Three-Dimensional ERT Advanced Detection Method with Source-Position Electrode Excitation for Tunnel-Boring Machines.

Tunnel-boring machines (TBMs) are widely used in urban underground tunnel construction due to their fast and efficient features. However, shield-tunnel construction faces increasingly complex geological environments and may encounter geological hazards such as faults, fracture zones, water surges, and collapses, which can cause significant property damage and casualties. Existing geophysical methods are subject to many limitations in the shield-tunnel environment, where the detection space is extremely small, and a variety of advanced detection methods are unable to meet the required detection requirements. Therefore, it is crucial to accurately detect the geological conditions in front of the tunnel face in real time during the tunnel boring process of TBM tunnels. In this paper, a 3D-ERT advanced detection method using source-position electrode excitation is proposed. First, a source-position electrode array integrated into the TBM cutterhead is designed for the shield-tunnel construction environment, which provides data security for the inverse imaging of the anomalous bodies. Secondly, a 3D finite element tunnel model containing high- and low-resistance anomalous bodies is established, and the GREIT reconstruction algorithm is utilized to reconstruct 3D images of the anomalous body in front of the tunnel face. Finally, a physical simulation experiment platform is built, and the effectiveness of the method is verified by laboratory physical modeling experiments with two different anomalous bodies. The results show that the position and shape of the anomalous body in front of the tunnel face can be well reconstructed, and the method provides a new idea for the continuous detection of shield construction tunnels with boring.

Charge-Coupled Frequency Response Multispectral Inversion Network-Based Detection Method of Oil Contamination on Airport Runway.

Aircraft failures can result in the leakage of fuel, hydraulic oil, or other lubricants onto the runway during landing or taxiing. Damage to fuel tanks or oil lines during hard landings or accidents can also contribute to these spills. Further, improper maintenance or operational errors may leave oil traces on the runway before take-off or after landing. Identifying oil spills in airport runway videos is crucial to flight safety and accident investigation. Advanced image processing techniques can overcome the limitations of conventional RGB-based detection, which struggles to differentiate between oil spills and sewage due to similar coloration; given that oil and sewage have distinct spectral absorption patterns, precise detection can be performed based on multispectral images. In this study, we developed a method for spectrally enhancing RGB images of oil spills on airport runways to generate HSI images, facilitating oil spill detection in conventional RGB imagery. To this end, we employed the MST++ spectral reconstruction network model to effectively reconstruct RGB images into multispectral images, yielding improved accuracy in oil detection compared with other models. Additionally, we utilized the Fast R-CNN oil spill detection model, resulting in a 5% increase in Intersection over Union (IOU) for HSI images. Moreover, compared with RGB images, this approach significantly enhanced detection accuracy and completeness by 25.3% and 26.5%, respectively. These findings clearly demonstrate the superior precision and accuracy of HSI images based on spectral reconstruction in oil spill detection compared with traditional RGB images. With the spectral reconstruction technique, we can effectively make use of the spectral information inherent in oil spills, thereby enhancing detection accuracy. Future research could delve deeper into optimization techniques and conduct extensive validation in real airport environments. In conclusion, this spectral reconstruction-based technique for detecting oil spills on airport runways offers a novel and efficient approach that upholds both efficacy and accuracy. Its wide-scale implementation in airport operations holds great potential for improving aviation safety and environmental protection.

Predictive value of contrast-enhanced ultrasonography for the early diagnosis of renal dysfunction after kidney transplantation: A systematic review and meta-analysis.

OBJECTIVES: We aimed to evaluate the changes in renal cortical microperfusion and quantitative contrast-enhanced ultrasonography (CEUS) parameters after kidney transplantation, and to determine the evidence-based value of CEUS in predicting renal dysfunction. METHODS: The Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched for relevant studies published from 2000 to 2023 on the use of CEUS to assess the renal cortical microcirculation after kidney transplantation. Subject terms and related keywords were combined, and a meta-analysis and systematic review were performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. RESULTS: The search yielded six studies involving 451 patients with moderate to high overall quality. The peak intensity (standardized mean difference [SMD]: -0.64, 95% confidence interval [CI] -1.13 to -0.15, p = 0.01) of CEUS was significantly lower in patients with renal dysfunction than in those with stable renal function. However, the time to peak (SMD: 0.28, 95% CI 0.04 to 0.52, p = 0.02) was significantly shorter in patients with renal dysfunction than in those with stable renal function. The total renal cortical microperfusion and renal cortical perfusion intensity were decreased, and the perfusion time was prolonged, in patients with renal dysfunction after kidney transplantation. CONCLUSION: CEUS parameters can reflect real-time changes in renal cortical microperfusion, thus providing a basis for the early diagnosis of renal dysfunction after kidney transplantation.

Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy.

Doxorubicin (DOX) is a powerful and commonly used chemotherapeutic drug, used alone or in combination in a variety of cancers, while it has been found to cause serious cardiac side effects in clinical application. More and more researchers are trying to explore the molecular mechanisms of DOX-induced cardiomyopathy (DIC), in which oxidative stress and inflammation are considered to play a significant role. This review summarizes signaling pathways related to oxidative stress and inflammation in DIC and compounds that exert cardioprotective effects by acting on relevant signaling pathways, including the role of Nrf2/Keap1/ARE, Sirt1/p66Shc, Sirt1/PPAR/PGC-1α signaling pathways and NOS, NOX, Fe2+ signaling in oxidative stress, as well as the role of NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-κB, mTOR/TFEB/NF-κB pathways in DOX-induced inflammation. Hence, we attempt to explain the mechanisms of DIC in terms of oxidative stress and inflammation, and to provide a theoretical basis or new idea for further drug research on reducing DIC. Video Abstract.

How Different Substitution Positions of F, Cl Atoms in Benzene Ring of 5-Methylpyrimidine Pyridine Derivatives Affect the Inhibition Ability of EGFRL858R/T790M/C797S Inhibitors: A Molecular Dynamics Simulation Study.

Lung cancer is the most frequent cause of cancer-related deaths worldwide, and mutations in the kinase domain of the epidermal growth factor receptor (EGFR) are a common cause of non-small-cell lung cancers, which is a major subtype of lung cancers. Recently, a series of 5-methylpyrimidine-pyridinone derivatives have been designed and synthesized as novel selective inhibitors of EGFR and EGFR mutants. However, the binding-based inhibition mechanism has not yet been determined. In this study, we carried out molecular dynamic simulations and free-energy calculations for EGFR derivatives to fill this gap. Based on the investigation, the three factors that influence the inhibitory effect of inhibitors are as follows: (1) The substitution site of the Cl atom is the main factor influencing the activity through steric effect; (2) The secondary factors are repulsion between the F atom (present in the inhibitor) and Glu762, and the blocking effect of Lys745 on the phenyl ring of the inhibitor. (3) The two factors function synergistically to influence the inhibitory capacity of the inhibitor. The theoretical results of this study can provide further insights that will aid the design of oncogenic EGFR inhibitors with high selectivity.

O2-evolving and ROS-activable nanoparticles for treatment of multi-drug resistant Cancer by combination of photodynamic therapy and chemotherapy.

Herein, a novel nano-system IF7-ROSPCNP, which is O2-evolving and reactive oxygen species (ROS)-activable, was developed for enhancing the combination chemotherapy and photodynamic therapy (PDT). The nanoparticles composed of photosensitizers (disulfonated meso-tetraphenylporphine, TPPS2a) and catalase in the inner core, doxorubicin (DOX) in the polymeric shell and functionalized on its surface with IF7 peptide, which specially bind to annexin 1. As confirmed that the structure of IF7-ROSPCNP was able to remain intact under normal physiological conditions. After IF7-ROSPCNP was selectively entrapped by the annexin 1-positive and ROS-abundant MCF-7/ADR cells, the shell of nanoparticles was ruptured and the entrapped photosensitizers were completely released out. Under irradiation, ROS was continuously produced and the DOX, which was conjugated to the terminal of polylactic copolymer (mPEG-PLA) by a ROS-cleavable linkage, was subsequently released. With such strategy, cellular uptake of drugs was dramatically improved resulted in an enhanced cytotoxicity and anti-tumor effect on drug resistant cancer.

