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Two-dimensional neuronal cultures have a limited ability to recapitulate the in vivo environment of the brain. Here, we introduce a three-dimensional in vitro model for human glia-to-neuron conversion, surpassing the spatial and temporal constrains of two-dimensional cultures. Focused on direct conversion to induced dopamine neurons (iDANs) relevant to Parkinson disease, the model generates functionally mature iDANs in 2 weeks and allows long-term survival. As proof of concept, we use single-nucleus RNA sequencing and molecular lineage tracing during iDAN generation and find that all glial subtypes generate neurons and that conversion relies on the coordinated expression of three neural conversion factors. We also show the formation of mature and functional iDANs over time. The model facilitates molecular investigations of the conversion process to enhance understanding of conversion outcomes and offers a system for in vitro reprogramming studies aimed at advancing alternative therapeutic strategies in the diseased brain.

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The aqueous FeIV-oxo complex and FeIII-peroxy complex (e.g., ligand-assisted or interfacial FeIII-hydroperoxo intermediates) have been recognized as crucial reactive intermediates for decontamination in iron-based Fenton-like processes. Intermediates with terminal oxo ligands can undergo the oxygen atom exchange process with water molecules, whereas peroxides are unable to induce such exchanges. Therefore, these distinct metal-oxygen complexes can be distinguished based on the above feature. In this study, we identified previously unknown intermediates with a peroxy moiety and cobalt center that were generated during peroxymonosulfate (PMS) activation via aqueous CoII ions under acidic conditions. Results of theoretical calculations and tip-enhanced Raman spectroscopy revealed that the CoII ion tended to coordinate with the PMS anion to form a bidentate complex with a tetrahedral structure. These reactive cobalt intermediates were collectively named the CoII-PMS* complex. Depending on the inherent characteristics of the target contaminants, the CoII-PMS* complex can directly oxidize organic compounds or trigger PMS disproportionation to release hydroxyl radicals and sulfate radicals for collaborative decontamination. This work provides a comparative study between iron- and cobalt-based Fenton-like processes and proposes novel insights from the standpoint of diverse metal-oxygen complexes.

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Introduction: coronavirus disease 2019 (COVID-19) transmission dynamics in the communities of low- and middle-income countries, particularly sub-Saharan African countries, are still not fully understood. This study aimed to determine the characteristics of COVID-19 secondary transmission during the first wave of the epidemic (March-October 2020) in Lusaka, Zambia. Methods: we conducted an observational study on COVID-19 secondary transmission among residents in Lusaka City, between March 18 and October 30, 2020. We compared the secondary attack rate (SAR) among different environmental settings of contacts and characteristics of primary cases (e.g, demographics, medical conditions) by logistic regression analysis. Results: out of 1862 confirmed cases of COVID-19, 272 primary cases generated 422 secondary cases through 216 secondary transmission events. More contacts and secondary transmissions were reported in planned residential areas than in unplanned residential areas. Households were the most common environmental settings of secondary transmission, representing 76.4% (165/216) of secondary transmission events. The SAR in households was higher than the overall events. None of the environmental settings or host factors of primary cases showed a statistically significant relationship with SAR. Conclusion: of the settings considered, households had the highest incidence of secondary transmission during the first wave in Lusaka, Zambia. The smaller proportion of contacts and secondary transmission in unplanned residential areas might have been due to underreporting of cases, given that those areas are reported to be vulnerable to infectious disease outbreaks. Continuous efforts are warranted to establish measures to suppress COVID-19 transmission in those high-risk environments.

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The recent COVID-19 pandemic underscores the significance of early stage nonpharmacological intervention strategies. The widespread use of masks and the systematic implementation of contact tracing strategies provide a potentially equally effective and socially less impactful alternative to more conventional approaches, such as large-scale mobility restrictions. However, manual contact tracing faces strong limitations in accessing the network of contacts, and the scalability of currently implemented protocols for smartphone-based digital contact tracing becomes impractical during the rapid expansion phases of the outbreaks, due to the surge in exposure notifications and associated tests. A substantial improvement in digital contact tracing can be obtained through the integration of probabilistic techniques for risk assessment that can more effectively guide the allocation of diagnostic tests. In this study, we first quantitatively analyze the diagnostic and social costs associated with these containment measures based on contact tracing, employing three state-of-the-art models of SARS-CoV-2 spreading. Our results suggest that probabilistic techniques allow for more effective mitigation at a lower cost. Secondly, our findings reveal a remarkable efficacy of probabilistic contact-tracing techniques in performing backward and multistep tracing and capturing superspreading events.

