Scutellaria baicalensis Pith-decayed Root Inhibits Macrophage-related Inflammation Through the NF-κB/NLRP3 Pathway to Alleviate LPS-induced Acute Lung Injury.

Acute lung injury (ALI) is one of the representative "lung heat syndromes" in traditional Chinese medicine (TCM). Scutellaria baicalensis is an herbal medicine used in TCM for treating lung diseases, due to its remarkable anti-inflammatory and antiviral effects. When used in TCM, S. baicalensis root is divided into two categories: S. baicalensis pith-not-decayed root (SN) and S. baicalensis pith-decayed root (SD). Compared to SN, SD has a better effect on lung diseases. We constructed a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model to study the pharmacodynamic mechanism of SD. The ethanolic extract of Scutellaria baicalensis pith-decayed root (EESD) significantly affected LPS-induced ALI by reducing alveolar interstitial thickening, pulmonary edema, and other pathological symptoms, decreasing the infiltration of inflammatory cells, especially macrophages, and inhibiting IL-1ß, TNF-α, and IL-6 transcription and translation. Furthermore, in the THP-1 macrophage model induced by LPS, EESD inhibited the expression of phosphorylated nuclear factor inhibitory protein alpha (p-IκBα), phosphorylated nuclear factor-κB P65 (p-p65), cleaved-caspase-1, cleaved-IL-1ß protein, and the release of inflammatory factors in the NF-κB/NLRP3 pathway, inhibiting macrophage function. In vivo experiments yielded similar results. Therefore, the present study clarified the potential of EESD in the treatment of ALI and revealed its potential pharmacodynamic mechanism by inhibiting the NF-κB/NLRP3 inflammasome pathway and suppressing the pro-inflammatory phenotype activation of lung tissue macrophages.

Atractylenolide-1 affects glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI to inhibit the proliferation and invasion of human triple-negative breast cancer cells.

Atractylenolide-1 (AT-1) is a major octanol alkaloid isolated from Atractylodes Rhizoma and is widely used to treat various diseases. However, few reports have addressed the anticancer potential of AT-1, and the underlying molecular mechanisms of its anticancer effects are unclear. This study aimed to assess the effect of AT-1 on triple-negative breast cancer (TNBC) cell proliferation and migration and explore its potential molecular mechanisms. Cell invasion assays confirmed that the number of migrating cells decreased after AT-1 treatment. Colony formation assays showed that AT-1 treatment impaired the ability of MDA-MB-231 cells to form colonies. AT-1 inhibited the expression of p-p38, p-ERK, and p-AKT in MDA-MB-231 cells, significantly downregulated the proliferation of anti-apoptosis-related proteins CDK1, CCND1, and Bcl2, and up-regulated pro-apoptotic proteins Bak, caspase 3, and caspase 9. The gas chromatography-mass spectroscopy results showed that AT-1 downregulated the metabolism-related genes TPI1 and GPI through the glycolysis/gluconeogenesis pathway and inhibited tumor growth in vivo. AT-1 affected glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI, inhibiting the proliferation, migration, and invasion of (TNBC) MDA-MB-231 cells and suppressing tumor growth in vivo.

Atractylenolide III Ameliorates Bile Duct Ligation-Induced Liver Fibrosis by Inhibiting the PI3K/AKT Pathway and Regulating Glutamine Metabolism.

Liver fibrosis is one of the leading causes of hepatic sclerosis and hepatocellular carcinoma worldwide. However, the complex pathophysiological mechanisms of liver fibrosis are unknown, and no specific drugs are available to treat liver fibrosis. Atractylenolide III (ATL III) is a natural compound isolated from the plant Atractylodes lancea (Thunb.) DC. that possesses antioxidant properties and the ability to inhibit inflammatory responses. In this study, cholestatic hepatic fibrosis was induced in mice using a bile duct ligation (BDL) model and treated with 10 mg/kg and 50 mg/kg of ATL III via gavage for 14 days. ATL III significantly reduced the liver index, lowered serum ALT and AST levels, and reduced liver injury in bile-duct-ligated mice. In addition, ATL III significantly attenuated histopathological changes and reduced collagen deposition. ATL III reduced the expression of fibrosis-related genes α-smooth muscle actin (α-SMA), Collagen I (col1a1), Collagen IV (col4a2), and fibrosis-related proteins α-SMA and col1a1 in liver tissue. Using RNA sequencing (RNA-seq) to screen molecular targets and pathways, ATL III was found to affect the PI3K/AKT singling pathway by inhibiting the phosphorylation of PI3K and AKT, thereby ameliorating BDL-induced liver fibrosis. Gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of ATL III on liver metabolites in BDL mice. ATL III further affected glutamine metabolism by down-regulating the activity of glutamine (GLS1) and glutamine metabolism. ATL III further affected glutamine metabolism by down-regulating the activity of glutaminase (GLS1), as well as glutamine metabolism. Therefore, we conclude that ATL III attenuates liver fibrosis by inhibiting the PI3K/AKT pathway and glutamine metabolism, suggesting that ATL III is a potential drug candidate for treating liver fibrosis.

