Construction of H-Doped PdB Nanocrystals as Electrocatalysts to Modulate Formic Acid Oxidation.

The strong ligand effect in B-doped Pd-based (PdB) catalysts renders them a promising anode for constructing formic acid fuel cells (FAFCs) exhibiting high power density and outstanding stability. However, the enhancement of the oxidation barrier is unavoidable in this alloy system owing to the electron transfer (ET) from B to Pd. In this study, a hydrogen doping strategy is employed to open charge freedom in PdB compounds and boost their formic acid oxidation reaction (FAOR) activity by suppressing the ET process. The resulting hydrogen-doped PdB (PdBH) exhibits an ultrahigh mass activity of up to 1.2A mg-1 Pd, which is 3.23 times that of the PdB catalyst and 9.55 times that of Pd black. Detailed experimental and theoretical studies show that the interstitial hydrogen leads to enhanced orbital hybridization and reduced electron density around Pd. This optimized ligand effect weakens the carbon monoxide adsorption and increases the direct pathway preference of PdBH, resulting in its outstanding catalytic activity for the FAOR. The development of this high-performance hydrogen-doped PdB catalyst is an important step toward the construction of advanced light element co-doped metal catalysts.

A fluorescence aptamer sensor utilizing WS2 nanosheets for sensitive detection of patulin: enhanced specificity and wide applicability.

A tungsten disulfide (WS2) nanosheet-based aptamer sensor was developed to detect patulin (PAT). The 5'-end of the PAT aptamer was modified with a cyanine 3 (Cy3) fluorophore, which self-assembled on WS2 nanosheets. The interaction between the Cy3 fluorophore at the 5'-end of the PAT aptamer and the WS2 nanosheets resulted in reduced fluorescence (FL) intensity due to fluorescence resonance energy transfer (FRET). The introduction of PAT into this sensing system led to hybridization with the PAT aptamer, forming a G-quadruplex/PAT complex with low affinity for the WS2 nanosheet surface. This hybridization increased the distance between the Cy3 fluorophore and the WS2 nanosheets, inhibiting FRET and producing a strong FL signal. Under optimal experimental conditions, the FL intensity of the sensing system demonstrated an excellent linear correlation with PAT concentrations ranging from 0.5 to 40.0 ng mL-1, and it achieved a detection limit (S/N = 3) of 0.23 ng mL-1. This sensing system offers enhanced specificity for PAT detection and has the potential for broad application in detecting other toxins by substituting the sequence of the recognition aptamer.

An ultrasensitive solid-state electrochemiluminescence sensor based on Ni-MOF@Ru(bpy)32+ and Au NPs@TiO2 for determination of permethrin.

The novel TiO2 and Ni-MOF materials were synthesized and utilized for the detection of permethrin (PET). A highly sensitive solid-state electrochemiluminescence (ECL) sensor was developed based on Ni-MOF@Ru(bpy)32+ and Au NPs@TiO2. In this sensing platform, Ru(bpy)32+-Tripropyl Amine (TPrA) was used as a luminescent signal, Ni-MOF acted as a carrier to carry more luminescent reagents Ru(bpy)32+. Au NPs acted as promoters facilitated electron transport and TiO2 could further enhance the luminescence intensity of the system by synergistical interaction with Au NPs. The possible mechanisms of signal amplification were investigated. The ECL intensity decreased significantly with increasing PET concentration, enabling the determination of PET amount through the observation of the change in ECL signal intensity (ΔI). Under optimal experimental conditions, the linear range of PET concentration from 1.0 × 10-11 mol L-1 to 1.0 × 10-6 mol L-1, with a detection limit of 3.3 × 10-12 mol L-1 (3S/N). This method was successfully applied to determine PET in various vegetable samples.

Understanding the dynamic evolution of hemicellulose during Pinus taeda L. growth.

