Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients’ survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.
Cypermethrin (CMN) is a man-made insecticide, and its abuse has led to potential adverse effects, particularly in sensitive populations such as aquatic organisms. The present study was focused on the toxic phenotype and detoxification mechanism in grass carp (Ctenopharyngodon idella) after treatment with waterborne CMN (0.651 μg/L) for 6 weeks in vivo or 6.392 μM for 24 h in vitro. In vivo, we describe the toxic phenotype of the liver of grass carp in terms of pathological changes, serum transaminase levels, oxidative stress indexes, and apoptosis rates. RNA-Seq analysis (2 × 3 cDNA libraries) suggested a compromise of proteasome and oxidative phosphorylation signaling pathways under CMN exposure. Thus, these two pathways were chosen for the in vitro study, which suggested that the CMN intoxicationinduced proteasome pathway caused hepatotoxicity in the liver cell line of grass carp (L8824 cells). Moreover, pretreatment with MG132, a proteasome inhibitor, displayed protection against the toxic effects of CMN by enhancing antioxidative and antiinflammatory capability by directly inhibiting the proteasomal degradation of nuclear factor erythroid-2 related factor (Nrf2) and IκB-α, thus turning on the transcription of downstream genes of Nrf2 and NF-κB, respectively. Taken together, these results suggest proteasome activity as a reason for CMN-induced hepatotoxicity.
Compared with regulation-weight baseballs, lightweight baseballs generate lower torque on the shoulder and elbow joints without altering the pitching movement and timing. This study investigates the throwing accuracy, throwing velocity, arm swing velocity, and maximum shoulder external rotation (MSER) of adolescent players after 10 weeks of pitching training with appropriate lightweight baseballs. We assigned 24 adolescent players to a lightweight baseball group (group L) and a regulation-weight baseball group (group R) based on their pretraining throwing velocity. Both groups received pitching training 3 times per week for 10 weeks with 4.4- and 5-oz baseballs. The players' throwing accuracy, throwing velocity, arm swing velocity, and MSER were measured from 10 maximum efforts throws using a regulation-weight baseball before and after undergoing the pitching training. The results showed that the players in group L significantly increased their throwing velocity and arm swing velocity (p < 0.05) after 10 weeks of pitching training with the 4.4-oz baseball, whereas group R did not (p > 0.05). Furthermore, the percentage change in the throwing velocity and arm swing velocity of group L was significantly superior to that of group R (p < 0.05). Thus, we concluded that the 10 weeks of pitching training with an appropriate lightweight baseball substantially enhanced the arm swing velocity and throwing velocity of the adolescent baseball players. These findings suggest that using a lightweight baseball, which can reduce the risk of injury without altering pitching patterns, has positive training effects on players in the rapid physical growth and technique development stage.
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