NAT10 regulates neutrophil pyroptosis in sepsis via acetylating ULK1 RNA and activating STING pathway.

Emerging evidence suggests that pyroptosis is involved in sepsis. However, the role of neutrophil pyroptosis in sepsis and the mechanisms remains elusive. We find that N-acetyltransferase 10 (NAT10), an acetyltransferase responsible for the N4-acetylation of Cytidine (ac4C) in mRNA, is significantly downregulated in neutrophils from septic mice. Neutrophil-specific over-expression of NAT10 improves the survival and ameliorates lung injury in septic mice by inhibiting neutrophil pyroptosis. Notably, UNC-52-like kinase 1 (ULK1) is identified as the target of NAT10 in neutrophils. The decreased expression of NAT10 resultes in the decay of ULK1 transcripts and therefore the reduced expression of ULK1. As a regulator of STING phosphorylation, the loss of ULK1 enhances the activation of STING-IRF3 signaling and subsequently the elevated pyroptosis-inducing NLRP3 inflammasome in neutrophils. While over-expression of NAT10 restrains pyroptosis in neutrophils as well as septic lethality in mice by reversing the ULK1-STING-NLRP3 axis. The decreased expression of NAT10 are also observed in sepsis patients and its correlation with clinical severity is found. Collectively, our findings disclose that NAT10 is a negative regulator of neutrophil pyroptosis and its downregulation contributes to the progress of sepsis by exacerbating pyroptosis via the ULK1-STING-NLRP3 axis, therefore revealing a potential therapeutic target for sepsis.

Transketolase Serves as a Biomarker for Poor Prognosis in Human Lung Adenocarcinoma.

Despite apparently having completed surgical resection, approximately half of resected early-stage lung cancer patients relapse and die of their disease. Adjuvant chemotherapy reduces this risk by only 5% to 8%. Thus, there is a need for better identifying the drivers of relapse, who benefits from adjuvant therapy, and novel targets in this setting. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and cancer, the role of transketolase (TKT), an enzyme in the nonoxidative branch of the PPP that connects PPP and glycolysis, remains obscure in Lung adenocarcinoma (LUAD). In this study, TKT expression was first identified in The Cancer Genome Atlas (TCGA) and then validated with our database. TKT was upregulated at protein levels in cancer compared with normal tissues (P <0.05), and high TKT expression was associated with advanced tumor stage in our cohorts. Besides, TKT inhibitor promotes tumor cell apoptosis and cell cycle blockade. Clearly, TKT plays a critical role in LUAD progression and prognosis and could be a potential biomarker for prediction of recurrence after lung cancer resection.

Reduction of cardiac motion artifact in step-and-shoot coronary CT angiography with third-generation as compared with second-generation dual-source CT scanners.

PURPOSE: We aimed to compare the effects of misregistration (stair-step artifact) occurrence during coronary computed tomography angiography (CCTA) using third- and second-generation dual-source computed tomography (DSCT) scanners. METHODSÇ: CCTA was performed in consecutive patients with suspected coronary heart disease. Patients were randomly assigned to two groups and imaged using a third-generation (n=68; group A) or second-generation (n=63; group B) DSCT scanner. Heart rate (HR), heart rate variability (HRV), the number of acquisition steps required, and the anatomical cardiac length of each patient were recorded and compared between the two groups. Qualitative interpretation and analyses were scored with respect to subjective image quality and misregistration (stair-step artifact) by two interpreters. Cohen's kappa was used to evaluate the consistency between the observers. RESULTS: All CCTA images (100%) on both DSCT scanners yielded satisfactory image quality, with a subjective image quality score of 4.21±0.17. The consistency between the two observers with respect to misregistration and subjective scores were good (κ= 0.91 and 0.92, respectively). Both the number of acquisition steps required and the scan length of each patient in group A differed significantly (p < 0.001) from those in group B; there were significantly fewer artifacts in group A than in group B (p < 0.001). Misregistration artifacts did not correlate with the HRs or HRVs between two required acquisition steps (p > 0.20). CONCLUSION: As compared with second-generation DSCT, the reduced number of acquisition steps required and the shorter scan length in third-generation DSCT reduced the occurrence of misregistration artifacts in CCTA images.

The role of long-acting muscarinic antagonist/long-acting ß agonist fixed-dose combination treatment for chronic obstructive pulmonary disease in China: a narrative review.