Localized terahertz electromagnetically-induced transparency-like phenomenon in a conductively coupled trimer metamolecule.

We experimentally investigate the terahertz (THz) electromagnetically-induced transparency (EIT)-like phenomenon in a metamolecule (MM) of three-body system. This system involves a couple of geometrically identical split-ring resonators (SRRs) in orthogonal layout conductively coupled by a cut-wire resonator. Such a three-body system exhibits two frequency response properties upon to the polarization of incident THz beam: One is the dark-bright-bright layout to the horizontally polarized THz beam, where there is no EIT-like effect; the other is bright-dark-dark layout to the vertically polarized THz beam, where an EIT-like effect is observable. The transparency window can be tuned from 0.71 THz to 0.74 THz by the displacement of cut-wire inside the trimer MM. A maximum of 7.5 ps group delay of THz wave is found at the transparent window of 0.74 THz. When the cut-wire moved to the mid-point of lateral-side of SRR, the EIT-like phenomenon disappears, this leads to a localized THz slow-light effect. The distribution of surface currents and electric energy reveals that the excited inductive-capacitive (LC) oscillation of bright-SRR dominates the high frequency side-mode, which is isolated to the displacement of cut-wire resonator. However, the low frequency side-mode originates from the constructive hybridization of LC resonance in dark-SRR coupled with a localized S-shaped dipole oscillator, which is tunable by the displacement of cut-wire. As a consequence, the group delay as well as the spectral configuration of transparency window can be manipulated by tuning one side-mode while fixing the other. Such an experimental finding reveal the EIT-like effect in a conductively coupled three-body system and manifests a novel approach to achieve tunable THz slow-light device.

Flexible focus function consisting of convex function and image enhancement filter.

We propose a new focus function Λ that, like many of the existing focus functions, consists of a convex function and an image enhancement filter. Λ is rather flexible because for any convex function and image enhancement filter, it is a focus function. We proved that Λ is a focus function using a model and Jensen's inequality. Furthermore, we generated random Λs and experimentally applied them to simulated and real blurred images, finding that 98% and 99% of the random Λs, respectively, have a maximum value at the best-focused image and most of them decrease as the defocus increases. We also applied random Λs to motion-blurred images, blurred images in different-sized windows, and blurred images with different types of noise. We found that Λ can be applied to motion blur and is robust to different-sized windows and different noise types.

Age differences in the association of body mass index-defined obesity with abdominal aortic calcification.

Objectives: In cardiovascular disease, previous studies have suggested young age as one of the reasons to explain the obesity paradox. This study attempts to provide a different opinion on this claim through unexpected findings. Methods: We used a cross-sectional analysis of the US nationally representative data, total of 10,175 participants were recruited in 2013-2014 from NHANES. A total of 947 participants were selected to be included in this study through inclusion criteria and exclusion criteria for statistical analysis of the relationship between obesity and abdominal aortic calcification(AAC). Smooth curve fitting and multivariate regression analyses were conducted to examine the associations of obesity with AAC after adjusting for age, gender and associated variates. Results: Depending on the age of the population, the relationship between obesity and AAC showed the different outcome. Obesity was associated with the lower risk of AAC among individuals older than 52 years of age. According to the difference of adjusted covariates, the AAC scores in the obesity group decreased by 0.92, 0.87, and 1.11 for 52 years old or older individuals. In particular, the risk of AAC was lower for patients with obesity with the following characteristics: male, low LDL, low triglyceride, DM, non-cancer patient, smoking, drinking, vigorous work activity, low annual household income, education of 9 - 11th grades and non-Hispanic white. Conclusions: In US, adults aged 52 years or older, obesity was associated with decreased AAC risk. Older age may be one potential reason for the obesity paradox.

Study of Aging Temperature on the Thermal Compression Behaviors and Microstructure of a Novel Ni-Cr-Co-Based Superalloy.

