Direct shear behaviors of excavated clay reinforced with geocomposite drainage layer encapsulated in thin sand layers.

The objective of this study is to assess the effectiveness of a novel structure comprising a geocomposite drainage layer and a thin sand layer (GDL + sand) in mitigating the rapid dumping of excavated clay and its associated issues, such as landslides. Two sets of direct shear tests were conducted to investigate the influence of sand layer thickness and compaction degree on the interface shear behavior of the GDL + sand structure. As the sand layer thickness increased, both the interface shear strength and friction angle gradually increased, first more sharply and then at a slower rate toward stability, while the interface cohesion decreased gradually. The optimal sand layer thickness for achieving the most effective reinforcement in stabilizing the clay was identified as 10 mm. A higher sand layer compaction degree was found to result in increased interface shear strength, interface friction angle, and interface cohesion. Building on these findings, the reinforcing efficiency of the GDL + sand structure was investigated through mechanism analysis in comparison to that of a geogrid + sand structure and GDL structure as per the interface friction coefficient. The ranking of interface friction coefficients among the three structures emerged as: geogrid + sand > GDL + sand > GDL. These results suggests that the GDL + sand structure exhibits superior reinforcement efficiency compared to the GDL structure and offers better drainage efficiency than the geogrid + sand structure.

Genetic variants, haplotype determination, and function of novel alleles of CYP2B6 in a Han Chinese population.

Amino acid variants in protein may result in deleterious effects on enzymatic activity. In this study we investigate the DNA variants on activity of CYP2B6 gene in a Chinese Han population for potential use in precision medicine. All exons in CYP2B6 gene from 1483 Chinese Han adults (Zhejiang province) were sequenced using Sanger sequencing. The effects of nonsynonymous variants on recombinant protein catalytic activity were investigated in vitro with Sf12 system. The haplotype of novel nonsynonymous variants with other single nucleotide variants in the same allele was determined using Nanopore sequencing. Of 38 alleles listed on the Pharmacogene Variation Consortium, we detected 7 previously reported alleles and 18 novel variants, of which 11 nonsynonymous variants showed lower catalytic activity (0.00-0.60) on bupropion compared to CYP2B6*1. Further, these 11 novel star-alleles (CYP2B6*39-49) were assigned by the Pharmacogene Variation Consortium, which may be valuable for pharmacogenetic research and personalized medicine.

Effect of superheated steam treatment on enzyme inactivation, morphostructural, physicochemical and digestion properties of sand rice (Agriophyllum squarrosum) flour.

The lipase (LA) and peroxidase (POD) activities, as well as morphological structure, physicochemical and digestion properties of sand rice flour (SRF) treated with superheated steam (SS), were investigated. SS treatment at 165 °C completely deactivated LA and resulted in a 98% deactivation of POD activities in SRF. This treatment also intensified gelatinization, induced noticeable color alterations, and decreased pasting viscosities. Furthermore, there was a moderate reduction in crystal structure, lamellar structure, and short-range ordered structure, with a pronounced reduction at temperatures exceeding 170 °C. These alterations significantly impacted SRF digestibility, leading to increased levels of rapidly digestible starch (RDS) and resistant starch (RS), with the highest RS content achieved at 165 °C. The effectiveness of SS treatment depends on temperature, with 165 °C being able to stabilize SRF with moderate changes in color and structure. These findings will provide a scientific foundation for SS applicated in SRF stabilization and modification.

Fixed Yellow-to-Blue Intensity Ratio of Dy3+ in KY(CO3)2 Host for Emission Color Tuning.

