Spatial Targeting Research Articles

Mechanics of reproductive differentiation in the land plants: a paradigm shift?

This article addresses the physical mechanics of gametogenesis in vascular plants. The earliest events that initiate reproductive differentiation in the land plants are not well understood. How are the few cells that initiate reproductive differentiation specified and how is that information translated into action at the cellular level? In this article I propose a physical mechanism that resolves the problem of spatial targeting without invoking dependence on diffusible morphogens or other external signals. I suggest that the initiation of archesporial differentiation can instead be attributed to the confluence of organ geometry, surficial topography, and the physical mechanics of sporangial growth, resulting in the spontaneous emergence of an isotropic singularity that locates and precipitates archesporial differentiation. In discussing the logic of single-cell target selection and the limits of stochastic molecular signaling I propose that the sporangium would be better understood as a pressurized stress-mechanical lens that focuses turgor-generated growth forces on a central location, generating a physical singularity that locates and specifies the cell or cells that become the archesporium and initiates their transition from somatic proliferation to reproductive differentiation.

Cetuximab functionalized chitosan/hyaluronic acid-based nanoparticles loaded with cabazitaxel enhances anti-tumor efficacy in DMBA-induced breast cancer model in rats through spatial targeting

The article discusses the ionic gelation of cationic chitosan (CS) with anionic hyaluronic acid (HA) sodium salt to form nanoparticles in the range of 125 nm. The particles were further functionalized with cetuximab to endow it with the ability to spatially target the tumor over-expressing EGFR. Solid-state characterization of the particles using XRD, FTIR, and DSC revealed the formation of stable nanoparticles with Cabazitaxel loaded in the amorphous nanostructure. XPS study used to assess the surface characteristics indicated that the cetuximab was successfully anchored on the surface of the particle. The prepared CS-HA-Cmab-NP elicited a pH-responsive drug release behavior due to the presence of CS in the matrix. In vitro performance of the nanoparticles was evaluated on MDA-MB-231 breast cancer cell lines showed overall increase in efficacy. In vivo pharmacokinetic and anti-tumor effect evaluated in female Sprague Dawley rats indicated that the Cmab-conjugated nanoparticles improved half-life of cabazitaxel and tumor reduction capability with higher survival rate and lower reduction in body weight. The results indicate that CS/HA nanoparticles anchored with cetuximab show enhanced efficacy in reducing the breast cancer tumor in DMBA-induced breast tumor model through spatial targeting, consequently reducing the systemic toxicity.

Trade-offs between grassland plant biodiversity and yields are heterogenous across Germany

Grasslands are key for food security and provide important ecosystem services. Intensive management, such as frequent mowing, increases productivity but decreases other ecosystem services as well as plant biodiversity. We here estimate large scale effects of mowing frequency on plant species richness and provide spatial assessments of yield-species richness trade-offs. We use a unique, multisource remote sensing-based dataset covering all permanent agricultural grassland fields across Germany (N = 1,313,073) over four years to estimate the causal impact of mowing frequency, as a proxy of grassland management intensity, on plant species richness. We identify spatially explicit and heterogeneous treatment effects using generalized random forests. We find that more frequent mowing significantly reduces plant species richness, but these effects vary by environmental and socioeconomic context. We quantify the trade-offs between species richness and yield due to changes in mowing frequency, finding an average cost of 126 euros per additional plant species, and demonstrate how spatial targeting can improve the cost-effectiveness of a hypothetical conservation policy, reducing this cost to 51 euros per species. Motivated by the 30 by 30 goal to protect 30% of terrestrial ecosystems by 2030, we further estimate opportunity cost of marginally extensifying 30% of German grasslands to be 131–181 million euros annually, depending on targeting priorities.

