Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery.

Tuberculosis (TB) remains a critical health threat, particularly with the emergence of multidrug-resistant strains. This demands attention from scientific communities and healthcare professionals worldwide to develop effective treatments. The enhanced intracellular survival (Eis) protein is an acetyltransferase enzyme of Mycobacterium tuberculosis that functions by adding acetyl groups to aminoglycoside antibiotics, which interferes with their ability to bind to the bacterial ribosome, thereby preventing them from inhibiting protein synthesis and killing the bacterium. Therefore, targeting this protein accelerates the chance of restoring the aminoglycoside drug activity, thereby reducing the emergence of drug-resistant TB. For this, we have screened 406,747 natural compounds from the Coconut database against Eis protein. Based on MM/GBSA rescoring binding energy, the top 5 most prominent natural compounds, viz. CNP0187003 (- 96.14 kcal/mol), CNP0176690 (- 93.79 kcal/mol), CNP0136537 (- 92.31 kcal/mol), CNP0398701 (- 91.96 kcal/mol), and CNP0043390 (- 91.60 kcal/mol) were selected. These compounds exhibited the presence of a substantial number of hydrogen bonds and other significant interactions confirming their strong binding affinity with the Eis protein during the docking process. Subsequently, the MD simulation of these compounds exhibited that the Eis-CNP0043390 complex was the most stable, followed by Eis-CNP0187003 and Eis-CNP0176690 complex, further verified by binding free energy calculation, principal component analysis (PCA), and Free energy landscape analysis. These compounds demonstrated the most favourable results in all parameters utilised for this investigation and may have the potential to inhibit the Eis protein. There these findings will leverage computational techniques to identify and develop a natural compound inhibitor as an alternative for drug-resistant TB.

Discarded vehicle tires and their association with mosquito vector abundance across socioenvironmental gradients in New Orleans, LA.

Discarded vehicle tires serve as habitat for mosquito vectors. In New Orleans, Louisiana, discarded tires are an increasingly important public concern, especially considering that the city is home to many medically important mosquito species. Discarded tires are known to be associated with mosquito abundance, but how their presence interacts with other socioenvironmental gradients to influence mosquito ecology is poorly understood. Here, we ask whether discarded tire distribution could be explained by social factors, particularly median income, home vacancy and human population density, and whether these factors interact with urban heat islands (UHI) to drive mosquito vector assemblages. We surveyed tire piles across the city and adult mosquitoes in 12 sites, between May and October of 2020. We compared this data with the social indicators selected and UHI estimates. Our results show that median income and human population density were inversely related to tire abundance. Tire abundance was positively associated with Aedes albopictus abundance in places of low heat (LS) severity. Heat was the only predictor for the other monitored species, where high heat corresponded to higher abundance of Aedes aegypti, and LS to higher abundance of Culex quinquefasciatus. Our results suggest that low-income, sparsely populated neighborhoods of New Orleans may be hotspots for discarded vehicle tires, and are associated with higher abundances of at least one medically important mosquito (Ae. albopictus). These findings suggest potential locations for prioritizing source reduction efforts to control mosquito vectors and highlight discarded tires as a potential exposure pathway to unequal disease risk for low-income residents.

Comparative analysis of visual-thermal perceptions and emotional responses in outdoor open spaces: Impacts of look-up vs. look-forward viewing perspectives.

Horizontal and vertical viewing perspectives exert varying influences on the environmental perceptions and emotional states of college students. Despite this, scant research addresses the impact on this demographic. We selected typical campus open spaces for comprehensive physical parameter assessments, encompassing meteorological and spatial characteristics. A cohort of 36 healthy college students participated in a questionnaire survey designed to ascertain shifts in visual comfort, thermal comfort, and emotional responses when viewing landscapes in look-forward and look-up orientations. Key findings following both viewing modalities included: 1) a notable rise in mean visual comfort vote (MVCV), by 1.22 for look-forward and 1.01 for look-up, with a pronouncedly higher sunlight sensation vote (SSV) for the latter orientation; 2) a significant increase in thermal comfort vote (TCV), although the difference in increments between the two viewing angles was minimal; 3) Positive affect (PA) exhibited considerable improvement in both viewing conditions, while negative affect (NA) was markedly reduced in the look-up condition relative to look-forward viewing; 4) The SSV was predominantly influenced by the trunk ratio and canopy-to-trunk ratio, with substantial weights of 31.47% and 32.15%, respectively. Landscape element diversity emerged as the most critical factor affecting visual comfort vote (VCV) and aesthetic assessment score (AAS), with overwhelming weights of 70.67% and 63.15%, respectively. Moreover, the leaf ratio was identified as the chief determinant of emotional responses. Our results provide insights into the design of campus spaces for enhanced student well-being.

