Delivery Pathways Research Articles

Characterizing HIV status documentation among cancer patients at regional cancer centers in Malawi, Zimbabwe, and South Africa

IntroductionIn East and Southern Africa, people with HIV (PWH) experience worse cancer-related outcomes and are at higher risk of developing certain cancers. Siloed care delivery pathways pose a substantial barrier to co-management of HIV and cancer care delivery.MethodsWe conducted cross-sectional studies of adult cancer patients at public radiotherapy and oncology units in Malawi (Kamuzu Central Hospital), Zimbabwe (Parirenyatwa Group of Hospitals), and South Africa (Charlotte Maxeke Hospital) between 2018 and 2019. We abstracted cancer- and HIV-related data from new cancer patient records and used Poisson regression with robust variance to identify patient characteristics associated with HIV documentation.ResultsWe included 1,648 records from Malawi (median age 46 years), 1,044 records from South Africa (median age 55 years), and 1,135 records from Zimbabwe (median age 52 years). Records from all three sites were predominately from female patients; the most common cancers were cervical (Malawi [29%] and Zimbabwe [43%]) and breast (South Africa [87%]). HIV status was documented in 22% of cancer records from Malawi, 92% from South Africa, and 86% from Zimbabwe. Patients with infection-related cancers were more likely to have HIV status documented in Malawi (adjusted prevalence ratio [aPR]: 1.92, 95% confidence interval [CI]: 1.56–2.38) and Zimbabwe (aPR: 1.16, 95%CI: 1.10–1.22). Patients aged ≥ 60 years were less likely to have HIV status documented (Malawi: aPR: 0.66, 95% CI: 0.50–0.87; Zimbabwe: aPR: 0.76, 95%CI: 0.72–0.81) than patients under age 40 years. Patient age and cancer type were not associated with HIV status documentation in South Africa.ConclusionDifferent cancer centers have different gaps in HIV status documentation and will require tailored strategies to improve processes for ascertaining and recording HIV-related information in cancer records. Further research by our consortium to identify opportunities for integrating HIV and cancer care delivery is underway.

Exosomes Highlight Future Directions in the Treatment of Acute Kidney Injury

Acute kidney injury (AKI) is a severe health problem associated with high morbidity and mortality rates. It currently lacks specific therapeutic strategies. This review focuses on the mechanisms underlying the actions of exosomes derived from different cell sources, including red blood cells, macrophages, monocytes, mesenchymal stem cells, and renal tubular cells, in AKI. We also investigate the effects of various exosome contents (such as miRNA, lncRNA, circRNA, mRNA, and proteins) in promoting renal tubular cell regeneration and angiogenesis, regulating autophagy, suppressing inflammatory responses and oxidative stress, and preventing fibrosis to facilitate AKI repair. Moreover, we highlight the interactions between macrophages and renal tubular cells through exosomes, which contribute to the progression of AKI. Additionally, exosomes and their contents show promise as potential biomarkers for diagnosing AKI. The engineering of exosomes has improved their clinical potential by enhancing isolation and enrichment, target delivery to injured renal tissues, and incorporating small molecular modifications for clinical use. However, further research is needed to better understand the specific mechanisms underlying exosome actions, their delivery pathways to renal tubular cells, and the application of multi-omics research in studying AKI.

Molecular camouflage by a context-specific hydrogel as the key to unlock the potential of viral vector gene therapy

Gene therapy offers hope for currently untreatable diseases; the patient’s own cellular machinery is recruited to create therapeutics. However, unpredictable responses that lead to neutralization by the host immune system and issues in constraining, controlling and sustaining delivery have presented clinical barriers to otherwise promising therapeutic developments. Here, we show that the protective environment provided by advanced biomaterials can function as injectable gene carriers to focus their therapeutic potential. Firstly, we investigated the potential of a tissue-specific molecular hydrogel to package recombinant adeno-associated viruses (rAAVs). Once a delivery pathway was confirmed, a set of rAAV variants were subsequently assessed for their ability to transduce various types of rodent and human neural cells in vitro and in vivo. Based on GFP expression, we identified a relatively new variant, rAAV-DJ, as showing desirable characteristics for constrained delivery and transduction efficiency. For the first time, we demonstrated precise control over the strength and type of interaction between biomaterials and rAAVs enabling the programmed release of viral payloads. This new approach enables specific infection of desired anatomical targets in a programmed fashion.