Nickel-based superalloys have been widely used in the aerospace industry, and regulating the reinforcing phases is the key to improving the high-temperature strength of the alloy. In this study, a series of aging treatments (650 °C, 750 °C, 850 °C and 950 °C for 8 h) were designed to study different thermal deformation behaviors and microstructure evolutions for a novel nickel-based superalloy. Among the aged samples, the 950 °C aged sample achieved the peak stress of ~323 MPa during the thermal deformation and the highest microhardness of ~315 HV after thermal compression, which were the greatest differences compared to before deformation. In addition, the grains of the 950 °C sample exhibit deformed fibrous shapes, and the grain orientation is isotropic, while the other samples exhibited isotropy. In the 850 °C and 950 °C high-temperature aging samples, the γ' precipitate (about 20 nm in size) is gradually precipitated, which inhibits the movement of dislocation in the grain during compression, thus inhibiting the occurrence of dynamic recrystallization and improving the high-temperature mechanical properties of the alloy.

The role of autophagy in Parkinson's disease: rotenone-based modeling.

BACKGROUND: Autophagy-mediated self-digestion of cytoplasmic inclusions may be protective against neurodegenerative diseases such as Parkinson's disease (PD). However, excessive autophagic activation evokes autophagic programmed cell death. METHODS: In this study, we aimed at exploring the role of autophagy in the pathogenesis of rotenone-induced cellular and animal models for PD. RESULTS: Reactive oxygen species over-generation, mitochondrial membrane potential reduction or apoptosis rate elevation occurred in a dose-dependent fashion in rotenone-treated human neuroblastoma cell line SH-SY5Y. The time- and dose-dependent increases in autophagic marker microtubule-associated protein1 light chain 3 (LC3) expression and decreases in autophagic adaptor protein P62 were observed in this cellular model. LC3-positive autophagic vacuoles were colocalized with alpha-synuclein-overexpressed aggregations. Moreover, the number of autophagic vacuoles was increased in rotenone-based PD models in vitro and in vivo. CONCLUSIONS: These data, along with our previous finding showing rotenone-induced toxicity was prevented by the autophagy enhancers and was aggravated by the autophagy inhibitors in SH-SY5Y, suggest that autophagy contributes to the pathogenesis of PD, attenuates the rotenone toxicity and possibly represents a new subcellular target for treating PD.

An update on the molecular mechanism and pharmacological interventions for Ischemia-reperfusion injury by regulating AMPK/mTOR signaling pathway in autophagy.

AMP-activated protein kinase (5'-adenosine monophosphate-activated protein kinase, AMPK)/mammalian target of rapamycin (mTOR) is an important signaling pathway maintaining normal cell function and homeostasis in vivo. The AMPK/mTOR pathway regulates cellular proliferation, autophagy, and apoptosis. Ischemia-reperfusion injury (IRI) is secondary damage that frequently occurs clinically in various disease processes and treatments, and the exacerbated injury during tissue reperfusion increases disease-associated morbidity and mortality. IRI arises from multiple complex pathological mechanisms, among which cell autophagy is a focus of recent research and a new therapeutic target. The activation of AMPK/mTOR signaling in IRI can modulate cellular metabolism and regulate cell proliferation and immune cell differentiation by adjusting gene transcription and protein synthesis. Thus, the AMPK/mTOR signaling pathway has been intensively investigated in studies focused on IRI prevention and treatment. In recent years, AMPK/mTOR pathway-mediated autophagy has been found to play a crucial role in IRI treatment. This article aims to elaborate the action mechanisms of AMPK/mTOR signaling pathway activation in IRI and summarize the progress of AMPK/mTOR-mediated autophagy research in the field of IRI therapy.

Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway.

Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.

Nano-assembly of ursolic acid with platinum prodrug overcomes multiple deactivation pathways in platinum-resistant ovarian cancer.

