Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m 2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51-64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol-related liver disease; 68% developed ≥ stage 3 CKD at the end of follow-up. The 1-year, 3-year, and 5-year incidence rates of post-SLKT stage 4-5 CKD were 10%, 12%, and 16%, respectively. Pre-SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00-2.15), NASH (HR, 1.58; 95% CI, 1.01-2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10-2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22-0.89) reduced the risk. Women (β = −6.22 ± 2.16 mL/minute/1.73 m 2 ; P = 0.004), NASH (β = −7.27 ± 3.27 mL/ minute/1.73 m 2 ; P = 0.027), and delayed kidney graft function (β = −7.25 ± 2.26 mL/minute/1.73 m 2 ; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow-up. Stage 4-5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.

The effects of reaction temperature, mass ratio of catalyst to oil, space velocity, and mass ratio of water to oil on the product distribution, the yields of light olefins (light olefins including ethylene, propylene and butylene) and the composition of the fluid catalytic cracking (FCC) gasoline upgraded over the self-made catalyst GL in a confined fluidized bed reactor were investigated. The experimental results showed that FCC gasoline was obviously reformulated under appropriate reaction conditions. The olefins (olefins with C atom number above 4) content of FCC gasoline was markedly reduced, and the aromatics content and octane number were increased. The upgraded gasoline met the new standard of gasoline, and meanwhile, higher yields of light olefins were obtained. Furthermore, higher reaction temperature, higher mass ratio of catalyst to oil, higher mass ratio of water to oil, and lower space velocity were found to be beneficial to FCC gasoline reformulation and light olefins production.

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BackgroundLoss of dendritic spine density in neocortical areas is a well‐known correlate of cognitive decline in Alzheimer Disease (AD), while preservation of dendritic spines in subjects containing AD‐related pathology is associated with cognitive resilience. Because normal aging is itself associated with dendritic spine loss, identifying upstream mediators of dendritic spine loss may provide an opportunity to develop targeted pharmacotherapies which enhance cognitive resilience and protect against dementia onset. We therefore quantified dendritic spine density and the abundance of over 5000 proteins in the precuneus, a cortical region that is selectively vulnerable early in AD progression.MethodThe right precuneus was isolated postmortem from 98 subjects, ages 20‐96 years, none of whom had a documented neurocognitive disorder. Quantitative immunohistochemistry and spinning disk microscopy were used to estimate dendritic spine density by detecting colocalization of spinophilin and filamentous actin. Gray matter was biochemically fractioned into cellular homogenate and synaptosome fractions, and protein abundance was quantified by liquid chromatography/tandem mass tag mass spectrometry. Proteins were assembled into correlated networks using Weighted Gene Co‐expression Network Analysis (WGCNA), and a statistical mediation analysis was used to identify protein networks which mediate the effect of age on dendritic spine density. WebGestalt was used to identify enrichment for gene ontology terms for protein networks relative to a background of all proteins detected in homogenate.ResultThe density of large dendritic spines exhibited a negative correlation with increasing age (Pearson R= ‐0.36, p<0.001) (Figure 1). A total of 1839 of 5032 proteins detected in cellular homogenate and 914 of 4754 proteins detected in synaptosomes was significantly correlated with age (q<0.05). Proteins segregated into 19 network modules, five of which significantly mediated the effect of age on dendritic spine density. The modules were enriched for gene ontology terms including “positive regulation of excitatory postsynaptic potential” (enrichment ratio=11.0, p=0.034), “neurotransmitter transport” (enrichment ratio=3.9, p=0.003) and “myelination” (enrichment ratio=21.5, p=<0.001).ConclusionDensity of large dendritic spines declines linearly with age within the precuneus. Network analysis revealed a novel role for myelination by oligodendrocytes in spine loss, identifying a potential target to increase cognitive resilience during aging.