Paraquat (1,1'-dimethyl-4,4'-bipyridinium chloride; PQ) is widely and commonly used as a herbicides in the world. PQ has been reported to be a major hazard because it causes lung injury. However, the molecular mechanisms underlying PQ-induced lung toxicity still need to be elucidated. Here, we found that PQ significantly decreases cell viability, increases sub-G1 hypodiploids DNA contents and caspase 3/7 activity in lung alveolar epithelial cell-derived L2 cells, which also caused mitochondrial dysfunction, and decreased the mRNA expression of Bcl-2 and increased that of Bax, Bak, and p53. Moreover, the protein expressions of Bax and Bak were increased in PQ-treated cells. In addition, when PQ was exposed to L2 cells, the expressions of ER stress-related signaling genes (including Grp78, CHOP, and caspase-12 mRNA) and proteins (including phospho-eIF-2α, CHOP, Grp78, calpain I and -II, and caspase-12) were significantly increased. PQ also decreased the protein expressions of pro-caspase-9/7/3. Next, we investigated the role of Nrf-2 in PQ-induced alveolar epithelial cell toxicity. In L2 cells, PQ induced Nrf-2 translocation from the cytosol to the nucleus. Cells transfected with Nrf-2 siRNA significantly reversed the PQ-induced toxicity, including depolarization of MMP, increased the Bax, Bak, p53 mRNAs expression, decreased the Bcl-2 mRNA expression, increased the caspase 3/7 activity, Grp78, CHOP, and caspase-12 mRNAs and protein expression, and decreased that of pro-caspase-3. Taken together, these results suggest that Nrf-2-regulated mitochondria and ER stress-related pathways are involved in the PQ-induced alveolar epithelial cell injury.

We used swine testicle (ST) cells infected with transmissible gastroenteritis virus (TGEV) and an indirect immunofluorescent assay with antibodies against TGEV spike and nucleocapsid proteins to screen smallmolecule compounds that inhibit TGEV replication. Analogues of initial hits were collected and subjected to a 3CL protease (3CL pro ) inhibition assay with recombinant 3CL pro and a fluorogenic peptide substrate. A series of benzothiazolium compounds were found to have inhibitory activity against TGEV 3CL pro and to exert anti-TGEV activities in terms of viral protein and RNA replication in TGEV-infected ST cells, with consequent protection of TGEV-infected ST cells from cytopathic effect by blocking the activation of caspase-3.

Rationale:Neonatal gastric perforation is a rare and life-threatening disorder in neonates and is associated with high morbidity and mortality. However, the exact mechanisms of neonatal gastric perforation remain unknown.Patient concerns:In this study, we reported 2 cases of neonatal gastric perforation and conducted a systematic review to analyze the prognostic factors for mortality.Diagnoses:Two neonates received a diagnosis of gastric perforation based on clinical presentation and imaging studies. The 2 patients underwent emergent surgery, which yielded favorable outcomes.Interventions:We reviewed 168 cases from the literature as well as our 2 cases to analyze whether mortality in neonatal gastric perforation is associated with sex, gestational age, operation type, perforation location, or timing of perforation.Outcomes:The results revealed that mortality was significantly higher in preterm neonates (n = 80, P < .01) and the mortality group had a lower birth weight (n = 73, P < .05). The timing of perforation in the preterm subgroup was significantly earlier than that in the full-term subgroup (n = 90, P < .05). The outcomes about mortality of gastric perforation were significantly associated with preterm neonates (adjusted odds ratio: 4.21, 95% confidence interval: 1.28–13.88, P < .05).Lessons:This study shows the prognostic factor of gastric perforation was significantly associated with preterm neonates. Furthermore, low-birth-weight full-term neonates had a relatively higher mortality rate than the normal-birth-weight full-term neonates. In addition, preterm neonates have an earlier timing of perforation.

The current study aimed to investigate whether prognostic nutritional index (PNI) is an independent predictor of acute kidney injury (AKI) and mortality of patients in the coronary care unit (CCU). In the present two-stage observational study of patients in the CCU, 6,444 patients from the Medical Information Mart for Intensive Care (MIMIC) III database were first enrolled (test cohort), after which 412 patients from Zhongnan Hospital of Wuhan University were recruited in the validation cohort. AKI was defined based on the Kidney Disease Improving Global Outcomes AKI criteria. The primary endpoint was the incidence of AKI stratified by severity, while the second endpoint included in-hospital mortality and 2-year mortality. In the test cohort, 4,457 (69.2%) patients developed AKI during hospitalization. Following multivariable adjustment, the highest quartile of the PNI value was associated with a 1.8-fold increased risk of AKI compared with the lowest quartile. For the prediction of AKI, the area under the receiver operating characteristic curve outperformed the acute physiology score III score and clinical model in patients with or without preexisting chronic kidney disease, and this was further validated in the hospital cohort used in the present study. A total of 2,219 patients suffered mortality during the 2-year follow-up, and PNI was indicated to independently predict the risk of in-hospital mortality and 2-year mortality in the test cohort and in the validation cohort. Decision curve analysis indicated that the PNI values were clinically useful; Therefore, the current study demonstrated that the PNI value is an independent predictor of AKI and mortality in patients within the CCU.

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