Search Results (3,088)

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous deletions or mutations in the SMN1 gene, leading to progressive motor neuron degeneration. While SMA has been classically viewed as a motor neuron-autonomous disease, increasing evidence indicates a significant role of glial cells—astrocytes, microglia, oligodendrocytes, and Schwann cells—in the disease pathophysiology. Astrocytic dysfunction contributes to motor neuron vulnerability through impaired calcium homeostasis, disrupted synaptic integrity, and neurotrophic factor deficits. Microglia, through reactive gliosis and complement-mediated synaptic stripping, exacerbate neurodegeneration and neuroinflammation. Oligodendrocytes exhibit impaired differentiation and metabolic support, while Schwann cells display abnormalities in myelination, extracellular matrix composition, and neuromuscular junction maintenance, further compromising motor function. Dysregulation of pathways such as NF-κB, Notch, and JAK/STAT, alongside the upregulation of complement proteins and microRNAs, reinforces the non-cell-autonomous nature of SMA. Despite the advances in SMN-restorative therapies, they do not fully mitigate glial dysfunction. Targeting glial pathology, including modulation of reactive astrogliosis, microglial polarization, and myelination deficits, represents a critical avenue for therapeutic intervention. This review comprehensively examines the multifaceted roles of glial cells in SMA and highlights emerging glia-targeted strategies to enhance treatment efficacy and improve patient outcomes. Full article

Polyimide-based dielectric materials, as excellent high-temperature-resistant polymers, play a crucial role in advanced electronic devices and power systems. However, given the limitations of composite PI materials, it is a significant challenge to simultaneously improve the dielectric constant and breakdown strength of intrinsic polyimide dielectric materials to achieve high energy density. In this study, an indiscriminate copolymerization method was proposed, which utilizes two different diamine monomers with bulky side groups (-CF3) and high polarity (C-O-C), respectively, to copolymerize with the same dianhydride monomer and prepare a series of intrinsic PI films. Remarkably, PI films with a highly dipolar rigid backbone maintain excellent thermal and mechanical properties while enhancing dipole polarization. Meanwhile, a high breakdown strength of PI is shown, because the bulky side groups act as deep traps to capture and disperse charges during the charge transfer process. Under the optimal copolymer ratio, the dielectric constant and dielectric loss are 4.2 and 0.008, respectively. At room temperature, the highest breakdown strength reaches 493MV/m, and the energy storage density and charge–discharge efficiency are 5.07 J/cm³ and 82%, respectively. Finally, based on density functional theory calculations, the copolymerization tendencies of the three monomers are verified, and it is speculated that the copolymerization ratio of PI-60% is the most stable and exhibits the best overall performance, which perfectly aligns with the experimental results. These experimental results demonstrate the exciting potential of intrinsic polyimide in thin film capacitors. Full article

During the early Republican years in China, through the publication of several prominent Western individuals’ view with respect to the Confucian religion in materials like Kong jiao lun 孔教论 (On the Confucian Religion) and 孔教会杂志 (The Confucian Association Monthly), Chen Huanchang, the director of the Confucian Association, appeared to have successfully enlisted the support for the Association from some renowned Western figures in China, including Timothy Richard, Gilbert Reid, Hermann Graf Keyserling, Hiram Stevens Maxim, and Reginald Fleming Johnston. Notwithstanding the Confucian Association’s propaganda, Timothy Richard and Gilbert Reid’s patronage of the Confucian Association in fact stemmed from their concept of “uniting all religions”. The praises heaped on Confucius by Hermann Graf Keyserling and Hiram Stevens Maxim were totally unrelated to the Confucian Association but were cleverly packaged by Chen Huanchang as an ideal resource through his ingenious translation. Reginald Fleming Johnston’s laudatory remarks with respect to the Confucian Association were inevitably motivated by his political speculation. The superficial respect for Confucius among Westerners in China belied more complex and nuanced attitudes towards making the Confucian religion the state religion of China. Such attitudes reveal the multiple facets of Confucianism in the early Republican era in response to some of the challenges posed by modernization. Full article