Dy3+, Ce3+ co-doped KY(CO3)2 phosphors with a monoclinic structure were synthesized using the hydrothermal method to create a fixed yellow-to-blue ratio emission. The [YO8] polyhedron, consisting of a Y atom and eight oxygen atoms, forms a relatively independent microstructure within the KY(CO3)2 host. Y3+ ions are partially replaced by Ce3+ or Dy3+ ions to construct the [CeO8] or [DyO8] polyhedral fluorescence emission unit. The spectral measurements indicate that Ce3+ and Dy3+ can maintain relatively independent fluorescence emission characteristics in the KY(CO3)2 host. The yellow-to-blue intensity ratio of Dy3+ remains close to 1 and does not change with the variation in the doping concentration of KY(CO3)2:Dy3+ and KY(CO3)2:Dy3+,Ce3+ phosphors. When Ce3+ and Dy3+ are co-doped with KY(CO3)2, the emission intensities of Dy3+ under 339 nm and 365 nm excitation increase by 8.43 and 2.32 times, respectively, through resonance energy transfer and cross-relaxation. All Ce3+-doped KY(CO3)2:Dy3+ phosphors can emit white light. Among them, the emitted light of KY(CO3)2:3%Dy3+,5%Ce3+ is closest to standard daylight. Therefore, a stable [YO8] polyhedral structure can be used to achieve more color tuning of light.

Facile superhydrophobic modification on HPMC film using polydimethylsiloxane and starch granule coatings.

The excessive water sensitivity of hydroxypropyl methylcellulose (HPMC) films prevent them from being used extensively. In order to overcome this limitation, superhydrophobic HPMC films were meticulously crafted through the utilization of a composite of polydimethylsiloxane (PDMS) and ball-milled rice starch, corn starch, or potato starch (RS/CS/PS) for the coating process. Initially possessing hydrophilic properties, the HPMC Film (CA = 49.3 ± 1.8°) underwent a transformative hydrophobic conversion upon the application of PDMS, resulting in a static contact angle measuring up to 103.4 ± 2.0°. Notably, the synergistic combination of PDMS-coated HPMC with ball-milled starch demonstrated exceptional superhydrophobic attributes. Particularly, the treated HPMC-based film, specifically the HP-CS-2 h film, showcased an impressive contact angle of 170.5° alongside a minimal sliding angle of 5.2°. The impact of diverse starch types and the ball milling treatment on the PDMS/starch coatings and HPMC film was thoroughly examined using scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXS), and particle size analysis. These studies demonstrated that the low surface energy and roughness required for the creation of superhydrophobic HPMC-based films were imparted by the hierarchical structure formed by the application of PDMS/ball-milled starch. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Polydimethylsiloxane (PubChem CID: 24764); Hydroxypropyl methylcellulose (PubChem CID: 671); Ethyl acetate (PubChem CID: 8857).

Effect of endogenous protein and lipid removal on the physicochemical and digestion properties of sand rice (Agriophyllum squarrosum) flour.

The study investigated the effect of removing protein and/or lipid on the physicochemical characteristics and digestibility of sand rice flour (SRF). Morphological images showed that protein removal had a greater impact on exposing starch granules, while lipids acted as an adhesive. The treatment altered starch content in SRF samples, leading to increased starch crystallinity, denser semi-crystalline region, lower onset gelatinization temperature (To), higher peak viscosity and gelatinization enthalpy (ΔH), where Protein removal showed a more pronounced effect on altering physicochemical properties compared to lipid removal. The research revealed a positive correlation between rapidly digestible starch (RDS), maximum degree of starch hydrolysis (C∞), digestion rate constant (k) values and 1047/1022 cm-1 ratio, showing a strong connection between short-range structure and starch digestibility. The presence of endogenous proteins and lipids in SRF hinder digestion by restricting starch swelling and gelatinization, and physically obstructing enzyme-starch interaction. Lipids had a greater impact on starch digestibility than proteins, possibly due to their higher efficacy in reducing digestibility, higher lipid content with greater potential to form starch-lipid complexes. This study provides valuable insights into the interaction between starch and proteins/lipids in the sand rice seed matrix, enhancing its applicability in functional and nutritional food products.

