Hypoxia-based classification and prognostic signature for clinical management of hepatocellular carcinoma.

OBJECTIVE: Intratumoral hypoxia is an essential feature of hepatocellular carcinoma (HCC). Herein, we investigated the hypoxia-based heterogeneity and relevant clinical implication in HCC. METHODS: Three HCC cohorts: TCGA-LIHC, LICA-FR, and LIRI-JP were retrospectively gathered. Consensus clustering analysis was utilized for hypoxia-based classification based upon transcriptome of hypoxia genes. Through LASSO algorithm, a hypoxia-relevant prognostic signature was built. Immunotherapeutic response was inferred through analyzing immune checkpoints, T cell inflamed score, TIDE score, and TMB score. RNF145 expression was measured in normoxic or hypoxic HCC cells. In RNF145-knockout cells, CCK-8, TUNEL, and scratch tests were implemented. RESULTS: HCC patients were classified into two hypoxia subtypes, with more advanced stages and poorer prognosis in cluster2 than cluster1. The heterogeneity in tumor infiltrating immune cells and genetic mutation was found between subtypes. The hypoxia-relevant prognostic model was proposed, composed of ANLN, CBX2, DLGAP5, FBLN2, FTCD, HMOX1, IGLV1-44, IL33, LCAT, LPCAT1, MKI67, PFN2, RNF145, S100A9, and SPP1). It was predicted that high-risk patients presented worse prognosis with an independent and reliable manner. Based upon high expression of immune checkpoints (CD209, CTLA4, HAVCR2, SIRPA, TNFRSF18, TNFRSF4, and TNFRSF9), high T cell inflamed score, low TIDE score and high TMB score, high-risk patients might respond to immunotherapy. Experimental validation showed that RNF145 was upregulated in hypoxic HCC cells, RNF145 knockdown attenuated proliferation and migration, but aggravated apoptosis in HCC cells. CONCLUSION: Altogether, the hypoxia-based classification and prognostic signature might be useful for prognostication and guiding treatment of HCC.

Molecular characterization reveals that OsSAPK3 improves drought tolerance and grain yield in rice.

BACKGROUND: Many data suggest that the sucrose non-fermenting 1-related kinases 2 (SnRK2s) are very important to abiotic stress for plants. In rice, these kinases are known as osmotic stress/ABA-activated protein kinases (SAPKs). Osmotic stress/ABA-activated protein kinase 3 (OsSAPK3) is a member of SnRK2II in rice, but its function is still unclear. RESULTS: The expression of OsSAPK3 was up regulated by drought, NaCl, PEG and ABA. OsSAPK3 mutated seedings (sapk3-1 and sapk3-2) showed reduced hypersensitivity to exogenous ABA. In addition, under drought conditions, sapk3-1 and sapk3-2 showed more intolerance to drought, including decreased survival rate, increased water loss rate, increased stomatal conductance and significantly decreased expression levels of SLAC1 and SLAC7. Physiological and metabolic analyses showed that OsSAPK3 might play an important role in drought stress signaling pathway by affecting osmotic adjustment and osmolytes, ROS detoxification and expression of ABA dependent and independent dehydration-responsive genes. All gronomic traits analyses demonstrated that OsSAPK3 could improve rice yield by affecting the regulation of tiller numbers and grain size. CONCLUSION: OsSAPK3 plays an important role in both ABA-dependent and ABA-independent drought stress responses. More interestingly, OsSAPK3 could improve rice yield by indirectly regulating tiller number and grain size. These findings provide new insight for the development of drought-resistant rice.

[Pollution Characteristics and Ecological Risk of PBDEs in Water and Sediment from an Electronic Waste Dismantling Area in Taizhou].

An e-waste dismantling industrial park of Taizhou was selected as the sampling center, within a radius of 16 km, and a total of 30 sampling sites were designed in three circles as follows: C (3 km), S (5-10 km) and R (10-16 km). Pollution characteristics and ecological risk of polybrominated diphenyl ethers (PBDEs) in water and sediments were investigated. The concentrations of PBDEs in water ranged from 9.4 to 57.2 ng · L⁻¹, with a mean value of 25.9 ng · L⁻¹; and 3.7 to 38,775 ng · g⁻¹, with an average of 2 779 ng · g⁻¹ in sediments. BDE-209 was the predominant congener. The spatial distribution patterns of PBDE levels in water and sediment were both in the following order: C > S > R. Furthermore, the concentrations of PBDEs in sediments showed significant negative correlation against the distance from the industrial park (P < 0.01). Compared with other regions around the world, the PBDEs contamination was more serious in the area, which indicated that e-waste dismantling activity was one of the significant sources for PBDEs pollution. It was estimated that a total of 30. 7 t PBDEs (including 28. 9 t BDE- 209) was discharged into surrounding environment as a result of dismantling industrial activities in last 40 years. A preliminary ecological risk assessment for PBDEs in water and sediments was conducted by hazard quotient method. The results demonstrated that the Penta-BDEs in the center of e-waste dismantling area ( a radius of 1.5 km) was at particularly high risk level and could cause serious influence on the ecological safety and human health.