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.

The roles of sirtuins in ferroptosis.

Ferroptosis represents a novel non-apoptotic form of regulated cell death that is driven by iron-dependent lipid peroxidation and plays vital roles in various diseases including cardiovascular diseases, neurodegenerative disorders and cancers. Plenty of iron metabolism-related proteins, regulators of lipid peroxidation, and oxidative stress-related molecules are engaged in ferroptosis and can regulate this complex biological process. Sirtuins have broad functional significance and are targets of many drugs in the clinic. Recently, a growing number of studies have revealed that sirtuins can participate in the occurrence of ferroptosis by affecting many aspects such as redox balance, iron metabolism, and lipid metabolism. This article reviewed the studies on the roles of sirtuins in ferroptosis and the related molecular mechanisms, highlighting valuable targets for the prevention and treatment of ferroptosis-associated diseases.

Remnant of the late Permian superplume that generated the Siberian Traps inferred from geomagnetic data.

Mantle plumes have played a key role in tectonic events such as continental break-up and large magmatic events since at least the formation of Gondwana. However, as their signatures on Earth's surface, many of large igneous provinces have disappeared into the mantle during Earth's long-term evolution, meaning that plume remnants in the mantle are crucial in advancing mantle plume theory and accurately reconstructing Earth history. Here we present an electrical conductivity model for North Asia constructed from geomagnetic data. The model shows a large high-electrical-conductivity anomaly in the mantle transition zone beneath the Siberian Traps at the time of their eruption that we interpret to be a thermal anomaly with trace amounts of melt. This anomaly lies almost directly over an isolated low-seismic-wave-velocity anomaly known as the Perm anomaly. The spatial correlation of our anomaly with the Siberian Traps suggests that it represents a remnant of a superplume that was generated from the Perm anomaly. This plume was responsible for the late Permian Siberian large igneous province. The model strengthens the validity of the mantle plume hypothesis.

Wogonin Restrains the Malignant Progression of Lung Cancer Through Modulating MMP1 and PI3K/AKT Signaling Pathway.

BACKGROUND: Wogonin, a natural flavonoid compound, represses cancer cell growth and induces cancer cell apoptosis in diverse malignancies. However, the function of Wogonin in lung cancer cells and its regulatory mechanism deserve to be identified. METHODS: A549 and H460 cells were treated with Wogonin, and the cell growth, apoptosis, migration and invasion were measured by CCK-8 and EdU, flow cytometry and Transwell assays. The targeted genes of Wogonin and lung cancer were identified from the TCMSP and Genecards databases, respectively. The STRING database and Cytoscape software were used to establish a PPI network and screen hub genes. GO and KEGG analysis was conducted to explore the functions and signal pathways related to the hub genes. MMP1 expression in lung cancer was analyzed using the UALCAN databases, and GSEA was performed utilizing LinkedOmics. Gelatin zymography assay was used to detect MMP1 activity. MMP1 mRNA expression was detected by qRT-PCR. Besides, MMP1, p-AKT and c-Myc protein were detected by Western Blot assay. RESULTS: Wogonin could suppress the proliferation, migration and invasion of A549 and H460 cells and induce apoptosis. GO and KEGG enrichment analysis revealed the hub genes were mostly enriched in re-entry into the mitotic cell cycle and apoptosis. The expression of MMP1 was markedly upregulated in lung squamous cell carcinoma, lung adenocarcinoma tissues, and lung cancer cell lines. Wogonin could significantly inhibit MMP1 expression and activity, and overexpression of MMP1 significantly reversed the effect of Wogonin on the malignant phenotypes of A549 and H460 cells. Wogonin inhibited the expression of p-AKT and c-Myc protein by regulating MMP1. CONCLUSION: Wogonin can repress lung cancer cells' growth and metastatic potential and promote cell apoptosis via repressing MMP1 expression and modulating PI3K/AKT signaling pathway.

Flexible, Transparent, and Hazy Composite Cellulosic Film with Interconnected Silver Nanowire Networks for EMI Shielding and Joule Heating.