Organic farming is more related to topography than to soil characteristics in extensively and intensively managed grasslands in Switzerland

Organic farming and other agri-environmental schemes (AES) are important policy tools to support environmental-friendly agriculture. Often, AES require a direct reduction of actual management intensity to sustain biodiversity and non-marketable ecosystem services. In addition to lower management intensity, differences in topography and soils between AES and non-AES land can occur, driven by the targeted placement of AES in the landscape. Many of the latter effects of an AES are, however, widely unknown and frequently ignored, limiting a comprehensive understanding of how organic farming and other AES deliver environmental outcomes. We analysed pedological, topographical and other spatial characteristics of parcels under two grassland AES, i.e., organic farming (vs. conventional) and extensive management (vs. intensive). Thus, this study assessed whether organic farming is related to differences in topography and soil conditions in both extensively and intensively managed grasslands in the study region in the north of Switzerland. Therefore, we combined a regional-scale spatial analysis of permanent grassland parcels and a soil survey. Both AES were tested not only in interaction with each other but also within the two main harvest types, i.e., meadows (mainly mown) and pastures (mainly grazed), resulting in eight distinct grassland types that were studied. Results show both AES to be linked to differences in soil nutrients as well as topographical and other spatial characteristics. We found interactions of the two AES with the harvest type, i.e., meadow versus pasture. This was particularly pronounced for extensively managed conventional meadows, which were frequent at low elevation and on land potentially suitable for arable farming. Extensively managed pastures and all organic grasslands exhibited reduced production conditions (i.e., higher elevation, steeper slope, lower soil phosphorus concentrations). Yet, differences between organic and conventional grasslands were by tendency more pronounced in intensively than extensively managed grasslands. Our results show that farmers preferentially adopted both AES on land not ideal for intensive production, with the exception of many extensively managed meadows in low elevations. Our study therefore demonstrated that an assessment of the ecological outcomes of an AES must not only account for direct effects via management restrictions but also for indirect effects via spatial targeting by farmers. More research is still needed to assess and compare direct and indirect effects of AES to support evidence-based policymaking and improve spatial targeting of different land-use types.

Modest forest and welfare gains from initiatives for reduced emissions from deforestation and forest degradation

Reduced emissions from deforestation and forest degradation (REDD+) projects and programmes promise to deliver performance-based, cost-effective climate change mitigation. Fifteen years after its conception, we analysed the rigorous counterfactual-based evidence for environmental and welfare effects from such national and subnational initiatives, along with a Theory of Change. Using machine-learning tools for literature review, we compared 32 quantitative studies including 26 primary forest-related and 12 socioeconomic effect sizes. Average environmental impacts were positively significant yet moderately sized, comparable to impacts from other conservation tools, and mostly impermanent over time. Socioeconomic impacts were welfare-neutral to slightly positive. Moderator analysis showed that environmental additionality was likely restricted by project proponents’ adverse spatial targeting of low-threat areas. Scarce funding flows from carbon markets and ill-enforced conditionality probably also limited impacts. Hence, important policy and implementation lessons emerge for boosting effectiveness in the current global transition towards larger-scale, jurisdictional action.

Spatial targeting of irrigation development and water resource management to mitigate vector-borne disease

Scaling irrigated agriculture is a global strategy to mitigate food insecurity concerns. While expanding irrigated agriculture is critical to meeting food production demands, it is important to consider how these land use and land cover changes (LULCC) may alter the water resources of landscapes and impact the spatiotemporal epidemiology of disease. Here, a generalizable method is presented to inform irrigation development decision-making aimed at increasing crop production through irrigation while simultaneously mitigating malaria risk to surrounding communities. Changes to the spatiotemporal patterns of malaria vector (Anopheles gambiae s.s.) suitability, driven by irrigated agricultural expansion, are presented for Malawi's rainy and dry seasons. The methods presented may be applied to other geographical areas where sufficient irrigation and malaria prevalence data are available. Results show that approximately 8.60% and 1.78% of Malawi is maximally suitable for An. gambiae s.s. breeding in the rainy and dry seasons, respectively. However, the proposed LULCC from irrigated agriculture increases the maximally suitable land area in both seasons: 15.16% (rainy) and 2.17% (dry). Proposed irrigation development sites are analyzed and ranked according to their likelihood of increasing malaria risk for those closest to the schemes. Results illustrate how geospatial information on the anticipated change to the malaria landscape driven by increasing irrigated agricultural extent can assist in altering development plans, amending policies, or reassessing water resource management strategies to mitigate expected changes in malaria risk.

