Clearance Of Particles Research Articles

Incense smoke (IS) inhalation exposure system: Physicochemical characterization, IS particle deposition and clearance in human airway using MPPD model

Incense smoke (IS) is source of indoor air pollution and key risk for diverse human diseases. Less information is available regarding controlled IS rodent inhalation exposure system and IS particulate matter (PM) deposition in human airways. Study aimed to demonstrate stable ISPM physicochemical parameters of 10 incense products inside the customized whole body inhalation exposure chamber (without animal) connected to smoke generation unit via aerosol mixing device. IS analyzed for size segregated PM emission, ISPM in vitro aerodynamics (MMAD and GSD determination), fine and ultrafine particle's SEM, SEM-EDX and PAH analysis. Using real life exposure scenario by utilizing MMAD, GSD and PM concentration after Tier 1 exposure assessment as key input parameters, ISPM dosimetry in infant (3 months) and adult (21 years male and female) human airways was calculated using multiple-path particle dosimetry (MPPD 3.04) modeling. Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) ranged between 0.55 and 2.10 μm and 1.22 to 1.77 (polydisperse) respectively. PM1.0 and PM0.1 showed multiple morphology and presence of heavy and trace elements. PAH like acenaphthylene, anthracene, fluorene, naphthalene and phenanthrene were detected (0.84–143.17 μg/g). MPPD results showed higher ISPM deposition in pulmonary region and lowest in trachea bronchial region. ISPM deposition in tissue was higher in lower, peripheral lung as compared to upper and central lung tissue. Whole body inhalation exposure system showed stable IS atmosphere (physicochemical parameters) indicating the device suitability in future inhalation studies. MPPD ISPM deposition fraction and clearance data showed deep lung penetrating and retention behavior with higher risk in infant followed by female and then male. These modeled particle deposition and clearance data may be useful in risk assessment analysis of IS.

Materials for Cell Surface Engineering.

Cell therapies are emerging as a promising new therapeutic modality in medicine, generating effective treatments for previously incurable diseases. Clinical success of cell therapies has energized the field of cellular engineering, spurring further exploration of novel approaches to improve their therapeutic performance. Engineering of cell surfaces using natural and synthetic materials has emerged as a valuable tool in this endeavor. This review summarizes recent advances in the development of technologies for decorating cell surfaces with various materials including nanoparticles, microparticles, and polymeric coatings, focusing on the ways in which surface decorations enhance carrier cells and therapeutic effects. Key benefits of surface-modified cells include protecting the carrier cell, reducing particle clearance, enhancing cell trafficking, masking cell-surface antigens, modulating inflammatory phenotype of carrier cells, and delivering therapeutic agents to target tissues. While most of these technologies are still in the proof-of-concept stage, the promising therapeutic efficacy of these constructs from in vitro and in vivo preclinical studies has laid a strong foundation for eventual clinical translation. Cell surface engineering with materials can imbue a diverse range of advantages for cell therapy, creating opportunities for innovative functionalities, for improved therapeutic efficacy, and transforming the fundamental and translational landscape of cell therapies.

Adding fish waste to the diet of Iceland scallop Chlamys islandica: effects on feeding and reproductive ability

Organic enrichment from fish farming may impact benthic species and habitats in adjacent areas. Norwegian salmon farming is continuously growing, but, due to area conflicts and severe sea-lice problems in the western areas, growth of the industry is focused in the northern areas. Knowledge is scarce on how an increase in fish farming will impact Arctic and subarctic species and habitats. One such species is the Iceland scallop Chlamys islandica, distributed from the Lofoten Islands in Nordland County to the Varangerfjord in Troms and Finnmark County. To study the impact of fine-particle fish faeces on feeding and reproductive ability in adult Iceland scallop, particles <41 µm of finfish waste were added to the diet. Effects were tested via short-term (weeks) feeding studies using 2 diets, 100% cultured algal species and a 50% mix of algae and fish waste. In addition, a 100% fish waste diet was used to study longer-term effects on reproductive ability (months). Feeding (% particle clearance and feeding rate) on the microalgae diet tended to be higher than that on the diet containing fish waste, but the difference was significant only in 2 out of 4 cases. We did not find any effect of diets on reproductive ability (gonad development and fatty acid profiles) of scallops. Lack of knowledge on sufficient food levels for gonad maturation in this species may have affected the results. We suggest that future work includes the transplant of scallops from a reference site to fish production sites and that investigations begin immediately after spawning early in scallop gonad development.

