N6-methyladenosine RNA modification promotes viral genomic RNA stability and infection

Molecular manipulation of susceptibility (S) genes that are antipodes to resistance (R) genes has been adopted as an alternative strategy for controlling crop diseases. Here, we show the S gene encoding Triticum aestivum m(6)A methyltransferase B (TaMTB) is identified by a genome-wide association study and subsequently shown to be a positive regulator for wheat yellow mosaic virus (WYMV) infection. TaMTB is localized in the nucleus, is translocated into the cytoplasmic aggregates by binding to WYMV NIb to upregulate the m(6)A level of WYMV RNA1 and stabilize the viral RNA, thus promoting viral infection. A natural mutant allele TaMTB-SNP176C is found to confer an enhanced susceptibility to WYMV infection through genetic variation analysis on 243 wheat varieties. Our discovery highlights this allele can be a useful target for the molecular wheat breeding in the future

Down-regulated βIII-tubulin Expression Can Reverse Paclitaxel Resistance in A549/Taxol Cells Lines

Background and objective Chemotherapy drug resistance is the primary causes of death in patients with pulmonary carcinoma which make tumor recurrence or metastasis. β-tubulin is the main cell targets of anti-microtubule drug. Increased expression of βIII-tubulin has been implicated in non-small cell lung cancer (NSCLC) cell lines. To explore the relationship among the expression level of βIII-tubulin and the sensitivity of A549/Taxolcell lines to Taxol and cell cycles and cell apoptosis by RNA interference-mediated inhibition of βIII-tubulin in A549/Taxol cells. Methods Three pairs of siRNA targetd βIII-tubulin were designed and prepared, which were transfected into A549/Taxol cells using LipofectamineTM 2000. We detected the expression of βIII-tubulin mRNA using Real-time fluorescence qRT-PCR. Tedhen we selected the most efficient siRNA by the expression of βIII-tubulin mRNA in transfected group. βIII-tubulin protein level were mesured by Western blot. The taxol sensitivity in transfected group were evaluated by MTT assay. And the cell apoptosis and cell cycles were determined by flow cytometry. Results βIII-tubulin mRNA levels in A549/Taxol cells were significantly decreased in transfected grop by Real-time qRT-PCR than control groups. And βIII-tubulin siRNA-1 sequence showed the highest transfection efficiency, which was (87.73±4.87)% (P<0.01); Western blot results showed that the expressional level of BIII tublin protein was significantly down-reulated in the transfectant cells than thant in the control cells. By MTT assay, we showed that the inhibition ratio of Taxol to A549/Taxol cells transfeced was higher than that of control group (51.77±4.60)% (P<0.01). The early apoptosis rate of A549/Taxol cells in transfected group were significantly higher than that of control group (P<0.01); G2-M content in taxol group obviously increased than untreated samples by the cell cycle (P<0.05). Conclusion βIII-tubulin down-regulated significantly sensitized NSCLC A549/Taxol cells to Paclitaxel

A Case Report of Primary Pulmonary Synovial Sarcoma with Postoperative Multiple Metastases Treated with Apatinib

Primary pulmonary synovial sarcoma is a rare pulmonary malignant tumor originated from primitive mesenchymal, which has short overall survival and poor prognosis. Related case reports are lacked at home and abroad. In recent years, the development of targeted therapy has brought remarkable benefits to cancer patients. Apatinib (Hengrui Pharmaceutical Co. Ltd, Jiangsu, People’s Republic of China) is a small molecule vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, which selectively inhibits VEGFR-2 and blocks the VEGF signal pathway, then strongly inhibiting the tumor angiogenesis. Apatinib has shown favorable therapeutic effect and acceptable toxicity on various tumors. Here we report a case of primary pulmonary synovial sarcoma with postoperative multiple metastases treated with apatinib, in order to provide a new considerable treatment

Gene Expression and Clinical Characteristics of Molecular Targeted Therapy in Non-small Cell Lung Cancer Patients in Shandong

