Search Results (57)

Beautimeter is a new tool powered by generative pre-trained transformer (GPT) technology, designed to evaluate architectural and urban beauty. Rooted in Christopher Alexander’s theory of centers, this work builds on the idea that all environments possess, to varying degrees, an innate sense of life. Alexander identified 15 fundamental properties, such as levels of scale and thick boundaries, that characterize living structure, which Beautimeter uses as a basis for its analysis. By integrating GPT’s advanced natural language processing capabilities, Beautimeter assesses the extent to which a structure embodies these 15 properties, enabling a nuanced evaluation of architectural and urban aesthetics. Using ChatGPT4o, the tool helps users generate insights into the perceived beauty and coherence of spaces. We conducted a series of case studies, evaluating images of architectural and urban environments, as well as carpets, paintings, and other artifacts. The results demonstrate Beautimeter’s effectiveness in analyzing aesthetic qualities across diverse contexts. Our findings suggest that by leveraging GPT technology, Beautimeter offers architects, urban planners, and designers a powerful tool to create spaces that resonate deeply with people. This paper also explores the implications of such technology for architecture and urban design, highlighting its potential to enhance both the design process and the assessment of built environments. Full article

Biophilic design is an architectural concept that bridges the gap between modern buildings and the innate human longing for nature. In addition, it promotes physical and mental well-being while aligning with several Sustainable Development Goals. Recent research highlights that the architectural language used to describe the attributes of biophilic architecture remains unclear. Previous research has shown that text-to-image AI enhances architects’ ability to articulate their ideas more effectively. Therefore, this study aims to address the following research question: What are the architectural languages of biophilic design after architects use text-to-image AI? The initial step involves generating images of biophilic architecture by using three popular text-to-image AI tools: DALL-E 3, MidJourney, and Stable Diffusion. The 30 selected images were used to help architects develop the architectural language to describe the characteristics of biophilic design across 10 categories: Form, Space, Movement, Light, Color, Material, Object, View, Sound, and Weather. The terms obtained were analyzed using natural language processing (NLP) techniques, including word cloud analysis, frequency analysis, and topic modeling. The results indicate that the architectural language of biophilic design exhibits greater detail and clarity after architects utilize text-to-image AI. Nevertheless, in some instances, the language used to describe biophilic design is also constrained by the images generated by the text-to-image AI that the architects observe. Full article

One of the main components of innate defense against invasive parasites is oxidative stress, which is brought on by reactive oxygen species (ROS). On the other hand, oxidative stressors serve two purposes: free radicals aid in the elimination of pathogens, but they can also set off inflammation, which leads to tissue damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that controls the expression of numerous genes involved in the body’s defense against oxidative stress brought on by aging, inflammation, tissue damage, and other pathological consequences. From cutaneous to visceral forms, Leishmania parasites invade macrophages and cause a wide range of human pathologies. Leishmania parasites have a wide range of adaptive mechanisms that disrupt several macrophage functions by altering host signaling pathways. An increasing amount of data are corroborating the idea that one of the primary antioxidant routes to counteract this oxidative burst against parasites is NRF2 signaling, which also interferes with immune responses. The nature and potency of the host immune response, as well as interactions between the invading Leishmania spp., will ascertain the course of infection and the parasites’ eventual survival or eradication. The molecular processes via which Nrf2 coordinates such intricate networks comprising various pathways remain to be completely understood. In light of NRF2’s significant contribution to oxidative stress, we examine the NRF2 antioxidant pathway’s activation mechanism in Leishmania infection in this review. Thus, this review will examine the relationship between Nrf2 signaling and leishmaniasis, as well as explore potential therapeutic strategies for modifying this system. Full article

The innate immune system (IIS) is an ancient and essential defense mechanism that protects animals against a wide range of pathogens and diseases. Although extensively studied in mammals, our understanding of the IIS in other taxa remains limited. The zebrafish (Danio rerio) serves as a promising model organism for investigating IIS-related processes, yet the immunogenetics of fish are not fully elucidated. To address this gap, we conducted a meta-analysis of single-cell RNA sequencing (scRNA-seq) datasets from zebrafish kidney marrow, encompassing approximately 250,000 immune cells. Our analysis confirms the presence of key genetic pathways in zebrafish innate immune cells that are similar to those identified in mammals. Zebrafish macrophages specifically express genes encoding cathepsins, major histocompatibility complex class II proteins, integral membrane proteins, and the V-ATPase complex and demonstrate the enrichment of oxidative phosphorylation ferroptosis processes. Neutrophils are characterized by the significant expression of genes encoding actins, cytoskeleton organizing proteins, the Arp2/3 complex, and glycolysis enzymes and have demonstrated their involvement in GnRH and CLR signaling pathways, adherents, and tight junctions. Both macrophages and neutrophils highly express genes of NOD-like receptors, phagosomes, and lysosome pathways and genes involved in apoptosis. Our findings reinforce the idea about the existence of a wide spectrum of immune cell phenotypes in fish since we found only a small number of cells with clear pro- or anti-inflammatory signatures. Full article