Assay of Diphenhydramine HCl in Syrup by High Performance Liquid Chromatography

Cough is a natural response from the respiratory tract by increasing the clearance of secretions and particles from mucus, irritants, foreign particles, and microbes, so that it can act as a body defense. One way that can be done to relieve cough symptoms is to use symptomatic drugs. Diphenhydramine HCl is an antihistamine that belongs to the first generation H1 receptor antagonist (H1 blocker) group which has sedative and anti-allergic properties. Diphenhydramine HCl is used to treat sneeze, runny nose, watery eyes, itches, skin rashes, and other cold symptoms or other allergies. Diphenhydramine HCl is also used to treat motion sickness and to induce sleep. The purpose of this study was to determine the contents of diphenhydramine HCl syrup sold in the market. This test uses the High Performance Liquid Chromatography (HPLC) method with acetonitrile as a mobile phase; water; triethylamine (50;50;0.5). The results obtained the average content of Diphenhydramine HCl 102.5%. So it can be concluded that the cough medicine sample meets the requirements because the contents are not less than 90% and not more than 110% based on the Indonesian Pharmacopoeia Edition VI 2020.
 Keywords: Cough, Diphenhydramine HCl, High Performance Liquid Chromatography (HPLC)

MULTIPLE PATH PARTICLE DOSIMETRY MODEL CONCEPT AND ITS APPLICATION TO DETERMINE RESPIRATORY TRACT HAZARDS IN THE 3D PRINTING

The Multiple Path Particle Dosimetry (MPPD) model is computer software that estimates and visualizes the deposition, clearance, and retention of particles in the respiratory tract systems of humans, rats, and other species. The mathematical model provides a broad spectrum of settings and input options. This research aims to explore the MPPD model concept and determine the deposition fraction (DF), clearance, and retained mass in the human respiratory tract (HRT) based on the geometric mean diameter (GMD) and mass concentration (MC) of particulate matter (PM) emitted during the 3D printing process. We used the real-time air sample data collected during the 8-hour working shift in the 3D printing office. Ultrafine PM deposits mainly in lungs (56%), fine PM mostly deposits in the upper respiratory tract (URT) (41%) and lungs (39%), but coarse PM mostly deposits in the URT (81%). The biggest DF in lower respiratory tract is ultrafine PM (487 μg), the smaller DF is coarse PM (185 μg) and the smallest DF is fine PM (123 μg). The biggest DF in lung for all PM - lower lobes (fine PM - 60%, ultrafine PM, coarse PM - 61%). In a model, where exposure was 5 hours a day, five days a week, during one month, followed by one year of post-exposure period, it was shown that retained mass in the tracheobronchial (TB) region was 1% for ultrafine and coarse PM each, 2% for fine PM, and 55% for all PM in the pulmonary region. The MPPD software is an easily accessible and valuable tool for assessing the impact of PM on the HRT. Particulate matter decreasing in diameter, tend to deposit mostly in the deeper levels of HRT. Tracheobronchial region clearance is more rapid than pulmonary region clearance. Potentially for persons using the 3D-printer regularly the worst health impact could be associated with smaller size of PM, due to tendency deposit mostly in pulmonary region where the clearance rate is slower.