Extremes of snow and temperature affect patterns of genetic diversity and differentiation in the alpine butterfly Parnassius smintheus.

Weather is an important short-term, local driver of population size and dispersal, which in turn contribute to patterns of genetic diversity and differentiation within species. Climate change is leading to greater weather variability and more frequent extreme weather events. While the effects of long-term and broad-scale mean climate conditions on genetic variation are well studied, our understanding of the effects of weather variability and extreme conditions on genetic variation is less developed. We assessed the influence of temperature and snow depth on genetic diversity and differentiation of populations of the alpine butterfly, Parnassius smintheus. We examined the relationships between a suite of variables, including those representing extreme conditions, and population-level genetic diversity and differentiation across 1453 single nucleotide polymorphisms, using both linear and gravity models. We additionally examined effects of land cover variables known to influence dispersal and gene flow in this species. We found that extreme low temperature events and the lowest recorded mean snow depth were significant predictors of genetic diversity. Extreme low temperature events, mean snow depth and land cover resistance were significant predictors of genetic differentiation. These results are congruent with known effects of early winter weather on population size and habitat connectivity on dispersal in P. smintheus. Our results demonstrate the potential for changes in the frequency or magnitude of extreme weather events to alter patterns of genetic diversity and differentiation.

Utilizing spiders for biomonitoring air pollution from road traffic: a novel approach and preliminary findings.

Polycyclic aromatic hydrocarbons (PAHs) are air pollutants generated mainly by fuel combustion, industry, and other anthropogenic sources. The level of these pollutants can be assessed by employing biomonitors, a cost-effective and less contaminating alternative than conventional methods. In the present study, we aimed to investigate whether spiders inhabiting areas around a major city like Córdoba, Argentina, adsorb and retain PAHs in their exoskeletons. Additionally, we aimed to determine if spiders' life traits influence their capacity to accumulate PAHs and explore potential relationships between PAH levels and the types of roads where they were collected. Specimens of a funnel-shaped web spider (Aglaoctenus lagotis) and an orb-weaver (Metepeira spp.) were collected from roadsides. Roads were classified into four categories based on their traffic intensity. Using high-performance liquid chromatography (HPLC), we identified 15 different PAHs. Both species exhibited varying concentrations of PAHs, although Metepeira spp. showed 15-18 times higher PAH levels compared to A. lagotis. Moreover, A. lagotis individuals living alongside highways accumulated up to six times more PAHs compared to those along other road types. These findings suggest that spiders' life traits may influence pollutant concentrations. Our study demonstrates that spiders near roads are exposed to and accumulate PAHs on their exoskeletons, likely sourced from petrogenic vehicular emissions, highlighting their value as biomonitors and emphasizing the need for mitigation measures to address air pollutants emitted from mobile sources.

Hadza Landscape Burning.

We present the first published ethnographic description of landscape burning by Hadza hunter-gatherers of northern Tanzania and identify environmental, social, and cultural influences on Hadza landscape burning, thereby broadening the ethnographic record of anthropogenic burning practices described for hunter-gatherer communities. We report interview data collected in 2022 and 2023, describing their practices and attitudes regarding the causes and consequences of burning. We provide context by comparing our observations with those recorded for hunting and gathering populations in Africa, Australia, and North America. Hadza landscape burning is generally a solitary and male-dominated activity, contrary to ethnographic accounts of Indigenous landscape burning from North America and Australia. The primary goals stated by Hadza for landscape burning were improved hunting, reduced hazards from dangerous animals, and to reduce the density of livestock. Firsthand observations suggest that landscape burning has decreased over the past 20 years, and this historical trend is supported by interviews. Satellite imagery also suggests an overall decrease in burning activity in the region from 2001 to 2022. Among the Hadza, landscape burning is a culturally influenced and strongly gender-biased activity that is rapidly disappearing. Because burning can radically transform landscapes, these practices often generate or amplify conflicts of interest between groups with different land use strategies. Hadza report serious social conflict with pastoralists over landscape burning, and our study suggests this tension has constrained the practice in the past two decades.

A novel M2-like tumor associated macrophages-related gene signature for predicting the prognosis and immunotherapy efficacy in gastric cancer.

