Coarse-Grained Molecular Dynamics Simulation of Heterogeneous Polysorbate 80 Surfactants and their Interactions with Small Molecules and Proteins.

Polysorbate 80 (PS80) is widely used in pharmaceutical formulations, and its commercial grades exhibit certain levels of structural heterogeneity. The objective of this study was to apply coarse-grained molecular dynamics simulations to better understand the effect of PS80 heterogeneity on micelle self-assembly, the loading of hydrophobic small molecules into the micelle core, and the interactions between PS80 and a protein, bovine serum albumin (BSA). Four representative PS80 variants with different head and tail structures were studied. Our simulations found that PS80 structural heterogeneity could affect blank micelle properties such as solvent-accessible surface area, aggregation number, and micelle aspect ratio. It was also found that hydrophobic small molecules such as ethinyl estradiol preferentially partitioned into the PS80 micelle core and PS80 dioleates formed a more hydrophobic core compared to PS80 monooleates. Furthermore, multiple PS80 molecules could bind to BSA, and PS80 heterogeneity profoundly changed the binding ratio as well as the surfactant-protein contact area.

Molecular Dynamics Simulation of an Iron(III) Binding Site on the Fc Domain of IgG1 Relevant for Visible Light-Induced Protein Fragmentation.

Molecular dynamics simulations were employed to investigate the interaction between Fe(III) and an iron-binding site composed of THR259, ASP252, and GLU261 on the Fc domain of an IgG1. The goal was to provide microscopic mechanistic information for the photochemical, iron-dependent site-specific oxidative fragmentation of IgG1 at THR259 reported in our previous paper. The distance between Fe(III) and residues of interest as well as the binding pocket size was examined for both protonated and deprotonated THR259. The Fe(III) binding free energy (ΔG) was estimated by using an umbrella sampling approach. The pKa shift of the THR259 hydroxyl group caused by the presence of nearby Fe(III) was estimated based on a thermodynamic cycle. The simulation results show that Fe(III) resides inside the proposed binding pocket and profoundly changes the pocket configuration. The ΔG values indicate that the pocket possesses a strong binding affinity for Fe(III). Furthermore, Fe(III) profoundly lowers the pKa value of the THR259 hydroxyl group by 5.4 pKa units.

Proportion, Correlates and the Associations of Meeting 24-h Movement Guidelines With Mental Well-Being and Psychological Distress: A Cross-Sectional Study of 10 589 Chinese Students.

BACKGROUND: The increased trends in psychological distress and mental illness have been of great significance in public health concerns. The study aimed to investigate the proportion and correlates of meeting 24-h movement guidelines (including moderate to vigorous physical activity, screen time and sleep duration) and the associations between 24-h movement guidelines met and mental well-being and psychological distress in a large sample of Chinese students. METHODS: All participants received a physical examination and filled out questionnaires in this study. Chi-square tests were used to analyse the proportion of reaching 24-h guidelines by gender and logistic regression was used to analyse correlates of meeting 24-h guidelines. Two binary logistic regression models were used to analyse the association between meeting 24-h guidelines and mental well-being and psychological distress. The back-propagation artificial neural network was used to describe the importance of the independent variables. RESULTS: The findings revealed a generally low rate of meeting the 24-h movement guidelines, particularly concerning moderate to vigorous physical activity (16.5%). Meeting all three guidelines was related to better mental health in both boys and girls. Particularly, meeting screen time guideline and meeting sleep duration guideline appeared to be more important on mental outcomes, compared to meeting moderate to vigorous physical activity guideline. Compared with boys, girls were more susceptible to the influences of 24-h movement guidelines on mental health. CONCLUSIONS: Meeting all three components of the 24-h movement guidelines was associated with the most favourable mental health outcomes for both boys and girls. Thus, maintaining a daily balance of sufficient physical activity, limited screen time, and adequate sleep is crucial for enhancing the mental health status of students.

Associations of multiple sleep dimensions with overall and abdominal obesity among children and adolescents: a population-based cross-sectional study.

