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• Good correlation of leaf tensity with dry weight biomass. • Establishing a non-destructive and rapid measurement of the dry weight biomass. • Investigation of the osmotic stress resistant traits of Orchophragmus violaceus. • Obtaining the re-watering time point via online electrophysiological parameters. Karst arid environments are not conducive to the normal growth of plants. Mastering the irrigation time point in advance can not only guarantee yield but can also save water resources in these regions. The seedlings of Orychophragmus violaceus L. during winter drought periods were processed by simulating a karst osmotic stress environment (high pH, high bicarbonate concentration, and drought) in a growth chamber to study the responses of photosynthesis, carbonic anhydrase (CA), leaf tensity (T d) and growth traits. All the plants were exposed to osmotic stress induced by poly-ethylene glycol (PEG 6000) at 5 levels (0, 10, 20, 40, and 80 g L−1 PEG) in the presence of 10 mmol L-1 NaHCO 3. The physiological osmotic stress tolerance threshold of O. violaceus was investigated. Leaf area and dry weight biomass (DW) estimation models were established, a non-destructive and rapid measurement of the DW was achieved. By analysing the temporal dynamic variations in the DW, combined with the relationship between T d and DW, a prediction of the re-watering time point of O. violaceus was achieved. The results indicated the following: (1) O. violaceus maintained good water status and high photosynthetic efficiency when the stress level was not higher than 20 g L-1 PEG, and its physiological osmotic stress tolerance threshold was 20 g L-1 PEG; (2) the growth rate of DW was calculated according to the derivative of the four-parameter logistic growth equation at each osmotic stress level. The appropriate percentage for the decline in growth rate under osmotic stress was 30% or 50% to achieve an improvement in product quality. The re-watering time points of O. violaceus that corresponded to the given decline in the growth rate at 10 g L-1 PEG was day 4.90 or day 2.66, and that at 20 g L-1 PEG was day 1.41. Subsequently, the T d corresponding to the above-mentioned re-watering time point was calculated according to the four-parameter logistic equation and mathematical model between T d and DW. O. violaceus at 10 g L-1 PEG should be re-watered when the T d is 0.99 or 0.48, and O. violaceus at 20 g L-1 PEG should be re-watered when the T d is 0.69. O. violaceus at 10 g L-1 PEG exhibited greater long-term osmotic stress resistance than that at 20 g L-1 PEG. Re-watering for O. violaceus at 10 g L-1 PEG could minimize the water demand with corresponding minimal impact on the DW, thereby leading to improved economic returns to water; and (3) as such, the rapid prediction of the re-watering time point can be achieved through online monitoring of electrophysiological parameters such as T d. [ABSTRACT FROM AUTHOR]

• Potential of using a spray tower for industrial CO 2 removal is numerically investigated. • Performance comparisons of various spray schemes are conducted. • Upward spray mode in lower layers shows a superior CO 2 removal performance. • Regulating mechanisms of spray schemes on CO 2 removal efficiency are illustrated. • Valuable insights for industrial CO 2 removal using a spray tower are supplied. The use of spray towers for post-combustion CO 2 capture has attracted growing industrial interest. However, its practical application is hampered by a lack of knowledge about CO 2 spray absorption on an industrial scale. Herein, we developed a numerical model to explore the potential of the spray tower for CO 2 removal at a 330 MW coal-fired power plant. The model was developed in the Euler-Lagrange framework integrated with interphase transfer models. The variations of gas-droplet flow, CO 2 removal efficiency, CO 2 loading of rich solution, and temperature distribution under different spray schemes were investigated. It was found that gas flow hydrodynamics and CO 2 removal performance can be regulated by the spray scheme. Compared to the conventional downward spray scheme, the lower nozzle layer adopted an upward spray scheme can improve the uniformity of the gas flow and results in several advantages: (1) average droplet residence time is extended by 5.2 %; (2) CO 2 removal efficiency increases from 79.1 % to 82.9 %. This improvement is attributed to two factors: one is the droplet's re-distribution, lowering the gas flow resistance in the region below the first spray layer near the inlet; the other is the change in gas-droplet interaction whereby the upward-moving droplets entrain the gas to flow upwards. Moreover, we investigated the effects of the spray schemes under varying flue gas loads. Under these conditions, the upward spray mode adopted in the first layer shows the best CO 2 removal performance. Further theoretical analysis reveals the mechanisms underlying the regulation effect. The findings in this work will benefit the design and optimization of the industrial-scale spray tower for CO 2 removal. [ABSTRACT FROM AUTHOR]

This study employed the Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) to investigate targeted droplet delivery in tracheal intubation. Our findings reveal that droplet behavior and deposition patterns are significantly influenced by droplet size. Smaller droplets (3 μm and 5 μm) closely follow airflow, showing similar deposition patterns in both CFD-DEM and CFD-DPM simulations. In contrast, larger droplets (7.5 μm and 10 μm) demonstrate increased deposition, particularly in the bent section of the Point Source Release tube (PSAR tube), due to enhanced inertia following collisions and coalescence. The study highlights that larger droplets experience a higher frequency of coalescence, especially in curved tube sections. This leads to altered droplet size distribution at the outlet, affecting deposition in the lower respiratory tract. These insights are crucial for optimizing inhalation therapy devices, emphasizing the importance of considering droplet interactions in CFD simulations to accurately predict aerosol behavior in pulmonary drug delivery systems. [Display omitted] • Innovative application of CFD-DEM for aerosol dynamics. • Customized collision model for liquid droplets. • Detailed analysis of droplet coalescence. • Quantitative evaluation of coalescence in PSAR tube sections. • Implications for targeted drug delivery in respiratory therapy. [ABSTRACT FROM AUTHOR]

Background: Congenital cataract, a kind of cataract presenting at birth or during early childhood, is a leading cause of childhood blindness. To date, more than 30 genes on different chromosomes are known to cause this disorder. This study aimed to identify the HSF4 mutations in a cohort from Chinese families affected with congenital cataracts. Methods: Forty-two unrelated non-syndromic congenital cataract families and 112 ethnically matched controls from southeast China were recruited from the southeast of China. We employed Sanger sequencing method to discover the variants. To confirm the novel mutations, STR haplotypes were constructed to check the co-segregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools including SIFT, Polyphen2, and Human Splicing Finder. The pathogenicity of all the mutations was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Results: No previously reported HSF4 mutations were found in all the congenital cataract families. Five novel HSF4 mutations including c.187 T > C (p.Phe63Leu), c.218G > T (p.Arg73Leu), c.233A > G (p.Tyr78Cys), IVS5 c.233-1G > A and c.314G > C (p.Ser105Thr) were identified in five unrelated families with congenital cataracts, respectively. These mutations co-segregated with all affected individuals in each family were not observed in the unaffected family members or in 112 unrelated controls. All five mutations were categorized to be the disease “pathogenic” according to ACMG guidelines and using InterVar software. Mutations in the HSF4 were responsible for 11.90% Chinese families with congenital cataracts in our cohort. Conclusions: In the study, we identified five novel HSF4 mutations in Chinese families with congenital cataracts. Our results expand the spectrum of HSF4 mutations causing congenital cataracts, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine. [ABSTRACT FROM AUTHOR]

• The evolution, transport and deposition of hygroscopic droplets are simulated in a highly idealized mouth-throat model. • The effects of different nebulization rates on aerosol evolution are considered. • The effects of different coupling methods on predicting droplet evolution are discussed. Inhalation therapy is widely used to treat various respiratory diseases. Nebulizers have been widely adopted due to their ease of operation, high drug delivery efficiency, and low residual volume. Traditional studies on drug delivery in the respiratory tract typically use a one-way coupled method to track drug transport and deposition for non-hygroscopic drug particles. However, neglecting the concentration of nebulized hygroscopic droplet aerosols can lead to significant discrepancies in the deposition efficiency (DE) of nebulized drugs in the airways. To investigate the effect of different nebulization rates on the evolution, transport, and deposition of droplets, a highly idealized mouth-throat (MT) model was selected as a testbed for the in silico trials of drug delivery to the respiratory tract. The interaction between continuous and discrete phases was modeled using a two-way coupled model of highly concentrated droplet aerosol-water vapor interaction, innovated by the particle parcel method. The effects of different coupling methods and boundary conditions on the average droplet diameter and droplet deposition distribution pattern at the outlet of the MT model were compared using a computational fluid dynamics (CFD) method. Simulation results indicate that neglecting the effect of water vapor evaporated from the droplets on the relative humidity (RH) in the oral cavity could lead to a 2.2-fold prediction error of the average droplet diameter at the outlet of the MT model for a conventional nebulization rate of 0.386 g/min. As the nebulization rate increases, the difference in the predicted average droplet diameter at the outlet of the MT model between the one-way coupled method and the two-way coupled method also increases. Increasing the nebulization rate during inhalation therapy could lead to incomplete evaporation of drug droplets, resulting in deposition of larger diameter drug droplets in the oral cavity. In contrast, a lower nebulization rate can reduce the droplet diameter at the outlet of the MT model, allowing it to enter deeper airways. [ABSTRACT FROM AUTHOR]

