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Abstract Background Angiopoietin-like protein 3(ANGPTL3) is well acknowledged as a key regulator of lipid metabolism. Now, there have not been enough data to explain the mechanism of hyperlipidemia related proteinuria. In this study, we hoped to investigate the changes of Angiopoietin-like protein 3(ANGPTL3) levels in hyperlipidemia patients with different proteinuria levels. Methods Seventy-one patients with hyperlipidemia were selected, who were hospitalized in Gansu Provincial People’s Hospital from September 2016 to September 2017, and 20 healthy people in the physical examination center were selected. We combed through medical history and conducted clinical biochemical indicators of blood urea nitrogen (BUN), serum creatinine (SCr), 24 h urine protein quantitation (24hUPro), cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low detection of density lipoproteins (LDL-C). The concentration of serum ANGPTL3 was measured by ELISA. Results 1. Serum ANGPTL3 in patients with hyperlipidemia related proteinuria was higher than that in the control group, and the difference was statistically significant (p

Background Shenghui Yizhi Decoction (SHYZD) has exhibited the capacity to enhance cognitive function and learning abilities in individuals diagnosed with Alzheimer’s disease (AD) while ameliorating pre-existing neuroinflammation. Nevertheless, the precise mechanism underlying its therapeutic effects on AD remains to be elucidated.Methods Twenty-four male SAMP8 mice were randomly divided into three groups, and eight male SAMR1 mice were used as a blank control, to examine their learning and spatial memory abilities. The expression of amyloid β1-42 (Aβ1-42) was detected by immunohistochemical staining of hippocampal tissue. ELISA was used to detect the interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) expressions. Real time PCR was used to detect NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1β mRNA expression. Western blot was used to detect nuclear factor kappa-B (NF-κB), inhibitor of NF-κB α (IκBα), IκB kinase α (IKKα), NLRP3, Caspase-1, and IL-1β protein expression.Results In this study, SAMP8 mice, employed as an AD model, displayed markedly diminished abilities in terms of spatial localization, navigation, and spatial exploration when compared to the blank control group. Additionally, there was a substantial upregulation of Aβ1-42 expression in the hippocampus of these mice, along with a significant increase in the levels of inflammation-associated factors, including IL-1β, IL-6, TNF-α, NLRP3, Caspase-1, as well as the NF-κB pathway-related proteins, namely, NF-κB, IκBα, and IKKα. Moreover, after treatment with positive drugs (donepezil hydrochloride) and SHYZD, the learning abilities of the mice exhibited significant improvements. Furthermore, the hallmark AD protein Aβ1-42, inflammatory factors, and NF-κB/NLRP3 signalling pathway proteins were significantly reduced. These findings collectively suggest that SHYZD exerts a therapeutic effect on AD.Conclusion In summary, the specific molecular mechanisms through which SHYZD alleviates AD and the potential role for SHYZD in the NF-κB/NLRP3 signalling pathway are identified in this study.

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr−/− mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

Numerical simulation of concrete-faced rockfill dams (CFRDs) considering the spatial variability of rockfill has become a popular research topic in recent years. In order to determine uncertain rockfill properties efficiently and reliably, this study developed an uncertainty inversion analysis method for rockfill material parameters using the stacking ensemble strategy and Jaya optimizer. The comprehensive implementation process of the proposed model was described with an illustrative CFRD example. First, the surrogate model method using the stacking ensemble algorithm was used to conduct the Monte Carlo stochastic finite element calculations with reduced computational cost and improved accuracy. Afterwards, the Jaya algorithm was used to inversely calculate the combination of the coefficient of variation of rockfill material parameters. This optimizer obtained higher accuracy and more significant uncertainty reduction than traditional optimizers. Overall, the developed model effectively identified the random parameters of rockfill materials. This study provided scientific references for uncertainty analysis of CFRDs. In addition, the proposed method can be applied to other similar engineering structures.

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Long-term continuous deposits and well-preserved thick loess sections are natural archives for the reconstruction of global climate change. However, the loess sections are often discontinuous owing to soil erosions and accumulations. This study aimed at reconstructing long-term continuous paleoclimatic records by integrating the target sections of two typical loess sequences in northeast (NE) China. One section, the Dajiugang (DJG) section, was investigated and sampled, and the Sanbahuo (SBH) section was used as the target for integrating and reconstructing the paleoclimate. Sedimentary, pedogenesis, and luminescence dating analyses were conducted to analyze the potentials for reconstructing the paleoclimate by integrating two typical loess sections. The results indicated that the paleoclimate records derived from the DJG section can be used to reconstruct the continuous paleoclimate of NE China by integrating them with the SBH section. The paleoclimate information inferred from the DJG section could impute paleoclimate data from 71 to 11.7 ka, which were missing in the SBH section. The paleoclimate of NE China generally consisted of three periods from 71 to 11.7 ka: cold and dry from 29 to 11.7 ka, alternately cold and warm from 57 to 29 ka, and warm and wet to cold and dry from 71 to 57 ka. Integrating the target loess sections can contribute to reconstructing regional long-term continuous paleoclimate records where discontinuous loess sequences occurred.