High Load Research Articles

Hollow mesoporous calcium peroxide nanoparticles for drug-free tumor calcicoptosis therapy

Calcium ions (Ca2+) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca2+ concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca2+, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy. The average pore size of the optimized HMCPN17 is 6.4 nm, and the surface area is 81.3 m2/g, which enables HMCPN17 with high drug loading capability. The Ca2+ release from HMCPN17 is much faster at pH 6.8 than that at pH 7.4, which can be ascribed to the acid-triggered conversion of HMCPN17 to Ca2+ and H2O2, indicating a pH-responsive decomposition behavior of HMCPN17. The high drug loading contents of doxorubicin (DOX) and/or sorafenib (SFN) indicate that HMCPN17 can be employed as a generic drug delivery system (DDS). The in vitro and in vivo results reinforce the high calcicoptosis therapeutic efficacy of tumors by our HMCPN17 without drug loading, which can be attributed to the efficient accumulation in tumors and the ability of H2O2 and Ca2+ production at acidic TME. Our HMCPN17 has broad application prospect for construction of multi-drug-loaded composite nanomaterials with diversified functions for the treatment of tumors. Statement of significanceThe combination of hollow mesoporous nanomaterials and calcium peroxide nanoparticles has a wide range of applications in the synergistic treatment of tumors. In this study, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed based on a simple hydrolysis-precipitation method for tumor calcicoptosis therapy without drug loading. The high drug loading contents of DOX and/or SFN indicate that our HMCPN can serve as a generic DDS. The experimental results demonstrated the high calcicoptosis therapeutic efficacy of HMCPN on tumors even without drug loading.

Cumulative Blood Pressure Load and Incident CKD

The association of long-term cumulative blood pressure (BP) loads with the risk of incident chronic kidney disease (CKD) remains a matter of debate. This study aimed to investigate this association among healthy Korean adults with normal kidney function. Prospective cohort study. We analyzed 5,221 participants without CKD in the Korean Genome and Epidemiology Study. Cumulative systolic and diastolic BP (SBP and DBP) loads were calculated as the ratios of the areas under the curve (AUC) for SBP ≥120 mmHg or ≥80 mmHg for DBP divided by the AUC for all SBP or DBP measurements during the exposure period. These AUCs were categorized into four groups: group 0 (reference), cumulative BP load of 0 and groups 1-3, tertiles of cumulative BP loads. Primary endpoint was incident CKD defined as a composite of an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 or proteinuria greater than 1+ on dipstick examination for at least two consecutive measurements ≥90 days apart. Multivariable Cox proportional hazards regression to estimate the independent association of cumulative BP loads with incident CKD. Higher cumulative SBP and DBP loads were associated with an increased risk of incident CKD (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.35 for SBP and HR 1.14, 95% CI 1.04-1.26 for DBP loads for each 1.0 unit greater load). Compared to SBP group 0, groups 2 and 3 were associated with 1.94- and 1.89-fold greater risk of incident CKD. Compared to DBP group 0, groups 2 and 3 were associated with 1.42- and 1.54-fold greater risks. These associations of high cumulative BP loads with an increased risk of incident CKD remained consistent even in subgroups not taking antihypertensive agents or without prior hypertension diagnosis. The assessment of CKD outcomes relied on eGFR and spot urine tests. These findings highlight the association between high cumulative SBP and DBP loads and the occurrence of CKD, even in individuals with normal BP levels.

Health professionals implicit bias of patients with low socioeconomic status (SES) and its effects on clinical decision-making: a scoping review

ObjectivesResearch indicates that people with lower socioeconomic status (SES) receive inferior healthcare and experience poorer health outcomes compared with those with higher SES, in part due to health professional (HP)...

Comparison of batch and continuous multi-column capture of monoclonal antibodies with convective diffusive membrane adsorbers