Pinus taeda L. is a fast-growing softwood with significant commercial value. Understanding structural changes in hemicellulose during growth is essential to understanding the biosynthesis processes occurring in the cell walls of this tree. In this study, alkaline extraction is applied to isolate hemicellulose from Pinus taeda L. stem segments of different ages (1, 2, 3, and 4 years old). The results show that the extracted hemicellulose is mainly comprised of O-acetylgalactoglucomannan (GGM) and 4-O-methylglucuronoarabinoxylan (GAX), with the molecular weights and ratios (i.e., GGM:GAX) of GGM and GAX increasing alongside Pinus taeda L. age. Mature Pinus taeda L. hemicellulose is mainly composed of GGM, and the ratio of (mannose:glucose) in the GGM main chain gradually increases from 2.45 to 3.60 with growth, while the galactose substitution of GGM decreases gradually from 21.36% to 14.65%. The acetylation of GGM gradually increases from 0.33 to 0.45 with the acetyl groups mainly substituting into the O-3 position in the mannan. Furthermore, the contents of arabinose and glucuronic acid in GAX gradually decrease with growth. This study can provide useful information to the research in genetic breeding and high-value utilization of Pinus taeda L.

A reliable fluorescence "turn-on" aptasensor based on dual-emitting europium metal-organic frameworks for ultrasensitive and selective detection of sulfamethazine.

A high-performance fluorescent "turn-on" aptasensor (Eu-MOFs@SMZ-Apt) for sulfamethazine (SMZ) determination was designed using dual-emitting europium metal-organic frameworks (Eu-MOFs) as a signal transducer and an amplifier. Eu-MOFs featuring dual emission peaks (430 nm and 620 nm) were first prepared via a facile self-assembly strategy employing Eu (III) ions and 2-aminoterephthalic acid as precursors. The high-affinity aptamer was bonded with Eu-MOFs to form Eu-MOFs@SMZ-Apt through the amidation reaction. Benefiting from the integration of inherent virtues from Eu-MOFs and aptamer, the Eu-MOFs@SMZ-Apt-based sensor allowed sensitive and selective determination of SMZ with good linear relationships in a range of 1.4-40 ng mL-1 and a low detection line (0.379 ng mL-1). This sensor was successfully applied to the determination of trace SMZ in real samples with satisfactory recoveries (86.47-113.52%) and a relative standard deviation (<6.51). Consequently, the Eu-MOFs@SMZ-Apt ratiometric fluorescence sensor furnishes new possibilities for the accurate detection of various pollutants in food.

Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in Mouse.

Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Contrary to prior publications, the KO was not neonatal lethal. Thus, we phenotyped the Adam19 KO. Results: KO mice had lower body weight and shorter tibial length than wild type (WT). Dual-energy X-ray Absorptiometry indicated lower soft weight, fat weight, and bone mineral content in KO mice. In lung function analyses using flexiVent, compared to WT, Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.

AKR1B10 accelerates glycolysis through binding HK2 to promote the malignant progression of oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) remains a rampant oral cavity neoplasm with high degree of aggressiveness. Aldo-keto reductase 1B10 (AKR1B10) that is an oxidoreductase dependent on nicotinamide adenine dinucleotide phosphate (NADPH) has been introduced to possess prognostic potential in OSCC. The present work was focused on specifying the involvement of AKR1B10 in the process of OSCC and its latent functional mechanism. METHODS: AKR1B10 expression in OSCC tissues and cells were detected by RT-qPCR and Western blot analysis. CCK-8 method, EdU staining, wound healing and transwell assays respectively assayed cell viability, proliferation, migration and invasion. Immunofluorescence staining and Western blot evaluated epithelial mesenchymal transition (EMT). Adenosine triphosphate (ATP) contents, glucose consumption and extracellular acidification rate (ECAR) were measured by relevant commercially available kits and Seahorse XF96 Glycolysis Analyzer, severally. The expressions of proteins associated with metastasis and glycolysis were examined with Western blot. Co-IP assay confirmed the binding between AKR1B10 and hexokinase 2 (HK2). RESULTS: It was observed that AKR1B10 expression was increased in OSCC tissues and cells. After AKR1B10 was knocked down, the proliferation, migration, invasion and EMT of OSCC cells were all hampered. Additionally, AKR1B10 silencing suppressed glycolysis and bound to HK2 in OSCC cells. Up-regulation of HK2 partially abolished the hampered glycolysis, proliferation, migration, invasion and EMT of AKR1B10-silenced OSCC cells. CONCLUSION: To sum up, AKR1B10 could bind to HK2 to accelerate glycolysis, thereby facilitating the proliferation, migration, invasion and EMT of OSCC cells.