Spatial and functional targeting of intratumoral Tregs reverses CD8+ T cell exhaustion and promotes cancer immunotherapy.

Intratumoral Tregs are key mediators of cancer immunotherapy resistance, including anti-programmed cell death (ligand) 1 [anti-PD-(L)1] immune checkpoint blockade (ICB). The mechanisms driving Treg infiltration into the tumor microenvironment (TME) and the consequence on CD8+ T cell exhaustion remain elusive. Here, we report that heat shock protein gp96 (also known as GRP94) was indispensable for Treg tumor infiltration, primarily through the roles of gp96 in chaperoning integrins. Among various gp96-dependent integrins, we found that only LFA-1 (αL integrin), and not αV, CD103 (αE), or β7 integrin, was required for Treg tumor homing. Loss of Treg infiltration into the TME by genetic deletion of gp96/LFA-1 potently induced rejection of tumors in multiple ICB-resistant murine cancer models in a CD8+ T cell-dependent manner, without loss of self-tolerance. Moreover, gp96 deletion impeded Treg activation primarily by suppressing IL-2/STAT5 signaling, which also contributed to tumor regression. By competing for intratumoral IL-2, Tregs prevented the activation of CD8+ tumor-infiltrating lymphocytes, drove thymocyte selection-associated high mobility group box protein (TOX) induction, and induced bona fide CD8+ T cell exhaustion. By contrast, Treg ablation led to striking CD8+ T cell activation without TOX induction, demonstrating clear uncoupling of the 2 processes. Our study reveals that the gp96/LFA-1 axis plays a fundamental role in Treg biology and suggests that Treg-specific gp96/LFA-1 targeting represents a valuable strategy for cancer immunotherapy without inflicting autoinflammatory conditions.

Celastrol-loaded polymeric mixed micelles shows improved antitumor efficacy in 4 T1 bearing xenograft mouse model through spatial targeting

In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (CLS-HF/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer

Species Abundance Modelling of Arctic-Boreal Zone Ducks Informed by Satellite Remote Sensing

The Arctic-Boreal zone (ABZ) covers over 26 million km2 and is home to numerous duck species; however, understanding the spatiotemporal distribution of their populations across this vast landscape is challenging, in part due to extent and data scarcity. Species abundance models for ducks in the ABZ commonly use static (time invariant) habitat covariates to inform predictions, such as wetland type and extent maps. For the first time in this region, we developed species abundance models using high-resolution, time-varying wetland inundation data produced using satellite remote sensing methods. This data captured metrics of surface water extent and inundated vegetation in the Peace Athabasca Delta, Canada, which is within the NASA Arctic Boreal Vulnerability Experiment core domain. We used generalized additive mixed models to demonstrate the improved predictive value of this novel data set over time-invariant data. Our findings highlight both the potential complementarity and efficacy of dynamic wetland inundation information for improving estimation of duck abundance and distribution at high latitudes. Further, these data can be an asset to spatial targeting of biodiversity conservation efforts and developing model-based metrics of their success under rapidly changing climatic conditions.

Spatially selective delivery of living magnetic microrobots through torque-focusing

Rotating magnetic fields enable biomedical microrobots to overcome physiological barriers and promote extravasation and accumulation in tumors. Nevertheless, targeting deeply situated tumors requires suppression of off-target actuation in healthy tissue. Here, we investigate a control strategy for applying spatially selective torque density to microrobots by combining rotating fields with magnetostatic selection fields. Taking magnetotactic bacteria as diffuse torque-based actuators, we numerically model off-target torque suppression, indicating the feasibility of centimeter to millimeter resolution for human applications. We study focal torque application in vitro, observing off-target suppression of actuation-dependent effects such as colonization of bacteria in tumor spheroids. We then design and construct a mouse-scale torque-focusing apparatus capable of maneuvering the focal point. Applying this system to a mouse tumor model increased accumulation of intravenously injected bacteria within tumors receiving focused actuation compared to non-actuated or globally actuated groups. This control scheme combines the advantages of torque-based actuation with spatial targeting.

