Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization.

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products.

Global PM2.5 Prediction and Associated Mortality to 2100 under Different Climate Change Scenarios.

Ambient fine particulate matter (PM2.5) has severe adverse health impacts, making it crucial to reduce PM2.5 exposure for public health. Meteorological and emissions factors, which considerably affect the PM2.5 concentrations in the atmosphere, vary substantially under different climate change scenarios. In this work, global PM2.5 concentrations from 2021 to 2100 were generated by combining the deep learning technique, reanalysis data, emission data, and bias-corrected CMIP6 future climate scenario data. Based on the estimated PM2.5 concentrations, the future premature mortality burden was assessed using the Global Exposure Mortality Model. Our results reveal that SSP3-7.0 scenario is associated with the highest PM2.5 exposure, with a global concentration of 34.5 µg/m3 in 2100, while SSP1-2.6 scenario has the lowest exposure, with an estimated of 15.7 µg/m3 in 2100. PM2.5-related deaths for individuals under 75 years will decrease by 16.3 and 10.5% under SSP1-2.6 and SSP5-8.5, respectively, from 2030s to 2090s. However, premature mortality for elderly individuals (>75 years) will increase, causing the contrary trends of improved air quality and increased total PM2.5-related deaths in the four SSPs. Our results emphasize the need for stronger air pollution mitigation measures to offset the future burden posed by population age.

Looking back, moving forward: protein corona of lipid nanoparticles.

Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's in vivo fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing ex vivo fluids (e.g., serum-containing culture media) and in vivo fluids (such as blood and tissue fluids). Hence, it is essential to claim the PC formation behaviors and mechanisms on the surface of LNPs. This overview provided a comprehensive examination of crucial aspects related to such issues, encompassing time evolution, controllability, and their subsequent impacts on LNPs. Classical studies of PC generation on the surface of LNPs were additionally integrated, and its decisive role in shaping the in vivo fate of LNPs was explored. The mechanisms underlying PC formation, including the adsorption theory and alteration theory, were introduced to delve into the formation process. Subsequently, the existing experimental outcomes were synthesized to offer insights into the research and application facets of PC, and it was concluded that the manipulation of PC held substantial promise in the realm of targeted delivery.

Nanocrystals: Versatile Platform for Traditional Chinese Medicine Delivery.

The medicinal value of Chinese medicines has been recognized since ancient times, and they have also been used to treat various diseases. However, in-depth studies on the active ingredients of Chinese medicines have shown that many of them suffer from poor water-solubility, stability, and bioavailability, which has severely limited their further development. The advent of nanomedicine represents a novel direction and paradigm for addressing these challenges. Particularly, within the framework of nanocrystal technology, enhancements in the water solubility, stability, and bioavailability of Chinese medicines are expected to significantly improve the therapeutic efficiency. This advancement also holds promise for unlocking new therapeutic capabilities. Nanocrystals offer significant advantages in oral, intravenous, intranasal and targeted delivery. The drug loading principle is "all in one", with hydrophobic-drug-in and hydrophilic-drug-out and stabilization by amphiphilic agents. Nanocrystal technology in traditional Chinese medicine (TCM) holds extensive application potential. Continuous refinement of preparation techniques, sound safety assessments, and the promotion of large-scale production are anticipated to augment its pivotal role in TCM formulations, thereby creating novel opportunities for clinical drug therapy.

Research on nanosciences involvement in pharmaceutical education should be reinforced.

Inclusion of nanoscience in pharmaceutical education should be reinforced, in order to match the demand of current pharmaceutical talent cultivation.

Concurrent measurements of nitrate at urban and suburban sites identify local nitrate formation as a driver for urban episodic PM2.5 pollution.