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Atmospheric deposition is a significant source of heavy metal (HM) pollution. In order to understand the migration and transformation process of atmospheric HMs within the watershed and quantify the amount transported offshore by rivers, the Soil and Water Assessment Tool (SWAT) was developed to trace the migration of HMs from atmospheric deposition. The model simulates HMs in three forms: dissolved, adsorbed, and granular. It quantifies the movements of Cd, Cr, Cu, Hg, Pb, and Zn from atmospheric deposition into the sea via rivers in five coastal watersheds in East China and analyzes the effects of meteorological factors, vegetation cover, and slope on non-point pollution of these metals by Spearman correlation analysis. The results showed that the annual flux of HMs from atmospheric deposition to the sea through rivers accounted for 5 %-69 % of the total rivers flux. Among meteorological factors, precipitation demonstrated the strongest correlation with the monthly loads of HMs entering rivers from atmospheric deposition. Additionally, HMs loads entering rivers from atmospheric deposition were more closely related to vegetation cover than topographic slope. This model provides a new approach to distinguishing the flux of atmospheric HMs entering offshore waters through rivers. The findings will deepen our understanding of the migration and transformation of HMs from atmospheric deposition, enhance the ability to control offshore HMs pollution, and reduce the ecological risks associated by HMs.

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Cyanobacterial blooms induced by excessive loadings of nitrogen (N) and other nutrients are a severe ecological problem in aquatic ecosystems. Previous studies of N removal have primarily focused on sediment-water interface, yet the role of cyanobacterial colonies has recently been attracting more research attention. In this study, N cycling processes were quantified for cyanobacterial colonies (primarily Microcystis colonies) and their contribution to N removal was estimated for a large, shallow eutrophic lake in China, Lake Taihu. Various N cycling processes were determined via stable 15N isotope, together with 16S rRNA gene sequencing and quantitative microbial element cycling (QMEC) chip. Denitrification was found the most prominent process which was estimated to be 36.63, 9.85, 3.35 and 3.15 times higher than dissimilatory nitrate reduction to ammonium (DNRA), nitrification, ammonium (NH4+) uptake and nitrate (NO3-) uptake rates, respectively. Denitrifiers accounted for a large part of the bacterial taxa (35.50 ±â€¯24.65 %), and the nirS gene was the most abundant among N cycling-related genes, with (2.54 ±â€¯0.51) × 109 copies g-1Microcystis colonies. A field investigation revealed a positive correlation between the potential denitrification rate and the Chl-a concentration (mostly derived from Microcystis colonies). Based on a multiple stepwise regression model and historical data from 2007 to 2015 for Lake Taihu, the total amount of N removed via denitrification by Microcystis colonies was estimated at 171.72 ±â€¯49.74 t yr-1; this suggests that Microcystis colonies have played an important role in N removal in Lake Taihu since the drinking water crisis in 2007. Overall, this study revealed the importance of denitrification within Microcystis colonies for N removal in eutrophic lakes, like Lake Taihu.

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BACKGROUND: Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. METHODS: In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. RESULTS: We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-ß1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. CONCLUSIONS: This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

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It is known that the primate amygdala forms projections to many areas of the ipsilateral cortex, but the extent to which it forms connections with the contralateral visual cortex remains less understood. Based on retrograde tracer injections in marmoset monkeys, we report that the amygdala forms widespread projections to the ipsilateral extrastriate cortex, including V1 and areas in both the dorsal (MT, V4T, V3a, 19M, and PG/PFG) and the ventral (VLP and TEO) streams. In addition, contralateral projections were found to target each of the extrastriate areas, but not V1. In both hemispheres, the tracer-labeled neurons were exclusively located in the basolateral nuclear complex. The number of labeled neurons in the contralateral amygdala was small relative to the ipsilateral connection (1.2% to 5.8%). The percentage of contralateral connections increased progressively with hierarchical level. An injection in the corpus callosum demonstrated that at least some of the amygdalo-cortical connections cross through this fiber tract, in addition to the previously documented path through the anterior commissure. Our results expand knowledge of the amygdalofugal projections to the extrastriate cortex, while also revealing pathways through which visual stimuli conveying affective content can directly influence early stages of neural processing in the contralateral visual field.