To identify RHO mutations in patients with non-syndromic retinitis pigmentosa (NS-RP). A total of 143 probands (46 family history and 97 sporadic cases) with NS-RP were recruited from Southeast China. The coding exons and adjacent intronic regions of RHO were PCR-amplified and sequenced by Sanger sequencing. The candidate variant was evaluated by the guidelines of American College of Medical Genetics and further validated through co-segregation analysis within the family. Five heterozygous mutations in RHO were detected in 5 out of 143 probands, where the frequency of RHO mutations in our cohort was approximately 3.5% (5/143) and 10.8% (5/46) for probands and families with NS-RP, respectively. Three known disease-causing mutations including c.C1030T (p.Q344X), c.C173G (p.T58R), and c.G266A (p.G89D) were identified in three unrelated families. The other two previously unreported mutations c.557C>A (p.S186X) and c.944delA (p.N315TfsX43) were confirmed in Family RP-087 and Family RP-139, respectively. These mutations co-segregated with available affected individuals in each family were not observed in the unaffected family members or in the 112 unrelated controls. This report expands the mutational spectrum of RHO gene associated with NS-RP and demonstrates the frequency of RP RHO mutations in Southeast Chinese populations. [ABSTRACT FROM AUTHOR]

Introduction: Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disease characterized by ocular albinism (OA) or oculocutaneous albinism (OCA), platelet dysfunction, and other symptoms. This study aimed to analyze the molecular defect in two Chinese families with suspected OA, as well as to investigate the profile of HPS6 variants and their genotype-phenotype correlations. Methods: Seven members from two families were recruited and underwent clinical ophthalmologic examinations. The genomic DNA was extracted from peripheral blood leukocytes. Whole-exome sequencing was performed on the proband of family JX. The single coding exon of HPS6 was directly Sanger sequenced based on PCR amplification in all available family members. An additional 46 probands from families or sporadic cases with the pathogenic variants of HPS6 reported in the literature were reviewed. Results: We identified two different compound heterozygous truncating variants of HPS6 in probands with suspected OA from two independent families. The proband of family JX had c.1674dup and c.503-504del variants, and the other proband from family CZ had a nonsense variant of c.1114C>T and a frameshift variant of c.1556del. Among them, c.1674dup and c.1556del variants in HPS6 have not been reported previously. Therefore, our patients were diagnosed as HPS6 disease by molecular diagnostics. In the retrospective cohort of HPS6 patients, we delineated the profile of HPS6 variants and revealed a significant overlap between CpG islands and the variants of HPS6, suggesting a potential link between DNA methylation and HPS6 variants. We also observed a spatial aggregation of the variants in 3D structure of HPS6 protein, implying the possible functional significance of these structural regions. In addition, we did not find any significant genotype-phenotype correlation of HPS6, and neither did we observe a correlation between the truncation length of the HPS6 protein and the phenotype of HPS6 disease. Conclusion: Our research expands the spectrum of HPS6 variants, providing a comprehensive delineation of their profile and systematically investigating genotype-phenotype correlations in HPS6. These findings could offer potentially valuable clues for investigating the molecular mechanism underlying HPS6 pathogenesis, as well as aiding the clinical diagnosis of HPS6 patients and improving disease prognosis. [ABSTRACT FROM AUTHOR]

Inhalation therapy is a practical approach to treat respiratory diseases. Vibrating mesh nebulizer (VMN), a device for inhalation therapy, is favored for its advantages, such as portability and noiselessness. The droplet deposition experiment using the VMN was carried out in an idealized mouth-throat (MT) model. This study used the 0.9% w/v concentration of nebulized sodium chloride (NaCl) droplet to measure the deposition fraction (DF). The inhalation flow rates were changed under two different temperature and humidity conditions, and the variation of droplet DFs as a function of inertial parameters was obtained under different inhalation flow rate conditions. The results show that the DF first decreases and then increases with the increasing inertial parameter, which is distinctly different from previous conclusions for dry powder or particle experiments and simulations. It indicates that the droplet evaporation substantially affects the transport and deposition. The results also show that increasing the mass fraction of water vapor in the air increases droplet DF in the airway. • Droplet deposition experiments were carried out in an idealized MT model. • DF of the droplets decreases first and then increases with the increasing inertial parameter. • Environmental condition impacts the DFs of nebulized droplets in the MT airway. • Increasing the mass fraction of water vapor in the air increases droplet DF. [ABSTRACT FROM AUTHOR]

Pneumonia is a common cause of hospitalization and death in children worldwide. Inhalation therapy is one of the methods treating pneumonia However, there are limited studies that distinguish between the physiology of children and adults, especially with respect to targeted drug delivery. A tracheobronchial (TB) tree model of an 11-year-old child with bronchopneumonia is selected as a testbed for in silico trials of targeted drug delivery. The airflow and particle transport are solved by the computational fluid dynamics method at an airflow rate of 15 LPM. The results indicate that the distribution of deposited particles shows aggregation on the particle release map. Point-source aerosol release (PSAR) method can significantly reduce the deposition efficiency (DE) of particles in the TB tree model. Specifically, the PSAR method can reduce the DE of large particles (i.e., 7.5 µm and 10 µm) by 7.57% and 9.61%, respectively. This enables rapid design of patient-specific treatment for different population age groups and different airway diseases. • A tracheobronchial tree model of a pediatric patient with bronchopneumonia was generated. • Release maps of particles with different diameters were obtained. • The locations for point-source aerosol release (PSAR) were optimized. • The optimized PSAR tubes can cover all diseased lung lobes. • The PSAR method can significantly reduce the deposition efficiency (DE) of large drug particles in the TB tree model. [ABSTRACT FROM AUTHOR]

The potential for essential oils (EOs) to act as a natural alternative for controlling mosquito populations has aroused extensive interest in recent years. Four EOs (Thymus vulgaris (thyme), Foeniculum vulgare (fennel), Citrus medica (lime), and Camellia sinensis (green tea)) were selected in our previous larvicidal screening assays against Aedes albopictus. In this study, the active constituents of each EO were identified. Next, their acetylcholinesterase (AChE) inhibitory activity was evaluated, and the binding mode was studied by molecular docking. To improve EO stability and duration of activity, nanoemulsions were prepared and characterized. Thirteen constituents of the four EOs at the 100 ppm level led to 100% mortality of the larvae, the four most active constituents being α-hexyl cinnamaldehyde (LC50 = 24.0 ± 0.3 ppm), limonene (LC50 = 34.1 ± 0.7 ppm), α-terpinene (LC50 = 50.0 ± 0.5 ppm), and carvacrol (LC50 = 54.7 ± 0.6 ppm). These compounds, with the exception of α-hexyl cinnamaldehyde, also showed potent AChE inhibitory activity. Nanoemulsions with droplet size of 56.8–224.9 nm were prepared by emulsification at a 1:1 (v/v) ratio of EO and Tween 80. These EO nanoemulsions showed equally potent larvicidal activity as EOs themselves; moreover, they showed better stability and were active for longer time. These results suggest that natural EOs and their constituents have potential as larvicides for mosquito vector control and that nanoemulsification is an effective method for improving their physicochemical properties and efficacy. [ABSTRACT FROM AUTHOR]

The adsorption of atmospheric pressure methanol on the polycrystalline copper surface has been studied by a combination of sum frequency generation imaging microscopy (SFGIM) and temperature programmed desorption (TPD). Methoxy species can be generated by exposing the polycrystalline copper surface to methanol vapor at room temperature. SFGIM results demonstrate that oxygen promotes the surface adsorption of methanol and the increase in the amount of methoxy produced on copper surface. SFGIM orientation analysis suggests the methoxy monolayer is oriented closer to the surface normal with introduction of oxygen. Employing the image statistical analysis approach, the heterogeneities and conformation distribution of methoxy monolayers on copper surface with and without oxygen adsorption are compared. These results illustrate SFGIM indeed could provide more insight for understanding the heterogeneous metal/metal oxide surface in the molecular level. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to the environment and human health concerns of synthetic repellents, essential oils (EOs) as natural alternatives have received increased attention. In this study, the repellent activity of 60 commercial EOs against Aedes albopictus was evaluated. In the initial screening, 8 active EOs including cinnamon, marjoram, lemongrass, bay, chamomile, jasmine, peppermint2, and thyme were selected. Twenty-one major constituents (>5% relative area) in the 8 active EOs were identified via gas chromatography-mass spectrometry (GC-MS) analysis. Cinnamaldehyde, citral and terpinene-4-ol displayed the highest repellent activity with more than 60% RR, which were more active than N,N-diethyl-3-methyl benzoyl amide (DEET). Next, their nanoemulsions were prepared and characterized. In the arm-in-cage assay, cinnamaldehyde- and citral-based nanoemulsions have prolonged mosquito protection time compared with their normal solutions. Mosquitoes are one of the most important disease vectors from a medical viewpoint in that they transmit several diseases such as malaria, filariasis, yellow and Dengue fever. Mosquito vector control and personal protection from mosquito bites are currently the most efficient ways to prevent these diseases. Several synthetic repellents such as DEET, ethyl butylacetylaminopropionate (IR3535) and 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine) (Picaridin), have been widely used to prevent humans from receiving mosquito bites. However, the use of synthetic repellents has raised several environment and health concerns. Therefore, essential oils (EOs) as natural alternatives receive our attention. In order to discover highly effective mosquito repellents from natural sources, the repellent activity of 60 commercial EOs against Ae. albopictus was screened in this study. Eight EOs including cinnamon, marjoram, lemongrass, bay, chamomile, jasmine, peppermint2, and thyme, showed a suitable repellent rate (>40%) at the tested dose of 10 μg/cm2. Then, their main constituents were analyzed by GC-MS, and the active constituents were identified. The most active compounds including cinnamaldehyde, citral and terpinen-4-ol, exhibited an 82%, 65% and 60% repellent rate, respectively. Moreover, the nanoemulsions of the three active compounds were prepared and characterized. In the arm-in-cage assay, the protection times of the nanoemulsions of cinnamaldehyde and citral were significantly extended compared with their normal solutions. This study provides several lead compounds to develop new mosquito repellents, and it suggests that nanoemulsification is an effective method for improving the duration of the activity of natural repellents. [ABSTRACT FROM AUTHOR]

Aryl quinolone derivatives can target the cytochrome bc 1 complex of Plasmodium falciparum , exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives. One such novel derivate, F14 , exhibited significant enhancements in both aqueous solubility (20 μM) and lipophilicity (Log D 2.7), whilst retaining nanomolar antimalarial activity against the W2 strain of P. falciparum (IC 50 = 235 nM). The pharmacokinetic studies reported, provide preliminary insights into the in vivo distribution and elimination of F14 , while findings from single crystal X-ray diffraction experiment rationalized the enhanced solubility. Protein X-ray crystallography and in silico docking simulations provide insight into the potential mode of action within the cytochrome bc 1 complex. These findings demonstrated the viability of this bioisostere replacement strategy and provided support for further exploration of in vivo efficacy in preclinical animal models and valuable insights for new drug design strategies in the fight against malaria. [Display omitted] • A series of novel 3-substituted quinolones isosteres were synthesized. • Modification of the quinolone scaffold improved DMPK properties and maintained nanomolar antimalarial activity. • F14 exhibited excellent metabolic stability and significant improvements in aqueous solubility. • These analogues share the same mode of action with the parental 3-substituted quinolones. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has led to severe social and economic disruption worldwide. Although currently no consent has been reached on a specific therapy that can treat COVID-19 effectively, several inhalation therapy strategies have been proposed to inhibit SARS-CoV-2 infection. These strategies include inhalations of antiviral drugs, anti-inflammatory drugs, and vaccines. To investigate how to enhance the therapeutic effect by increasing the delivery efficiency (DE) of the inhaled aerosolized drug particles, a patient-specific tracheobronchial (TB) tree from the trachea up to generation 6 (G6) with moderate COVID-19 symptoms was selected as a testbed for the in silico trials of targeted drug delivery to the lung regions with pneumonia alba, i.e., the severely affected lung segments (SALS). The 3D TB tree geometry was reconstructed from spiral computed tomography (CT) scanned images. The airflow field and particle trajectories were solved using a computational fluid dynamics (CFD) based Euler-Lagrange model at an inhalation flow rate of 15 L/min. Particle release maps, which record the deposition locations of the released particles, were obtained at the inlet according to the particle trajectories. Simulation results show that particles with different diameters have similar release maps for targeted delivery to SALS. Point-source aerosol release (PSAR) method can significantly enhance the DE into the SALS. A C++ program has been developed to optimize the location of the PSAR tube. The optimized simulations indicate that the PSAR approach can at least increase the DE of the SALS by a factor of 3.2× higher than conventional random-release drug-aerosol inhalation. The presence of the PSAR tube only leads to a 7.12% change in DE of the SALS. This enables the fast design of a patient-specific treatment for reginal lung diseases. [Display omitted] • A patient-specific tracheobronchial tree with moderate COVID-19 was generated. • Release maps of particles with different diameters were obtained. • The locations for point-source aerosol-release (PSAR) were optimized. • Delivery efficiency to designated lung sites was increased by 3.2 times using PSAR. • Presence of PSAR geometry has a negligible effect on drug delivery efficiency. [ABSTRACT FROM AUTHOR]

Analysis of elements in liquid samples via X-ray fluorescence (XRF) faces challenges due to diverse matrix effects. To address this, the use of glass fiber filters (GFFs) as effective substrates for XRF analysis was explored. The matrix compositions of various commercial GFFs were comprehensively analyzed and compared to assess their applicability in liquid analysis. Most GFFs do not contain heavy elements, exhibit highly consistent filter weights, and have matrix element contents with relative standard deviations (RSDs) below 3%, which are ideal for detecting heavy elements. GFFs were also demonstrated to have superior analytical sensitivity compared to alternative filters. Optimal analytical performance can be achieved by utilizing a 30 mm sample holder, dripping 50 μL of the sample on the uniformly pressed GFFs, and drying it via infrared heating. Most heavy elements showed wide linear concentration ranges spanning over three orders of magnitudes and limits of detection (LOD) lower than mg/L. The results of standard addition and recoveries in natural lake water were promising. Furthermore, GFFs proved capable of verifying the composition and quality of particulate materials. The used GFFs can also be easily regenerated through acid washing for reuse. Therefore, GFFs are optimal XRF substrates for analyzing liquid samples containing heavy metal ions and materials. [Display omitted] • The application of GFFs in liquid sample detection via XRF was comprehensively analyzed. • The criteria for selecting an ideal GFF by analyzing matrix elements were proposed for the first time. • The pretreatment and detection conditions of GFFs were optimized to achieve higher analytical performance than other filters. • Analysis of heavy elements by GFFs shows wide linear concentration ranges of 0.1–1000 mg/L. • GFFs can analyze nanomaterials' particle and composition uniformity and reused after acid washing. [ABSTRACT FROM AUTHOR]

This study delves into the dynamics of respiratory droplet dispersion in indoor settings, focusing on three pivotal aspects: the use of Respiratory Models (RM) versus Non-Respiratory Models (NRM), the influence of social distancing, and the size of exhaled droplets. Our advanced simulations reveal that RMs are essential for accurately predicting airflow and droplet trajectories, whereas NRMs tend to overestimate deposition. We further explore how variations in the distance between an infector and a susceptible individual significantly affect droplet behavior and potential transmission. Additionally, our findings highlight the critical role of droplet size in determining their travel and deposition patterns. These insights collectively provide a comprehensive understanding of aerosol transmission in indoor environments, offering valuable contributions to public health strategies aimed at controlling airborne diseases. [Display omitted] • Integrating respiratory models: boosts droplet trajectory prediction accuracy. • Simulating exhaled droplets: accounts for evaporation, heat, and mass transfer. • Analyzing social distance impact: varies droplet deposition on susceptible. • Assessing exhalation flow: crucial to determining exhaled droplets' fate. [ABSTRACT FROM AUTHOR]