BACKGROUND: The relationship of insufficient sleep with the increased risk of obesity has been reported, but less is known about other sleep dimensions in the sleep-obesity associations. OBJECTIVES: To assess the associations of multiple sleep dimensions with overall and abdominal obesity among Chinese students. METHODS: This was a cross-sectional study involving 10,686 Han students aged 9-18 from Chinese National Survey on Students' Constitution and Health (CNSSCH). We collected sex, age, regions, parental educational levels, physical activity duration and sleep-related information by questionnaire survey, and also conducted anthropometric measurements including height, weight and waist circumference (WC). Unadjusted and adjusted binary logistic regression models were used to estimate the associations of sleep-related dimensions with obesity-related indicators. RESULTS: Short sleep duration was associated with higher body mass index (BMI), larger WC and higher waist-to-height ratio (WHtR) in 9-12 and 16-18 age groups, whereas prolonged sleep duration on weekday was associated with higher BMI in 13-15 age group. Non-habitual midday napping and midday napping ≤0.5 h/d (vs 0.5 to 1 h/d) increased the risk of higher BMI in 13-15 age group, and the former was also associated with larger WC in 9-12 age group. Late bedtime was associated with larger WC and higher WHtR in 9-12 age group and with higher BMI and WHtR in 13-15 age group. Students aged 9-12 with social jet lag ≥2 h were found to have greater BMI after adjustment (Odds Ratio: 1.421; 95% confidence interval: 1.066-1.894). CONCLUSIONS: Short or overlong sleep duration, late bedtime and great social jet lag were associated with higher prevalence of overall or abdominal obesity, while moderate midday napping can effectively decrease the risk. Those findings may assist in developing preventive strategies to combat obesity epidemic.

Jasmonate-based warfare between the pathogenic intruder and host plant: who wins?

Plants and microbial pathogens often engage in a fierce war that determines their survival. Host plants have evolved sophisticated regulatory mechanisms to fine-tune defense responses to counter attacks from pathogens, while pathogens often hijack the lipid-derived phytohormone jasmonate to cause hormonal signaling imbalances for efficient infection. This review focuses on the jasmonate-based warfare between host plants and pathogenic intruders, and further discusses approaches to uncouple plant growth and defense tradeoffs in crop breeding.

Emerging Process Modeling Capabilities for Dry Powder Operations for Inhaled Formulations.

Dry powder inhaler (DPI) products are commonly formulated as a mixture of micronized drug particles and large carrier particles, with or without additional fine particle excipients, followed by final powder filling into dose containment systems such as capsules, blisters, or reservoirs. DPI product manufacturing consists of a series of unit operations, including particle size reduction, blending, and filling. This review provides an overview of the relevant critical process parameters used for jet milling, high-shear blending, and dosator/drum capsule filling operations across commonly utilized instruments. Further, this review describes the recent achievements regarding the application of empirical and mechanistic models, especially discrete element method (DEM) simulation, in DPI process development. Although to date only limited modeling/simulation work has been accomplished, in the authors' perspective, process design and development are destined to be more modeling/simulation driven with the emphasis on evaluating the impact of material attributes/process parameters on process performance. The advancement of computational power is expected to enable modeling/simulation approaches to tackle more complex problems with better accuracy when dealing with real-world DPI process operations.

Temporal trends in physical fitness among Chinese children and adolescents from 2000 to 2019 and analysis of social-ecological factors.

This study aimed to estimate temporal trends in physical fitness (PF) by regions, age groups and nutritional status among Chinese children and adolescents and to longitudinally examine PF determinants based on social-ecological model. Participants (n = 68,265) aged 7-18 were from five successive national surveys (2000 to 2019). Six tested items of PF were calculated as PF indicator (PFI), which was used to divide participants into two categories: low vs. moderate/high. One-way analysis of variance was used to compare difference and change trend of PFI. Linear regression evaluated relationship between PFI and body mass index (BMI), and logistic regression assessed association between PFI and factors of behaviours and lifestyles on individual-, family- and school-level based on the social-ecological model. PFI declined sharply from 2000 to 2010, increased slightly from 2010 to 2014 and then edged down in 2019. Students with moderate BMI and students in urban areas tended to have higher PFI, and larger increase of PFI was found in students aged 7-9 and 13-15 after 2010. Several determinants on individual-, family- and school-level related to PFI. Efforts to develop PF mainly include increasing PA and reducing sedentary behaviours by facilitating home-school collaboration and emphasizing age-, region- and BMI-specific actions.

Development of an In Vitro System To Emulate an In Vivo Subcutaneous Environment: Small Molecule Drug Assessment.

