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Background: Efgartigimod (Efgartigimod alpha fcab, Vyvgart™) is a pioneering neonatal Fc receptor (FcRn) antagonist for the treatment of severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies, including myasthenia gravis (MG). It is a well-tolerated drug with minor side effects, such as headache and upper respiratory (lung) and urinary tract infections. Here, we present a case of Kaposi's varicelliform eruption (KVE) and herpetic conjunctivitis related to efgartigimod in a 60-year-old patient with ocular MG (OMG). Case description: A 60-year-old Chinese male suffered from acetylcholine receptor antibody positive (AChR Ab+) OMG for 8 years. During this period, he underwent first-line treatment with systemic corticosteroids, cyclosporine, cyclophosphamide, and so on, but had poor symptom improvement. On the recommendation of his attending neurologist, he received one cycle of intravenous efgartigimod (10mg/kg, once weekly for 4 weeks). The patient experienced fever, widespread painful blisters, and edema on the face on the third day after his last intravenous infusion. The patient also complained of increased secretions and a foreign body sensation in both eyes. Laboratory tests confirmed infection with herpes simplex virus (HSV). A diagnosis of efgartigimod-associated KVE and herpetic conjunctivitis was made. After intravenous administration (5mg/kg, 3 times a day, every 8 hours) for 10 days, the patient was cured without residual complications. Conclusions: This case is the first report of a patient with KVE and herpetic conjunctivitis related to efgartigimod in PubMed. This is rare and unusual. Clinicians should be alert to the rare symptoms related to efgartigimod.
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Erupción Variceliforme de Kaposi , Miastenia Gravis , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/inducido químicamente , Miastenia Gravis/inmunología , Miastenia Gravis/diagnóstico , Erupción Variceliforme de Kaposi/tratamiento farmacológico , Herpes Simple/tratamiento farmacológico , Herpes Simple/diagnóstico , Herpes Simple/inmunología , Conjuntivitis Viral/tratamiento farmacológico , Conjuntivitis Viral/diagnósticoRESUMEN
Ultraviolet-B (UV-B) radiation overexposure causes function impairment of epidermal stem cells (ESCs). We explored the mechanism of Annexin A1 (ANXA1) ameliorating UV-B-induced ESC mitochondrial dysfunction/cell injury. ESCs were cultured in vitro and irradiated with different doses of UV-B. Cell viability/ANXA1 protein level were assessed. After oe-ANXA1 transfection, ESCs were treated with oe-ANXA1/UV-B irradiation/CCCP/CCG-1423/3-methyladenine for 12 h. Cell viability/death, and adenosine triphosphate (ATP)/reactive oxygen species (ROS) levels were determined. Mitochondrial membrane potential (MMP) changes/DNA (mtDNA) content/oxygen consumption and RhoA activation were assessed. ROCK1/p-MYPT1/MYPT1/(LC3BII/I)/Beclin-1/p62 protein levels were determined. Mitochondrial morphology was observed. Mito-Tracker Green (MTG) and LC3B levels were determined. UV-B irradiation decreased cell viability/ANXA1 expression in a dose-dependent manner. UV-B-treated ESCs exhibited reduced cell viability/ATP content/MMP level/mitochondrial respiratory control ratio/mtDNA number/RhoA activity/MYPT1 phosphorylation/MTG+LC3B+ cells/(LC3BII/I) and Beclin-1 proteins, increased cell death/ROS/p62/IL-1ß/IL-6/TNF-α expression, contracted mitochondrial, disappeared mitochondrial cristae, and increased vacuolar mitochondria, which were averted by ANXA1 overexpression, suggesting that UV-B induced ESC mitochondrial dysfunction/cell injury/inflammation by repressing mitophagy, but ANXA1 promoted mitophagy by activating the RhoA/ROCK1 pathway, thus repressing UV-B's effects. Mitophagy activation ameliorated UV-B-caused ESC mitochondrial dysfunction/cell injury/inflammation. Mitophagy inhibition partly diminished ANXA1-ameliorated UV-B's effects. Conjointly, ANXA1 promoted mitophagy by activating the RhoA/ROCK1 pathway, thereby improving UV-B-induced ESC mitochondrial dysfunction/cell injury.