Inhalation therapy is widely used in the treatment of acute epiglottitis (AE). However, few studies specifically consider the anatomical variations in pediatric AE treatment. This study aims to evaluate the deposition pattern of inhalation corticosteroids (ICS) in realistic upper airway models of pediatric AE patients. The epiglottic angle increases with the severity of AE, and five models of epiglottic angle were constructed. The computational fluid-particle dynamics (CFPD) was employed to simulate the airflow transport of pediatric AE and the particle deposition in the target area. The results show that as AE progressed, worsened airway narrowing was observed in the epiglottis region, accompanied by a decreasing trend in the optimal ICS particle size. The deposition pattern of ICS in pediatric AE is closely linked to the disease severity. Furthermore, the airway resistance increases significantly at 75°AE, providing an aerodynamic basis for assessing the severity of laryngeal obstruction. [Display omitted] • The inhalation of corticosteroids in different cases of acute epiglottitis was conducted virtually. • Pediatric acute epiglottitis with varying severity levels was firstly studied to date. • A substantial increase in airway resistance was observed at 75° acute epiglottitis. • Optimal inhaled corticosteroid particle size negatively correlated with epiglottis swelling. [ABSTRACT FROM AUTHOR]

• 30% −40% of patients with rheumatoid arthritis treated with anti-TNF-α antibodies are ineffective. • V5-3 can accurately target and neutralize the two key targets of VEGF and TNF-α in RA. • V5-3 effectively inhibits joint inflammation in CIA mice. • V5-3 significantly inhibits the proliferation of RA-FLS. Anti-TNF-α therapy fails in 30% of patients, where TNF-α may not be the key causative factor in these patients. We developed a bispecific single-domain antibody block TNF-α and VEGF (V5-3).The experiments showed that V5-3 effectively activated proliferation and migration of RA-FLS and HUVEC, tube-forming role of HUVEC, and expression of inflammatory factors in vitro. Besides, the experiments indicated that the anti-RA activity of V5-3 was superior to Anbainuo in vivo. Application of V5-3 reduced the expression of inflammatory factors, extent of synovial inflammation and angiogenesis and attenuated the severity of autoimmune arthritis in collagen-induced arthritis (CIA) mice. Mechanistically, V5-3 suppressed p65, AKT and VEGFR2 phosphorylation, as well as production of TNF-α and VEGF in joint tissues. These results demonstrated that V5-3 displayed a superior effect of anti-RA, may be a new therapy to overcome the limitations of anti-TNF - α monoclonal antibody. [ABSTRACT FROM AUTHOR]

CO 2 capture in the spray tower using aqueous ammonia solution has been proved a potential approach for the post-combustion CO 2 capture. To improve the performance of spray absorption, a new three-dimensional numerical model integrating the complex gas-liquid hydrodynamics and the chemistry of the NH 3 -CO 2 -H 2 O system has been proposed and developed in this paper. In the model, the gas-liquid hydrodynamics was simulated using the Euler-Lagrange method, while the chemistry of the NH 3 -CO 2 -H 2 O system, including both thermodynamic and kinetic characteristics, was modeled using user-defined modules implemented in the CFD package. Moreover, a laboratory scale spray absorption system was built, and run under various operating conditions were carried out in order to validate the model developed. Subsequently, the predicted results using different kinetic models were compared with the experimental results. It was found the model using Liu’s kinetics showed a better agreement with the experiments, especially when the liquid temperature and NH 3 concentration of solution vary. Furthermore, the validated model was used to study the fundamentals of spray absorption. It has been found that the gas temperature profile as well as gaseous CO 2 and NH 3 concentration profile depends on the velocity field, indicating the hydrodynamics should be considered when optimizing the design of reactor. It has also been found that the residence time of droplets increases with the increase of gas flow rate, leading to an increase in average droplets temperature and CO 2 loading, while the increase of ammonia concentration of solution could significantly improve the overall CO 2 mass transfer coefficient. When the solution temperature increases from 293 K to 303 K, the overall CO 2 mass transfer coefficient gradually increases, resulting in CO 2 removal efficiency improvement. However, when the solution temperature increases from 303 K to 313 K, the promotion of reverse reaction leads to the reduction of CO 2 removal efficiency. In addition, the increase of ammonia solution flow rate would mainly increase the interphase area and promote both CO 2 absorption and NH 3 escape. The model developed in this paper can be used to optimize the design and operation of such reactors in practice. [ABSTRACT FROM AUTHOR]

Abstract: Amphibian skin secretions are rich sources of biologically-active peptides with antimicrobial peptides predominating in many species. Several studies involving molecular cloning of biosynthetic precursor-encoding cDNAs from skin or skin secretions have revealed that these exhibit highly-conserved domain architectures with an unusually high degree of conserved nucleotide and resultant amino acid sequences within the signal peptides. This high degree of nucleotide sequence conservation has permitted the design of primers complementary to such sites facilitating “shotgun” cloning of skin or skin secretion-derived cDNA libraries from hitherto unstudied species. Here we have used such an approach using a skin secretion-derived cDNA library from an unstudied species of Chinese frog – the Fujian large-headed frog, Limnonectes fujianensis – and have discovered two 16-mer peptides of novel primary structures, named limnonectin-1Fa (SFPFFPPGICKRLKRC) and limnonectin-1Fb (SFHVFPPWMCKSLKKC), that represent the prototypes of a new class of amphibian skin antimicrobial peptide. Unusually these limnonectins display activity only against a Gram-negative bacterium (MICs of 35 and 70 μM) and are devoid of haemolytic activity at concentrations up to 160 μM. Thus the “shotgun” cloning approach described can exploit the unusually high degree of nucleotide conservation in signal peptide-encoding domains of amphibian defensive skin secretion peptide precursor-encoding cDNAs to rapidly expedite the discovery of novel and functional defensive peptides in a manner that circumvents specimen sacrifice without compromising robustness of data. [Copyright &y& Elsevier]

A new method for measuring self-discharge of lithium-ion graphite anodes is reported. First, the anode lithium content is calculated from the open-circuit potential as a function of open-circuit time (OCP versus OCT) using equilibrium potential–composition isotherms. Then, the self-discharge rate is obtained from the differential of lithium content with respect to time on open circuit. The self-discharge rate measured by this means after the first charge–discharge cycle to 0.0 V versus Li/Li+ is largely controlled by the growth of the solid electrolyte interphase (SEI) film, with some influence from stage transformation. [Copyright &y& Elsevier]

Calcium looping process (CaL) is a promising thermochemical energy storage technology for the application in the 3rd generation concentrated solar power plants (CSP). Hence, it is necessary to develop the highly efficient CaO-based heat storage composite materials. The structurally improved, CaO-based pellets were prepared via adding cellulose as the pore-forming template. Furthermore, the approach of TiO 2 incorporation was adopted aiming to enhance the anti-sintering ability of the structurally improved, CaO-based pellets. It is found that the structurally improved, TiO 2 -incorporated, CaO-based pellets that containing 25 wt% of TiO 2 exhibit the highest CaO carbonation conversion and energy density of 57.5% and 1827.7 kJ/kg after 20 cycles, which are nearly 1.3 times as high as those of the pure Ca(OH) 2 pellets. The superiority of the structurally improved, TiO 2 -incorporated, CaO-based pellets on cyclic heat energy storage/release is more prominent under harsh calcination conditions (950 °C, pure CO 2). The evenly distributed CaTiO 3 grains, providing structural stability to the CaO-based pellets and also enhancing the anti-sintering ability, are responsible for the improved cyclic energy storage/release performance. Additionally, the desirable compression strength (16.67 ± 1.05 MPa) contributes to strengthen the practicability of structurally improved, TiO 2 -incorporated, CaO-based pellets applied in the CaL-CSP system. [Display omitted] • Highly efficient CaO-based pellets were prepared for thermochemical energy storage. • Cellulose addition generates abundant pore and cavity within CaO-based pellets. • TiO 2 incorporation provides structural stability to the CaO-based pellets. • Structurally improved TiO 2 -incorporated CaO-based pellets possess desirable mechanical property. [ABSTRACT FROM AUTHOR]

Aryl quinolone derivatives can target the cytochrome bc 1 complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives. One such novel derivate, F14, exhibited significant enhancements in both aqueous solubility (20 μM) and lipophilicity (LogD 2.7), whilst retaining nanomolar antimalarial activity against the W2 strain of P. falciparum (IC 50  = 235 nM). The pharmacokinetic studies reported, provide preliminary insights into the in vivo distribution and elimination of F14, while findings from single crystal X-ray diffraction experiment rationalized the enhanced solubility. Protein X-ray crystallography and in silico docking simulations provide insight into the potential mode of action within the cytochrome bc 1 complex. These findings demonstrated the viability of this bioisostere replacement strategy and provided support for further exploration of in vivo efficacy in preclinical animal models and valuable insights for new drug design strategies in the fight against malaria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Zhaojun Sheng reports financial support was provided by Wuyi University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In the present study, a zeolitic imidazolate framework with mixed ligands, ZIF-8-90, was synthesized and embedded into an ultrathin polydimethyldiethoxysilane (PDMDES) matrix to prepare a ZIF-8-90/PDMDES mixed matrix membrane (MMM) for the enhanced recovery of alcohols from dilute aqueous solutions via pervaporation, using a facile solution coating method. The synthesized ZIF-8-90 particles demonstrated superior hydrophobicity and thermal stability compared to those of both ZIF-8 and ZIF-90 particles. Furthermore, the hydrophobicity, thermal stability, and sorption ability for alcohols of the ZIF-8-90/PDMDES MMM were significantly improved, attributed to the incorporation of mixed-ligand ZIF-8-90. Notably, the MMMs displayed two distinct cross-sectional morphologies: (1) ZIF-8-90 particles enveloped by PDMDES polymer forming filler bulges and (2) an accumulation of ZIF-8-90 particles resembling a brick-wall-like structure. The MMM incorporating 2.5 wt % ZIF-8-90 exhibited the optimal performance among the fabricated MMMs with various ZIF-8-90 loadings, spanning from 0 to 3.2 wt %. The effects of feed concentrations and operation temperatures were systematically investigated. The best pervaporation performance was achieved using the 2.5 wt % ZIF-8-90-filled MMM, effectively separating a 5.0 wt % ethanol/water mixture at 60 °C, yielding a distinguished total flux of 7.70 kg·m -2 ·h -1 , an improved separation factor of 9.96, and an extraordinarily high PSI of 68.99 kg·m -2 ·h -1 . Comparative analyses highlighted the superior pervaporation performance of the ZIF-8-90/PDMDES MMM over ZIF-8/PDMDES MMM, ZIF-90/PDMDES MMM, and other MMMs, underscoring its potential for practical applications in alcohol recovery.

Respiratory infections are currently understood to be caused by pathogens released through the nose or mouth of an infected individual, and subsequently transmitted to susceptible hosts. These pathogens are enclosed in liquid particles that are aerosolized from the respiratory tract during activities such as breathing, speaking, sneezing, and coughing. These particles vary widely in size, ranging from submicron to several microns. While past research has largely overlooked the human respiratory system, recent analysis has revealed that the actual structure of the nasal cavity significantly influences the prediction of aerosol transmission during exhalation. In this study, computational fluid dynamics (CFD) simulations were conducted to analyze the aerosol transmission generated during exhalation from the nasal and oral cavities. Realistic nasal and oral cavity structures were taken into account, and authentic temperature distributions were applied to the surfaces. Additionally, inhalation conditions for susceptible individuals were established to evaluate the risk of inhalation-generated exposure. Through various simulation scenarios, we separately discussed the impact of environmental wind speed, separation distance, and exhalation flow rate. The simulation results indicate that environmental wind amplifies the complexity of the flow field and the transmission and deposition of particles between two individuals. Under ambient wind velocities of 0.5 m/s and 1 m/s, it was observed that over 80% of the particles with a diameter of 1 µm inhaled through the nasal cavity accounted for the total deposition on the infected individual. Furthermore, high exhalation flow rates exhibited higher deposition ratios at close distances, in line with our expectations. Therefore, it is advisable to minimize close contact as much as possible during periods of frequent respiratory infections, and to wear masks in order to reduce the risk of inhalation exposure. Implications : During the activities such as breathing, speaking, sneezing, and coughing, liquid particles containing pathogens are aerosolized from the respiratory tract and are released from nose or mouth through the nebulization. In this study, we investigated the transmission of aerosols from human exhalation in the outdoor environment, innovatively taking the real oral-nasal structure and the active inhalation of vulnerable people into consideration, and explored the human-to-human transmission of respiratory viruses. The results are beneficial for public health assessment and policy development.

Objective: This study aimed to investigate factors influencing fetal growth restriction (FGR) occurrence and assess the clinical significance of fetal cardiac parameters in FGR prediction., Methods: Pregnant women with clinically suspected FGR (n=179) and uncomplicated pregnancies (n=53) were included. All had undergone routine obstetric ultrasonography and fetal echocardiography. Umbilical artery flow (UAF) and fetal cardiac parameters (left atrial transverse diameter (LAd), right atrial transverse diameter (RAd), left ventricular transverse diameter (LVd), right ventricular transverse diameter (RVd), foramen ovale width, atrial septum diameter, interventricular septal thickness, left ventricular posterior wall thickness, right ventricular free wall thickness, aortic diameter, pulmonary artery diameter, mitral E velocity, mitral A velocity, tricuspid E velocity, tricuspid A velocity, aortic valve peak flow velocity, and pulmonary valve peak flow velocity) were detected. Follow up was conducted until birth, various fetal clinical parameters were collected: maternal body mass index (BMI), hypertensive disorders complicating pregnancy (HDCP), abnormal umbilical artery flow, placental or umbilical cord anomalies, low amniotic fluid volume, preterm birth, emergency cesarean delivery, maternal height, maternal age, gestational diabetes mellitus (GDM), hypothyroidism, assisted reproductive technology (ART), parity, and neonatal gender. Participants were categorized into confirmed FGR (n=119) and control (n=113) groups based on neonatal birth weight., Results: Significant differences were observed between groups in maternal BMI, HDCP, abnormal UAF, placental or umbilical cord anomalies, low amniotic fluid volume, preterm birth, and emergency cesarean delivery. FGR was positively related to abnormal UAF, placental or umbilical cord anomalies, preterm birth and emergency cesarean delivery and negatively to maternal BMI (r=-0.276). Compared to the control group, the FGR group exhibited significantly larger RAd, RVd, RA/LA, and RV/LV., Conclusion: Fetal growth-restricted fetuses have enlarged right heart structures. Fetal cardiac examinations are valuable for early FGR diagnosis, potentially improving neonatal body weight and reducing adverse pregnancy outcomes., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chen et al.)

The coronavirus disease 2019 (COVID-19) pandemic, which caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to a crisis with devastating disasters to global public economy and health. Several studies suggest that the SARS-CoV-2 nucleocapsid protein (N protein) is one of uppermost structural constituents of SARS-CoV-2 and is relatively conserved which could become a specific diagnostic marker. In this study, eight single domain antibodies recognized the N protein specifically which were named pN01-pN08 were screened using human phage display library. According to multiple sequence alignment and molecular docking analyses, the interaction mechanism between antibody and N protein was predicted. ELISA results indicated pN01-pN08 with high affinity to protein N. To improve their efficacy, two fusion proteins were prepared and their affinity was tested. These finding showed that fusion proteins had higher affinity than single domain antibodies and will be used as diagnosis for the pandemic of SARS-CoV-2., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yang et al.)

