Search Results (85)

This study presents a comprehensive analysis of the microphysical structures of Meiyu heavy rainfall (near-surface rainfall intensity > 8 mm/h) across different life stages in the Yangtze-Huaihe River Valley (YHRV). We classified the heavy rainfall events into three life stages of developing, mature, and dissipating using ERA5 reanalysis and IMERG precipitation estimates, and examined vertical microphysical structures using Dual-frequency Precipitation Radar (DPR) data from the Global Precipitation Measurement (GPM) satellite during the Meiyu period from 2014 to 2023. The results showed that convective heavy rainfall during the mature stage exhibits peak radar reflectivity and surface rainfall rates, with the largest near-surface mass weighted diameter (D_m ≈ 1.8 mm) and the smallest droplet concentration (dBN_w ≈ 38). Downdrafts in the dissipating stage preferentially remove large ice particles, whereas sustained moisture influx stabilizes droplet concentrations. Stratiform heavy rainfall, characterized by weak updrafts, displays narrower particle size distributions. During dissipation, particle breakups dominate, reducing D_m while increasing dBN_w. The analysis of the relationship between microphysical parameters and rainfall rate revealed that convective heavy rainfall shows synchronized growth of D_m and dBN_w during the developing stage, with D_m peaking at about 2.1 mm near 70 mm/h before stabilizing in the mature stage, followed by small-particle dominance in the dissipating stage. In contrast, stratiform rainfall exhibits a “small size, high concentration” regime, where the rainfall rate correlates primarily with increasing dBN_w. Additionally, convective heavy rainfall demonstrates about 22% higher precipitation efficiency than stratiform systems, while stratiform rainfall shows a 25% efficiency surge during the dissipation stage compared to other stages. Full article

Respiratory syncytial virus (RSV) is a major human respiratory pathogen, particularly affecting infants, the elderly, and immunocompromised individuals. RSV exists in both spherical and filamentous forms, with the filamentous morphology associated with enhanced infectivity and cell-to-cell spread. Here, we demonstrate that RhoA, a small GTPase involved in cytoskeletal regulation, is essential for filamentous RSV morphogenesis through its role in organizing lipid raft microdomains. Rhosin, a selective RhoA inhibitor developed through structure-guided screening, disrupts GEF–RhoA interactions to block RhoA activation. The pharmacological inhibition of RhoA with Rhosin significantly reduced filamentous virion formation, disrupted RSV fusion (F) protein colocalization with lipid rafts, and diminished cell-to-cell fusion, without affecting overall viral replication. Scanning electron microscopy revealed that Rhosin-treated infected HEp-2 cells exhibited fewer and shorter filamentous projections compared to the extensive filament formation seen in untreated cells. β-galactosidase-based fusion assays confirmed that reduced filamentation corresponded with decreased cell-to-cell fusion. The biophysical separation of RSV spherical and filamentous particles by sucrose gradient velocity sedimentation, coupled with fluorescence and transmission electron microscopy, showed that Rhosin treatment shifted virion morphology toward spherical forms. This suggests that RhoA activity is critical for filamentous virion assembly, which may enhance viral spread. Immunofluorescence microscopy using lipid raft-selective dyes (DiIC₁₆) and fusion protein-specific antibodies revealed the strong co-localization of RSV proteins with lipid rafts. Importantly, the pharmacological inhibition of RhoA with Rhosin disrupted F protein partitioning into raft domains, underscoring the requirement for intact lipid rafts in assembly. These findings highlight a novel role for host RhoA signaling in regulating viral assembly through raft microdomain organization, offering a potential target for host-directed antiviral intervention aimed at altering RSV structural phenotypes and limiting pathogenesis. Full article

