Aims/hypothesis The unfolded protein response (UPR) in endoplasmic reticulum (ER) and autophagy are known to be related. We investigated the role of autophagy in UPR of pancreatic beta cells and the susceptibility of autophagydeficient beta cells to the ER stress that is implicated in the development of diabetes. Methods Rat insulin promoter (RIP)-Cre + ;autophagy-related 7 (Atg7) F/W mice were bred with ob/w mice to derive RIP-Cre + ;Atg7 F/F -ob/ob mice and to induce ER stress in vivo. GFP-LC3 + -ob/ob mice were generated to examine in vivo autophagic activity. Real-time RT-PCR was performed to study the expression of the genes of the UPR machinery. Proteolysis was assessed by determining release of incorporated radioactive leucine.Results Production of UPR machinery was reduced in autophagy-deficient beta cells, which was associated with diminished production of p85α and p85β regulatory subunits of phosphoinositide 3-kinase. Because of compromised UPR machinery, autophagy-deficient beta cells were susceptible to ER stressors in vitro. When mice with beta cell-specific autophagy deficiency, which have mild hyperglycaemia, were bred with ob/ob mice to induce ER stress in vivo, severe diabetes developed, which was accompanied by an increase in beta cell death and accumulation of reactive oxygen species. The increased demand for UPR present in obesity was unmet in autophagy-deficient beta cells. Autophagy level and autophagic activity were enhanced by lipid, while proteolysis was reduced. Conclusions/interpretation These results suggest that autophagy is important for intact UPR machinery and appropriate UPR in response to lipid injury that increases demand for UPR. Autophagy deficiency in pancreatic beta cells may contribute to the progression from obesity to diabetes.

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Recently, extremely small bubbles, referred to as nanobubbles, have drawn increased attention due to their novel properties and great potential for various applications. In this study, a novel method for the generation of bulk nanobubbles (BNBs) was introduced, and stability of fabricated BNBs was investigated. BNBs were created from CO gas with a mixing method; the chemical identity and phase state of these bubbles can be determined via infrared spectroscopy. The presence of BNBs was observed with a nanoparticle tracking analysis (NTA). The ATR-FTIR spectra of BNBs indicate that the BNBs were filled with CO gas. Furthermore, the BNB concentration and its ζ-potential were about 2.94 × 10 particles/mL and -20 mV, respectively (24 h after BNB generation with a mixing time of 120 min). This indicates the continued existence and stability of BNBs in water for an extended period of time.

We evaluated the predictive value of serum biomarkers and various clinical risk scales for the 28-day mortality of community-acquired pneumonia (CAP). Serum biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) were evaluated in the emergency department. Scores for the pneumonia severity index (PSI); CURB65 (confusion, urea, respiration, blood pressure; age >65 years); Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) guidelines for severe CAP; Acute Physiology, Chronic Health Evaluation (APACHE) II; Sequential Organ Failure Assessment (SOFA); and quick SOFA (qSOFA) were calculated. Receiver-operating characteristic curves for 28-day mortality were calculated for each predictor using cut-off values, and we applied logistic regression models and area under the curve (AUC) analysis to compare the performance of predictors. Of the 125 enrolled patients, 13 died within 28 days. The AUCs of the PCT and CRP were 0.83 and 0.77, respectively. Using a PCT level >5.6 μg/L as the cut-off, the sensitivity and specificity for mortality were 76.9% and 90.2%, respectively. The three pneumonia severity scales showed an AUC of 0.86 (PSI), 0.87 (IDSA/ATS) and 0.77 (CURB65). The AUCs of the APACHE II, SOFA and qSOFA scores were 0.85, 0.83 and 0.81, respectively. The models combining CRP and/or PCT with PSI or the IDSA/ATS guidelines demonstrated superior performance to those of either PSI or the IDAS/ATS guidelines alone. In conclusion, serum PCT is a reliable single predictor for short-term mortality. Inclusion of CRP and/or PCT could significantly improve the performance of the PSI and IDAS/ATS guidelines.