Manipulating HGF signaling reshapes the cirrhotic liver niche and fills a therapeutic gap in regeneration mediated by transplanted stem cells.

Long-term stem cell survival in the cirrhotic liver niche to maintain therapeutic efficacy has not been achieved. In a well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhosis animal model, we previously showed that liver-resident stem/progenitor cells (MLpvNG2+ cells) or immune cells have improved survival in the fibrotic liver environment but died via apoptosis in the cirrhotic liver environment, and increased levels of hepatocyte growth factor (HGF) mediated this cell death. We tested the hypothesis that inhibiting HGF signaling during the cirrhotic phase could keep the cells alive. We used adeno-associated virus (AAV) vectors designed to silence the c-Met (HGF-only receptor) gene or a neutralizing antibody (anti-cMet-Ab) to block the c-Met protein in the DEN-induced liver cirrhosis mouse model transplanted with MLpvNG2+ cells between weeks 6 and 7 after DEN administration, which is the junction of liver fibrosis and cirrhosis at the site where most intrahepatic stem cells move toward apoptosis. After 4 weeks of treatment, the transplanted MLpvNG2+ cells survived better in c-Met-deficient mice than in wild-type mice, and cell activity was similar to that of the mice that received MLpvNG2+ cells at 5 weeks after DEN administration (liver fibrosis phase when most of these cells proliferated). Mechanistically, a lack of c-Met signaling remodeled the cirrhotic environment, which favored transplanted MLpvNG2+ cell expansion to differentiation into mature hepatocytes and initiate endogenous regeneration by promoting mature host hepatocyte generation and mediating functional improvements. Therapeutically, c-Met-mediated regeneration can be mimicked by anti-cMet-Ab to interfere functions, which is a potential drug for cell-based treatment of liver fibrosis/cirrhosis.

Etiological Mechanisms and Genetic/Biological Modulation Related to PTH1R in Primary Failure of Tooth Eruption.

Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.

Incremental prognostic value of 18F-fluorodeoxyglucose myocardial ischemic memory imaging for major adverse cardiovascular events in patients with suspected unstable angina.

BACKGROUND: The additional prognostic value of 18F-flurodeoxyglucose positron emission tomography (18F-FDG PET) myocardial ischemic memory imaging for patients with suspected unstable angina (UA) is not well established. This study aimed to determine whether 18F-FDG PET imaging provides incremental prognostic information for predicting major adverse cardiac events (MACEs) compared to clinical risk factors, Global Registry of Acute Coronary Events (GRACE) score, and coronary artery calcium score (CACS) in patients with suspected UA. METHODS: In this post hoc analysis of a prospective study, 265 patients suspected with UA (62.3% male, mean age: 65.0±9.4 years) were enrolled. 18F-FDG positivity was defined as focal or focal on diffuse uptake patterns. MACEs included cardiovascular death, acute myocardial infarction, heart failure, rehospitalization for UA, and stroke. Multivariable Cox regression was used to identify predictors of MACEs, and the incremental prognostic value of 18F-FDG PET imaging was assessed using the Concordance Index (C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Over a median follow-up of 25 months, 51 patients (19.2%) experienced MACEs. 18F-FDG positivity (hazard ratio [HR]=3.220, 95% confidence interval [CI]: 1.630-6.360, P<.001), as well as 18F-FDG standardized uptake ratio (HR=1.330, 95% CI: 1.131-1.564, P=.0006) and Extent (HR=1.045, 95% CI: 1.028-1.062, P<.0001), were independent predictors of MACE. The addition of 18F-FDG PET imaging significantly improved risk stratification beyond clinical factors, the GRACE score, and CACS, with improved C-index (.769 vs .688, P=.045), NRI (.324, P=.020), and IDI (.055, P=.027). CONCLUSION: 18F-FDG PET myocardial ischemic memory imaging significantly improves prognostic assessment for patients with suspected UA, providing valuable additional risk stratification beyond clinical risk factors, GRACE score, and CACS.