BACKGROUND: M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified. METHODS: Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC. RESULTS: A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes. CONCLUSION: These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.

Evolutionary stability of developmental commitment.

Evolution of unicellular to multicellular organisms must resolve conflicts in reproductive interests between individual cells and the group. The social amoeba Dictyostelium discoideum is a soil-living eukaryote with facultative sociality. While cells grow in the presence of nutrients, cells aggregate under starvation to form fruiting bodies containing spores and altruistic stalk cells. Once cells socially committed, they complete formation of fruiting bodies, even if a new source of nutrients becomes available. The persistence of this social commitment raises questions as it inhibits individual cells from swiftly returning to solitary growth. I hypothesize that traits enabling premature de-commitment are hindered from being selected. Recent work has revealed outcomes of the premature de-commitment through forced refeeding; The de-committed cells take an altruistic prestalk-like position due to their reduced cohesiveness through interactions with socially committed cells. I constructed an evolutionary model assuming their division of labor. The results revealed a valley in the fitness landscape that prevented invasion of de-committing mutants, indicating evolutionary stability of the social commitment. The findings provide a general scheme that maintains multicellularity by evolving a specific division of labor, in which less cohesive individuals become altruists.

How far do forest container mosquitoes (Diptera: Culicidae) invade rural and urban areas in Japan? - Simple landscape ecology with comparison of the invasive Aedes ecology between native and invasive ranges.

The distribution of container mosquitoes in relation to distances from forests was studied in temperate Japan. Mosquito larvae were collected between May and September in 4 years from tree holes, bamboo stumps, riverine rock pools, and artificial containers; sampling ranged spatially from the mountain forest across the deforested plain developed as agriculture and urban areas to the seacoast. Although tree holes, bamboo stumps, and artificial containers existed throughout the deforested plain area, 10 container species of 6 genera were found virtually only within 5 km from the nearest forest edge. Worldwide invasive Aedes albopictus (Skuse) and Aedes japonicus (Theobald) of Asian origin showed unique occurrence patterns different from other container species and from each other. Ae. japonicus was dominant in artificial containers in and near the forest but minor in forest natural containers and only occurred within 5 km from the forest. Ae. albopictus was minor in the forest irrespective of container types but not bound to the forest and dominant in natural and artificial containers throughout rural and urban areas. The 5-km range was designated as the circum-forest zone for container mosquitoes (except Ae. albopictus) in Japan, and an expanded concept, circum-boundary zone, is proposed. The widths of these zones primarily depend on the dispersal traits of mosquitoes. Whether the relation of Ae. albopictus and Ae. japonicus to forests we observed are common in the native and invasive ranges is discussed. The study of across-ecosystem dispersal is important for mosquito management under anthropogenically changing environments due to either deforestation or green restoration.

Identification of metacommunities in bioregions with historical habitat networks.

Although metacommunity theory provides many useful insights for conservation planning, the transfer of this knowledge to practice is hampered due to the difficulty of identifying metacommunities in bioregions. This study aims to identify the spatial extent of metacommunities at bioregional scales using current and historical habitat data, especially because contemporary biodiversity patterns may be a result of time-lagged responses to historical habitat configurations. Further, this estimation of the metacommunity spatial extent is based on both the habitat structure and the dispersal ability of the species. Focusing on dragonfly and damselfly (odonate) species in the eastern Swiss Plateau, the research uses wetland habitat information spanning over 110 years to create a time series of nine habitat networks between 1899 and 2010. From these networks, we identified the spatial extents of metacommunities based on the year of habitat information as well as on watershed boundaries. To identify the best metacommunity spatial extents, the study investigates whether patch pairs within a metacommunity exhibit greater similarity in species composition (i.e. lower beta-diversity) than patch pairs between metacommunities. For the different metacommunities, we further investigated correlations between gamma diversity and metacommunity size and compare them to theoretical expectations. In both analyses we found that augmenting spatial metacommunity identification with historical geographical proximity results in stronger associations with biodiversity patterns (beta and gamma diversity) than when using only current-day habitat or watershed information.

The Governance, Policy, Process, and Capacity of Health Workforce Regulation and Accreditation: Qualitative Policy Analysis and Evidence from Palestine.