Background and objective Molecular targeted therapy has gradually become an important treatment for lung cancer, the aim of this research is to analyze the clinicopathologic features associated with the gene mutation status of epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and Kirsten rat sarcoma viral oncogene (KRAS) in non-small cell lung cancer (NSCLC) patients and determine the most likely populations to benefit from molecular target therapy treatment. Methods The mutation status of EGFR, EML4-ALK fusion gene, ROS1 and KARS gene were determined by Real-time PCR, the relationship between clinical pathologic features and concomitant gene were analyzed with χ2 test by SPSS software 19.0. Results A total of 514 specimens from Shandong tumor hospital were collected from NSCLC patients between January 2014 and May 2016. The total mutation rate of EGFR gene was 36.70%, major occurred in exon 19 (36.61%) and exon 21 (51.36%), respectively, and EGFR mutations usually occurred in female, non-smoking and adenocarcinoma patients (P0.05). ROS1 fusion gene was detected in 136 cases, the positive rate was 3.67%, all patients were 60 years old, and the difference was statistically significant (P<0.05). Only 23 samples were tested KARS gene mutations, two of them were positive and the positive rate was 8.70%. They all occurred in non-smoker and adenocarcinoma patients. No mutation was detected to coexist in EGFR, EML4-ALK and KARS gene mutation. Conclusion EGFR, EML4-ALK, ROS1 and KRAS defines different molecular subset of NSCLC with distinct characteristic, which provides a new option for the clinical treatment of patients with NSCLC

Influence of Sediment, Plants, and Microorganisms on Nitrogen Removal in Farmland Drainage Ditches

The removal of nitrogen from water is a consequence of the synergistic action of plant uptake, sediment sorption, and microbial decomposition. However, there is a lack of long-term experimental studies on the effects of each component in the process of nitrogen removal. In this study, we investigated the effect of sediment, plants, and microorganisms on nitrogen removal by setting up three systems: water–sterilized sediment, water–sediment, and water–sediment–plant. The nitrogen removal effect followed the following rank order of effectiveness: the “water–sediment–plant” system > the “water–sediment” system > the “water–sterilized sediment” system. The ditch sediment had a strong enrichment effect for nitrogen. In addition, the migration rate of nitrogen in the sediment with different depths was different. The ammonia-nitrogen migration rate in the sediment showed an increasing trend with time and depth. The nitrate-nitrogen migration process in the sediment showed a trend of enrichment toward the middle layer (15.0–25.0 cm). Aquatic plants and microorganisms can promote the removal of nitrogen in water, with the average purification rates of 13.92% and 19.92%, respectively

The effect of impurity oxygen solution and segregation on Mo/Cr interface stability by multi-scale simulations

The adhesion strength mechanism of an interface forming from Cr coating deposited on the Mo matrix surface has been performed using a DFT + U method. First, we have obtained the lattice constant, bulk modulus, shear modulus, Young’s modulus and Poisson’s ratio for Mo and Cr bulk, respectively. The oxygen atom is inclined to solute in the tetrahedral interstitial site for Mo; while for Cr, an octahedral location is well to contain an impurity oxygen atom. By substitute mechanism, it has suggested that a Cr atom is easier to take over a Mo atom. Subsequently, based on the surface energy and work function analysis, we have established the corresponding the optimum surface and interface models. Our results suggested that Mo(110)/Cr(110) interface was most stable among the possible Mo/Cr interfaces. In additions, the effect of the impurity oxygen atom on the interface stability has also been studied. It has been predicted that the impurity O atom prefers to solute into the near Cr surface edge. The work of adhesion for interface with impurity O atom is higher than the clean interface without O atom, which means that the impurity O atom could generate the positive effect on the adhesion mechanism of Cr-coating Mo alloys. Furthermore, to analyze the interface cracking, we have performed the SEDG distributions to study fracture behavior along the cracking paths through the CFE method

