MARCO+ lymphatic endothelial cells sequester arthritogenic alphaviruses to limit viremia and viral dissemination.

Viremia in the vertebrate host is a major determinant of arboviral reservoir competency, transmission efficiency, and disease severity. However, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, arthritogenic alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, alphavirus particles are cleared from the circulation by MARCO-expressing Kupffer cells in the liver, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the draining lymph node and liver is an important host defense mechanism as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease is more severe. In contrast to prior studies implicating a key role for lymph node macrophages in limiting viral dissemination, these findings exemplify a previously unrecognized arbovirus-scavenging role for lymphatic endothelial cells and improve our mechanistic understanding of viremia control during arthritogenic alphavirus infection.

Loss of the scavenger receptor MARCO results in uncontrolled vomocytosis of fungi from macrophages.

Vomocytosis, also known as nonlytic exocytosis, is a process whereby fully phagocytosed microbes are expelled from phagocytes without discernible damage to either the phagocyte or microbe. Although this phenomenon was first described in the opportunistic fungal pathogen Cryptococcus neoformans in 2006, to date, mechanistic studies have been hampered by an inability to reliably stimulate or inhibit vomocytosis. Here we present the fortuitous discovery that macrophages lacking the scavenger receptor MAcrophage Receptor with COllagenous domain (MARCO), exhibit near-total vomocytosis of internalised cryptococci within a few hours of infection. Marco-/- macrophages also showed elevated vomocytosis of a yeast-locked C. albicans strain, suggesting this to be a broadly relevant observation. We go on to show that MARCO's role in modulating vomocytosis is independent of its role as a phagocytic receptor, suggesting that this protein may play an important and hitherto unrecognised role in modulating macrophage behaviour.

Superenhancer drives a tumor-specific splicing variant of MARCO to promote triple-negative breast cancer progression.

The transcription variation, leading to various forms of transcripts and protein diversity, remains largely unexplored in triple-negative breast cancers (TNBCs). Here, we presented a comprehensive analysis of RNA splicing in breast cancer to illustrate the biological function and clinical implications of tumor-specific transcripts (TSTs) arising from these splicing junctions. Aberrant RNA splicing or TSTs were frequently harbored in TNBC and were correlated with a poor outcome. We discovered a tumor-specific splicing variant of macrophage receptor with collagenous structure-TST (MARCO-TST), which was distinguished from myeloid cell-specific wild-type MARCO. MARCO-TST expression was associated with poor outcomes in TNBC patients and could promote tumor progression in vitro and in vivo. Mechanically, MARCO-TST interacted with PLOD2 and enhanced the stability of HIF-1α, which resulted in the metabolic dysregulation of TNBC to form a hypoxic tumor microenvironment. MARCO-TST was initiated from a de novo alternative transcription initiation site that was activated by a superenhancer. Tumors with MARCO-TST expression conferred greater sensitivity to bromodomain and extraterminal protein inhibitors. This treatment strategy was further validated in patient-derived organoids. In conclusion, our results revealed the transcription variation landscape of TNBC, highlighting MARCO-TST as a crucial oncogenic transcript and therapeutic target.

Lessons from COP15 on effective scientific engagement in biodiversity policy processes.

The Kunming-Montreal Global Biodiversity Framework was adopted by parties to the Convention on Biological Diversity in December 2022. The aftermath of these negotiations provides an opportunity to draw lessons as to how ecological and evolutionary science can more effectively inform policy. We examined key challenges that limit effective engagement by scientists in the biodiversity policy process, drawing parallels with analogous challenges within global climate negotiations. Biodiversity is multifaceted, yet represents only one framing for nature's contributions to people, complicating the nexus between evidence and values in development of the framework's targets. Processes generating biodiversity and driving its loss are multiscalar, challenging development of an evidence base for globally standardized targets. We illustrated these challenges by contrasting development of 2 key elements of the framework. The genetic diversity element of the framework's target 4 is directly related to the framework's primary goals, but its complexity required development of novel engagement skills. The target for protected areas was easily communicated but more indirectly related to biodiversity outcomes; evidence from ecological and social science was essential to communicating the context and limitations of this relationship. Scientists can strengthen the effectiveness of global agreements and address challenges arising from complexity, scaling, capacity limitations, and the interplay of science and values, if they can prioritize communication, consensus-building, and networking skills and engage throughout the process, from development of an evidence base to implementation.

Lecciones de la COP15 sobre la participación científica efectiva en los procesos políticos de biodiversidad Resumen El Marco Global de la Biodiversidad de Kunming­Montreal lo adoptaron los participantes de la Convención sobre la Diversidad Biológica en diciembre 2022. Las consecuencias de estas negociaciones proporcionan una oportunidad para tomar lecciones de cómo la ciencia evolutiva y ecológica puede orientar de mejor manera a las políticas. Examinamos los retos clave que limitan la participación efectiva de los científicos en el proceso de políticas de la biodiversidad, estableciendo paralelismos con los retos análogos en las negociaciones climáticas mundiales. La biodiversidad es multifacética y aun así representa sólo un marco para las contribuciones que tiene la naturaleza para las personas, lo que complica el nexo entre la evidencia y los valores en el desarrollo de los objetivos del marco. Los procesos que generan la biodiversidad y causan su pérdida son multiescalares, lo que representa un reto para el desarrollo de una base de evidencias para tener objetivos mundiales estandarizados. Ilustramos estos retos con el contraste del desarrollo de dos elementos clave del marco. El elemento de la diversidad genética en el objetivo 4 del marco está relacionado directamente con los objetivos principales del marco, pero su complejidad requiere el desarrollo de habilidades novedosas de participación. El objetivo para las áreas protegidas se comunicó con facilidad, pero estuvo relacionado de forma más indirecta con los resultados de biodiversidad; la evidencia de las ciencias sociales y ecológicas fue esencial para comunicar el contexto y las limitaciones de esta relación. Los científicos pueden fortalecer la efectividad de los acuerdos globales y abordar los retos que surgen de la complejidad, el escalamiento, las limitaciones en la capacidad y la interacción de la ciencia y los valores, si pueden priorizar la comunicación, la llegada a consensos y el conocimiento de redes y participan durante el proceso, a partir del desarrollo de una evidencia base hasta la implementación.