A spatiotemporal assessment of occupants' infection risks in a multi-occupants space using modified Wells-Riley model.

Escalating demands of assessing airborne disease infection risks had been awakened from ongoing pandemics. An inhalation index linked to biomedical characteristics of pathogens (e.g. TCID 50 for coronavirus delta variant) was proposed to quantify human uptake dose. A modified Wells-Riley risk-assessment framework was then developed with enhanced capability of integrating biological and spatiotemporal features of infectious pathogens into assessment. The instantaneous transport characteristics of pathogens were traced by Eulerian-Lagrangian method. Droplets released via speaking and coughing in a conference room with three ventilation strategies were studied to assess occupants' infection risks using this framework. Outcomes revealed that speaking droplets could travel with less distance (0.5 m) than coughing droplets (1 m) due to the frequent interaction between speaking flow and thermal plume. Quantified analysis of inhalation index revealed a higher inhalation possibility of droplets with nuclei size smaller than 5 µ m , and this cut-off size was found sensitive to ventilation. With only 60-second exposure, occupants in the near-field of host started to have considerable infection risks (approximately 20%). This risk was found minimising over distance exponentially. This modified framework demonstrated the systematic analysis of airborne transmission, from quantifying particle inhalation possibility, targeting specific disease's TCID 50 , to ultimate evaluation of infection risks.

An improved numerical model for epidemic transmission and infection risks assessment in indoor environment.

Social distance will remain the key measure to contain COVID-19 before the global widespread vaccination coverage expected in 2024. Containing the virus outbreak in the office is prioritised to relieve socio-economic burdens caused by COVID-19 and potential pandemics in the future. However, "what is the transmissible distance of SARS-CoV-2" and "what are the appropriate ventilation rates in the office" have been under debate. Without quantitative evaluation of the infection risk, some studies challenged the current social distance policies of 1-2 m adopted by most countries and suggested that longer social distance rule is required as the maximum transmission distance of cough ejected droplets could reach 3-10 m. With the emergence of virus variants such as the Delta variant, the applicability of previous social distance rules are also in doubt. To address the above problem, this study conducted transient Computational Fluid Dynamics (CFD) simulations to evaluate the infection risks under calm and wind scenarios. The calculated Social Distance Index (SDI) indicates that lower humidity leads to a higher infection risk due to weaker evaporation. The infection risk in office was found more sensitive to social distance than ventilation rate. In standard ventilation conditions, social distance of 1.7 m-1.8 m is sufficient distances to reach low probability of infection (PI) target in a calm scenario when coughing is the dominant transmission route. However in the wind scenario (0.25 m/s indoor wind), distance of 2.8 m is required to contain the wild virus type and 3 m is insufficient to contain the spread of the Delta variant. The numerical methods developed in this study provide a framework to evaluate the COVID-19 infection risk in indoor environment. The predicted PI will be beneficial for governments and regulators to make appropriate social-distance and ventilation rules in the office.

Protective Effects of Atractylodis lancea Rhizoma on Lipopolysaccharide-Induced Acute Lung Injury via TLR4/NF-κB and Keap1/Nrf2 Signaling Pathways In Vitro and In Vivo.

