ARF2-PIF5 interaction controls transcriptional reprogramming in the ABS3-mediated plant senescence pathway.

One of the hallmarks of plant senescence is the global transcriptional reprogramming coordinated by a plethora of transcription factors (TFs). However, mechanisms underlying the interactions between different TFs in modulating senescence remain obscure. Previously, we discovered that plant ABS3 subfamily MATE transporter genes regulate senescence and senescence-associated transcriptional changes. In a genetic screen for mutants suppressing the accelerated senescence phenotype of the gain-of-function mutant abs3-1D, AUXIN RESPONSE FACTOR 2 (ARF2) and PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) were identified as key TFs responsible for transcriptional regulation in the ABS3-mediated senescence pathway. ARF2 and PIF5 (as well as PIF4) interact directly and function interdependently to promote senescence, and they share common target genes such as key senescence promoting genes ORESARA 1 (ORE1) and STAY-GREEN 1 (SGR1) in the ABS3-mediated senescence pathway. In addition, we discovered reciprocal regulation between ABS3-subfamily MATEs and the ARF2 and PIF5/4 TFs. Taken together, our findings reveal a regulatory paradigm in which the ARF2-PIF5/4 functional module facilitates the transcriptional reprogramming in the ABS3-mediated senescence pathway.

A novel metabolic-related gene signature for predicting clinical prognosis and immune microenvironment in head and neck squamous cell carcinoma.

OBJECTIVES: Metabolic reprogramming is not only an essential hallmark in the progression of head and neck squamous cell carcinoma (HNSCC), but also an important regulator of cancer cell adaptation to tumor microenvironment (TME). However, the potential mechanism of metabolic reprogramming in TME of HNSCC is still unknown. METHODS: The head and neck squamous cell carcinoma with survival information were obtained the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The metabolic-related genes were identified by differential analysis and survival analysis. Univariate and multivariate Cox regression analyses were applied to determine an overall estimate of metabolic-related risk signature and related clinical parameters. The sensitivity and specificity of the risk signature were evaluated by time-dependent receiver operation characteristic (ROC) curves. TME immune cell infiltration mediated by metabolic-related genes was explored by gene set enrichment analysis (GSEA) and correlation analysis. RESULTS: Seven metabolic-related genes (SMS, MTHFD2, HPRT1, DNMT1, PYGL, ADA, and P4HA1) were identified to develop a metabolic-related risk signature. The low-risk group had a better overall survival compared to that of the high-risk group in the TCGA and GSE65858 cohorts. The AUCs for 1-, 3-, and 5-year overall survival were 0.646 vs. 0.673, 0.694 vs. 0.639, and 0.673 vs. 0.573, respectively. The AUC vale of risk score was 0.727 vs. 0.673. The low-risk group was associated with immune cell infiltration in the TME. CONCLUSIONS: The metabolic-related risk signature were constructed and validated, which could involve in regulating the immune cell infiltration in the TME and act as an independent biomarker that predicted the prognosis of HNSCC.

Melatonin reverses EGFR-TKI therapeutic resistance by modulating crosstalk between circadian-related gene signature and immune infiltration patterns in patients with COVID-19 and lung adenocarcinoma.

BACKGROUND: Patients with lung cancer exhibit the poorest outcomes when infected with coronavirus disease 2019 (COVID-19). However, the potential impact of COVID-19 on the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) remains unknown. METHODS: Expression data and clinical information were sourced from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognostic, differentially expressed circadian-related genes (CRGs) were identified using multivariate Cox regression and LASSO regression analyses to establish an immune-related gene signature. The clinical value, immune landscape, somatic mutations, and drug sensitivity of high- and low-risk groups were assessed using Kaplan-Meier curves and immunotherapy cohorts. Finally, in vitro and in vivo experiments were conducted to elucidate the molecular function of melatonin in regulating the immune microenvironment and therapeutic resistance. RESULTS: Three circadian-related patterns and distinct CRGs clusters were identified based on the abnormal expression of 13 CRGs. Circadian genomic phenotypes were identified based on 13 circadian phenotype-related differentially expressed genes (DEGs). A CRGs risk signature was constructed; the high CRGs risk group displayed an immunosuppressive TME, poor survival, and therapy resistance. Melatonin reversed EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance by regulating immune cell infiltration into the TME, both in vitro and in vivo. CONCLUSIONS: The investigation revealed crosstalk between CRGs signatures and immune infiltration patterns in LUAD and COVID-19. Melatonin acted as a promising agent to suppress the malignant features of lung cancer and enhance treatment sensitivity by modulating the TME.