OBJECTIVE: To provide an overview of the existing international and Chinese evidence regarding dual bronchodilator inhalation therapy and to make recommendations for the further improvement of chronic obstructive pulmonary disease (COPD) management in clinical practice in China. BACKGROUND: COPD is a progressive lung disease that is characterized by persistent airflow limitation and is a major contributor to the disease burden in China. Symptoms in Chinese patients are relatively more severe. Currently, many Chinese COPD patients are undertreated. Dual bronchodilator therapy consisting of a long-acting muscarinic antagonist (LAMA) and a long-acting ß agonist (LABA) is considered a good choice for COPD patients due to the increased bronchodilation without an increase in adverse events; these combinations can fill in the gap in currently available COPD treatments and provide new pharmacotherapy options for Chinese patients. LAMA/LABA fixed-dose combinations (FDCs) have become more important in clinical practice and guidelines in China regarding their therapeutic effects and safety. METHODS: Clinical trials on LAMA/LABA in COPD were retrieved in ClinicalTrials.gov, while important COPD guidelines published in English or Chinese were found in PubMed and Wanfang Database. CONCLUSIONS: We recommend the adoption of a clinical pathway in China that includes an assessment and management algorithm that considers the clinical characteristics in China and classifies the phenotypic characteristics of COPD according to a suitable system. Based on the current information, we can conclude that LAMA/LABA FDCs are a suitable and economically viable choice to reduce symptoms and improve the quality of life (QoL) of patients.

Facile synthesis of a flame retardant melamine phenylphosphate and its epoxy resin composites with simultaneously improved flame retardancy, smoke suppression and water resistance.

A flame retardant melamine phenylphosphate (MPhP) was facilely synthesized by the reaction of phenylphosphoric acid (PPA) and melamine (MEL), and was characterized by FTIR and NMR. Epoxy resin (EP) composites containing MPhP were prepared, and the effect of MPhP content on flame retardancy, smoke suppression, mechanical properties and thermal stability of the composites was investigated. It is observed that the LOI of the EP composite with 20 wt% MPhP (EP/MPhP20) is 26.5%, and the composite EP/MPhP20 reaches a UL 94 V-0 rating. Cone calorimeter test results show that the peak heat release rate, total heat release and total smoke release of EP/MPhP20 decrease by 51%, 34%, and 24%, respectively compared with those of pure EP. The flame retardancy of the EP/MPhP composites after the water treatment at 80 °C for 72 h is basically maintained, indicating that the composites have good water resistance. The mechanical strengths of the EP/MPhP composites decrease gradually with an increase in the MPhP content. Moreover, the thermal stability of the EP/MPhP composites was studied.

A "turn-on" lanthanide complex chemosensor for recognition of lead(ii) based on the formation of nanoparticles.

A functional amide-type pincer ligand was designed and synthesized, which could effectively capture Tb3+ ions to form a phosphorescence complex-based chemosensor Tb-1. The chemosensor could further coordinate with Pb2+ ions and display a turn-on phosphorescence response. This sensing process was analyzed in detail by steady-state luminescence spectroscopy, time-resolved luminescence spectroscopy, electron microscopy and dynamic light scattering, which suggest that the formation of Pb2+-induced hydroxide nanoclusters can adjust the optical signal of the external luminescence compound by embedment and fixation of Tb3+ complexes. Furthermore, Tb-1 could effectively eliminate the signal interference from the short-lived fluorescence and improve the signal-to-noise ratio to increase the accuracy of the detection for Pb2+. An understanding of the recognition mechanism of the Tb3+ complex-based chemosensor and the application of the characteristic spectra of lanthanide ions might be able to provide more opportunities to develop highly selective optical chemosensors.

A highly selective fluorescence "turn-on" probe for Cu(II) based on reaction and its imaging in living cells.

A new oxidative C-O bond cleavage reaction-based probe FluHMPP was designed and prepared. FluHMPP displays excellent selective turn-on fluorescence response for Cu(II) in aqueous solution under visible light excitation. The cleavage products are fully characterized. Fluorescein fragment is further oxidized to highly fluorescent MFME (3'-O-methylfluorescein methyl ester), and benzyl ether of imine fragment has been transformed to carboxyl. Confocal microscopy experiments have demonstrated that FluHMPP could also be used in live cells for the detection of Cu(II).

An 1,3,4-oxadiazole-based OFF-ON fluorescent chemosensor for Zn2+ in aqueous solution and imaging application in living cells.

A new 1,3,4-oxadiazole-based fluorescence chemosensor 1, N-(2-ethoxy-2-oxoethyl)-N-(5-(2-hydroxy-3,5-di-tert-butylphenyl)-[1,3,4]oxadiazol-2-yl)glycine ethyl ester, has been designed and synthesized. Its fluorescence properties and selectivity for various metal ions were investigated in detail. A prominent fluorescence enhancement only for Zn(2+) was found in aqueous acetonitrile solution and the response mechanism of 1 was analyzed by time-resolved fluorescence decay and DFT calculations. Furthermore, the fluorescence imaging of Zn(2+) in living cells was successfully applied.