Low-Cost Photoelectric Flow Rate Sensors Based on a Flexible Planar Curved Beam Structure for Clinical Treatments.

In clinical treatments, reliable flow rate measurements ensure accurate drug delivery during infusions, precise gas delivery during artificial ventilations, etc., thereby reducing patient morbidity and mortality. However, precise flow rate sensors are costly, so medical devices with limited budgets choose cheaper but unsatisfactory flow rate measurement approaches, leading to increased medical risks. Here, a photoelectric flow rate sensor based on a flexible planar curved beam structure (FPCBS) is proposed. The FPCBS ensures low out-of-plane stiffness of the sensitive sheet and allows large deformation in the elastic range, enabling the flow rate sensor to measure the flow rate with high sensitivity over a wide range. Meanwhile, the flow rate sensor can be mass-produced using mature materials and manufacturing technology at less than $5 each. The flow rate sensors are integrated into a commercial infusion pump to measure drug infusion and a home ventilator to monitor respiration. The results are comparable to those measured by a commercial flow rate sensor, demonstrating the applicability of the sensor. Considering its proven outstanding performance at low cost, the flow rate sensor shows great potential in clinical treatment, medical diagnosis, and other medical fields.

Proximal tubular MBD2 promotes autophagy to drive the progression of AKI caused by vancomycin via regulation of miR-597-5p/S1PR1 axis.

Our recent investigation has indicated that the global deletion of MBD2 can mitigate the progression of AKI induced by VAN. Nevertheless, the role and regulatory mechanisms of proximal tubular MBD2 in this pathophysiological process have yet to be elucidated. Our preceding investigation revealed that autophagy played a crucial role in advancing AKI induced by VAN. Consequently, we postulated that MBD2 present in the proximal tubule could upregulate the autophagic process to expedite the onset of AKI. In the present study, we found for the first time that MBD2 mediated the autophagy production induced by VAN. Through the utilization of miRNA chip analysis, we have mechanistically demonstrated that MBD2 initiates the activation of miR-597-5p through promoter demethylation. This process leads to the suppression of S1PR1, which results in the induction of autophagy and apoptosis in renal tubular cells. Besides, PT-MBD2-KO reduced autophagy to attenuate VAN-induced AKI via regulation of the miR-597-5p/S1PR1 axis, which was reversed by rapamycin. Finally, the overexpression of MBD2 aggravated the diminished VAN-induced AKI in autophagy-deficient mice (PT-Atg7-KO). These data demonstrate that proximal tubular MBD2 facilitated the process of autophagy via the miR-597-5p/S1PR1 axis and subsequently instigated VAN-induced AKI through the induction of apoptosis. The potentiality of MBD2 being a target for AKI was established.

Engineering Pseudomonas chlororaphis HT66 for the Biosynthesis of Copolymers Containing 3-Hydroxybutyrate and Medium-Chain-Length 3-Hydroxyalkanoates.

Polyhydroxyalkanoates (PHAs) are promising alternatives to petroleum-based plastics, owing to their biodegradability and superior material properties. Here, the controllable biosynthesis of scl-co-mcl PHA containing 3-hydroxybutyrate (3HB) and mcl 3-hydroxyalkanoates was achieved in Pseudomonas chlororaphis HT66. First, key genes involved in fatty acid ß-oxidation, the de novo fatty acid biosynthesis pathway, and the phaC1-phaZ-phaC2 operon were deleted to develop a chassis strain. Subsequently, an acetoacetyl-CoA reductase gene phaB and a PHA synthase gene phaC with broad substrate specificity were heterologously expressed for producing and polymerizing the 3HB monomer with mcl 3-hydroxyalkanoates under the assistance of native ß-ketothiolase gene phaA. Furthermore, the monomer composition of scl-co-mcl PHA was regulated by adjusting the amount of glucose and dodecanoic acid supplemented. Notably, the cell dry weight and scl-co-mcl PHA content reached 14.2 g/L and 60.1 wt %, respectively, when the engineered strain HT11Δ::phaCB was cultured in King's B medium containing 5 g/L glucose and 5 g/L dodecanoic acid. These results demonstrated that P. chlororaphis can be a platform for producing scl-co-mcl PHA and has the potential for industrial application.