Accumulation and speciation of arsenic in Eisenia fetida in sodium arsenite spiked soils - A dynamic interaction between soil and earthworms.

Arsenic (As) is a toxic metalloid that is a significant global pollutant of the environment and a persistent bioaccumulation carcinogen. Earthworms are frequently employed as sentinel organisms to investigate the bioavailability of As in contaminated soils. However, the process of As accumulation in earthworms and the mechanism of transformation of As species in their bodies are not well understood. The accumulation of As and variation of As species in the earthworms (Eisenia fetida) exposed to sodium arsenite (0, 20, and 80 mg kg-1 As) were investigated in this study. The total As concentration of earthworms in the three treatments at various sample times was dose-dependent on soil As content. After 56 days of exposure, the high concentration treatment had the highest total As content (772 ± 21 mg kg-1) in earthworms, followed by the low concentration treatment (579 ± 42 mg kg-1) and control (31 ± 1 mg kg-1). During 56 days, the proportion of trivalent As in earthworms increased from 70% to more than 90%, while pentavalent As decreased by 11-18%. On day 28, the sum of the four organic As species reached a maximum (<1%). Changes in soil As species and an increase in bioavailable As cause earthworms to accumulate more As. The total As in soil after 56 days of exposure was 9.51 ± 0.50, 25.6 ± 0.60, and 82.8 ± 0.28 mg kg-1, which was not significantly different from the total As in soil before the experiment. These findings are useful in assessing the risk of earthworm exposure to sodium arsenite in the soil.

Cadmium and lead bioavailability to poultry fed with contaminated soil-spiked feed.

Geophagy is common for free-range chickens, however, the relative bioavailability (RBA) of heavy metals in contaminated soils consumed by chickens has not fully investigated. In this work, chickens were fed diets increasingly spiked with a contaminated soil (Cd = 105, Pb = 4840 mg kg-1; 3, 5, 10, 20 and 30 % of overall feed by weight), or Cd/Pb reagent spikes (from CdCl2 or Pb(Ac)2), for 23 d. After the study period, chicken liver, kidney, femur and gizzard samples were analyzed for Cd and Pb concentrations, and organ/tissue metal concentrations were used to calculate Cd and Pb RBA. Linear dose response curves (DRCs) were established for both Cd/Pb reagents-spiked and soil-spiked treatments. Femur Cd concentrations of soil-spiked treatments were two times of Cd-spiked treatments with similar feed Cd levels, while feed spiked with Cd or Pb also resulted in elevated Pb or Cd concentrations in some organ/tissues. Metal RBA was calculated using three different methods. Most Cd and Pb RBA values were in the range 50-70 %, with the chicken gizzard as a potential endpoint for bioaccessible Cd and Pb. Cadmium and Pb bioavailability values can help with more precise estimation of Cd and Pb accumulation in chicken following heavy metal-contaminated soil ingestion, with overall results helping to protect human health.

The wheat TaIQD3D-6 gene encodes a microtubule-associated protein and regulates cell morphogenesis in Arabidopsis.

A plethora of microtubule-associated proteins (MAPs) modulate the dynamics of microtubules (MTs) to ensure the proper elaboration of developmental programs in plants. Among the plant-specific MAPs are the IQ67 domain (IQD) family proteins. Despite the great progress in elucidating IQD protein functions, the majority of IQD proteins, especially IQDs in crop species, remain to be functionally explored. In this study, we identified 78 putative IQD family genes in the genome of hexaploid wheat (Triticum aestivum). Phylogenetic analysis of wheat and Arabidopsis IQDs supports the previous notion that the expansion of the IQD family coincides with plant terrestrialization. Further characterization of one TaIQD, TaIQD3D-6, revealed that TaIQD3D-6 directly binds to MTs and free tubulins in vitro and is associated with cortical MTs in interphase cells in vivo. Overexpressing TaIQD3D-6 in Arabidopsis leads to a spectrum of phenotypes that are indicative of perturbed MT homeostasis, including spiral growth, hypersensitivity to MT-destabilizing drugs, defects in cell morphogenesis, and altered organization of cMT arrays. Finally, we determined that TaIQD3D-6-GFP localizes to the expanding cell plate during cytokinesis and the overexpression of TaIQD3D-6 interferes with asymmetric cell division in the stomatal lineage in Arabidopsis. In summary, our findings establish that TaIQD3D-6 is a MAP that regulates plant cell and organ morphogenesis and provide new insights into the functions of crop IQD proteins.