Acute lung injury (ALI) is a syndrome caused by an excessive inflammatory response characterized by intractable hypoxemia both inside and outside the lung, for which effective therapeutic drugs are lacking. Atractylodis rhizoma, a traditional Chinese medicine, has excellent anti-inflammatory and antiviral properties in addition to protecting the integrity of the cellular barrier. However, few studies of Atractylodis rhizoma for the treatment of ALI have been published, and its mechanism of action remains unclear. In the present study, the chemical composition of the ethanolic extract of Atractylodis rhizoma (EEAR) was initially clarified by high performance liquid chromatography (HPLC), after which it was studied in vivo using a lipopolysaccharide (LPS)-induced ALI rat model. Treatment with EEAR significantly reduced the lung wet/dry (W/D) ratio, neutrophil infiltration, and malondialdehyde (MDA) and myeloperoxidase (MPO) formation, and enhanced superoxide dismutase (SOD) and glutathione (GSH) depletion in rats with ALI, thereby improving lung barrier function and effectively reducing lung injury. In addition, EEAR significantly reduced histopathological changes, decreased the expression of inflammatory factors (such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), inducible nitric oxide synthase (INOS), and cyclooxygenase-2 (COX-2)), and inhibited the activation of the NF-κB signaling pathway, thus reducing inflammation. In addition, EEAR was found to also reduce oxidative stress in ALI by upregulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins heme oxygenase-1 (HO-1) and NADPH quinone acceptor oxidoreductase 1 (NQO-1). EEAR also reduced LPS-induced inflammatory factor expression in THP-1 cells in vitro by inhibition of the NF-κB signaling pathway, and reduced damage from lipopolysaccharide (LPS)-induced oxidative stress in THP-1 cells by promoting the expression of Nrf2 and its downstream targets HO-1 and NQO-1, the molecular mechanism of which was consistent with in vivo observations. Therefore, we conclude that EEAR attenuates oxidative stress and inflammatory responses via TLR4/NF-κB and Keap1/Nrf2 signaling pathways to alleviate LPS-induced ALI, suggesting that Atractylodis rhizoma is a potential drug candidate for the treatment of ALI.

[Active ingredients and in vitro anti-inflammatory effects of Polygoni Cuspidati Rhizoma et Radix decoction pieces by integrated processing and traditional processing: a comparative analysis].

The present study explored the differences in active ingredients and in vitro anti-inflammatory effects of the decoction pieces by integrated processing(IPDP) and traditional processing(TPDP) of Polygoni Cuspidati Rhizoma et Radix(PCRER).The content of polydatin, resveratrol, emodin-8-O-ß-D-glucoside, emodin, and physcion in IPDP and TPDP was determined by high-performance liquid chromatography(HPLC).The inflammation model was induced by lipopolysaccharide(LPS) in RAW264.7 cells.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in 60% ethanol extracts of IPDP and TPDP of different concentrations(5 and 10 µg·mL~(-1)) were determined by PCR.The results showed that the content of polydatin and emodin-8-O-ß-D-glucoside in IPDP was significantly higher than that in TPDP, while the content of resveratrol, emodin, and physcion was higher in TPDP.The anti-inflammatory results showed that ethanol extracts of IPDP of different concentrations(5 and 10 µg·mL~(-1)) significantly inhibited the increase in the mRNA levels of IL-1ß and TNF-α induced by LPS, whereas TPDP only had a significant inhibitory effect on IL-1ß.This study preliminarily showed that the total content of five active ingredients in IPDP was higher than that in TPDP, and IPDP was superior to TPDP in anti-inflammatory activity in vitro, which provided an experimental basis for the production and application of IPDP.

Peptide Nucleic Acid-Functionalized Nanochannel Biosensor for the Highly Sensitive Detection of Tumor Exosomal MicroRNA.

Compared with free miRNAs in blood, miRNAs in exosomes have higher abundance and stability. Therefore, miRNAs in exosomes can be regarded as an ideal tumor marker for early cancer diagnosis. Here, a peptide nucleic acid (PNA)-functionalized nanochannel biosensor for the ultrasensitive and specific detection of tumor exosomal miRNAs is proposed. After PNA was covalently bound to the inner surface of the nanochannels, the detection of tumor exosomal miRNAs was achieved by the charge changes on the surface of nanochannels before and after hybridization (PNA-miRNA). Due to the neutral characteristics of PNA, the efficiency of PNA-miRNA hybridization was improved by significantly reducing the background signal. This biosensor could not only specifically distinguish target miRNA-10b from single-base mismatched miRNA but also achieve a detection limit as low as 75 aM. Moreover, the biosensor was further used to detect exosomal miRNA-10b derived from pancreatic cancer cells and normal pancreatic cells. The results indicate that this biosensor could effectively distinguish pancreatic cancer tumor-derived exosomes from the normal control group, and the detection results show good consistency with those of the quantitative reverse-transcription polymerase chain reaction method. In addition, the biosensor was used to detect exosomal miRNA-10b in clinical plasma samples, and it was found that the content of exosomal miRNA-10b in cancer patients was generally higher than that of healthy individuals, proving that the method is expected to be applied for the early diagnosis of cancer.