Nitrate (NO3-) is often among the leading components of urban particulate matter (PM) during PM pollution episodes. However, the factors controlling its prevalence remain inadequately understood. In this work, we analyzed concurrent hourly monitoring data of NO3- in PM2.5 at a pair of urban and suburban locations (28 km apart) in Hong Kong for a period of two months. The concentration gradient in PM2.5 NO3- was 3.0 ± 2.9 (urban) vs. 1.3 ± 0.9 µg m-3 (suburban) while that for its precursors nitrogen oxides (NOx) was 38.1 vs 4.1 ppb. NO3- accounted for 45 % of the difference in PM2.5 between the sites. Both sites were characterized to have more available NH3 than HNO3. Urban nitrate episodes, defined as periods of urban-suburban NO3- difference exceeding 2 µg m-3, constituted 21 % of the total measurement hours, with an hourly NO3- average gradient of 4.2 and a peak value of 23.6 µg m-3. Our comparative analysis, together with 3-D air quality model simulations, indicates that the high NOx levels largely explain the excessive NO3- concentrations in our urban site, with the gas phase HNO3 formation reaction contributing significantly during the daytime and the N2O5 hydrolysis pathway playing a prominent role during nighttime. This study presents a first quantitative analysis that unambiguously shows local formation of NO3- in urban environments as a driver for urban episodic PM2.5 pollution, suggesting effective benefits of lowering urban NOx.

Effect of bromine and iodine chemistry on tropospheric ozone over Asia-Pacific using the CMAQ model.

Recent studies have focused on the chemistry of tropospheric halogen species which are able to deplete tropospheric ozone (O3). In this study, the effect of bromine and iodine chemistry on tropospheric O3 within the annual cycle in Asia-Pacific is investigated using the CMAQ model with the newly embedded bromine and iodine chemistry and a blended and customized emission inventory considering marine halogen emission. Results indicate that the vertical profiles of bromine and iodine species show distinct features over land/ocean and daytime/nighttime, related to natural and anthropogenic emission distributions and photochemical reactions. The halogen-mediated O3 loss has a strong seasonal cycle, and reaches a maximum of -15.9 ppbv (-44.3%) over the ocean and -13.4 ppbv (-38.9%) over continental Asia among the four seasons. Changes in solar radiation, dominant wind direction, and nearshore chlorophyll-a accumulation all contribute to these seasonal differences. Based on the distances to the nearest coastline, the onshore and offshore features of tropospheric O3 loss caused by bromine and iodine chemistry are studied. Across a coastline-centric 400-km-wide belt from onshore to offshore, averaged maximum gradient of O3 loss reaches 1.1 ppbv/100 km at surface level, while planetary boundary layer (PBL) column mean of O3 loss is more moderate, being approximately 0.7 ppbv/100 km. Relative high halogen can be found over Tibetan Plateau (TP) and the largest O3 loss (approximately 4-5 ppbv) in the PBL can be found between the western boundary of the domain and the TP. Halogens originating from marine sources can potentially affect O3 concentration transported from the stratosphere over the TP region. As part of efforts to improve our understanding of the effect of bromine and iodine chemistry on tropospheric O3, we call for more models and monitoring studies on halogen chemistry and be considered further in air pollution prevention and control policy.

Development and application of a hybrid long-short term memory - three dimensional variational technique for the improvement of PM2.5 forecasting.

The current state-of-the-art three-dimensional (3D) numerical model for air quality forecasting is restricted by the uncertainty from the emission inventory, physical/chemical parameterization, and meteorological prediction. Forecasting performance can be improved by using the 3D-variational (3D-VAR) technique for assimilating the observation data, which corrects the initial concentration field. However, errors from the prognostic model cause the correction effects at the first hour to be erased, and the bias of the forecast increases relatively fast as the simulation progresses. As an emerging alternative technique, long short-term memory (LSTM) shows promising performance in air quality forecasting for individual stations and outperforms the traditional persistent statistical models. In this study, a new method was developed to combine a 3D numerical model with 3D-VAR and LSTM techniques. This method integrates the advantage of LSTM, namely its high-accuracy forecasting for a single station and that of the 3D-VAR technique, namely its ability to extend improvement to the whole simulation domain. This hybrid method can effectively improve PM2.5 forecasting for the next 24 h, relative to forecasting with the 3D-VAR technique which uses the initial hour concentration correction. Results showed that the root-mean-square error and normalized mean error were decreased by 29.3% and 33.3% in the validation stations, respectively. The LSTM-3D-VAR method developed in this study can be further applied in other regions to improve the forecasting of PM2.5 and other ambient pollutants.

