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Recent studies have uncovered intriguing connections between Parkinson’s disease (PD) and cancer, two seemingly distinct disease categories. Disulfidptosis has garnered attention as a novel form of regulated cell death that is implicated in various pathological conditions, including neurodegenerative disorders and cancer. Disulfidptosis involves the dysregulation of intracellular redox homeostasis, leading to the accumulation of disulfide bonds and subsequent cell demise. This has sparked our interest in exploring common molecular mechanisms and genetic factors that may be involved in the relationship between neurodegenerative diseases and tumorigenesis. The Gene4PD database was used to retrieve PD differentially expressed genes (DEGs), the biological functions of differential expression disulfidptosis-related genes (DEDRGs) were analyzed, the ROCs of DEDRGs were analyzed using the GEO database, and the expression of DEDRGs was verified by an MPTP-induced PD mouse model in vivo. Then, the DEDRGs in more than 9000 samples of more than 30 cancers were comprehensively and systematically characterized by using multi-omics analysis data. In PD, we obtained a total of four DEDRGs, including ACTB, ACTN4, INF2, and MYL6. The enriched biological functions include the regulation of the NF-κB signaling pathway, mitochondrial function, apoptosis, and tumor necrosis factor, and these genes are rich in different brain regions. In the MPTP-induced PD mouse model, the expression of ACTB was decreased, while the expression of ACTN4, INF2, and MYL6 was increased. In pan-cancer, the high expression of ACTB, ACTN4, and MYL6 in GBMLGG, LGG, MESO, and LAML had a poor prognosis, and the high expression of INF2 in LIHC, LUAD, UVM, HNSC, GBM, LAML, and KIPAN had a poor prognosis. Our study showed that these genes were more highly infiltrated in Macrophages, NK cells, Neutrophils, Eosinophils, CD8 T cells, T cells, T helper cells, B cells, dendritic cells, and mast cells in pan-cancer patients. Most substitution mutations were G-to-A transitions and C-to-T transitions. We also found that miR-4298, miR-296-3p, miR-150-3p, miR-493-5p, and miR-6742-5p play important roles in cancer and PD. Cyclophosphamide and ethinyl estradiol may be potential drugs affected by DEDRGs for future research. This study found that ACTB, ACTN4, INF2, and MYL6 are closely related to PD and pan-cancer and can be used as candidate genes for the diagnosis, prognosis, and therapeutic biomarkers of neurodegenerative diseases and cancers.

In Alzheimer’s Disease (AD), amyloidogenic proteins (APs), such as β-amyloid (Aβ) and tau, may act as alarmins/damage-associated molecular patterns (DAMPs) to stimulate neuroinflammation and cell death. Indeed, recent evidence suggests that brain-specific type 2 immune networks may be important in modulating amyloidogenicity and brain homeostasis. Central to this, components of innate neuroimmune signaling, particularly type 2 components, assume distinctly specialized roles in regulating immune homeostasis and brain function. Whereas balanced immune surveillance stems from normal type 2 brain immune function, appropriate microglial clearance of aggregated misfolded proteins and neurotrophic and synaptotrophic signaling, aberrant pro-inflammatory activity triggered by alarmins might disrupt this normal immune homeostasis with reduced microglial amyloid clearance, synaptic loss, and ultimately neurodegeneration. Furthermore, since increased inflammation may in turn cause neurodegeneration, it is predicted that AP aggregation and neuroinflammation could synergistically promote even more damage. The reasons for maintaining such adverse biological conditions which have not been weeded out during evolution remain unclear. Here, we discuss these issues from a viewpoint of amyloidogenic evolvability, namely, aEVO, a hypothetic view of an adaptation to environmental stress by AP aggregates. Speculatively, the interaction of AP aggregation and neuroinflammation for aEVO in reproduction, which is evolutionally beneficial, might become a co-activating relationship which promotes AD pathogenesis through antagonistic pleiotropy. If validated, simultaneously suppressing both AP aggregation and specific innate neuroinflammation could greatly increase therapeutic efficacy in AD. Overall, combining a better understanding of innate neuroimmunity in aging and disease with the aEVO hypothesis may help uncover novel mechanism of pathogenesis of AD, leading to improved diagnostics and treatments.

