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Autophagy, an evolutionarily conserved cytoplasmic degradation system, has been implicated as a convergent mechanism in various longevity pathways. Autophagic activity decreases with age in several organisms, but the underlying mechanism is unclear. Here, we show that the expression of Rubicon, a negative regulator of autophagy, increases in aged worm, fly and mouse tissues at transcript and/or protein levels, suggesting that an age-dependent increase in Rubicon impairs autophagy over time, and thereby curtails animal healthspan. Consistent with this idea, knockdown of Rubicon extends worm and fly lifespan and ameliorates several age-associated phenotypes. Tissue-specific experiments reveal that Rubicon knockdown in neurons has the greatest effect on lifespan. Rubicon knockout mice exhibits reductions in interstitial fibrosis in kidney and reduced α-synuclein accumulation in the brain. Rubicon is suppressed in several long-lived worms and calorie restricted mice. Taken together, our results suggest that suppression of autophagic activity by Rubicon is one of signatures of aging. Autophagic activity decreases with age via unknown mechanisms. Here the authors show that expression of the negative autophagy regulator Rubicon increases with age, that its genetic ablation improves lifespan and ameliorates a number of age-associated phenotypes in invertebrates and in mouse models.

Fabrication and characterization of methylammonium lead iodide perovskite solar cells incorporated with methylammonium bromide (MABr), formamidinium bromide (FABr), and decaphenylcyclopentasilane (DPPS) were performed. Additive effect of MABr or FABr into the perovskite layers inserted with DPPS as hole-transporting layer was investigated. Addition of 5% MABr or FABr into the perovskite layer improved the short-circuit current density, shunt resistance, and open-circuit voltages, which depended on the uniform morphologies while suppressing defects and pinholes in the perovskite layer. The stabilities of the photovoltaic performance depended on the degree of incorporation of MABr or FABr with the DPPS layer, which suppressed decomposition in the perovskite layer.

Background No literature review exists on Mycoplasma pneumoniae -associated mild encephalitis/encepharopathy with a reversible splenial lesion (MERS). Methods M.pneumoniae -associated MERS cases were searched till August 2016 using PubMed/Google for English/other-language publications and Ichushi ( http://www.jamas.or.jp/ ) for Japanese-language publications. Inclusion criteria were children fulfilling definition for encephalitis, M.pneumoniae infection, and neuroimaging showing hyperintensity in the splenium of the corpus callosum (SCC) alone (type I) or SCC/other brain areas (type II). Results We described two children with type I and II M.pneumoniae -associated MERS. Thirteen cases found by the search and our 2 cases were reviewed. Mean age, male/female ratio, duration of prodromal illness was 8.3 years, 1.5 and 3.5 days. The most common neurological symptom was drowsiness, followed by abnormal speech/behavior, ataxia, seizure, delirium, confusion, tremor, hallucination, irritability, muscle weakness, and facial nerve paralysis. Fever was the most common non-neurological symptom, followed by cough, headache, gastrointestinal symptoms, headache, lethargy and dizziness. Seizure and respiratory symptoms were less common. All were diagnosed for M.pneumoniae by serology. Cerebrospinal fluid (CSF) M.pneumoniae was undetectable by PCR in the 3 patients. Three patients were clarithromycin-resistant. Leukocytosis, positive C-reactive protein, hyponatremia, CSF pleocytosis and slow wave on electroencephalography frequently occurred. All except 2 were type I MERS. Neuroimaging abnormalities disappeared within 18 days in the majority of patients. All type I patients completely recovered within 19 days. Two type II patients developed neurological sequelae, which recovered 2 and 6 months after onset. Conclusions Prognosis of M.pneumoniae -associated MERS is excellent. Type II MERS may increase a risk of neurological sequelae.

Autophagy is a conserved cellular degradation system that maintains intracellular homeostasis. Cytoplasmic components are engulfed into double-membrane vesicles called autophagosomes, which fuse with lysosomes, and resulting in the degradation of sequestered materials. Recently, a close association between autophagy and the pathogenesis of metabolic diseases and ageing has become apparent: autophagy is dysregulated during metabolic diseases and ageing; dysregulation of autophagy is intimately associated with the pathophysiology. Rubicon (Run domain Beclin-1 interacting and cysteine-rich containing protein) has been identified as a Beclin-1 associated protein. Notably, Rubicon is one of few negative regulators of autophagy whereas many autophagy-related genes are positive regulators of autophagy. Rubicon also has autophagy-independent functions including phagocytosis and endocytosis. In this mini-review, we focus on the various roles of Rubicon in different organs in the settings of metabolic diseases and ageing, and discuss its potential role as a promising therapeutic target.