Background: Celastrol (Cela), a phytochemical extracted from Tripterygium wilfordii, has been extensively investigated for its potential anti-inflammatory, anti-psoriatic, antioxidant, neuroprotective, and antineoplastic properties. However, its clinical translation is limited due to poor bioavailability, low solubility, and nonspecific toxicity. This study aimed to develop and evaluate an inhalable Cela-loaded nanoemulsion (NE) formulation to enhance targeted drug delivery and therapeutic efficacy in non-small cell lung cancer (NSCLC). Methods: The NE formulation was optimized using Capmul MCM (25%), Tween 80 (20%), Transcutol HP (5%), and water (50%) as the oil, surfactant, co-surfactant, and aqueous phase, respectively. Physicochemical characterization included globule size, zeta potential, and drug release in simulated lung fluid. In vitro aerosolization performance, cytotoxicity in NSCLC cell lines (A549), scratch and clonogenic assays, and 3D tumor spheroid models were employed to assess therapeutic potential. Results: The NE showed a globule size of 201.4 ± 3.7 nm and a zeta potential of −15.7 ± 0.2 mV. Drug release was sustained, with 20.4 ± 5.5%, 29.1 ± 10%, 64.6 ± 4.1%, and 88.1 ± 5.2% released at 24, 48, 72, and 120 h, respectively. In vitro aerosolization studies indicated a median aerodynamic particle size of 4.8 ± 0.2 μm, confirming its respirability in the lung. Cell culture studies indicated higher toxicity of NE-Cela in NSCLC cells. NE-Cela significantly reduced A549 cell viability, showing a ~6-fold decrease in IC₅₀ (0.2 ± 0.1 μM) compared to Cela alone (1.2 ± 0.2 μM). Migration and clonogenic assays demonstrated reduced cell proliferation, and 3D spheroid models supported its therapeutic activity in tumor-like environments. Conclusions: The inhalable NE-Cela formulation improved Cela’s physicochemical limitations and demonstrated enhanced anti-cancer efficacy in NSCLC models. These findings support its potential as a targeted, well-tolerated therapeutic option for lung cancer treatment. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) constitutes over 84% of all lung cancer cases and is a leading cause of cancer-related mortality globally. Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, is effective in ALK-positive NSCLC; however, its clinical potential is hampered by poor aqueous solubility and limited oral bioavailability. This study aimed to develop Alectinib-loaded chitosan–alginate nanoparticles (ACANPs) to enhance its solubility, oral bioavailability, and therapeutic efficacy. Methods: ACANPs were synthesized using a novel combined solid/oil/water (s/o/w) emulsification technique with ionotropic gelation. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with ACANPs. Cytotoxicity against NSCLC cell lines (A549 and H460) was assessed using MTT assays. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: ACANPs showed a high encapsulation efficiency (~97%), an average particle size of 161 nm, and a positive zeta potential of +21 mV. In vitro release studies revealed a threefold increase in drug release from ACANPs over 48 h compared to free Alectinib. Cytotoxicity assays demonstrated significantly reduced IC₅₀ values for ACANPs. Pharmacokinetic analyses showed an enhanced maximum plasma concentration (C_max) and area under the curve (AUC), indicating a 78% increase in oral bioavailability. Conclusions: ACANPs substantially improved the solubility, cytotoxic efficacy, and oral bioavailability of Alectinib, suggesting their potential as a promising nanocarrier system for enhancing NSCLC treatment outcomes. Full article

A diagnostic chemical analysis has been performed on a Roman Cippus funebris in precious white marble located close to an ancient Roman road. The Cippus was in good condition but almost completely covered by a black patina, requiring a conservative cleaning intervention. The restorer in charge of the restoration asked us to make a preliminary diagnosis, on the basis of which we could suggest the most appropriate intervention. The Cippus was dedicated to the young Quintus Cornelius Proclianus, who died at the age of 15, by his mother Valeria Calpurnia Scopele. It perfectly fits into the Roman funerary liturgy and also shows an Etruscan-type iconography that seems to confirm the Etruscan Gens of the family and its dating to the 1st century AD. Ion chromatography (IC) analyses were performed to determine anions and cations on solutions obtained from the extraction of salts from the four samples of the Cippus. pH, conductivity, and red-ox potential measures, as well as UV-visible spectra were carried out on the same solutions. A small fragment, spontaneously fallen from the Cippus’ surface, was also observed by optical microscopy (OM) and scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). From the analyses, the dark patina that covered the surface before cleaning turned out to be made of black crusts, that is, smog particles adsorbed on sulfates, but above all, by a layer of microflora. The results allowed us to suggest some conservative interventions. Full article