Novel 131-iodine labeled and ultrasound-responsive nitric oxide and reactive oxygen species controlled released nanoplatform for synergistic sonodynamic/nitric oxide/chemodynamic/radionuclide therapy.

Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn2+ can make H2O2 to produce .OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO-, which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for cancer.

Role of neuropeptides in orofacial pain: A literature review.

BACKGROUND: Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides' pain modulation in the orofacial region, especially in the trigeminal system. OBJECTIVES: The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain. METHODS: We review and summarise current studies related to calcitonin gene-related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides' functions and mechanisms as well as promising targets for orofacial pain control. RESULTS: A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated. CONCLUSIONS: Various neuropeptides play important but distinct (pro-nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK-1, VIP mainly play proinflammatory and pro-nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain.

Association of phthalate metabolites with periodontitis: a population-based study.

BACKGROUND: Widespread exposure to phthalates may raise the probability of various diseases. However, the association of phthalate metabolites with periodontitis remains unclear. METHODS: Totally 3402 participants from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014 cycles were enrolled in the cross-sectional investigation. We utilized weighted logistic regression to evaluate the association of ten phthalate metabolites with periodontitis. Restricted cubic spline analysis was applied to investigate potential nonlinear relationships. RESULTS: The weighted prevalence of periodontitis in the study was 42.37%. A one standard deviation (SD) rise in log-transformed levels of mono-2-ethyl-5-carboxypenty phthalate (MECPP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-isobutyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP) was associated with higher odds of periodontitis, with odds ratios (95% confidence intervals) of 1.08 (1.02-1.14), 1.07 (1.02-1.11), 1.10 (1.05-1.15), 1.05 (1.01-1.09), 1.09 (1.04-1.14), and 1.08 (1.03-1.13), respectively. Individuals with the highest quartile concentrations of MECPP, MnBP, MEHHP, MEOHP, and MBzP were associated with 32%, 20%, 30%, 25%, and 26% increased odds of periodontitis, respectively, compared to those with the lowest quartile. Additionally, mono-(3-carboxypropyl) phthalate (MCPP) demonstrated an interesting inverted J-shaped relationship with periodontitis. CONCLUSIONS: The findings indicate an association of certain phthalate metabolites with periodontitis among US adults.

scHiCPTR: unsupervised pseudotime inference through dual graph refinement for single-cell Hi-C data.

MOTIVATION: The emerging single-cell Hi-C technology provides opportunities to study dynamics of chromosomal organization. How to construct a pseudotime path using single-cell Hi-C contact matrices to order cells along developmental trajectory is a challenging topic, since these matrices produced by the technology are inherently high dimensional and sparse, they suffer from noises and biases, and the topology of trajectory underlying them may be diverse. RESULTS: We present scHiCPTR, an unsupervised graph-based pipeline to infer pseudotime from single-cell Hi-C contact matrices. It provides a workflow consisting of imputation and embedding, graph construction, dual graph refinement, pseudotime calculation and result visualization. Beyond the few existing methods, scHiCPTR ties to optimize graph structure by two parallel procedures of graph pruning, which help reduce the spurious cell links resulted from noises and determine a global developmental directionality. Besides, it has an ability to handle developmental trajectories with multiple topologies, including linear, bifurcated and circular ones, and is competitive with methods developed for single-cell RNA-seq data. The comparative results tell that our scHiCPTR can achieve higher performance in pseudotime inference, and the inferred developmental trajectory exhibit a reasonable biological significance. AVAILABILITY AND IMPLEMENTATION: scHiCPTR is freely available at https://github.com/lhqxinghun/scHiCPTR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors.

Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) for the synthesis of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68Ga-labeled ornithine derivative ([68Ga]Ga-NOTA-Orn). The synthesis time of [68Ga]Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45-50% (uncorrected), and the radiochemical purity was > 98%. [68Ga]Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of [68Ga]Ga-NOTA-Orn was similar to that of L-ornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micro-positron emission tomography (Micro-PET) imaging studies showed that [68Ga]Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that [68Ga]Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

Value of rest 18F-FDG myocardial imaging in the diagnosis of obstructive coronary artery disease in Chinese patients with suspected unstable angina: A prospective real-world clinical study.

BACKGROUND: This study aimed to determine the clinical value of rest 18F-FDG imaging in Chinese patients with non-acute chest pain, normal ECG, negative troponin, and suspected UA. METHODS: 136 patients were prospectively included and underwent rest 18F-FDG PET imaging and coronary arteriography within 1 week. RESULTS: Obstructive CAD was diagnosed in 71 patients, and stenosis ≥ 70% was confirmed in 130 vascular territories. At patients and vascular level, rest 18F-FDG imaging showed sensitivity of 62.0%, 47.7%, specificity of 92.3%, 94.2%, accuracy of 76.5%, 79.4%, PPV of 89.8% and 79.5%, and NPV of 69.0% and 79.4%. The AUCs were 0.771 and 0.710. Of 71 patients with obstructive CAD, rest 18F-FDG imaging showed sensitivity of 47.7% and 58.8%, specificity of 91.6% and 91.2%, accuracy of 64.8% and 80.4%, PPV of 89.9% and 76.9% and NPV of 52.8% and 81.6% in all vascular level and single-vessel disease. In patients with two- or three-vessel disease, rest 18F-FDG imaging had a diagnostic sensitivity, specificity, accuracy, PPV, and NPV of 43.8%, 93.3%, 50.5%, 97.7%, and 20.6%. The AUCs were 0.696, 0.750, and 0.685. CONCLUSION: Rest 18F-FDG imaging performed certain overall diagnostic efficiency for obstructive CAD in Chinese patients with suspected UA, especially the excellent high PPV in identifying culprit ischemic territory in patients with multivessel disease.

Detection of prohibited and restricted object X-ray images based on Hi color space segmentation.

BACKGROUND: X-ray imaging plays an important role in security inspection. However, the objects are complex, which makes it difficult to automatically detect prohibited and restricted objects. OBJECTIVE: This study aims to develop and test a detection method based on a new image segmentation scheme to solve the problem of detecting prohibited and restricted objects from pseudo-color X-ray images with complex backgrounds. METHODS: The internal mechanism of the influence of different color spaces on image segmentation effect is explored, and the color space component Hi is studied. Furthermore, the mechanism of the new Hi component and the influence law of its adjustable coefficient are revealed. Additionally, a detection method based on Hi color space segmentation for pseudo-color X-ray images is proposed. The segmentation and detection methods are then tested on actual X-ray images. RESULTS: The results show that hue has the greatest influence on image segmentation effect of the pseudo-color X-ray images. For different pseudo-color X-ray images with complex backgrounds, applying the proposed new Hi color space segmentation method achieves overall accuracy of 0.974 and 1.0 in detecting the gun and knife, respectively. CONCLUSION: The new X-ray image detection method based on the Hi color space segmentation proposed in this paper enables to better solve the complex background problem including object overlap and adhesion and thus more effectively meet the requirements of actual security inspection.

Management Of Ectopic Eruption Of Bilateral Mandibular First Permanent Molars: A Case Report And Literature Review.

Ectopic eruption of the first permanent molars is a local eruption disturbance. The frequency of ectopically erupted first permanent molars is predominant in boys and primarily affects the maxilla. Interceptive treatment for irreversible ectopic eruptions should be initiated early to prevent space loss and the impaction of the second premolars. Herein, we report the case of a six-year-old girl with irreversible ectopic eruption of the bilateral mandibular first permanent molarstreated with a modified lingual arch. The mandibular first permanent molars were successfully distalised after six months of treatment, and one year of follow-up showed a satisfactory outcome. The modified lingual arch satisfies not only the clinical aspects of treatment but also the patient's well-being. However, the lingual arch may disturb tooth eruption in the mixed dentition stage.