As the most common cause of gynecological cancer-related deaths worldwide, ovarian cancer requires novel therapy strategies. Pt(ii)-Based antitumor drugs (e.g. cisplatin) are one of the most successful and frequently used drugs in ovarian cancer chemotherapy at present. However, drug resistance and severe side effects are the major problems in cancer treatment. Herein, the design of a reduction responsive platinum(iv) (Pt(iv))/ursolic acid (UA)/polyethylene glycol (PEG) dual prodrug amphiphile (Pt(iv)-UA-PEG) to treat cisplatin-resistant ovarian cancer is reported for the first time. Pt(iv)-UA-PEG could self-assemble into nanoparticles (Pt(iv)-UA NPs) with a fixed and precise Pt/UA ratio, and a constantly high content of drugs. Pt(iv)-UA NPs could be efficiently taken up by cisplatin-resistant ovarian cancer cells and release the drug in intracellular reductive and acidic environments. In vitro studies show that the released UA and cisplatin have different anticancer mechanisms, and their synergistic effects overcome the detoxification and anti-apoptotic mechanisms of cancer cells. Furthermore, the in vivo results indicate that Pt(iv)-UA NPs have a prolonged blood circulation time, enhanced tumor accumulation, and significantly improved antitumor efficacy in A2780/DDP tumor-bearing mice, without causing any side effects. In summary, our results demonstrate that the development of the stimuli-responsive dual prodrug amphiphile nano-assembly provides a new strategy to overcome drug resistance.

Quantitative Evaluation of Renal Cortex Perfusion Using Contrast-Enhanced Ultrasound Imaging Parameters in Ischemia-Reperfusion Injury in Rabbits.

The aim of this study was to evaluate blood perfusion of the renal cortex during ischemia-reperfusion (I/R) injury using quantitative contrast-enhanced ultrasound (CEUS) parameters. In this experiment, 24 rabbits were randomly divided into four groups (N = 6): sham-operated group, 24-h post-operation for I/R injury group (24-h I/R), 3-d post-operation for I/R injury group (3-d I/R) and 5 d post-operation for I/R injury group (5 d I/R). All quantitative CEUS parameters were monitored and included the gradient from the start frame to the peak frame (Grad), area under the curve (Area), time-to-peak (TTP), difference between B(intercept intensity at t=0) and A(the intensity attenuation t= 0) and arrival time (AT). Subsequently, we analyzed the changes in these parameters, as well as the correlation between changes in CEUS parameters and pathological parameters. AT and TTP values peaked 3 d after I/R surgery, which correlated with the most significant pathological changes at the same time point. These parameters (such as AT, TTP and Grad) may be useful in dynamically monitoring the severity of tissue damage at the early stage of I/R injury.

In vitro antioxidant and antitumor study of zein/SHA nanoparticles loaded with resveratrol.

Resveratrol (RES) loaded Zein-SHA (low-molecular-weight sodium hyaluronate) nanoparticles with average diameter of about 152.13 nm and polydispersity index (PDI) of 0.122, which can be used to encapsulate, protect and deliver resveratrol. By measuring ABTS free radical scavenging ability and iron (III) reducing power, it was determined that encapsulated resveratrol has higher in vitro antioxidant activity than free resveratrol. When tested with murine breast cancer cells 4T1, the encapsulated resveratrol also showed higher antiproliferative activity than free resveratrol, with IC50 values of 14.73 and 17.84 µg/ml, respectively. The colloidal form of resveratrol developed in this research may be particularly suitable for functional foods and beverages, as well as dietary supplements and pharmaceutical products.

Engineering Endogenous Tumor-Associated Macrophage-Targeted Biomimetic Nano-RBC to Reprogram Tumor Immunosuppressive Microenvironment for Enhanced Chemo-Immunotherapy.

Immunotherapy has shown encouraging results in various cancers, but the response rates are relatively low due to the complex tumor immunosuppressive microenvironment (TIME). The presence of tumor-associated macrophages (TAMs) and tumor hypoxia correlates significantly with potent immunosuppressive activity. Here, a hemoglobin-poly(ε-caprolactone) (Hb-PCL) conjugate self-assembled biomimetic nano red blood cell (nano-RBC) system (V(Hb)) is engineered to deliver chemotherapeutic doxorubicin (DOX) and oxygen for reprogramming TIME. The Hb moiety of V(Hb)@DOX can bind to endogenous plasma haptoglobin (Hp) and specifically target the M2-type TAMs via the CD163 surface receptor, and effectively kill the cells. In addition, the O2 released by the Hb alleviates tumor hypoxia, which further augments the antitumor immune response by recruiting fewer M2-type macrophages. TAM-targeting depletion and hypoxia alleviation synergistically reprogram the TIME, which concurrently downregulate PD-L1 expression of tumor cells, decrease the levels of immunosuppressive cytokines such as IL-10 and TGF-ß, elevate the immunostimulatory IFN-γ, enhance cytotoxic T lymphocyte (CTL) response, and boost a strong memory response. The ensuing TAM-targeted chemo-immunotherapeutic effects markedly inhibit tumor metastasis and recurrence. Taken together, the engineered endogenous TAM-targeted biomimetic nano-RBC system is a highly promising tool to reprogram TIME for cancer chemo-immunotherapy.