Application of air parcel residence time analysis for air pollution prevention and control policy in the Pearl River Delta region.

In this study, the concept of air parcel residence time was raised and the APRT was investigated to study its potential application in air pollution prevention and control in the Pearl River Delta (PRD) region. The APRT in the PRD region was defined as the total period for which an air parcel stays within the PRD region. The Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model was used to calculate the hourly APRT in 2012, 2014, and 2015 based on forward trajectories from 16,720 starting locations. The seasonal APRT results revealed that long APRT was mainly distributed in southern PRD in the summer half year, but in northeastern PRD in the winter half year. This is related to the prevailing wind directions in the summer and winter monsoons. Moreover, the comparison of APRT in different years revealed that the dispersion condition was relatively poor in fall in 2012 and throughout 2014 but was relatively favorable in 2015, which also corresponded to the pollutant concentrations. The APRT calculated from regional air pollution days indicated that the emission reduction strategy should be implemented in the key areas, namely the eastern and central Guangzhou, western Huizou, and the border between Foshan and Jiangmen, and the construction of new factories should not be allowed in these areas. Compared to the APRT, which was investigated to trace the air pollution source, population exposure to air parcels (PEAP) was investigated to orient the influence of path-and-time-weighted sources to population. Consequently, a high PEAP was found to be distributed mainly in the central Guangzhou and Shenzhen and scattered in other urban areas.

Analysis of the adverse health effects of PM2.5 from 2001 to 2017 in China and the role of urbanization in aggravating the health burden.

In this study, the trend of PM2.5 concentrations and its adverse health effects in China from 2001 to 2017 are estimated utilizing 1-km high-resolution annual satellite-retrieved PM2.5 data. PM2.5 concentrations for most of the provinces/cities remained stable from 2001 to 2012; however, following the issue of the Air Pollution Prevention and Control Action Plan (APPCAP) by the central government of China, a dramatic decrease in PM2.5 concentrations from 2013 to 2017 occurred. Premature mortality caused by PM2.5 dropped from 1,078,800 in 2014 to 962,900 in 2017. The PM2.5 caused 17-year average mortality ranges from 3800 in Hainan Province to 124,800 in Henan Province. The health cost benefits gained by the reduction of PM2.5 pollution amounted to US $193,800 in 2017 (compared to the costs due to PM2.5 concentrations in 2013), amounting to 1.58% of the total national GDP. The impacts of urbanization on PM2.5 concentration and mortality are analyzed. The PM2.5 concentration and its induced mortality density in dense urban areas are much higher than those in rural areas. The aggravation of PM2.5 associated premature mortality in urban areas is mainly due to the larger amount of emissions and to urban migration, and 6500 deaths in 2014 could have been avoided were the population ratios in dense-urban/normal-urban/rural areas to be reversed to the ones in 2001. It is recommended that people with respiratory-related diseases live in rural areas, where the pollutant concentration is relatively low.

Differences in concentration and source apportionment of PM2.5 between 2006 and 2015 over the PRD region in southern China.

During China's 11th Five Year Plan (FYP) and 12th FYP (2006-2015), a series of air pollution control measures was implemented in the Pearl River Delta (PRD) region. Therefore, it is vital to determine how the concentration and sources of fine particulate matter (PM2.5) in this region changed between 2006 and 2015. In this work, using 2006 and 2015 emission inventories, the concentration and source apportionment of PM2.5 were simulated using the Weather Research and Forecast - Comprehensive Air Quality Model with Extensions (WRF-CAMx) for January, April, July and October in the PRD region. The PM2.5 in 10 cities and the contributions made by sources in six major categories were tracked using the Particulate Source Apportionment Technology (PSAT) module. The results showed that the PM2.5 concentration was lower across the entire PRD region in the 2015 emission scenario than in the 2006 scenario, and that the degree of this reduction exceeded 40 µg/m3 in some places. The PM2.5 contributed by mobile emissions decreased the most, especially in Guangzhou, Foshan and Shenzhen, where mobile contributions decreased from 15.0, 17.9 and 13.0 µg/m3 in 2006 to 2.6, 3.1 and 4.1 µg/m3 in 2015, respectively. The PM2.5 contributed by power plants also decreased, and in Dongguan and Guangzhou, the extent of this reduction reached 2.5 and 3.4 µg/m3 respectively. However, due to an increase in industrial production and population size, the PM2.5 from industrial point sources and area sources also increased between 2006 and 2015 in some of the cities. Investigation of the source apportionment for city centers yielded similar results. In addition to emissions within the PRD region, outside-PRD non-local contribution is still an important PM2.5 contributor. Hence, more stringent policies for controlling industrial and area sources and deepening province-to-province cooperation are urgently needed as the next step in PM2.5 control.