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging; they have a great impact on the aging process and are the main risk factors for neurodegeneration. Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases. This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s chorea, and Parkinson’s disease. This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states. Therefore, inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

ABSTRACTAlthough multiple sclerosis (MS) and multiple system atrophy (MSA) are both characterized by impaired oligodendrocytes (OLs), the aetiological relevance remains obscure. Given inherent stressors affecting OLs, the objective of the present study was to discuss the possible role of amyloidogenic evolvability (aEVO) in these conditions. Hypothetically, in aEVO, protofibrils of amyloidogenic proteins (APs), including β-synuclein and β-amyloid, might form in response to diverse stressors in parental brain. Subsequently, the AP protofibrils might be transmitted to offspring via germ cells in a prion-like fashion. By virtue of the stress information conferred by protofibrillar APs, the OLs in offspring’s brain might be more resilient to forthcoming stressors, perhaps reducing MS risk. aEVO could be comparable to a gene for the inheritance of acquired characteristics. On the contrary, during ageing, MSA risk is increased through antagonistic pleiotropy. Consistently, the expression levels of APs are reduced in MS, but are increased in MSA compared to controls. Furthermore, β-synuclein, the non-amyloidogenic homologue of β-synuclein, might exert a buffering effect on aEVO, and abnormal β-synuclein could also increase MS and MSA disease activity. Collectively, a better understanding of the role of aEVO in the OL diseases might lead to novel interventions for such chronic degenerative conditions.

Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a critical role in the cardiovascular system but also plays an important role in the protection, development, and inflammation regulation of the nervous system. The COVID-19 pandemic further highlights the importance of ACE2 in the nervous system. SARS-CoV-2 enters host cells by binding to ACE2, which may directly or indirectly affect the nervous system, leading to a range of neurological symptoms. This review aims to explore the function of ACE2 in the nervous system as well as its potential impact and therapeutic potential in various neurological diseases, providing a new perspective for the treatment of neurological disorders.

Magnesium (Mg) alloys have great potential as biodegradable materials for medical device. However, their susceptibility to corrosion poses a significant challenge for practical applications. In this study, the poly(trimethylene carbonate)-dimethacrylate (PTMC-dMA) was employed as a coating material for ZE21B magnesium alloys. Upon UV irradiation, the PTMC-dMA macromer undergoes cross-linking to form a uniform PTMC coating with a thickness of approximately 5 μm, effectively protecting the magnesium alloy. The corrosion resistance in simulated body fluid (SBF) was evaluated through immersion testing, which showed minimal hydrogen generation (0.16 mL/cm2) during the initial 24-h period and slight corrosion observed on the PTMC-coated magnesium alloy surface after continuous immersion for 21 days. The silane coupling agent significantly enhanced the adhesive performance between the polymer and alloy. Micro-scratch tests revealed adhesion forces of 3.79 N and 5.75 N for coatings without and with the silane agent, respectively. Electrochemical tests also demonstrated the efficacy of silane treatment, showing corrosion currents of 2.100 × 108 A/cm2 for silane-treated samples compared 6.263 × 107 A/cm2 for untreated ones. Given its exceptional tensile and protective properties, this coated material is ideal for intricate bioresorbable applications, like endovascular bioresorbable stents.

Tumor protein P53 (TP53) is an important tumor suppressor gene in humans. Under normal circumstances, TP53 can help repair mutated genes, or promote the death of cells with severe gene mutations (specifically, TP53 prevents cells from arrest in the G1/S phase when deoxyribonucleic acid (DNA) is damaged and promotes apoptosis if not repaired), and prevents normal cells from becoming malignant cells. TP53 mutations affect its tumor suppressor function, leading to the development of malignant tumors. In this study, using a public database, we explored the pan-cancer expression of TP53, its impact on patient survival and prognosis, the types of gene mutations, its correlation with immunity, and its regulation of other transcription factors and micro RNA (miRNA). The docking sites of therapeutic drugs and key amino acid sites of action provide a basis for future targeted therapies. TP53 has important biological functions in the human body. This study provides a theoretical basis for clinical TP53 gene therapy.

