Mitochondrial protein dysfunction in pathogenesis of neurological diseases

Mitochondria are essential organelles for neuronal function and cell survival. Besides the well-known bioenergetics, additional mitochondrial roles in calcium signaling, lipid biogenesis, regulation of reactive oxygen species, and apoptosis are pivotal in diverse cellular processes. The mitochondrial proteome encompasses about 1,500 proteins encoded by both the nuclear DNA and the maternally inherited mitochondrial DNA. Mutations in the nuclear or mitochondrial genome, or combinations of both, can result in mitochondrial protein deficiencies and mitochondrial malfunction. Therefore, mitochondrial quality control by proteins involved in various surveillance mechanisms is critical for neuronal integrity and viability. Abnormal proteins involved in mitochondrial bioenergetics, dynamics, mitophagy, import machinery, ion channels, and mitochondrial DNA maintenance have been linked to the pathogenesis of a number of neurological diseases. The goal of this review is to give an overview of these pathways and to summarize the interconnections between mitochondrial protein dysfunction and neurological diseases.Peer reviewe

The final step effect

Suppose you need to complete a task of 5 steps, each of which has equal difficulty and pass rate. You somehow have a privilege that can ensure you pass one of the steps, but you need to decide which step to be privileged before you start the task. Which step do you want to privilege? Mathematically speaking, the effect of each step on the final outcome is identical, and so there seems to be no prima facie reason for a preference. Five studies were conducted to explore this issue. In Study 1, participants could place the privilege on any of steps 1–5. Participants were most inclined to privilege step 5. In Study 2, participants needed to pay some money to purchase the privilege for steps 1–5, respectively. Participants would pay most money for step 5. Study 3 directly reminded participants that the probability of success of the whole task is mathematically the same, no matter on which step the privilege is placed, but most of the participants still prefer to privilege the final step. Study 4 supposed that the outcomes of all steps were not announced until all steps were finished, and asked how painful participants would feel if they passed all steps but one. People thought they would feel most painful when they failed at the final step. In Study 5, an implicit association test showed that people associated the first step with easy and the final step with hard. These results demonstrated the phenomenon of the final step effect and suggested that both anticipated painfulness and stereotype may play a role in this phenomenon

Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials

Introduction: Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors — alirocumab and evolocumab — are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels. Material and methods: Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1. Results: Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): –20.10%, 95% confidence interval (CI): –25.59% to –14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: –19.98%, 95% CI: –25.23% to –14.73%), there was no difference with alirocumab (WMD: –20.54%, 95% CI: –30.07% to –11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: –17.61%, 95% CI: –23.84% to –11.38%) was lower than in the group of ≥ 24 weeks’ duration (WMD: –22.81%, 95% CI: –31.56% to –14.07%). In the participants’ characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: –20.07%, 95% CI: –26.07% to –14.08%; homozygous FH [HoFH] WMD: –20.04%, 95% CI: –36.31% to –3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98–1.12] implied no obvious difference between the 2 groups. Conclusions: Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors. However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH

Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer

Acknowledgement. BGS acknowledges work performed at the Center for Nanophase Materials Sciences, a DOE Office of Science User Facility. VB acknowledges Laboratory Directed Research and Development program of Oak Ridge National Laboratory, managed by UTBattelle, LLC, for the U.S. Department of Energy.Peer reviewedPostprin

Surface passivation for highly active, selective, stable, and scalable CO2 electroreduction

Electrochemical conversion of CO2 to formic acid using Bismuth catalysts is one the most promising pathways for industrialization. However, it is still difficult to achieve high formic acid production at wide voltage intervals and industrial current densities because the Bi catalysts are often poisoned by oxygenated species. Herein, we report a Bi3S2 nanowire-ascorbic acid hybrid catalyst that simultaneously improves formic acid selectivity, activity, and stability at high applied voltages. Specifically, a more than 95% faraday efficiency was achieved for the formate formation over a wide potential range above 1.0 V and at ampere-level current densities. The observed excellent catalytic performance was attributable to a unique reconstruction mechanism to form more defective sites while the ascorbic acid layer further stabilized the defective sites by trapping the poisoning hydroxyl groups. When used in an all-solid-state reactor system, the newly developed catalyst achieved efficient production of pure formic acid over 120 hours at 50 mA cm–2 (200 mA cell current)

Educational Programming Application for Preschool Students Using Virtual Tangible Interface Implemented by Microsoft Hololens

In the 1960s, pioneer of constructionist learning, Professor Emeritus Seymour Papert envisioned that future education with computers would promote a more dynamic environment where children could take charge of the machines and build their own creations, as opposed to simply following prepackaged instructions. Thus, a tangible interface was first introduced by his team, aiming to take away the abstraction of computer screens and replace controls with direct and intuitive manipulation of physical toys. While tangible interfaces have created an enormous field of research, the evolution of pure on-line programming education has also begun. With the emerging technology of augmented reality such as Microsoft HoloLens, the dilemma might find its final resolution. With its transparent vision, a pair of HoloLens glasses, along with its clicker for intuitive manipulation, allows the rework and combination of concepts in both tangible user interface and on-line programming tools. The first part of this research is to study relevant work, analyze interfaces and systems built by other groups, and identify the key factors that have made their work successful. Then, a HoloLens application was carefully designed and crafted on top of the key concepts, aiming to combine the advantages of both areas. During testing, we found that part of the experience was limited by the physical hardware as the technology was still at its initial stage. However, the application itself was able to inherit the successes and make the user experience immediate, accessible and intuitive.U of I OnlySenior thesis not recommended for open acces

A Method for Filtering Pages by Similarity Degree based on Dynamic Programming

To obtain the target webpages from many webpages, we proposed a Method for Filtering Pages by Similarity Degree based on Dynamic Programming (MFPSDDP). The method needs to use one of three same relationships proposed between two nodes, so we give the definition of the three same relationships. The biggest innovation of MFPSDDP is that it does not need to know the structures of webpages in advance. First, we address the design ideas with queue and double threads. Then, a dynamic programming algorithm for calculating the length of the longest common subsequence and a formula for calculating similarity are proposed. Further, for obtaining detailed information webpages from 200,000 webpages downloaded from the famous website “www.jd.com„, we choose the same relationship Completely Same Relationship (CSR) and set the similarity threshold to 0.2. The Recall Ratio (RR) of MFPSDDP is in the middle in the four filtering methods compared. When the number of webpages filtered is nearly 200,000, the PR of MFPSDDP is highest in the four filtering methods compared, which can reach 85.1%. The PR of MFPSDDP is 13.3 percentage points higher than the PR of a Method for Filtering Pages by Containing Strings (MFPCS)

A Reliability Calculation Method for Web Service Composition Using Fuzzy Reasoning Colored Petri Nets and Its Application on Supercomputing Cloud Platform

In order to develop a Supercomputing Cloud Platform (SCP) prototype system using Service-Oriented Architecture (SOA) and Petri nets, we researched some technologies for Web service composition. Specifically, in this paper, we propose a reliability calculation method for Web service compositions, which uses Fuzzy Reasoning Colored Petri Net (FRCPN) to verify the Web service compositions. We put forward a definition of semantic threshold similarity for Web services and a formal definition of FRCPN. We analyzed five kinds of production rules in FRCPN, and applied our method to the SCP prototype. We obtained the reliability value of the end Web service as an indicator of the overall reliability of the FRCPN. The method can test the activity of FRCPN. Experimental results show that the reliability of the Web service composition has a correlation with the number of Web services and the range of reliability transition values