Deposition features of inhaled viral droplets may lead to rapid secondary transmission of COVID-19.

Inhaled viral droplets may immediately be expelled and cause an escalating re-transmission. Differences in the deposition location of inhaled viral droplets may have a direct impact on the probability of virus expelling. This study develops a numerical model to estimate the region-specific deposition fractions for inhalable droplets (1-50 µ m) in respiratory airways. The results identified a higher deposition fraction in the upper airways than the lower airways. Particularly for droplets larger than 10 µ m, the relatively high deposition fraction in the oral/laryngeal combined region warns of its easy transmission through casual talking/coughing. Moreover, considering droplet sizes' effect on virus loading capacity, we built a correlation model to quantify the potential of virus expelling hazards, which suggests an amplified cascade effect on virus transmission on top of the existing transmission mechanism. It therefore highlights the importance of considering the instant expelling possibilities from inhaled droplets, and also implies potentials in restricting a rapid secondary transmission by measures that can lower down droplet deposition in the upper airways.

[A review of clinical specifications of Scutellariae Radix pieces in ancient and modern literature].

Scutellariae Radix is a commonly used Chinese medicinal first recorded in the Shennong's Classic of Materia Medica. In the ancient books of traditional Chinese medicine(TCM), Scutellariae Radix is used in two specifications, solid one(Ziqin) and hollow one(Kuqin). In the current rules and regulations of Chinese medicine, Scutellariae Radix is used without the specific requirements for the specifications applied. To clarify the evolution of Scutellariae Radix specifications and analyze the current specifications of Scutellariae Radix pieces, the present study reviews the Scutellariae Radix from ancient literature, modern rules and regulations, and differences between Ziqin and Kuqin in composition, efficacy, and transformation mechanism. According to the research on ancient books, Kuqin is effective in clearing the fire of the upper energizer, and Ziqin in purging the heat of the lower energizer. Modern studies have revealed that Kuqin and Ziqin are significantly different in chemical components, and Ziqin and Kuqin target the colon and lung, respectively, which are consistent with the relevant records in ancient books. The review study suggests that the two specifications of Scutellariae Radix are reasonable since they can facilitate the precise treatment of Scutellariae Radix.

Evaluation of cough-jet effects on the transport characteristics of respiratory-induced contaminants in airline passengers' local environments.

Urgent demands of assessing respiratory disease transmission in airliner cabins had awakened from the COVID-19 pandemics. This study numerically investigated the cough flow and its time-dependent jet-effects on the transport characteristics of respiratory-induced contaminants in passengers' local environments. Transient simulations were conducted in a three-row Boeing 737 cabin section, while respiratory contaminants (2 µm-1000 µm) were released by different passengers with and without coughing and were tracked by the Lagrangian approach. Outcomes revealed significant influences of cough-jets on passengers' local airflow field by breaking up the ascending passenger thermal plumes and inducing several local airflow recirculation in the front of passengers. Cough flow could be locked in the local environments (i.e. near and intermediate fields) of passengers. Results from comparative studies also revealed significant increases of residence times (up to 50%) and extended travel distances of contaminants up to 200 µm after considering cough flow, whereas contaminants travel displacements still remained similar. This was indicating more severe contaminate suspensions in passengers' local environments. The cough-jets was found having long and effective impacts on contaminants transport up to 4 s, which was 8 times longer than the duration of cough and contaminants release process (0.5 s). Also, comparing to the ventilated flow, cough flow had considerable impacts to a much wider size range of contaminants (up to 200 µm) due to its strong jet-effects.

Correlation of regional deposition dosage for inhaled nanoparticles in human and rat olfactory.

BACKGROUND: Nose-to-brain transport of airborne ultrafine particles (UFPs) via the olfactory pathway has been verified as a possible route for particle translocation into the brain. The exact relationship between increased airborne toxicant exposure and neurological deterioration in the human central nervous system, is still unclear. However, the nasal olfactory is undoubtedly a critical junction where the time course and toxicant dose dependency might be inferred. METHOD: Computational fluid-particle dynamics modeling of inhaled nanoparticles (1 to 100 nm) under low to moderate breathing conditions (5 to 14 L/min - human; and 0.14 to 0.40 L/min - rat) were performed in physiologically realistic human and rat nasal airways. The simulation emphasized olfactory deposition, and variations in airflow and particle flux caused by the inter-species airway geometry differences. Empirical equations were developed to predict regional deposition rates of inhaled nanoparticles on human and rat olfactory mucosa in sedentary breathing. Considering, breathing and geometric differences, quantified correlations between human and the rat olfactory deposition dose against a variety of metrics were proposed. RESULTS: Regional deposition of nanoparticles in human and the rat olfactory was extremely low, with the highest deposition (< 3.5 and 8.1%) occurring for high diffusivity particles of 1.5 nm and 5 nm, respectively. Due to significant filtering of extremely small particles (< 2 nm) by abrupt sharp turns at front of the rat nose, only small fractions of the inhaled nanoparticles (in this range) reached rat olfactory than that in human (1.25 to 45%); however, for larger sizes (> 3 nm), significantly higher percentage of the inhaled nanoparticles reached rat nasal olfactory than that in human (2 to 32 folds). Taking into account the physical and geometric features between human and rat, the total deposition rate (#/min) and deposition rate per unit surface area (#/min/mm2) were comparable for particles> 3 nm. However, when body mass was considered, the normalized deposition rate (#/min/kg) in the rat olfactory region exceeded that in the human. Nanoparticles < 1.5 nm were filtered out by rat anterior nasal cavity, and therefore deposition in human olfactory region exceeded that in the rat model. CONCLUSION: Regional deposition dose of inhaled nanoparticles in a human and rat olfactory region was governed by particle size and the breathing rate. Interspecies correlation was determined by combining the effect of deposition dosage, physical\geometric features, and genetic differences. Developed empirical equations provided a tool to quantify inhaled nanoparticle dose in human and rat nasal olfactory regions, which lay the ground work for comprehensive interspecies correlation between the two species. Furthermore, this study contributes to the fields in toxicology, i.e., neurotoxicity evaluation and risk assessment of UFPs, in long-term and low-dose inhalation exposure scenarios.

Deep-Fried Atractylodis Rhizoma Protects against Spleen Deficiency-Induced Diarrhea through Regulating Intestinal Inflammatory Response and Gut Microbiota.

According to the theories of traditional Chinese medicine, spleen deficiency often leads to diarrhea, and deep-fried Atractylodis Rhizoma (DAR) is commonly used for the treatment. However, the association between spleen deficiency and diarrhea remains unclear. The present study aimed to investigate the therapeutic effect of DAR for the treatment of diarrhea caused by spleen deficiency and analyze the related mechanisms. It was found that a high dose group of an ethanolic extract of deep-fried Atractylodis Rhizoma (EEDAR-H) significantly inhibited weight loss, diarrhea, and pathological changes in colon tissue induced by rhubarb. EEDAR-H was found to significantly reduce the level of intestinal inflammatory cytokines and increase the expression of gastrointestinal motility hormones. In addition, EEDAR-H significantly increased the expression of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) and restored abnormal water metabolism; Shen-Ling-Bai-Zhu-San (SLBZS) induced the same effect as EEDAR-H. Additional tests on the mechanism found that EEDAR-H and SLBZS promoted the integrity of the intestinal barrier. Both significantly increased the expression of the tight junction protein ZO-1 and Occludin, inhibited the phosphorylation of p38MAPK and MLC, and significantly reduced the expression levels of PAR-2. Analysis of the gut microbiota indicated that overall changes in its structure were reversed after treatment with EEDAR-H or SLBZS, in addition to significant modulation of the abundance of different phyla. At the genus level, EEDAR-H or SLBZS significantly reduced the levels of potential pathogens and increased those of beneficial bacteria.

Fate of the inhaled smoke particles from fire scenes in the nasal airway of a realistic firefighter: A simulation study.

Understanding the inhalation, transport and deposition of smoke particles during fire missions are important to evaluating the health risks for firefighters. In this study, measurements from Underwriters Laboratories' large-scale fire experiments on smoke particle size distribution and concentration in three residential fire scenes were incorporated into models to investigate the fate of inhaled toxic ultrafine particulates in a realistic firefighter nasal cavity model. Deposition equations were developed, and the actual particle dosimetry (in mass, number and surface area) was evaluated. A strong monotonic growth of nasal airway dosages of simulated smoke particles was identified for airflow rates and fire duration across all simulated residential fire scene conditions. Even though the "number" dosage of arsenic in the limited ventilation living room fire was similar to the "number" dosage of chromium in the living room, particle mass and surface area dosages simulated in the limited living room were 90-200 fold higher than that in the ventilated living room. These were also confirmed when comparing the dosimetry in the living room and the kitchen. This phenomenon implied that particles with larger size were the dominant factors in mass and surface area dosages. Firefighters should not remove the self-contained breathing apparatus (SCBA) during fire suppression and overhaul operations, especially in smoldering fires with limited ventilation.