LncRNA LBX2-AS1 promotes proliferation and migratory capacity of clear cell renal cell carcinoma through mitophagy.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been extensively investigated in the field of cancer, among which, lncRNA ladybird homeobox 2-antisense RNA 1 (LBX2-AS1) has been demonstrated to exert carcinogenic effects on a variety of malignancies. However, the biological functions of LBX2-AS1 in clear cell renal cell carcinoma (ccRCC) have not been explicitly elucidated. METHODS: Arraystar lncRNA chip and qRT-PCR verify the expression of LncRNA LBX2-AS1 in ccRCC. CCK-8 assay and cell cloning assay were used to assess the proliferative capacity of ccRCC cells. Migration abilities were quantified by scratch assay and transwell assay. Potential molecular signaling pathways were determined by high-throughput whole transcriptomics analysis. WB analysis was performed to validate the relationship between LBX2-AS1 and key molecules of mitophagy pathway. The effect of LBX2-AS1 on mitophagy was observed by laser confocal microscopy. Rescue experiments further validated the role of downstream gene FOXO3A in the LBX2-AS1 signaling pathway. Finally, the authentic effect of LBX2-AS1 was verified in vivo. RESULTS: LncRNA LBX2-AS1 was over expressed in ccRCC tissues and could enhance the proliferation and migration of ccRCC cells. Autophagic pathway was identified as a possible mechanism involved in the oncogenic effect of LBX2-AS1. Mitophagy levels were observed in LBX2-AS1 low-expressing cells through laser confocal microscopy. Knockdown of LBX2-AS1 significantly elevated mitophagy levels as observed using laser confocal microscopy and led to FOXOA3 decreasing in and BNIP3L and LC3 enrichment. Meanwhile, LBX2-AS1 knocking down dampened the proliferation of ccRCC cells in vivo.

The combination of propylene glycol and vegetable glycerin e-cigarette aerosols induces airway inflammation and mucus hyperconcentration.

Despite concerns over their safety, e-cigarettes (e-cigs) remain a popular tobacco product. Although nicotine and flavors found in e-cig liquids (e-liquids) can cause harm in the airways, whether the delivery vehicles propylene glycol (PG) and vegetable glycerin (VG) are innocuous when inhaled remains unclear. Here, we investigated the effects of e-cig aerosols generated from e-liquid containing only PG/VG on airway inflammation and mucociliary function in primary human bronchial epithelial cells (HBEC) and sheep. Primary HBEC were cultured at the air-liquid interface (ALI) and exposed to e-cig aerosols of 50%/50% v/v PG/VG. Ion channel conductance, ciliary beat frequency, and the expression of inflammatory markers, cell type-specific markers, and the major mucins MUC5AC and MUC5B were evaluated after seven days of exposure. Sheep were exposed to e-cig aerosols of PG/VG for five days and mucus concentration and matrix metalloproteinase-9 (MMP-9) activity were measured from airway secretions. Seven-day exposure of HBEC to e-cig aerosols of PG/VG caused a significant reduction in the activities of apical ion channels important for mucus hydration, including the cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated, and voltage-dependent K+ (BK) channels. PG/VG aerosols significantly increased the mRNA expression of the inflammatory markers interleukin-6 (IL6), IL8, and MMP9, as well as MUC5AC. The increase in MUC5AC mRNA expression correlated with increased immunostaining of MUC5AC protein in PG/VG-exposed HBEC. On the other hand, PG/VG aerosols reduced MUC5B expression leading overall to higher MUC5AC/MUC5B ratios in exposed HBEC. Other cell type-specific markers, including forkhead box protein J1 (FOXJ1), keratin 5 (KRT5), and secretoglobin family 1A member 1 (SCGB1A1) mRNAs, as well as overall ciliation, were significantly reduced by PG/VG exposure. Finally, PG/VG aerosols increased MMP-9 activity and caused mucus hyperconcentration in sheep in vivo. E-cig aerosols of PG/VG induce airway inflammation, increase MUC5AC expression, and cause dysfunction of ion channels important for mucus hydration in HBEC in vitro. Furthermore, PG/VG aerosols increase MMP-9 activity and mucus concentration in sheep in vivo. Collectively, these data show that e-cig aerosols containing PG/VG are likely to be harmful in the airways.