Using Mass Spectrometry Imaging to Visualize Pesticide Accumulation and Time-Dependent Distribution in Fungicide-Coated Seeds.

Pesticide seed treatment provides efficient crop protection in the early season and enables a reduction in the quantity of fungicides used later. Hence, it has been a practical application for crop protection in major crop sectors such as corn, soybean, wheat, and cotton. The chemicals on pesticide-treated seeds may show different distributions depending on the structure of the seeds and the physical properties of the chemicals, but they have not been well studied because of a lack of versatile analytical tools. Here, we used mass spectrometry imaging to visualize the distribution of a fungicide (ethaboxam) in corn and soybean seeds coated with it. Contrasting distribution patterns were noted, which are likely dependent on the seed structure. We also obtained information on fungicide distribution after the seedings, which will contribute to a better understanding of the fungicide delivery pathway within plants. Using this new analytical method, we were able to obtain hitherto unavailable time-dependent, dynamic information on the ethaboxam. We expect that this method will be a useful tool with widespread applications in pesticide development and use. Copyright © 2023 Shuichi Shimma, Hiromi Saito, Takuya Inoue, and Fukumatsu Iwahashi. This is an open-access article distributed under the terms of Creative Commons Attribution Non-Commercial 4.0 International License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Role of the Extracellular Matrix in Candida Biofilm Antifungal Resistance.

Clinical infection due to Candida species frequently involve growth in biofilm communities. Recalcitrance despite antifungal therapy leads to disease persistence associated with high morbidity and mortality. Candida possesses several tools allowing evasion of antifungal effects. Among these, protection of biofilm cells via encasement by the extracellular matrix is responsible for a majority drug resistance phenotype. The Candida matrix composition is complex and includes a mannan-glucan complex linked to antifungal drug sequestration. This mechanism of resistance is conserved across the Candida genus and impacts each of the available antifungal drug classes. The exosome pathway is responsible for delivery and assembly of much of the Candida extracellular matrix as functional vesicle protein and polysaccharide cargo. Investigations demonstrate the vesicle matrix delivery pathway is a useful fungal biofilm drug target. Further elucidation of the vesicle pathway, as well as understanding the roles of biofilm driven cargo may provide additional targets to aid the diagnosis, prevention, and treatment of Candida biofilms.

Intranasal Nanoemulsions A Potential Strategy for Targeting The Neurodegenerative Disorder: Parkinson's.

Intranasal delivery has great potential to cross the blood-brain barrier and deliver the drug molecule into the central nervous system faster than traditional methods. The olfactory neuronal and trigeminal pathways both are involved in intranasal delivery. The nano-technology is an innovative strategy for the nose to brain delivery. The mucoadhesive nanoemulsion formulation is a modified technology that increases the duration of drug accumulation and provides prolonged delivery at a targeted site. The nanoemulsion formulation oil, surfactant, and co-surfactant components maintain lower surface tension and particle coalescence. The globule dimension and zeta potential are affected in brain targeting. The globule size of the innovative formulation should be < 200 nm for drug permeation because, in humans, the average axon magnitude ranges from around 100 to 700. Furthermore, modified technology of nanoemulsion like nanogel and nanoemulsion in-situ gel provide a great advantage to cure neurodegenerative disorders. Therefore, focusing on the innovative pharmaceutical approaches of nanoemulsion in intranasal drug delivery, the current review provides insight into the applications of nanoemulsion in neurodegenerative disorders like Parkinson's disease, which are due to the depletion of dopamine in substania nigra resulting in cardinal motor activity bradykinesia and tremors. The review also touches upon the pathways for intranasal delivery of nanoemulsion, the pathogenesis of Parkinson's disease, and the future direction of the research on intranasal nanoemulsion.