The preventive effect of Xuebijing injection against cytokine storm for severe patients with COVID-19: A prospective randomized controlled trial.

INTRODUCTION: COVID-19 is severely affecting countries globally and mortality is high. Xuebijing (XBJ) injection is widely used in the treatment of severe pneumonia and sepsis in China due to its anti-inflammatory effect and immunoregulation. This study investigated whether Xuebijing injection can prevent the cytokine storm and reduce the mortality from severe COVID-19. METHODS: This was a randomized, double-blinded trial in which 60 eligible patients were recruited from the First people's Hospital of Jingzhou from February 16 to March 25 in 2020. A total of 57 completed the trial, 3 dropped out. The treatment group received routine medication plus Xuebijing injection while the control group received routine medication plus saline. RESULTS: The secretion of interleukin-6(IL-6), interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) was suppressed significantly (P < 0.05) by Xuebijing. After 14 days treatment, lymphocyte levels in Xuebijing group was substantially higher than control, C-reactive protein (CRP) level in Xuebijing group was remarkably lower. The 28-day mortality was not significantly different between the two group. After 14 days of treatment, there were significant differences in the rate of mechanical ventilation, rate of septic shock, the proportion of patients severely affected who became critically ill, the duration of improvement of main clinical symptoms (P < 0.05) and the length of ICU hospitalization stay (P < 0.01) for the Xuebijing group compared with controls. No serious adverse reactions were identified in either group. CONCLUSIONS: This study demonstrates that Xuebijing injection may suppress the cytokine storm in severe COVID-19 patients by regulating the secretion of pro- inflammatory cytokine IL-6, IL-8 and TNF -α. However, Xuebijing did not significantly reduce the 28-day mortality.

Quantitative evaluation of dexamethasone treatment effects in renal ischemia-reperfusion injury using contrast enhanced ultrasonography in rats.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury often occurs in various clinical events, and its incidence and mortality have been increasing. OBJECTIVE: To investigate the value of contrast enhanced ultrasonography (CEUS) in the monitoring of dexamethasone in the improvement of renal I/R injury in rats. METHODS: Eighteen healthy male Sprague-Dawley rats were randomly divided into sham-operated, I/R, and I/R surgery plus dexamethasone treatment (Dexa) groups. In the I/R group 45-minute renal ischemia with 24 h reperfusion period was monitored. Time-intensity curve (TIC)-derived parameters, which included peak value, time to peak (TP), area under the curve (AUC), and mean transit time (MTT) were compared to the blood creatinine, urea, Caspase-1, and NLRP3 levels. RESULTS: The I/R group showed an increased peak value, prolonged TP and MTT, and greater AUC (P < 0.05). The Dexa group showed shorter TP and MTT, and smaller AUC (P < 0.05). Results show that the associations between (i) TP, AUC, and MTT and (ii) creatinine, urea, Caspase-1, and NLRP3 levels were significant (P < 0.05). CONCLUSION: Dexamethasone can alleviate renal I/R injury in rats, which may be related to the inhibition of NLRP3 and caspase-1. CEUS can quantitatively measure this change, in which the changes in TP, AUC and MMT values have considerable reference values.

miR-4721, Induced by EBV-miR-BART22, Targets GSK3ß to Enhance the Tumorigenic Capacity of NPC through the WNT/ß-catenin Pathway.

Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo. Mechanism analysis indicated that miR-4721 directly targetes GSK3ß and reduces its expression, which therefore elevates ß-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3ß are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3ß, which thus activates the WNT/ß-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future.