A molecule-imprinted electrochemiluminescence sensor based on CdS@MWCNTs for ultrasensitive detection of fenpropathrin.

A molecularly-imprinted electrochemiluminescence sensor was constructed for the determination of fenpropathrin (FPT) by molecular imprinting technology. In this sensing platform, the introduction of CdS@MWCNTs significantly enhanced the initial ECL signal of the luminol-O2 system. Specifically, MWCNTs was used as a carrier to adsorb more CdS, in which CdS acted as a co-reaction promoter for luminescence. Molecularly imprinted polymer (MIP) containing specific recognition sites of FPT was used as the material for selective recognition. With increasing amount of FPT the ECL signal decreased. Under the optimum conditions, the ECL response was linearly related to the logarithm of FPT concentration. The developed ECL sensor allowed for sensitive determination of FPT and exhibited a wide linear range from 1.0 × 10- 10 mol L- 1 to 1.0 × 10- 6 mol L- 1. The limit of detection was 3.3 × 10- 11 mol L- 1 (S/N = 3). It can be used for the detection of FPT in vegetable samples.

Investigating the Mechanism of Chinese Medicine Formula AACO Against Chronic Heart Failure by Network Pharmacology Analysis and Experimental Validation.

Background: A traditional Chinese medicine (TCM) formula, containing Astragalus membranaceus (Fisch.) Bunge, Aconitum wilsonii Stapf ex Veitch, Curcuma longa L., and Radix ophiopogonis (AACO), has therapeutic value for the treatment of chronic heart failure (CHF). Objective: This study intends to explore the pharmacological mechanism underlying the activity of the AACO formula against CHF. Materials and Methods: Using the TCM Systems Pharmacology database and Bioinformatics Analysis Tool for Molecular Mechanism of TCM, the active ingredients contained in the herbs of the AACO formula were screened. Meanwhile, the target genes related to these active ingredients were identified and genes correlated with CHF were screened. Protein-protein interaction networks were built to elucidate the relationships between the AACO formula and CHF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis were carried out using the DAVID database. A "drug-component-target-disease" network was constructed with Cytoscape 3.7.0. The therapeutic effect of the AACO formula was proven by hemodynamic study, echocardiography evaluation, and histological analysis in transverse aortic constriction-induced CHF mice and was validated in vitro. Results: A total of 105 active ingredients and 1026 related targets were screened and identified, and 240 related targets overlapping with CHF were selected. According to GO analysis, the enriched genes participated in gene expression and cardiac contraction regulation by Ca2+ regulation. From KEGG analysis, the calcium axis was identified as one of the main mechanisms through which the AACO formula exerts an anti-CHF effect. AACO was validated to significantly improve cardiac diastolic and systolic functions in vivo via an increase in the rate of Ca2+ reuptake of the myocardial sarcoplasmic reticulum and improved myocardial contractility in vitro. Conclusions: Network pharmacology is a convenient method to study the complex pharmacological mechanisms of TCM. The calcium axis likely participates in the anti-CHF mechanism of AACO.

TXA2 attenuates allergic lung inflammation through regulation of Th2, Th9, and Treg differentiation.