Policy incentives and technological advancements are driving the rapid expansion of renewable energy industries. However, as speculative investment intensifies, concerns about the potential formation of financial bubbles are growing. This paper examines financial saturation in renewable energy markets, emphasizing key bifurcation and overheating thresholds that indicate speculative risks. Using a financial saturation model, the study evaluates market overheating across three major renewable energy sectors—solar PV, wind energy, and battery storage—based on a scenario analysis from Bloomberg’s New Energy Outlook (NEO) 2024. The findings reveal that battery storage is the most susceptible to speculative investment, with bifurcation (~70% market saturation) projected by 2031 (medium term) and by 2038 (long term) under the Net-Zero Scenario (NZS), and by 2042 under the Economic Transition Scenario (ETS). In the long term, financial overheating (~90% market saturation) in battery storage is projected by 2048 under the ETS. Solar PV also faces speculative risks, with bifurcation expected by 2030 (ETS, medium term), 2039 (ETS, long term), and 2041 (NZS, long term). Overheating in the solar sector is projected by 2048 (ETS, long term) and 2050 (NZS, long term). Wind energy exhibits a more gradual saturation pattern, with bifurcation expected by 2031 (ETS, medium term), 2038 (ETS, long term), and 2045 (NZS, long term), while overheating is anticipated by 2049 (ETS, long term). These findings highlight the need for regulatory oversight to mitigate speculative investment risks. To enhance financial stability, policy recommendations include gradual subsidy phase-outs, financial stress testing, and diversified investment strategies. Maintaining a stable investment environment is essential for long-term climate goals and energy security. Full article

Background: The Automated Test of Embodied Cognition (ATEC) is a new system for measuring cognition in action that uses cognitively demanding physical tasks and motion capture technology. Rhythm is one of the domains assessed by the ATEC across a number of tasks and is a domain for which there is no broadly accepted neurocognitive measure. Method: Rhythm was assessed in a sample of 104 participants that included those at risk of cognitive decline and community controls. At-risk participants were also administered standard measures of executive functioning (EF), verbal list-learning, story memory, visual memory, and pre-morbid IQ. Results: The ATEC Rhythm Domain was found in the factor analysis with Varimax rotation to be loaded distinctly on the EF factor. ATEC Rhythm was significantly correlated with EF neurocognitive measures, and, in a Chi-square analysis, significantly differentiated the community control participants from those at risk for cognitive decline. ATEC Rhythm was significantly correlated with story memory and visual memory but not verbal list-learning. Age was negatively correlated with ATEC Rhythm, and women performed slightly better than men. ATEC Rhythm was also significantly correlated with the years of education and an estimate of pre-morbid IQ. Discussion: ATEC Rhythm was found to have discriminant and concurrent validity with EF measures and was significantly correlated with measures of story memory and visual memory, but not verbal list-learning. We speculate on rhythm’s relationship to story narrative and visual sequencing, and on rhythm’s relationship to cognitive reserve, as represented by education and the pre-morbid IQ estimate. Conclusions: The ATEC is a promising new measure that provides a systematic assessment of rhythm as a domain of embodied cognition. It may be useful in studies of neurodevelopment and neurocognitive decline, it and may be especially useful in assessing the effects of interventions that use physical activities, including dance and music therapies. Full article

The existence of the spiritual can be deduced from knowledge of the material. There is an inherent affinity between speculation and spirituality: an embrace of gaps in knowledge. Speculative Realisms’ rejection of both existential anthropocentrism and correlationism in favor of more empathetic, a-, pan-, or metacentric perspectives, allows for a flat ontology where all objects equally exist and allow us to describe how the spiritual exists outside of thought. This perspective allows us to derive the existence of the spiritual via the examination of interactions between material objects. By showing how all objects, whether material or abstract, have a spiritual aspect, this paper advocates for a holistic understanding of reality that recognizes the interconnectedness of all objects. Full article