Background: Cuproptosis induction is seen as a promising alternative for immunotherapies and targeted therapies in breast cancer. The objective of this research was to examine the prognostic and biological importance of cuproptosis-related genes (CRGs) in lung adenocarcinoma (LUAD). Methods: The following methods were used: GSE10072 dataset and TCGA database analysis, differential expression analysis of CRGs, and biological function (BP) and signaling pathway enrichment analysis, prognostic analysis and clinical analysis of CRGs, construction of the prognostic signature and RNA modified genes and miRNA analysis of CRGs in LUAD, immunoinfiltration analysis and immunohistochemical staining of DβH, UBE2D3, SOD1, UBE2D1 and LOXL2. Results: AOC1, ATOX1, CCL8, CCS, COX11, CP, LOXL2, MAP2K2, PDK1, SCO2, SOD1, UBE2D1, UBE2D3 and VEGFA showed significantly higher expression, while ATP7B, DβH, PDE3B, SLC31A2, UBE2D2, UBE2D4 and ULK2 showed lower expression in LUAD tissues than normal tissues. We also found that ATP7B (4%), AOC1 (3%) PDE3B (2%), DβH (2%), CP (1%), ULK2 (1%), PDK1 (1%), LOXL2 (1%) and UBE2D3 (1%) showed higher mutation frequencies. The univariate Cox analysis was used to identify CRGs that have prognostic value. It identified 21 genes that showed significant prognostic value, containing DβH, UBE2D3, SOD1, UBE2D1 and LOXL2. Patients with DβH up–expression have a longer survival time and patients with UBE2D3, SOD1, UBE2D1 and LOXL2 down–expression also have a longer survival time. hsa–miR–29c–3p, hsa–miR–29a–3p, hsa–miR–181c–5p, hsa–miR–1245a, etc., play an important role in the miRNA regulatory network, and in LUAD, miR–29a, miR–29c and miR–181c high expression survival was longer, and miR–1245a low expression survival was longer. We also performed an analysis to examine the relationships between DβH, LOXL2, SOD1, UBE2D1 and UBE2D3 and immune infiltration in LUAD, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and DCs. Conclusion: DβH, UBE2D3, SOD1, UBE2D1, and LOXL2 are potential candidates implicated in LUAD and can be further explored for their application as diagnostic, prognostic, and therapeutic biomarkers for LUAD.

Parkinson’s disease (PD), as a neurologically implemented disease with complex etiological factors, has a complex and variable pathogenesis. Accompanying further research, neuroinflammation has been found to be one of the possible factors in its pathogenesis. Microglia, as intrinsic immune cells in the brain, play an important role in maintaining microenvironmental homeostasis in the brain. However, over-activation of neurotoxic microglia in PD promotes neuroinflammation, which further increases dopaminergic (DA) neuronal damage and exacerbates the disease process. Therefore, targeting and regulating the functional state of microglia is expected to be a potential avenue for PD treatment. In addition, plant extracts have shown great potential in the treatment of neurodegenerative disorders due to their abundant resources, mild effects, and the presence of multiple active ingredients. However, it is worth noting that some natural products have certain toxic side effects, so it is necessary to pay attention to distinguish medicinal ingredients and usage and dosage when using to avoid aggravating the progression of diseases. In this review, the roles of microglia with different functional states in PD and the related pathways inducing microglia to transform into neuroprotective states are described. At the same time, it is discussed that abscisic acid (ABA) may regulate the polarization of microglia by targeting them, promote their transformation into neuroprotective state, reduce the neuroinflammatory response in PD, and provide a new idea for the treatment of PD and the selection of drugs.

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world, and alpha-synuclein (α-syn) abnormal aggregate and mitochondrial dysfunction play a crucial role in its pathological development. Recent studies have revealed that proteins can form condensates through liquid–liquid phase separation (LLPS), and LLPS has been found to be widely present in α-syn aberrant aggregate and mitophagy-related protein physiological processes. This review summarizes the occurrence of α-syn LLPS and its influencing factors, introduces the production and transformation of the related protein LLPS during PINK1-Parkin-mediated mitophagy, hoping to provide new ideas and methods for the study of PD pathology.