In lung, thromboxane A2 (TXA2) activates the TP receptor to induce proinflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and TXA2 synthase inhibitors have been tested as potential asthma therapeutics in humans. Th9 cells play key roles in asthma and regulate the lung immune response to allergens. Herein, we found that TXA2 reduces Th9 cell differentiation during allergic lung inflammation. Th9 cells were decreased approximately 2-fold and airway hyperresponsiveness was attenuated in lungs of allergic mice treated with TXA2. Naive CD4+ T cell differentiation to Th9 cells and IL-9 production were inhibited dose-dependently by TXA2 in vitro. TP receptor-deficient mice had an approximately 2-fold increase in numbers of Th9 cells in lungs in vivo after OVA exposure compared with wild-type mice. Naive CD4+ T cells from TP-deficient mice exhibited increased Th9 cell differentiation and IL-9 production in vitro compared with CD4+ T cells from wild-type mice. TXA2 also suppressed Th2 and enhanced Treg differentiation both in vitro and in vivo. Thus, in contrast to its acute, proinflammatory effects, TXA2 also has longer-lasting immunosuppressive effects that attenuate the Th9 differentiation that drives asthma progression. These findings may explain the paradoxical failure of anti-thromboxane therapies in the treatment of asthma.

A dual-mode ratiometric probe using europium-doped cyclen-functional carbon dots for fluorescent and point-of-care detection of tetracycline.

The overuse of tetracycline (TC) has led to the accumulation of antibiotic residues in drinking water and animal products, which can consequently lead to bacteria resistance and chronic disease in humans. Urgently addressing the need for a rapid, user-friendly, and point-of-care test for TC detection. In this work, we use cyclen and citric acid to synthesise carbon dots (CDs) with a unique ring-shaped structure on their surface and combine them with europium (Eu3+) to form an Eu-CDs fluorescent probe. In the presence of TC in aqueous systems, the Eu-CDs probe emits two distinctive fluorescent signals: the stable blue emission from cyclen-modified CDs and the red emission from Eu3+,showing a proportional increase with TC concentration. The developed Eu-CDs probe demonstrates accurate and selective detection capabilities for TC class antibiotics among various interfering factors. The Eu-CDs probe exhibits excellent linearity within the concentration range of 0.04-2.4 µM and achieves an impressive detection limit of 2.7 nM. Moreover, point-of-care Eu-CDs test strips are designed, allowing convenient on-site TC analysis through the detection of a colour change from blue to red under a portable UV light. The results highlight the effectiveness of the proposed dual-mode ratiometric fluorescent Eu-CDs probe and test strips, offering a practical point-of-care testing strategy for real-world TC detection applications.

Ultrasensitive solid-state electrochemiluminescence sensor based on lotus root shaped carbon fiber, CdSe QDs and Fe3O4 synergically amplify Ru(bpy)32+ luminophore signal for detection of cyfluthrin.

An efficient and innovative electrochemiluminescence (ECL) sensor was developed for trace detection of cyfluthrin. The sensor utilized materials such as lotus root shaped carbon fiber (Co CNFs), cadmium selenide quantum dots (CdSe QDs), and Fe3O4 to amplify Ru(bpy)32+ signals. Co CNFs, with its large specific surface area and porosity, served the purpose of not only enhancing the stability of the sensor by fixing CdSe QDs and Ru(bpy)32+ on the Co CNFs/GCE, but also facilitating electron transfer. CdSe QDs was involved in the luminescence reaction and collaborated with Ru(bpy)32+ to enhance the sensor's sensitivity, while Fe3O4 promoted electron transfer in the system due to its large surface area. The solid-state ECL sensor achieved satisfactory signal under the synergistic action of these components. The ECL signal of the sensor was quenched by cyfluthrin, and a favorable linear relationship was observed between the sensor and cyfluthrin in the concentration range 1 × 10-12 to 1 × 10-6 M. The detection limit of the sensor was 3.3 × 10-13 M (S/N = 3). The utilization of lotus root shaped carbon fiber, CdSe QDs, and Fe3O4 in the Ru(bpy)32+ system demonstrated a synergistic effect for cyfluthrin detection, presenting a new approach for the rapid determination analysis of pesticide residues in foods.

Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury.

