.4 kcal/mol) by distortion–interaction analysis.
Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic ...leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1
+
seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.
Cases of both of small- (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) were rarely reported. Although typical cases are morphologically distinct, the distinction between LCNEC and SCLC ...is still controversial, with some LCNECs showing close morphologies with SCLC. Here, we reported on a patient who had tumor with a mix of SCLC and LCNEC and uncovered these components' histological and genomic features.
A 59-year-old man was diagnosed with lung cancer and had resection surgery in our hospital. The H&E and immunohistochemistry staining revealed that the tumor had 30%-35% LCNEC and 65%-70% SCLC cells. The whole-exome sequencing (WES) identified no potentially actionable alteration in the tumor sample but found five alterations all with allele frequency over 90%, including
p.R273H,
p.Q1814K,
p.W505L,
p.M40I, and
p.L267X. The genomic results supported that these two different components shared a similar dominant clonal origin. Furthermore, fluorescence
hybridization analysis revealed that the LCNECs have a higher copy number of MET than the SCLC component while without notable difference in the copy number of HER2 and TP53. Chemotherapy with pemetrexed and carboplatin was administrated for two cycles after the surgery. Although the chest CT showed remission in the lung, he was diagnosed with bone metastasis in 1 year later. Then, he received chemotherapy with etoposide and carboplatin but had severe side effect, leading to the discontinuation of the regime. Unfortunately, he returned to the local hospital with supportive care and died shortly after.
Based on these observations, we proposed that LCNEC and SCLC components in this patient may have a common clonal origin with dual mutations in
and
, while the chromosome instability may cause multiple independent conversion that leads to LCNEC or SCLC morphologies.
Tumor mutational burden (TMB) calculated by whole-exome sequencing (WES) is proved to be effective to predict the clinical benefit of immune checkpoint blockades. However, WES is not commonly used in ...China. We aimed to determine if a 381-caner-gene panel (CGP) could be used to estimate TMB, delineate the landscape of TMB of Chinese patients and identify mutated genes and pathways related to higher TMB.
We first evaluated the correlation between the TMB estimated by a 381-cancer-gene panel MasterView and WES using the data from the melanoma sample cohort. 3023 formalin fixed, paraffin-embedded tumor specimens from 2932 Chinese patients with advanced solid tumor were profiled for 381 gene sequencing, the baits of which covered 4,557 exons of 365 cancer-related genes and 47 introns of 25 genes frequently rearranged in cancer (All performed in a lab who achieved full marks five times in the external quality assessment by College of American Pathologists CAP). Using the sequencing data, we estimated the TMB of Chinese advanced solid tumor and identified mutated genes and pathways related to higher TMB level.
381-CGP-mutational burden was strongly associated with those calculated by WES (R
= 0.978). The median TMB for each tumor type was 5.65 (colorectal cancer), 4.84 (lung cancer), 4.03 (hepatobiliary cancer), 4.03 (gastric carcinoma), 4.03 (breast cancer) mutations/mb respectively. No correlation was observed between TMB level and age (P = 0.577) or gender (P = 0.307). The TMB of patients with mismatch repair (MMR) or DNA repair response (DDR) pathway deficiency was significantly higher than that without MMR or DDR pathway deficiency (P < 0.001).
The 381-cancer gene panel is a clinical practicable method to assess tumor mutational burden compared with whole exome sequencing. MMR and DDR deficiency are correlated with higher tumor mutational burden of Chinese patients with advanced solid tumors.
Abbreviations NGS next-generation sequencing SNV single nucleotide variation indel insertion-or-deletion PANO-Seq parallel amplification and numerically optimized sequencing NTRK neurotrophic ...receptor tyrosine kinase LoD limit of detection MAF mutant allele frequency TKI tyrosine receptor kinase inhibitor EGFR epidermal growth factor receptor KRAS KRAS proto-oncogene PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha BRAF B-Raf proto-oncogene, serine/threonine kinase MET MET proto-oncogene ALK anaplastic lymphoma kinase ROS1 ROS proto-oncogene 1 RET ret proto-oncogene NRG1 neuregulin 1 CHMP2A charged multivesicular body protein 2A HLA-DRB1 human leukocyte antigen DRB1 TPR translocated promoter region protein SQSTM1 sequestosome 1 RFWD2 RING finger and WD repeat domain 2 MSN moesin PR partial response SD stable disease PD progressive disease SPATA46 spermatogenesis associated 46 LMNA lamin A/C ETV6 ETS translocation variant 6 Dear Editor, Although fusion events involving neurotrophic receptor tyrosine kinase 1, 2, and 3 genes (NTRK1, NTRK2, and NTRK3, encoding TRKA/B/C respectively) were found in diverse tumor types, only 0.1%-0.3% of lung cancer patients harbor an NTRK (and mostly NTRK1) fusion as the primary oncogenic event 1. Durable responses to tyrosine receptor kinase inhibitors (TKI) such as larotrectinib and entrectinib have been observed in a broad range of malignancies 5, 6, and the next-generation inhibitor repotrectinib exhibited promising activity against solvent-front substitution mutations 7, while inhibitors such as crizotinib initially developed for other kinases may also be effective in targeting TRK 8. TRK-fusion protein consists of an intact oncogenic kinase domain, either constitutively activated by a 5’ partner domain or overexpressed due to a stronger partner gene promoter. Since the RNA-containing tissue specimen was no longer obtainable, a modified assay targeting NTRK1 introns 7-14 (Fig. 1A) was performed, revealing a TPR-NTRK1 fusion in the plasma cell-free DNA, validated by Sanger sequencing (Fig. 1E).
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•Different Mn (II) precursors’ effects of MnO2 on toluene oxidation were observed.•MnO2-Ac showed the best activity, and good stability when 5% H2O in exhaust gas.•Specific surface ...areas, Mn3+/Mn4+ and surface adsorbed oxygen affected the activity.•Reaction pathway of toluene oxidation was presented over MnO2-Ac sample.
MnO2-Ac, MnO2-N, MnO2-Cl and MnO2-S samples were prepared by the redox reaction between potassium permanganate and manganese acetate, manganese nitrate, manganese chloride and manganese sulfate and the effect of Mn (II) precursor on the toluene oxidation was studied. The physicochemical properties of these samples were characterized by XRD, TEM, N2 asdorption-desorption isotherms, H2-TPR and XPS. Results showed that the catalytic activity of the four samples decreased in the order of MnO2-Ac > MnO2-N > MnO2-Cl > MnO2-S, which was highly related to the specific surface areas, oxygen vacancy concentration and the content of adsorbed oxygen. MnO2-Ac owned potential for practical applications. It showed superior toluene oxidation activity with T90 of 200 °C, as well as excellent water-resistance and stability during 50 h at 300 °C. The good catalytic activities under high WHSV and high toluene concentration were also observed over MnO2-Ac. Moreover, the reaction pathway of toluene oxidation was presented with the aid of In-situ DRIFTS.
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