Knowledge Level of Synthetic Cough Medicine Self-Medication and List of Traditional Medicines Used by the Insignia Oasis Housing Society

Coughing is a natural response by increasing the clearance of mucus secretions and particles, irritants, foreign particles, and microbes, so that it becomes the body's defense mechanism. Self-medication practitioners must know about synthetic drugs and traditional medicines used to treat coughs. This study aims to determine the level of self-medication knowledge of synthetic cough medicines and a list of traditional medicines used by the Insignia Oasis housing community which will be held in March 2023 at Insignia Oasis Housing. The type of research used is descriptive observational research using a questionnaire to obtain data with a total of 56 respondents. The results of this study indicate that the percentage of respondents' answers is 89.91%. Based on these results it can be concluded that the level of self-medication knowledge of synthetic cough medicine and the list of traditional medicines used by the Insignia Oasis housing community is in the high category and uses ginger the most.

Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract

Inhalation is a portal-of-entry for aerosols via the respiratory tract where particulate burden accumulates depending on sites of particle deposition, normal clearance mechanisms, and particle solubility. The time available for dissolution of particles is determined by the balance between the rate of particle clearance from a region and their solubility in respiratory solvents. Dissolution is a function of particle surface area divided by particle volume or mass (i.e., dissolution is inversely proportional to the physical diameter of particles). As a conservative approach, investigators commonly assume the complete and instantaneous dissolution of metals from particles depositing in the alveolar region of the respiratory tract. We derived first-order dissolution rate constants to facilitate biokinetic modeling of particle clearance, dissolution, and absorption into the blood. We then modeled pulmonary burden and total dissolution of particles over time as a function of particle size, density, and solubility. We show that assuming poorly soluble particle forms will enter the blood as quickly as highly soluble forms causes an overestimation of concentrations of the compound of interest in blood and other extrapulmonary tissues while also underestimating its pulmonary burden. We conclude that, in addition to modeling dose rates for particle deposition into the lung, physiologically based pharmacokinetic modeling of pulmonary and extrapulmonary tissues concentrations of moderately and poorly soluble materials can be improved by including estimates of lung burden and particle dissolution over time.

Air filtration mitigates aerosol levels both during and after endoscopy procedures.

Upper gastrointestinal endoscopies are aerosol-generating procedures, increasing the risk of spreading airborne pathogens. We aim to quantify the mitigation of airborne particles via improved ventilation, specifically laminar flow theatres and portable high-efficiency particulate air (HEPA) filters, during and after upper gastrointestinal endoscopies. This observational study included patients undergoing routine upper gastrointestinal endoscopy in a standard endoscopy room with 15-17 air changes per hour, a standard endoscopy room with a portable HEPA filtration unit, and a laminar flow theatre with 300 air changes per hour. A particle counter (diameter range 0.3μm-25μm) took measurements 10cm from the mouth. Three analyses were performed: whole procedure particle counts, event-based counts, and air clearance estimation using post-procedure counts. Compared to a standard endoscopy room, for whole procedures we observe a 28.5x reduction in particle counts in laminar flow (p < 0.001) but no significant effect of HEPA filtration (p = 0.50). For event analysis, we observe for lateral flow theatres reduction in particles >5μm for oral extubation (12.2x, p < 0.01), reduction in particles <5μm for coughing/gagging (6.9x, p < 0.05), and reduction for all sizes in anesthetic throat spray (8.4x, p < 0.01) but no significant effect of HEPA filtration. However, we find that in the fallow period between procedures HEPA filtration reduces particle clearance times by 40%. Laminar flow theatres are highly effective at dispersing aerosols immediately after production and should be considered for high-risk cases where patients are actively infectious or the supply of personal protective equipment is limited. Portable HEPA filers can safely reduce the fallow time between procedures by 40%.

Epigenetic combined with transcriptomic analysis of the m6A methylome after spared nerve injury-induced neuropathic pain in mice.

Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuropathic pain. N6-methyladenosine (m6A) is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases. However, the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown. In this study, we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve. High-throughput methylated RNA immunoprecipitation sequencing results showed that after spared nerve injury, there were 55 m6A methylated and differentially expressed genes in the spinal cord. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury. Over time, the differential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell proliferation." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance. Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes, such as "very-low-density lipoprotein particle clearance," "negative regulation of cholesterol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling. We speculate that m6A reader enzymes also have an important role in neuropathic pain. These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at different stages after injury.