Numerical simulations for the sources apportionment and control strategies of PM2.5 over Pearl River Delta, China, part I: Inventory and PM2.5 sources apportionment.

This article uses the WRF-CMAQ model to systematically study the source apportionment of PM2.5 under typical meteorological conditions in the dry season (November 2010) in the Pearl River Delta (PRD). According to the geographical location and the relative magnitude of pollutant emission, Guangdong Province is divided into eight subdomains for source apportionment study. The Brute-Force Method (BFM) method was implemented to simulate the contribution from different regions to the PM2.5 pollution in the PRD. Results show that the industrial sources accounted for the largest proportion. For emission species, the total amount of NOx and VOC in Guangdong Province, and NH3 and VOC in Hunan Province are relatively larger. In Guangdong Province, the emission of SO2, NOx and VOC in the PRD are relatively larger, and the NH3 emissions are higher outside the PRD. In northerly-controlled episodes, model simulations demonstrate that local emissions are important for PM2.5 pollution in Guangzhou and Foshan. Meanwhile, emissions from Dongguan and Huizhou (DH), and out of Guangdong Province (SW) are important contributors for PM2.5 pollution in Guangzhou. For PM2.5 pollution in Foshan, emissions in Guangzhou and DH are the major contributors. In addition, high contribution ratio from DH only occurs in severe pollution periods. In southerly-controlled episode, contribution from the southern PRD increases. Local emissions and emissions from Shenzhen, DH, Zhuhai-Jiangmen-Zhongshan (ZJZ) are the major contributors. Regional contribution to the chemical compositions of PM2.5 indicates that the sources of chemical components are similar to those of PM2.5. In particular, SO42- is mainly sourced from emissions out of Guangdong Province, while the NO3- and NH4+ are more linked to agricultural emissions.

Numerical simulations for the sources apportionment and control strategies of PM2.5 over Pearl River Delta, China, part II: Vertical distribution and emission reduction strategies.

The contribution of various emission sources to the vertical structure of the PM2.5 concentration and the modeling of emission reduction strategies are emphasized in this study. Analysis of vertical distribution of PM2.5 concentration in the planetary boundary layer (PBL) reveals that strong diurnal cycle exists during the pollution episodes, with heavier surface pollution in nocturnal periods. Contributions from transportation and agriculture are mainly restricted to the surface, while contributions from industry and power are distributed in a relatively higher layer. In the northerly-controlled episodes, the contribution of local emissions mainly accumulates below 300 m and the impact of the emissions from surrounding cities can reach 500-600 m during nocturnal periods. The contributions outside of Guangdong are uniformly distributed within 1000 m altitude. In the daytime, the contribution of emissions is basically uniform throughout the PBL. In the southerly-controlled episodes, the contribution of local emission mainly concentrates below 400 m during the nocturnal periods. Emissions from surrounding cities can exert the influence below 1000 m height, and the contribution outside of Guangdong reaches even 1500 m. In the daytime, the contribution of emissions in the PBL is distributed evenly. The highest altitude of the contribution from different subdomains that can reach is closely related to the physical property of the PBL. The industrial and agricultural emissions are the most important contributors for the surface PM2.5 concentration. Results from emission reduction experiments show that PM2.5 reduces significantly near the pollution center. Although control efficiency decreases with the increasing reduction ratio, the efficiency differences between 30% and 50% reduction is limited. In particular, 10% reduction in industrial emission causes PM2.5 concentration to be slightly higher in the afternoon. Furthermore, below 200-m height, emission reduction experiments perform the effective reduction in PM2.5 concentration, and higher reduction ratio results in larger reduced PM2.5 concentration on almost all layers in the PBL.