Thermally driven local-scale precipitation (LSP) is an important type of summer precipitation over China, but the prestorm environmental conditions remain unclear. In order to investigate the major factors controlling the LSP intensity, the meteorological parameters preceding the occurrence of light and heavy afternoon LSP over Eastern China during 2018–2022 are examined using rain gauge, radiosonde sounding, and satellite observations. The temperature differences between heavy and light LSP events are relatively small, but heavy LSP events exhibit larger water vapor mixing ratios (Q_v) below a 5 km altitude than light LSP. With an almost identical vertical temperature distribution, an increment in Q_v increases the relative humidity (RH) in the lower troposphere. Furthermore, large eddy simulations with spectral bin microphysics are performed to investigate the impacts of humidity and aerosols on the LSP intensity. Increased low-level RH leads to larger mass concentrations of rain and graupel at the expense of cloud droplets due to enhanced drop collisions and the riming of ice particles, respectively, thereby reinforcing the LSP. However, an increased aerosol concentration leads to more cloud water but reduced rain water content, resulting mainly from suppressed drop collisions. The graupel mixing ratio exhibits a non-monotonic trend with aerosols, mostly contributed by riming. As a result, the LSP intensity first increases and then decreases with an increment in the aerosol concentration in both dry and humid air. Moreover, more aerosols lead to the humidification of the surrounding air due to the enhanced evaporation of cloud droplets, particularly under lower-RH conditions. These findings provide an enhanced understanding of the effects of covariations in humidity and aerosol concentrations on the afternoon LSP intensity over Eastern China. Full article

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths globally. The most extensive treatment is Tyrosine Kinase Inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) overexpression. Osimertinib, a third-generation TKI is approved to target EGFR exon 19 deletions or exon 21 L858R mutations. However, resistance is inevitable due to emergence of triple mutations (sensitizing mutations, T790M and C797S). To overcome this challenge, a combinatorial approach was used wherein Osimertinib liposomes were conjugated with cetuximab (CTX), an anti-EGFR monoclonal antibody, to improve drug efficacy and delivery. Additionally, pulmonary administration was employed to minimize systemic toxicity and achieve high lung concentrations. Methods: Osimertinib liposomes (OB-LPs) were prepared using thin film hydration method and immunoliposomes (CTX-OB-LPs) were prepared by conjugating the OB-LPs surface with CTX. Liposomes were characterized for particle size, zeta-potential, drug loading, antibody conjugation efficiency, in vitro drug release, and aerosolization performance. Further, the in vitro efficacy of immunoliposomes was evaluated in H1975 cell line. Results: Immunoliposomes exhibited a particle size of 150 nm, high antibody conjugation efficiency (87%), efficient drug release, and excellent aerosolization properties with an aerodynamic diameter of 3 μm and fine particle fraction of 88%. Furthermore, in vitro studies in H1975 cells showed enhanced cytotoxicity with CTX-OB-LPs displaying 1.7-fold reduction and 1.2-fold reduction in IC₅₀ compared to Osimertinib and OB-LPs, respectively. The CTX-OB-LPs also significantly reduced tumor cell migration and colonization compared to Osimertinib and OB-LPs. Conclusions: These successful results for EGFR-targeting inhalable immunoliposomes exhibited potential for contributing to greater anti-tumor efficacy for the treatment of non-small cell lung cancer. Full article

Background/Objectives: Effective airway delivery of a fixed-dose combination of triple-aerosolized inhaled corticosteroid (ICS)/long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) is likely to positively affect therapeutic responses predicted in patients with asthma and chronic obstructive pulmonary disease. This study aimed to conduct in vitro fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide depositions in a Next Generation Impactor. The aerodynamic properties of these inhaled medications influence the spatial distribution and drug abundance, particularly in the smaller airways, to reverse or alleviate disease pathology. Methods: The Next Generation Impactor was used to demonstrate the aerodynamic particle size distributions of fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide delivered from a dry powder inhaler at different flow rates across all stages of the impactors. This in vitro study analyzed the distribution pattern of individual drug components to simulate mono-component deposition and co-deposition in the official model in the United States Pharmacopeia. An Andersen cascade impactor together with scanning electron microscope–energy-dispersive X-ray was employed to observe the drug deposition on each stage of the impactor. Results: We found that the distribution pattern of each component at the same cascade level was comparable, and the aerosol particles of the three drugs reached the in vitro representation of the lower airway compartment. The specified flow rates generated the desired fine particle fraction, fine particle dose, and mass median aerodynamic diameter. Our results also demonstrated visualized deposition patterns of the delivered drugs from different stages of the cascade impactor that may predict deposition as it occurs in vivo. Conclusions: Spatial distribution and abundance of ICS/LABA/LAMA in the same cascade levels were closely comparable, and the aerosol particles were able to reach the small aerosol-sized cascades at the lower levels to some extent. Full article