Progress developing the concept of other effective area-based conservation measures.

In 2010, the introduction of other effective area-based conservation measures (OECMs) into international policy caused a paradigm shift in area-based conservation, which included consideration of areas outside formal protected areas and places where biodiversity conservation may not be a management objective for the site. Despite the importance of this shift for global conservation, conservation science and policy have been slow to engage with the concept of OECMs. As the world moves toward protecting 30% of the Earth by 2030, it is imperative to develop evidence-based guidance for how to identify effective conservation measures, especially tools to help evaluate and monitor the biodiversity outcomes associated with potential OECMs. To understand the current progress in developing the concept of OECMs, I evaluated the peer-reviewed literature to consolidate and synthesize current knowledge. I conducted a thematic analysis of papers to identify the types of challenges and opportunities being discussed and lessons from studies evaluating the effectiveness of OECMs. Only 105 studies mentioned OECMs, and those that did rarely move beyond superficial mention of OECMs as part of area-based conservation. Around one-half of studies listed potential risks or benefits of OECMs but none provided evidence these issues have materialized. Twenty-three studies attempted to identify potential OECMs, although specific case studies were rare. The 7 studies that evaluated existing OECMs were highly critical of how they had been implemented to date. Studies that evaluated conservation outcomes were extremely rare, and suggested effectiveness must be judged on a case-by-case basis. The current literature not only leaves many gaps in the science required to operationalize the concept of OECMs, but also often raises additional questions that need to be addressed. If these gaps are not filled by robust science, the promised benefits for biodiversity from OECMs may never be realized.

Progreso en el desarrollo del concepto de otras medidas efectivas de conservación basadas en el área Resumen En 2010, la introducción de otras medidas eficaces de conservación basadas en zonas geográficas específicas (OECM) en la política internacional provocó un cambio de paradigma en la conservación basada en el área, que incluyó la consideración de zonas situadas fuera de las áreas protegidas formales y lugares donde la conservación de la biodiversidad puede no ser un objetivo de gestión para el sitio. A pesar de la importancia de este cambio para la conservación mundial, la ciencia y la política de la conservación han tardado en comprometerse con el concepto de OECM. A medida que el mundo avanza hacia la protección del 30% de la Tierra para 2030, es imperativo desarrollar orientaciones basadas en pruebas sobre cómo identificar medidas de conservación eficaces, especialmente herramientas que ayuden a evaluar y supervisar los resultados de biodiversidad asociados a posibles OECM. Para comprender los avances actuales en el desarrollo del concepto de OECM, evalué la bibliografía revisada por pares para consolidar y sintetizar los conocimientos actuales. Realicé un análisis temático de los artículos para identificar los tipos de retos y oportunidades que se debatían y las lecciones extraídas de los estudios que evaluaban la eficacia de las OECM. Sólo 105 estudios mencionaron las OECM, y los que lo hicieron rara vez iban más allá de la mención superficial de las OECM como parte de la conservación basada en el área. Aproximadamente la mitad de los estudios mencionaron los riesgos o beneficios potenciales de las OECM, pero ninguno aportó pruebas de que estos problemas se hubieran materializado. Veintitrés estudios intentaron identificar OECM potenciales, aunque los estudios de casos fueron escasos. Los siete estudios que evaluaron las OECM existentes fueron muy críticos con la forma en que se habían aplicado hasta la fecha. Los estudios que evaluaban los resultados de la conservación eran muy escasos y sugerían que la eficacia debía juzgarse caso por caso. La bibliografía actual no sólo deja muchos vacíos en la ciencia necesaria para hacer operativo el concepto de OECM, sino que a menudo plantea cuestiones adicionales que deben abordarse. Si estos vacíos no se cubren con una ciencia sólida, es posible que los beneficios prometidos de las OECM para la biodiversidad nunca lleguen a materializarse.

The application of MARCO for immune regulation and treatment.

Macrophage receptor with collagen structure (MARCO) is a member of scavenger receptor class A (SR-A) and shares structural and functional similarities with SR-A1. In recent years, many studies have shown that MARCO can trigger an immune response and has therapeutic potential as a target for immunotherapy. Studies have shown that alterations in MARCO expression following pathogen infection cause changes in the functions of innate and adaptive immune cells, including macrophages, dendritic cells, B cells, and T cells, affecting the body's immune response to invading pathogens; thus, MARCO plays a crucial role in triggering the immune response, bridging innate and adaptive immunity, and eliminating pathogens. This paper is a comprehensive summary of the recent research on MARCO. This review focuses on the multiple functions of MARCO, including adhesion, migration, phagocytosis, and cytokine secretion with special emphasis on the complex interactions between MARCO and various types of cells involved in the immune response, as well as possible immune-related mechanisms. In summary, in this review, we discuss the structure and function of MARCO and its role in the immune response and highlight the therapeutic potential of MARCO as a target for immunotherapy. We hope that this review provides a theoretical basis for future research on MARCO.

Colorectal cancer-derived extracellular vesicles containing HSP70 enhance macrophage phagocytosis by up-regulating MARCO expression.

In recent years, we have realized that extracellular vesicles (EVs) play a critical role in regulating the intercellular communication between tumor and immune cells in the tumor microenvironment (TME). Tumor-derived extracellular vesicles (TDEVs) profoundly affect the functional changes of tumor-associated macrophages (TAMs) and promote their M2 polarization. Meanwhile, macrophages have a strong phagocytic ability in phagocytosing apoptotic cells. Especially in the course of chemotherapy or radiotherapy, TAMs can phagocytose and remove apoptotic tumor cells, showing anti-inflammatory and pro-tumor effects. However, the underlying mechanisms by which TDEVs regulate macrophage phagocytosis of apoptotic tumor cells have not been fully elucidated. In this study, we focused on the effect of colorectal cancer-derived extracellular vesicles (CRC-EVs) on macrophages. We demonstrated that CRC-EVs enhanced macrophage phagocytosis of apoptotic CRC cells. We then determined that heat shock protein 70 (HSP70) carried in CRC-EVs was responsible for this effect by using mass spectrometry-based proteomic analysis and the CRISPR-Cas9 system. Through transcriptome sequencing of macrophages, we found that the enhanced phagocytosis of macrophages was mainly due to the up-regulation of the macrophage receptor with collagenous structure (MARCO). In addition, we confirmed that the up-regulation of MARCO was mediated by the AKT-STAT3 signaling pathway. Taken together, this study revealed a novel EVs-mediated macrophage phagocytosis mechanism involved in the clearance of apoptotic tumor cells in the TME. Targeting TDEVs may have potential therapeutic applications in tumor treatment.