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Anexina A1 , Supervivencia Celular , Potencial de la Membrana Mitocondrial , Mitocondrias , Células Madre , Rayos Ultravioleta , Rayos Ultravioleta/efectos adversos , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación , Anexina A1/metabolismo , Supervivencia Celular/efectos de la radiación , Células Madre/metabolismo , Células Madre/efectos de la radiación , Humanos , Potencial de la Membrana Mitocondrial/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Células Epidérmicas/metabolismo , Células Epidérmicas/efectos de la radiación , Células CultivadasRESUMEN
Climate change and anthropogenic activities are reshaping dryland ecosystems globally at an unprecedented pace, jeopardizing their stability. The stability of these ecosystems is crucial for maintaining ecological balance and supporting local communities. Yet, the mechanisms governing their stability are poorly understood, largely due to the scarcity of comprehensive field data. Here we show the patterns of community temporal stability and its determinants across an aridity spectrum by integrating a transect survey across China's drylands with remote sensing. Our results revealed a U-shaped relationship between community temporal stability and aridity, with a pivotal shift occurring around an aridity level of 0.88. In less arid areas (aridity level below 0.88), enhanced precipitation and biodiversity were associated with increased community productivity and stability. Conversely, in more arid zones (aridity level above 0.88), elevated soil organic carbon and biodiversity were linked to greater fluctuations in community productivity and reduced stability. Our study identifies a critical aridity threshold that precipitates significant changes in community stability in China's drylands, underscoring the importance of distinct mechanisms driving ecosystem stability in varying aridity contexts. These insights are pivotal for developing informed ecosystem management and policy strategies tailored to the unique challenges of dryland conservation.
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Climate change is expected to lead to greater variability in precipitation and drought in different regions. However, the responses of ecosystem carbon and water cycles (i.e., water use efficiency, WUE) to different levels of drought stress are not fully understood. Here, we examined the relationship between WUE and precipitation anomalies and identified the critical drought threshold (DrCW) above which WUE showed substantial decrease. The results revealed that 85.56 % of the study area had nonlinear WUE responses to drought stress; that is, the WUE decreased sustainably and steeply when the precipitation deficit exceeded the DrCW. DrCW indicates inflection points for changing ecosystem responses from relatively resistant to vulnerable to drought stress, thus providing an instructive early warning for intensifying suppressive impacts on vegetation growth. Additionally, DrCW varies across aridity gradients and among vegetation types. Based on the DrCW at the pixel level, the future eco-drought is projected to increase in >67 % of the study area under both the SSP2&RCP4.5 and SSP5&RCP8.5 scenarios by the end of the 21st century. Our study elucidates the response of the ecosystem function to drought and supports the development of accurate ecosystem adaptation policies for future drought stress.
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Ecosistema , Agua , Sequías , Cambio Climático , Ciclo HidrológicoRESUMEN
Intact forests and protected areas (PAs) are central to global biodiversity conservation and nature-based climate change mitigation. However, cropland encroachment threatens the ecological integrity and resilience of their functioning. Using satellite observations, we find that a large proportion of croplands in the remaining forests globally have been gained during 2003-2019, especially for high-integrity forests (62%) and non-forest biomes (60%) and tropical forests (47%). Cropland expansion during 2011-2019 in forests globally has even doubled (130% relative increase) than 2003-2011, with high medium-integrity (190%) and high-integrity (165%) categories and non-forest (182%) and tropical forest biomes (136%) showing higher acceleration. Unexpectedly, a quarter of croplands in PAs globally were gained during 2003-2019, again with a recent accelerated expansion (48%). These results suggest insufficient protection of these irreplaceable landscapes and a major challenge to global conservation. More effective local, national, and international coordination among sustainable development goals 15, 13, and 2 is urgently needed.
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Drylands cover about 40% of the terrestrial surface and are sensitive to climate change, but their relative contributions to global vegetation greening and productivity increase in recent decades are still poorly known. Here, by integrating satellite data and biosphere modeling, we showed that drylands contributed more to global gross primary productivity (GPP) increase (65% ± 16%) than to Earth greening (33% ± 15%) observed during 1982-2015. The enhanced productivity per unit leaf area, i.e., light-use efficiency (LUE), was the mechanism behind this pattern. We also found that LUE was more sensitive to soil moisture than to atmospheric vapor pressure deficit (VPD) in drylands, while the opposite was observed (i.e., LUE was more sensitive to VPD) in humid areas. Our findings suggest the importance of using different moisture stress metrics in projecting the vegetation productivity changes of dry versus humid regions and highlight the prominent role of drylands as key controllers of the global carbon cycle.
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Croplands expanded in Africa over recent decades, even though the increasing trends are spatially heterogeneous.