Abstract In Parkinson's disease (PD), neurotoxic microglia, Th1 cells, and Th17 cells are overactivated. Overactivation of these immune cells exacerbates the disease process and leads to the pathological development of pro-inflammatory cytokines, chemokines, and contact-killing compounds, causing the loss of dopaminergic neurons. So far, we have mainly focused on the role of the specific class of immune cells in PD while neglecting the impact of interactions among immune cells on the disease. Therefore, this review demonstrates the reciprocal interplays between microglia and T cells and the associated subpopulations through cytokine and chemokine production that impair and/or protect the pathological process of PD. Furthermore, potential targets and models of PD neuroinflammation are highlighted to provide the new ideas/directions for future research.

Abstract Background Exercises are an effective treatment in Parkinson’s disease (PD), but there is still controversy over which types should be used. We aimed to compare and rank the types of exercise that improve PD symptoms by quantifying information from randomised controlled trials. Methods We performed a systematic review and network meta-analysis and searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and China National Knowledge Infrastructure (CNKI) from their inception date to June 30, 2022. We included randomized controlled trials of 24 types of exercise for the interventional treatment of adults (≥ 50 years old) with PD. Effect size measures were standardized mean differences (SMDs) with 95% credible intervals (CrIs). The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). Results We identified 10 474 citations and included 250 studies involving 13 011 participants. Results of NMA showed that power training (PT) had the best benefits for motor symptoms compared with the control group (CON), with SMDs (95% CrI) (-1.46, [-2.18 to -0.74]). Body weight support treadmill training (BWS_TT) showed the best improvement in balance (1.55, [0.72 to 2.37]), gait velocity (1.15 [0.57 to 1.31]) and walking distance (1.96, [1.18 to 2.73]), and robotic assisted gait training (RA_GT) had the most benefits for freezing of gait (-1.09, [-1.80 to -0.38]). For non-motor symptoms, Dance showed the best benefits for depression (-1.71, [-2.79 to -0.73]). Only Yoga significantly reduced anxiety symptom compared with CON (-0.53, [0.96 to -0.11]). Only resistance training (RT) significantly enhanced sleep quality and cognition (-1.42, [-2.60 to -0.23]; 0.51, [0.09 to 0.94]). For muscle strength, PT showed the best advance (1.04, [0.64 to 1.44]). For concern of falling, five types of exercise were more effective than CON. Conclusions There is low quality evidence that PT, Yoga, BWS_TT, Dance, and RT are the most effective treatments, pending outcome of interest, for adults with PD. Trial registration PROSPERO (CRD42021220052).

Obesity is a global and rising multifactorial pandemic associated with the emergence of several comorbidities that are risk factors for malignant cardiac remodeling and disease. High-intensity interval training (HIIT) has gained considerable attention due to its favorable outcomes of cardiometabolic health in individuals with overweight or obese. The primary aim of this review is to discuss the fundamental processes through which HIIT improves cardiac impairment in individuals with obesity to develop viable treatments for obesity management. In this review, a multiple database search and collection were conducted from the earliest record to January 2013 for studies included the qualitative component of HIIT intervention in humans and animals with overweight/obesity related to cardiac remodeling and fitness. We attempt to integrate the main mechanisms of HIIT in cardiac remolding improvement in obesity into an overall sequential hypothesis. This work focus on the ameliorative effects of HIIT on obesity-induced cardiac remodeling with respect to potential and pleiotropic mechanisms, including adipose distribution, energy metabolism, inflammatory response, insulin resistance, and related risk profiles in obesity. In conclusion, HIIT has been shown to reduce obesity-induced risks of cardiac remodeling, but the long-term effects of HIIT on obesity-induced cardiac injury and disease are presently unknown. Collective understanding highlights numerous specific research that are needed before the safety and effectiveness of HIIT can be confirmed and widely adopted in patient with obesity.

As a newly discovered regulated cell death mode, ferroptosis is associated with the development of Parkinson’s disease (PD) and has attracted much attention. Nonetheless, the relationship between ferroptosis and PD pathogenesis remains unclear. The GSE8397 dataset includes GPL96 and GPL97 platforms. The differential genes were analyzed by immune infiltration and Gene Set Enrichment Analysis (GSEA) (p < 0.05), and differential multiple |logFC| > 1 and weighted gene coexpression network analysis (WGCNA) were used to screen differential expression genes (DEGs). The intersection with 368 ferroptosis-related genes (FRGs) was conducted for gene ontology/Kyoto encyclopedia of gene and genome (GO/KEGG) enrichment analysis, gene expression analysis, correlation analysis, single-cell sequencing analysis, and prognosis analysis (area under the curve, AUC) and to predict relevant miRNAs and construct network diagrams using Cytoscape. The intersection genes of differentially expressed ferroptosis-related genes (DEFRGs) and mitochondrial dysfunction genes were validated in the substantia nigra of MPTP-induced PD mice models by Western blotting and immunohistochemistry, and the protein-binding pocket was predicted using the DoGSiteScorer database. According to the results, the estimated scores were positively correlated with the stromal scores or immune scores in the GPL96 and GPL97 platforms. In the GPL96 platform, the GSEA showed that differential genes were mainly involved in the GnRH signaling pathway, B cell receptor signaling pathway, inositol phosphate metabolism, etc. In the GPL97 platform, the GSEA showed that differential genes were mainly involved in the ubiquitin-mediated proteolysis, axon guidance, Wnt signaling pathway, MAPK signaling pathway, etc. We obtained 26 DEFRGs, including 12 up-regulated genes and 14 down-regulated genes, with good correlation. The area under the prognostic analysis curve (AUC > 0.700) showed a good prognostic ability. We found that they were enriched in different neuronal cells, oligodendrocytes, astrocytes, oligodendrocyte precursor cells, and microglial cells, and their expression scores were positively correlated, and selected genes with an AUC curve ≥0.9 were used to predict miRNA, including miR-214/761/3619-5p, miR-203, miR-204/204b/211, miR-128/128ab, miR-199ab-5p, etc. For the differentially expressed ferroptosis–mitochondrial dysfunction-related genes (DEF-MDRGs) (AR, ISCU, SNCA, and PDK4), in the substantia nigra of mice, compared with the Saline group, the expression of AR and ISCU was decreased (p < 0.05), and the expression of α-Syn and PDK4 was increased (p < 0.05) in the MPTP group. Therapeutic drugs that target SNCA include ABBV-0805, Prasinezumab, Cinpanemab, and Gardenin A. The results of this study suggest that cellular DEF-MDRGs might play an important role in PD. AR, ISCU, SNCA, and PDK4 have the potential to be specific biomarkers for the early diagnosis of PD.

Abstract Plasticizer migration is responsible for premature coating failure in polyvinyl chloride (PVC) synthetic materials that continue to benefit our daily life as a reliable and cost-efficient simulant of genuine leather. In this context, the establishment of standard assays that measure the migration rate of plasticizers under varying scenarios plays a pivotal role in comparing durability of those PVC-derived leather-simulants. In this review, multiple methodologies developed over the last decade for determining plasticizer migration from PVC coating are compiled, with their operational principles, merits, and limitations being taken into consideration along with specific apparatus required for each. A concluding section discusses current challenges in this field, and highlights how nuclear magnetic resonance and computational simulation surpass conventional assays in yielding intercomparable results, and hence screening migration-resistant plasticizers in a labor- and time-saving way. Since migration resistance represents a decisive performance indicator of plasticizers, this systematic review may provide guidance to quite a few practitioners in PVC synthetic material industry, who are now engaged in validating various sustainable alternatives with performance allegedly equal to conventional but toxic di-(2-ethylhexyl) phthalate plasticizer. Graphical abstract

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common rapidly developing neurodegenerative diseases that lead to serious health and socio-economic consequences. Ferroptosis is a non-apoptotic form of cell death; there is growing evidence to support the notion that ferroptosis is involved in a variety of pathophysiological contexts, and there is increasing interest in the role of ferroptosis in PD and AD. Simultaneously, cells may have evolved four defense systems to counteract the toxic effects of ferroptosis occasioned by lipid peroxidation. This review, which focuses on the analysis of ferroptosis in the PD and AD context, outlines four cellular defense systems against ferroptosis and how each of them is involved in PD and AD.

