Search

Abstract The impact of various organic amendments on soil organic carbon (SOC) have rarely been reported. To address this, a laboratory experiment was designed to scrutinize the effects of different amendments on soil carbon fractions, microbial communities, and the underlying interactive mechanisms. The experiment encompassed a no-amendment control (CK), as well as treatments with corn straw (CS), tobacco stalks (TS), and peanut shell biochar (PB). Over a 70-day incubation, the SOC in plots amended with CS, TS, and PB displayed significant boosts of 13.9%, 17.5%, and 44.8%, respectively, compared to the CK. For soil carbon fractions, amendments with PB, TS, and CS led to a dramatic rise in particulate organic carbon (POC) of 27.4%, 20.2%, and 105.7%, respectively, in contrast to the CK plots. Mantel analysis and structural Equation Modeling uncovered strong interrelationships among the cbbL, cbbM, Bacteroidota, TOC, and POC. Organic amendments enhance soil carbon fractions, modulating the microbial community by increasing Bacteroidetes abundance and suppressing Acidobacteria richness, thereby influencing the abundance of key carbon cycle genes such as cbbL and cbbM. These results suggest that the addition of peanut shell biochar significantly boosted TOC and key carbon fractions, enhancing carbon content and soil fertility.

Abstract Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Understanding the response of microbial communities and their potential functions is essential for sustainability of agroecosystems under long-term continuous cropping. However, limited research has focused on investigating the interaction between soil physicochemical factors and microbial community dynamics in agroecosystems under long-term continuous cropping. This study probed into the physicochemical properties, metabolites, and microbial diversity of tobacco rhizosphere soils cropped continuously for 0, 5, and 20 years. The relative abundance of bacterial genera associated with nutrient cycling (e.g., Sphingomonas) increased while potential plant pathogenic fungi and beneficial microorganisms showed synergistic increases with the duration of continuous cropping. Variations in soil pH, alkeline nitrogen (AN) content, and soil organic carbon (SOC) content drove the shifts in soil microbial composition. Metabolites such as palmitic acid, 3-hydroxypropionic acid, stearic acid, and hippuric acid may play a key role in soil acidification. Those results enhance our ability to predict shifts in soil microbial community structure associated with anthropogenic continuous cropping, which can have long-term implications for crop production.

Introduction: The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has facilitated the development of precision oncology. Two first-generation NTRK inhibitors (larotrectinib and entrectinib) are currently approved for the treatment of patients with solid tumors harboring NTRK gene fusions. Nevertheless, comprehensive NTRK profiling at the pan-cancer genomic level and real-world studies pertaining to the adverse events of NTRK inhibitors are lacking.Methods: We characterize the genome of NTRK at the pan-cancer level through multi-omics databases such as The Cancer Genome Atlas (TCGA). Through the FDA Adverse Event Reporting System (FAERS) database, we collect reports of entrectinib and larotrectinib-induced adverse events and perform a pharmacovigilance analysis using various disproportionality methods.Results:NTRK1/2/3 expression is lower in most tumor tissues, while they have higher methylation levels. NTRK gene expression has prognostic value in some cancer types, such as breast invasive carcinoma (BRCA). The cancer type with highest NTRK alteration frequency is skin cutaneous melanoma (SKCM) (31.98%). Thyroid carcinoma (THCA) has the largest number of NTRK fusion cases, and the most common fusion pair is ETV6-NTRK3. Adverse drug events (ADEs) obtained from the FAERS database for larotrectinib and entrectinib are 524 and 563, respectively. At the System Organ Class (SOC) level, both drugs have positive signal value for “nervous system disorder”. Other positive signals for entrectinib include “cardiac disorders”, “metabolism and nutrition disorders”, while for larotrectinib, it is “hepatobiliary disorders”. The unexpected signals are also listed in detail. ADEs of the two NTRK inhibitors mainly occur in the first month. The median onset time of ADEs for entrectinib and larotrectinib was 16 days (interquartile range [IQR] 6–86.5) and 44 days ([IQR] 7–136), respectively.Conclusion: Our analysis provides a broad molecular view of the NTRK family. The real-world adverse drug event analysis of entrectinib and larotrectinib contributes to more refined medication management.