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La pintura tradicional china –para nosotros similar a un tipo de dibujo– presenta rasgos inequívocamente modernos en su concepción; su poética construye el espacio y el tiempo de forma análoga a la arquitectura. Este artículo analiza la manera en que las estructuras visuales de esas obras crean una peculiar experiencia narrativa espacio-temporal. Veremos cómo diferentes arquitectos contemporáneos chinos idean, a partir de esa pintura, una serie de arquitecturas que toman de su tradición pictórica su base conceptual y su forma de expresión. Evitan imitar acríticamente modelos internacionales e incorporan sutilmente rasgos específicos de la propia cultura; dotan de significado a la arquitectura mediante el contraste entre conceptos modernos y tradicionales. La comprensión de la forma sutil en que estos recursos son aplicados a sus procesos de ideación, nos permite intuir, también en nuestro contexto occidental, la posibilidad de nuevas formas de enriquecer el proyecto, conectándolo poéticamente con elementos de nuestra tradición y corregir así su frecuente deriva hacia lo utilitario, lo icónico o la simple banalidad.

El artículo, que forma parte de una tesis doctoral, analiza un proyecto experimental de regeneración urbana en el centro histórico de Barcelona. Ante los resultados insatisfactorios de intervenciones anteriores en casos similares, se acuerda proceder según una estrategia alternativa que permita una respuesta adecuada a las reivindicaciones históricas de regeneración del barrio: conservar los rasgos esenciales que históricamente han configurado el carácter del lugar y respetar la memoria histórica de sus habitantes. El proyecto arquitectónico sustituye aquí a los instrumentos urbanísticos clásicos en la fase inicial de análisis y exploración. Se procede ignorando el planeamiento existente y al final, una vez contrastada en la práctica la bondad del proyecto, se rehace la norma de manera que recoja y legalice las peculiaridades del nuevo diseño. Se invierte así la secuencia habitual, evitando los errores habituales debidos a la rigidez e insensibilidad de los planes al uso ante estas realidades urbanas complejas. El inicio del proceso “determinante en el resultado“ es un análisis prioritariamente gráfico, sensible, perceptivo y vivencial. El artículo aporta material gráfico inédito del estudio de Enric Miralles autor del planeamiento urbano de remodelación.

Según Wang Shu, su arquitectura produce una experiencia análoga a la que ofrece la contemplación de la pintura tradicional china. Esta se diferencia del arte occidental en que no trata de expresar la sensibilidad visual de su autor a través de la descripción de la luz, el espacio y los objetos. No define los temas a través del color sino perfilándolos con líneas oscuras y unas pocas tonalidades. El pintor no trabaja del natural; normalmente es, también, filósofo y poeta, además de dominar muchas otras disciplinas técnicas y humanísticas; vive aislado en los parajes elegidos antes de pintarlos, para captar el funcionamiento estructural del mundo natural del que forma parte y compartir después, a través de su arte, ese conocimiento. Provocar ese mismo tipo de vivencias es también para Wang Shu el principal propósito de su arquitectura.

Abstract Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.

KRAS is one of the most frequently activated oncogenes in human cancers. Although the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship between KRAS and the tumor immune microenvironment is not fully understood. Here, we identified a role of KRAS in driving tumor evasion from innate immune surveillance. In samples of lung adenocarcinoma from patients and Kras-driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K/STAT3 signaling, which restrained miR-34a expression and relieved the posttranscriptional repression of miR-34a on CD47. In 3 independent cohorts of patients with lung cancer, the KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS/CD47 signaling axis with KRAS siRNA, the KRASG12C inhibitor AMG 510, or a miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages, and restored innate immune surveillance. Our results reveal a direct mechanistic link between active KRAS and innate immune evasion and identify CD47 as a major effector underlying the KRAS-mediated immunosuppressive tumor microenvironment.

Abstract Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks’ continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.

BackgroundType A aortic dissection (TAAD) has a rapid onset and high mortality. Currently, aortic diameter is the major criterion for evaluating the risk of TAAD. We attempted to find other aortic morphological indicators to further analyze their relationships with the risk of type A dissection.MethodsWe included the imaging and clinical data of 112 patients. The patients were divided into three groups, of which Group 1 had 49 patients with normal aortic diameter, Group 2 had 22 patients with ascending aortic aneurysm, and Group 3 had 41 patients with TAAD. We used AW Server software, version 3.2, to measure aorta-related morphological indicators.ResultsFirst, in Group 1, the univariate analysis results showed that ascending aortic diameter was correlated with patient age (r2 = 0.35) and ascending aortic length (AAL) (r2 = 0.43). AAL was correlated with age (r2 = 0.12) and height (r2 = 0.11). Further analysis of the aortic morphological indicators among the three groups found that the median aortic diameter was 36.20 mm in Group 1 (Q1–Q3: 33.40–37.70 mm), 42.5 mm in Group 2 (Q1–Q3: 41.52–44.17 mm) and 48.6 mm in Group 3 (Q1–Q3: 42.4–55.3 mm). There was no significant difference between Groups 2 and 3 (P > 0.05). Group 3 had the longest AAL (median: 109.4 mm, Q1–Q3: 118.3–105.3 mm), followed by Group 2 (median: 91.0 mm, Q1–Q3: 95.97–84.12 mm) and Group 1 (81.20 mm, Q1–Q3: 76.90–86.20 mm), and there were statistically significant differences among the three groups (P < 0.05). The Aortic Bending Index (ABI) was 14.95 mm/cm in Group 3 (Q1–Q3: 14.42–15.78 mm/cm), 13.80 mm/cm in Group 2 (Q1–Q3: 13.42–14.42 mm/cm), and 13.29 mm/cm in Group 1 (Q1–Q3: 12.71–13.78 mm/cm), and the difference was statistically significant in comparisons between any two groups (P < 0.05). Regression analysis showed that aortic diameter + AAL + ABI differentiated Group 2 and Group 3 with statistical significance (area under the curve (AUC) = 0.834), which was better than aortic diameter alone (AUC = 0.657; P < 0.05).ConclusionsWe introduced the new concept of ABI, which has certain clinical significance in distinguishing patients with aortic dissection and aneurysm. Perhaps the ascending aortic diameter combined with AAL and ABI could be helpful in predicting the occurrence of TAAD.