Background: The significant health development achieved in Palestine last decades has been lost, in Gaza particularly. This requires fundamental health system reform and rebuilding, including health workforces. Strengthening health workforces involves essential elements: leadership, finance, policy, education, partnership, and management. The current unprecedented catastrophe in Gaza and overall instability in Palestine show the utmost necessity for rethinking and reforming all pillars of the already collapsed health system, including the workforce. Health Workforce Accreditation and Regulation (HWAR) standardizes healthcare evaluations, representing a critical research area in Palestine due to limited existing knowledge. Objective: This study aims to enhance understanding of the HWAR in Palestine, and identify gaps and weaknesses, thereby enhancing the HWAR's development and optimization. Methods: This qualitative study used an inductive approach to explore the landscape of HWAR. Data were collected from October to November 2019, when 22 semi-structured in-depth interviews - were conducted with experts, academics, leaders, and policymakers purposely selected from government, academia, and non-governmental organization sectors. Data analysis, namely, thematic and ground theory, was performed using Excel and MS programs. Findings: The study revealed an absence of transparent governance and ineffective communication within HWAR systems. National policies and guidelines are problematic, with HWAR mechanisms fractured and needing reform. Licensing for healthcare workers hinges on local education, while monitoring and evaluation of HWAR are deficient. Some institutions adhere to HWAR standards, yet widespread updates and applications are necessary. Coordination among educational, accreditation, and practice sectors is non-systematic. Adequate human resources exist, but we need to improve HWAR management. Operational and political challenges limit HWAR, leading to a focus on immediate responses over sustainable system integration. Conclusion: Boosting HWAR is critical for Palestine, especially after the ongoing conflict and humanitarian crisis that led to the dysfunction of the entire health system facilities. A collaborative strategy across sectors is needed to improve governance and outcomes. It is essential to foster strategic dialogue among academia, regulatory entities, and healthcare providers to enhance the HWAR system. Further study on HWAR's effectiveness is recommended.

The diffuse interface description of fluid lipid membranes captures key features of the hemifusion pathway and lateral stress profile.

Topological transitions of lipid membranes are ubiquitous in key biological processes for cell life, like neurotransmission, fertilization, morphogenesis, and viral infections. Despite this, they are not well understood due to their multiscale nature, which limits the use of molecular models and calls for a mesoscopic approach such as the celebrated Canham-Helfrich one. Unfortunately, such a model cannot handle topological transitions, hiding the crucial involved forces and the appearance of the experimentally observed hemifused intermediates. In this work, we describe the membrane as a diffuse interface preserving the Canham-Helfrich elasticity. We show that pivotal features of the hemifusion pathway are captured by this mesoscopic approach, e.g. a (meta)stable hemifusion state and the fusogenic behavior of negative monolayer spontaneous curvatures. The membrane lateral stress profile is calculated as a function of the elastic rigidities, yielding a coarse-grained version of molecular models findings. Insights into the fusogenic mechanism are reported and discussed.

[Effects of Landscape Pattern on Water Quality at Different Spatial and Temporal Scales in Wuding River Basin and Yanhe River Basin].

To explore the relationship between land use and water quality in basins with different land use patterns at different spatial and temporal scales, the Wuding River Basin and Yanhe River Basin were taken as research objects. Based on land use data in 2020 and water quality monitoring data during two periods, the redundancy analysis method was adopted to quantitatively explore the impact of land use on water quality at multiple scales. The results showed that： ① The main land use types in the two basins were cultivated land and grassland, and the difference was mainly in the proportion of bare land and forest land. ② The water quality in spring was better than that in autumn, and the water quality in the middle and lower reaches was worse. ③ The interpretation rate of land use on the riparian scale was the highest in the two basins. ④ The effect of land use on water quality was more significant in the Wuding River Basin in autumn than in spring, whereas the Yanhe River Basin showed the opposite trend. ⑤ Different land uses had different impacts on water quality. Bare land, cultivated land, and Shannon diversity index （SHDI） in the Wuding River Basin had significant impacts on water quality, whereas grassland, cultivated land, artificial surface, patch density （PD）, and SHDI were significant in the Yanhe River Basin. Cultivated land and artificial surfaces in the Wuding River Basin had a negative impact on water quality. Grassland and bare land had a negative correlation with most chemical indicators. Artificial surfaces and grasslands in the Yanhe River Basin had a negative impact on water quality, whereas forest land had a significant purification effect. The research results provide important information for sustainable land use and multi-scale landscape planning, which can be used to improve water quality.

[Source Apportionment and Response to Landscape Pattern of Health Risk of Cultivated Soil Heavy Metals].

