Potential Biomarker of Acute Anthracycline-induced Cardiotoxicity Among Children With Acute Lymphoblastic Leukemia: Cardiac Adriamycin-responsive Protein.

ABSTRACT: This study aimed to investigate whether serum cardiac adriamycin-responsive protein (CARP) can serve as a sensitive and specific biomarker of anthracyclines (ANT)-induced cardiotoxicity. Fifty-five children with acute lymphoblastic leukemia were recruited. Before and after the administration of ANT, serum levels of CARP, high-sensitivity troponin T, creatine kinase-MB, and electrocardiogram were measured. Postchemotherapeutic clinical manifestations of cardiotoxicity were also investigated. Adverse cardiac events (ACEs) were graded according to the Common Terminology Criteria for Adverse Events 4.0. Then, the CARP expression was statistically analyzed among different groups. The receiver operating characteristic curve was used to evaluate the efficacy of CARP in predicting acute ANT-induced cardiotoxicity. After ANT chemotherapy, the serum CARP concentration increased in the non-ACEs group but decreased in the ACEs group ( P < 0.05). In addition, not only the serum CARP levels (△CARP) was negatively correlated with the grade of ACEs (R=-0.754, P < 0.0001) but also the extent of QT interval corrected (QTc) prolongation (△QTc; R=-0.5592, P < 0.01). The area under the receiver operating characteristic curve of CARP was 90.94% ( P < 0.0001), and the sensitivity and specificity were 88.64% and 91.67%, respectively, all of which are superior to △high-sensitivity troponin T, △creatine kinase-MB, and △QTc. In conclusion, serum CARP could serve as a novel sensitive and specific biomarker of acute ANT-induced cardiotoxicity, which is negatively associated with ACE grade.

Fenofibrate reverses liver fibrosis in cholestatic mice induced by alpha-naphthylisothiocyanate.

Cholestatic liver fibrosis occurs in liver injuries accompanied by inflammation, which develops into cirrhosis if not effectively treated in early stage. The aim of the study is to explore the effect of fenofibrate on liver fibrosis in chronic cholestatic mice. In this study, wild-type (WT) and Pparα-null (KO) mice were dosed alpha-naphthylisothiocyanate (ANIT) diet to induce chronic cholestasis. Induced liver fibrosis was determined by pathological biomarkers. Then fenofibrate 25 mg/kg was orally administrated to mice twice/day for 14 days. Serum and liver samples were collected for analysis of biochemistry and fibrosis. In WT mice, cholestatic biomarkers were increased by 5-8-fold and the expression of tissue inhibitors of metalloproteinases 1 (TIMP-1), Monocyte chemoattractant protein 1 (MCP-1), Collagen protein I (Collagen I) was increased by more than 10-fold. Fenofibrate significantly downgraded the biochemical and fibrotic biomarkers. In Western blot analysis, levels of collagenI and alpha-smooth muscle actin (α-SMA) were strongly inhibited by fenofibrate. In KO mice, liver fibrosis was induced successfully, but no improvement after fenofibrate treatment was observed. These data showed low-dose fenofibrate reverses cholestatic liver fibrosis in WT mice but not in KO mice, suggesting the dependence of therapeutic action on peroxisome proliferator-activated receptor alpha (PPARα). The study offers an additional therapeutic strategy for cholestatic liver fibrosis in practice.

Tunable bending stiffness of MoSe2/WSe2 heterobilayers from flexural wrinkling.

Understanding the mechanical behaviors of van der Waals heterogeneous 2D materials is important for their actual applications. Our extensive first-principles calculations and continuum mechanical modeling on the wrinkling of MoSe2/WSe2 heterobilayers caused by compression reveal that the bending stiffness of MoSe2/WSe2 wrinkles strongly depend on the wrinkle structures, which first increase and then decrease with increasing the compressive strain. The bending stiffness of MoSe2/WSe2 wrinkles could be effectively mediated and tuned by adjusting the wrinkle geometry and size. The underlying mechanisms are elucidated by the differences in electronic structures and bonding states at the top, middle and bottom parts of the wrinkles, and the relevance of the changes of bond lengths to flexural deformation. Our results suggest a feasible way to develop flexible devices and nanoelectromechanical systems by utilizing the correlation and coupling between the mechanical and electronic properties in MoSe2/WSe2 wrinkles.

Mechanical and electronic coupling in few-layer graphene and hBN wrinkles: a first-principles study.

Wrinkle engineering is an important pathway to develop novel functional devices of two-dimensional materials. By combining first-principles calculations and continuum mechanics modelling, we have investigated the wrinkling of few-layer graphene and hexagonal boron nitride (hBN) and provide a way to estimate their bending stiffness. For few-layer wrinkles under the same strain, the magnitude of structural deformation of each constituent layer gradually decreases from bottom to top layers, while interlayer interaction increases with increasing layer number. Comparing with monolayer wrinkles, the electronic properties of few-layer wrinkles are more sensitive to bending deformation as mechanical and electronic coupling induce charge redistribution at the wrinkles, making few-layer graphene and hBN wrinkles suitable for electromechanical system application.