Protein A affinity membrane adsorbers are a promising alternative to resins to intensify the manufacturing of monoclonal antibodies. This study examined the process performance of convective diffusive membrane adsorbers operated in batch and continuous multi-column mode. Therefore, three different processes were compared regarding membrane utilization, productivity, and buffer consumption: the batch process, the rapid cycling parallel multi-column chromatography process, and the rapid cycling simulated moving bed process. The influence of the monoclonal antibody loading concentration (between 0.5 g L-1 and 5.2 g L-1) and the loading flow rate (between 1.25 MV min-1 and 10 MV min-1) on the monoclonal antibody binding behavior of the membrane adsorber were studied with breakthrough curve experiments. The determined breakthrough curves were used to calculate the monoclonal antibody dynamic binding capacity, the duration of the loading steps for each process, and the number of required membrane adsorbers for the continuous processes rapid cycling parallel multi-column chromatography and rapid cycling simulated moving bed. The highest productivity for the batch (176 g L-1 h-1) and rapid cycling parallel multi-column chromatography process (176 g L-1 h-1) was calculated for high monoclonal antibody loading concentrations and low loading flow rates. In contrast, the rapid cycling simulated moving bed process achieved the highest productivity (217 g L-1 h-1) for high monoclonal antibody loading concentrations and loading flow rates. Furthermore, due to the higher membrane utilization, the buffer consumption of the rapid cycling simulated moving bed process (1.1 L g-1) was up to 1.9 times lower than that of the batch or rapid cycling parallel multi-column chromatography operation (2.1 L g-1).

Hydrogen Use in a Dual-Fuel Compression Ignition Engine with Alternative Biofuels

Recent progress has been made towards decarbonisation of transport, which accounts for one quarter of global carbon dioxide emissions. For the short to medium term, new European Union (EU) and national energy and climate plans agree on a strategy based on the combination of increasing shares of electric vehicles with the promotion of sustainable fuels, especially if produced from residual feedstock and routes with low or zero net carbon emission. Hydrogen stands out among these fuels for its unique properties. This work analyses the potential of using hydrogen in a dual-fuel, compression ignition (CI) engine running with three diesel-like fuels (conventional fossil diesel, advanced biodiesel (BD) and hydrotreated vegetable oil (HVO)) and different hydrogen energy substitution ratios. The results were confronted with conventional diesel operation, revealing that dual-fuel combustion with hydrogen demands higher exhaust gas recirculation (EGR) rates and more advance combustion, leading to a remarked reduction of NOx emission at the expense of a penalty in energy consumption due mainly to unburnt hydrogen and wall heat losses. Unreacted hydrogen was ameliorated at high load. At low load, the use of BD dual combustion permitted higher hydrogen substitution ratios and higher efficiencies than diesel and HVO.

Laboratory Testing and Numerical Modeling of Creep Behavior of HDPE Geomembranes under Multistage Loading

Abstract Geomembranes are essential impermeable materials commonly employed in the fields of hydraulic engineering and geoenvironmental engineering. However, their long-term operation may result in significant creep deformation, particularly under high loads. This paper mainly presents the effect of loading mode on the creep characteristics of high-density polyethylene (HDPE) geomembranes. A series of creep tests of geomembranes under multistage loading were conducted and compared with single loading creep tests. Under multistage loading, creep strain increased in a step-like manner. When the cumulative load level is lower than 50 %, the creep of geomembranes can attain a stable state. When the cumulative load level attains 60 %, the creep may enter a constant-rate creep stage. Compared with single loading creep, the creep under multistage loading attained a stable state earlier for a relatively low load level, and the deformations were smaller. The creep strain rate was significantly reduced at a constant-rate creep stage for a relatively high load level. The multistage loading was beneficial to the creep deformation control of geomembranes. Furthermore, an enhanced creep model was proposed to describe the creep behavior under multistage loading, including the stable state and constant-rate creep stage. The predictions were in good agreement with the experimental data.

Symbiotic species diversity can explain invasion success and host–parasite system stability: The case of gammarid hosts

AbstractA major current challenge related to invasions is the absence of a comprehensive theoretical basis for preventing the introduction of alien species and controlling their populations. By using a macroecological framework, we aim to examine patterns of symbiotic species diversity across native and invasive hosts to understand the mechanisms underlying the host–parasite system stability. The symbiotic communities of seven gammarid species, two native and five invasive, were analyzed at 16 fresh and brackish water sites along the Baltic coast of Poland. We investigated the influence of four factors—locality, habitat, host species, and host origin—on diversity patterns and assessed their relative contribution to diversity variation. Our results indicate that all factors are crucial in determining the composition and abundance of symbiotic communities in gammarids. Among these factors, locality and host species apparently have a greater influence on symbiotic communities than habitat conditions and host origin. Comparative analysis of diversity indexes of symbiotic organisms from native and invasive hosts showed that the richer communities of native gammarids were paradoxically less diverse. We assume that these rich and uneven symbiotic communities keep the host–parasite system of native gammarids in equilibrium. Highly dominant symbiotic species with a high load per host individual may stabilize the growth of the host population. Symbiotic communities of the invasive host exhibited lower species richness but displayed a relatively even distribution of species with moderate loads per individual, resulting in a scarcity of heavily infected gammarids within the population. Thus, the survival rate of invasive gammarids is expected to be relatively high, facilitating their population growth and further spread. We conclude that complex communities of native gammarids constructed from many symbiotic species may prevent host populations from undergoing explosive growth, while such mechanisms may be completely or partially reduced in invasive hosts.