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Hematopoiesis is the process that generates the cells of the blood and immune system from hematopoietic stem and progenitor cells (HSPCs) and represents the system with the most rapid cell turnover in a mammalian organism. HSPC differentiation trajectories, their underlying molecular mechanisms, and their dysfunctions in hematologic disorders are the focal research questions of experimental hematology. While HSPC transplantations in murine models are the traditional tool in this research field, recent advances in genome editing and next generation sequencing resulted in the development of many fundamentally new approaches for the analyses of mammalian hematopoiesis in situ and at single cell resolution. The current review will cover many recent developments in this field in murine models, from the bulk lineage tracing studies of HSPC differentiation to the barcoding of individual HSPCs with Cre-recombinase, Sleeping Beauty transposase, or CRISPR/Cas9 tools, to map hematopoietic cell fates, together with their transcriptional and epigenetic states. We also address studies of the clonal dynamics of human hematopoiesis, from the tracing of HSPC clonal behaviours based on viral integration sites in gene therapy patients to the recent analyses of unperturbed human hematopoiesis based on naturally accrued mutations in either nuclear or mitochondrial genomes. Such studies are revolutionizing our understanding of HSPC biology and hematopoiesis both under homeostatic conditions and in the response to various forms of physiological stress, reveal the mechanisms responsible for the decline of hematopoietic function with age, and in the future may advance the understanding and management of the diverse disorders of hematopoiesis.

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Groundwater pollution resulting from leachate leakage at landfill sites has garnered significant attention. Investigating the migration of pollutants from these landfills to adjacent groundwater is crucial for understanding the diffusion patterns and extent of contamination. It is imperative to develop cost-effective yet highly efficient tracer techniques to aid landfill operators in monitoring groundwater contamination stemming from their operations. The primary objective of this research was to compare the roles of conservative tracers sodium (Na+) and chloride (Cl-), and conventional pollutants permanganate oxidation (CODMn), ammonium nitrogen (NH4 +-N), lead (Pb), and zinc (Zn) in assessing pollution levels from municipal solid waste landfills to groundwater. For this purpose, a typical municipal solid landfill was selected to investigate the origin of Cl-, groundwater quality, and spatiotemporal variations of multiple contaminations. Geochemistry analyses revealed that Na-Cl and Ca-HCO3 were the dominant groundwater type in this study and landfill was the primary source of Cl- in groundwater, with an average contribution of 78 %. Groundwater in proximity to the landfill (5#, 2#, 22#, 23#) exhibited elevated concentrations of Na+ (15.6-914.0 mg/L), Cl- (8.9-1352.0 mg/L), CODMn (0.54-95.9 mg/L), and NH4 +-N (0.33-49.0 mg/L), yet demonstrated reduced levels of Pb (0.2-391.0 µg/L) and Zn (2.0-112.8 µg/L). In contrast, groundwater located at a considerable distance from the landfill (13#, 18#, 15#, 26#) displayed the inverse trend, with relatively low concentration of Na+ (3.2-8.5 mg/L), Cl- (0.1-0.7 mg/L), CODMn (0.28-4.78 mg/L), and NH4 +-N (0.03-0.52 mg/L), but increased levels of Pb (1.2-483.0 µg/L) and Zn (1.6-357.0 µg/L). The primary determinant of groundwater quality near the landfill was NH4 +-N, with the highest pollution index (Pi) of 492.85, whereas Pb was the predominant factor affecting water quality in areas distant from the landfill, with the highest pollution index (Pi) of 10.9. While no discernible seasonal variation was detected for all pollutants, spatial variation can be observed that pollution levels decreased progressively with increasing distance from the landfill, a trend particularly corroborated by the conservative Cl- and Na+ measurements. This research suggests that conservative ions, such as Cl- and Na+, exhibit superior efficacy in tracing the pollution range from municipal solid landfills to groundwater. Therefore, monitoring these conservative ions in groundwater can yield a more precise understanding of the extent of groundwater contamination originated from landfills.