Autoantibody-mediated Macrophage Dysfunction in Patients with Severe Asthma with Airway Infections.

Rationale: Localized autoimmune responses have been reported in patients with severe eosinophilic asthma, characterized by eosinophil degranulation and airway infections. Objective: To determine the presence of autoantibodies against macrophage scavenger receptors within the airways and their effects on macrophage function and susceptibility to infection. Methods: Anti-EPX (eosinophil peroxidase), anti-MARCO (macrophage receptor with collagenous structure) IgG titers, and T1 and T2 (type 1/2) cytokines were measured in 221 sputa from 143 well-characterized patients with severe asthma. Peripheral monocytes and MDMs (monocyte-derived macrophages) isolated from healthy control subjects were treated with immunoprecipitated immunoglobulins from sputa with high anti-MARCO titers or nonspecific IgG to assess uptake of Streptococcus pneumoniae or response to the bacterial product LPS. Measurements and Main Results: Anti-MARCO IgG was detected in 36% of patients, with significantly higher titers (up to 1:16) in patients with mixed granulocytic sputa, indicative of airway infections. Multivariate regression analysis confirmed increased frequency of degranulation (free eosinophil granules), increased blood eosinophils (indicative of high T2 burden), increased sputum total cell count, peripheral blood leukocytes (indicative of infection), and lymphopenia were associated with increased anti-MARCO IgG titers; IL-15 (odds ratio [OR], 1.79; confidence interval [CI], 1.19-2.70), IL-13 (OR, 1.06; CI, 1.02-1.12), and IL-12p70 (OR, 3.34; CI, 1.32-8.40) were the associated cytokines. Patients with anti-MARCO antibodies had higher chances of subsequent infective versus eosinophilic exacerbations (P = 0.01). MDMs treated with immunoprecipitated immunoglobulins (anti-MARCO+ sputa) had reduced bacterial uptake by 39% ± 15% and significantly reduced release of IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.05) in response to an LPS stimulus. Conclusions: Autoantibodies against macrophage scavenger receptors in eosinophilic asthma airways may impede effective host defenses and lead to recurrent infective bronchitis.

The inhibition of MARCO by PolyG alleviates pulmonary fibrosis via regulating mitochondrial function in a silicotic rat model.

Silicon dioxide (SiO2)-induced pulmonary fibrosis is potentially associated with the impairment of mitochondrial function. Previous research found that inhibition of macrophage receptor with collagenous structure (MARCO) could alleviate particle-induced lung injury by regulating phagocytosis and mitigating mitochondrial damage. The present study aims to explore the underlying anti-fibrosis mechanism of polyguanylic acid (PolyG, MARCO inhibitor) in a silicotic rat model. Hematoxylin and eosin and Masson staining were performed to visualize lung tissue pathological changes. Confocal microscopy, transmission electron microscope, western blot analysis, quantitative real-time PCR (qPCR), and adenosine triphosphate (ATP) content assay were performed to evaluate collagen content, mitochondrial function, and morphology changes in SiO2-induced rat pulmonary fibrosis. The results suggested that SiO2 exposure contributed to reactive oxygen species aggregation and the reduction of respiratory complexes and ATP synthesis. PolyG treatment could effectively reduce MARCO expression and ameliorate lung injury and fibrosis by rectifying the imbalance of mitochondrial respiration and energy synthesis. Furthermore, PolyG could maintain mitochondrial homeostasis by promoting peroxisome proliferator-activated receptor-coactivator 1 α (PGC1α)-mediated mitochondrial biogenesis and regulating fusion and fission. Together, PolyG could ameliorate SiO2-induced pulmonary fibrosis via inhibiting MARCO to protect mitochondrial function.

Four challenges to an effective national nature assessment.

Comprehensive biodiversity assessments play an essential role in strengthening global and national conservation strategies. The recently announced first U.S. National Nature Assessment (NNA) provides an unparalleled opportunity to comprehensively review status and trends of biodiversity at all levels. This broad context can help in the coordination of actions to conserve individual species and ecosystems. The scientific assessments that informed the Kunming-Montreal Global Biodiversity Framework adopted at the 2022 Convention on Biological Diversity (CBD) conference of parties provide models for synthesizing information on trends at multiple levels of biodiversity, including decline in abundance and distribution of species, loss of populations and genetic diversity, and degradation and loss of ecosystems and their services. The assessments then relate these trends to data on drivers of biodiversity loss and pathways to their mitigation. The U.S. NNA can augment such global analyses and avoid the pitfalls encountered by previous U.S. efforts by ensuring policy-relevant design, data accessibility, and inclusivity in process and product and by incorporating spatial data relevant to national and subnational audiences. Although the United States is not formally a CBD party, an effective NNA should take full advantage of the global context by including indicators adopted at the 2022 meeting and incorporating an independent review mechanism that supports periodic stocktaking and ratcheting up of ambition in response to identified shortfalls in stemming biodiversity loss. The challenges to design of an effective U.S. assessment are relevant globally as nations develop assessments and reporting to support the new global biodiversity framework's targets. By considering and incorporating the diverse ways in which society values and benefits from nature, such assessments can help bridge the gap between research and conservation practice and communicate the extent of the biodiversity crisis to the public, fostering broad-based support for transformative change in humanity's relationship to the natural world.