An optical transparent and hazy film with admirable flexibility, electromagnetic interference (EMI) shielding, and Joule heating performance meeting the requirements of optoelectronic devices is significantly desirable. Herein, a cellulose paper was infiltrated by epoxy resin to fabricate a transparent cellulose paper (TCP) with high transparency, optical haze, and favorable flexibility, owing to effective light scattering and mechanical enhancement of the cellulose network. Moreover, a highly connected silver nanowire (AgNW) network was constructed on the TCP substrate by the spray-coating method and appropriate thermal annealing technique to realize high electrical conductivity and favorable optical transmittance of the composite film at the same time, followed by coating of a polydimethylsiloxane (PDMS) layer for protection of the AgNW network. The obtained PDMS/AgNWs/TCP composite film features considerable optical transmittance (up to 86.8%) and haze (up to 97.7%), while satisfactory EMI shielding effectiveness (SE) (up to 39.1 dB, 8.2-12.4 GHz) as well as strong mechanical strength (higher than 41 MPa) were achieved. The coated PDMS layer prevented the AgNW network from falling off and ensured the long-term stability of the PDMS/AgNWs/TCP composite film under deformations. In addition, the multifunctional PDMS/AgNWs/TCP composite film also exhibited excellent Joule heating performance with low supplied voltages, rapid response, and sufficient stability. This work demonstrates a novel pathway to improve the performance of multifunctional transparent composite films for future advanced optoelectronic devices.

Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis.

Lung cancer is the most frequent malignancy, and non-small cell lung cancer (NSCLC) is its most common pathological type. Molecular targeted therapy has been testified to be effective in intervening in the occurrence and development of malignancies. This study investigates the effect of lncRNA Regulatory Factor X3- antisense RNA 1 (RFX3-AS1) in NSCLC progression. The RFX3-AS1 profile in NSCLC tissues and cells was measured by quantitative reverse transcription PCR (qRT-PCR). The RFX3-AS1 overexpression model was constructed. The cell counting kit-8 (CCK-8) experiment and cell colony formation assay were adopted to test cell viability. The cell apoptosis was determined by flow cytometry (FCM). Cell migration and invasion were monitored by the Transwell assay, and Western blot was implemented to verify the protein profiles of signal transducer and activator of transcription 3 (STAT3), E-cadherin, Vimentin and N-cadherin. In vivo, we validated the impact of RFX3-AS1 overexpression on the NSCLC xenograft mouse model. The targeting relationships between RFX3-AS1 and miR-577, miR-577 and STAT3 were confirmed by the dual-luciferase reporter assay. The results manifested that overexpressing RFX3-AS1 markedly facilitated NSCLC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and suppressed cell apoptosis. In contrast, miR-577, which was a downstream target of RFX3-AS1, dramatically impeded the malignant biological behaviors of NSCLC cells. STAT3 was a direct target of miR-577, and it was negatively regulated by the latter. STAT3 activation reversed miR-577-mediated anti-tumor roles. In brief, RFX3-AS1 aggravated NSCLC progression by regulating the miR-577/STAT3 axis.

An Ultrastrong and Antibacterial Silver Nanowire/Aligned Cellulose Scaffold Composite Film for Electromagnetic Interference Shielding.

Constructing multifunctional electromagnetic interference (EMI) shielding films with superior mechanical strength has sparked a lot of interest in the fields of wearable electronics. In this work, the conductive silver nanowires (AgNWs) were synthesized and impregnated into the highly aligned cellulose scaffold (CS) fabricated by wood delignification followed by hot-pressing and polydimethylsiloxane (PDMS) dipping processes to obtain the outstanding EMI shielding cellulosic film (d-AgNWs@CS-PDMS). The consecutively conductive pathway of AgNWs was constructed in the microchannels of the CS as a result of the hydrogen bonding between AgNWs and cellulose fibers, which is conducive to the reflection of incident EM waves. The higher degree of nanofiber alignment and the compact conductive network were improved by densification upon hot pressing, which endows the composite film with striking mechanical properties (maximum tensile strength of 511.8 MPa) and superb EMI shielding performance (shielding effectiveness value of 46 dB with a filler content of 21.6 wt %) at the X band (8.2-12.4 GHz). Moreover, the existence of an intensive AgNWs network and the introduction of the PDMS layer improve the hydrophobicity and antibacterial activity of the composite film, avoiding serious health concerns in the long-term wearing. These results demonstrate that the obtained d-AgNWs@CS-PDMS composite film has high potential as an EMI shielding material used for wearable devices.