Application of an improved simulated annealing algorithm in satellite network routing

Abstract Satellite communication is integral to modern communication systems, yet navigating the intricacies of routing in networks characterized by high loads and dynamic evolution poses a significant challenge. This research is dedicated to enhancing satellite communication routing algorithms, with the goal of bolstering network efficiency and amplifying the success rate of business transmissions. Our approach introduces an improved simulated annealing algorithm incorporating adaptive temperature control and innovative path neighborhood exploration strategies. This novel algorithm is adept at adjusting to ever-shifting network topologies and meeting various business requirements. Our simulation results reveal that this refined algorithm outperforms traditional annealing methods in several critical aspects. It elevates the success rate of business transmissions, reduces the average number of forwardings by 6.546% across various load scenarios, and diminishes system response time by 15.05%, thereby marking a substantial improvement in network performance.

Environmental and performance impacts of 2-ethylhexyl nitrate and ethanol in diesel blends: A comprehensive study

This study investigates the performance and emissions of a compression ignition engine fueled with blends of ethanol and petroleum diesel with 2-EHN (2 ethylhexyl nitrate) as a cetane improver. Three blends, named E20 (20% ethanol with 80% diesel), E20A (20% ethanol, 0.1% 2-EHN, and 79.9% petroleum diesel), E20B (20% ethanol, 0.2% 2-EHN, and 79.8% petroleum diesel), and petroleum diesel were analyzed for their brake thermal efficiency (BTHE), specific fuel consumption, net heat release rate, indicated thermal efficiency, and emissions of carbon monoxide (CO), CO2, hydrocarbon (HC), and NOx. The experiments were conducted at variable loading conditions and at compression ratio of 16.5. Results showed that at no load conditions, petroleum diesel exhibited higher indicated power (IP) compared to E20, E20A, and E20B. However, at full load conditions, blend E20B showed higher IP compared to petroleum diesel, E20, and E20A. The blend E20B at a compression ratio of 16.5 showed the highest BTHE of 27%, compared to petroleum diesel (25%) under full load conditions, making it a better performing fuel. However, at higher loads and compression ratio of 16.5, the blends E20A and E20B exhibited emissions of CO, HC, CO2, and NOx that were significantly higher than diesel and E20 at all load conditions. Specifically, at full load conditions and compression ratio of 16.5, the emissions for each fuel were as follows: CO emission for E20, E20A, and E20B was around 0.01%, much less than petroleum diesel (0.1%); HC emission for E20 (15 ppm), E20A (17 ppm), E20B (10 ppm) was much higher than petroleum diesel (2.5 ppm); CO2 emission for E20, E20A, and E20B was about 13% less than petroleum diesel (15%); and NOx emission for E20, E20A, and E20B was around 150 ppm, comparable with petroleum diesel (140 ppm). These results imply that further improvements are required in using ethanol blended alternate fuel in diesel engines with 2-EHN (cetane improver) to reduce emissions with improved performance.

Tribo-informatics analysis of in-situ TiC reinforced ZA27 alloy: Microstructural insights and wear performance modeling by machine learning

The study examines the performance of ZA27 alloy reinforced with in-situ TiC under high-stress abrasive wear conditions. The ZA27 + 10 wt% TiC composite demonstrates superior wear resistance among all the materials tested. Response surface analysis revealed that increasing the applied load reduces the wear resistance of the specimens. Analysis of worn-out surfaces revealed mild grooves at low loads and deeper grooves at higher loads. The removal of material is mainly caused by ploughing and cutting actions from abrasive surfaces. Machine Learning models were employed to forecast wear rate, coefficient of friction, and temperature. The MLP model excelled, achieving an R² value of 0.88 during testing. Furthermore, feature importance analysis revealed that reinforcement wt% has the maximum influence in predicting the wear rate.