The innate immune system, composed of neutrophils, basophils, eosinophils, myeloid-derived suppressor cells (MDSCs), macrophages, dendritic cells (DCs), mast cells (MCs), and innate lymphoid cells (ILCs), is the first line of defense. Growing evidence demonstrates the crucial role of innate immunity in tumor initiation and progression. Several studies support the idea that innate immunity, through the release of pro- and/or anti-inflammatory cytokines and tumor growth factors, plays a significant role in the pathogenesis, progression, and prognosis of cutaneous malignant melanoma (MM). Cutaneous melanoma is the most common skin cancer, with an incidence that rapidly increased in recent decades. Melanoma is a highly immunogenic tumor, due to its high mutational burden. The metastatic form retains a high mortality. The advent of immunotherapy revolutionized the therapeutic approach to this tumor and significantly ameliorated the patients’ clinical outcome. In this review, we will recapitulate the multiple roles of innate immune cells in melanoma and the related implications for immunotherapy. Full article

Animal-based tests are used for the control of vaccine quality. However, because highly purified and safe vaccines are now available, alternative approaches that can replace or reduce animal use for the assessment of vaccine outcomes must be established. In vitro tests for vaccine quality control exist and have already been implemented. However, these tests are specifically designed for some next-generation vaccines, and this makes them not readily available for testing other vaccines. Therefore, universal non-animal tests are still needed. Specific signatures of the innate immune response could represent a promising approach to predict the outcome of vaccines by non-animal methods. Type I interferons (IFNs) have multiple immunomodulatory activities, which are exerted through effectors called interferon stimulated genes (ISGs), and are one of the most important immune signatures that might provide potential candidate molecular biomarkers for this purpose. This paper will mainly examine if this idea might be feasible by analyzing all relevant published studies that have provided type I IFN-related biomarkers for evaluating the safety and efficacy profiles of vaccines using an advanced transcriptomic approach as an alternative to the animal methods. Results revealed that such an approach could potentially provide biomarkers predictive of vaccine outcomes after addressing some limitations. Full article

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis. Full article

Neisseria meningitidis is commensal of the human pharynx and occasionally invades the host, causing the life-threatening illness invasive meningococcal disease. The meningococcus is a highly diverse and adaptable organism thanks to natural competence, a propensity for recombination, and a highly repetitive genome. These mechanisms together result in a high level of antigenic variation to invade diverse human hosts and evade their innate and adaptive immune responses. This review explores the ways in which this diversity contributes to the evolutionary history and population structure of the meningococcus, with a particular focus on microevolution. It examines studies on meningococcal microevolution in the context of within-host evolution and persistent carriage; microevolution in the context of meningococcal outbreaks and epidemics; and the potential of microevolution to contribute to antimicrobial resistance and vaccine escape. A persistent theme is the idea that the process of microevolution contributes to the development of new hyperinvasive meningococcal variants. As such, microevolution in this species has significant potential to drive future public health threats in the form of hypervirulent, antibiotic-resistant, vaccine-escape variants. The implications of this on current vaccination strategies are explored. Full article

The innate immune system is the first line of defense against pathogens. Its composition includes barriers, mucus, and other substances as well as phagocytic and other cells. The purpose of the present paper is to compare tissues with regard to their immune response to infections and to cancer. Simple ideas and the qualitative theory of differential equations are used along with general principles such as the minimization of the pathogen load and economy of resources. In the simplest linear model, the annihilation rate of pathogens in any tissue should be greater than the pathogen’s average replication rate. When nonlinearities are added, a stability condition emerges, which relates the strength of regular threats, barrier height, and annihilation rate. The stability condition allows for a comparison of immunity in different tissues. On the other hand, in cancer immunity, the linear model leads to an expression for the lifetime risk, which accounts for both the effects of carcinogens (endogenous or external) and the immune response. The way the tissue responds to an infection shows a correlation with the way it responds to cancer. The results of this paper are formulated in the form of precise statements in such a way that they could be checked by present-day quantitative immunology. Full article