Cuatro obstáculos para una eficaz evaluación nacional de la naturaleza Resumen Las evaluaciones completas de la biodiversidad tienen un papel esencial en el fortalecimiento de las estrategias de conservación nacional y mundial. La recién anunciada Evaluación Nacional de la Naturaleza (ENN) de los EE. UU. proporciona una oportunidad sin precedentes para revisar de manera completa el estado y las tendencias de la biodiversidad en todos los niveles. Este contexto generalizado puede ayudar a la coordinación de acciones para la conservación de especies individuales y ecosistemas. Las evaluaciones científicas que guiaron el Marco Mundial de la Biodiversidad de Kumming-Montreal adoptado en la conferencia de las partes de la Convención sobre la Diversidad Biológica (CBD) de 2022 proporcionan modelos para sintetizar la información sobre las tendencias de la biodiversidad a varios niveles, incluyendo la declinación en abundancia y distribución de especies, pérdida de poblaciones y diversidad genética y la degradación y pérdida de los ecosistemas y sus servicios. Después de esto, las evaluaciones relacionan estas tendencias con la información sobre los causantes de la pérdida de la biodiversidad y las maneras de mitigarla. La ENN de los EE. UU. pueden aumentar estos análisis mundiales y evitar las dificultades enfrentadas por los esfuerzos previos al garantizar un diseño relevante para las políticas, la disponibilidad de datos y la inclusión en el proceso y el producto y también mediante la incorporación de datos espaciales relevantes para el público nacional y subnacional. Aunque los EE. UU. no son una parte formal de la CBD, una ENN efectiva debería aprovechar de lleno el contexto global al incluir los indicadores adoptados en la reunión de 2022 e incorporar un mecanismo independiente de revisión que respalde el balance periódico y el aumento de la ambición en respuesta a las deficiencias detectadas en la contención de la pérdida de biodiversidad. Los retos para diseñar una evaluación estadunidense son relevantes a nivel mundial ya que los países evalúan y reportan para mantener los objetivos mundiales de biodiversidad post-2020. Si consideramos las diferentes maneras en las que la sociedad valora y se beneficia de la naturaleza, dichas evaluaciones pueden ayudar a cerrar la brecha entre la investigación y la práctica de la conservación y a comunicarle al público el nivel de la crisis de la biodiversidad, lo que fomenta el apoyo generalizado para transformar la relación entre la humanidad y el mundo natural.

Obstruction of biodiversity conservation by minimum patch size criteria.

Minimum patch size criteria for habitat protection reflect the conservation principle that a single large (SL) patch of habitat has higher biodiversity than several small (SS) patches of the same total area (SL > SS). Nonetheless, this principle is often incorrect, and biodiversity conservation requires placing more emphasis on protection of large numbers of small patches (SS > SL). We used a global database reporting the abundances of species across hundreds of patches to assess the SL > SS principle in systems where small patches are much smaller than the typical minimum patch size criteria applied for biodiversity conservation (i.e., ∼85% of patches <100 ha). The 76 metacommunities we examined included 4401 species in 1190 patches. From each metacommunity, we resampled species-area accumulation curves to evaluate how biodiversity responded to habitat existing as a few large patches or as many small patches. Counter to the SL > SS principle and consistent with previous syntheses, species richness accumulated more rapidly when adding several small patches (45.2% SS > SL vs. 19.9% SL > SS) to reach the same cumulative area, even for the very small patches in our data set. Responses of taxa to habitat fragmentation differed, which suggests that when a given total area of habitat is to be protected, overall biodiversity conservation will be most effective if that habitat is composed of as many small patches as possible, plus a few large ones. Because minimum patch size criteria often require larger patches than the small patches we examined, our results suggest that such criteria hinder efforts to protect biodiversity.

Obstrucción de la conservación de la biodiversidad por el criterio del tamaño mínimo del fragmento Resumen Los criterios de tamaño mínimo de los fragmentos para la protección de los hábitats reflejan el principio de conservación según el cual un fragmento único grande (UG) de hábitat tiene mayor biodiversidad que varios fragmentos pequeños (VP) de la misma superficie total (UG > VP). Sin embargo, este principio a menudo es incorrecto; en su lugar, la conservación de la biodiversidad debería enfatizar más la protección de un gran número de pequeñas parcelas (VP > UG). Utilizamos una base de datos mundial que recopila la abundancia de especies en cientos de fragmentos para evaluar el principio UG > VP en sistemas donde los fragmentos pequeños son mucho menores que los criterios comunes de tamaño mínimo de fragmento aplicados para la conservación de la biodiversidad (es decir, ∼85% de parches <100 ha). Las 76 metacomunidades analizadas incluyeron 4,401 especies en 1,190 parcelas. Volvimos a muestrear las curvas de acumulación especie-área en cada metacomunidad para evaluar cómo respondía la biodiversidad al hábitat: como unas pocas manchas grandes o como fragmentos de muchas manchas pequeñas. Contrario al principio UG > VP y en congruencia con síntesis anteriores, la riqueza de especies se acumuló con mayor rapidez al añadir varios fragmentos pequeños (45.2% VP > UG frente a 19.9% UG > VP) para alcanzar la misma área acumulada, incluso para los fragmentos muy pequeños de nuestro conjunto de datos. Las respuestas de los taxones a la fragmentación del hábitat fueron diferentes, lo que sugiere que, cuando se trata de proteger una determinada superficie total de hábitat, la conservación global de la biodiversidad será más efectiva si ese hábitat está compuesto por el mayor número posible de pequeños fragmentos, más unos cuantos fragmentos grandes. Dado que los criterios de tamaño mínimo exigen a menudo fragmentos más grandes que los pequeños que examinamos, nuestros resultados sugieren que tales criterios dificultan los esfuerzos por proteger la biodiversidad.

Retaining natural vegetation to safeguard biodiversity and humanity.