Zero-valent copper and silver metals (Ms) nanoparticles (NPs) supported on carboxymethylcellulose (CMC) were synthesized for treating Enterotoxigenic Escherichia coli fimbriae 4 (ETEC:F4), a major cause of diarrhea in post-weaned pigs. The antibacterial properties of Cu⁰/CMC and Ag⁰/CMC were assessed on infected porcine intestinal enterocyte IPEC-J2, an in vitro model mimicking the small intestine. The lower average particle size (218 nm) and polydispersity index [PDI]: 0.25) for Ag⁰/CMC, when compared with those of Cu⁰/CMC (367 nm and PDI 0.96), were explained by stronger Ag⁰/CMC interactions. The minimal inhibitory concentration (MIC) and half inhibitory concentration (IC₅₀) of Ag⁰/CMC were lower in both bacteria and IPEC-J2 cells than those of Cu⁰/CMC, confirming that silver nanoparticles are more bactericidal than copper counterparts. IPEC-J2, less sensitive in MNP/CMC treatment, was used to further investigate the infective process by ETEC:F4. The IC₅₀ of MNP/CMC increased significantly when infected IPEC-J2 cells and ETEC were co-treated, showing an inhibition of the cytotoxicity effect of ETEC:F4 infection and protection of treated IPEC-J2. Thus, it appears that metal insertion in CMC induces an inhibiting effect on ETEC:F4 growth and that MNP/CMC dispersion governs the enhancement of this effect. These results open promising prospects for metal-loaded biopolymers for preventing and treating swine diarrhea. Full article

Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV–vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025–0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation. Full article

Area selective deposition (ASD) is a promising IC fabrication technique to address misalignment issues arising in a top–down litho-etch patterning approach. ASD can enable resist tone inversion and bottom–up metallization, such as via prefill. It is achieved by promoting selective growth in the growth area (GA) while passivating the non-growth area (NGA). Nevertheless, preventing undesired particles and defect growth on the NGA is still a hurdle. This work shows the selectivity of Ru films by passivating the Si oxide NGA with self-assembled monolayers (SAMs) and small molecule inhibitors (SMIs). Ru films are deposited on the TiN GA using a metal-organic precursor tricarbonyl (trimethylenemethane) ruthenium (Ru TMM(CO)₃) and O₂ as a co-reactant by atomic layer deposition (ALD). This produces smooth Ru films (<0.1 nm RMS roughness) with a growth per cycle (GPC) of 1.6 Å/cycle. Minimizing the oxygen co-reactant dose is necessary to improve the ASD process selectivity due to the limited stability of the organic molecule and high reactivity of the ALD precursor, still allowing a Ru GPC of 0.95 Å/cycle. This work sheds light on Ru defect generation mechanisms on passivated areas from the detailed analysis of particle growth, coverage, and density as a function of ALD cycles. Finally, an optimized ASD of Ru is demonstrated on TiN/SiO₂ 3D patterned structures using dimethyl amino trimethyl silane (DMA-TMS) as SMI. Full article

Silver oxide (Ag₂O) particles are wonderful candidates due to their unique properties, and their use in a wide range of research, industrial and biomedical applications is rapidly increasing. This makes it fundamental to develop simple, environmentally friendly methods with possible scaling. Herein, sodium borohydride and Datura innoxia leaf extract were applied as chemical and biological stabilizing and reducing agents to develop Ag₂O particles. The primary aim was to evaluate the anticancer and antiviral activity of Ag₂O particles prepared via two methods. XRD, UV-visible and SEM analyses were used to examine the crystallite structure, optical properties and morphology, respectively. The resulting green-synthesized Ag₂O particles exhibited small size, spherically agglomerated shape, and high anticancer and antiviral activities compared to chemically synthesized Ag₂O particles. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium-bromide) assay of green-synthesized Ag₂O particles showed high anticancer activity against MCF-7 cells with IC₅₀ = 17.908 µg/mL compared to chemically synthesized Ag₂O particles with IC₅₀ = 23.856 µg/mL. The antiviral activity of green-synthesized Ag₂O particles and chemically synthesized Ag₂O particles was also evaluated by a plaque-forming assay, and green-synthesized Ag₂O particles showed higher antiviral ability with IC₅₀ = 0.618 µg/mL as compared to chemically synthesized Ag₂O particles with IC₅₀ = 6.129 µg/mL. We propose the use of green-synthesized Ag₂O particles in cancer treatment and drug delivery. Full article