Outcomes of structure, function and flavor of pea protein isolate treated by AC, DC and pulsed electric fields.

Based on the standpoint of low carbon footprint processing and less denaturation of plant protein ingredient, the effects of pulsed electric field (PEF), direct current electric field (DCEF), and alternating current electric field (ACEF) treatments on the structure, functional properties and volatile compounds of pea protein isolate were investigated. The results showed that the electric fields (EFs) caused both blueshifts (max. âˆ¼8 cm-1) and redshifts (max. âˆ¼7 cm-1) in the IR spectra and blueshifts (max. âˆ¼5 nm) in the UV spectra. PEF caused an increase of emulsifying activity index and a decrease of emulsion stability index to DCEF and ACEF. A total of 27 volatile compounds were identified and the EFs could cause emerging of new volatiles and disappearing of inherent volatiles potentially to modify the flavor of products. Alterations were significantly observed among the types of EF, but seldomly among the operating parameter levels in the same EF.

A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner.

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.

Human-influenced changes in pollution status and potential risk of sediment heavy metals in Xincun Bay, a typical lagoon of Hainan, China.

Pollution status and ecological risks associated with sediment heavy metals (Cu, Pb, Zn, Cd, and Cr) were investigated around Xincun Bay, assessing their spatial variations and relationship with sediment physiochemical factors. Higher concentrations and associated risks were observed in the central region, where mariculture activities were concentrated, compared to non-maricultured areas. Despite with overall low concentrations, Cd had a higher ecological risk. Correlation and principal component analyses revealed similar sources for all metals in Xincun Bay. Heavy metal concentrations varied with expansion of mariculture operations in terms of quantity and scale, confirming the influence of mariculture activities. Sediments around mariculture had higher contents of clay, silt, and total organic carbon (TOC), and finer particle sizes. Quantitative analyses through correlation and linear regression indicated that TOC significantly regulated heavy metal concentration and distribution (p < 0.05). Considering its significant association with TOC, the influence of mean grain size should not be overlooked.

Enhanced interfacial boiling of impacting droplets upon vibratory surfaces.

HYPOTHESIS: Despite the flourishing studies of droplet interfacial boiling, the boiling upon vibratory surfaces, which may cause vigorous liquid-vapor-solid interactions, has rarely been investigated. Enhanced boiling normally can be gained from rapid removal of vapor and disturbance of liquid-vapor interface. We hypothesize that the vibratory surfaces enhance both effects with new intriguing phenomena and thus, attain an enhanced boiling heat transfer. EXPERIMENTS: We experimentally investigated the impacting fluid dynamics and coupled heat transfer patterns of multiple droplets and a single droplet impinging on still and vibratory surfaces of various materials and different wettability. FINDINGS: The boiling under vibratory surfaces with increased vibration velocity amplitude and enhanced wettability can be enhanced by 80% in heat transfer coefficient and Nusselt number, which is attributed to several reasons: shortened bubble lifespan, thinner and smaller bubbles, and enhanced disturbances in liquid-vapor interfaces. The vibration also delays the Leidenfrost point when the droplet impacts a descending surface, which shows that the droplet impact moment (vibration phase angle) is particularly crucial. The descending surface releases the generated vapor actively and facilitates liquid-solid contact, thereby delaying the Leidenfrost. From fundamentals to application, this article strengthens our understanding of vibrated interfacial boiling in scenarios closer to multiple natural processes and practical industries.

80 × 120 AI-enhanced LiDAR system based on a lightweight intensity-RGB-dToF sensor fusion neural network deployed on an edge device.

Collecting higher-quality three-dimensional points-cloud data in various scenarios practically and robustly has led to a strong demand for such dToF-based LiDAR systems with higher ambient noise rejection ability and limited optical power consumption, which is a sharp conflict. To alleviate such a clash, an idea of utilizing a strong ambient noise rejection ability of intensity and RGB images is proposed, based on which a lightweight CNN is newly, to the best of our knowledge, designed, achieving a state-of-the-art performance even with 90 × less inference time and 480 × fewer FLOPs. With such net deployed on edge devices, a complete AI-LiDAR system is presented, showing a 100 × fewer signal photon demand in simulation experiments when creating depth images of the same quality.