Thermal effect of human body on cough droplets evaporation and dispersion in an enclosed space.

This study numerically investigated the thermal effect of human body on the time-dependent dispersion of cough droplets with evaporation process. The thermal flow of human body was imitated using a 3D thermal manikin with real body features, while a recent developed multi-component Eulerian-Lagrangian approach was used to address the effects of inhomogeneous temperature and humidity fields on droplet evaporation. By comparing the results yielded without and with the human body heat, the outcomes demonstrated strong impact of human body heat on the droplets mass fraction and local air velocity distributions. Inspirable droplets could potentially drop into respirable droplets by evaporation, although the evaporation rate was not significantly affected by body heat. The thermal effect of human body revealed its vital impacts on the time-dependent droplets dispersion. Due to the buoyancy driven thermal flow, both the vertical velocity and displacement of small droplets (≤20 µm) were completely reversed from descending to ascending, while the deposition time of large droplets (≥50 µm) were significantly delayed. With the reduced droplet size by evaporation and droplets lifted into breathing zone by human thermal effect, the inhalability and infection risks of cough droplets would be much higher in real occupied indoor spaces.

Characterisation and analysis of indoor tornado for contaminant removal and emergency ventilation.

As an essential emergency management strategy, innovative emergency ventilation schemes that can quickly remove infectious and fatal contaminants without further spreading are highly demanded for public and commercial buildings. This study numerically investigated a vortex flow driven ventilation in a model room to explore the dynamic characteristics and 3D visualisation of vortex-driven indoor tornados. Four approaches to identify the core region of the indoor tornado were developed and compared against each other. By successfully capturing the continuously changing centre of the vortex and significant core region size variations at different heights, the swirl vector method was recommended as a quantifiable approach to identify the core region of indoor tornados. The numerical outcomes also revealed a strong connection between the lift angle, vortex intensity, overall size of indoor tornado and maximum size of core region. The best contaminants control and removal was achieved at lift angle of 20° in this study and an optimum lift angle ranging from 10° to 20° was recommended for future study.

Detailed deposition analysis of inertial and diffusive particles in a rat nasal passage.

Rats have been widely used as surrogates for evaluating the health effects of inhaled airborne particulate matter. To provide a thorough understanding of particle transport and deposition mechanisms in the rat nasal airway, this article presents a computational fluid dynamics (CFD) study of particle exposure in a realistic rat nasal passage under a resting flow condition. Particles covering a diameter range from 1 nm to 4 µm were passively released in front of the rat's breathing zone, and the Lagrangian particle tracking approach was used to calculate individual particle trajectories. Detailed particle deposition analysis shows the deposition of inertial particles >2 µm is high in the rat nasal vestibule and more than 70% of all inhaled inertial particles were trapped in this region. While for diffusive nanoparticles, the vestibule filtration effect is reduced, only less than 60% of inhaled nanoparticles were blocked by the anterior nasal structures. The particle exposure in the olfactory region only shows notable deposition for diffusive nanoparticles, which peaks at 9.4% for 5 nm particles. Despite the olfactory deposition remains at a low level, the ratio between the olfactory and the main passage is kept around 30-40% for 10-800 nm particles, which indicates a particle-size-independent distribution pattern in the main nasal passage and olfactory. This study provides a deep understanding of particles deposition features in a rat nasal passage, and the research findings can aid toxicologist in inter-species exposure-response extrapolation study.

Modelling of evaporation of cough droplets in inhomogeneous humidity fields using the multi-component Eulerian-Lagrangian approach.

