Biochar application can influence soil nitrogen (N) cycle through biological and abiotic processes. However, studies on comprehensive examination of the effects of biochar application on microbially mediated N‐cycling processes (N mineralization, nitrification, denitrification, and fixation) and soil N fate (i.e., plant N uptake, soil N₂O emission, and N leaching) are warranted. Therefore, the aim of this study was to examine the effects of biochar application on soil N transformation, microbial functional gene abundance, enzyme activity, and plant N uptake. To achieve the objective of this study, a meta‐analysis involving 131 peer‐reviewed field experiments was conducted. Results showed that field application of biochar significantly enhanced soil and content, N mineralization, nitrification, N₂ fixation, and plant N uptake by 5.3%, 3.7%, 15.3%, 48.5%, 14.7%, and 18.3%, respectively, but reduced N₂O emissions and N leaching by 14.9% and 10.9%, respectively. Biochar application also increased the abundance of soil denitrifying/nitrifying genes (amoA, narG, nirS/nirK+S, and nosZ), proportion of N₂ fixation bacteria, and N‐acetyl‐glucosaminidase activity by 18.6%–87.6%. Soil content was positively correlated with AOA‐amoA abundance, and soil N₂O emission was positively correlated with the relative abundance of genes (e.g., amoA, narG, and nirS/nirK) involved in N₂O production. Furthermore, long‐term biochar application tended to increase AOB‐amoA and nirK+S abundance, especially soil N₂O emission and N leaching. Overall, the findings of this study indicated that biochar application accelerated microbially mediated N‐cycling processes under field conditions, thereby enhancing soil N availability and plant productivity. However, long‐term biochar application may increase N losses. Therefore, future studies should be conducted to examine the effect of long‐term biochar application on the soil N cycle and the underlying microbial mechanisms.

Considerable attention has been raised on crizotinib- and sunitinib-induced hepatotoxicity, but the underlying mechanisms need further examination. In addition, limited therapeutic strategies exist to reduce the liver damage caused by crizotinib and sunitinib. This study investigated the mechanisms of crizotinib- and sunitinib-induced hepatotoxicity and the potential mitigation through ROS and Nrf2 signaling. Firstly, crizotinib and sunitinib reduced cell viability in human liver cells (L02 cells) and triggered dramatic liver injury in mice. Subsequently, we found that crizotinib and sunitinib activated the oxidative stress response (decreased level of GPx and SOD, and increased MDA content) in vivo. Crizotinib and sunitinib also stimulated hepatocyte mitochondrial apoptosis and necrosis in L02 cells in a dose-dependent manner. In vivo studies further confirmed that crizotinib and sunitinib decreased mitochondrial membrane potential and activated apoptosis-associated proteins (cleaved-PARP, cleaved caspase3, cytochrome c, Bcl2 and Bax). Furthermore, mechanistic investigations demonstrated that crizotinib and sunitinib accumulated ROS and inhibited Nrf2 signaling, and that ROS scavenger NAC and Nrf2 agonist tBHQ alleviated the extent of cell damage and the mitochondrial apoptosis during crizotinib- and sunitinib-induced hepatotoxicity in L02 cells. Collectively, these findings indicated that NAC and tBHQ play the crucial roles in crizotinib- and sunitinib-induced mitochondrial apoptosis via the regulation of oxidative stress.

Background: Colorectal cancer (CRC) is the most common type of gastrointestinal malignant tumour. Colorectal adenocarcinoma (COAD)—the most common type of CRC—is particularly dangerous. The role of the immune system in the development of tumour-associated inflammation and cancer has received increasing attention recently. Methods: In this study, we compiled the expression profiles of 262 patients with complete follow-up data from the Cancer Genome Atlas (TCGA) database as an experimental group and selected 65 samples from the GEO dataset (of which 46 samples with M0) as a verification group. First, we screened the immune Th17 cells related to the prognosis of COAD. Subsequently, we identified Th17-cells-related hub genes by utilizing co-expression network analysis (WGCNA) and LASSO regression analysis. Six genes associated with the prognosis in patients with COAD were identified ,including : KRT23, ULBP2, ASRGL1, SERPINA1, SCIN, and SLC28A2. We constructed a clinical prediction model and analysed its predictive power. Results: The identified hub genes are involved in developing many diseases and closely linked to digestive disorders. Our results suggested that the hub genes could influence the prognosis of COAD by regulating Th17 cells’ infiltration. Conclusions: These newly discovered hub genes contribute to clarifying the mechanisms of COAD development and metastasis. Given that they promote COAD development, they may become new therapeutic targets and biomarkers of COAD.

Both crizotinib and sunitinib, novel orally-active multikinase inhibitors, exhibit antitumor activity and extend the survival of patients with a malignant tumor. However, some patients may suffer liver injury that can further limit the clinical use of these drugs, however the mechanisms underlying hepatotoxicity are still to be elucidated. Thus, our study was designed to use HepG2 cells in vitro and the ICR mice model in vivo to investigate the mechanisms of hepatotoxicity induced by crizotinib and sunitinib. Male ICR mice were treated orally with crizotinib (70 mg/kg/day) or sunitinib (7.5 mg/kg/day) for four weeks. The results demonstrated that crizotinib and sunitinib caused cytotoxicity in HepG2 cells and chronic liver injury in mice, which were associated with oxidative stress, apoptosis and/or necrosis. Crizotinib- and sunitinib-induced oxidative stress was accompanied by increasing reactive oxygen species and malondialdehyde levels and decreasing the activity of superoxide dismutase and glutathione peroxidase. Notably, the activation of the Kelch-like ECH-associated protein-1/Nuclear factor erythroid-2 related factor 2 signaling pathway was involved in the process of oxidative stress, and partially protected against oxidative stress. Crizotinib and sunitinib induced apoptosis via the mitochondrial pathway, which was characterized by decreasing Bcl2/Bax ratio to dissipate the mitochondrial membrane potential, and increasing apoptotic markers levels. Moreover, the pan-caspase inhibitor Z-VAD-FMK improved the cell viability and alleviated liver damage, which further indicated the presence of apoptosis. Taken together, this study demonstrated that crizotinib- and sunitinib-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and markedly increased levels of serum alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase.