Association between the AHA life's essential 8 and prediabetes/diabetes: a cross-sectional NHANES study.

Background and aims: The American Heart Association (AHA) recently introduced the Life's Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes. Methods and Results: This cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education. Conclusion: CVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes.

Attentional bias to social media stimuli is moderated by fear of missing out among problematic social media users.

Background and aims: Previous evidence has indicated that problematic social media use (PSMU) is characterized by an attentional bias to social media icons (such as Facebook icons), but not to social webpages (such as Facebook webpages). They suggest that there may be other factors influencing attentional bias like fear of missing out (FoMO). But it remains unclear how FoMO moderates attentional bias in PSMU. This study aims to investigate whether PSMU show attentional bias for stimuli associated with social media, and how FoMO moderates on attentional bias among PSMU through experimental methods. Methods: Based on the Interaction of Person-Affect-Cognition-Execution (I-PACE) model, this study explored mechanisms of attentional bias to social media icons (such as WeChat) related to PSMU and further examined the role of FoMO in this relationship. Specifically, attentional bias patterns to social media icons of 62 participants (31 PSMU and 31 control group) were explored during a dot-probe paradigm combined with eye-tracking in Experiment 1, and attentional bias patterns to social media icons of another 61 individuals with PSMU with different FoMO levels was explored during a dot-probe paradigm combined with eye-tracking in Experiment 2. Results: Results revealed that individuals with PSMU had an attentional bias toward social media icons, demonstrated by attentional maintenance, and such bias such bias was moderated by FoMO negatively, demonstrated by attentional vigilance and maintenance in PSMU/high FoMO. Conclusion: These results suggest that attentional bias is a common mechanism associated with PSMU, and FoMO is a key factor on the development of PSMU.

The Interplay Between Health Disparities and Acceptability of Virtual Reality: A Survey Study.

Virtual reality (VR) has emerged as a nonpharmacological adjuvant to manage acute and chronic pain symptoms. The goal of this survey study was to determine the acceptability of VR among chronic pain participants hailing from distressed and prosperous neighborhoods in the state of Maryland. We hypothesized that pain severity and interference vary in groups experiencing health disparities, potentially influencing VR's acceptability. From March 11 to March 15, 2020, we surveyed a cohort of clinically phenotyped participants suffering from chronic orofacial pain. Participants were asked to express their willingness to participate in a longitudinal VR study and their expectation of pain relief from using VR. Seventy out of 350 participants with chronic pain completed the survey (response rate: 20%). There was no difference in the likelihood of responding to the survey based on their neighborhood distress. Among survey respondents and nonrespondents, similar proportions of participants were from distressed neighborhoods. Among the respondents, 63 (90%) and 59 (84.3%) were willing to participate and expected to experience pain relief from the VR intervention, respectively. Age, sex, race, neighborhood distress, severity of pain, and prior VR experience did not influence willingness to participate in the VR trial or the expectations of VR-induced improvement. These findings suggest that VR as an adjuvant intervention is potentially accepted by chronic pain participants, irrespective of neighborhood-level social determinants of health.

FDG PET/CT in Staging of α-Fetoprotein-Producing Hepatoid Adenocarcinoma of the Pancreas.

ABSTRACT: Hepatoid adenocarcinoma of the pancreas is a rare aggressive tumor with poor prognosis. We describe contrast-enhanced CT and FDG PET/CT findings in a case of pancreatic hepatoid adenocarcinoma with significantly elevated α-fetoprotein level presenting as acute pancreatitis. The primary pancreatic tumor diffusely involved the pancreas and showed heterogeneous enhancement mimicking acute necrotizing pancreatitis on contrast-enhanced CT. FDG PET/CT showed intense FDG uptake (SUVmax, 24.5) of the left supraclavicular and retroperitoneal lymph node metastases, suggesting FDG PET/CT may be useful for staging of this aggressive tumor.

Evaluating the Efficacy of CortexID Quantitative Analysis in Localization of the Epileptogenic Zone in Patients with Temporal Lobe Epilepsy.

INTRODUCTION: There remains a critical need for precise localization of the epileptogenic foci in individuals with drug-resistant epilepsy (DRE). 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging can reveal hypometabolic regions during the interval between seizures in patients with epilepsy. However, visual-based qualitative analysis is time-consuming and strongly influenced by physician experience. CortexID Suite is a quantitative analysis software that helps to evaluate PET imaging of the human brain. Therefore, we aimed to evaluate the efficacy of CortexID quantitative analysis in the localization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE). METHODS: A total of 102 patients with epilepsy who underwent 18F-FDG-PET examinations were included in this retrospective study. The PET visual analysis was interpreted by two nuclear medicine physicians, and the quantitative analysis was performed automatically using CortexID analysis software. The assumed epileptogenic zone was evaluated comprehensively by two skilled neurologists in the preoperative assessment of epilepsy. The accuracy of epileptogenic zone localization in PET visual analysis was compared with that in CortexID quantitative analysis. RESULTS: The diagnostic threshold for the difference in the metabolic Z-score between the right and left sides of medial temporal lobe epilepsy (MTLE) was calculated as 0.87, and that for lateral temporal lobe epilepsy (LTLE) was 2.175. In patients with MTLE, the area under the curve (AUC) was 0.922 for PET visual analysis, 0.853 for CortexID quantitative analysis, and 0.971 for the combined diagnosis. In patients with LTLE, the AUC was 0.842 for PET visual analysis, 0.831 for CortexID quantitative analysis, and 0.897 for the combined diagnosis. These results indicate that the diagnostic efficacy of CortexID quantitative analysis is not inferior to PET visual analysis (p > 0.05), while combined analysis significantly increases diagnostic efficacy (p < 0.05). Among the 23 patients who underwent surgery, the sensitivity and specificity of PET visual analysis for localization were 95.4% and 66.7%, and the sensitivity and specificity of CortexID quantitative analysis were 100% and 50%. CONCLUSION: The diagnostic efficacy of CortexID quantitative analysis is comparable to PET visual analysis in the localization of the epileptogenic zone in patients with TLE. CortexID quantitative analysis combined with visual analysis can further improve the accuracy of epileptogenic zone localization.

High-Order Harmonic Generation in Photoexcited Three-Dimensional Dirac Semimetals.

High-order harmonic generation (HHG) in condensed matter is highly important for potential applications in various fields, such as materials characterization, all-optical switches, and coherent light source generation. Linking HHG to the properties or dynamic processes of materials is essential for realizing these applications. Here, a bridge has been built between HHG and the transient properties of materials through the engineering of interband polarization in a photoexcited three-dimensional Dirac semimetal (3D-DSM). It has been found that HHG can be efficiently manipulated by the electronic relaxation dynamics of 3D-DSM on an ultrafast time scale of several hundred femtoseconds. Furthermore, time-resolved HHG (tr-HHG) has been demonstrated to be a powerful spectroscopy method for tracking electron relaxation dynamics, enabling the identification of electron thermalization and electron-phonon coupling processes and the quantitative extraction of electron-phonon coupling strength. This demonstration provides insights into the active control of HHG and measurements of the electron dynamics.

Enhanced specific surface area and mechanical property of silk nanofibers aerogel for potential hemostasis applications.

Biopolymer aerogel is a new type of material with potential applications in the biomedical field. Silk fibroin is of particular interest as a raw material with good biocompatibility and degradable. However, the low mechanical strength and small specific surface area of silk fibroin aerogels limit its further development. Herein, a fast water absorption, highly specific surface area and mechanically strong of aerogels were prepared using low crystal silk fibroin nanofibers (SNF), sol-gel process, solvent exchange and supercritical carbon dioxide (CO2) drying method. The resulting Aero-Sc displayed highly specific surface area (251 m2/g), porosity (97.6 %) and water absorption capacity (1200 %). Furthermore, with rapid water absorption and stronger erythrocyte adhesion, the Aero-Sc showed highly effective hemostasis in vitro. In vivo, animal experiments on rat liver hemorrhage model confirmed that SNF aerogels have a less blood loss (312 ± 29 mg) and faster hemostatic time (92 ± 13 s) than commercially gelatin sponge (p < 0.05). The unique properties of silk fibroin nanofibers aerogel developed in this study has great potential to be a safe and effective hemostatic medical device.

Biomimetic mineralization of hydrated magnesium carbonate for hydrogel reinforcement and heavy metal adsorption.

With excessive Mn(Ⅱ) and Cu(Ⅱ) pollution in aquatic environments posing potential health risks to inhabitants, the emergence of carbon capture, utilization and storage (CCUS) technology has promoted the improvement of heavy metal remediation technologies. Using hydrothermal sediment as a crystal seed, rhamnolipid was used to mediate biomimetic mineralization to prepare hydrated magnesium carbonate (HMC) composites to enhance the Mn(Ⅱ)/Cu(Ⅱ) adsorption performance of alginate hydrogels. Hydrothermal sediment is beneficial for accelerating biomimetic mineralization, while rhamnolipid can induce a crystalline phase transformation from dypingite to nesquehonite. The addition of sediment significantly enhanced the compressive mechanical properties and thermal stability of the hydrogels. The adsorption performances of the nesquehonite and dypingite hydrogels were better for Mn(II) and Cu(II), respectively. An increase in the amount of sediment improved the adsorption of Cu(II) by the hydrogels appropriately, resulting in stronger selectivity for Cu(II). The adsorption of Mn(II) and Cu(II) on the hydrogel beads was thermodynamically spontaneous. The inhibitory effects of sodium dodecyl benzene sulfonate (SDBS), fulvic acid (FA) and alginate on Cu(II) adsorption were more obvious than those of bovine serum albumin (BSA). Both the complexation of functional groups on alginate and mineralization by HMC participated in the adsorption of Mn(II) and Cu(II).

A lightweight method of integrated local load forecasting and control of edge computing in active distribution networks.

The strong resource constraints of edge-computing devices and the dynamic evolution of load characteristics put forward higher requirements for forecasting methods of active distribution networks. This paper proposes a lightweight adaptive ensemble learning method for local load forecasting and predictive control of active distribution networks based on edge computing in resource constrained scenarios. First, the adaptive sparse integration method is proposed to reduce the model scale. Then, the auto-encoder is introduced to downscale the model variables to further reduce computation time and storage overhead. An adaptive correction method is proposed to maintain the adaptability. Finally, a multi-timescale predictive control method for the edge side is established, which realizes the collaboration of local load forecasting and control. All cases can be deployed on an actual edge-computing device. Compared to other benchmark methods and the existing researches, the proposed method can minimize the model complexity without reducing the forecasting accuracy.

Exploring the common mechanisms and biomarker ST8SIA4 of atherosclerosis and ankylosing spondylitis through bioinformatics analysis and machine learning.

Background: Atherosclerosis (AS) is a major contributor to cerebrovascular and cardiovascular events. There is growing evidence that ankylosing spondylitis is closely linked to AS, often co-occurring with it; however, the shared pathogenic mechanisms between the two conditions are not well understood. This study employs bioinformatics approaches to identify common biomarkers and pathways between AS and ankylosing spondylitis. Methods: Gene expression datasets for AS (GSE100927, GSE28829, GSE155512) and ankylosing spondylitis (GSE73754, GSE25101) were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes for AS and ankylosing spondylitis were identified using the Limma R package and weighted gene co-expression network analysis (WGCNA) techniques, respectively. The machine learning algorithm SVM-RFE was applied to pinpoint promising biomarkers, which were then validated in terms of their expression levels and diagnostic efficacy in AS and ankylosing spondylitis, using two separate GEO datasets. Furthermore, the interaction of the key biomarker with the immune microenvironment was investigated via the CIBERSORT algorithm, single-cell analysis was used to identify the locations of common diagnostic markers. Results: The dataset GSE100927 contains 524 DEGs associated with AS, whereas dataset GSE73754 includes 1,384 genes categorized into modules specific to ankylosing spondylitis. Analysis of these datasets revealed an overlap of 71 genes between the DEGs of AS and the modular genes of ankylosing spondylitis. Utilizing the SVM-RFE algorithm, 15 and 24 central diagnostic genes were identified in datasets GSE100927 and GSE73754, respectively. Further validation of six key genes using external datasets confirmed ST8SIA4 as a common diagnostic marker for both conditions. Notably, ST8SIA4 is upregulated in samples from both diseases. Additionally, ROC analysis confirmed the robust diagnostic utility of ST8SIA4. Moreover, analysis through CIBERSORT suggested an association of the ST8SIA4 gene with the immune microenvironment in both disease contexts. Single-cell analysis revealed that ST8SIA4 is primarily expressed in Macrophages, Monocytes, T cells, and CMPs. Conclusion: This study investigates the role of ST8SIA4 as a common diagnostic gene and the involvement of the lysosomal pathway in both AS and ankylosing spondylitis. The findings may yield potential diagnostic biomarkers and offer new insights into the shared pathogenic mechanisms underlying these conditions.

A new UiO-66-NH2 MOF-based nano-immobilized DFR enzyme as a biocatalyst for the synthesis of anthocyanidins.

Anthocyanidins and anthocyanins are one subclass of flavonoids in plants with diverse biological functions and have health-promoting effects. Dihydroflavonol 4-reductase (DFR) is one of the important enzymes involved in the biosynthesis of anthocyanidins and other flavonoids. Here, a new MOF-based nano-immobilized DFR enzyme acting as a nano-biocatalyst for the production of anthocyanidins in vitro was designed. We prepared UiO-66-NH2 MOF nano-carrier and recombinant DFR enzyme from genetic engineering. DFR@UiO-66-NH2 nano-immobilized enzyme was constructed based on covalent bonding under the optimum immobilization conditions of the enzyme/carrier ratio of 250 mg/g, 37 °C, pH 6.5 and fixation time of 10 min. DFR@UiO-66-NH2 was characterized and its catalytic function for the synthesis of anthocyanidins in vitro was testified using UPLC-QQQ-MS analysis. Compared with free DFR enzyme, the enzymatic reaction catalyzed by DFR@UiO-66-NH2 was more easily for manipulation in a wide range of reaction temperatures and pH values. DFR@UiO-66-NH2 had better thermal stability, enhanced adaptability, longer-term storage, outstanding tolerances to the influences of several organic reagents and Zn2+, Cu2+ and Fe2+ ions, and relatively good reusability. This work developed a new MOF-based nano-immobilized biocatalyst that had a good prospect of application in the green synthesis of anthocyanins in the future.

Knowledge and attitude toward proton radiotherapy among oncology patients: a multi-center, cross-sectional study.

Aim: To explore the knowledge and attitude among oncology patients toward proton radiotherapy. Materials & methods: This cross-sectional study was performed using self-designed questionnaire. Results: Based on 546 valid questionnaires, mean knowledge and attitude scores of 3.4 ± 3.6 (range: 0-12) and 31.1 ± 3.5 (range: 10-50) were observed. Multivariate analysis demonstrated that higher education (p = 0.021), higher monthly income (p = 0.005), and proton radiotherapy history (p < 0.001) were independently associated with higher knowledge scores. Higher knowledge (p = 0.020), older age (p = 0.030), not smoking (p = 0.032) and medication use (p = 0.035) were independently associated with higher attitude scores. Conclusion: Oncology patients have insufficient knowledge and negative attitude toward proton radiotherapy, which might be affected by their age, education, income, proton radiotherapy history, employment, smoking and medication use.

[Box: see text].

Effect of differences in proximal neck angles on biomechanics of abdominal aortic aneurysm based on fluid dynamics.

BACKGROUND: This study aimed to analyze the effect of proximal neck angulation on the biomechanical indices of abdominal aortic aneurysms (AAA) and to investigate its impact on the risk of AAA rupture. METHODS: CT angiography (CTA) data of patients with AAA from January 2015 to January 2022 were collected. Patients were divided into three groups based on the angle of the proximal neck: Group A (âˆ ß ≤ 30°), Group B (30°<âˆ ß ≤ 60°), and Group C (âˆ ß > 60°). Biomechanical indices related to the rupture risk of AAA were analyzed using computational fluid dynamics modeling (CFD-Post) based on the collected data. RESULTS: Group A showed slight turbulence in the AAA lumen with a mixed laminar flow pattern. Group B had a regular low-speed eddy line characterized by cross-flow dominated by lumen blood flow and turbulence. In Group C, a few turbulent lines appeared at the proximal neck, accompanied by eddy currents in the lumen expansion area following the AAA shape. Significant differences were found in peak wall stress, shear stress, and the maximum blood flow velocity impact among the three groups. The maximum blood flow velocity at the angle of the proximal neck impact indicated the influence of the proximal neck angle on the blood flow state in the lumen. CONCLUSION: As the angle of the proximal neck increased, it caused stronger eddy currents and turbulent blood flow due to a high-speed area near the neck. The region with the largest diameter in the abdominal aortic aneurysm was prone to the highest stress, indicating a higher risk of rupture. The corner of the proximal neck experienced the greatest shear stress, potentially leading to endothelial injury and further enlargement of the aneurysm.

Synergistic insights: the integrated role of CT/CTP and clinical parameters in hemorrhagic transformation prediction.

BACKGROUND: Acute ischemic stroke presents significant challenges in healthcare, notably due to the risk and poor prognosis associated with hemorrhagic transformation (HT). Currently, there is a notable gap in the early clinical stage for a valid and reliable predictive model for HT. METHODS: This single-center retrospective study analyzed data from 224 patients with acute ischemic stroke due to large vessel occlusion. We collected comprehensive clinical data, CT, and CTP parameters. A predictive model for HT was developed, incorporating clinical indicators alongside imaging data, and its efficacy was evaluated using decision curve analysis and calibration curves. In addition, we have also built a free browser-based online calculator based on this model for HT prediction. RESULTS: The study identified atrial fibrillation and hypertension as significant risk factors for HT. Patients with HT showed more extensive initial ischemic damage and a smaller ischemic penumbra. Our novel predictive model, integrating clinical indicators with CT and CTP parameters, demonstrated superior predictive value compared to models based solely on clinical indicators. CONCLUSIONS: The research highlighted the intricate interplay of clinical and imaging parameters in HT post-thrombectomy. It established a multifaceted predictive model, enhancing the understanding and management of acute ischemic stroke. Future studies should focus on validating this model in broader cohorts, further investigating the causal relationships, and exploring the nuanced effects of these parameters on patient outcomes post-stroke.