Cicero’s seminal treatise, De Divinatione, demonstrates a nuanced approach that concurrently affirms and questions the significance and suitableness of divinatory practices. This dialectical perspective finds a parallel when looking at two ancient Confucian scholars, Dong Zhongshu and Xunzi, each of them offering a version of the conundrum highlighted by Cicero’s treatise. A comparative examination of Stoic philosophy, as expounded by Cicero, and of Dong Zhongshu’s The Interactions between Heaven and Humankind underscores the fact that both traditions assert that some form of interconnection between natural and supranatural phenomena is to be found. In parallel the comparison between Cicero and Xunzi (both exponents of classical rationalism) reveals their shared rejection of divinatory speculations, albeit with an acknowledgment of the political and cultural necessity of maintaining and supporting the associated ritualistic practices. Our dual comparison reveals the complex tension that was at play between speculative constructs and practical rationality in the ancient Chinese and Greco-Latin intellectual traditions. Full article

The development of cooperatives represents an effective solution to address the looming issue of “who will harvest the rubber”. Participation in cooperatives has the potential to increase the income of natural rubber farmers, enhance agricultural operational efficiency, and mitigate risks inherent in agricultural production. Livelihood capital and speculative preferences are key factors influencing natural rubber farmers’ decisions to participate in cooperatives. However, the existing literature has largely overlooked the intrinsic relationship between livelihood capital, speculative preferences, and the participation of natural rubber farmers in cooperatives. This study employs data from a field survey of 506 natural rubber farmers in Hainan Province, utilizing a Logit model to assess the impact of livelihood capital on farmers’ participation in cooperatives. The results indicate that (1) Livelihood capital encourages natural rubber farmers’ participation in cooperatives at the 5% significance level; (2) Speculative preferences negatively moderate the effect of livelihood capital on farmers’ participation in cooperatives. Therefore, the government can enhance farmers’ livelihood capital through education and training while providing financial instruments, such as insurance, to reduce speculative demand, thereby encouraging their participation in cooperatives. Full article

Hair care products that have oxidative hair dye ingredients have been widely used to permanently change hair color for the characteristic and younger appearance of people and/or their companion animals. In the European Union and the Republic of Korea, these ingredients have been carefully used or prohibited for cosmetic products according to their genotoxic potential. There is a growing demand for reliable quantification methods to monitor oxidative hair dye ingredients in hair care products. However, accurately quantifying oxidative dyes in cosmetic samples is challenging due to their high reactivity and chemical instability under both basic and ambient conditions. For this reason, for the quantification methods, elaborate sample preparation procedures should be accompanied by chemical derivatization to avoid chemical reactions between hair dye ingredients, before instrumental analysis. Therefore, this study utilized a gas chromatography–mass spectrometry (GC-MS) method combined with in situ chemical derivatization to quantify 26 oxidative hair dye ingredients in hair care products. In situ derivatization using acetic anhydride provided the characteristic [M-CH₂CO]⁺ ions at m/z (M-42), produced by the loss of a ketene from the hair dye ingredient derivatives. These characteristic ions can be used to establish a selective ion monitoring (SIM) mode of GC-MS. The established method was successfully applied to hair dye products (n = 13) and hair coloring shampoos (n = 12). Most products contained unintended hair dye ingredients including catechol without labeling. It was cautiously speculated that these unintended hair dye ingredients might be caused by biodegradation due to various enzymes in natural product extracts. This study presents a reliable GC-MS method with in situ derivatization to quantify 26 oxidative hair dye ingredients in hair care products, addressing challenges related to their chemical instability. This method is crucial for public health and regulatory compliance. Full article

Background: The spontaneous rupture of the internal iliac artery (IIA) is an exceedingly rare vascular event, typically associated with congenital anomalies or degenerative conditions. This report details an unprecedented case of isolated IIA rupture in an elderly patient with evidence of plaque rupture but devoid of congenital vascular pathology. Case Presentation: An 81-year-old Caucasian male presented to the Emergency Department following a syncopal episode and acute right iliac fossa pain. His significant medical history was atrial fibrillation managed with anticoagulation (Apixaban), non-insulin-dependent diabetes mellitus, and recent hospitalization for multidrug-resistant Klebsiella pneumoniae pneumonia. Initial imaging with contrast-enhanced computed tomography revealed an aneurysmatic dilatation of the right IIA, indicative of rupture. An endovascular repair was performed, employing a combination of stent grafts to achieve proximal and distal sealing and to restore vascular continuity. Outcome: The patient exhibited hemodynamic stability throughout the perioperative period and was transferred to the general ward postoperatively. However, he suffered a recurrent rupture on the 30th postoperative day, prompting a second endovascular intervention to extend the graft landing zone into the common iliac artery. Intraoperative findings confirmed localized plaque rupture as the underlying trigger for the initial vessel rupture. He ultimately achieved clinical stability and was discharged on the 35th postoperative day. Discussion: This case illustrates the critical importance of recognizing spontaneous IIA rupture as a potential complication in elderly patients, particularly in the context of recent severe infections. While the relationship between the rupture and the Klebsiella pneumoniae infection remains speculative, this report underscores the necessity of further research into the role of infectious processes in vascular integrity and susceptibility to rupture. Conclusions: The successful management of this rare and complex vascular emergency using endovascular techniques underscores the evolving landscape of minimally invasive interventions. This case contributes to the limited existing literature on spontaneous IIA rupture and highlights the need for increased clinical vigilance regarding atypical presentations in similar patient populations. Full article

The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain–gut–microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior. Emerging evidence suggests that the gut microbiome regulates brain function and behavior, particularly through microbial influences on tryptophan metabolism and the serotonergic system, both of which are essential for normal functioning. Additionally, sex differences exist in multiple aspects of serotonin-mediated modulation within the brain–gut–microbiome axis, affecting feeding and affective behaviors. This review summarizes the current knowledge from human and animal studies on the influence of tryptophan and its metabolite serotonin on metabolic and behavioral regulation involving the brain and gut microbiome, with a focus on sex differences and the role of sex hormones. We speculate that gut-derived tryptophan and serotonin play essential roles in the pathophysiology that modifies neural circuits, potentially contributing to eating and affective disorders. We propose the gut microbiome as an appealing therapeutic target for metabolic and affective disorders, emphasizing the importance of understanding sex differences in metabolic and behavioral regulation influenced by the brain–gut–microbiome axis. The therapeutic targeting of the gut microbiota and its metabolites may offer a viable strategy for treating serotonin-related disorders, such as eating and affective disorders, with potential differences in treatment efficacy between men and women. This review would promote research on sex differences in metabolic and behavioral regulation impacted by the brain–gut–microbiome axis. Full article

Social distancing, hand hygiene, mask wearing, surface decontamination, travel restrictions, and school closures have been implemented worldwide to control coronavirus disease 2019 (COVID-19). It was reported that the number of EBV infections as well as the age characteristics of infected persons before and after the COVID-19 pandemic significantly decreased in children from China. Since no studies have explored the changes in EBV-associated lymphomas so far, our aim was to explore EBV infection and viral-associated Hodgkin lymphoma (HL) in a pediatric cohort from a single center. A decrease in EBV+ children by serology was proved, in particular, in those undergoing primary infection, along with a significant increase in the mean age of healthy carriers. Furthermore, a decrease in EBV-associated pediatric cHL was observed post-pandemic, particularly in the NS subtype, with a marked decrease in cases diagnosed from 2022 onward. Even though the underlying reasons for the change in incidence rates seen in this study still remain speculative, it could be hypothesized that, after the pandemic, older children have a better ability to control the EBV-mediated lymphomagenesis, based on the fact that the age of infected patients increased. Full article

The plastic manufacturing industry has a crucial role in the global economy with a significant impact in a wide range of fields. The chemical risk to which workers are potentially exposed is difficult to characterize and strictly related to both the products and processes adopted. Among the chemicals used, we can cite styrene, phenol, butadiene and phthalates, but nano- and microplastic particles can also be released in the work environment. In this pilot study, we present for the first time an NMR-based metabolomic approach for assessing urinary profiles of workers employed in a plastic manufacturing company. Urine samples from twelve workers and thirteen healthy volunteers were collected and analyzed by NMR spectroscopy. Forty-six urinary metabolites belonging to different chemical classes were univocally identified and quantified. The dataset so obtained was then subjected to multivariate statistical analysis to characterize each profile and highlight any differences. An alteration in some metabolites involved in several pathways, such as amino acid metabolism and NAD metabolism, was found, and a strong impact on gut microflora was also speculated. Ultimately, our work has the objective of adding a tile to the knowledge of biological effects possibly related to occupational exposure even if it is below the threshold limit values. Full article

Background/Objectives: Mechanical compression of the median nerve is believed to be responsible for idiopathic carpal tunnel syndrome (CTS) due to fibrosis of the subsynovial connective tissue (SSCT). Vascular consequences have also been observed in structures of the carpal tunnel, raising speculation regarding the role of factors such as ischemia and edema in CTS pathology. Methods: We performed a mega-analysis from our database of over 10 years of studies. Mixed-effects models were used to address the disconnect between mechanical and vascular influences on CTS; the effects of biomechanical factors and CTS status were evaluated on carpal tunnel tissue mechanics and blood flow. Altered blood flow was also induced during tissue motion to draw inferences regarding the cyclical relationship between tissue mechanics and fluid flow changes on CTS pathology. Results: Greater movement speed and flexed wrist postures were found to contribute to greater shear strain. Flexed wrist postures and greater fingertip force were found to increase median nerve blood flow. Greater CTS severity was associated with lower median nerve blood flow. Finally, brachial blood flow restriction as a surrogate for elevated carpal tunnel pressure was found to alter tissue motion and increase carpal tunnel tissue shear strain. Conclusions: Finger movement speed, force application, wrist posture, and altered fluid flow in the carpal tunnel contribute to changes in outcomes associated with the development of CTS. The mechanistic findings from this paper should be incorporated into future research to update the damage model for CTS pathology. Full article

The appearance of cancer progresses through a multistep process that includes genetic, epigenetic, mutational, inflammatory and metabolic disturbances to signaling pathways within an organ. The combined influence of these changes will dictate the growth properties of the cells; the direction of further malignancy depends on the severity of these “disturbances”. The molecular mechanisms driving abnormal inflammation and metabolism are beginning to be identified and, in some cases, are quite prominent in pre-condition states of cancer and are significant drivers of the malignant phenotype. As such, utilizing signaling pathways linked to inflammation and metabolism as biomarkers of cancer is an emerging method and includes pathways beyond those well characterized to drive metabolism or inflammation. In this review, we will discuss several emerging elements influencing proliferation, inflammation and metabolism that may play a part as drivers of the cancer phenotype. These include AMPK and leptin (linked to metabolism), NOD2/RIPK2, TAK1 (linked to inflammation), lactate and pyruvate transporters (monocarboxylate transporter [MCT], linked to mitochondrial biogenesis and metabolism) and RASSF1A (linked to proliferation, cell death, cell cycle control, inflammation and epigenetics). We speculate that the aforementioned elements are important drivers of carcinogenesis that should be collectively referenced as being involved in “ImmunoMET Oncogenesis”, a new tripartite description of the role of elements in driving cancer. This term would suggest that for a better understanding of cancer, we need to understand how proliferation, inflammation and metabolic pathways are impacted and how they influence classical drivers of malignant transformation in order to drive ImmunoMET oncogenesis and the malignant state. Full article