A reliable in vitro system can support and guide the development of subcutaneous (SC) drug products. Although several in vitro systems have been developed, they have some limitations, which may hinder them from getting more engaged in SC drug product development. This study sought to develop a novel in vitro system, namely, Emulator of SubCutaneous Absorption and Release (ESCAR), to better emulate the in vivo SC environment and predict the fate of drugs in SC delivery. ESCAR was designed using computer-aided design (CAD) software and fabricated using the three-dimensional (3D) printing technique. ESCAR has a design of two acceptor chambers representing the blood uptake pathway and the lymphatic uptake pathway, respectively, although only the blood uptake pathway was investigated for small molecules in this study. Via conducting a DoE factor screening study using acetaminophen solution, the relationship of the output (drug release from the "SC" chamber to the "blood circulation" chamber) and the input parameters could be modeled using a variety of methods, including polynomial equations, machine learning methods, and Monte Carlo simulation-based methods. The results suggested that the hyaluronic acid (HA) concentration was a critical parameter, whereas the influence of the injection volume and injection position was not substantial. An in vitro-in vivo correlation (IVIVC) study was developed using griseofulvin suspension to explore the feasibility of applying ESCAR in formulation development and bioequivalence studies. The developed LEVEL A IVIVC model demonstrated that the in vivo PK profile could be correlated with the in vitro release profile. Therefore, using this model, for new formulations, only in vitro studies need to be conducted in ESCAR, and in vivo studies might be waived. In conclusion, ESCAR had important implications for research and development and quality control of SC drug products. Future work would be focused on further optimizing ESCAR and expanding its applications via assessing more types of molecules and formulations.

Contextual and own-age effects in age perception.

Our judgement of certain facial characteristics such as emotion, attractiveness or age, is affected by context. Faces that are flanked by younger faces, for example, are perceived as being younger, whereas faces flanked by older faces are perceived as being older. Here, we investigated whether contextual effects in age perception are moderated by own age effects. On each trial, a target face was presented on the screen, which was flanked by two faces. Flanker faces were either identical to the target face, were 10 years younger or 10 years older than the target face. We asked 40 older (64-69 years) and 43 younger adults (24-29) to estimate the age of the target face. Our results replicated previous studies and showed that context affects age estimation of faces flanked by target faces of different ages. These context effects were more pronounced for younger compared to older flankers but present across both tested age groups. An own-age advantage was observed for older adults for unflanked faces who had larger estimation errors for younger faces compared to older faces and younger adults. Flanker effects, however, were not moderated by own-age effects. It is likely that the increased effect of younger flankers is due to mechanisms related to perceptual averaging.

Multidimensional self-rating biological rhythm disorder and its association with depression and anxiety symptoms among adolescents aged 11-23 years: a school-based cross-sectional study from China.

BACKGROUND: Depression and anxiety are topical concerns worldwide, especially among adolescents. Besides, biological rhythm disorder as a candidate mechanism for mood disorders is highly prevalent, but relevant research among adolescents in China is presently limited. We conducted the present study to investigate the distribution of multi-dimensional self-rating biological rhythm disorder and the association of self-rating biological rhythm disorders with depression and anxiety symptoms among Chinese adolescents in different academic stages. METHODS: In the cross-sectional study, 3693 students aged 11-23 from Zhengzhou City, Henan Province, China were included. The Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) were used to evaluate symptoms of depression and anxiety, respectively. Additionally, the Self-Rating of Biological Rhythm Disorder for Adolescents (SBRDA) was used to assess status of biological rhythm disorders. Multivariate logistic regression was developed to explore factors potentially associated with symptoms of depression and anxiety stratified by academic stages. RESULTS: Among all participants, 44.14 and 36.15% suffered from depression and anxiety symptoms, respectively. On average, participants scored 74.66 ± 19.37 on the measure of total biological rhythm disorder. Adjusted for demographic confounding factors, the logistic regression analysis showed higher scores of total biological rhythm disorder were associated with more severe depression (OR = 14.38, 95%CI: 11.38-18.16) and anxiety symptoms (OR = 11.63, 95%CI: 9.14-14.81). The similar results were also found in the stratified analysis by academic stages. CONCLUSIONS: Self-rating biological rhythm disorders are significantly associated with depression and anxiety symptoms among adolescents. Discrepancy across academic stages should also be taken into account in establishing public health strategies.

The dissociation between age of acquisition and word frequency effects in Chinese spoken picture naming.

This study aimed to examine the locus of age of acquisition (AoA) and word frequency (WF) effects in Chinese spoken picture naming, using a picture-word interference task. We conducted four experiments manipulating the properties of picture names (AoA in Experiments 1 and 2, while controlling WF; and WF in Experiments 3 and 4, while controlling AoA), and the relations between distractors and targets (semantic or phonological relatedness). Both Experiments 1 and 2 demonstrated AoA effects in picture naming; pictures of early acquired concepts were named faster than those acquired later. There was an interaction between AoA and semantic relatedness, but not between AoA and phonological relatedness, suggesting localisation of AoA effects at the stage of lexical access in picture naming. Experiments 3 and 4 demonstrated WF effects: pictures of high-frequency concepts were named faster than those of low-frequency concepts. WF interacted with both phonological and semantic relatedness, suggesting localisation of WF effects at multiple levels of picture naming, including lexical access and phonological encoding. Our findings show that AoA and WF effects exist in Chinese spoken word production and may arise at related processes of lexical selection.

Effects of cue validity on attentional selection.

Visual attention can be allocated to locations or objects, leading to enhanced processing of information at the specific location (space-based effects) or specific object (object-based effects). Previous studies have observed object-based effects to be smaller and less robust than space-based effects, with large individual differences in their temporal occurrence. Studies on space- and object-based effects are often based on a two-rectangle paradigm in which targets appear at cued locations more often than uncued locations. It is, however, unclear whether and how the target's spatial probability affects the temporal occurrence of these effects. In three experiments with different cue validities (80%, 50% and 33%), we systematically changed the interval between the cue and the target from 50 to 600 ms. On a group level and for individuals, we examined how cue validity affects the occurrence of object- and space-based effects. We observed that the magnitude and the prevalence of space-based effects heavily decreased with reduced cue validity. Object-based effects became even more sparse and turned increasingly negative with decreasing cue validity, representing a different-object rather than a same-object advantage. These findings indicate that changes in cue-validity affect both space- and object-based effects, but it does not account for the low prevalence and magnitude of object-based effects.

Machine Learning Attempts for Predicting Human Subcutaneous Bioavailability of Monoclonal Antibodies.

PURPOSE: One knowledge gap related to subcutaneous (SC) delivery is unpredictable and variable bioavailability. This study was aimed to develop machine learning methods to predict whether mAb's bioavailability was ≥70% or below, without completely knowing the mechanism and causality between inputs and outputs. METHODS: A database of mAb SC products was built. The model training and validation were accomplished based on this database and a set of the inputs (product properties) were mapped to the output (bioavailability) using different machine learning algorithms. Dimensionality reduction was undertaken using principal component analysis (PCA). RESULTS: The bioavailability of the mAb products being investigated varied from 35% to 90%. The tree-based methods, including random forest (RF), Adaptive Boost (AdaBoost), and decision tree (DT) presented the best predictability and generalization power on bioavailability classification. The models based on Multi-layer perceptron (MLP), Gaussian Naïve Bayes (GaussianNB), and k nearest neighbor (kNN) algorithms also provided acceptable prediction accuracy. CONCLUSION: Machine learning could be a potential tool to predict mAb's bioavailability. Since all input features were acquired using theoretical calculations and predictions rather than experiments, the models may be particularly applicable to some early-stage research activities such as mAb molecule triage, design/optimization, mutant screening, molecule selection, and formulation design.

Investigating the Influence of Tablet Location Inside Dissolution Test Apparatus on Polymer Erosion and Drug Release of a Surface-Erodible Sustained-Release Tablet Using Computational Simulation Methods.

The objective of this work was to investigate the influence of tablet location along the bottom of a USP apparatus II vessel on polymer erosion and drug release of surface-erodible sustained-release tablets using computational simulation methods. Computational fluid dynamics (CFD) methods were performed to simulate the velocity distribution. A mathematical model was developed to describe polymer erosion and tablet deformation according to the mass transfer coefficient. Numerical analysis was used to simulate drug release controlled by drug diffusion and polymer erosion. The results indicated that tablets located at the off-center position deformed faster than the tablets located at the center position. However, tablet location had no profound impact on drug release rate since all drug release profiles were "similar" according to the f2 similarity values which were above 50. Hence, our simulation supported that the USP apparatus II was a reliable and robust device for the dissolution testing of surface-erodible sustained-release tablets.

In Vivo Evaluation of Transdermal Iodide Microemulsion for Treating Iodine Deficiency Using Sprague Dawley Rats.