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Establishing a highly efficient photoactivatable Cre recombinase PA-Cre3.0 can allow spatiotemporal control of Cre recombinase activity. This technique may help to elucidate cell lineages, as well as facilitate gene and cell function analysis during development. This study examined the blue light-mediated optical regulation of Cre-loxP recombination using PA-Cre3.0 transgenic early mouse pre-implantation embryos. We found that inducing PA-Cre3.0 expression in the heterozygous state did not show detectable recombination activation with blue light. Conversely, in homozygous embryos, DNA recombination by PA-Cre3.0 was successfully induced by blue light and resulted in the activation of the red fluorescent protein reporter gene, while almost no leaks of Cre recombination activity were detected in embryos without light illumination. Thus, we characterize the conditions under which the PA-Cre3.0 system functions efficiently in early mouse embryos. These results are expected to provide a new optogenetic tool for certain biological studies, such as developmental process analysis and lineage tracing in early mouse embryos.

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Tractography algorithms are used extensively to delineate white matter structures, by operating on the voxel-wise information generated through the application of diffusion tensor imaging (DTI) or other models to diffusion weighted (DW) magnetic resonance imaging (MRI) data. Through statistical modelling, we demonstrate that these methods commonly yield substantial and systematic associations between streamline length and several tractography derived quantitative metrics, such as fractional anisotropy (FA). These associations may be described as piecewise linear. For streamlines shorter than an inflection point (determined for a group of tracts delineated for each individual brain), estimates of FA exhibit a positive linear relation with streamline length. For streamlines longer than the point of inflection, the association is weaker, with the slope of the relationship between streamline length and FA differing only marginally from zero. As the association is most pronounced for a range of streamline lengths encountered typically in DW imaging of the human brain (less than ~ 100 mm), our results suggest that some quantitative metrics derived from diffusion tractography have the potential to mislead, if variations in streamline length are not considered. A method is described, whereby an Akaike information weighted average of linear, Blackman and piecewise linear model predictions, may be used to compensate effectively for the association of FA (and other quantitative metrics) with streamline length, across the entire range of streamline lengths present in each specimen.

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BACKGROUND AND AIMS: Most experimental studies of allograft vasculopathy (AV) have relied on transplantation between major histocompatibility complex-mismatched inbred mouse strains, but this leads to the complete eradication of donor smooth muscle cells (SMCs) and lesions formed by recipient cells. This is unlike human AV which is thought to form mainly by donor SMCs. Here, we studied sources of neointimal cells in a minor histocompatibility antigen-mismatched AV model by combining male-to-female orthotopic carotid transplantations and lineage tracing by SMC-specific expression of fluorescent proteins. METHODS: To track SMC-derived cells in allograft vasculopathy, we used male donor mice with SMC-restricted Cre recombination of the mT/mG reporter transgene, which switches expression of membrane-bound red fluorescent protein (RFP) to green fluorescent protein (GFP), or the stochastically recombining Confetti reporter transgene, which yields a mosaic expression of four fluorescent proteins. Donor carotid segments were harvested and orthotopically allografted to female recipients that were wildtype or had non-recombined reporter transgenes. Inhibition of T cell responses by CTLA4Ig was used in some experiments. Sections of lesions harvested after 4 weeks were analyzed by fluorescence microscopy. RESULTS: Donor-derived SMCs survived and gave rise to part of the neointimal cells in experiments where carotid segments from recombined mT/mG male mice were transplanted into wild-type or non-recombined mT/mG female mice. Sex-mismatched transplants developed significant lesions, increasing the intimal and medial area 4.6-fold (p = 0.038) and 2.0-fold (p = 0.024) compared to sex- and fluorescence-matched controls, respectively. Interestingly, sex-matched fluorescence-positive transplants developed intimal lesions in 50% of fluorescence-naïve recipient controls. To study the clonal structure of the neointimal donor-derived SMC lineage cells, we then transplanted male carotids with heterozygous or homozygous recombined Confetti transgenes into female recipients. These transplants developed lesions with few surviving donor SMCs, indicating that expression of the Confetti reporter increased rejection and donor-specific SMC death. Some of the few remaining donor SMCs underwent clonal expansion. CTLA4Ig administration at the time of surgery did not improve SMC survival in mT/mG or Confetti transplants. CONCLUSION: Male-to-female transplant models feature donor-derived SMCs, some of which undergo clonal expansion, but immune rejection to fluorescence reporters appears to bias results in lineage tracing models. Overcoming these challenges with alternative reporter transgenes or tolerant recipients is necessary to study the mechanisms by which donor SMCs contribute to allograft vasculopathy.

