RNA-binding proteins signature is a favorable biomarker of prognosis, immunotherapy and chemotherapy response for cervical cancer.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) still present a huge threaten to women's health, especially the local advanced patients. Hence, developing more effectiveness prognostic signatures is urgently needed. This study constructed and verified a robust RNA-binding proteins (RBPs) related signature through a series of bioinformatics methods and explored the biological function of hub RBP in vitro experiments. As a result, the 10 RBPs signature was successfully established and could act as an independent prognostic biomarker in CESC patients, which displayed the highest sensitivity and specificity in prognosis prediction compared with other clinicopathological parameters. The risk model also presented good performance in risk stratification among CESC patients. Besides, a nomogram was constructed based on pathological stage and the risk signature and exhibited satisfactory accuracy in prognosis prediction. Functional enrichment indicated that the risk signature mainly participated in immune-related pathways and cancer-related pathways, and the infiltration level of immune cells and immune checkpoints showed a significantly higher degree in low-risk patients compared with high-risk patients. Notably, the 10 RBPs signature act as a novel biomarker in immunotherapy and chemotherapy response. In addition, PRPF40B was selected as hub RBP and its transcription and translation levels were obviously increased in CESC tissues, as well as Hela and Siha cells. Knockdown of PRPF40B inhibits the proliferation, migration and invasion of Hela and Siha cells in vitro. In conclusion, our research provides a noticeable strategy in prognostic prediction among CESC patients, which may illuminate the prospect of CESC patients' clinical outcome.

HSP90/CDC37 inactivation promotes degradation of LKB1 protein to suppress AMPK signaling in bronchial epithelial cells exposed to sulfur mustard analog, 2-chloroethyl ethyl sulfide.

To investigate the role of the liver kinase (LK) B1 protein, an activator of AMP-activated protein kinase (AMPK), in AMPK signaling suppression when exposed to vesicant, a kind of chemical warfare agent. Cultured human bronchial epithelial cells were inflicted with sulfur mustard (SM) analog, 2-chloroethyl ethyl sulfide (CEES) of 0.2-1.0 mM concentration, and cell proliferation, apoptosis, autophagy, and cellular ATP level were analyzed up to 24 h after the exposure. Focusing on LKB1, heat shock protein (HSP) 90, and cell division cycle (CDC) 37 proteins, the protein expression, phosphorylation, and interaction were examined with western blot, immunofluorescence staining, and/or immunoprecipitation. AMPK signaling was found to be inhibited 24 h after being exposed to either sub-cytotoxic (0.5 mM) or cytotoxic (1.0 mM) concentration of CEES based on MTS assay. Consistently, the degradation of the LKB1 protein and its less interaction with the HSP90/CDC37 complex was confirmed. It was found that 1.0, not 0.5 mM CEES also decreased the CDC37 protein, proteasome activity, and cellular ATP content that modulates HSP90 protein conformation. Inhibiting proteasome activity could alternatively activate autophagy. Finally, either 0.5 or 1.0 mM CEES activated HSP70 and autophagy, and the application of an HSP70 inhibitor blocked autophagy and autophagic degradation of the LKB1 protein. In conclusion, we reported here that AMPK signaling inactivation by CEES was a result of LKB1 protein loss via less protein complex formation and enhanced degradation.

Predisposed obesity and long-term metabolic diseases from maternal exposure to fine particulate matter (PM2.5) - A review of its effect and potential mechanisms.

Ambient air pollution is one of the most serious public health problems over the last decade. It causes about 4.2 million deaths worldwide each year, and fine particulate matter (PM2.5) is one of the major components of air pollution. Many chronic non-communicable diseases may originate from the early-life environment that alters the development of offspring. Pregnancy and lactation are plastic "window periods" for offspring metabolism, during which PM2.5 exposure is associated with long-term metabolic dysfunction in offspring. In this review, we summarized the scientific evidence from both epidemiological and toxicological studies, which suggest that perinatal exposure to PM2.5 causes obesity and metabolic diseases in progeny, including hypertension, cardiometabolic dysfunction, diabetes, and non-alcoholic fatty liver disease (NAFLD). Therefore, prevention strategies are needed to inform government policies and clinical counseling to reduce maternal exposure and its associated health hazards, and ultimately improve the quality of the newborn population.