Parkinson’s disease (PD) is the second most common rapidly progressive neurodegenerative disease and has serious health and socio-economic consequences. Mitochondrial dysfunction is closely related to the onset and progression of PD, and the use of mitochondria as a target for PD therapy has been gaining traction in terms of both recognition and application. The disruption of mitochondrial proteostasis in the brain tissue of PD patients leads to mitochondrial dysfunction, which manifests as mitochondrial unfolded protein response, mitophagy, and mitochondrial oxidative phosphorylation. Physical exercise is important for the maintenance of human health, and has the great advantage of being a non-pharmacological therapy that is non-toxic, low-cost, and universally applicable. In this review, we investigate the relationships between exercise, mitochondrial proteostasis, and PD and explore the role and mechanisms of mitochondrial proteostasis in delaying PD through exercise.

During heart failure, the heart is unable to regenerate lost or damaged cardiomyocytes and is therefore unable to generate adequate cardiac output. Previous research has demonstrated that cardiac regeneration can be promoted by a hypoxia-related oxygen metabolic mechanism. Numerous studies have indicated that exercise plays a regulatory role in the activation of regeneration capacity in both healthy and injured adult cardiomyocytes. However, the role of oxygen metabolism in regulating exercise-induced cardiomyocyte regeneration is unclear. This review focuses on the alteration of the oxygen environment and metabolism in the myocardium induced by exercise, including the effects of mild hypoxia, changes in energy metabolism, enhanced elimination of reactive oxygen species, augmentation of antioxidative capacity, and regulation of the oxygen-related metabolic and molecular pathway in the heart. Deciphering the regulatory role of oxygen metabolism and related factors during and after exercise in cardiomyocyte regeneration will provide biological insight into endogenous cardiac repair mechanisms. Furthermore, this work provides strong evidence for exercise as a cost-effective intervention to improve cardiomyocyte regeneration and restore cardiac function in this patient population.

The majority of Parkinson’s disease (PD) is sporadic in elderly and is characterized by α-synuclein (αS) aggregation and other alterations involving mitochondria, ubiquitin-proteasome, and autophagy. The remaining are familial PD associated with gene mutations of either autosomal dominant or recessive inheritances. However, the former ones are similar to sporadic PD, and the latter ones are accompanied by impaired mitophagy during the reproductive stage. Since no radical therapies are available for PD, the objective of this paper is to discuss a mechanistic role for amyloidogenic evolvability, a putative physiological function of αS, among PD subtypes, and the potential relevance to therapy. Presumably, αS evolvability might benefit familial PD due to autosomal dominant genes and also sporadic PD during reproduction, which may manifest as neurodegenerative diseases through antagonistic pleiotropy mechanism in aging. Indeed, there are some reports describing that αS prevents apoptosis and mitochondrial alteration under the oxidative stress conditions, notwithstanding myriads of papers on the neuropathology of αS. Importantly, β-synuclein (βS), the nonamyloidogenic homologue of αS, might buffer against evolvability of αS protofibrils associated with neurotoxicity. Finally, it is intriguing to predict that increased αS evolvability through suppression of βS expression might protect against autosomal recessive PD. Collectively, further studies are warranted to better understand αS evolvability in PD pathogenesis, leading to rational therapy development.

Abstract Protein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therapeutic target for these disorders. Among various strategies, amyloid β immunotherapy has been extensively investigated in Alzheimer’s disease, followed by similar studies of α-synuclein in Parkinson’s disease. Notably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer’s disease, but also for other neurodegenerative disorders, including Parkinson’s disease. Thus, it is expected that further refinement of immunotherapy against neurodegenerative diseases may lead to increasing efficacy. Meanwhile, type II diabetes mellitus has been associated with an increased risk of neurodegenerative disease, such as Alzheimer’s disease and Parkinson’s disease, and studies have shown that metabolic dysfunction and abnormalities surrounding insulin signaling may underlie disease progression. Naturally, “anti-insulin resistance” therapy has emerged as a novel paradigm in the therapy of neurodegenerative diseases. Indeed, incretin agonists, which stimulate pancreatic insulin secretion, reduce dopaminergic neuronal loss and suppress Parkinson’s disease disease progression in clinical trials. Similar studies are ongoing also in Alzheimer’s disease. This paper focuses on critical issues in “immunotherapy” and “anti-insulin resistance” therapy in relation to therapeutic strategies against neurodegenerative disease, and more importantly, how they might merge mechanistically at the point of suppression of protein aggregation, raising the possibility that combined immunotherapy and “anti-insulin resistance” therapy may be superior to either monotherapy.

Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by autosomal recessive mutations of the glucocerebrosidase gene, GBA1. In the majority of cases, GD has a non-neuropathic chronic form with adult onset (GD1), while other cases are more acute and severer neuropathic forms with early onset (GD2/3). Currently, no radical therapies are established for GD2/3. Notably, GD1, but not GD2/3, is associated with increased risk of Parkinson’s disease (PD), the elucidation of which might provide a clue for novel therapeutic strategies. In this context, the objective of the present study is to discuss that the evolvability of α-synuclein (αS) might be differentially involved in GD subtypes. Hypothetically, aging-associated PD features with accumulation of αS, and the autophagy-lysosomal dysfunction might be an antagonistic pleiotropy phenomenon derived from αS evolvability in the development in GD1, without which neuropathies like GD2/3 might be manifested due to the autophagy-lysosomal dysfunction. Supposing that the increased severity of GD2/3 might be attributed to the decreased activity of αS evolvability, suppressing the expression of β-synuclein (βS), a potential buffer against αS evolvability, might be therapeutically efficient. Of interest, a similar view might be applicable to Niemann-Pick type C (NPC), another LSD, given that the adult type of NPC, which is comorbid with Alzheimer’s disease, exhibits milder medical symptoms compared with those of infantile NPC. Thus, it is predicted that the evolvability of amyloid β and tau, might be beneficial for the adult type of NPC. Collectively, a better understanding of amyloidogenic evolvability in the pathogenesis of LSD may inform rational therapy development.

The leading cause of heart failure is cardiomyopathy and damage to the cardiomyocytes. Adult mammalian cardiomyocytes have the ability to regenerate, but this cannot wholly compensate for myocardial cell loss after myocardial injury. Studies have shown that exercise has a regulatory role in the activation and promotion of regeneration of healthy and injured adult cardiomyocytes. However, current research on the effects of aerobic exercise in myocardial regeneration is not comprehensive. This review discusses the relationships between aerobic exercise and the regeneration of cardiomyocytes with respect to complex molecular and cellular mechanisms, paracrine factors, transcriptional factors, signaling pathways, and microRNAs that induce cardiac regeneration. The topics discussed herein provide a knowledge base for physical activity-induced cardiomyocyte regeneration, in which exercise enhances overall heart function and improves the efficacy of cardiac rehabilitation.

Paper-based analytical devices (PADs) are very convenient for determining biomarkers in point-of-care (POC) diagnosis while requiring sample pre-treatment or impurity separation. This study reports a novel hydrogel-coupled, paper-based analytical device (PAD) for separation-free H2O2 colorimetric detection in both aqueous solution and cell lysis with sample-to-answer analysis by directly loading into the sample test zone. By encapsulating an inorganic mimic enzyme and chromogenic substrate into the sodium alginate (SA) hydrogel, amplification of the color signal after catalyzing the substrate could be achieved. Taking advantage of the nanoscale porous structure of the hydrogel and the lateral flow channel of the PAD, large interference fragments or bio-macromolecules are prevented from diffusing into the chromogenic reaction, whereas the small target molecules enter the sensing region to trigger the catalytic reaction. This method demonstrated a rapid and accurate analysis with a limit of detection as low as 0.06 mM and detection selectivity. Our proposed device requires no enzyme and is separation-free, portable, easy-to-fabricate, and low-cost, and may offer a platform for quantitative or qualitative analysis of other analytes in body fluids for POC applications. [ABSTRACT FROM AUTHOR]