Clinical Potential of Transcranial Focused Ultrasound for Neurorehabilitation in Pediatric Cancer Survivors.

Cancer survivors are at a high risk for treatment-related late effects, particularly neurocognitive impairment in the attention and executive function domains. These can be compounded in pediatric populations still undergoing neural development, which has increased interest in survivorship studies and neurorehabilitation approaches to mitigate these effects. Cognitive training regimens have shown promise as a therapeutic intervention for improving cognitive function. Therapist-guided and computerized training programs with adaptive paradigms have been successfully implemented in pediatric populations, with positive outcomes on attention and working memory. Another interventional approach is neuromodulation to alter plasticity. Transcranial electrical stimulation can modulate cortical surface activity, and cranial nerve stimulation alters autonomic activity in afferent brainstem pathways. However, they are more systemic in nature and have diffuse spatial targeting. Transcranial focused ultrasound (tFUS) modulation overcomes these limitations with high spatial specificity and the ability to target deeper brain regions. In this review, we discuss the efficacy of tFUS for modulating specific brain regions and its potential utility to augment cognitive training programs as a complementary intervention.

Predicting the spatial variation in cost-efficiency for agricultural greenhouse gas mitigation programs in the U.S.

BackgroundTwo major factors that determine the efficiency of programs designed to mitigate greenhouse gases by encouraging voluntary changes in U.S. agricultural land management are the effect of land use changes on producers’ profitability and the net sequestration those changes create. In this work, we investigate how the interaction of these factors produces spatial heterogeneity in the cost-efficiency of voluntary programs incentivizing tillage reduction and cover-cropping practices. We map county-level predicted rates of adoption for each practice with the greenhouse gas mitigation or carbon sequestration benefits expected from their use. Then, we use these bivariate maps to describe how the cost efficiency of agricultural mitigation efforts is likely to vary spatially in the United States.ResultsOur results suggest the combination of high adoption rates and large reductions in net emissions make reduced tillage programs most cost efficient in the Chesapeake Bay watershed or the Upper Mississippi and Lower Missouri sub-basins of the Mississippi River. For programs aiming to reduce net emissions by incentivizing cover-cropping, we expect cost-efficiency to be greatest in the areas near the main stem of the Mississippi River within its Middle and Lower sections.ConclusionsMany voluntary agricultural conservation programs offer the same incentives across the United States. Yet spatial variation in profitability and efficacy of conservation practices suggest that these uniform approaches are not cost-effective. Spatial targeting of voluntary agricultural conservation programs has the potential to increase the cost-efficiency of these programs due to regional heterogeneity in the profitability and greenhouse gas mitigation benefits of agricultural land management practices across the continental United States. We illustrate how predicted rates of adoption and greenhouse gas sequestration might be used to target regions where efforts to incentivize cover-cropping and reductions in tillage are most likely to be cost -effective.

Geospatial and environmental determinants of stunting, wasting, and underweight: Empirical evidence from rural South and Southeast Asia