The dendritic cell (DC) vaccine anti-cancer strategy involves tumour-associated antigen loading and maturation of autologous ex vivo cultured DCs, followed by infusion into the cancer patient. This strategy stemmed from the idea that to induce a robust anti-tumour immune response, it was necessary to bypass the fundamental immunosuppressive mechanisms of the tumour microenvironment that dampen down endogenous innate immune cell activation and enable tumours to evade immune attack. Even though the feasibility and safety of DC vaccines have long been confirmed, clinical response rates remain disappointing. Hence, the full potential of DC vaccines has yet to be reached. Whether this cellular-based vaccination approach will fully realise its position in the immunotherapy arsenal is yet to be determined. Attempts to increase DC vaccine immunogenicity will depend on increasing our understanding of DC biology and the signalling pathways involved in antigen uptake, maturation, migration, and T lymphocyte priming to identify amenable molecular targets to improve DC vaccine performance. This review evaluates various genetic engineering strategies that have been employed to optimise and boost the efficacy of DC vaccines. Full article

Many modern rabbis insist that original sin was invented by St. Paul, and that it does not have a Jewish antecedent. Instead, rabbinic Judaism explains human evil in terms of “yeṣer ha-raʻ,” “the evil inclination.” But evidence from Second Temple period wisdom and apocalyptic literature suggests that ideas like Paul’s were indeed common in certain quarters of Jewish thought in the first century. Paul’s doctrine of original sin draws from an assortment of Old Testament texts. What seems novel in Romans 5 is essentially an aspect of his apocalyptic vision. Rabbinic texts from the Mishnah onwards intentionally suppress this apocalyptic account of original sin. Instead of original sin, rabbinic doctrine posits the yeṣer ha-raʻ as the explanation for human wickedness. This is an innate aspect of human nature. But it is something that good discipline, and especially the practice of Torah, can amend. Some aspects of Pauline teaching actually run parallel to these later texts pertaining to the yeṣer ha-raʻ, as well. In particular, his use of sarx seems to be a theological cognate to this concept of an evil inclination. Full article

(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process of osteoarthritis (OA). Melatonin may be a new hope for the treatment of OA because of its antioxidant capacity. However, the mechanism of melatonin in the treatment of OA is still not completely clear, and the physiological characteristics of articular cartilage make melatonin unable to play a long-term role in OA. (2) The effects of melatonin on ROS and the innate immune response system in OA chondrocytes and the therapeutic effect in vivo were evaluated. Then, a melatonin-loaded nano-delivery system (MT@PLGA-COLBP) was prepared and characterized. Finally, the behavior of MT@PLGA-COLPB in cartilage and the therapeutic effect in OA mice were evaluated. (3) Melatonin can inhibit the activation of the innate immune system by inhibiting the TLR2/4-MyD88-NFκB signal pathway and scavenging ROS, thus improving cartilage matrix metabolism and delaying the progression of OA in vivo. MT@PLGA-COLBP can reach the interior of cartilage and complete the accumulation in OA knee joints. At the same time, it can reduce the number of intra-articular injections and improve the utilization rate of melatonin in vivo. (4) This work provides a new idea for the treatment of osteoarthritis, updates the mechanism of melatonin in the treatment of osteoarthritis, and highlights the application prospect of PLGA@MT-COLBP nanoparticles in preventing OA. Full article

The human nervous system exhibits limited regenerative capabilities following damage to the central nervous system (CNS), leading to a scarcity of effective treatments for nerve function recovery. In contrast, zebrafish demonstrate remarkable regenerative abilities, making them an ideal model for studying the modulation of inflammatory processes after injury. Such research holds significant translational potential to enhance our understanding of recovery from damage and disease. Macrophages play a crucial role in tissue repair and regeneration, with their subpopulations indirectly promoting axonal regeneration through developmental signals. The AP-1 signaling pathway, mediated by TNF/Tnfrsf1a, can elevate HDAC1 expression and facilitate regeneration. Furthermore, following spinal cord injury (SCI), pMN progenitors have been observed to switch between oligodendrocyte and motor neuron fates, with macrophage-secreted TNF-α potentially regulating the differentiation of ependymal–radial glia progenitors and oligodendrocytes. Radial glial cells (RGs) are also essential for CNS regeneration in zebrafish, as they perform neurogenesis and gliogenesis, with specific RG subpopulations potentially existing for the generation of neurons and oligodendrocytes. This review article underscores the critical role of macrophages and their subpopulations in tissue repair and regeneration, focusing on their secretion of TNF-α, which promotes axonal regeneration in zebrafish. We also offer insights into the molecular mechanisms underlying TNF-α’s ability to facilitate axonal regeneration and explore the potential of pMN progenitor cells and RGs following SCI in zebrafish. The review concludes with a discussion of various unresolved questions in the field, and ideas are suggested for future research. Studying innate immune cell interactions with neuroglia following injury may lead to the development of novel strategies for treating the inflammatory processes associated with regenerative medicine, which are commonly observed in injury and disease. Full article

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. Unfortunately, the degree of inflammation produced by COVID-19 mRNA vaccines is variable, probably depending on genetic background and previous immune experiences, which through epigenetic modifications could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V). Full article

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3’s and other inflammasomes’ regulation, while minimizing failure risks in candidate drug trials. Full article