Ion Irradiation Defects and Hardening in FeCrAl Alloy

The self-ion irradiation experiments of FeCrAl and Y−FeCrAl alloys are carried out at 330 °C to 1–10 displacements per atom (dpa). The formation of dislocation loops in these alloys is investigated by transmission electron microscopy (TEM) and nano-indentation tests are used to assess the irradiation hardening. A large number of dislocation loops are formed after irradiation, and dislocation network gradually develops above 2.5 dpa. The average size of dislocation loops increases while the number density decreases when the dose was increased. In comparison to a/2 dislocation loops, a dislocation loops have a larger average size and higher proportion. Higher temperatures and dose rate can increase the proportion of a dislocation loops. As the dose is increasing, irradiation hardening increases. The addition of yttrium increases the proportion of a dislocation loops and reduces the irradiation hardening due to the high binding energy between yttrium atom and vacancy

Effects of Nitrogen Input and Aeration on Greenhouse Gas Emissions and Pollutants in Agricultural Drainage Ditches

Understanding the patterns of greenhouse gas emissions and the changes in pollution load in terrestrial freshwater systems is crucial for accurately assessing the global carbon cycle and overall greenhouse gas emissions. However, current research often focuses on wetlands and rivers, with few studies on agricultural drainage ditches, which are an important part of the agricultural ecosystem. Investigating the greenhouse gas emission patterns and pollution load changes in agricultural drainage ditches can help accurately assess the greenhouse effect of agricultural systems and improve fertilization measures in farmlands. This study explored the effects of nitrogen input and aeration on the pollution load and greenhouse gas emission processes in paddy field drainage ditches. The results showed that aeration significantly reduced the concentration of ammonium nitrogen (NH4+) in the water, decreased the emissions of nitrous oxide (N2O) and methane (CH4), and slightly increased the emission of carbon dioxide (CO2), resulting in an overall reduction of the global warming potential (GWP) by 34.02%. Nitrogen input significantly increased the concentration of ammonium nitrogen in the water, slightly reduced the emissions of N2O and CH4, and increased the CO2 emissions by 46.60%, thereby increasing the GWP by 15.24%. The drainage ditches reduced the pollution load in both the water and sediment, with the overall GWP downstream being 9.34% lower than upstream

Effects of Aeration on Pollution Load and Greenhouse Gas Emissions from Agricultural Drainage Ditches

Human activities input a large amount of carbon and nitrogen nutrients into water, resulting in inland freshwater becoming an important source of greenhouse gas (GHG) emissions. Agricultural drainage ditches are the main transport route of non-point source pollution. Understanding the rules for how greenhouse gas emissions from drainage ditches impact the environment can help to accurately estimate the greenhouse effect of agricultural systems. However, current research mainly focuses on the effect of different measures on the migration and transformation process of pollutants in drainage ditches. The process of greenhouse gas emissions when the non-point source of pollution is transported by drainage ditches is still unclear. In this study, the influence of aeration on the pollution load and GHG emission process of a drainage ditch in a paddy field was explored. The following conclusions were drawn: Aeration reduced the content of nitrate nitrogen in the water but had no significant effect on the content of ammonium nitrogen and it reduced the chemical oxygen demand (COD) of water by 24.9%. Aeration increased the potential of hydrogen (PH), dissolved oxygen (DO) and oxidation–reduction potential (ORP) of water and reduced the total organic carbon content, microbial carbon content and soluble carbon content of the soil in the sediment. Aeration reduced the N2O and CH4 emission fluxes and increased the CO2 emission fluxes in the drainage ditch, but it reduced the greenhouse effect generated by the drainage ditch by 33.7%. This study shows that aeration can reduce both the pollution load and the greenhouse gas emission flux in drainage ditches

Tislelizumab plus chemotherapy for patients with EGFR-mutated non-squamous non-small cell lung cancer who progressed on EGFR tyrosine kinase inhibitor therapy

Background Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+ beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported.Methods In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided α of 0.05, and a power of 85%.Results Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90% CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95% CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3–4 TEAEs occurred in 40.6% (28/69) of patients. Grades 3–4 immune-related AEs occurred in 5 (7.2%) patients.Conclusion The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for EGFR-mutated non-squamous NSCLC after EGFR TKI failure