N6-methyladenosine (m6A) is the most abundant inner RNA modification in eukaryotes. Due to the development of RNA sequencing technology, the distribution pattern of m6A in the transcriptome has been uncovered. Dynamically, the reversible N6-methylation is mediated by two types of proteins, which are classified as “writers” and “erasers”. Under the association of specific co-factors, writers show spatiotemporal N6-methyltransferase activity. Mechanically, m6A can be recognized by “reader” proteins or can directly modify RNA conformation, and it widely affects gene expression by mediating RNA stability, translation, splicing and export. m6A is involved in a series of physiology processes. Dysregulation of m6A is gradually defined as the pathogenesis of some diseases, e.g., cancer and cardiovascular disease. Therefore, a good understanding of m6A is essential for molecular biology and pathology research. In this article we systemically present an overview of the functions and mechanisms of identified m6A regulators. The discovered biological and pathological processes affected by m6A are also summarized. We hope that readers with related research interests benefit from our review.

Due to the unique and contactless way of identification, radio-frequency identification is becoming an emerging technology for objects tracking. As radio-frequency identification does not provide any distance or bearing information, positioning using radio-frequency identification sensor itself is challenging. Two-dimensional laser range finders can provide the distance to the objects but require complicated recognition algorithms to acquire the identity of object. This article proposes an innovative method to track the locations of dynamic objects by combining radio-frequency identification and laser ranging information. We first segment the laser ranging data into clusters using density-based spatial clustering of applications with noise (DBSCAN). Velocity matching–based approach is used to track the location of object when the object is in the radio-frequency identification reading range. Since the radio-frequency identification reading range is smaller than a two-dimensional laser range finder, velocity matching–based approach fails to track location of the object when the radio-frequency identification reading is not available. In this case, our approach uses the clustering results from density-based spatial clustering of applications with noise to continuously track the moving object. Finally, we verified our approach on a Scitos robot in an indoor environment, and our results show that the proposed approach reaches a positioning accuracy of 0.43 m, which is an improvement of 67.6% and 84.1% as compared to laser-based and velocity matching–based approaches, respectively.

RFID (Radio Frequency Identification) offers a way to identify objects without any contact. However, positioning accuracy is limited since RFID neither provides distance nor bearing information about the tag. This paper proposes a new and innovative approach for the localization of moving object using a particle filter by incorporating RFID phase and laser-based clustering from 2d laser range data. First of all, we calculate phase-based velocity of the moving object based on RFID phase difference. Meanwhile, we separate laser range data into different clusters, and compute the distance-based velocity and moving direction of these clusters. We then compute and analyze the similarity between two velocities, and select K clusters having the best similarity score. We predict the particles according to the velocity and moving direction of laser clusters. Finally, we update the weights of the particles based on K clusters and achieve the localization of moving objects. The feasibility of this approach is validated on a Scitos G5 service robot and the results prove that we have successfully achieved a localization accuracy up to 0.25 m.

The article analyzes an urban regeneration project in the historic old city center of Barcelona. Given the unsatisfactory outcome of all previous interventions on similar cases, the key decision here was to proceed according to an alternative strategy which would produce a proper response to some historical users vindications for the neighborhood regeneration such as maintaining the main essential features which have historically determined the site's character, as well as showing some respect for the historic memory of the inhabitants. Here, architectural design substitutes the usual urban planning tools both in previous analysis and exploration stages. Its starting point ignores all current regulations and only at the final stage, once the proper effectiveness of the project has been checked, those planning regulations are adapted to include the specificities of the new design. In this way, the usual design process sequence is inverted, so to avoid the frequent mistakes which occur due to excessive rigidity and lack of sensitivity in current urban planning regulation procedures when it comes to deal with so complex realities. In the initial analysis we give priority to all the graphic, sensitive, perceptive and experiential aspects. The article also introduces some unpublished materials from Enric Miralles' studio, author of the Santa Caterina urban planning project. [ABSTRACT FROM AUTHOR]

According to Wang Shu, the experience generated by his architecture is analogous to the one of looking at Chinese traditional painting. Said discipline differs from Western art in that it does not seek to showcase the author's visual sensitivity through the description of light, objects and space. Nor does it define its subjects through colour, but by a combination of dark outlines and a few thinly laid hues. The painter, furthermore, does not work from life. He is also a philosopher, a poet and a master of a wide array of other technical and humanist fields of his time. Prior to painting a site, he lives there in solitary retreat and studies the constellation of universal structures and natural forces at play and be able to, later, share that knowledge through his art. It is producing that same type of experience that lies at the heart of Wang Shu's architecture's motivation. [ABSTRACT FROM AUTHOR]