Polysilane-inserted CH3NH3PbI3 perovskite photovoltaic devices combined with potassium and formamidinium iodides were fabricated and characterized. Decaphenylcyclopentasilane layers were inserted at the perovskite/hole transport interface and annealed across a temperature range of 180–220 °C. These polysilane-coated cells prevented PbI2 formation, and the conversion efficiencies were improved over extended periods of time.

CH3NH3PbI3 perovskite photovoltaic devices treated with a polysilane layer were fabricated and characterized. Decaphenylcyclopentasilane (DPPS) in chlorobenzene solution was deposited at the surface of the perovskite layer, and the resulting device was annealed at 140–260 °C. The photoconversion efficiencies of the DPPS-treated device remained high even after 255 days in ambient air. Raman scattering spectroscopy and ab initio molecular orbital calculations of DPPS suggested that it increased hole transport efficiency in the treated devices, which was confirmed from the high shunt resistances of the DPPS-treated devices.

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic target of rapamycin kinase complex 1 pathway in a Rag GTPase-dependent manner, though these effects gradually diminished after extended treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney disease. Proximal tubular epithelial cell-specific (PTEC-specific) Tfeb-deficient mice fed a high-fat diet (HFD) exhibited greater phospholipid accumulation in enlarged lysosomes, which manifested as multilamellar bodies (MLBs). Activated TFEB mediated lysosomal exocytosis of phospholipids, which helped reduce MLB accumulation in PTECs. Furthermore, HFD-fed, PTEC-specific Tfeb-deficient mice showed autophagic stagnation and exacerbated injury upon renal ischemia/reperfusion. Finally, higher body mass index was associated with increased vacuolation and decreased nuclear TFEB in the proximal tubules of patients with chronic kidney disease. These results indicate a critical role of TFEB-mediated lysosomal exocytosis in counteracting renal lipotoxicity.

BackgroundTolvaptan (TLV) promotes aquaresis; however, little is known about its effect on solute excretion in chronic kidney disease (CKD).MethodsWe retrospectively studied CKD patients with decompensated heart failure (HF) or those with autosomal dominant polycystic kidney disease (ADPKD) receiving TLV. Patients with an increased urine volume of more than twice of daily variance were defined as “responders” in HF. We compared the ability of the urinary osmolality (U-OSM) change and urinary creatinine concentration ([U-Cr]) change to discriminate “responders”. The fractional excretion of sodium (FeNa) and urea nitrogen (FeUN), and blood urea nitrogen (BUN) were monitored.ResultsIn 30 responders among 53 HF patients, TLV increased FeUN significantly from 36.1 to 44.2% after starting TLV, but not FeNa. Since U-OSM is determined partially by urinary UN concentration, the decrease of [U-Cr] after treatment outperformed the U-OSM decrement to discriminate responders, as shown in receiver operating characteristic curve analysis and significantly higher net reclassification index. In 13 ADPKD patients, TLV increased FeUN (34.8, 47.3%, p = 0.02), and significant decrease of BUN by 2.3 (95% confidence interval 0.4–4.2) mg/dL was observed even 3 months after the intervention. Systolic blood pressure decreased significantly by 14.2 (95% confidence interval 4.0–24.4) mmHg along with the increase in FeNa, leading to reduced dosage of antihypertensives in 6 patients.ConclusionTLV promotes the excretion of sodium and urea. The change in [U-Cr] is useful for early discrimination of responders. Hypotension should be carefully monitored during high-dose TLV therapy.

Effects of polysilane additions on CH3NH3PbI3 perovskite solar cells were investigated. Photovoltaic cells were fabricated by a spin-coating method using perovskite precursor solutions with polymethyl phenylsilane, polyphenylsilane, or decaphenyl cyclopentasilane (DPPS), and the microstructures were examined by X-ray diffraction and optical microscopy. Open-circuit voltages were increased by introducing these polysilanes, and short-circuit current density was increased by the DPPS addition, which resulted in the improvement of the photoconversion efficiencies to 10.46%. The incident photon-to-current conversion efficiencies were also increased in the range of 400~750 nm. Microstructure analysis indicated the formation of a dense interfacial structure by grain growth and increase of surface coverage of the perovskite layer with DPPS, and the formation of PbI2 was suppressed, leading to the improvement of photovoltaic properties.