Background: While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer. This study investigated the potential of combining a non-invasive liquid biopsy technique, along with a methylation analysis, to assess the surgical perforation risk of ESCA patients., Methods: In this study, we conducted an analysis of gene expression differences between stage I esophageal squamous carcinoma samples and healthy tissue samples using data from The Cancer Genome Atlas (TCGA) database. We also identified the genes associated with progression-free survival (PFS) in esophageal squamous carcinoma. Integrating the framework of the methylation analysis, we explored the methylated sites of these distinct genes. To refine this process, we used the Shiny Methylation Analysis Resource Tool (SMART) to conduct a comprehensive analysis of these sites. We then confirmed the stability of the methylation sites in different lesion conditions using methylation-specific quantitative polymerase chain reaction (MS-qPCR) with paraffin tissue samples collected after ESD., Results: We analyzed RNA-sequencing data from 42 early stage ESCA patients and 17 controls, identifying 1,263 up-regulated and 460 down-regulated genes. Functional analyses revealed involvement in key pathways such as cell cycle regulation and immune responses. Furthermore, we identified 38 differentially expressed genes associated with PFS. Using SMART analysis, we found 217 hyper-methylated regions in 38 genes, suggesting potential early markers for ESCA. Validation experiments confirmed the reliability of 29 hyper-methylated regions in FFPE tissue samples and 6 regions in cfDNA. A LunaCAM model showed high accuracy [area under the curve (AUC) =0.89] in discriminating early ESCA. Integrated assessment of six highly methylated regions significantly improved predictive performance, with 90.56% sensitivity, highlighting the importance of combinatorial biomarker evaluation for early cancer detection., Conclusions: This study established a novel approach that integrates non-invasive testing with a methylation analysis to assess the surgical risk of early ESCA patients. The significance of changes in methylation sites in relation to lesion status should not be underestimated, as they have the potential to offer vital insights for proactive risk assessments before surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-314/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease. Its pathogenesis has not yet been clarified, so it is urgent to explore therapeutic targets. Here, we clarified the role of HDAC6 in the mechanism of action of RA through mediating chaperone-mediated autophagy (CMA) to provide a clinical treatment of RA., Methods: We used rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis mice (CIA mice) as models of RA and pharmacological inhibitors as well as genetic interference with adeno-associated viruses to reduce the expression of HDAC6. We explored the influence of CAY10603 on RA-FLS proliferation and inflammation, as well as the expression of proteins related to the CMA signaling pathway. CIA model was constructed using DBA/1J mice. Arthritis symptoms in CIA mice were evaluated, and the expression and localization of CMA-related proteins in mouse ankle joints were examined., Results: CAY10603 inhibited proliferation as well as the level of the molecular chaperone autophagy in RA-FLS. HDAC6 shRNA significantly reduced the clinical signs of arthritis in CIA mice, as did the expression of HDAC6 in the serum and ankle synovial tissues of CIA mice. Finally, it significantly inhibited the level of Hsc70 and LAMP-2A, which are involved in the CMA signaling pathway, in ankle joint tissues., Conclusion: Downregulation of HDAC6 may inhibit CMA and thereby ameliorate RA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Lai, Zheng, Luo, Chen, Que and Zhang.)

Herein, burdock polysaccharide (BP) and modified burdock polysaccharide (MBP) were prepared, followed by the fabrication of chlorogenic acid (CA)-BP, CA-MBP, isochlorogenic acid A (ICA)-BP, and ICA-MBP nanoparticles. Afterward, the structural characteristics, physical stability, digestive characteristics, and antioxidant activity of hydrogen peroxide (H 2 O 2 )-damaged HepaRG cells were evaluated. The result indicated that the loading capacities of CA in BP-CA and MBP-CA were 0.14 and 0.53 μg/mg, respectively. Conversely, the loading capacities of ICA in BP-ICA and MBP-ICA were 0.36 and 0.60 μg/mg, respectively. Four complex nanoparticles exhibited excellent physical stability under different pH values, temperatures, and ionic concentrations, especially MBP-CA and MBP-ICA . Moreover, four complex nanoparticles could protect caffeoylquinic acid from being released in gastric fluid. All six samples exhibited high antioxidant activity in H 2 O 2 -induced HepaRG cells, especially BP and MBP-CA. These findings indicated that caffeoylquinic acid-polysaccharide complexes were successfully prepared and highlighted the potential of polysaccharides as natural carriers for hydrophobic bioactive molecules., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Unmanned transportation in construction scenarios presents a significant challenge due to the presence of complex dynamic on-ground obstacles and potential airborne falling objects. Consequently, the typical methodology for composite air-ground risk avoidance in construction scenarios holds enormous importance. In this paper, an integrated potential-field-based risk assessment approach is proposed to evaluate the threat severity of the environmental obstacles. Meanwhile, the self-adaptive dynamic window approach is suggested to manage the real-time motion planning solution for air-ground risks. By designing the multi-objective velocity sample window, we constrain the vehicle's speed planning instructions within reasonable limits. Combined with a hierarchical decision-making mechanism, this approach achieves effective obstacle avoidance with multiple drive modes. Simulation results demonstrate that, in comparison with the traditional dynamic window approach, the proposed method offers enhanced stability and efficiency in risk avoidance, underlining its notable safety and effectiveness.

The first approved RNAi therapeutics, ONPATTRO, in 2017 moves the concept of RNA interference (RNAi) therapy from research to clinical reality, raising the hopes for the treatment of currently incurable diseases. However, RNAi therapeutics are still facing two main challenges-susceptibility to enzymatic degradation and low ability to escape from endo/lysosome into the cytoplasm. Therefore, we developed disulfide-based nanospheres (DBNPs) as universal vehicles to achieve efficient RNA delivery to address these problems. Notably, the DBNPs possess unique and desirable features, including improved resistance to nuclease degradation, direct cytoplasmic delivery through thiol-mediated cellular uptake, and cytosolic environment-responsive release, greatly enhancing the bioavailability of RNA therapeutics. Additionally, DBNPs are superior in terms of overcoming formidable physiological barriers, including vascular barriers and impermeable tumor tissues. Owning to these advantages, the DBNPs exhibit efficient gene silencing effect when delivering either small interfering RNA (siRNA) or microRNA in various cell lines and generate remarkable growth inhibition in the zebrafish and mouse model of pancreatic tumors as compared to traditional delivery vectors, such as PEI. Therefore, DBNPs have potential application prospect in RNAi therapy both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: RNA interference (RNAi) therapeutics could target and alter any disease-related mRNA translation, thus have great potential in clinical application. Delivery efficiency of RNA modalities into cell cytoplasm is the main problem that currently limit RNAi therapeutics to release their full potential. Most of the known delivery materials suffer from the endo/lysosomal entrapment and enzymatic degradation during endocytosis-dependent uptake, resulting unsatisfied efficiency of the cytoplasmic release. Here, we developed disulfide-based nanospheres could directly transfer RNA modalities into the cytoplasm and significantly enhance the delivery efficiency, thus holding great potential in RNAi therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Fine particulate matter is a leading air pollutant, and its composition profile relates to sources and health effects. The human respiratory tract hosts a warmer and more humid microenvironment in contrast with peripheral environments. However, how the human respiratory tract impacts the transformation of the composition of environmental PM 2.5 once they are inhaled and consequently changes of source contribution and health effects are unknown. Here, we show that the respiratory tract can make these properties of PM 2.5 reaching the lung different from environmental PM 2.5 . We found via an in vitro model that the warm and humid conditions drive the desorption of nitrate (about 60%) and ammonium (about 31%) out of PM 2.5 during the inhalation process and consequently make source contribution profiles for respiratory tract-deposited PM 2.5 different from that for environmental PM 2.5 as suggested in 11 Chinese cities and 12 US cities. We also observed that oxidative potential, one of the main health risk causes of PM 2.5 , increases by 41% after PM 2.5 travels through the respiratory tract model. Our results reveal that PM 2.5 inhaled in the lung differs from environmental PM 2.5 . This work provides a starting point for more health-oriented source apportionment, physiology-based health evaluation, and cost-effective control of PM 2.5 pollution.

This study focuses on the transport, deposition, and triggered immune response of intranasal vaccine droplets to the angiotensin-converting-enzyme-2-rich region, i.e., the olfactory region (OR), in the nasal cavity of a 6-year-old female to possibly prevent corona virus disease 19 (COVID-19). To investigate how administration strategy can influence nasal vaccine efficiency, a validated multi-scale model, i.e., computational fluid-particle dynamics (CFPD) and host-cell dynamics (HCD) model, was employed. Droplet deposition fraction, size change, residence time, and the area percentage of OR covered by the vaccine droplets, and triggered immune system response were predicted with different spray cone angles, initial droplet velocities, and compositions. Numerical results indicate that droplet initial velocity and composition have negligible influences on the vaccine delivery efficiency to OR. In contrast, the spray cone angle can significantly impact the vaccine delivery efficiency. The triggered immunity was not significantly influenced by the administration investigated in this study due to the low percentage of OR area covered by the droplets. To enhance the effectiveness of the intranasal vaccine to prevent COVID-19 infection, it is necessary to optimize the vaccine formulation and administration strategy so that the vaccine droplets can cover more epithelial cells in OR to minimize the number of available receptors for SARS-CoV-2., Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article., (© Tsinghua University Press 2023.)