Hydrobiogeochemical Controls on the Delivery of Dissolved Organic Matter to Boreal Headwater Streams

AbstractUnderstanding controls on the delivery of dissolved organic matter (DOM) from terrestrial to aquatic systems is key for constraining carbon balances and fluxes in boreal headwater catchments. The largest export of DOM generally occurs during intense periods of water delivery to the landscape (e.g., rain events); however, the timing and magnitude of DOM is complicated by geomorphological, hydrometeorological, and biogeochemical variability. To better assess mechanisms controlling the delivery of DOM to boreal streams, DOM was investigated in two morphologically distinct catchments of an experimental forest watershed in western Newfoundland, one dominated by low relief wetlands and the other by steep hillslopes. The DOM was compared during two fall storms of similar magnitude but contrasting moisture conditions during the autumn transition. Variable concentrations and optical character highlighted antecedent conditions are important for the delivery of DOM to boreal streams. Concentration‐discharge relationships with stream hydrograph separation analysis suggest preferential flowpaths through shallow mineral horizons as a key pathway for delivery of DOM in the hillslope dominated catchment compared to rapid input from near‐stream wetlands in the low relief catchment. Loss of DOM via preferential pathways suggests an additional mechanism for surface soil carbon loss not directly informed by lateral flow and soil hydrology, which has important implications for our conceptualization and modeling of carbon fluxes in boreal systems. These results suggest watershed scale responses of DOM in boreal headwater catchments are complex, and better linkages between catchment scale hydrology and landscape hydrobiogeochemistry are required to constrain terrestrial to aquatic carbon fluxes in boreal landscapes.

Managing Local Health System Interdependencies: Referral and Outreach Systems for Maternal and Newborn Health in Three South African Districts

In complex health systems, referral and outreach systems (ROS) are formal strategies for connecting and managing interdependencies between facilities in service delivery pathways. Well-functioning maternal and newborn ROS are critical to successful outcomes, and therefore, a good lens through which to examine the management of local interdependencies. We conducted a qualitative study of maternal–newborn ROS, involving interviews with 52 senior, middle, and frontline managers, in three health districts of three different provinces in South Africa. We analyse the differences in functioning of ROS as an interplay of setting (urban, rural), individual facility strengths and weaknesses, the quality of emergency medical services (EMS), and the wider provincial strategic and organisational context. ROS are strengthened by sub-district governance arrangements that recognise and enable connectedness—in particular, between primary health care and district hospital services; by informal, day-to-day communication and collaboration across levels and professions; and by hybrid clinical–managerial players as system brokers and systems thinkers. We also identify leverage points, places where small shifts could have wider system effects, most notably in the design and functioning of EMS, and in addressing small, but significant bottlenecks in supply chains in lower level facilities that negatively impact the system as a whole.

Rubusoside As a Multifunctional Stabilizer for Novel Nanocrystal-Based Solid Dispersions with a High Drug Loading: A Case Study

The oral bioavailability of poorly soluble drugs has always been the focus of pharmaceutical researchers. We innovatively combined nanocrystal technology and solid dispersion technology to prepare novel nanocrystalline solid dispersions (NCSDs), which enable both the solidification and redispersion of nanocrystals, offering a promising new pathway for oral delivery of insoluble Chinese medicine ingredients. The rubusoside (Rub) was first used as the multifunctional stabilizer of novel apigenin nanocrystal-based solid dispersions (AP-NSD), improving the in vitro solubilization rate of the insoluble drug apigenin(AP). AP-NSD has been produced using a combination of homogenisation and spray-drying technology. The effects of stabilizer type and concentration on AP nanosuspensions (AP-NS) particles, span, and zeta potential were studied. And the effects of different types of protective agents on the yield and redispersibility of AP-NSD were also studied. Furthermore, AP-NSD was characterized by infrared spectroscopy (IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). Solubility was used to assess the in vitro dissolution of AP-NSD relative to APIs and amorphous solid dispersions (AP-ASD), and AP-ASD was prepared by the solvent method. The results showed that 20% Rub stabilized AP-NSD exhibited high drug-loading and good redispersibility and stability, and higher in vitro dissolution rate, which may be related to the presence of Rub on surface of drug. Therefore provides a natural and safe option for the development of formulations for insoluble drugs.

Chitosan-Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery.