Heavy metal pollution mainly caused by human activities is becoming increasingly prominent and threatening human health and ecosystem safety in soil, which is a non-renewable natural resource that humans rely on for survival and development. Assessment and analysis of soil heavy metal health risk is significant for protecting human health, preventing soil pollution, and maintaining ecosystem security. Based on the investigation of heavy metals, including Cr, Pb, Cd, As, and Hg, in cultivated soil in Liuhe District, the health risk assessment model was used to identify the health risk characteristics of heavy metals, and the spatial distribution, main sources, and responses to landscape patterns were explored by using inverse distance weight interpolation, positive definite matrix factorization, landscape pattern index, and redundancy analysis. The results showed that the coefficients of variation corresponding to Cr, Pb, Cd, As, and Hg in the study area were 0.19, 0.36, 0.23, 0.52, and 1.16, respectively, all of which belonged to moderate or high variability, indicating that they had high spatial heterogeneity and were susceptible to human factors. Cr, Pb, and As were the main health risk characteristic factors in the study area, with the carcinogenic risks to children ranging from 13.307×10-6 to 38.400×10-6, 0.839×10-6 to 3.250×10-6, and 4.548×10-6 to 16.680×10-6, respectively, which were higher than those in adults. Agricultural production activities, industrial production, and transportation activities were the main sources of heavy metals, with carcinogenic risks to children of 17.946×10-6 and 12.941×10-6, respectively. Furthermore, high-risk areas caused by agricultural production activities were mainly concentrated in the northern area of Liuhe District and showed an increasing trend from south to north and from the center to the periphery. The surrounding areas caused by industrial production activities and transportation were mainly concentrated in the chemical industry park and economic development zone of Liuhe District and showed a spatial agglomeration feature of decreasing from south to north and from the core to the periphery. The cumulative explanatory value of the landscape pattern index for the comprehensive carcinogenic risk to children was 0.463, and patch density, patch proportion in landscape area, patch aggregation degree, and maximum patch index had significant effects on the comprehensive carcinogenic risk in children, and the corresponding explanatory values were 0.422, 0.274, 0.351, and 0.232, respectively. This study had important theoretical and practical significance for expanding the perspective of environmental health research, promoting the transformation of soil heavy metal management methods and safeguarding regional population health.

Large carpenter bees show high dispersal in a tropical semi-arid region susceptible to desertification.

Desertification is a major threat to biodiversity in arid areas of the world, partly because many organisms in these regions already exist at or near the limits of their movement and physiology. Here, we used molecular data to investigate patterns of persistence and dispersal in an ecologically and economically important carpenter bee (Xylocopa grisescens Lepeletier) found throughout the semiarid Caatinga region of Brazil. We used a genome-wide approach (double digest restriction-site associated DNA, ddRAD) to gather genetic data from bees sampled from eight sites within a semiarid region subject to desertification in Northeastern Brazil. Across all populations, we observed a consistent heterozygosity and effective population size deficit along with low genetic differentiation. We did not find strong evidence of dispersal limitations caused by desertification in this study system despite data collection from sites up to 300 km distant. Thus, our data suggest that human-mediated changes in the Caatinga, such as habitat loss, have impacted the population genetic patterns of X. grisescens. However, these impacts have also been softened by the species' biological characteristics, such as its relatively high capacity for movement. This study provides insights into how habitat changes might impact the long-term survival of large solitary bees.

Interrelation of the spatial and genetic structure of tick-borne encephalitis virus, its reservoir host (Myodes glareolus), and its vector (Ixodes ricinus) in a natural focus area.

Tick-borne encephalitis (TBE) virus is considered the medically most important arthropod-borne virus in Europe. Although TBE is endemic throughout central Europe, ticks and rodents determine its maintenance in small, difficult-to-assess, natural foci. We investigated the interrelation between the population genetics of the main TBE virus (TBEV) vector tick (Ixodes ricinus), the most important reservoir host (Myodes glareolus, syn. Clethrionomys glareolus), and TBEV. Rodents and ticks were sampled on 15 sites within an exploratory study area, which has been screened regularly for TBEV occurrence in ticks for more than 10 years. On all 15 sites, ticks and bank voles were sampled, screened for TBEV presence via serology and RT-PCR, and genetically examined. Moreover, TBEV isolates derived from these analyses were sequenced. In long-term TBEV foci bank vole populations show extraordinary genetic constitutions, leading to a particular population structure, whereas ticks revealed a panmictic genetic structure overall sampling sites. Landscape genetics and habitat connectivity modeling (analysis of isolation by resistance) showed no landscape-related barriers explaining the genetic structure of the bank vole populations. The results suggest that bank voles do not simply serve as TBEV reservoirs, but their genetic composition appears to have a significant influence on establishing and maintaining long-term natural TBEV foci, whereas the genetic structure of TBEV's main vector I. ricinus does not play an important role in the sustainability of long-term TBEV foci. A thorough investigation of how and to which extent TBEV and M. glareolus genetics are associated is needed to further unravel the underlying mechanisms.