Lupus Recipe inhibits cGVHD-induced lupus nephritis in mice and promote renal LC3-associated autophagy.

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well-established model of SLE. LC3-associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3-associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3-associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD-induced LN, which may attribute to the increased levels of LC3-associated autophagy.

Severe influenza infection is associated with inflammatory programmed cell death in infected macrophages.

Influenza A virus (IAV) is one of the leading causes of respiratory tract infections in humans, representing a major public health concern. The various types of cell death have a crucial role in IAV pathogenesis because this virus may trigger both apoptosis and necroptosis in airway epithelial cells in parallel. Macrophages play an important role in the clearance of virus particles, priming the adaptive immune response in influenza. However, the contribution of macrophage death to pathogenesis of IAV infection remains unclear. In this work, we investigated IAV-induced macrophage death, along with potential therapeutic intervention. We conducted in vitro and in vivo experiments to evaluate the mechanism and the contribution of macrophages death to the inflammatory response induced by IAV infection. We found that IAV or its surface glycoprotein hemagglutinin (HA) triggers inflammatory programmed cell death in human and murine macrophages in a Toll-like receptor-4 (TLR4)- and TNF-dependent manner. Anti-TNF treatment in vivo with the clinically approved drug etanercept prevented the engagement of the necroptotic loop and mouse mortality. Etanercept impaired the IAV-induced proinflammatory cytokine storm and lung injury. In summary, we demonstrated a positive feedback loop of events that led to necroptosis and exacerbated inflammation in IAV-infected macrophages. Our results highlight an additional mechanism involved in severe influenza that could be attenuated with clinically available therapies.

Severe Dyslipidemia Mimicking Familial Hypercholesterolemia Induced by High-Fat, Low-Carbohydrate Diets: A Critical Review

Emerging studies in the literature describe an association between high-fat, low-carbohydrate diets and severe hypercholesterolemia consistent with the levels observed in patients with (homozygous) familial hypercholesterolemia (FH). High levels of low-density lipoprotein cholesterol (LDL-C) may result from the reduced clearance of LDL particles from the circulation, the increased production of their precursor, or a combination of both. The increased intake of (saturated) fat and cholesterol, combined with limited to no intake of carbohydrates and fiber, are the main features of diets linked to hypercholesterolemia. However, several observations in previous studies, together with our observations from our lipid clinic, do not provide a definitive pathophysiological explanation for severe hypercholesterolemia. Therefore, we review these findings and possible pathophysiological explanations as well as opportunities for future research. Altogether, clinicians should rule out high-fat, low-carbohydrate diets as a possible cause for hypercholesterolemia in patients presenting with clinical FH in whom no mutation is found and discuss dietary modifications to durably reduce LDL-C levels and cardiovascular disease risk.

Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

Epithelial tissues provide front-line barriers shielding the organism from invading pathogens and harmful substances. In the airway epithelium, the combined action of multiciliated and secretory cells sustains the mucociliary escalator required for clearance of microbes and particles from the airways. Defects in components of mucociliary clearance or barrier integrity are associated with recurring infections and chronic inflammation. The timely and balanced differentiation of basal cells into mature epithelial cell subsets is therefore tightly controlled. While different growth factors regulating progenitor cell proliferation have been described, little is known about the role of metabolism in these regenerative processes. Here we show that basal cell differentiation correlates with a shift in cellular metabolism from glycolysis to fatty acid oxidation (FAO). We demonstrate both in vitro and in vivo that pharmacological and genetic impairment of FAO blocks the development of fully differentiated airway epithelial cells, compromising the repair of airway epithelia. Mechanistically, FAO links to the hexosamine biosynthesis pathway to support protein glycosylation in airway epithelial cells. Our findings unveil the metabolic network underpinning the differentiation of airway epithelia and identify novel targets for intervention to promote lung repair.