The current study paves the way for improved chemotherapy by creating pH-responsive nanogels (NGs) (GC1 and GC2) loaded with synthetic ruthenium(II) arene complexes to increase biological potency. NGs are fabricated by the conjugation of chitosan (CTS)-biotin biopolymers that selectively target the cancer cells as CTS has the pH-responsive property, which helps in releasing the drug in cancer cells having pH ∼ 5.5, and biotin provides the way to target the cancer cells selectively due to the overexpression of integrin. The synthesized compounds and NGs were thoroughly characterized using various spectroscopic and analytical techniques such as NMR, electrospray ionization-mass spectrometry, Fourier transform infrared, UV-vis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, rheology, Brunauer-Emmett-Teller, and others. NGs displayed exceptional increased efficacy toward cancerous cells with IC50 values ranging from 7.50 to 18.86 μM via induced apoptosis in three human cancer cell lines. Apart from its potency, NGs were found to be highly selective toward cancer cells. Moreover, based on the results of immunoblot analysis, it was observed that the synthesized compounds exhibit a significant increase in the expression of cleaved caspase-3 and a decrease in the expression of the antiapoptotic protein BCL-XL. Interestingly, the complexes were discovered to have the additional capability of catalyzing the conversion of NADH to NAD+, leading to the generation of radical oxygen species within the cells. Additionally, it was discovered that NG-induced apoptosis depends on ROS production and DNA binding. A narrower range of LD50 values (1185.93 and 823.03 μM) was seen after administering NGs to zebrafish embryos in vivo. The results support the use of drug-loaded NGs as potential chemotherapeutic and chemopreventive agents for human cancer cells.

Inferring drivers of nitrate and sediment event dynamics from hysteresis metrics for two large agricultural watersheds

AbstractExcess nitrate and sediment, mobilized by precipitation events and transported into surface waters, is a global water quality challenge. Recent advances in high‐frequency in situ water quality monitoring sensors have created opportunities to investigate constituent concentration dynamics during short‐term hydrological changes. In this study, we characterized the event‐scale variability of nitrate () and turbidity (a surrogate for sediment transport) in two large agricultural watersheds of the Upper Mississippi River Basin using hysteresis loop characteristics to determine sources and dominant transport mechanisms. We then applied factor analysis to detect variable groupings and thus determine controls on nitrate and sediment dynamics. We observed consistent counterclockwise hysteresis patterns between the two watersheds. This was indicative of distal contributions and/or late‐event mobilization and flushing, which was controlled by the characteristics of the event hydrology (such as, event duration and magnitude of event discharge). However, turbidity hysteresis loops indicated different sediment delivery behaviours between the two watersheds. The smaller watershed with more diverse land use demonstrated consistent clockwise hysteresis patterns indicating early event flushing or rapidly responding pathways. The time lag between turbidity and discharge peaks was identified as a driver of hysteresis magnitude for the smaller site. In contrast, the larger and more agricultural watershed showed variability between dilution versus flushing as well as delivery pathways between events. The hysteresis magnitude was driven by the event peak discharge and discharge range demonstrating an increase in stream power with scale influenced sediment dynamics at the larger site that switched behaviour. This result is critical for watershed water quality management, especially in the context of a changing climate and further underscores the utility of high‐frequency sensors monitoring data to offer deep insights into hydrological processes controls on contaminant transport and delivery.