Global efforts to deliver internationally agreed goals to reduce carbon emissions, halt biodiversity loss, and retain essential ecosystem services have been poorly integrated. These goals rely in part on preserving natural (e.g., native, largely unmodified) and seminatural (e.g., low intensity or sustainable human use) forests, woodlands, and grasslands. To show how to unify these goals, we empirically derived spatially explicit, quantitative, area-based targets for the retention of natural and seminatural (e.g., native) terrestrial vegetation worldwide. We used a 250-m-resolution map of natural and seminatural vegetation cover and, from this, selected areas identified under different international agreements as being important for achieving global biodiversity, carbon, soil, and water targets. At least 67 million km2 of Earth's terrestrial vegetation (∼79% of the area of vegetation remaining) required retention to contribute to biodiversity, climate, soil, and freshwater conservation objectives under 4 United Nations' resolutions. This equates to retaining natural and seminatural vegetation across at least 50% of the total terrestrial (excluding Antarctica) surface of Earth. Retention efforts could contribute to multiple goals simultaneously, especially where natural and seminatural vegetation can be managed to achieve cobenefits for biodiversity, carbon storage, and ecosystem service provision. Such management can and should co-occur and be driven by people who live in and rely on places where natural and sustainably managed vegetation remains in situ and must be complemented by restoration and appropriate management of more human-modified environments if global goals are to be realized.

Retención de la vegetación natural para salvaguardar la biodiversidad y la humanidad Resumen Hoy en día hay muy poca integración de los esfuerzos mundiales para alcanzar los objetivos internacionales de reducción de las emisiones de carbono, impedimento de la pérdida de biodiversidad y conservación de los servicios ambientales esenciales. Estos objetivos dependen parcialmente de la conservación de los bosques, selvas y praderas naturales (por ejemplo, nativos y en su mayoría sin alteraciones) y seminaturales (por ejemplo, de uso humano sostenible o de baja intensidad). Obtuvimos de manera empírica objetivos espacialmente explícitos, cuantitativos y basados en áreas para la conservación de la vegetación terrestre natural y seminatural (por ejemplo, nativa) en todo el mundo para mostrar cómo unificar los objetivos internacionales. Usamos un mapa de 250 m de resolución de la cubierta vegetal natural y seminatural y, a partir de él, seleccionamos las áreas identificadas como importantes en diferentes acuerdos internacionales para alcanzar los objetivos globales de biodiversidad, carbono, suelo y agua. Al menos 67 millones de km2 de la vegetación terrestre de la Tierra (∼79% de la superficie de vegetación restante) requieren ser conservados para contribuir a los objetivos de conservación de la biodiversidad, el clima, el suelo y el agua dulce en virtud de cuatro de las resoluciones de las Naciones Unidas. Esto equivale a conservar la vegetación natural y seminatural en al menos el 50% de la superficie terrestre total de la Tierra (sin contar a la Antártida). Los esfuerzos de retención podrían contribuir a alcanzar múltiples objetivos simultáneamente, especialmente en donde la vegetación natural y seminatural puede gestionarse para lograr beneficios colaterales para la biodiversidad, el almacenamiento de carbono y la provisión de servicios ambientales. Esta gestión puede y debe ser impulsada y llevada a cabo por las personas que viven en y dependen de los lugares donde la vegetación natural y gestionada de forma sostenible permanece in situ y debe complementarse con la restauración y la gestión adecuada de entornos modificados por el hombre si se quieren alcanzar los objetivos globales.

UGRP1-modulated MARCO+ alveolar macrophages contribute to age-related lung fibrosis.

The aging lungs are vulnerable to chronic pulmonary diseases; however, the underlying mechanisms are not well understood. In this study, we compared the aging lungs of 20-24-month-old mice with the young of 10-16-week-old mice, and found that aging airway epithelial cells significantly upregulated the expression of uteroglobin-related protein 1 (UGRP1), which was responsible for the higher levels of CCL6 in the aging lungs. Alveolar macrophages (AMs) changed intrinsically with aging, exhibiting a decrease in cell number and altered gene expression. Using terminal differentiation trajectories, a population of MARCO+ AMs with the ability to produce CCL6 was identified in the aging lungs. Upregulated UGRP1was demonstrated to modulate CCL6 production of AMs in the UGRP1-MARCO pair in vivo and in vitro. Furthermore, MARCO+ AMs aggravated bleomycin-induced pulmonary fibrosis in a CCL6-dependent manner in the aged mice, and blocking MARCO or neutralizing CCL6 significantly inhibited pulmonary fibrosis, similar to the depletion of AMs. The age-related upregulation of UGRP1 and MARCO+ AMs, involved in the progression of lung fibrosis, was also observed in human lung tissues. Thus, UGRP1 modulated MARCO+ AMs regarding the age-related lung fibrosis in a CCL6-dependent manner, which is key to establishing optimal targeting for the aging population.

Recognition of lipoproteins by scavenger receptor class A members.

Scavenger receptor class A (SR-A) proteins are type II transmembrane glycoproteins that form homotrimers on the cell surface. This family has five known members (SCARA1 to 5, or SR-A1 to A5) that recognize a variety of ligands and are involved in multiple biological pathways. Previous reports have shown that some SR-A family members can bind modified low-density lipoproteins (LDLs); however, the mechanisms of the interactions between the SR-A members and these lipoproteins are not fully understood. Here, we systematically characterize the recognition of SR-A receptors with lipoproteins and report that SCARA1 (SR-A1, CD204), MARCO (SCARA2), and SCARA5 recognize acetylated or oxidized LDL and very-low-density lipoprotein in a Ca2+-dependent manner through their C-terminal scavenger receptor cysteine-rich (SRCR) domains. These interactions occur specifically between the SRCR domains and the modified apolipoprotein B component of the lipoproteins, suggesting that they might share a similar mechanism for lipoprotein recognition. Meanwhile, SCARA4, a SR-A member with a carbohydrate recognition domain instead of the SRCR domain at the C terminus, shows low affinity for modified LDL and very-low-density lipoprotein but binds in a Ca2+-independent manner. SCARA3, which does not have a globular domain at the C terminus, was found to have no detectable binding with these lipoproteins. Taken together, these results provide mechanistic insights into the interactions between SR-A family members and lipoproteins that may help us understand the roles of SR-A receptors in lipid transport and related diseases such as atherosclerosis.

Characterization of scavenger receptor MARCO in orange-spotted grouper, Epinephelus coioides.