Widespread convergence towards functional optimization in the lower jaws of crocodile-line archosaurs.

Extant crocodilian jaws are subject to functional demands induced by feeding and hydrodynamics. However, the morphological and ecological diversity of extinct crocodile-line archosaurs is far greater than that of living crocodilians, featuring repeated convergence towards disparate ecologies including armoured herbivores, terrestrial macropredators and fully marine forms. Crocodile-line archosaurs, therefore, present a fascinating case study for morphological and functional divergence and convergence within a clade across a wide range of ecological scenarios. Here, we build performance landscapes of two-dimensional theoretical jaw shapes to investigate the influence of strength, speed and hydrodynamics in the morphological evolution of crocodile-line archosaur jaws, and test whether ecologically convergent lineages evolved similarly optimal jaw function. Most of the 243 sampled jaw morphologies occupy optimized regions of theoretical morphospace for either rotational efficiency, resistance to Von Mises stress, hydrodynamic efficiency or a trade-off between multiple functions, though some seemingly viable shapes remain unrealized. Jaw speed is optimized only in a narrow region of morphospace whereas many shapes possess optimal jaw strength, which may act as a minimum boundary rather than a strong driver for most taxa. This study highlights the usefulness of theoretical morphology in assessing functional optimality, and for investigating form-function relationships in diverse clades.

Integrating Multi-omics to Identify Age-Related Macular Degeneration Subtypes and Biomarkers.

Age-related macular degeneration (AMD) is one of the most common causes of irreversible vision loss in the elderly. Its pathogenesis is likely multifactorial, involving a complex interaction of metabolic and environmental factors, and remains poorly understood. Previous studies have shown that mitochondrial dysfunction and oxidative stress play a crucial role in the development of AMD. Oxidative damage to the retinal pigment epithelium (RPE) has been identified as one of the major mediators in the pathogenesis of age-related macular degeneration (AMD). Therefore, this article combines transcriptome sequencing (RNA-seq) and single-cell sequencing (scRNA-seq) data to explore the role of mitochondria-related genes (MRGs) in AMD. Firstly, differential expression analysis was performed on the raw RNA-seq data. The intersection of differentially expressed genes (DEGs) and MRGs was performed. This paper proposes a deep subspace nonnegative matrix factorization (DS-NMF) algorithm to perform a multi-layer nonlinear transformation on the intersection of gene expression profiles corresponding to AMD samples. The age of AMD patients is used as prior information at the network's top level to change the data distribution. The classification is based on reconstructed data with altered distribution. The types obtained significantly differ in scores of multiple immune-related pathways and immune cell infiltration abundance. Secondly, an optimal AMD diagnosis model was constructed using multiple machine learning algorithms for external and qRT-PCR verification. Finally, ten potential therapeutic drugs for AMD were identified based on cMAP analysis. The AMD subtypes identified in this article and the diagnostic model constructed can provide a reference for treating AMD and discovering new drug targets.

Coupled relationships between landscape pattern and ecosystem health in response to urbanization.

Rapid urbanization has highlighted ecological problems in the metropolitan area, with increasing landscape fragmentation and severe threats to ecosystem health (EH). Studying the spatio-temporal coupled relationship between landscape pattern and EH and its response to urbanization in the Fuzhou metropolitan area (FMA) can provide scientific reference for its long-term development planning. We examined the coupled relationship between landscape pattern and EH and its driving mechanism in the FMA at grid and township scales to address the gap. The results show that landscape heterogeneity, diversity, and dispersion are gradually increasing, and EH is rising progressively in the FMA from 2000 to 2020. The spatial distribution of landscape pattern indices and EH indicators showed a "high in the south and low in the north" trend. During the study period, the coupled relationship between landscape patterns and EH was increasingly powerful but with remarkable spatial heterogeneity. The study also found an inverted U-shaped relationship between urbanization and coupled relationships. Ecological landscapes' heterogeneity, diversity, and connectivity in low-urbanization areas are conducive to EH. The opposite is true for high-urbanization areas. This study provides a valuable reference for optimizing landscape planning and ecological management in metropolitan areas.