THE MANAGEMENT OF DELIVERY PAIN: A BIBLIOMETRIC ANALYSIS

&lt;p&gt;&lt;strong&gt;Introduction&lt;/strong&gt;: Management of delivery pain was part of the most important tasks that health workers need to focus on. Non-pharmacological and pharmacological approaches have been shown to provide significant benefits in managing delivery pain and ensuring the well-being of the mother and her baby. This study analyses research trends on management of delivery pain.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The documents from 2013 to 2022 (December 31, 2022) were searched, in English, Article and Review. The implementation date of the strategy is April 11, 2023 and search terms and strategies are as follows “delivery” OR “pain management” AND “Articles and Reviews” AND “English”. Visualization and analysis of research trends from downloaded article data in CSV format using VOSviewer 1.6.18.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results&lt;/strong&gt;: To achieve this goal, a bibliometric analysis was conducted on 469 articles obtained from the Scopus database, which identified the most productive countries/regions, journals, authors, and potential future topics of this research field. According to this study, 2017 saw the most significant growth; the United States was the most productive country in this field; BMC Pregnancy and Childbirth was the most prestigious journal in this field; Khildea, S., contributed the most significant research in this field. The use of complementary therapies, drug administration and maternal care requires further study in the future.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion&lt;/strong&gt;: The conclusion of this study was that pain management continues to grow in research across different countries, fields and expertise. The future needs to focus on the use of complementary therapies, drug delivery pathways and maternal care for further research.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Extracellular vesicles targeting tumor microenvironment in ovarian cancer

Ovarian cancer (OC) is a prevalent neoplastic condition affecting women. Extracellular vesicles (EVs), nano-sized membrane vesicles, are secreted by various cells in both physiological and pathological states. The profound interplay between EVs and the tumor microenvironment (TME) in ovarian cancer is crucial. In this review, we explores the pivotal role of EVs in facilitating intercellular communication between cancer cells and the TME, emphasizing the potential of EVs as promising diagnostic markers and innovative therapeutic targets for ovarian cancer. The comprehensive analysis outlines the specific mechanisms by which EVs engage in communication with the constituents of the TME, including the modulation of tumor growth through EVs carrying matrix metalloproteinases (MMPs) and EV-mediated inhibition of angiogenesis, among other factors. Additionally, the we discuss the potential clinical applications of EVs that target the TME in ovarian cancer, encompassing the establishment of novel treatment strategies and the identification of novel biomarkers for early detection and prognosis. Finally, this review identifies novel strategies for therapeutic interventions, such as utilizing EVs as carriers for drug delivery and targeting specific EV-mediated signaling pathways. In summary, this manuscript offers valuable insights into the role of EVs in ovarian cancer and highlights the significance of comprehending intercellular communication in the realm of cancer biology.

Foraging on sand particles: Coatings of soft radular teeth (Paludomidae, Gastropoda, Mollusca)

AbstractThe radula is the ingesta‐gathering structure in Mollusca. As interface, it has to perform various tasks without functional deterioration caused by wear. Wear prevention is well investigated in mollusks that forage on rocks and that generate high punctual pressure with their hard teeth, which contain high inorganic contents at their tips. In mollusks that forage on softer substrate, such as sand surfaces, and have relatively soft teeth, wear prevention has not been a focus of study before. Here, we studied the teeth of Limnotrochus thomsoni, which are used for raking algae from sand. For comparison, we investigated the soft outer teeth of Lavigeria grandis, which are used in gathering particles after the ingesta is loosed from the rock surface. SEM revealed scratches on all surfaces of the teeth and suggests that every tooth side interacts with abrasive particles during foraging. Analysis of stomach content revealed that sand particles of 10–20 μm diameter are ingested. By EDX/EDS, we studied the composition of the teeth and determined that high proportions of Ca are present on all surfaces, which could be an adaptation to reduce abrasion. Finally, we here present evidence for the existence of a canal within the teeth, which could potentially serve as delivery pathway of minerals during tooth maturation and has not been previously detected in Gastropoda.

Contrasting mercury contamination scenarios and site susceptibilities confound fish mercury burdens in Suriname, South America

In Suriname, mercury (Hg) use has recently increased because of gold mining, which has put fish-reliant communities (e.g., Indigenous and Tribal) at risk of enhanced Hg exposure through the riverine fish these communities consume. To quantify how the magnitude of these risks change according to location and time, we measured total mercury (HgT) in fish at sites downstream and upstream of an artisanal and small-scale gold mining (ASGM) operation in 2004–2005 and in 2017–2018. We tested whether fish HgT burdens over dynamic ranges were increased. Surprisingly, our findings did not support broadly increased fish Hg burden over time or that proximity to ASGM was diagnostic to fish HgT-burden. Subsequently, we elected to test the HgT stable isotope ratios on a set of freshly collected 2020 fish to determine whether differences in Hg source and delivery pathways might cofound results. We found that remote unmined sites were more susceptible to gaseous elemental Hg deposition pathways, leading to enhanced risk of contamination, whereas ASGM proximate sites were not. These results highlight that elemental mercury releases from ASGM practices may have significant impact on fish-reliant communities that are far removed from ASGM point source contamination.