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor that plays a crucial role in the immune response against microbial infections. To clarify the roles of fish MARCO in Singapore grouper iridovirus (SGIV) infection, we identified and characterized Ec-MARCO in the orange-spotted grouper (Epinephelus coioides). The Ec-MARCO encoded a 370-amino acid protein with transmembrane region, coiled coil region and SR domain, which shared high identities with reported MARCO. The abundant transcriptional level of Ec-MARCO was found in spleen, head kidney and blood. And the Ec-MARCO expression was significantly up-regulated in grouper spleen (GS) cells after infection with SGIV in vitro. Subcellular localization analysis revealed that Ec-MARCO was mainly distributed in the cytoplasm and on the cell membrane. Ec-MARCO knockdown in vitro significantly inhibited SGIV infection in GS cells, as evidenced by reduced decreased SGIV major capsid protein (MCP) transcription and MCP protein expression. Further studies showed that Ec-MARCO knockdown positively regulated proinflammatory cytokines and interferon-stimulated genes, and enhanced IFN and ISRE promoter activities. However, overexpression of Ec-MARCO did not affect SGIV entry into host cells. In summary, our results suggested that Ec-MARCO affected SGIV infection by regulating antiviral innate immune response.

Impact of multiple small and persistent threats on extinction risk.

Many species may face multiple distinct and persistent drivers of extinction risk, yet theoretical and empirical studies tend to focus on the single largest driver. This means that existing approaches potentially underestimate and mischaracterize future risks to biodiversity. We synthesized existing knowledge on how multiple drivers of extinction can interact to influence a species' overall extinction probability in a probabilistic model of extinction risk that incorporated the impacts of multiple drivers of extinction risk, their interactions, and their accumulative effects through time. We then used this model framework to explore how different threats, interactions between them, and time trends may affect a species' overall extinction probability. Multiple small threats together had potential to pose a large cumulative extinction risk; for example, 10 individual threats posed a 1% extinction risk each and cumulatively posed a 9.7% total extinction risk. Interactions among drivers resulted in escalated risk in some cases, and persistent threats with a small (1%) extinction risk each decade ultimately posed large extinction risk over 100 (9.6% total extinction risk) to 200 years (18.2% total extinction risk). By estimating long-term extinction risk posed by several different factors and their interactions, this approach provides a framework to identify drivers of extinction risk that could be proactively targeted to help prevent species currently of least concern from becoming threatened with extinction.

Muchas especies pueden enfrentarse a múltiples impulsores distintivos y persistentes del riesgo de extinción, aunque los estudios teóricos y empíricos tienden a enfocarse en el impulsor más relevante. Esto significa que las estrategias existentes tienen el potencial de subestimar y caracterizar erróneamente los riesgos para la biodiversidad en el futuro. Sintetizamos el conocimiento existente sobre cómo los múltiples impulsores de la extinción pueden interactuar para influir sobre la probabilidad general de extinción de una especie en un modelo probabilístico del riesgo de extinción, el cual incorporó los impactos de los múltiples impulsores del riesgo de extinción, sus interacciones y sus efectos acumulativos a través del tiempo. Después usamos este modelo para explorar cómo las diferentes amenazas, las interacciones entre ellas y las tendencias temporales pueden afectar la probabilidad general de extinción de una especie. El conjunto de múltiples amenazas pequeñas tuvo el potencial de representar un gran riesgo de extinción acumulativo; por ejemplo, cada una de diez amenazas individuales representó 1% de riesgo de extinción, y acumuladas representaron un riesgo total de extinción de 9.7%. Las interacciones entre los impulsores resultaron en un riesgo escalado en algunos casos, y las amenazas persistentes con un riesgo pequeño (1%) de extinción durante cada década al final representaron un gran riesgo de extinción después de 100 (9.6% del riesgo total de extinción) y 200 años (18.2% del riesgo total de extinción). Mediante la estimación del riesgo de extinción a largo plazo que presentan los diferentes factores y sus interacciones, esta estrategia proporciona un marco para identificar los impulsores del riesgo de extinción que podrían focalizarse proactivamente para ayudar a prevenir que las especies que actualmente están en menor riesgo se conviertan en especies amenazadas.

Improving protected area effectiveness through consideration of different human-pressure baselines.

Previous assessments of the effectiveness of protected areas (PAs) focused primarily on changes in human pressure over time and did not consider the different human-pressure baselines of PAs, thereby potentially over- or underestimating PA effectiveness. We developed a framework that considers both human-pressure baseline and change in human pressure over time and assessed the effectiveness of 338 PAs in China from 2010 to 2020. The initial state of human pressure on PAs was taken as the baseline, and changes in human pressure index (HPI) were further analyzed under different baselines. We used the random forest models to identify the management measures that most improved effectiveness in resisting human pressure for the PAs with different baselines. Finally, the relationships between the changes in the HPI and the changes in natural ecosystems in PAs were analyzed with different baselines. Of PAs with low HPI baselines, medium HPI baselines, and high HPI baselines, 76.92% (n=150), 11.11% (n=12), and 22.86% (n=8) , respectively, showed positive effects in resisting human pressure. Overall, ignoring human-pressure baselines somewhat underestimated the positive effects of PAs, especially for those with low initial human pressure. For PAs with different initial human pressures, different management measures should be taken to improve effectiveness and reduce threats to natural ecosystems. We believe our framework is useful for assessing the effectiveness of PAs globally, and we recommend it be included in the Convention on Biological Diversity Post-2020 Strategy.

Las evaluaciones previas de la efectividad de las áreas protegidas (AP) se han enfocado principalmente en los cambios de las presiones humanas con el tiempo y no han considerado las diferentes líneas base de las presiones humanas en las AP, por lo que potencialmente han sobrestimado o subestimado su efectividad. Desarrollamos un marco de trabajo que considera las líneas base de presión humana y los cambios de las presiones humanas con el tiempo y evaluamos a la efectividad de 338 AP en China entre 2010 y 2020. Consideramos el estado inicial de la presión humana en las AP como la línea base y analizamos los cambios en el índice de presión humana (IPH) bajo diferentes líneas base. Utilizamos modelos de bosque aleatorio para identificar las medidas de gestión que más aumentaron la efectividad de la resistencia a las presiones humanas en las AP con líneas base diferentes. Finalmente, analizamos con diferentes líneas base las relaciones entre los cambios en el IPH y los cambios en los ecosistemas naturales de las AP. De las AP con líneas base de IPH bajas, medianas y altas, 76.92% (n=150), 11.11% (n=12) y 22.86% (n=8), respectivamente, mostraron efectos positivos de resistencia a las presiones humanas. En general, si ignoramos las líneas base de las presiones humanas, se subestiman los efectos positivos de las AP de una u otra manera, especialmente aquellas con poca presión humana al inicio. En el caso de las AP que al inicio tienen diferentes presiones humanas, se deben tomar diferentes medidas de gestión para mejorar la efectividad y reducir las amenazas a los ecosistemas naturales. Creemos que nuestro marco de trabajo sirve para evaluar la efectividad mundial de las AP y recomendamos que se incluya en la Estrategia Post-2020 de la Convención sobre la Diversidad Biológica. Mejoría de la Efectividad de un Área Protegida al Considerar Diferentes Líneas Base de Presión Humana.