Association between the RETN -420C/G polymorphism and type 2 diabetes mellitus susceptibility: A meta-analysis of 23 studies.

Background: The published findings on the link between the resistin (RETN) gene polymorphism and type 2 diabetes mellitus (T2DM) risk are still contradictory. Here, through a meta-analysis, we summarized a more precise evaluation of their connection by synthesizing existing research. Methods: PubMed, Google Scholar, and Web of Science were electronically searched, and all cited sources were manually searched. The heterogeneity of effects was tested and all statistical analyses were performed in Stata 12.0. Results: A total of 23 studies with 10,651 cases and 14,366 controls on RETN -420C/G polymorphism were included. The overall results showed that the association of RETN -420C/G polymorphism and T2DM susceptibility was not significant [for the allelic model: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.87-1.10, pheterogeneity <.001; I 2 = 84.6%; for the dominant model: OR = 0.96, 95% CI = 0.80-1.15, pheterogeneity <.001; I 2 = 87.1%; and for the recessive model: OR = 0.96, 95% CI = 0.82-1.12, pheterogeneity <.001; I 2 = 56.9%] but with high heterogeneity across studies (p <.0001). Meta-regression found that the median age of T2DM participants (using age 50 as the cutoff) could be a factor in the observed variation. The RETN -420C/G polymorphism seems to be linked to an increased risk of T2DM in younger individuals [for dominant: OR = 0.84 (95% CI, 0.72-0.98; pheterogeneity <.001; I 2 = 80.9%)] and decreased risk in older people [for dominant: OR = 3.14 (95% CI, 2.35-4.19; pheterogeneity = .98; I 2 = 0.0%)]. Conclusions: Current results found no evidence that the RETN -420C/G variant was linked to T2DM susceptibility, but the patient's age appears to be a potential factor that contributed to high heterogeneity across studies. Additional high-quality and well-designed investigations are required to confirm these results.

[Acupuncture Treatment Reduces Body Weight Possibly by Down-regulating Insulin and Leptin Resistance, and Up-regulating Soluble Leptin Receptor Level in Prediabetic Patients].

OBJECTIVE: To observe the effect of acupuncture of Feishu (BL 13), Pishu (BL 20), etc. on body weight, blood lipid, leptin (LP) and soluble leptin receptor (sOB-R) levels in prediabetic patients, so as to explore its mechanisms underlying treatment and prevention of prediabetes. METHODS: A total of 100 prediabetic patients were randomly assigned to medication (Metformin) group (n＝35), acupuncture group (n＝35) and simple lifestyle intervention group (n＝30) with random number table method. All the patients of the 3 groups were treated with lifestyle intervention (reasonable diet and moderate physical exercise) and ordered to stop administration of any hypoglycemic drugs during the treatment period. Bilateral Feishu (BL 13), Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23), Zusanli (ST 36) and Sanyinjiao (SP 6) were punctured with filiform needles which were manipulated by lifting, thrusting and twirling repeatedly for about 2 min every 5 min during 30 minutes' needle retaining. The acupuncture treatment was conducted once every other day for 12 weeks. Patients of the medication group were ordered to orally take Metformin tablets (0.5 g/time, twice a day) for continuous 12 weeks. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), 2 h-postprandial blood glucose (2 h-PBG), fasting blood glucose (FBG), glycosyla-ted hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), fasting insulin (FINS), serum LP and sOB-R levels were measured before and after the treatment. RESULTS: After the treatment, the BMI in the acupuncture group, and BMI, WC and WHR in the medication group were significantly decreased relevant to their own pre-treatment in each group (P<0.05, P<0.01). Following the treatment, the levels of FBG, 2 h-PBG, HbA1C, TC, TG, FINS, HOMA-IR and LP in both acupuncture and medication groups, and FBG in the simple lifestyle intervention group were significantly decreased in comparison with their own pre-treatment in each group (P<0.01, P<0.05), and the levels of FBG, 2 h-PBG, HbA1C, TC and TG, HOMA-IR and LP in both acupuncture and medication groups were all considerably lower than those of the simple lifestyle intervention group (P<0.01，P<0.05). The level of FINS in the medication group was significantly lower than that of the simple lifestyle intervention group (P<0.05). Additionally, following the treatment, serum sOB-R contents in both acupuncture and medication groups were obviously increased compared with their own pre-treatment in each group and also relevant to the simple lifestyle intervention group (P<0.01). No significant changes were found in the simple lifestyle intervention group in all the above-mentioned blood indexes except FBG (P>0.05). CONCLUSION: Acupuncture can induce body weight loss, down-regulate FINS, insulin resistance and LP resistance, and up-regulate sOB-R content in prediabetic patients, displaying a positive role in the treatment of prediabetes.

