Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis

BackgroundBrain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC.MethodChronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1–4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations.ResultsContrasting with lyn1, ipsilateral metastatic lesions (lyn2–4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC

Influence of fault slip on mining-induced pressure and optimization of roadway support design in fault-influenced zone

This paper presents an investigation on the characteristics of overlying strata collapse and mining-induced pressure in fault-influenced zone by employing the physical modeling in consideration of fault structure. The precursory information of fault slip during the underground mining activities is studied as well. Based on the physical modeling, the optimization of roadway support design and the field verification in fault-influenced zone are conducted. Physical modeling results show that, due to the combined effect of mining activities and fault slip, the mining-induced pressure and the extent of damaged rock masses in the fault-influenced zone are greater than those in the uninfluenced zone. The sharp increase and the succeeding stabilization of stress or steady increase in displacement can be identified as the precursory information of fault slip. Considering the larger mining-induced pressure in the fault-influenced zone, the new support design utilizing cables is proposed. The optimization of roadway support design suggests that the cables can be anchored in the stable surrounding rocks and can effectively mobilize the load bearing capacity of the stable surrounding rocks. The field observation indicates that the roadway is in good condition with the optimized roadway support design

Image_1_Integration analysis identifies MYBL1 as a novel immunotherapy biomarker affecting the immune microenvironment in clear cell renal cell carcinoma: Evidence based on machine learning and experiments.tif

BackgroundPrevious studies have identified MYBL1 as a cancer-promoting molecule in numerous types of cancer. Nevertheless, the role of MYBL in renal cancer remains unclear.MethodsGenomic and clinical data of clear cell renal cell carcinoma (ccRCC) was get from the Cancer Genome Atlas (TCGA) database. CCK8, colony formation, and 5-ethynyl-2’-deoxyuridine assay were utilized to evaluate the performance of cell proliferation. Cell apoptosis was detected using the flow cytometric analysis. The protein level of MYBL1 in different tissues was evaluated using immunohistochemistry. A machine learning algorithm was utilized to identify the prognosis signature based on MYBL1-derived molecules.ResultsHere, we comprehensively investigated the role of MYBL1 in ccRCC. Here, we noticed a higher level of MYBL1 in ccRCC patients in both RNA and protein levels. Further analysis showed that MYBL1 was correlated with progressive clinical characteristics and worse prognosis performance. Biological enrichment analysis showed that MYBL1 can activate multiple oncogenic pathways in ccRCC. Moreover, we found that MYBL1 can remodel the immune microenvironment of ccRCC and affect the immunotherapy response. In vitro and in vivo assays indicated that MYBL1 was upregulated in ccRCC cells and can promote cellular malignant behaviors of ccRCC. Ultimately, an machine learning algorithm – LASSO logistics regression was utilized to identify a prognosis signature based on the MYBL1-derived molecules, which showed satisfactory prediction ability on patient prognosis in both training and validation cohorts.ConclusionsOur result indicated that MYBL1 is a novel biomarker of ccRCC, which can remodel the tumor microenvironment, affect immunotherapy response and guide precision medicine in ccRCC.</p

Image_2_Integration analysis identifies MYBL1 as a novel immunotherapy biomarker affecting the immune microenvironment in clear cell renal cell carcinoma: Evidence based on machine learning and experiments.tif

BackgroundPrevious studies have identified MYBL1 as a cancer-promoting molecule in numerous types of cancer. Nevertheless, the role of MYBL in renal cancer remains unclear.MethodsGenomic and clinical data of clear cell renal cell carcinoma (ccRCC) was get from the Cancer Genome Atlas (TCGA) database. CCK8, colony formation, and 5-ethynyl-2’-deoxyuridine assay were utilized to evaluate the performance of cell proliferation. Cell apoptosis was detected using the flow cytometric analysis. The protein level of MYBL1 in different tissues was evaluated using immunohistochemistry. A machine learning algorithm was utilized to identify the prognosis signature based on MYBL1-derived molecules.ResultsHere, we comprehensively investigated the role of MYBL1 in ccRCC. Here, we noticed a higher level of MYBL1 in ccRCC patients in both RNA and protein levels. Further analysis showed that MYBL1 was correlated with progressive clinical characteristics and worse prognosis performance. Biological enrichment analysis showed that MYBL1 can activate multiple oncogenic pathways in ccRCC. Moreover, we found that MYBL1 can remodel the immune microenvironment of ccRCC and affect the immunotherapy response. In vitro and in vivo assays indicated that MYBL1 was upregulated in ccRCC cells and can promote cellular malignant behaviors of ccRCC. Ultimately, an machine learning algorithm – LASSO logistics regression was utilized to identify a prognosis signature based on the MYBL1-derived molecules, which showed satisfactory prediction ability on patient prognosis in both training and validation cohorts.ConclusionsOur result indicated that MYBL1 is a novel biomarker of ccRCC, which can remodel the tumor microenvironment, affect immunotherapy response and guide precision medicine in ccRCC.</p

PLLA Nanofibrous Paper-Based Plasmonic Substrate with Tailored Hydrophilicity for Focusing SERS Detection

We report a new paper-based surface enhanced Raman scattering (SERS) substrate platform contributed by a poly­(l-lactic acid) (PLLA) nanofibrous paper adsorbed with plasmonic nanostructures, which can circumvent many challenges of the existing SERS substrates. This PLLA nanofibrous paper has three-dimensional porous structure, extremely clean surface with good hydrophobicity (contact angle is as high as 133.4°), and negligible background interference under Raman laser excitation. Due to the strong electrostatic interaction between PLLA nanofiber and cetyltrimethylammonium bromide (CTAB) molecules, the CTAB-coated gold nanorods (GNRs) are efficiently immobilized onto the fibers. Such a hydrophobic paper substrate with locally hydrophilic SERS-active area can confine analyte molecules and prevent the random spreading of molecules. The confinement leads to focusing effect and the GNRs-PLLA SERS substrate is found to be highly sensitive (0.1 nM Rhodamine 6G and malachite green) and exhibit excellent reproducibility (∼8% relative standard deviation (RSD)) and long-term stability. Furthermore, it is also cost-efficient, with simple fabrication methodology, and demonstrates high sample collection efficiency. All of these benefits ensure that this GNRs-PLLA substrate is a really perfect choice for a variety of SERS applications

Efficient Enrichment and Self-Assembly of Hybrid Nanoparticles into Removable and Magnetic SERS Substrates for Sensitive Detection of Environmental Pollutants

A structure consisting of a low surface energy substrate and low surface tension liquid is designed and prepared by taking advantage of perfluorinated fluid infusion into the porous Teflon membrane. This slippery platform allows efficient enrichment and self-assembly of hybrid nanoparticles and the assembled structure can be detached from the membrane. A macroscale superlattice array of Au nanorods doped with magnetic Fe₃O₄ nanoparticles is obtained by suppressing the outward capillary flow and coffee-ring effect during evaporative self-assembly. In SERS (surface enhanced Raman scattering) detection of environmental pollutants including thiram, diquat and polycyclic aromatic hydrocarbons, the removable plasmonic superlattice array with magnetic properties enables rapid separation of analytes from the solution resulting in excellent sensitivity and detection limits down to the nanomolar level. The self-assembly strategy shows great potential in the fabrication of removable 3D plasmonic superlattice arrays for SERS detections