ObjectiveChild malnutrition, comprising of undernutrition and obesity, is a global concern with severe implications for survival, leading to acute and chronic diseases that adversely affect the productivity of individuals and society. Asia shoulders the greatest burden, with 7 out of 10 undernourished children residing in the region. Despite the decline in global child stunting, particularly in Asia, its prevalence remains significant. In 2017, an estimated 151 million children under five experienced stunting, and an additional 38 million were overweight, with Africa and Asia accounting for 25% and 46% of the global figures, respectively. Therefore, this paper aims to analyze the geospatial and environmental determinants of undernutrition in rural South and Southeast Asia. MethodsTo explore the geospatial and environmental determinants of undernutrition (stunting, wasting, and underweight), we use Poisson regression and the data from recent rounds of the Demographic and Health Survey (DHS) from India, Bangladesh, Pakistan, Nepal, Cambodia, and Timor-Leste. ResultsThis study found a high prevalence of stunting, wasting, and underweight among children aged 0 to 59 months in rural areas of South and Southeast Asia, with considerable variation between countries and clusters/primary sampling units. Results show a positive association between child malnutrition and factors such as maternal illiteracy, unsafe drinking water, and dirty cooking fuel in South and Southeast Asia. Children from impoverished households in India, Pakistan, and Cambodia were disproportionately affected. In addition to socio-economic factors, climatic risks such as temperature increase and rainfall variations also emerged as important determinants of child malnutrition in India, Bangladesh, and Timor-Leste. ConclusionsThis paper emphasizes the role of environmental and climatic factors on child nutrition, underscoring their significance regardless of socio-economic conditions. As the impacts of climate change continue to intensify, and agrarian societies bear the brunt, these factors will play a critical role in shaping child nutritional outcomes. Thus, amid growing climate change, nutritional security should be prioritized, considering the spatial domain and targeting climate distress areas along with other socio-economic and demographic aspects.

Sustained participation in a Payments for Ecosystem Services program reduces deforestation in a Mexican agricultural frontier

Payments for Ecosystem Services (PES) provide conditional incentives for forest conservation. PES short-term effects on deforestation are well-documented, but we know less about program effectiveness when participation is sustained over time. Here, we assess the impact of consecutive renewals of PES contracts on deforestation and forest degradation in three municipalities of the Selva Lacandona (Chiapas, Mexico). PES reduced deforestation both after a single 5-year contract and after two consecutive contracts, but the impacts are only detectable in higher deforestation-risk parcels. Enrollment duration increases PES impact in these parcels, which suggests a positive cumulative effect over time. These findings suggest that improved spatial targeting and longer-term enrollment are key enabling factors to improve forest conservation outcomes in agricultural frontiers.

Our national nutrient reduction needs: Applying a conservation prioritization framework to US agricultural lands

Targeted conservation approaches seek to focus resources on areas where they can deliver the greatest benefits and are recognized as key to reducing nonpoint source nutrients from agricultural landscapes into sensitive receiving waters. Moreover, there is growing recognition of the importance and complementarity of in-field and edge-of-field conservation for reaching nutrient reduction goals. Here we provide a generic prioritization that can help with spatial targeting and applied it across the conterminous US (CONUS). The prioritization begins with identifying areas with high agricultural nutrient surplus, i.e., where the most nitrogen (N) and/or phosphorus (P) inputs are left on the landscape after crop harvest. Subwatersheds with high surplus included 52% and 50% of CONUS subwatersheds for N and P, respectively, and were located predominantly in the Midwest for N, in the South for P, and in California for both N and P. Then we identified the most suitable conservation strategies using a hierarchy of metrics including nutrient use efficiency (proportion of new nutrient inputs removed by crop harvest), tile drainage, existing buffers for agricultural run-off, and wetland restoration potential. In-field nutrient input reduction emerged as a priority because nutrient use efficiency fell below a high but achievable goal of 0.7 (30% of nutrients applied are not utilized) in 45% and 44% of CONUS subwatersheds for N and P, respectively. In many parts of the southern and western US, in-field conservation (i.e., reducing inputs + preventing nutrients from leaving fields) alone was likely the optimal strategy as agriculture was already well-buffered. However, stacking in-field conservation with additional edge-of-field buffering would be important to conservation strategies in 35% and 29% of CONUS subwatersheds for N and P, respectively. Nutrient use efficiencies were often high enough in the Midwest that proposed strategies focused more on preventing nutrients from leaving fields, managing tile effluent, and buffering agricultural fields. Almost all major river basins would benefit from a variety of nutrient reduction conservation strategies, underscoring the potential of targeted approaches to help limit excess nutrients in surface and ground waters.