Hygrothermal resilience of typical lightweight steel-framed wall assemblies in hot-humid areas under future climate uncertainty

Ensuring the hygrothermal performance of lightweight steel-framed (LSF) wall assemblies is critical for the sustainability of LSF buildings in hot-humid regions; however, climate change poses new challenges. Therefore, this study aimed to bridge the gap in understanding the characteristics of hygrothermal load changes and the hygrothermal resilience of different LSF wall assemblies. Future climate data for each decade of this century (from 2030 to 2090), under various carbon emission scenarios, were generated based on a typical meteorological year (TMY) for hot-humid areas to evaluate the impact of climate change on hygrothermal loads. The hygrothermal resilience of four typical LSF wall assemblies, with either ventilated rainscreen cladding or face-sealed stucco cladding, with or without external insulation, was evaluated through simulation and comparative analysis. The results indicated that the thermal load would increase with increasing carbon emissions and over time, with the annual average external temperature peaking at 25.8 °C by the end of this century. The frequency of months with a high or critical moisture load would increase, although the moisture load may fluctuate across scenarios and years. Consequently, the cooling and dehumidification loads may increase by 52–60 % and 40–88 %, respectively. The hygrothermal risk within the walls may increase, with maximum increases of 2.8–8.0 % in the annual average relative humidity, 2.7–3.0 °C in the annual average temperature, and 10–35 % in the wetness duration. However, the impacts could be reduced by using ventilated rainscreens and external insulation, with further precautions needed to mitigate the increasing hygrothermal risk in areas with thermal bridges and rainwater leakage, as well as at the outer interface of the external insulation. These findings could provide a reference for the design of LSF buildings adapted to climate change in hot-humid areas.

Cultivation of a naturally resilient Chlorella sp.: A bioenergetic strategy for valorization of cheese whey for high nutritional biomass production

This study investigated Chlorella's capacity to treat cheese whey (CW) effluent and produce a high-nutritional value biomass, by using a systematic sequential experimental design. Physicochemical analysis of CW revealed its high pollution load, characterized by elevated levels of lactose, phosphorus, and nitrogen, as well as high turbidity due to the presence of whey solids. Screening experiments demonstrated that trace mineral addition and continuous air supply are essential factors for Chlorella biomass production in CW (>800 mg·mL−1). Furthermore, whey solids did not hinder Chlorella growth, with notable biomass production observed even in undiluted CW, demonstrating this microalga's ability to adapt metabolically to the complex environment. Laboratory-scale photobioreactor experiments confirmed Chlorella's ability to produce biomass in CW, outperforming controls (>800 mg·mL−1). Bioremediation potential assessment exhibited significant reductions in organic pollutants (>14 g·L−1 COD), nitrogen (>400 mg·L−1), phosphorus (>140 mg·L−1) and sodium (>650 mg·L−1). CW solids were also removed with Chlorella harvesting (>99 %). Harvested algal biomass was enriched with proteins (>40 g·100 g−1), polyunsaturated fatty acids (>9 % TFA) and pigments, offering potential applications in nutraceutical and pharmaceutical industries. Overall, this study highlights Chlorella's efficacy in CW treatment and biomass valorization, offering a sustainable solution for dairy wastewater management while producing valuable resources.

Combinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs.

Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that the combined actions of both cytokines are essential for resistance to OPC. Mice lacking IL-17RA and IL-22RA1 exhibited high fungal loads in esophagus- and intestinal tract, severe weight loss, and symptoms of colitis. Ultimately, mice succumbed to infection. Dual loss of IL-17RA and IL-22RA impaired expression of small proline rich proteins (SPRRs), a class of antimicrobial effectors not previously linked to fungal immunity. Sprr2a1 exhibited direct candidacidal activity in vitro, and Sprr1-3a-/- mice were susceptible to OPC. Thus, cooperative actions of Type 17 cytokines mediate oral mucosal anti-Candida defenses and reveal a role for SPRRs.

Wind Tunnel Testing of Tethered Inflatable Wings

A wind tunnel testing approach for tethered inflatable wings is presented. Use cases for such wings range from airborne wind energy systems to high-altitude communication platforms. The tests were conducted for two tethered inflatable wings, one made out of nylon fabric and the other an ultra-high-molecular-weight polyethylene fabric. They were tested within a speed range of 15–32.5 m/s for three tether attachment configurations. Stereo photogrammetry data, force and moment measurements, and wake pressure measurements were recorded for each speed and test configuration. These measurements provide an experimental database for aeroelastic model validation and comparison with high-fidelity computational fluid dynamics studies. The effects of wing fabric material and tether attachment configurations on aerodynamic performance were explored and found to have a profound impact. These tests also highlight the possibility of passive aeroelastic tailoring of the wing configuration to achieve desired aerodynamic performance in the form of high lift and load alleviation. Some testing challenges and possible sources of measurement uncertainty are also discussed.