The surgery outcomes after fixing nasal airway obstruction (NAO) are sometimes not satisfactory in improving ventilations of airflow. A case study is presented in this paper with computational fluid dynamics applied to determine the key factors for successful septoplasty plans for a patient with a deviated nasal septum. Specifically, airflow, as well as particle transport and deposition were predicted in a pre-surgery nasal cavity model reconstructed from patient-specific Computer Tomography (CT) images and two post-surgery nasal cavity models (i.e., VS1 and VS2) with different virtual surgery plans A and B. Plan A corrected the deviated septal cartilage, the perpendicular plate of the ethmoid bone, vomer, and nasal crest of the maxilla. Plan B further corrected the obstruction in the nasal vestibule and caudal nasal septal deviation based on Plan A. Simulations were performed in the three nose-to-throat airway models to compare the airflow velocity distributions and local particle depositions. Numerical results indicate that the VS2 model has a better improvement in airflow allocation between the two sides than the VS1 model. In addition, the deposition fractions in the VS2 model are lower than that in both the original and VS1 models, up to 25.32%. The better surgical plan (i.e., Plan B) reduces the particle deposition on the convex side, but slightly increases the deposition on the concave side. However, the overall deposition in the nasal cavity is reduced., Competing Interests: No potential conflict of interest was reported by the authors.

The defect detection of fiber-optic coils (FOCs) plays an important role in the quality control of the FOC production. In order to overcome the problems of poor performance and low reliability of existing methods, this paper provides a solution for winding defect detection of FOCs based on low-rank representation (LRR) technology. First, we design a feature matrix, which represents the image. Then the LRR model is employed to formulate the defect detection task as a problem of low rank and sparse matrix decomposition. Meanwhile, Laplacian regularization is introduced as a smoothness constraint to expand the distance between defect regions and low-rank background. Experiments are performed on a real dataset to verify the algorithm. The results show that the proposed winding defect detection method of FOCs achieves the highest detection accuracy and lowest false alarm rate compared to other methods, verifying the effectiveness of the proposed method.

The aim of our study was to synthesize a pumpkin peel polysaccharide (PPP)-Cr(III) complex and investigate its hypoglycemic activity. Firstly, a novel PPP-Cr(III) complex with a Cr content of 23.77 mg/g was synthesized and characterized. Physicochemical characterization indicated that PPP-Cr(III) had some changes in chemical composition, monosaccharide composition, and morphological structure compared with PPP. The molecular weights of PPP-Cr(III) and PPP were 1.398 × 10 6 g/mol and 3.386 × 10 6 g/mol, respectively, showing a lower molecular weight after the introduction of Cr(III). Fourier transform infrared spectroscopy showed that a new characteristic absorption peak of Cr-O appeared at 534 cm -1 in PPP-Cr(III), indicating that Cr(III) was successfully complexed with PPP. Secondly, the hypoglycemic activity of PPP-Cr(III) based on α-glucosidase inhibitory and insulin resistance (IR)-HepG2 cells was evaluated. Compared with PPP, PPP-Cr(III) exhibited a more significantly α-glucosidase inhibitory activity. The IR-HepG2 cells confirmed an obvious increase in glucose consumption. Western blot analysis demonstrated that the treated IR-HepG2 cells were able to increase the protein levels of p-AMPK and p-GSK-3β, indicating that IR-HepG2 cells exerted hypoglycemic activity via the AMPK/GSK-3β signaling pathway. These results suggested that PPP-Cr(III) had good hypoglycemic activity, which could provide theoretical support for the development of novel hypoglycemic products.

Long non-coding RNA (lncRNA) is involved in the regulation of rheumatoid arthritis (RA) and many other diseases. In this study, a new lncRNA, NR-133666, was identified to be highly expressed in the adjuvant-induced arthritis rat model using the Agilent lncRNA microarray assay. qRT-PCR verified that NR-133666 was upregulated in fibroblast-like synoviocyte of a collagen-induced arthritis (CIA) rat model. Fluorescence in situ hybridization analysis showed that NR-133666 is mainly expressed in the cytoplasm of collagen-induced arthritis FLS. MTT assay and EdU staining results showed that the proliferation of CIA FLS was inhibited after NR-133666 was knocked down, and the wound healing assay showed that the migration of CIA FLS was also suppressed. Dual luciferase detection was used to confirm the relationship among NR-133666, miR-133c and MAPK1. MAPK1 is the target gene of miR-133c, where NR-133666 acts as a sponge of miR-133c to reduce the inhibitory effect of miR-133c on MAPK1. Overexpression of NR-133666 and MAPK1 can promote the proliferation and migration of CIA FLS, and overexpression of miR-133c can reverse this phenomenon. Western blot indicated that it may be related to the ERK/MAPK signaling pathway. Collectively, we identified that lncRNA NR-133666 acted as a miR-133c sponge that can promote the proliferation and migration of CIA FLS through regulating the miR-133c/MAPK1 axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zheng, Luo, Lin, Que, Wang, Huang, Yang, Ye and Chen.)

Sepsis caused by a dysregulated host response to infection is a life-threatening disease that can lead to organ dysfunction. Due to its unclear and complex mechanism, effective medicine for the treatment of sepsis is urgently required. The extensive release of cytokines and other mediators like TNF-α and interleukin-6 (IL-6) play critical roles in the development of sepsis. The present study aims to evaluate the potential protective effects of an anti-TNF-α/HSA/IL-6R triple-specific fusion protein (TAL-6) under septic experimental conditions. The anti-TNF-α/HSA/IL-6R triple-specific fusion protein (TAL-6), which links three published single domain antibodies, was designed and constructed in our lab. High purity fusion proteins were obtained with high binding affinity for TNF-α (94.75 pM), human serum albumin (1.83 nM) and IL-6R (2.29 nM). TAL-6 protected mouse fibroblast fibrosarcoma cells (L929) from apoptosis induced by TNF-α, establishing that the expressed fusion proteins can selectively interact with TNF-α in vitro. In vivo, the survival rate of cecal ligation and puncture (CLP) was notably increased in the group with TAL-6 treatment and significantly higher compared with the single-targeted IL-6R and TNF-α fusion protein at the same dose. After treatment with TAL-6, the serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased, and sepsis-induced pathological injuries in the kidney were remarkably attenuated. TAL-6 is therefore a potential candidate for the development of new drugs against sepsis in human., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractive candidates for the next-generation biologic drug study. In this study, we established a simple prokaryotic expression system for a dual target-directed single domain-based fusion protein against the interleukin-6 receptor and human serum, albumin, the recombinant anti-IL-6R fusion protein (VHH-0031). VHH-0031 exhibited potent anti-inflammatory effects produced by LPS on cell RAW264.7, where the major cytokines and NO production were downregulated after 24 h incubation with VHH-0031 in a dose-dependent manner. In vivo, VHH-0031 presented significant effects on the degree reduction of joint swelling in the adjuvant-induced arthritis (AIA) rat, having a healthier appearance compared with the dexamethasone. The expression level of JNK protein in the VHH-0031 group was significantly decreased, demonstrating that VHH-0031 provides a low-cost and desirable effect in the treatment of more widely patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose : To investigate the protective effects of nicotinamide riboside (NR) on oxidative damage in hydrogen peroxide (H 2 O 2 )-exposed human lens epithelial cell lines (SRA01/04) and the possible mechanisms underlying its protective effects. Materials and methods : SRA01/04 cells were divided into three groups: the control (CON) group, model (H 2 O 2 ) group and treatment (NR+H 2 O 2 ) group. Superoxide dismutase (SOD), catalase (CAT) and total glutathione (GSH) levels were detected to evaluate oxidative damage induced by different concentrations of H 2 O 2 in SRA01/04 cells. After SRA01/04 cells were treated with NR and/or H 2 O 2 , cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining, cell apoptosis was analysed using flow cytometry, reactive oxygen species (ROS) were measured with the DCFH-DA probe, and mitochondria were stained with MitoTracker to measure the mitochondrial membrane potential (MMP). In addition, western blotting was performed to detect the levels of proteins associated with apoptosis and related signalling pathways. Results : H 2 O 2 induced oxidative damage in SRA01/04 cells by inhibiting the activity of SOD and CAT and reducing total GSH levels. Treatment of SRA01/04 cells with NR significantly increased cell viability and reduced cell apoptosis and ROS generation, whereas SOD and CAT activities and total GSH and MMP levels were improved by the NR treatment in an H 2 O 2 -exposed cell model. Furthermore, NR significantly inhibited the activation of the MAPK pathway but promoted activation of the JAK2/Stat3 pathway compared with the model group. Conclusions : NR may alleviate oxidative damage by targeting the MAPK and JAK2/Stat3 pathways in H 2 O 2 -treated SRA01/04 cells. NR may represent anovel drug for preventing or treating cataracts.