In Alzheimer’s Disease (AD), amyloidogenic proteins (APs), such as β-amyloid (Aβ) and tau, may act as alarmins/damage-associated molecular patterns (DAMPs) to stimulate neuroinflammation and cell death. Indeed, recent evidence suggests that brain-specific type 2 immune networks may be important in modulating amyloidogenicity and brain homeostasis. Central to this, components of innate neuroimmune signaling, particularly type 2 components, assume distinctly specialized roles in regulating immune homeostasis and brain function. Whereas balanced immune surveillance stems from normal type 2 brain immune function, appropriate microglial clearance of aggregated misfolded proteins and neurotrophic and synaptotrophic signaling, aberrant proinflammatory activity triggered by alarmins might disrupt this normal immune homeostasis with reduced microglial amyloid clearance, synaptic loss, and ultimately neurodegeneration. Furthermore, since increased inflammation may in turn cause neurodegeneration, it is predicted that AP aggregation and neuroinflammation could synergistically promote even more damage. The reasons for maintaining such adverse biological conditions which have not been weeded out during evolution remain unclear. Here, we discuss these issues from a viewpoint of amyloidogenic evolvability, namely, aEVO, a hypothetic view of an adaptation to environmental stress by AP aggregates. Speculatively, the interaction of AP aggregation and neuroinflammation for aEVO in reproduction, which is evolutionally beneficial, might become a co-activating relationship which promotes AD pathogenesis through antagonistic pleiotropy. If validated, simultaneously suppressing both AP aggregation and specific innate neuroinflammation could greatly increase therapeutic efficacy in AD. Overall, combining a better understanding of innate neuroimmunity in aging and disease with the aEVO hypothesis may help uncover novel mechanism of pathogenesis of AD, leading to improved diagnostics and treatments. [ABSTRACT FROM AUTHOR]

Background and Purpose: To determine the effects of resistance training (RT) on symptoms, function, and lower limb muscle strength in patients with knee osteoarthritis (KOA), and to determine the optimal dose-response relationships. Data Sources: We searched the PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and ClinicalTrials.gov databases from inception to January 23, 2022. Eligibility Criteria: Randomized controlled trials that examined the effects of RT in KOA patients (mean age≥50 years) were included. Data Synthesis: We applied Hedges' g of the random-effects model to calculate the between-subject standardized mean difference (SMDbs). A random-effects metaregression was calculated to explain the influence of key training variables on the effectiveness of RT. We used the Grading of Recommendations Assessments, Development and Evaluation (GRADE) method to appraise the certainty of evidence. Results: A total of 46 studies with 4289 participants were included. The analysis revealed moderate effects of RT on symptoms and function (SMDbs= -0.52; 95% CI: -0.64 to -0.40), and lower limb muscle strength (SMDbs= 0.53; 95% CI: 0.42 to 0.64) in the intervention group compared with the control group. The results of the metaregression revealed that only the variable "training period" (P < .001) had significant effects on symptoms, function, and lower limb muscle strength, and the 4 to 8 weeks of training subgroup showed greater effects than other subgroups (SMDbs= -0.70, -0.91 to -0.48; SMDbs= 0.76, 0.56 to 0.96). Conclusions: Compared with inactive treatments, RT is strongly recommended to improve symptoms, function, and muscle strength in individuals with KOA. Dose-response relationship analysis showed that 4 to 8 weeks of RT had more benefits. [ABSTRACT FROM AUTHOR]

To address the problems of scientific theory, common technology and engineering application of multimedia and multimodal information computing, this paper is focused on the theoretical model, algorithm framework, and system architecture of brain and mind inspired intelligence (BMI) based on the structure mechanism simulation of the nervous system, the function architecture emulation of the cognitive system and the complex behavior imitation of the natural system. Based on information theory, system theory, cybernetics and bionics, we define related concept and hypothesis of brain and mind inspired computing (BMC) and design a model and framework for frontier BMI theory. Research shows that BMC can effectively improve the performance of semantic processing of multimedia and cross-modal information, such as target detection, classification and recognition. Based on the brain mechanism and mind architecture, a semantic-oriented multimedia neural, cognitive computing model is designed for multimedia semantic computing. Then a hierarchical cross-modal cognitive neural computing framework is proposed for cross-modal information processing. Furthermore, a cross-modal neural, cognitive computing architecture is presented for remote sensing intelligent information extraction platform and unmanned autonomous system. [ABSTRACT FROM AUTHOR]