Graphene Quantum Dots for Multifaceted Diagnostics

Due to their unique physical and electronic properties as well as high biocompatibility and water solubility, functionalized graphene quantum dots (GQDs) have found utilization in a variety of biomedical applications. GQDs can serve as carriers for drugs and genes while tracing their delivery pathways in vitro and in vivo with their visible and near-infrared fluorescence. In addition to therapeutic applications, our recent work explores diagnostic modalities of these novel nanomaterials. GQDs synthesized bottom-up form a single glucosamine precursor, or top-down from reduced graphene oxide can serve as nanoscale temperature sensors for biological processes. They exhibit linear and reversible visible/NIR fluorescence quenching by up to 19.3 % in suspension with temperature increase form 25 to 49 ⁰C. A more pronounced trend is observed in HeLa cells with over 40% quenching in that temperature range. Our findings suggest that such deterministic response can serve as non-invasive reversible/photostable mechanism for temperature sensing in microscopic subcellular biological environments. Another diagnostic modality of GQDs involves their capability for magnetic resonance imaging. When doped with Mn2+ ions during their bottom-up synthesis, GQDs exhibit substantial r₂/r₁ relaxation parameter ratios of 11.19, showing potential as dual-mode T1 or T2 contrast agents. Their Gd3+-doped counterparts possess r₂/r₁ ratios of 1.148 with high r1 of 9.546 mM-1s-1 compared to commercial contrast agents, suggesting their utilization as T1 contrast agents. Given that doping did not affect their biocompatibility or fluorescence properties, such doped GQDs can serve as multimodal MR and fluorescence imaging agents. Metal-doped GQDs possess the capability ultrasonic contrast imaging that can be utilized for higher precision and deeper tissue diagnostic applications. They demonstrate high-contrast properties in ultrasound brightness mode by a factor of 10 surpassing undoped GQD structures. The successful imaging enhancement was observed in tissue phantom and animal tissue, suggesting that GQDs can be tracked by ultrasound imaging and used as contrast agents for the improvement of the deterministic power of this widely available imaging approach. GQD intrinsic fluorescence can itself serve as a non-invasive diagnostic sensing tool, as it can be affected by the binding of different drugs, genes and biomolecules to the GQDs. This optical sensing mechanism is used in our work for identifying trace quantities of cancer-generated genes for early personalized cancer detection. The sensor is prepared from GQDs complexed with the bait DNA sequence complementary to the target pancreatic cancer miRNA. It effectively discriminates between complementary single-stranded DNA sequences and random control genes with the sensitivity in the nanomolar range. Cancer gene detection is further verified by identifying both, the stem and the loop portions of the pancreatic cancer-generated pre-miR-132. Given the success of these different diagnostic applications, GQDs can be considered a highly perspective theragnostic tool for a variety of disease targets.

Lipid-based nanoparticles via nose-to-brain delivery: a mini review.

Central nervous system disorders significantly affect the lives and health of millions of people worldwide. Despite many therapeutic drugs are available that could potentially target central nervous system disorders, their clinical utility is severely constrained by their inability to cross the blood-brain barrier (BBB). Fortunately, nanotechnology has been advanced to offers a solution to allow drugs reaching the targeted brain regions safely, efficiently, and precisely through nasal drug delivery system (NDDS), bypassing the BBB completely. This strategy can promote the drug accumulated in the targeted brain region, improve drug bioavailability, and minimal side effects and mucociliary clearance effectively. In this review, we elaborate recent advances in the use of lipid-based nanoparticles, involving liposomes, nanoemulsions, nanostructured lipid carriers, and solid lipid nanoparticles. Besides, we particularly introduced the nasal cavity physiological structure, and further summarized the nose-to-brain drug delivery pathways, including olfactory, trigeminal, and blood circulation pathway. Moreover, the mechanism and route of NDDS by various types of nanoparticles are also highlighted.