Retinal degeneration diseases (RDDs) are common and devastating eye diseases characterized by the degeneration of photoreceptors, which are highly associated with oxidative stress. Previous studies reported that mitochondrial dysfunction is associated with various neurodegenerative diseases. However, the role of mitochondrial proteostasis mainly regulated by mitophagy and mitochondrial unfolded protein response (mtUPR) in RDDs is unclear. We hypothesized that the mitochondrial proteostasis is neuroprotective against oxidative injury in RDDs. In this study, the data from our hydrogen peroxide (H 2 O 2 )-treated mouse retinal cone cell line (661w) model of RDDs showed that nicotinamide riboside (NR)-activated mitophagy increased the expression of LC3B II and PINK1, and promoted the co-localization of LC3 and mitochondria, as well as PINK1 and Parkin in the H 2 O 2 -treated 661w cells. However, the NR-induced mitophagy was remarkably reversed by chloroquine (CQ) and cyclosporine A (CsA), mitophagic inhibitors. In addition, doxycycline (DOX), an inducer of mtUPR, up-regulated the expression of HSP60 and CHOP, the key proteins of mtUPR. Activation of both mitophagy and mtUPR increased the cell viability and reduced the level of apoptosis and oxidative damage in the H 2 O 2 -treated 661w cells. Furthermore, both mitophagy and mtUPR played a protective effect on mitochondria by increasing mitochondrial membrane potential and maintaining mitochondrial mass. By contrast, the inhibition of mitophagy by CQ or CsA reversed the beneficial effect of mitophagy in the H 2 O 2 -treated 661w cells. Together, our study suggests that the mitophagy and mtUPR pathways may serve as new therapeutic targets to delay the progression of RDDs through enhancing mitochondrial proteostasis.

Objective: To investigate the therapeutic effect of the Jianpi Liqi Fang ( ，JPLQF) combined with transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and spleen deficiency syndrome (SDS) and identify a potential indicator of efficacy., Methods: Ninety-nine patients with HCC who were diagnosed with SDS, non-spleen deficiency syndrome (NSDS), or no syndrome (NS) were treated with JPLQF combined with TACE for three periods. Therapeutic efficacy was compared among the groups. Plasma proteins were screened using label-free discovery analysis and verified via enzyme-linked immunosorbent assay (ELISA). Furthermore, receiver operating characteristic (ROC) curves were analyzed to evaluate therapeutic indicators., Results: After treatment, the Karnofsky Performance Status was significantly improved in the SDS group and significantly better than that in the NS group. The Traditional Chinese Medicine (TCM) syndrome scores were lower in the SDS group after treatment and lower than those in the NSDS group. However, alanine aminotransferase, carbohydrate antigen 19-9, alpha-fetoprotein, and carcinoembryonic antigen levels and white blood cell and platelet counts did not differ among the groups. Serum aspartate aminotransferase levels in the SDS group were significantly lower after treatment than before treatment, and total bilirubin levels were significantly lower in the SDS group than in the NSDS group. Label-free analysis identified 24 differentially expressed proteins (DEPs) between the SDS and NS groups, including 17 and 7 upregulated and downregulated proteins, respectively. Fibulin-5 (FBLN5) displayed the largest difference in expression between the groups. ELISA confirmed that FBLN5 levels were significantly lower in the NSDS and NS groups than in the SDS group. Following treatment with JPLQF and TACE, FBLN5 expression was upregulated only in the SDS group. Furthermore, ROC curve analysis indicated that FBLN5 may serve as a potential indicator of the efficacy of JPLQF combined with TACE in patients with HCC and SDS., Conclusion: JPLQF combined with TACE improved quality of life, clinical TCM symptoms, and liver function in patients with HCC and SDS. FBLN5 expression was significantly altered by treatment with JPLQF and TACE in patients with HCC and SDS.

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family, and contains two carbonyl groups, a methine group and two hydroxyl groups. With embelin as the lead compound, more than one hundred derivatives have been reported. Embelin is well known for its ability to antagonize the X-linked inhibitor of apoptosis protein (XIAP) with an IC50 value of 4.1 μM. The potential of embelin and its derivatives in the treatment of various cancers has been extensively studied. In addition, these compounds display a variety of other biological effects: antimicrobial, antioxidant, analgesic, anti-inflammatory, anxiolytic and antifertility activity. This paper reviews the recent progress in the synthesis and biological activity of embelin and its derivatives. Their cellular mechanisms of action and prospects in the research and development of new drugs are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pressure bearing capability of a folded multi-port flat tube (MPFT), which has the advantage of retaining the corrosion property of corrosion resistant materials, was investigated in this study with both a burst pressure test and finite element simulation. Results show that the folded tube's failure is mainly caused by the breaking of the inner ribs. Instead of detecting inner pressure, the bulging ratio, which is supposed to be small under service pressure, rises rapidly before failure. Therefore, it is suggested to use bulging ratio to visibly determine the working status of folded MPFTs. Based on FE simulations, the pressure bearing capability of the folded MPFT was improved by optimizing the relevant folding parameters. In addition, the influence of in-plane bending was also investigated. It is found that the folded MPFTs can still retain most of the pressure bearing capability after in-plane bending.

Purpose: To identify mutations in crystallin genes in Chinese families with congenital cataracts., Methods: Forty-two unrelated families with non-syndromic congenital cataracts were enrolled in this study. The coding exons and adjacent intronic regions of crystallin genes, including CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD and CRYGS , were analyzed with Sanger sequencing. Novel variants were further evaluated in 112 ethnically matched controls. To confirm the novel mutations, short tandem repeat (STR) haplotypes were constructed to check the cosegregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools, including Sorting Intolerant From Tolerant v5.1.1 (SIFT), Polymorphism Phenotyping v2 (PolyPhen-2), and Human Splicing Finder. The pathogenicity of all the mutations was evaluated according to the guidelines of the American College of Medical Genetics (ACMG) and InterVar software., Results: Seven previously reported mutations in crystallin genes identified in ten unrelated families were associated with the congenital nuclear cataracts. Four novel mutations in crystallin genes, including c.35G>T (p.R12L) in CRYAA , c.463C>A (p.Q155K) in CRYBB2 , IVS1 c.10-1G>A in CRYGC , and c.346delT (p.F116Sfsx29) in CRYGD , were identified in four unrelated families with congenital cataracts. These mutations cosegregated with all affected individuals in each family were not observed in the unaffected family members or in the 112 unrelated controls. All four novel mutations were categorized as disease "likely pathogenic" except IVS1 c.10-1G>A in CRYGC "pathogenic" using InterVar software in accordance with the ACMG standard. Mutations in crystallin genes were responsible for 33.33% of the Chinese families with congenital cataracts in this cohort., Conclusions: In this study, we identified four novel mutations in crystallin genes in Chinese families with congenital cataracts. The results expand the mutational spectrum of crystallin genes, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.

A proteomic and transcriptomic comparative analysis of the venoms of three Atheris species (A. squamigera, A. nitschei and A. chlorechis) was carried out by size exclusion liquid chromatography, gel electrophoresis, mass spectrometry, and mRNA sequencing. The improved proteomic profiling utilised in this work was combined with transcript studies, advancing our insights into venom composition, protein distribution and inter-species variation among the three bush vipers. Crude venoms of all three samples contained at least 10-20 protein components, ranging in size from ≤ 3 to > 98 kDa. Both approaches yielded converging overall information, pointing to phospholipases, disintegrins, serine proteases and metalloproteases as the major toxin classes, which are likely to explain the local and systemic symptoms observed in envenomation by Atheris genus. Being considered as the main factors involved in the distinct venom-induced pathologies, these identified snake venom proteins are of particular interest in terms of understanding their physiological and biological function as well as for their contribution in potential medical treatments.

Heat shock protein 90 (Hsp90) contains amino (N)-terminal domain, carboxyl(C)-terminal domain, and middle domains, which activate Hsp90 chaperone function cooperatively in tumor cells. One terminal occupancy might influence another terminal binding with inhibitor. The Bcr-Abl kinase is one of the Hsp90 clients implicated in the pathogenesis of chronic myeloid leukemia (CML). Present studies demonstrate that double inhibition of the N- and C-terminal termini can disrupt Hsp90 chaperone function synergistically, but not antagonistically, in Bcr-Abl-positive human leukemia cells. Furthermore, both the N-terminal inhibitor 17-AAG and the C-terminal inhibitor cisplatin (CP) have the capacity to suppress progenitor cells; however, only CP is able to inhibit leukemia stem cells (LSCs) significantly, which implies that the combinational treatment is able to suppress human leukemia in different mature states.