Anti-arthritic activity of ethanol extract of Fagopyrum cymosum with adjuvant-induced arthritis in rats.

CONTEXT: Fagopyrum cymosum (Trey.) Meisn (Polygonaceae) (EFC) has long been used as a folk medicine to treat various ailments of the lung, dysentery and rheumatism in China. OBJECTIVE: The present study evaluated the anti-arthritic effect of 95% ethanol extract of EFC (extract of Fagopyrum cymosum). MATERIALS AND METHODS: The anti-arthritic activity was investigated by adjuvant arthritic (AA) rat model induced by Freund's complete adjuvant (FCA). The AA rats were randomly separated into different groups and then treated with EFC (40, 80 and 160 mg/kg) from day 7 to day 28 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index, body weight and index of immune organs. In addition, the severity of arthritis in the knee joints was evaluated by histopathological and hemorheological examination. The levels of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α) in the serum were assessed by ELISA. RESULTS: The high dose level of EFC (160 mg/kg) significantly suppressed the swelling of hind paw of AA rats (p < 0.01) and inhibited their body weight loss (p < 0.01). Based on histopathological examination, all EFC groups showed great amelioration compared with the model group. EFC (80 and 160 mg/kg) also decreased the plasma viscosity in different shear rates (p < 0.01). Moreover, EFC significantly reduced the production of IL-1 and TNF-α in the serum of AA (p < 0.01). DISCUSSION AND CONCLUSION: This study provides a scientific basis for the claims that F. cymosum is effective in preventing and suppressing the development and progression of experimental arthritis, with reductions in inflammatory response.

[Effect of acupuncture on serum leptin level in patients with type II diabetes mellitus].

OBJECTIVE: To study the relationship between serum leptin and insulin resistance, and to analyze the effect of acupuncture on serum leptin level in patients with type-II diabetes mellitus (DM). METHODS: A total of 80 type-II DM patients were randomized into acupuncture and medication groups. Acupuncture was applied to Yishu (EX), Feishu (BL13), Pishu (BL 20), etc. according to syndrome identification. The treatment was given once every other day for 12 weeks. For patients in the medication group, Glibenclamide (2.5-7.5 mg/time, 1-2 times/d according to blood sugar level) was given for 12 weeks. Fasting blood glucose (FBG), fasting insulin (FINS) and fasting leptin (FLP) were detected by using glucose oxidase method, radioimmunoassay and ELISA, respectively. Insulin sensitivity index (ISI) and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated. RESULTS: In comparison with pre-treatment, FBG levels and HOMA-IR in both acupuncture and medication groups, and FINS and FLP levels in the acupuncture group were decreased significantly (P < 0.01), while ISI in both acupuncture and medication groups, and FINS level in the medication group were increased remarkably after the treatment (P < 0.01). Comparison between two groups showed that after the treatment, FINS and FLP levels, and HOMA-IR of the acupuncture group were considerably lower than those of the medication group (P < 0.01), while ISI of the acupuncture group was significantly higher than that of the medication group (P < 0.01). CONCLUSION: Acupuncture therapy is effective in lowering FLP level, which may contribute to its clinical effect in improving type-II DM.