Saikosaponins ameliorate hyperlipidemia in rats by enhancing hepatic lipid and cholesterol metabolism

Ethnopharmacological relevanceHyperlipidemia is the systemic manifestation of abnormal lipid metabolism, characterized by elevated circulating levels of cholesterol and triglyceride and a high risk of cardiovascular events. Radix Bupleuri (RB) is a traditional Chinese herbal product used to treat liver diseases. Our previous study demonstrated that Saikosaponins (SSs), the most potent bioactive ingredients in RB, ameliorate hepatic steatosis. However, whether SSs have anti-hyperlipidemia effects and plausible underlying mechanisms remain elusive. Aim of the studyTo comprehensively evaluate the lipid-lowering potential of SSs against hyperlipidemia in rats. Materials and methodsRNA sequencing and untargeted metabolomics approaches were applied to analyze the changes in the liver transcriptome and serum lipid profile in long-term high-fat diet feeding-induced hyperlipidemia rats in response to SSs or positive drug simvastatin (SIM) intervention. ResultsOur data revealed that SSs significantly alleviated HFD-induced hypertriglyceridemia and hypercholesterolemia. Combined with the analysis of gene ontology enrichment analysis and gene set enrichment analysis, we found that SSs remarkably repaired the unbalanced blood lipid metabolic spectrum in a dose-dependent manner by increasing the hepatic uptake of circulating fatty acids and facilitating mitochondrial respiration in fatty acid oxidation, comparable to SIM group. In addition, SSs markedly modulated cholesterol clearance by promoting intracellular cholesterol efflux, HDL remodeling, LDL particle clearance, and bile acid synthesis. SSs also efficiently protected the liver from lipid overload-related oxidative stress and lipid peroxidation, as well as substantially exaggerated inflammatory response. ConclusionOur research not only unraveled the intricate mechanisms underlying the lipid-lowering functions of SSs but also provided novel perspectives on developing an SSs-based therapeutic strategy for the treatment of hyperlipidemia. ClassificationMetabolism.

Analysis of network pharmacology and experimental verification to explore the mechanism of Modified Guilu Erxian Glue in the treatment of low immune function

ObjectiveThe aim of this study was to investigate the therapeutic effect of modified Guilu Erxian Gum (MGEG) on cyclophosphamide (Cy) induced immunosuppression in mice. Based on network pharmacology, the comprehensive mechanism of immune hypofunction was preliminarily discussed. MethodsCyimmunosuppression model was established to observe the effect of MGEG compound on immune injury in mice. The best compound was screened for network pharmacological analysis, and the "drug component" and "disease drug target" networks were established by network pharmacological methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted according to the common target between Chinese herbal medicine and low immunity to determine the biological process and signal pathway. The core components and targets obtained by network pharmacology were verified by Western blot analysis (WB). ResultsIn vivo experiments showed that the weight, thymus index, organ index, carbon particle clearance index, phagocytosis index, foot thickening level, macrophage phagocytosis and natural killer cell killing activity of immunosuppressed mice induced by Cy were significantly increased by Codonopsis pilosula, Guilu Erxian Jiaowei Wuxing Powder (CGW) (p<0.05 or p<0.01). In addition, CGW significantly increased the humoral and cellular immunity of immunosuppressed mice (p<0.05 or p<0.01). Based on the network pharmacological analysis, it is predicted that CGW contains 125 potential bioactive components, involving 489 action targets, and 125 common targets that may be related to immunosuppressive diseases. Based on the establishment of protein protein interaction network, five central nodes were identified as active factors involved in major biological functions. David, ClueGO and Metascape enrichment analysis all proved that CGW plays an important role in the regulation of immune function. By KEGG analysis, TNF signaling pathway is considered to be one of the main signaling pathways of CGW in the treatment of immunosuppression, including a wide range of intracellular signaling pathways. NF-κB signaling pathway regulates inflammation and immunity in TNF signaling pathway. WB showed that CGW significantly promoted NF-κB The expression of signal pathway further confirms that Chinese herbal compound can enhance the body's immunity and NF-κB signal path activation. ConclusionBased on network pharmacology and experimental verification, the potential targets and pathways of CGW to improve Cy induced immunosuppression and its potential therapeutic mechanism were revealed, providing a theoretical basis for development of traditional Chinese medicine. Guilu Erxian Gum (龟鹿二仙胶, GEG) is a traditional Chinese medicine prescription, which is widely used to treat low immunity and immune function impairment caused by chemotherapy. However, its potential pharmacological mechanism remains largely unknown.