Multi-omics analysis reveals genes and metabolites involved in Streptococcus suis biofilm formation.

BACKGROUND: Streptococcus suis is an important zoonotic pathogen. Biofilm formation largely explains the difficulty in preventing and controlling S. suis. However, little is known about the molecular mechanism of S. suis biofilm formation. RESULTS: In this study, transcriptomic and metabolomic analyses of S. suis in biofilm and planktonic states were performed to identify key genes and metabolites involved in biofilm formation. A total of 789 differential genes and 365 differential metabolites were identified. By integrating transcriptomics and metabolomics, five main metabolic pathways were identified, including amino acid pathway, nucleotide metabolism pathway, carbon metabolism pathway, vitamin and cofactor metabolism pathway, and aminoacyl-tRNA biosynthesis metabolic pathway. CONCLUSIONS: These results provide new insights for exploring the molecular mechanism of S. suis biofilm formation.

Causal diagnostic model and governance strategies to reduce pollution from ship accidents in Chinese waters.

Ship transportation is a primary mode for global trade and cargo transport, yet even minor discrepancies can lead to ship accidents, causing severe secondary environmental pollution. Maritime accidents involve complex and numerous factors. Formal Concept Analysis (FCA) can identify the key contributing factors and their impact levels by eliminating homogenization factors in maritime accidents. This study constructs an innovative FCA model of ship accidents in Chinese waters, utilizing 172 ship accident reports released by the China Maritime Safety Administration. The analysis reveals seven reduced sets and 23 diagnostic rules of ship accidents. Results show that failed ship registration/security inspection, deficient nautical data and instruments, and management issues are the most critical factors. Three accident chains are identified and corresponding mitigation strategies are proposed to reduce potential pollution from ship accidents. These strategies offer significant reference value for preventing ship accidents and reducing their environmental impact in China and globally.

Genomic anatomy of homozygous XX females and YY males reveals early evolutionary trajectory of sex-determining gene and sex chromosomes in Silurus fishes.

Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type-II receptor (amhr2y), which is consistent with findings in two other Silurus species but on different chromosomes (Chr24 of S. meridionalis and Chr5 of S. asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.

The potential role of Akkermansia muciniphila in liver health.

Akkermansia muciniphila (A. muciniphila) is a 'star strain' that has attracted much attention in recent years. A. muciniphila can effectively regulate host metabolism, significantly affect host immune function, and play an important role in balancing host health and disease. As one of the organs most closely related to the gut (the two can communicate through the hepatic portal vein and bile duct system), liver is widely affected by intestinal microorganisms. A growing body of evidence suggests that A. muciniphila may alleviate liver-related diseases by improving the intestinal barrier, energy metabolism and regulating inflammation through its protein components and metabolites. This paper systematically reviews the key roles of A. muciniphila and its derivatives in maintaining liver health and improving liver disease.

[Box: see text].

Galacto-oligosaccharides modified whey protein isolate ameliorates cyclophosphamide-induced immunosuppression.

The effect of whey protein isolate (WPI)- galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS) conjugates on RAW264.7 cells, and further the effect of WPI-GOS conjugates on CTX-induced immunosuppressed mice were investigated. Compared to WPI-FOS conjugates, WPI-GOS conjugates exhibited deeper glycation extent, more pronounced structural unfolding and helix-destabilizing, and obviously improved functional indicators of RAW264.7 macrophages. In addition, WPI-GOS conjugates also repaired immune organ and intestinal barrier and increased IL-1ß and IFN-γ levels in immunosuppressed mice. The alteration of gut microbiota induced by WPI-GOS conjugates changed the serum metabolites, causing the activation of NFκB pathway, which strengthens the immune system. The activation of NFκB pathway maybe associated with the mTOR signal pathway and ABC transporters. However, the precise mechanisms by which NFκB pathway interacts with mTOR signal pathway and ABC transporters to modulate the immune response need for further research.