Upconversion NaYF4:Yb/Er-TiO2-Ti3C2 Heterostructure-Based Near-Infrared Light-Driven Photoelectrochemical Biosensor for Highly Sensitive and Selective d-Serine Detection.

A near-infrared (NIR) light-driven NaYF4:Yb/Er-TiO2-Ti3C2 (NYF-TiO2-Ti3C2) heterostructure-based photoelectrochemical (PEC) biosensing platform was constructed for highly sensitive d-serine (d-ser) detection. Accurate d-ser detection depends on the model biocatalyst, d-amino acid oxidase (DAAO), which converts d-ser into hydroxypyruvate and an equimolar concentration of hydrogen peroxide (H2O2) via an enzymatic reaction. The TiO2-Ti3C2 semiconductor and NaYF4:Yb/Er optical transducer formed a Schottky junction that provided an irreversible channel for electron transfer. Infrared light was converted into absorbable multiemission light, thereby effectively increasing light absorption. Simultaneously, the generated H2O2 rapidly scavenged photogenerated holes to separate electron-hole pairs, which amplified the photocurrent signal. Under optimal conditions, the NIR light-driven PEC biosensor exhibited an excellent PEC performance for d-ser detection, with a wide linear range of 2-1650 µmol L-1 and detection limit as low as 0.286 µmol L-1. Importantly, high detection reproducibility and accuracy were achieved using this strategy for analyzing human serum and rat cerebrospinal fluid (CSF) specimens. The admirable applicability of the NYF-TiO2-Ti3C2-based PEC biosensor for detecting d-ser may lead to further opportunities for detecting other disease-related biomarkers.

In-line Mach-Zehnder interferometer and Bragg grating integrated by femtosecond laser for discrimination of temperature and directional torsion.

Femtosecond laser micromachining has been considered as a powerful tool for fabricating versatile fiber devices and received increasing attention in recent years. Here, we report on a compact sensor by integrating a bridge-like waveguide inside a single-mode fiber to construct an in-line Mach-Zehnder interferometer and then inscribing a second-order Bragg grating in the core of the same fiber. The interference dip shows good performance in torsion sensing - the maximum torsion sensitivity of 1.5573 nm/(rad/m), the ability to identify the torsion direction, and low perturbation of axial strain. In order to compensate the cross impact of temperature, the fiber Bragg grating dip is employed as the second indicator and combined with the interference dip for discriminating temperature and directional torsion simultaneously. The proposed device also has the merits such as compact size, high thermal stability, and so on.

Efficient thermally activated delayed fluorescence organic light-emitting device based on an exciplex.

An exciplex with significant thermally activated delayed fluorescence properties was realized, comprising diphenyl-[3'-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)-biphenyl-4-yl]-amine as a donor and 2,4,6-tris[3-(diphenylphosphinyl)phenyl]-1,3,5-triazine as an acceptor. A very small energy difference between the singlet and triplet levels and a large rate constant of the reverse intersystem crossing were attained simultaneously, contributing to the efficient upconversion of triplet excitons from the triplet state to the singlet state and thermally activated delayed fluorescence emission. A high-efficiency organic light-emitting device based on the exciplex was fabricated, which exhibited a maximum current efficiency, power efficiency, external quantum efficiency, and exciton utilization efficiency of 23.1 cd/A, 24.2 lm/W, 7.32%, and 54%, respectively. The efficiency roll-off of the exciplex-based device was slight, as illustrated by a large critical current density of 34.1 mA/cm2. This efficiency roll-off was ascribed to triplet-triplet annihilation, as confirmed by the triplet-triplet annihilation model. We proved the high binding energy of the excitons and excellent charge confinement within the exciplex by performing transient electroluminescence measurements.

High-Q-factor phase-shifted helical fiber Bragg grating by one-step femtosecond laser inscription for high-temperature sensing.