Clearance of Metal Particles After Percutaneous Nephrolithotomy with Trilogy Lithotripter.

Purpose: To evaluate the clearance of metal particles produced and released in the pelvicaliceal system (PCS) during percutaneous nephrolithotomy (PCNL) with the use of the Swiss Lithoclast® Trilogy dual-energy (EMS Urology, Nyon, Switzerland) lithotripter. Methods: An experimental in vivo study and a clinical investigation of case series were conducted. An in vivo porcine model with two pigs for lithotripsy (after inserting artificial stones into the collecting system) and two pigs for submucosal injection of metal particles (provided by the manufacturer of Trilogy) was conducted. Porcine kidney histology analysis for metal leftovers was conducted immediately or 2 weeks after the surgery. A prospective observational study design included 10 consecutive patients treated with conventional 30F PCNL or with 22F mini-PCNL technique. Only the patients with the confirmed metal particles in the PCS during the initial PCNL and the need for additional retrograde intrarenal surgery over a period of 2-4 weeks were selected. The presence of metal particles was evaluated during the second endoscopic surgery. Results: The generated metal particles during PCNL and the submucosally injected particles were not found macroscopically 2 weeks postoperatively in porcine models. No pathologic changes such as foreign body granuloma or inflammation were found. Similarly, no metal particles were observed during the second look endoscopy (n = 10). Conclusion: Metal particles observed endoscopically using the Trilogy lithotripter are cleared with no pathologic evidence of tissue damage from the metal particles 2 weeks after the procedure. Thus, the intraoperative release of any particle by the Trilogy lithotripter should not raise any safety concerns.

Evaluation of Interventions to Improve Ventilation in Households to Reduce Risk for Transmission of Severe Acute Respiratory Syndrome Coronavirus 2.

Inadequate ventilation may contribute to the high risk for household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the effectiveness of several interventions recommended to improve ventilation in households. In 7 residential homes, carbon dioxide monitoring was conducted to assess ventilation in occupied open areas such as family rooms and in bedrooms and/or offices. Carbon dioxide levels above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation for the number of people present. In 1 of the 7 homes, various interventions to improve ventilation or to filter air were assessed in a kitchen area by measuring clearance of aerosol particles produced using an aerosol-based spray system and carbon dioxide generated by cooking with a gas stove. Carbon dioxide levels rose above 800 ppm in bedrooms and offices with 2 occupants when windows and doors were closed and in open areas during gatherings of 5 to 10 people; carbon dioxide levels decreased when windows or doors were opened. Clearance of carbon dioxide and aerosol particles significantly increased with interventions including running fans, operating portable air cleaners, and opening windows, particularly when there was a noticeable breeze or when a window fan was used to blow contaminated air outside. In households, several measures to improve ventilation or air filtration were effective in reducing carbon dioxide accumulation or enhancing clearance of carbon dioxide and aerosol particles. Studies are needed to determine if interventions to improve ventilation can reduce the risk for airborne transmission of SARS-CoV-2 in households.

Exploring the Genetic Association between Obesity and Serum Lipid Levels Using Bivariate Methods.