How percentage-protected targets can support positive biodiversity outcomes.

Global targets for the percentage area of land protected, such as 30% by 2030, have gained increasing prominence, but both their scientific basis and likely effectiveness have been questioned. As with emissions-reduction targets based on desired climate outcomes, percentage-protected targets combine values and science by estimating the area over which conservation actions are required to help achieve desired biodiversity outcomes. Protected areas are essential for achieving many biodiversity targets, in part because many species are highly sensitive to human-associated disturbance. However, because the contribution of protected areas to biodiversity outcomes is contingent on their location, management, governance, threats, and what occurs across the broader landscape matrix, global percentage-protected targets are unavoidably empirical generalizations of ecological patterns and processes across diverse geographies. Percentage-protected targets are insufficient in isolation but can complement other actions and contribute to biodiversity outcomes within a framework that balances accuracy and pragmatism in a global context characterized by imperfect biodiversity data. Ideally, percentage-protected targets serve as anchors that strengthen comprehensive national biodiversity strategies by communicating the level of ambition necessary to reverse current trends of biodiversity loss. If such targets are to fulfill this role within the complex societal process by which both values and science impel conservation actions, conservation scientists must clearly communicate the nature of the evidence base supporting percentage-protected targets and how protected areas can function within a broader landscape managed for sustainable coexistence between people and nature. A new paradigm for protected and conserved areas recognizes that national coordination, incentives, and monitoring should support rather than undermine diverse locally led conservation initiatives. However, the definition of a conserved area must retain a strong focus on biodiversity to remain consistent with the evidence base from which percentage-protected targets were originally derived.

RESUMEN: Las metas globales del porcentaje de área de suelo protegido, como el de 30% para el 2030, han obtenido una prominencia incrementada, a pesar de que se les cuestionen sus bases científicas y la probabilidad de su efectividad. Así como las metas de reducción de emisiones, las metas de porcentaje de protección combinan valores y ciencia mediante la estimación del área que requiere acciones de conservación para ayudar a lograr los resultados deseados de biodiversidad. Las áreas protegidas son esenciales para alcanzar muchas metas de biodiversidad, en parte porque muchas especies son altamente sensibles a las perturbaciones asociadas con el humano. Sin embargo, debido a que la contribución de las áreas protegidas a los resultados de biodiversidad depende de su ubicación, gestión, manejo, amenazas y lo que ocurra a lo largo de la amplia matriz del paisaje, las metas de porcentaje de protección son generalizaciones empíricas inevitables de los patrones y procesos ecológicos en la geografía diversa. Las metas de porcentaje de protección son insuficientes por sí solas, pero pueden complementar a otras acciones y contribuir a los resultados de biodiversidad dentro de un marco de trabajo que balancee la exactitud y el pragmatismo dentro de un contexto global caracterizado por datos imperfectos de la biodiversidad. Idealmente, las metas de porcentaje de protección fungen como pilares que fortalecen las estrategias nacionales integrales de biodiversidad mediante la comunicación del nivel de ambición necesaria para revertir las tendencias actuales de pérdida de la biodiversidad. Si se espera que dichas metas realicen este papel dentro del complejo proceso social en el que tanto los valores como la ciencia impulsan las acciones de conservación, los científicos de la conservación deben comunicar claramente la naturaleza de la base de evidencias que respalda las metas de porcentaje de protección y cómo las áreas protegidas pueden funcionar dentro de un paisaje más amplio gestionado por la coexistencia sustentable entre la naturaleza y las personas. Un nuevo paradigma para las áreas protegidas y conservadas reconoce que la coordinación nacional, los incentivos y el monitoreo deberían respaldar, y no debilitar, a las diferentes iniciativas de conservación llevadas por la población local. Sin embargo, la definición de un área conservada debe mantener un enfoque sólido sobre la biodiversidad para seguir siendo coherente con la base de evidencias de la cual derivaron originalmente las metas de porcentaje de protección.

Transcending capitalism growth strategies for biodiversity conservation.

The unlimited economic growth that fuels capitalism's metabolism has profoundly transformed a large portion of Earth. The resulting environmental destruction has led to an unprecedented rate of biodiversity loss. Following large-scale losses of habitats and species, it was recognized that biodiversity is crucial to maintaining functional ecosystems. We sought to continue the debate on the contradictions between economic growth and biodiversity in the conservation science literature and thus invite scholars to engage in reversing the biodiversity crisis through acknowledging the impacts of economic growth. In the 1970s, a global agenda was set to develop different milestones related to sustainable development, including green-blue economic growth, which despite not specifically addressing biodiversity reinforced the idea that economic development based on profit is compatible with the planet's ecology. Only after biodiversity loss captured the attention of environmental sciences researchers in the early 2000s was a global biodiversity agenda implemented. The agenda highlights biodiversity conservation as a major international challenge and recognizes that the main drivers of biodiversity loss derive from economic activities. The post-2000 biodiversity agendas, including the 2030 Agenda for Sustainable Development and the post-2020 Convention on Biological Diversity Global Strategy Framework, do not consider the negative impacts of growth-oriented strategies on biodiversity. As a result, global biodiversity conservation priorities are governed by the economic value of biodiversity and its assumed contribution to people's welfare. A large body of empirical evidence shows that unlimited economic growth is the main driver of biodiversity loss in the Anthropocene; thus, we strongly argue for sustainable degrowth and a fundamental shift in societal values. An equitable downscaling of the physical economy can improve ecological conditions, thus reducing biodiversity loss and consequently enhancing human well-being.

Trascendiendo las Estrategias de Crecimiento Capitalista para la Conservación de la Biodiversidad Resumen El crecimiento económico ilimitado que alimenta el metabolismo del capitalismo ha transformado profundamente una gran parte del planeta Tierra. La destrucción ambiental resultante ha traído como consecuencia una tasa sin precedentes de pérdida de diversidad biológica. Después de la pérdida a gran escala de hábitats y especies, se reconoció que la biodiversidad es crucial para mantener el funcionamiento de los ecosistemas. En este articulo buscamos seguir con el debate sobre las contradicciones entre el crecimiento económico y la biodiversidad en la literatura de las ciencias de la conservación y así invitar a los académicos a participar en la reducción de la crisis de biodiversidad dando a conocer los impactos del crecimiento económico. En la década de 1970, se estableció una agenda global para desarrollar diferentes metas relacionadas con el desarrollo sustentable, incluyendo el crecimiento económico verde y azul, la cual a pesar de no mencionar específicamente la biodiversidad reforzó la idea de que el desarrollo económico basado en ganancias es compatible con la ecología del planeta. Fue solamente después de que la pérdida de biodiversidad captó la atención de los investigadores de las ciencias ambientales a principios de la década de los 2000 que se implementó una agenda para la diversidad biológica. La agenda resalta que la conservación de la biodiversidad es un gran reto internacional y reconoce que las pincipales causas de la pérdida de la diversidad biológica derivan de las actividades económicas. Las agendas para la biodiversidad creadas después del 2000, incluyendo la Agenda 2030 para el Desarrollo Sustentable y el Marco de Trabajo de la Estrategia Mundial de la Convención sobre la Diversidad Biológica posterior a 2020, no consideran los impactos negativos de las estrategias para la biodiversidad orientadas por el crecimiento. Como resultado, las prioridades de la conservación mundial de la biodiversidad están gobernadas por el valor económico de la biodiversidad y la supuesta contribución que tiene para el bienestar de las personas. Una gran cantidad de evidencia empírica muestra que el crecimiento económico ilimitado es el principal conductor de la pérdida de diversidad biológica en el Antropoceno; por lo tanto, abogamos fuertemente por un decrecimiento sustentable y un cambio fundamental en los valores sociales. Una reducción equitativa de la economía física puede mejorar las condiciones ecológicas, reduciendo así la pérdida de biodiversidad y mejorando como consecuencia el bienestar humano.

Importance of health assessments for conservation in noncaptive wildlife.

Wildlife health assessments help identify populations at risk of starvation, disease, and decline from anthropogenic impacts on natural habitats. We conducted an overview of available health assessment studies in noncaptive vertebrates and devised a framework to strategically integrate health assessments in population monitoring. Using a systematic approach, we performed a thorough assessment of studies examining multiple health parameters of noncaptive vertebrate species from 1982 to 2020 (n = 261 studies). We quantified trends in study design and diagnostic methods across taxa with generalized linear models, bibliometric analyses, and visual representations of study location versus biodiversity hotspots. Only 35% of studies involved international or cross-border collaboration. Countries with both high and threatened biodiversity were greatly underrepresented. Species that were not listed as threatened on the International Union for Conservation of Nature Red List represented 49% of assessed species, a trend likely associated with the regional focus of most studies. We strongly suggest following wildlife health assessment protocols when planning a study and using statistically adequate sample sizes for studies establishing reference ranges. Across all taxa blood analysis (89%), body composition assessments (81%), physical examination (72%), and fecal analyses (24% of studies) were the most common methods. A conceptual framework to improve design and standardize wildlife health assessments includes guidelines on the experimental design, data acquisition and analysis, and species conservation planning and management implications. Integrating a physiological and ecological understanding of species resilience toward threatening processes will enable informed decision making regarding the conservation of threatened species.

Importancia de los exámenes diagnósticos para la conservación de fauna silvestre Resumen Los exámenes diagnósticos de fauna silvestre ayudan a identificar poblaciones en riesgo por desnutrición, enfermedades infecciosas y disminución poblacional, causadas por impactos antropogénicos. Revisamos los estudios disponibles que llevaron a cabo exámenes diagnósticos en fauna silvestre y diseñamos un marco de trabajo para integrar dichos exámenes en monitoreos poblacionales. Empleando un enfoque sistemático, evaluamos aquellos estudios que examinaban múltiples indicadores de salud en vertebrados no cautivos entre 1982 y 2020 (n = 261 estudios). Cuantificamos las tendencias estadísticas, clasificadas por taxones, del diseño del estudio y de los métodos diagnósticos usando modelos lineales generalizados, análisis bibliométricos y representaciones visuales del lugar de estudio versus los hotspots (puntos calientes) de biodiversidad. Sólo el 35% de los estudios incluían colaboraciones internacionales o transfronterizas, y los países ricos en biodiversidad y especies amenazadas estaban gravemente subrepresentados. Las especies no clasificadas como amenazadas en la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza representaban el 49% de las especies examinadas; una tendencia posiblemente asociada al enfoque regional de la mayoría de los estudios. Recomendamos encarecidamente seguir protocolos diagnósticos y manuales de técnicas del estudio de la fauna silvestre, además de usar tamaños muestrales estadísticamente adecuados al establecer rangos de referencia. Los métodos diagnósticos más comunes para todos los taxones fueronanálisis sanguíneos (89%), evaluaciones de composición corporal (81%), exámenes físicos (72%) y análisis fecales (24% de los estudios). Presentamos un marco conceptual para mejorar y estandarizar los exámenes diagnósticos en estudios de fauna silvestre; dicho marco incluye guías para el diseño experimental, para la obtención y el análisis de datos, y para elaborar planes de acción para especies amenazadas. La combinación de conocimientos fisiológicos y ecológicos, relacionados con la resiliencia biológica de especies amenazadas, facilitará una toma de decisiones eficiente para el manejo y para la conservación de la biodiversidad.