The objective of this study was to evaluate the transdermal efficiency of iodide microemulsion in treating iodine deficiency using rats as an animal model. Animals were fed either iodine-deficient diet (20 µg/kg iodide) or control diet (200 µg/kg iodide) over a 17-month period. At month 14, iodide microemulsion was applied topically in iodine-deficient group and physiological evaluations of thyroid gland functions were characterized by monitoring the thyroid hormones (T3, T4), thyroid-stimulating hormone (TSH), iodide ion excretion in urine, and the overall rat body weights in both groups. Moreover, morphological evaluations of thyroid gland before and after treatment were performed by ultrasound imaging and through histological assessment. Prior to microemulsion treatment, the levels of T3, T4, and TSH in iodine-deficient group were statistically significant as compared to that in the control group. The levels of T3 and T4 increased while TSH level decreased significantly in iodine-deficient group within the first 4 weeks of treatment. After treatment, iodide concentration in urine increased significantly. There was no statistical difference in weight between the two groups. Ultrasound imaging and histological evaluations showed evidence of hyperplasia in iodine-deficient group. Topical iodide microemulsion has shown a promising potential as a novel delivery system to treat iodine deficiency.

Evaluation of Chlorpheniramine Maleate microparticles in orally disintegrating film and orally disintegrating tablet for pediatrics.

OBJECTIVE: To mask the bitterness of Chlorpheniramine Maleate via encapsulating drug into Eudragit EPO microparticles, and then incorporate these microparticles into orally disintegrating films (ODF) and orally disintegrating tablets (ODT) for pediatric uses. METHODS: Spray drying of water-in-oil emulsion was utilized to encapsulate Chlorpheniramine Maleate into Eudragit EPO microparticles. Based on an orthogonal experimental design L9 (3(3)), polynomial regression models were developed to evaluate correlation between microparticle properties (encapsulation efficiency and drug release) and variables (X1: weight ratio of polymer to drug, X2: volume ratio of oil to water and X3: Q-flow of spray dryer). ODF and ODT formulations were evaluated including weight variation, content uniformity, tensile strength, disintegration time, friability and dissolution profiles. The bitterness taste test was evaluated in 10 adult volunteers. RESULTS AND DISCUSSION: From polynomial regression analysis, the best values of variables leading to the optimized microparticles were X1 = 10, X2 = 3 and X3 = 45. The optimized microparticles were incorporated into ODF and ODT with satisfactory weight and drug content uniformity, and acceptable physical strength. Both dosage forms disintegrated immediately (less than 40 s) in simulated saliva solutions. The outcome of taste-masking test indicated that microparticles alleviated drug bitterness significantly; bitterness was not discernible with microparticles incorporated in ODT, whereas only slight bitterness was detected from microparticles incorporated into ODF. CONCLUSION: Both ODF and ODT are shown to be suitable vehicles for taste masked Chlorpheniramine Maleate microparticles with potential for pediatric uses.

The influence of sodium salts (iodide, chloride and sulfate) on the formation efficiency of sulfamerazine nanocrystals.

OBJECTIVE: The purpose of this study is to evaluate the influence of sodium iodide, sodium chloride and sodium sulfate on the formation efficiency of sulfamerazine nanocrystals by wet ball milling. METHODS: Sulfamerazine was milled using zirconium oxide beads in a solution containing polyvinylpyrrolidone (PVP) and a sodium salt (iodide, chloride or sulfate). Particle size distributions were evaluated by light diffraction before and after milling. High-performance liquid chromatography was utilized to determine the amount of PVP adsorbed onto sulfamerazine surface. Lyophilized nanocrystals were further characterized by differential scanning calorimetry and dissolution testing. RESULTS: Sulfate ion had more profound effect on reducing particle size via milling than iodide or chloride. We linked our findings to Hofmeister ion series, which indicates that sulfate ions tends to break the water structure, increases the surface tension and lowers the solubility of hydrocarbons in water. We hypothesized that the addition of sulfate ions dehydrated the PVP molecules and enhanced its adsorption onto the sulfamerazine particle surfaces. Consequently, the adsorbed PVP helped to stabilize of the nanosuspension. The nanocrystals that were obtained from the lyophilized milled suspensions exhibited a notable increase in dissolution rate. CONCLUSION: The addition of sodium sulfate enhanced the formation efficiency of sulfamerazine nanocrystals.

CDC6 may serve as an indicator of lung adenocarcinoma prognosis and progression based on TCGA and GEO data mining and experimental analyses.