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Ecosistema , Incendios , ÁfricaRESUMEN
Dynamics of fires in Africa are of critical importance for understanding changes in ecosystem properties and effects on the global carbon cycle. Given increasing fire risk from projected warming on the one hand and a documented human-driven decline in fires on the other, it is still unknown how the complex interplay between climate and human factors affects recent changes of fires in Africa. Moreover, the impact of recent strong El Niño events on fire dynamics is not yet known. By applying an ensemble empirical mode decomposition method to satellite-derived fire burned area, we investigated the spatio-temporal evolution of fires in Africa over 2001-2016 and identified the potential dominant drivers. Our results show an overall decline of fire rates, which is continuous over the time period and mainly caused by cropland expansion in northern sub-Saharan Africa. However, we also find that years of high precipitation have caused an initial increase in fire rates in southern Africa, which reversed to a decline in later years. This decline is caused by a high frequency of dry years leading to very low fuel loads, suggesting that recent drought causes a general reduction of burned areas, in particular in xeric savannas. In some mesic regions (10°-15°S), solar radiation and increased temperature caused increase in fires. These findings show that climate change overrules the impact of human expansion on fire rates at the continental scale in Africa, reducing the fire risk.
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Ecosistema , Dinámicas no Lineales , África del Sur del Sahara , Cambio Climático , HumanosRESUMEN
Oncogenic alterations in the BRAF gene are identified in an estimate of 50% of melanomas and cause melanoma development. BRAF kinase inhibitors (BRAFi), including vemurafenib and dabrafenib, were discovered and used in the clinical treatment of BRAF-mutant metastatic melanoma. Though, BRAFi's therapeutic advantages are short term and short-lived associated with drug resistance. Although a few pathways of developed BRAFi resistance have also been established, in approximately 40% of melanomas, the cause for inherited resistance remains unclear. Recognizing a new process of developed BRAFi resistance might provide new possibilities to successfully treat BRAF mutant melanoma. In this study, we are exploring the compensatory alternative pathway followed by BRAFi/MEKi treated resistant cell for maintaining the long-term integrity and survival.
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Citoprotección , Resistencia a Antineoplásicos , Melanoma/patología , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Transducción de Señal , Neoplasias Cutáneas/patología , Humanos , Proteínas Proto-Oncogénicas B-raf/metabolismo , Melanoma Cutáneo MalignoRESUMEN
The dramatic increase in anthropogenic activity severely threatens the biodiversity and life-support services that underpin human well-being. The broadened focus of protecting ecosystem services (ESs) better aligns the interests of people and biodiversity conservation. In this study, we used species richness as a surrogate for biodiversity and mapped the key ESs in East Africa with the goal to assess the spatial congruence between biodiversity and ESs, and evaluate the representation of current protected areas (PAs) network for biodiversity and ESs. The results showed that PAs well represented for species richness and regulating services but underrepresented for provisioning services. The PAs network occupies 10.96% of East Africa's land surface, and captures 20.62-26.37% of conservation priorities for vertebrate and plant species. It encompasses more than 16.23% of priority areas for three regulating services, but only 6.17% and 5.22% for crop and livestock production, respectively. Strong correlations and high overlaps exist between species richness and regulating services, particularly for carbon storage, water yield and plants. Thus, we believe that actions taken to conserve biodiversity also will protect certain ESs, which in turn will create new incentives and funding sources for the conservation of biodiversity. Overall, our results have wide-ranging policy implications and can be used to optimize conservation strategies for both biodiversity and multiple ESs in East Africa.
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Conservación de los Recursos Naturales , Ecosistema , África Oriental , Biodiversidad , Carbono , HumanosRESUMEN
BACKGROUND: Discoid lupus erythematosus (DLE) is a most well-known clinical variation of chronic cutaneous lupus erythematosus inside the spectrum of lupus erythematosus (LE). Cutaneous trauma remains a significant and peculiar causative factor for DLE. AIMS: We present a case wherein the patient demonstrated unilateral distribution of DLE on a clinically normal appearing occult facial scald of edible oil, representing Koebner phenomenon (KP) i.e. occurrence of a new skin disease at the site of an unrelated and already healed one. PATIENT/METHODS: The 53 years old female patient was unique because she experienced DLE on the nasal back. RESULTS: The injury was totally settled following a month treatment of oral hydroxychloroquine and topical 0.03% tacrolimus ointment. After three months, she encountered an accidental edible oil scald on the right upper cheek. Several small vesicles appeared on a soybean-sized erythema base with a burning sensation. CONCLUSION: We review the literature and conclude by discussing important histologic highlights to think about while endeavoring to perceive the fundamental character and pathogenicity of such sores.