Approximately 60% of septic patients developed acute kidney injury (AKI). The mortality rate of septic AKI (SA-AKI) is two to three times higher than that of septic without AKI (SA-non-AKI). The actual functions and mechanisms of CircRNAs in the pathophysiology of SA-AKI remain incompletely understood. Herein, we observed that the mmu_Circ_26986 could be induced by lipopolysaccharide (LPS) and cecum ligation and puncture (CLP) in BUMPT cell line and C57BL/6 mouse kidney, respectively. Functionally, mmu_Circ_26986 suppressed BUMPT cell apoptosis induced by LPS. Mechanistically, mmu_Circ_26986 sponged miRNA-29b-1-5p to upregulate the expression of PAK7. Overexpression of mmu_Circ_26986 ameliorated the progression of CLP-stimulated AKI through miRNA-29b-1-5p/PAK7 axis. In addition, we found that hsa_Circ_0072463, homologous to mmu_Circ_26986, suppressed LPS-induced HK-2 cells apoptosis via regulation of miRNA-29b-1-5p/PAK7 axis. Furthermore, sepsis patients with AKI had a higher level of hsa_Circ_0072463 compared to those without AKI. The sensitivity, specificity and AUC of hsa_Circ_0072463 were 78.8%, 87.9% and 0.866, respectively. Spearman's test indicated a noticeable positive correlation between plasma hsa_Circ_0072463 and serum creatinine in sepsis patients (r = 0.725). In summary, this study reveals that the mmu_Circ_26986/hsa_Circ_0072463 miRNA-29b-1-5p/PAK7 axis mediates septic AKI, and hsa_Circ_0072463 is a potential diagnostic marker for septic AKI.

The Left Amygdala and Right Frontoparietal Cortex Support Emotional Adaptation Aftereffects.

Adaptation aftereffects-in which prolonged prior experience (adaptation) can bias the subsequent judgment of ambiguous stimuli-are a ubiquitous phenomenon. Numerous studies have found behaviorally stable adaptation aftereffects in a variety of areas. However, it is unclear which brain regions are responsible for this function, particularly in the case of high-level emotional adaptation aftereffects. To address this question, the present study used fMRI technology to investigate the neural mechanism of emotional adaptation aftereffects. Consistent with previous studies, we observed typical emotional adaptation effects in behavior. Specifically, for the same morphed facial images, participants perceived increased sadness after adapting to a happy facial image and increased happiness after adapting to a sad facial image. More crucially, by contrasting neural responses to ambiguous morphed facial images (i.e., facial images of intermediate morph levels) following adaptation to happy and sad expressions, we demonstrated a neural mechanism of emotional aftereffects supported by the left amygdala/insula, right angular gyrus, and right inferior frontal gyrus. These results suggest that the aftereffects of emotional adaptation are supported not only by brain regions subserving emotional processing but also by those subserving cognitive control.

Electrochemiluminescent assay based on Co-MOF and TiO2 for determination of bisphenol A.

An electrochemiluminescence (ECL) sensor for determining bisphenol A (BPA) was prepared based on titanium dioxide (TiO2) and Co-MOF. TiO2 is a co-reaction promoter that amplifies the ECL signal in the Ru(bpy)32+-trinpropylamine (TPrA) system. When the electrode is modified with Co-MOF the ECL signal is significantly enhanced. This is because Co-MOF can not only be used as a co-reaction accelerator but also as a carrier to adsorb more luminescent substances. Possible mechanisms for amplifying the original signal through the synergistic action of the two substances are investigated. The ECL strength decreases with increasing concentrations of BPA, and the amount of BPA can be determined by the change in ECL signal strength (ΔI). Under optimal experimental conditions, the linear range of BPA was 2.0 × 10-10 to 2.0 × 10-5 M, with a determination limit of 6.7 × 10-11 M (3σ/m). The relative standard deviation (RSD) of the signal for ten consecutive measurements was 1.5%. The sensor can be used to detect BPA in bottled samples with recoveries of 96 to 105%.

