Effectiveness of high-dose third-generation EGFR-tyrosine kinase inhibitors in treating EGFR-mutated non-small cell lung cancer patients with leptomeningeal metastasis.

BACKGROUND: Leptomeningeal metastasis (LM) is associated with an extremely poor prognosis in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The third-generation EGFR-tyrosine kinase inhibitors (TKIs), currently the preferred drug of choice, have significantly improved treatment outcomes in these patients. However, the optimal dose of third-generation EGFR-TKIs for clinical use remains undetermined in NSCLC patients with LM. METHODS: We retrospectively analyzed the clinical characteristics and treatment outcomes of 105 patients with EGFR-mutated NSCLC and cytologically confirmed LM who had received third-generation EGFR-TKI treatment after LM diagnosis. Patients were stratified into high- and standard-dose groups based on the treatment dose of third-generation EGFR-TKI. Subsequent treatments for LM were collected, particularly the efficacy of different doses of third-generation EGFR-targeted drugs. RESULTS: The median follow-up period was 28.7 months (range 0.6-40.2) at the cut-off date of August 27, 2023. The 105 included patients who received third-generation EGFR-TKI treatment had a clinical response rate (CRR) of 54.3 % (57/105), and the median overall survival (OS) from LM diagnosis was 12.3 months (95 % confidence interval [CI] = 10.0-15.0). Among them, 46 (43.8 %) patients received a high-dose regimen, and the remaining 59 (56.2 %) patients were treated with standard-dose drugs. Patients treated with high-dose third-generation EGFR-TKIs showed a higher CRR and longer OS than those treated with standard-dose therapy (65.2 % vs. 45.8 %, p = 0.047; 15.0 vs. 10.2 months, p = 0.014). Importantly, high-dose third-generation EGFR-TKI showed superior OS than standard-dose treatment in all subgroups (prior first-/second-generation EGFR-TKI resistance group, 19.5 vs. 9.8 months, p = 0.047; third-generation EGFR-TKI resistance group, 10.0 vs. 4.3 months, p = 0.045; EGFR-TKI naive group, not reach vs. 15.6 months, p = 0.031). Multivariate analysis revealed that high-dose third-generation EGFR-TKIs, intrathecal chemotherapy, previous TKI treatment history, and Karnofsky Performance Status score were independent predictors of OS (all p < 0.05). CONCLUSIONS: High-dose third-generation EGFR-TKIs are effective treatments for NSCLC patients with EGFR mutations and LM, regardless of previous EGFR-TKI exposure.

Transcriptome and Gene Editing Analyses Reveal MOF1a Defect Alters the Expression of Genes Associated with Tapetum Development and Chromosome Behavior at Meiosis Stage Resulting in Low Pollen Fertility of Tetraploid Rice.

Autotetraploid rice is a useful rice germplasm for polyploid rice breeding. However, low fertility limits its commercial production. A neo-tetraploid rice with high fertility was developed from the progenies of crossing between autotetraploid lines by our research group. Our previous study showed that a myeloblastosis (MYB) transcription factor, MOF1, might be associated with the pollen development in tetraploid rice. However, little information is available about its role in pollen development in tetraploid rice. Here, we identified a new haplotype of MOF1 from neo-tetraploid rice and marked it as MOF1a. Transcriptome and qRT-PCR analysis demonstrated that MOF1a highly expressed in anthers, and displayed differential expression in neo-tetraploid rice compared to tetraploid rice line with low pollen fertility. The mutant (mof1a) of MOF1a, which was generated by CRISPR/Cas9 knockout in neo-tetraploid rice, showed low pollen fertility, and also exhibited abnormal tapetum and middle layer development, and defective chromosome behaviors during meiosis. A total of 13 tapetal related genes were found to be up-regulated in meiotic anthers of MOF1a compared with wild type plants by RNA-seq analysis, including CYP703A3, PTC1, and OsABCG26, which had been demonstrated to affect tapetal development. Moreover, 335 meiosis-related genes displayed differential expression patterns at same stage, including nine important meiosis-related genes, such as metallothionein OsMT1a. These results demonstrated that MOF1a plays an important role in pollen development and provides a foundation for understanding the molecular mechanism underlying MOF1a in reproduction of tetraploid rice.