Spatial targeting of fibrosis-promoting macrophages with nanoscale metal-organic frameworks for idiopathic pulmonary fibrosis therapy

Targeted delivery of therapeutic drugs to fibrosis-promoting macrophages (FPMs) holds promise as a challenging yet effective approach for the treatment of idiopathic pulmonary fibrosis (IPF). Here, nanocarriers composed of Mn-curcumin metal-organic frameworks (MOFs) were utilized to deliver the immune inhibitor BLZ-945 to the lungs, with the goal of depleting fibrosis-promoting macrophages (FPMs) from fibrotic lung tissues. FPM targeting was achieved by functionalizing the nanocarrier surface with an M2-like FPM binding peptide (M2pep). As a result, significant therapeutic benefits were observed through the successful depletion of approximately 80 % of the M2-like macrophages (FPMs) in a bleomycin-induced fibrosis mouse model treated with the designed M2-like FPM-targeting nanoparticle (referred to as M2NP-BLZ@Mn-Cur).Importantly, the released Mn2+ and curcumin after the degradation of M2NP-BLZ@Mn-Cur accumulated in the fibrotic lung tissue, which can alleviate inflammation and oxidative stress reactions, thereby further improving IPF therapy. This study presents a novel strategy with promising prospects for molecular-targeted fibrosis therapy. Statement of significanceMetal−organic frameworks (MOFs)- based nanocarriers equipped with both fibrosis-promoting macrophage (FPM)-specific targeting ability and therapeutic drugs are appealing for pulmonary fibrosis treatment. Here, we prepared M2pep (an M2-like FPM binding peptide)-modified and BLZ945 (a small molecule inhibitor of CSF1/CSF-1R axis)-loaded Mn-curcumin MOF nanoparticles (M2NP-BLZ@Mn-Cur) for pulmonary fibrosis therapy. The functionalized M2NP-BLZ@Mn-Cur nanoparticles can be preferentially taken up by FPMs, resulting in their depletion from fibrotic lung tissues. In addition, Mn2+and curcumin released from the nanocarriers have anti-inflammation and immune regulation effects, which further enhance the antifibrotic effect of the nanoparticles.

Magnetic Cellular Backpacks for Spatial Targeting, Imaging, and Immunotherapy.

Adoptive cell transfer (ACT) therapies are growing in popularity due to their ability to interact with diseased tissues in a specific manner. Disc-shaped particles, or "backpacks", that bind to cellular surfaces show promise for augmenting the therapeutic potential of adoptively transferred cells by resisting phagocytosis and locally releasing drugs to maintain cellular activity over time. However, many ACTs suffer from limited tumor infiltration and retention and lack a method for real-time spatial analysis. Therefore, we have designed biodegradable backpacks loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to improve upon current ACT strategies by (i) controlling the localization of cell-backpack complexes using gradient magnetic fields and (ii) enabling magnetic particle imaging (MPI) to track complexes after injection. We show that magnetic backpacks bound to macrophages and loaded with a proinflammatory drug, resiquimod, maintain anticancer phenotypes of carrier macrophages for 5 days and create cytokine "factories" that continuously release IL-12. Furthermore, we establish that forces generated by gradient magnet fields are sufficient to displace cell-backpack complexes in physiological settings. Finally, we demonstrate that MPI can be used to visualize cell-backpack complexes in mouse tumors, enabling a potential strategy to track the biodistribution of ACTs in real time.