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Previously focused primarily on enteric neurons, studies of the enteric nervous system (ENS) in both health and disease are now broadening to recognize the equally significant role played by enteric glial cells (EGCs). Commensurate to the vast array of gastrointestinal functions they influence, EGCs exhibit considerable diversity in terms of location, morphology, molecular profiles, and functional attributes. However, the mechanisms underlying this diversification of EGCs remain largely unexplored. To begin unraveling the mechanistic complexities of EGC diversity, the current study aimed to examine its spatiotemporal aspects in greater detail, and to assess whether the various sources of enteric neural progenitors contribute differentially to this diversity. Based on established topo-morphological criteria for categorizing EGCs into four main subtypes, our detailed immunofluorescence analyses first revealed that these subtypes emerge sequentially during early postnatal development, in a coordinated manner with the structural changes that occur in the ENS. When combined with genetic cell lineage tracing experiments, our analyses then uncovered a strongly biased contribution by Schwann cell-derived enteric neural progenitors to particular topo-morphological subtypes of EGCs. Taken together, these findings provide a robust foundation for further investigations into the molecular and cellular mechanisms governing EGC diversity.

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In karst areas, the dissolved inorganic carbon (DIC) concentrations in aquatic systems are typically higher than that in non-karst areas due to intensive carbonate rock weathering. Understanding the sources and input fluxes of DIC in karst reservoirs is crucial for regional carbon cycle studies. This study utilized dual carbon isotopes (δ13CDIC and Δ14CDIC) to estimate the contribution rates and input fluxes of DIC from various sources in Aha Reservoir (AHR), located in southwestern China. Our results indicated that the DIC concentrations (22.33-32.79 mg L-1) and δ13CDIC values (-10.02‰ to -8.55‰) were nearly homogeneous both vertically and laterally in the reservoir (p > 0.05). The Δ14CDIC values (-246.31‰ to -137.86‰) were homogeneous along the vertical profile (p > 0.05), but showed significant horizontal variation (p < 0.05), with values decreasing from -149.57 ± 10.27‰ to -232.85 ± 2.37‰ at the mouths of the inflowing rivers. We found that the inflowing rivers were the primary DIC sources to AHR, contributing 70% of the total input, while groundwater and atmospheric CO2 contributions were relatively minor, at 18% and 12%, respectively. The Jinzhong River (JZR), influenced by industrial and domestic wastewater discharge, contributed the largest DIC input flux at 2.01 t/(km2·mon). In contrast, the Youyu River (YYR), influenced by acidic mine drainage, and the Baiyan River (BYR), influenced by agricultural activities, contributed relatively smaller DIC input fluxes of 1.29 t/(km2·mon) and 1.03 t/(km2·mon), respectively. This study highlights the significant impact of anthropogenic activities on DIC input in AHR, with industrial and domestic wastewater discharges having a greater influence than agricultural activities and acidic mine wastewater inputs. These findings underscore the critical need to manage and mitigate the impacts of human activities on karst reservoir ecosystems.

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BACKGROUND: Digital public health (DiPH) interventions may help us tackle substantial public health challenges and reach historically underserved populations, in addition to presenting valuable opportunities to improve and complement existing services. However, DiPH interventions are often triggered through technological advancements and opportunities rather than public health needs. To develop and evaluate interventions designed to serve public health needs, a comprehensive framework is needed that systematically covers all aspects with relevance for public health. This includes considering the complexity of the technology, the context in which the technology is supposed to operate, its implementation, and its effects on public health, including ethical, legal, and social aspects. OBJECTIVE: We aimed to develop such a DiPH framework with a comprehensive list of core principles to be considered throughout the development and evaluation process of any DiPH intervention. METHODS: The resulting digital public health framework (DigiPHrame) was based on a scoping review of existing digital health and public health frameworks. After extracting all assessment criteria from these frameworks, we clustered the criteria. During a series of multidisciplinary meetings with experts from the Leibniz ScienceCampus Digital Public Health, we restructured each domain to represent the complexity of DiPH. In this paper, we used a COVID-19 contact-tracing app as a use case to illustrate how DigiPHrame may be applied to assess DiPH interventions. RESULTS: The current version of DigiPHrame consists of 182 questions nested under 12 domains. Domain 1 describes the current status of health needs and existing interventions; domains 2 and 3, the DiPH technology under assessment and aspects related to human-computer interaction, respectively; domains 4 and 5, structural and process aspects, respectively; and domains 6-12, contextual conditions and the outcomes of the DiPH intervention from broad perspectives. In the CWA use case, a number of questions relevant during its development but also important for assessors once the CWA was available were highlighted. CONCLUSIONS: DigiPHrame is a comprehensive framework for the development and assessment of digital technologies designed for public health purposes. It is a living framework and will, therefore, be updated regularly and as new public health needs and technological advancements emerge.

