Abstract Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. Although the development of modern medicine has promoted human health and greatly extended life expectancy, with the aging of society, a variety of chronic diseases have gradually become the most important causes of disability and death in elderly individuals. Current research on aging focuses on elucidating how various endogenous and exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss of proteostasis, compromise of autophagy, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing) participate in the regulation of aging. Furthermore, thorough research on the pathogenesis of aging to identify interventions that promote health and longevity (such as caloric restriction, microbiota transplantation, and nutritional intervention) and clinical treatment methods for aging-related diseases (depletion of senescent cells, stem cell therapy, antioxidative and anti-inflammatory treatments, and hormone replacement therapy) could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity. 

/pdf/aging-and-aging-related-diseases-from-molecular-mechanisms-3t6fqopn.pdf

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

A computational framework for coating fatigue analysis of wind turbine blades due to rain erosion

Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.

https://www.mdpi.com/2218-273X/12/11/1676/pdf?version=1668749242

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1–5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or the Amyloid precursor protein (APP). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aβ) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.

/pdf/alzheimers-disease-an-updated-overview-of-its-genetics-1ds9lkq6.pdf

Alzheimer’s Disease: An Updated Overview of Its Genetics

Abstract Design is a high-level and complex thinking activity of human beings, using existing knowledge and technology to solve problems and create new things. With the rise and development of intelligent manufacturing, design has increasingly reflected its importance in the product life cycle. Firstly, the concept and connotation of complex product design is expounded systematically, and the different types of design are discussed. The four schools of design theory are introduced, including universal design, axiomatic design, TRIZ and general design. Then the research status of complex product design is analyzed, such as innovative design, digital design, modular design, reliability optimization design, etc. Finally, three key scientific issues worthy of research in the future are indicated, and five research trends of “newer, better, smarter, faster, and greener” are summarized, aiming to provide references for the equipment design and manufacturing industry. 

/pdf/design-theory-and-method-of-complex-products-a-review-1ddb9xi2.pdf

Design Theory and Method of Complex Products: A Review

Alzheimer’s disease (AD) is a neurodegenerative disease with unknown pathogenesis and complex pathological manifestations. At present, a large number of studies on targeted drugs for the typical pathological phenomenon of AD (Aβ) have ended in failure. Although there are some drugs on the market that indirectly act on AD, their efficacy is very low and the side effects are substantial, so there is an urgent need to develop a new strategy for the treatment of AD. An increasing number of studies have confirmed epigenetic changes in AD. Although it is not clear whether these epigenetic changes are the cause or result of AD, they provide a new avenue of treatment for medical researchers worldwide. This article summarizes various epigenetic changes in AD, including DNA methylation, histone modification and miRNA, and concludes that epigenetics has great potential as a new target for the treatment of AD.

/pdf/epigenetics-in-alzheimers-disease-2kbrzymu.pdf

Epigenetics in Alzheimer’s Disease

A computational model of wind turbine blade erosion induced by raindrop impact

Since the COVID-19 pandemic, governments have implemented lockdowns and movement restrictions to contain the disease outbreak. Previous studies have reported a significant positive correlation between NO2 and mobility level during the lockdowns in early 2020. Though NO2 level and mobility exhibited similar spatial distribution, our initial exploration indicated that the decreased mobility level did not always result in concurrent decreasing NO2 level during a two-year time period in Southeast Asia with human movement data at a very high spatial resolution (i.e., Facebook origin-destination data). It indicated that factors other than mobility level contributed to NO2 level decline. Our subsequent analysis used a trained Multi-Layer Perceptron model to assess mobility and other contributing factors (e.g., travel modes, temperature, wind speed) and predicted future NO2 levels in Southeast Asia. The model results suggest that, while as expected mobility has a strong impact on NO2 level, a more accurate prediction requires considering different travel modes (i.e., driving and walking). Mobility shows two-sided impacts on NO2 level: mobility above the average level has a high impact on NO2, whereas mobility at a relatively low level shows negligible impact. The results also suggest that spatio-temporal heterogeneity and temperature also have impacts on NO2 and they should be incorporated to facilitate a more comprehensive understanding of the association between NO2 and mobility in the future study.

/pdf/long-term-association-between-no2-and-human-mobility-a-two-38i8sdf3.pdf

J. Tan

Papers

Epigenetics in Alzheimer’s Disease

A computational model of wind turbine blade erosion induced by raindrop impact

Long-term Association between NO2 and Human Mobility: A Two-year Spatiotemporal Study during the COVID-19 Pandemic in Southeast Asia