Development and validation of a clinical factors and body fat distribution-based nomogram to predict refractoriness of transarterial chemoembolization in hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) is an important treatment modality for hepatocellular carcinoma (HCC). However, some patients may develop TACE refractoriness during treatment. We aimed to construct a prediction model incorporating computed tomography (CT) body composition and clinical factors to preoperatively predict the risk of developing TACE refractoriness in patients with HCC, enabling the rapid identification of patients at high risk of TACE refractoriness. Methods: This study included 128 HCC patients treated with TACE who were randomly assigned to the training (n=89) and validation groups (n=39) in a 7:3 ratio. Multiple body-composition parameters were outlined from CT images of the third lumbar vertebra level of each patient. Standardized values of body-composition parameters were calculated, such as visceral-to-subcutaneous adipose tissue area ratio (VSR). Multifactor logistic regression analysis was performed to identify independent predictors of TACE-refractoriness in patients and to develop predictive models. High- and low-risk subgroup analyses were performed for the predictive model. Results: Alpha-fetoprotein (AFP) level (P=0.041), tumor size (P=0.001), and VSR (P=0.043) were independent risk factors for TACE refractoriness. The combined clinical-body composition model had an area under the curve (AUC) value of 0.875 in the training cohort and an AUC value of 0.837 in the validation cohort. Calibration curves and decision curves revealed the specific optimal performance and clinical utility of the combined model. Subgroup analysis showed differences in predicted TACE refractoriness between the high- and low-risk groups (P<0.001). Conclusions: The combined clinical-body fat distribution model has the good performance in predicting a patient's risk of TACE refractoriness preoperatively and can help clinicians make the best clinical decisions in advance for the treatment of high-risk patients.

Pharmacokinetics and pharmacodynamics of perfluoropropane after intra-venous bolus injection of perflutren lipid microsphere injection (DEFINITY®) in healthy Chinese volunteers.

BACKGROUND AND OBJECTIVE: Definity is an ultrasound contrast agent consisting of phospholipids-encapsulated perfluoropropane (PFP), also known as perflutren, microspheres, which is initially designed to enhance echocardiographic ultrasound images. With no pharmacologic action, Definity can increase the backscatter of ultrasound resulting enhanced ultrasound signals. The objective of this study was to determine the pharmacokinetics (PKs), Pharmacodynamics (PDs) and safety of Definity in healthy male and female Chinese volunteers. METHODS: A simple GC-MS method was developed and applied to simultaneously quantify PFP both in human whole blood and in expired air using Perfluorobutane (PFB) as internal standard. Meanwhile, the blood microbubble Doppler intensities were continuously monitored as companion PDs by a Doppler ultrasonography system using a non-imaging method. RESULTS: After intravenous infusion of 10 µL/kg of PFP within 30 seconds, the mean AUClast of the pharmacokinetic analysis set was 0.000653 (uL/mL)*min, the average AUC∞ was 0.001051 (uL/mL)*min. The main coefficient of variation of parameters were within 30%. In this trial, the blood drug concentration of female subjects was lower than that of males. Female Cmax, AUClast and AUC∞ were lower than males', Tmax and t1/2 was close to males', Vss and CL were slightly higher than males'. The concentration of PFP in the expired air of the subject reached the maximum value 1-2 min after administration and the PFP accumulation curve in the expired air began to become flat at 9.5-11 min after administration. The PFP in the expired air at the last sampling point of most subjects was still measurable. The results of the analysis showed that female subjects had slightly more and faster PFP excretion via the lungs than males. The change of blood drug concentration in this trial was related to the change process of Doppler signal intensity. The trend of the two was close, but the peak time of blood drug concentration was slightly delayed compared with the peak time of the Doppler signal intensity. The results showed that female tmax-pd, t10 was earlier than male, and women have lower AUCpd than men. CONCLUSION: The pharmacokinetics and pharmacodynamics of Definity in blood and expired air were systematically evaluated for the first time in this study. The PK/PD analysis results of this trial showed that the change of blood concentration was related to the change process of Doppler signal intensity, the trend of the two was close and expired air are the main excretion pathways of Definity. Definity was well tolerated by all subjects in the trial. TRIAL REGISTRATION: This study was registered on 08 December 2017 at the Chinese Clinical Trial Registry (CTR20171087).