This study employed a multi-component Eulerian-Lagrangian approach to model the evaporation and dispersion of cough droplets in quiescent air. The approach is featured with a continuity equation being explicitly solved for water vapor, which allows comprehensively considering the effects of inhomogeneous humidity field on droplets evaporation and movement. The computational fluid dynamics (CFD) computations based on the approach achieved a satisfactory agreement with the theoretical models reported in the literature. The results demonstrated that the evaporation-generated vapor and super-saturated wet air exhaled from the respiratory tracks forms a "vapor plume" in front of the respiratory track opening, which, despite the short life time, significantly impedes the evaporation of the droplets captured in it. The study also revealed that due to the droplet size reduction induced by evaporation, both the number density of airborne droplets and mass concentration of inhalable pathogens remarkably increased, which can result in a higher risk of infection. Parametric studies were finally conducted to evaluate the factors affecting droplet evaporation. SUMMARY: The study demonstrated the importance of considering inhomogeneous humidity field when modelling the evaporation and dispersion of cough droplets. The multi-component Eulerian-Lagrangian model presented in this study provides a comprehensive approach to address different influential factors in a wide parametric range, which will enhance the assessment of the health risks associated with droplet exposure.

[Study on dryness effect of Atractylodis Rhizoma based on theory of dry-dry and dryness-induced Yin deficiency].

In order to establish a more perfect evaluation system for dryness effect of Atractylodis Rhizoma, determine the main dry parts of Atractylodis Rhizoma，and further define the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness. The healthy rats were given with different doses of water extract and volatile oil of raw Atractylodis Rhizoma and stir-baked Atractylodis Rhizoma for 21 days. Based on the theory of the dry-dry and dryness-induced Yin deficiency, the amount of drinking water, tissue morphology of submandibular glands, urine volume and the expression of aquaporin 2 (AQP2) in the kidneys, as well as blood rheology, ratio of cAMP/cGMP in serum and the content of Na⁺-K⁺-ATP enzyme were selected as the evaluation indexes. The results indicated that the rats with high dose volatile oil from raw Atractylodis Rhizoma had a significant increase in the amount of drinking water, urine volume, blood viscosity, ratio of cAMP/cGMP and content of Na⁺-K⁺-ATP enzyme in the serum（P<0.05）as compared with the soybean oil group; meanwhile, atrophy of submandibular acinar gland was obvious，and the expression of aquaporin 2 was reduced significantly（P<0.05）. There were significant differences between volatile oil high dose group of raw Atractylodis Rhizoma and volatile oil high dose group of stir-baked Atractylodis Rhizoma. There was no significant difference between the water extract groups of raw and stir-baked Atractylodis Rhizoma and the saline group. A comprehensive evaluation system for the dryness effect of Atractylodis Rhizoma was established. It was confirmed that the volatile oil part was the main dry part of Atractylodis Rhizoma. It revealed that the mechanism of dryness effect of Atractylodis Rhizoma was not only related to the decrease of the total content of the volatile oil, but also may be related to the transformation of dryness components in the volatile oil. It provides references for the study of material basis of Atractylodis Rhizoma dryness, provides an experimental basis for the clinical application of Atractylodis Rhizoma, further clarifies the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness, and provides thoughts for the evaluation of other dry traditional Chinese medicines.

Toehold Mediated One-Step Conformation-Switchable "Signal-On" Electrochemical DNA Sensing Enhanced with Homogeneous Enzymatic Amplification.

The development of highly sensitive and sequence-specific electrochemical DNA (E-DNA) sensors, featuring flexible, one-step, and "signal-on" design, is a long-lasting goal. Here, we present a single-step, toehold-triggered structure-switchable signaling design that is "signal-on" and compatible with homogeneous enzyme-assisted target recycling (EATR). In this design, a partially hybridized duplex is bifunctional, which consists of a signal probe having foldable hairpin sequence and a target recognition probe with exposed toehold domain. In the presence of both target and exonuclease, the toehold sequence rapidly fuels the strand displacement reaction, liberating the surface-confined toehold-target duplex into homogeneous solution for target recycling and meanwhile leaving the dehybridized signal probe to form a stem-loop structure for signaling. Through such an 1:N enzymatic catalysis, more and more unfolded probes self-hybridize to their original folded configuration, giving a remarkable signal gain. This enzyme-assisted toehold E-DNA (etE-DNA) sensor achieves a satisfactory detection limit down to 42 fM, which is lower than that of the routine switchable E-DNA sensor by several orders of magnitude. In addition, the strategy shows high selectivity against a single-base mismatch and is capable of probing low abundant target DNA directly in human serum with minimal interference. By synergizing the toehold-based high selectivity, EATR, and one-step conformation-switchable signaling, this functional etE-DNA sensor appears to be a promising bioassay approach for clinical diagnostics.