An Image Study on Local Anesthetic Spread in Healthy Volunteers Receiving Subcostal Exterior Semilunaris Transversus Abdominis Plane (SE-TAP) Block.

BACKGROUND: Despite the popularity of the ultrasound-guided transversus abdominis plane (TAP) block and the diversity of advancing approaches, the extent of injectate spread limits its clinical benefits. This study used three-dimensional computed tomography (3D-CT) imaging and a cold stimulus to evaluate the spread of a local anesthetic injected through the subcostal exterior semilunaris to transversus abdominis plane (SE-TAP) block in healthy volunteers. METHODS: Eight healthy volunteers received a right-side ultrasound-guided SE-TAP block with 25 mL of 0.3% ropivacaine. The sensory block was assessed by a cold stimulus at 30 min, 2 h, 4 h, and 8 h following the SE-TAP block according to the 18-zone division method. A CT scan and 3D imaging were performed after the first sensory assessment. RESULTS: The injectate spread into the transversus abdominis space in all eight volunteers. 3D imaging confirmed that the injectate spread extensively along the costal margin in the plane of the transverse abdominis muscle and that it surpassed the semilunaris. Regarding the assessment using cold stimulus, five of six anterior zones and three of six lateral zones obtained successful rates of cutaneous sensory block higher than 75% 30 min after SE-TAP. Sensory block was achieved in the ventral dermatomes of all volunteers. CONCLUSION: Our study showed that the SE-TAP injectate, which was administered using simple anatomical landmarks to provide reliable analgesia for abdominal surgery, consistently spread along the costal margin and extensively blocked cutaneous sensitivity in the anterior and lateral abdominal walls.

[The cholestatic fibrosis induced by α-naphthylisothiocyanate in mice and the inflammation pathway].

Objective: To explore the development of cholestatic fibrosis induced by α-naphthylisothiocyanate (ANIT) and the inflammation pathways. Methods: Fifteen 129/Sv mice weighing (23±2) g were randomly divided into 2 groups: control group (n=5) and experiment group (n=10). The control group was fed commercial chow diet and the experiment group was fed the same diet supplemented with 0. 05% ANIT. Five mice in the experiment group were sacrificed on day 14 and 28 respectively. The gallbladder, serum and liver samples were collected. Biochemical indicators of cholestasis were detected following the procedures in the kit. Liver injury was evaluated by histopathological. Hepatic fibrosis and inflammatory response were analyzed by Q-PCR and WB. Results: Compared with the control group, total bile acid (TBA), the main cholestasis biomarker, was increased from (3. 2±0. 9) µmol/L to (31. 6±4. 3) µmol/L in A-D14 group. AST and ALT, the biomarkers of liver injury, were also increased significantly (P＜0. 05). The expression levels of fibrotic factor tissue inhibitors of metalloproteinases 1 (TIMP-1), monocyte chemoattractant protein 1 (MCP-1) and collagen protein I (Collagen I) were higher than those of control group (P＜0. 05). The expressions of fibrosis protein Collagen I and α-SMA were also up-regulated. The collagen fibers of the liver were largely deposited and the liver fibrosis occurred (P＜0. 05). The expression of inflammatory factors was higher than the control group, JNK, c-Jun and STAT3 were activated (P＜0. 05). In A-D28 group, except AST, matrix metalloproteinases 2 (MMP-2) and Collagen I indicators were slightly decreased, other indicators of cholestasis, liver injury, liver fibrosis and inflammation continued to be up-regulated or stable (P＜0. 05). Conclusion: After 14-day treatment with 0. 05% ANIT diet, significant cholestatic liver fibrosis occurred in mice. After 28 days of treatment, cholestasis liver fibrosis kept stable. The JNK inflammatory pathway played a crucial role in the development of liver fibrosis.

Reduction of interfacial friction in commensurate graphene/h-BN heterostructures by surface functionalization.

The reduction of interfacial friction in commensurately stacked two-dimensional layered materials is important for their application in nanoelectromechanical systems. Our first-principles calculations on the sliding energy corrugation and friction at the interfaces of commensurate fluorinated-graphene/h-BN and oxidized-graphene/h-BN heterostructures show that the sliding energy barriers and shear strengths for these heterostructures are approximately decreased to 50% of those of commensurate graphene/h-BN. The adsorbed F and O atoms significantly suppress the interlayer electrostatic and van der Waals energy corrugations by modifying the geometry and charge redistribution of the graphene layers. Our empirical registry index models further reveal the difference between the roles of the F and O atoms in affecting the sliding energy landscapes, and are also utilized to predict the interlayer superlubricity in a large-scale oxidized-graphene/h-BN system. Surface functionalization is a valid way to control and reduce the interlayer friction in commensurate graphene/h-BN heterostructures.