Atmospheric microplastic transport and deposition to urban and pristine tropical locations in Southeast Asia

Atmospheric microplastic transport is an important delivery pathway with the deposition of microplastics to ecologically important regions raising environmental concerns. Investigating atmospheric delivery pathways and their deposition rates in different ecosystems is necessary to understanding its global impact. In this study, atmospheric deposition was collected at three sites in Malaysia, two urban and one pristine, covering the Northeast and Southwest monsoons to quantify the role of this pathway in Southeast Asia. Air mass back trajectories showed long-range atmospheric transport of microplastics to all sites with atmospheric deposition varying from 114 to 689 MP/m2/day. For the east coast of Peninsular Malaysia, monsoonal season influenced microplastic transport and deposition rate with peak microplastic deposition during the Northeast monsoon due to higher wind speed. MP morphology combined with size fractionation and plastic type at the coastal sites indicated a role for long-range marine transport of MPs that subsequently provided a local marine source to the atmosphere at the coastal sites.

Transport by circulating myeloid cells drives liposomal accumulation in inflamed synovium.

The therapeutic potential of liposomes to deliver drugs into inflamed tissue is well documented. Liposomes are believed to largely transport drugs into inflamed joints by selective extravasation through endothelial gaps at the inflammatory sites, known as the enhanced permeation and retention effect. However, the potential of blood-circulating myeloid cells for the uptake and delivery of liposomes has been largely overlooked. Here we show that myeloid cells can transport liposomes to inflammatory sites in a collagen-induced arthritis model. It is shown that the selective depletion of the circulating myeloid cells reduces the accumulation of liposomes up to 50-60%, suggesting that myeloid-cell-mediated transport accounts for more than half of liposomal accumulation in inflamed regions. Although it is widely believed that PEGylation inhibits premature liposome clearance by the mononuclear phagocytic system, our data show that the long blood circulation times of PEGylated liposomes rather favours uptake by myeloid cells. This challenges the prevailing theory that synovial liposomal accumulation is primarily due to the enhanced permeation and retention effect and highlights the potential for other pathways of delivery in inflammatory diseases.

RECONSTRUCTION OF SEDIMENT RUNOFF FORMATION FEATURES IN THE LAKE KHORLAKEL (NORTH CAUCASUS) CATCHMENT FOR THE LAST 8 THOUSAND YEARS (ACCORDING TO GEOMORPHOLOGICAL AND LITHOSTRATIGRAPHIC DATA)&lt;a href="#FN2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/a&gt;

The change in sediment yield is an important indicator of the natural environment dynamics, depending on the combination of landscape, tectonic and climatic conditions. Assessment of sediment yield often based on the results of studying the bottom sediments of mountain lakes with relatively compact catchments. However, for correct reconstructions, in addition to analyzing lake sediments, it is necessary to study the causes and mechanizm of sediment redistribution in their catchments, to identify sediment delivery pathways to the reservoir and their possible changes over different time windows. The drainless Lake Khorlakel, located at the altitude of 2045.0 m above sea level on the northern macroslope of the Greater Caucasus. It is a suitable testing ground for complex research: on the one hand, the relict reservoir is an ideal sedimentation trap, and on the other, it is located with in an area of intensive exogenous processes and tectonic activity. The two boreholes were drilled in 2017 in the deepest (≈8 m) part of the lake and 17 samples collected taken from the cores for radiocarbon dating, which made it possible to build an age model for the range from 8000 to 500 yr. BP. Complex geological and geomorphological studies were carried out in 2021 to interpret the obtained data. It was found that sedimentation in the lake is associated with runoff and sediment redistribution in the Elbashi creek catchment. A number of episodes of proluvial activation with the formation of an outflow cone, followed by lake accumulation, have been traced for the last 8 kyr. The connection between lake and catchment ceased only in the last 1 kyr. BP. Two main stages of lake sedimentation with a boundary of 3 kyr. BP and 10 episodes, that are characterized by different proportions of mineral and organic components in bottom sediments were established. Some of the lithostratigraphic boundaries correlate with strong earthquakes that occurred in the Elbrus region, and some – with climatic events.