This study utilizes comprehensive observational data from a stratiform mixed-cloud precipitation event in Liupan Mountains, combined with ground-based millimeter-wave cloud radar (CR), micro rain radar (MRR), and microwave radiometer (MR) data, to study the evolution characteristics and conversion efficiency of precipitation particles in the ice–water mixed layer, melting layer, and below these layers during the formation and dissipation of precipitation. The results show the following: (1) When precipitation particles occupy more than 20% of cloud layers detected by cloud radar, the ice–water mixed cloud layer descends and evolves into a precipitating cloud. (2) During surface precipitation periods, the proportion of raindrops forming precipitation was equivalent to that of small-scale precipitation particles in the cloud layers. The proportion of precipitation particles in the cloud layers with temperatures below 0 °C averaged 25%. Ice-phase particles within the bright band (BB) melted, coalesced, and grew into larger precipitation particles, increasing their proportion to 55%. (3) After surface precipitation ended, the water content and precipitation rate of the cloud layer were 60% and 52% of those during the precipitation process, respectively. The proportion of small-scale precipitation particles in the cloud layers was approximately half of that during the precipitation period. A large number of evaporated small-scale precipitation particles floated in the air layer below the clouds, occupying less than 6.0% of the cloud layers. Full article

Progress in numerical models and improved computational capabilities have significantly advanced our comprehension of how aerosol particles impact thunderstorm clouds. Yet, much of this research has focused on employing bulk microphysics models to explain the impacts of aerosol particles acting as cloud condensation nuclei (CCN) on electrical activities in thunderstorm clouds. The bulk thunderstorm models use mean sizes of particles and terminal-fall velocities. This causes calculation deviation in the electrification simulation, which in turn leads to deviations in the simulation of lightning processes. Developing this further, we established a three-dimensional high-resolution cloud–aerosol bin thunderstorm model with electrification and lightning to provide more accurate microphysics and dynamic fields for studying electrical activities. For evaluating the impacts of aerosol particles, specifically CCN, on the properties of continental thunderclouds, aerosols from both clean and polluted continental environments were selected. Cloud simulations indicate that droplets develop a narrower spectrum in polluted continental conditions, and weakened ice crystal growth increases the number of small ice crystals compared to clean conditions. Smaller droplets and ice crystals result in less effective riming and decreased graupel concentration and mass. Consequently, a significant decrease in large ice particles leads to a weakened process of charge separation under conditions of pollution. As a direct result, there is about a 43% reduction in lightning frequency and a delay of approximately 5 min in the lightning process under polluted conditions. Full article

The long-term use of fertilizers and pesticides in conventional cultivation has resulted in a decrease in soil productivity and vegetable yields in greenhouses. However, there is little research exploring the changes in soil organic carbon and the microbial community mediated by soil aggregates, or their impacts on soil productivity. This study investigated the properties of soil aggregates, including the levels of organic carbon fractions, microbial community, and enzyme activity with the three aggregate classes: microaggregates (<0.25 mm), small macroaggregates (2–0.25 mm) and large macroaggregates (>2 mm) under conventional cultivation (CC), integrated cultivation (IC), and organic cultivation (OC) in greenhouses. The results showed that (1) OC and IC promoted the formation of small macroaggregates and enhanced aggregate stability compared to CC; (2) SOC in the three size fractions of OC increased by 92.06–98.99% compared to CC; EOC increased by 98.47–117.59%; POC increased by 138.59–208.70%; MBC increased by 104.71–230.61%; and DOC increased by 21.93–40.90%, respectively; (3) organic cultivation significantly increased enzyme activity in all three particle-size aggregates and increased the relative abundance of bacteria in microaggregates as well as the relative abundance of fungi in small macroaggregates. Structural equation model (SEM) analysis revealed that organic farming practices fostered the development of smaller macroaggregates, elevated microbial and enzyme activities within soil aggregates, and facilitated the conversion of soil nutrients and carbon sequestration. Therefore, long-term organic cultivation increases soil carbon content and vegetable yield in greenhouses by increasing the proportion of small aggregates. In conclusion, long-term organic cultivation in greenhouses improves soil structure, increase soil fertility and vegetable yield, and has a positive impact on the environment. Organic cultivation increases soil fertility and contributes to maintaining ecological balance and protecting the environment in greenhouses. Full article