Recycling of phosphorus-containing plastic based on the dual effects of switchable hydrophilicity solvents.

Plastic waste has caused severe environmental problems. Some additives in plastics, like organophosphates, enter the environment with plastic waste, causing significant harm to plants and creatures. However, the primary method of recycling phosphorus-containing plastic, especially polycarbonate and acrylonitrile-butadiene-styrene copolymer (PC/ABS), is a mechanical method, which not only does not effectively separate plastics and organophosphates but also tends to cause polymer degradation during recycling. In order to overcome these problems, we proposed an efficient and sustainable approach to recycle of phosphorus-containing plastic. In this method, N, N-dimethylcyclohexylamine (DMCHA), a switchable hydrophilicity solvent (SHS), was used to react with and extract organophosphates in plastic, achieving the goal of complete separation of plastic and organophosphates. PC/ABS can be recovered by precipitation. Dissolved organophosphates can also be easily recovered due to the switching characteristics of SHS. Both of recovered materials were of high purity and were close to virgin materials. This technique is an easy and efficient approach to separate plastic and organophosphates, which has excellent application prospects in recycling phosphorus-containing plastic.

The texture, structure and nutrient availability of artificial soil on cut slopes restored with OSSS - Influence of restoration time.

Outside soil spray seeding (OSSS) is widely used to restore cut slopes in southwest of China, and artificial soil is often sprayed onto cut slopes to establish a soil layer for revegetation. The stability of artificial soil layer and its supply of water and nutrients for plants is crucial for successful restoration. To evaluate the long-term effectiveness of OSSS, the texture, structure and nutrient availability of artificial soil were studied, various soil samples were obtained from three cut slopes with different restoration time (restored with OSSS in 1996, 2003 and 2007 respectively) and one natural developed slope (NS). The properties measured including soil particle size distribution (PSD), texture, fractal dimension of PSD (Dm), the bias (CS) and peak convex (CE) coefficients of aggregate size distribution, structure failure rate, bulk density, moisture, pH, soil organic carbon (SOC), calcium carbonate content, Available nitrogen (NA), Available phosphorus (PA), and Available potassium (KA). The results showed that different restoration time resulted in significant differences in soil PSD, Dm, CS, CE, structure failure rate, bulk density, moisture, pH, NA, and KA. And these properties improved with increasing restoration age. However, there is still a huge disparity in soil texture, structure, and the availability of nutrients and moisture between the cut slopes and NS over a restoration period of up to 17 years, and this is caused by the little fine particles and the lack of slow release fertilizers and organic fertilizers in the artificial soil, resulting in poorer soil structure stability, retention and availability of moisture and nutrients on the cut slopes. Overall, the OSSS technique shows a long-term effectiveness in southwest of China, but there is still room for improvement.

Distribution and phytoavailability of heavy metal chemical fractions in artificial soil on rock cut slopes alongside railways.

Artificial soil is often sprayed onto cut slopes alongside railroad tracks to promote revegetation. This study evaluated the heavy metal content and the distribution of heavy metal chemical fractions in the soil, as well as the uptake of heavy metals by plants. The soil at four sites was determined to be considerably contaminated with Cd and Pb. The concentrations of Cd and Pb increased with the length of time the railway had been in use and decreased further away from the railway tracks. Pb primarily existed in reducible form but as residual fractions, whereas Cd was predominantly in exchangeable form. A correlation analysis indicated that pH, organic matter, and total phosphorus levels were important factors affecting the distribution of the heavy metal chemical fractions. The amounts of exchangeable Pb and Cd in the soil were highly correlated with their amounts in the plants sampled, indicating that the exchangeable fraction is a better indication of heavy metal phytoavailability than the total amount of heavy metals in the soil. Bioaccumulation and translocation factors indicated that Indigofera amblyantha had moderate tolerance and bioaccumulation capability for Pb, as did Leucaena leucocephala for Cd. These two plant species can serve as ideal slope remediation plants.