Phase evolution of Nd3+-doped natural garnet minerals systems: A potential host phase for trivalent actinide immobilization

The immobilization of long-lived actinides produced from spent fuel reprocessing poses a significant environmental concern. In this work, we synthesized glass-ceramics at low temperatures using natural garnet minerals as precursors to immobilize trivalent actinides. Two primary metrics, the quantitative distribution of Nd3+ in glass-ceramics and its leaching rate, were employed to explore the mechanism of Nd3+ immobilization in glass-ceramic products. XRD results show that the primary crystalline phase of the glass-ceramics transitions from calcium feldspar and spinel to oxyapatite with increasing Nd2O3 content. Within a specific range, the proportion of Ca2Nd8(SiO4)6O2 in the samples increases from 37.9 % to 57.9 % with rising Nd2O3 content, while the glassy phase proportion decreases. The distribution of Nd3+ in Ca2Nd8(SiO4)6O2-based glass-ceramics was quantitatively investigated using a combination of TEM-EDX and Rietveld refinement calculations. Nearly 70 % of Nd was found to benefit from a double sealing barrier (Oxyapatite + glass) even under high Nd2O3 loading. A 42-day leaching experiment was conducted using deionized water as the medium. The data demonstrated that Ca2Nd8(SiO4)6O2-based glass-ceramics exhibited a lower Nd-normalized leaching rate(LRNd∼10−5 g m−2 d−1) in solution compared to products solely relying on the glass network for actinide immobilization. This work introduces a cost-effective natural solution for trivalent actinide immobilization.

Avian influenza overview March-June 2024.

Between 16 March and 14 June 2024, 42 highly pathogenic avian influenza (HPAI) A(H5) virus detections were reported in domestic (15) and wild (27) birds across 13 countries in Europe. Although the overall number of detections in Europe has not been this low since the 2019-2020 epidemiological year, HPAI viruses continue to circulate at a very low level. Most detections in poultry were due to indirect contact with wild birds, but there was also secondary spread. Outside Europe, the HPAI situation intensified particularly in the USA, where a new A(H5N1) virus genotype (B3.13) has been identified in >130 dairy herds in 12 states. Infection in cattle appears to be centred on the udder, with milk from infected animals showing high viral loads and representing a new vehicle of transmission. Apart from cattle, HPAI viruses were identified in two other mammal species (alpaca and walrus) for the first time. Between 13 March and 20 June 2024, 14 new human cases with avian influenza virus infection were reported from Vietnam (one A(H5N1), one A(H9N2)), Australia (with travel history to India, one A(H5N1)), USA (three A(H5N1)), China (two A(H5N6), three A(H9N2), one A(H10N3)), India (one A(H9N2)), and Mexico (one fatal A(H5N2) case). The latter case was the first laboratory-confirmed human infection with avian influenza virus subtype A(H5N2). Most of the human cases had reported exposure to poultry, live poultry markets, or dairy cattle prior to avian influenza virus detection or onset of illness. Human infections with avian influenza viruses remain rare and no human-to-human transmission has been observed. The risk of infection with currently circulating avian A(H5) influenza viruses of clade 2.3.4.4b in Europe remains low for the general public in the EU/EEA. The risk of infection remains low-to-moderate for those occupationally or otherwise exposed to infected animals or contaminated environments.

High HTLV-1 Proviral Load Predates and Predicts HTLV-1-Associated Disease: Literature Review and the London Experience.

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood mononuclear cells (PBMCs) using quantitative polymerase chain reaction. In this narrative review, we discuss the usefulness of HTLV-1 PVL quantification and share our experience acquired during more than 30 years of follow-up of people living with HTLV-1 in the UK. Patients with HTLV-1-associated myelopathy have higher PVL than those with asymptomatic infection. This is consistent across studies in different countries. High PVL predates symptom onset for both inflammatory and proliferative diseases. High PVL is essential but not sufficient for the development of HTLV-1-associated diseases. Therefore, PVL quantification can be used to support the care of people living with HTLV-1 by identifying those most at risk of HTLV-1-associated diseases.