It is crucial to understand the genetic mechanisms and biological pathways underlying the relationship between obesity and serum lipid levels. Structural equation models (SEMs) were constructed to calculate heritability for body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the genetic connections between BMI and the four classes of lipids using 1197 pairs of twins from the Chinese National Twin Registry (CNTR). Bivariate genomewide association studies (GWAS) were performed to identify genetic variants associated with BMI and lipids using the records of 457 individuals, and the results were further validated in 289 individuals. The genetic background affecting BMI may differ by gender, and the heritability of males and females was 71% (95% CI [.66, .75]) and 39% (95% CI [.15, .71]) respectively. BMI was positively correlated with TC, TG and LDL-C in phenotypic and genetic correlation, while negatively correlated with HDL-C. There were gender differences in the correlation between BMI and lipids. Bivariate GWAS analysis and validation stage found 7 genes (LOC105378740, LINC02506, CSMD1, MELK, FAM81A, ERAL1 and MIR144) that were possibly related to BMI and lipid levels. The significant biological pathways were the regulation of cholesterol reverse transport and the regulation of high-density lipoprotein particle clearance (p < .001). BMI and blood lipid levels were affected by genetic factors, and they were genetically correlated. There might be gender differences in their genetic correlation. Bivariate GWAS analysis found MIR144 gene and its related biological pathways may influence obesity and lipid levels.

Exploring the potential mechanism of Yixiang capsule immune-enhancing function based on Network Pharmacology, Molecular docking, and Animal function experiment.

The Yixiang capsule with traditional Chinese herbs Cistanches Herba, Hedysarum multijugum Maxim,Fructus Ligustri Lucidi,and Fructus lycii are the main raw materials in a modern herbal medicine preparation containing corresponding bioactive ingredients after extraction and processing. This study aimed to investigate the immune-enhancing function of the Yixiang capsule and explore its potential mechanism. After oral administration of the Yixiang capsule to mice for 30 days, the spleen lymphocyte transformation activity, NK cell activity, DTH, macrophage phagocytosis, HC50 value, amounts of antibody-producing cells, carbon particle clearance rate, spleen, and thymus index were determined to evaluate the regulation effect of the Yixiang capsule on immune function. The potential mechanism underlying the immune-enhancing function of the Yixiang capsule was studied based on network pharmacology and molecular docking. The results showed that the Yixiang capsules can obviously increase the HC50 values in all groups, significantly enhance the DTH reaction of mice, the carbon clearance function in medium and high dose groups,and the phagocytic function of macrophages in high dose groups, but had no significant effect on NK cell activity, T lymphocyte proliferation, body weight and immune organ weight of mice. A total of 78 compounds of the Yixiang capsule may affect 123 metabolic pathways and 1022 GO terms by regulating 232 targets, such as the cancer signaling pathway ad the signal pathways of response to lipopolysaccharide, and the key targets predicted could stably bind to the core active components of the Yixiang capsule. These results suggested that the Yixiang capsule could enhance the immune function of mice and have the characteristics of a multi-component and multi-target synergistic effect on the enhanced immunity function, which provides the basis for the follow-up study.

Development and in vivo validation of phospholipid-based depots for the sustained release of bupivacaine

By direct deposition of the drug at the local site of action, injectable depot formulations – intended for treatment of a local disease or for local intervention – are designed to limit the immediate exposure of the active principle at a systemic level and to reduce the frequency of administration. To overcome known drawbacks in the production of some marketed phospholipid-based depots, here we propose to manufacture drug-loaded negatively charged liposomes through conventional technologies and to control their aggregation mixing a solution of divalent cations prior to administration. We identified phosphatidylglycerol (PG) as the most suitable phospholipid for controlled aggregation of the liposomes and to modulate the release of the anesthetic bupivacaine (BUP) from liposomal depots. In vivo imaging of the fluorescently-labelled liposomes showed a significantly higher retention of the PG liposomes at the injection site with respect to zwitterionic ones. In situ mixing of PG liposomes with calcium salts significantly extended the area under the curve of BUP in plasma compared to the non-depot system. Overall, controlling the aggregation of negatively charged liposomes with divalent cations not only modulated the particle clearance from the injection site but also the release in vivo of a small amphipathic drug such as BUP.