Lung adenocarcinoma (LUAD) is one of the most lethal types of cancer worldwide, and accurately predicting patient prognosis is an important challenge. Gene prediction models, which are known for their simplicity and efficiency, have the potential to be used for prognostic predictions. However, the availability of models with true clinical value is limited. The present study integrated tissue sequencing and the clinical information of patients with LUAD from The Cancer Genome Atlas and Gene Expression Omnibus databases using bioinformatics. This comprehensive approach enabled the identification of 252 differentially expressed genes. Subsequently, univariate and multivariate Cox analyses were performed using these genes, and 14 and 3 genes [including cell division cycle 6 (CDC6), hyaluronan mediated motility receptor and STIL centriolar assembly protein] were selected for the construction of two prognostic models. Notably, the 3­gene prognostic model exhibited a comparable predictive ability to that of the 14­gene model. Functionally, pathway enrichment analysis revealed that CDC6 played a role in regulating the cell cycle and promoting tumor staging. To further investigate the relevance of CDC6, in vitro experiments involving the downregulation of CDC6 expression were conducted, which resulted in significant inhibition of tumor cell migration, invasion and proliferation. Moreover, in vivo experiments demonstrated that downregulating CDC6 expression significantly reduced the burden and metastasis of in situ lung tumors in mice. These findings suggested that CDC6 may be a critical gene involved in the development and prognosis of LUAD. In summary, the present study successfully constructed a simple yet accurate prognostic prediction model consisting of 3 genes. Additionally, the functional importance of CDC6 as a key gene in the model was identified. These findings lay a crucial foundation for further exploration of prognostic prediction models and a deeper understanding of the functional mechanisms of CDC6. Notably, these results have potential clinical implications for improving personalized treatment and prognosis evaluation for patients with LUAD.

Development of a drying method for proteins based on protein-hyaluronic acid precipitation.

This study aims to develop a new method to dry proteins based on protein-hyaluronic acid (HA) precipitation and apply the precipitation-redissolution technique to develop highly concentrated protein formulations. Lysozyme was used as a model protein and HA with various molecular weights (MW) were investigated. Under low ionic strength, low-MW HA (e.g., MW: around 5 K) did not induce lysozyme precipitation. Conversely, high-MW HA (e.g., MW: approximately from 40 K to 1.5 M) precipitated more than 90 % of lysozyme. The dried lysozyme-HA precipitates had moisture levels between 4 % and 5 %. The lysozyme-HA precipitates could be redissolved using PBS (pH 7.4, ionic strength: ∼ 163 mM). The viscosity of the reconstituted solution was dependent on HA MW, e.g., 4 cP for HA40K, and 155 cP for HA1.5 M, suggesting low-MW HA might be a proper excipient for highly concentrated solution formulations for subcutaneous/intraocular injection and high-MW HA may fit for other applications. The tertiary structure of lysozyme after the precipitation-redissolution steps had no significant difference from that of the original lysozyme as confirmed by fluorescence spectroscopy. The denaturation temperature of lysozyme after the precipitation-redissolution steps and that of the original lysozyme were close, indicating they possessed similar thermal stability. The accelerated stability study revealed that lysozyme stored in the dry precipitates was more physically stable than that in the buffer solution. Overall, this new drying technique is suitable for drying proteins and exhibits several benefits such as minimum energy consumption, cost effectiveness, high production yield, and mild processing conditions. In addition, the precipitation-redissolution technique proposed in this study can potentially be used to develop highly concentrated formulations, especially for proteins experiencing poor stability in the liquid state.

Construction of an Anoikis-Related Gene Prognostic Signature and Identification of ANGPTL4 as a Key Oncogene in Lung Adenocarcinoma.

Anoikis plays an important role in cancer invasion and metastasis. However, the role of anoikis-related genes, AnRGs, in lung adenocarcinoma (LUAD) is not clear. First, anoikis-related genes (AnRGs) were obtained from the Genecard database. Second, the prognostic risk model of AnRGs was established by univariate Cox analysis, the Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and multivariate Cox analysis. Finally, in vitro cell experiments were carried out to determine the expression and function of the key gene AnRGs. Three AnRGs (angiopoietin-like 4, ANGPTL4; Cyclin-Dependent Kinase Inhibitor 3, CDKN3; Solute Carrier Organic Anion Transporter Family Member 1B3, SLCO1B3) were screened for the construction of risk prediction model. Additionally, ANGPTL4 was significantly highly expressed in tumor cells, and the knockdown of ANGPTL4 expression on tumor cells could inhibit tumor cell migration and apoptosis. Constructing a risk model based on anoikis-related genes can effectively differentiate the prognosis of LUAD. ANGPTL4 can be used as a potential new target for LUAD treatment.