Low-toxic gelcasting of zircon ceramics

Zircon (ZrSiO4) ceramics are highly valued in various industries due to their exceptional physical and chemical properties. In the present work, zircon ceramics with high-density and desirable mechanical properties were successfully prepared using an aqueous gelcasting method, involving the use of a low-toxic and water-soluble monomer, N,N-dimethylacrylamide (DMAA), as the binder. A high solid loading and low viscosity zircon slurry was achieved by optimizing the pH and the dosage of the ammonium polyacrylate (PAA-NH3) dispersant. Zircon green bodies fabricated through the gelcasting method exhibited uniform microstructures and relatively high mechanical strength exceeding 11.0 MPa. The impact of solid loading on the density, decomposition, flexural strength, micro-hardness, and microstructure of the final ceramics were carefully studied. Notably, the ceramics, prepared by solidifying the slurry with a 45 vol% solid loading and sintering the green body at 1550 °C for 2 h, exhibited a relative density of 96.3 %, high phase purity, a uniform microstructure, and the highest flexural strength of 407.9 MPa. The results demonstrate that mechanically robust dense zircon ceramics can be effectively prepared using the low-toxic gelcasting method.

Enhancing efficiency in ethanol production from high solid corn stover: Insights into enzymatic hydrolysis parameters and cellulase recovery

BackgroundThe simultaneous saccharification and co-fermentation (SSCF) at high solid loading is an effective approach to improve the economic feasibility of bioethanol. MethodsIn this study, the high-solid SSCF of superfine grinding corn stover was treated with cheap and readily available deionized water (DW) instead of sodium citrate buffer solution (SCBS). Additionally, the evaluation of temperature, enzyme loading, solid loading, and cellulose recovery were carried out to determine their impact on ethanol production. Significant FindingsThe results of the analysis indicated that replacing SCBS with DW had negligible effects on the SSCF of ethanol and byproducts (acetic acid and glycerol). The ethanol yield increased by 18 % at 35 °C compared to the yield at 30 °C. As enzyme loading increased, more cellulose active sites in corn stover were bound by cellulase, which increased the ethanol yield by improving the efficiency of enzymatic hydrolysis. The SSCF process didn't incorporate any buffer, resulting in an even higher ethanol titer (55.42 g/L). Furthermore, the cellulase productivity increased by 71 % after recovery, compared to the non-recovery. The results indicated that the optimized SSCF process is a potential technique for producing bioethanol on a commercial level because it improves the production efficiency while keeping costs low.

Targeted therapy of glomerulonephritis via salvianolic acid b-loaded biomimetic hybrid nanovesicles driven by homing

BackgroundMesangial cell (MC)-mediated immune inflammatory injury is a basic pathological process in glomerulonephritis. However, due to the limited drug accumulation and serious adverse effects, it remains challenging to explore a rational delivery system integrating high efficiency and low toxicity to deliver anti-inflammatory drugs to the glomerular MC region. ResultsSalvianolic acid B (SAB)-loaded hybrid membrane biomimetic nanovesicles (SAB@HMVs) were developed by fusing erythrocyte membrane nanovesicles with mesenchymal stem cells biomimetic membrane nanovesicles. SAB@HMVs had a spheroidal structure, low cytotoxicity, particle size of 143.83 ± 1.33 nm and exhibited a high drug loading capacity (7.02 %±0.30 %) along with a good sustained release function. The in vitro anti-inflammatory results revealed that HMVs were effectively taken up by MCs and showed significant anti-inflammatory activity. Furthermore, in vivo pharmacodynamic studies revealed that SAB@HMVs could deliver SAB to kidney tissue and elicit an effective anti-inflammatory response to improve the pathological changes in the glomerular mesangial region, significantly reducing the levels of cytokines and alleviating kidney inflammation. Especially, noteworthy was the observation that SAB@HMVs augmented the renal delivery of SAB, downregulated the gene expression of p38 MAPK and NF-κB, inhibited the levels of MMP9 and TNF-α proteins as well as elevated the level of iκB protein, indicating that the anti-inflammatory mechanism of SAB@HMVs should be based on regulating MAPK and NF-κB signaling pathways. ConclusionWe provided a novel strategy to increase nanovesicles accumulation in MCs with the potential to exert anti-inflammatory regulatory effects in glomerulonephritis. Furthermore, this biomimetic hybrid membrane loaded with pure drugs may offer a functional platform to address multiple clinical needs.