Immobilized doxorubicin and ribociclib carbamate linkers encaged in surface modified cubosomes spatially target tumor reductive environment to enhance antitumor efficacy

In the present investigation, we have strategically synthesized Glutathione (GSH) stimuli-sensitive analogues using carbamate linkers (CL) of DOX (DOX-CL) and RB (RB-CL) which were then anchored to gold nanoparticles (Au-DOX-CL, Au-RB-CL) using mPEG as a spacer. It was observed that carbamate linkage (CL) with four carbon spacer is critical, to position the terminal thiol group, to access the carbamate group efficiently to achieve GSH-assisted release of DOX and RB in tumor-specific environment. When assessed for GSH reductase activity in MDA-MB 231 cell lines, Au-DOX-CL and Au-RB-CL showed nearly 4.18 and 3.13 fold higher GSH reductive activity as compared to the control group respectively. To achieve spatial tumor targeting with a high payload of DOX and RB, Au-DOX-CL and Au-RB-CL were encapsulated in the cell-penetrating peptide (CPP) modified liquid crystalline cubosomes i.e. CPP-Cu(Au@CL-DR). After internalization, the prototype nanocarriers release respective drugs at a precise GSH concentration inside the tumor tissues, amplifying drug concentration to a tune of five-fold. The drug concentrations remain within the therapeutic window for 72 h with a significant reduction of RB (7.8-fold) and DOX (6-fold) concentrations in vital organs, rendering reduced toxicity and improved survival. Overall, this constitutes a promising chemotherapeutic strategy against cancer and its potential application in the offing.

Relaxing the production-conservation trade-off: Biodiversity spillover in the bioeconomic performance of ecological networks

Ecological networks (ENs) aim to accommodate production and conservation within landscapes by shaping the spatial scope of conservation policies based on ecological criteria. The environmental effectiveness of these networks has been extensively studied; however, it has rarely been linked to their economic cost. This paper investigates whether EN-based spatial targeting relaxes the production-conservation trade-off and, if so, what the processes underlying its performance may be. We design an EN at the national level (France), with common farmland birds defined as a conservation goal and grassland expansion defined as a conservation lever. A dynamic, mechanistic, ecological-economic model simulates policy scenarios up to 2050 with alternative targeting strategies, including the EN. The results reveal that EN targeting is almost twice as cost-effective as a nationally homogeneous policy and about as cost-effective as focusing on biodiversity reservoirs, but with higher biodiversity gains. These outcomes rely on higher initial bird abundance in targeted regions, as well as positive feedback and spillover supported by bird dispersal. However, the EN's superiority only appears in the medium term because of ecological inertia. These interdisciplinary insights on a tool from ecology and conservation biology echo policy needs for the design and implementation of sustainable landscape management strategies.

Spatially targeting national-scale afforestation for multiple ecosystem services

The potential for large-scale afforestation, as a climate change mitigation strategy, has led to national afforestation targets being proposed. These targets raise many questions, including how to optimise carbon storage, whilst enhancing other ecosystem services (ES). Here, we assess how decision-making at different scales might affect the spatial distribution of new tree planting in England and hence ES provision. This was achieved by modelling the impact of afforestation on three example ES (carbon sequestration, recreation, and flood mitigation) to identify the best areas for planting at five scales of decision-making: national, regional, county, district, and parish. The modelling shows that carbon sequestration rates are relatively invariant across England (once unsuitable areas are excluded), whilst recreation and flood mitigation are more spatially variable, so full simultaneous optimisation of the three ES is not possible. Consequently, recreation and flood mitigation are also more impacted by changes in planning-scale than carbon, with the modelling showing over 200% difference between the parish and national-scenarios for flood mitigation benefits. Overall, targeted afforestation at national scale maximises ES benefits, but risks overwhelming some landscapes with trees. Targeting afforestation using smaller planning units generates more evenly distributed planting, but lower ES benefits. Our results show national-scale planning produces over 35% more combined ecosystem value than planning at parish-scale, and over 65% more than randomized planting. This highlights the benefits of targeting at a relevant scale, but also the potential trade-offs between widely-distributed new tree planting (e.g., parish-scenario), versus planting to optimise ES provision (e.g., the national-scenario). These results do not imply a single ‘correct’ scale for planning, but instead highlight the importance of considering the impact of a specific scale on the different ES, and that even spatial targeting at the smallest scale produces higher ES benefits than random planting.