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The COVID-19 pandemic highlighted the importance of addressing social needs in a crisis context. Some US jurisdictions integrated a social service component into case investigation and contact tracing (CI/CT) programs, including the New York City (NYC) Test & Trace (T2) Program; the Take Care initiative referred NYC residents who tested positive or were exposed to COVID-19 to services to support isolation and quarantine and meet basic needs. More research is needed to determine effective implementation strategies for integrating social needs provision into CI/CT programs. To identify barriers and facilitators to the implementation of the Take Care initiative, we conducted key informant interviews with program staff, community-based organization partners, and cases and contacts as part of a larger evaluation of the T2 program. Interviews were recorded, transcribed, and analyzed using rapid qualitative methods. Key facilitators to implementation included utilizing a case management software system, employing strategies to encourage service uptake, leveraging cross-agency collaborations, and partnering with community-based organizations for resource navigation. Barriers identified included external management of the software system, challenges reaching and engaging the public, administrative complications due to shifting collaborations, and management of CBO partners' structure and hiring. Based on our findings, we provide recommendations to support effective planning and implementation of social needs service provision in a crisis context. Future research should focus on testing promising implementation strategies highlighted in this study and applying them to varied contexts and crisis situations.

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The insular cortex is an important hub for sensory and emotional integration. It is one of the areas consistently found activated during pain. While the insular's connections to the limbic system might play a role in the aversive and emotional component of pain, its connections to the descending pain system might be involved in pain intensity coding. Here, we used anterograde tracing with viral expression of mCherry fluorescent protein, to examine the connectivity of insular axons to different brainstem nuclei involved in the descending modulation of pain in detail. We found extensive connections to the main areas of descending pain control, namely, the periaqueductal gray (PAG) and the raphe magnus (RMg). In addition, we also identified an extensive insular connection to the parabrachial nucleus (PBN). Although not as extensive, we found a consistent axonal input from the insula to different noradrenergic nuclei, the locus coeruleus (LC), the subcoereuleus (SubCD) and the A5 nucleus. These connections emphasize a prominent relation of the insula with the descending pain modulatory system, which reveals an important role of the insula in pain processing through descending pathways.

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The environmental risk of Cd in soils strongly depends on the mobilization of Cd in soils. However, limited knowledge exists on the redistribution of exogenic Cd inputs in soils, especially across diverse lithological regions. Herein, we aimed to investigate the fate of Cd in soils from two mining areas with contrasting lithologies (siliceous and calcareous) using stable Cd isotopes. The isotope tracing results confirm that mining activities are the main Cd source in both areas. The positive correlation between δ114/110Cd values and goethite/dolomite content indicates the release of heavy Cd isotopes during the dissolution of exogenetic minerals. Additionally, high contents of exchangeable Cd (11 % to 36 %) and Fe oxide-bound Cd (29 % to 42 %) drive plant pumps to transport heavy Cd isotopes from the deeper to upper horizons of the soils from the siliceous area. In the calcareous area, the total organic carbon content is positively correlated with the Cd concentration and δ114/110Cd value, suggesting potential complexation of Cd with organic matter due to the stabilizing effect of carbonate minerals on soil organic matter. This study highlights the different redistributions of exogenous Cd in soils from diverse lithological regions, emphasizing the need to consider regional lithology when developing soil quality standards for Cd.

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Lung injury activates epithelial stem or progenitor cells for alveolar repair and regeneration. Unraveling the origin and fate of injury-induced progenitors is crucial for elucidating lung repair mechanisms. Here, we report that p63-expressing progenitors emerge upon bleomycin-induced mouse lung injury. Single-cell RNA sequencing and clonal analysis reveal that these p63+ progenitors proliferate rapidly and differentiate into alveolar type 1 and type 2 cells through different trajectories. Dual recombinase-mediated sequential genetic-lineage tracing demonstrates that p63+ progenitors originate from airway secretory cells and subsequently generate alveolar cells. Functionally, p63 activation is essential for efficient alveolar regeneration from secretory cells post injury. Our study identifies secretory-cell-derived p63+ progenitors as contributors to alveolar repair, suggesting a potential therapeutic avenue for lung regeneration following injury.