RRGA-Net: Robust Point Cloud Registration Based on Graph Convolutional Attention.

The problem of registering point clouds in scenarios with low overlap is explored in this study. Previous methodologies depended on having a sufficient number of repeatable keypoints to extract correspondences, making them less effective in partially overlapping environments. In this paper, a novel learning network is proposed to optimize correspondences in sparse keypoints. Firstly, a multi-layer channel sampling mechanism is suggested to enhance the information in point clouds, and keypoints were filtered and fused at multi-layer resolutions to form patches through feature weight filtering. Moreover, a template matching module is devised, comprising a self-attention mapping convolutional neural network and a cross-attention network. This module aims to match contextual features and refine the correspondence in overlapping areas of patches, ultimately enhancing correspondence accuracy. Experimental results demonstrate the robustness of our model across various datasets, including ModelNet40, 3DMatch, 3DLoMatch, and KITTI. Notably, our method excels in low-overlap scenarios, showcasing superior performance.

Formation Mechanism of Starch-Based Double Emulsions from the Interfacial Perspective.

Double emulsions are of significant practical value in protecting the core material owing to their multicomponent structure and have thus been applied in various fields, such as food, cosmetics, and drugs. However, the mechanism of double emulsion formation by native starch is not well established. Herein, we demonstrate a facile route to develop type-A, type-B, and type-C double emulsions using native starch and develop an innovative design for a carrier. Interfacial interaction, enthalpy changes of starch, and interfacial properties are key factors governing the formation of double emulsions and controlling the type of double emulsions formed. Therefore, the results of this study provide a better understanding of how and what type of starch-based double emulsions are formed.

Effect of melting combined with ice recrystallization on porous starch preparation: Pore-forming properties, granular morphology, functionality, and multi-scale structures.

In this work, critical melting (CM) combined with freeze-thawing treatment (FT, freezing at -20 â„ƒ and -80 â„ƒ, respectively) was used to prepare porous starch. The results showed that CM combined with the slow freezing rate (-20 â„ƒ) can prepare porous starch with characteristics of grooves and cavities, while combined with the rapid freezing rate (-80 â„ƒ) can prepare with holes and channels, especially after repeating FT cycles. Compared with the native counterpart, the specific surface area, pore volume, and average diameter of CMFT-prepared porous starch were significantly increased to 4.07 m2/g, 7.29 cm3/g × 10-3, and 3.57 nm, respectively. CMFT significantly increased the thermal stability of starch, in which the To, Tp, and Tc significantly increased from 63.32, 69.62, and 72.90 (native) to ∼69, 72, and 76 °C, respectively. CMFT significantly increased water and oil absorption of porous starch from 91.20 % and 72.00 % (native) up to ∼163 % and 94 %, respectively. Moreover, CMFT-prepared porous starch had a more ordered double-helical structure, which showed in the significantly increased relative crystallinity, semi-crystalline lamellae structure, and the proportion of the double helix structure of starch. The synergistic effect of melting combined with ice recrystallization can be used as an effective way to prepare structure-stabilized porous starch.

The decreased risk of hepatocellular carcinoma in hepatitis B virus-related cirrhotic portal hypertension patients after laparoscopic splenectomy and azygoportal disconnection.

BACKGROUND: Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH). METHODS: A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan-Meier curves, and logistic regression to estimate survival and risk differences. RESULTS: Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan-Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928-8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343-0.776; P = 0.002). CONCLUSION: Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors.

Effect of apatinib on the pharmacokinetics of tramadol and O-desmethyltramadol in rats.

Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP2D6.1. The samples were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo results showed that compared with the control group, apatinib increased the AUC(0-t), AUC(0-∞) and Cmax values of tramadol and O-desmethyltramadol, and decreased the values of VZ/F and CLz/F. In addition, the MRT(0-t), MRT(0-∞) values of O-desmethyltramadol were increased. In vitro, apatinib inhibited the metabolism of tramadol by a mixed way with IC50 of 1.927 µM in RLMs, 2.039 µM in HLMs and 15.32 µM in CYP2D6.1. In summary, according to our findings, apatinib has a strong in vitro inhibitory effect on tramadol, and apatinib can increase the analgesic effect of tramadol and O-desmethyltramadol in rats.

Impact of Regional Collaborative Network on the Rescue of Patients with ST-Elevation Myocardial Infarction First Visit to non-PCI Hospitals.

Objective: To assess the effect of a regional collaborative network on the treatment of ST-elevation myocardial infarction (STEMI) patients first admitted to non- percutaneous coronary intervention (PCI) hospitals. Methods: Using data from Kunshan Hospital of Traditional Chinese Medicine's chest pain center database, patients were grouped based on the establishment of the regional collaborative rescue network. Key timepoints and in-hospital complications were analyzed. Results: A total of 152 ST-elevation myocardial infarction patients were included in the study. Compared to control group, symptom-to-balloon time (S-B), time of first medical contact to balloon and inter-hospital referral time in observation group were significantly shorter [(314.03 ± 209.26) min vs (451.27 ± 290.44) min, P = .001], [(115.32 ± 54.73) min vs (191.67 ± 130.30) min, P = .001], [(55.09 ± 37.23) min vs (112.67 ± 95.90) min, P = .001], but time of symptom to first medical contact were not statistically significant[(210.27±217.07) min vs (239.61 ± 200.92) min, P = .136].The incidence of heart failure and total complications during hospitalization decreased [7 (8.14%) vs 13 (19.70%), P = .037] and [14 (16.28%) vs 24 (36.36%), P = .004]. However no statistically significant difference were observed in rate of death during hospitalization [2 (2.33%) vs 3 (4.55%), P = .450], ventricular fibrillation [2 (2.33%) vs 3 (4.55%), P = .450], left ventricular thrombosis [2 (2.33%) vs 4 (6.06%), P = .244] and recurrent myocardial infarction[1 (1.16%) vs 1 (1.52%), P = .851]. Conclusions: The regional cooperative rescue network notably reduces ischemic and referral times for STEMI patients, lowering the incidence of heart failure during their hospital stay.

Functional evaluation of CYP2C19 and CYP3A4 gene polymorphism on ibuprofen metabolism.

AIM: Ibuprofen is the most commonly used analgesic. CYP polymorphisms are mainly responsible for the differences in drug metabolism among individuals. Variations in the ability of populations to metabolize ibuprofen can lead to drug exposure events. The aim of this study was to evaluate the effects of CYP2C19 and CYP3A4 polymorphisms on ibuprofen metabolism in a Chinese population. METHODS: First, 31 CYP2C19 and 12 CYP3A4 microsomal enzymes were identified using an insect expression system. Then, variants were evaluated using a mature incubation system. Moreover, ibuprofen metabolite content was determined via ultra-performance liquid chromatography-tandem mass spectrometry analysis. Finally, kinetic parameters of CYP2C19 and CYP3A4 genotypes were determined via Michaelis-Menten curve fitting. RESULTS: Most variants exhibited significantly altered intrinsic clearance compared to the wild type. In the CYP2C19 metabolic pathway, seven variants exhibited no significant alterations in intrinsic clearance (CLint), six variants exhibited significantly high CLint (121-291%), and the remaining 15 variants exhibited substantially reduced CLint (1-71%). In the CYP3A4 metabolic pathway, CYP3A4*30 was not detected in the metabolite content due to the absence of activity, and 10 variants exhibited significantly reduced CLint. CONCLUSION: To the best of our knowledge, this is the first study to assess the kinetic characteristics of 31 CYP2C19 and 12 CYP3A4 genotypes on ibuprofen metabolism. However, further studies are needed on poor metabolizers as they are more susceptible to drug exposure. Our findings suggest that the kinetic characteristics in combination with artificial intelligence to predict the toxicity of ibuprofen and reduce any adverse drug reactions.