The phase-shifted fiber Bragg grating (FBG) plays an important role in optical communication and sensing due to its ultra-narrow 3-dB bandwidth. Here, we demonstrate the fabrication and thermal property of a high-quality (Q)-factor phase-shifted helical fiber Bragg grating (PS-HFBG). A single-mode fiber is twisted and then inscribed point-by-point with a third-order uniform FBG by a single round of laser irradiation. The grating is curved slightly into a helical shape after the torsion is released, generating a phase shift in the grating. With annealing treatment, the PS-HFBG responds very stably to temperature with a linear sensitivity of 15.24 pm/°C within the range from 100 to 1100°C. Moreover, the PS-HFBG peak tends to narrower for higher temperature and the minimum 3-dB bandwidth is as low as 32 pm, indicating the highest Q-factor of 4.91 × 104. In addition, the PS-HFBG shows a low strain sensitivity (0.896 pm/µ ε). The proposed device is very promising to be applied as a high-precision and stable high-temperature sensor.

Impaired coronary flow reserve in patients with supra-normal left ventricular ejection fraction at rest.

PURPOSE: Recently, a "U" hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar "U" curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%). METHODS: Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated 13 N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose-response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan-Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome. RESULTS: An inverted "U" curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF < 55%) (n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF < 65%) (n = 106) (57.9% vs 54.5% vs 34.3%, p < 0.01, respectively). Both snLVEF (p < 0.01) and rLVEF (p < 0.05) remained independent predictors for reduced cCFR after multivariable adjustment. Patients with snLVEF encountered more MACE than those with nLVEF (10.5% vs 0.9%, log-rank p = 0.01). CONCLUSIONS: Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.

Polydopamine-based molecularly imprinted electrochemical sensor for the highly selective determination of ecstasy components.

3,4-Methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) are the main components of illicit stimulant drugs, also known as "ecstasy", which belong to psychoactive medicine and tend to be increasingly abused among drug addicts worldwide. Herein, an electrochemical sensor based on molecularly imprinted polydopamine (MIP@PDA) was developed to detect MDA and MDMA using differential pulse voltammetry (DPV). An MIP film on a Au electrode was synthesized via electrochemical polymerization with the safe chemical DA as the polymerization monomer and the uncontrolled pharmaceutical intermediate 3,4-methylenedioxyphenethylamine (MDPEA) as the template molecule, which can provide a great quantity of specific binding sites and expand the practical application of the sensor. Due to the superior affinity of MIP@PDA to the target, the proposed sensor displayed excellent analytical performance, with LODs of 37 nM and 54 nM for the determination of MDA and MDMA, respectively. Additionally, this sensor presented suitable selectivity, stability, reproducibility and detection ability in practical urine samples, which suggested that it is a promising candidate as a rapid diagnostic method in drug investigations.

Inhibition mechanism of melanin formation based on antioxidant scavenging of reactive oxygen species.

The production of reactive oxygen species (ROS) leads to the generation of oxidative stress, which will result in the excessive production and accumulation of melanin in the body and even the occurrence of some skin diseases. The intervention of antioxidants can slow down the rate of melanin formation to some extent. In order to explore the relationship between ROS, melanin and antioxidants, this work investigated the effects of antioxidants on melanin formation by the scavenging of ROS in vitro, where zebrafish were used as the model organism in in vivo experiments. The results showed that the inhibition order of natural antioxidants on melanin formation was GSH > AA > GA and PG > BHT > BHA for synthetic antioxidants. Between natural antioxidants and synthetic antioxidants, the former mainly have a strong scavenging ability on ˙OH and 1O2, while the latter have a strong scavenging ability on O2˙-. At the same time, the results in vivo showed that GSH and PG within a certain concentration not only did not affect the hatchability, survival rate and teratogenic rate of zebrafish embryos, but also can significantly inhibit melanin formation in zebrafish embryos. The results of this study have an important guiding significance for the dosage of antioxidants used in the cosmetics and food industries.