An efficient and high-water-content enzymatic esterification method for the synthesis of ß-sitosterol conjugated linoleate via a sodium citrate-based three-liquid-phase system.

Three-liquid-phase systems (TLPSs) are novel interfacial enzymatic reaction systems that have been successfully applied in many valuable reactions. However, these systems are suitable only for hydrolysis reactions and not for more widely used esterification reactions. Surprisingly, our recent research revealed that two water-insoluble substrates (ß-sitosterol and conjugated linoleic acid) could be rapidly esterified in this system. The initial rate of the esterification reaction in the TLPS based on sodium citrate was enhanced by approximately 10-fold relative to that in a traditional water/n-hexane system. The special emulsion structure (S/W1/W2 emulsion) formed may be vital because it not only provides a larger reaction interface but also spontaneously generates a middle phase that might regulate water activity to facilitate esterification. Furthermore, the lipase-enriched phase could be reused at least 8 times without significant loss of catalytic efficiency. Therefore, this TLPS is an ideal enzymatic esterification platform for ester synthesis because it is efficient, convenient to use, and cost-effective.

Effect of In Situ Heating on the Growth and Electrochromic Properties of Tungsten Trioxide Thin Films.

Electrochromism has emerged as a pivotal technology in the pursuit of energy efficiency and environmental sustainability, spurring significant research efforts aimed at the creation of advanced electrochromic devices. Most electrochromic materials are used for smart window applications. However, current electrochromic materials have been applied to new energy vehicles, cell phone back covers, AR glasses, and so on. More application scenarios put forward more requirements for the color of the colored states. Choosing the right color change in the application will be the trend in the future. In this work, tungsten trioxide (WO3) thin films were prepared by adjusting the in situ heating temperature. WO3 with a crystalline structure showed excellent cyclic stability (5000 cycles), electrochromic performance (ΔT = 77.7% at 633 nm, CE = 37.1 cm2/C), relatively fast bleaching/coloring speed (20.0 s/19.4 s), and the darkest coloring effect (L* = 29.32, a* = 7.41, b* = -22.12 for the colored state). These findings offer valuable insights into the manipulation of smart materials and devices, contributing to the advancement of electrochromic technology.

An Integrated Network Pharmacology and RNA-seq Approach for Exploring the Protective Effect of Andrographolide in Doxorubicin-Induced Cardiotoxicity.

PURPOSE: Doxorubicin (Dox) is clinically limited due to its dose-dependent cardiotoxicity. Andrographolide (Andro) has been confirmed to exert cardiovascular protective activities. This study aimed to investigate protective effects of Andro in Dox-induced cardiotoxicity (DIC). METHODS: The cardiotoxicity models were induced by Dox in vitro and in vivo. The viability and apoptosis of H9c2 cells and the myocardial function of c57BL/6 mice were accessed with and without Andro pretreatment. Network pharmacology and RNA-seq were employed to explore the mechanism of Andro in DIC. The protein levels of Bax, Bcl2, NLRP3, Caspase-1 p20, and IL-1ß were qualified as well. RESULTS: In vitro, Dox facilitated the downregulation of cell viability and upregulation of cell apoptosis, after Andro pretreatment, the above symptoms were remarkably reversed. In vivo, Andro could alleviate Dox-induced cardiac dysfunction and apoptosis, manifesting elevation of LVPWs, LVPWd, EF% and FS%, suppression of CK, CK-MB, c-Tnl and LDH, and inhibition of TUNEL-positive cells. Using network pharmacology, we collected and visualized 108 co-targets of Andro and DIC, which were associated with apoptosis, PI3K-AKT signaling pathway, and others. RNA-seq identified 276 differentially expressed genes, which were enriched in response to oxidative stress, protein phosphorylation, and others. Both network pharmacology and RNA-seq analysis identified Tap1 and Timp1 as key targets of Andro in DIC. RT-QPCR validation confirmed that the mRNA levels of Tap1 and Timp1 were consistent with the sequenced results. Moreover, the high expression of NLRP3, Caspase-1 p20, and IL-1ß in the Dox group was reduced by Andro. CONCLUSIONS: Andro could attenuate DIC through suppression of Tap1 and Timp1 and inhibition of NLRP3 inflammasome activation, serving as a promising cardioprotective drug.

Rapid Fabrication of Flexible Cu@Ag Flake/SAE Composites with Exceptional EMIS and Joule Heating Performance.

High electromagnetic interference shielding (EMIS) effectiveness and good thermal management properties are both required to meet the rapid development of integrated electronic components. However, it remains challenging to obtain environmentally friendly and flexible films with high EMIS and thermal management performance in an efficient and scalable way. In this paper, an environmentally friendly strategy is proposed to synthesize multifunctional waterborne Cu@Ag flake conductive films using water as the solvent and silicone-acrylic emulsion (SAE) as a matrix. The obtained films show high electrical conductivity and exceptional EMI SE and electrothermal conversion properties. The EMI SE in the X-band is higher than 76.31 dB at a thickness of 60 µm owing to the ultrahigh electrical conductivity of 1073.61 S cm-1. The film warms up quickly to 102.1 °C within 10 s under a low voltage of 2.0 V. In addition, the shielding coating is sufficiently flexible to retain a conductivity of 93.4% after 2000 bending-release cycles with a bending radius of 3 mm. This work presents an alternative strategy to produce high EMIS effectiveness and Joule heating films for highly integrated and flexible electronic components in a green, scalable, and highly efficient way.

Phloretin alleviates doxorubicin-induced cardiotoxicity through regulating Hif3a transcription via targeting transcription factor Fos.

BACKGROUND: Doxorubicin (Dox), a chemotherapeutic agent known for its efficacy, has been associated with the development of severe cardiotoxicity, commonly referred to as doxorubicin-induced cardiotoxicity (DIC). The role and mechanism of action of phloretin (Phl) in cardiovascular diseases are well-established; however, its specific function and underlying mechanism in the context of DIC have yet to be fully elucidated. OBJECTIVE: This research aimed to uncover the protective effect of Phl against DIC in vivo and in vitro, while also providing a comprehensive understanding of the underlying mechanisms involved. METHODS: DIC cell and murine models were established. The action targets and mechanism of Phl against DIC were comprehensively examined by systematic network pharmacology, molecular docking, transcriptomics technologies, transcription factor (TF) prediction, and experimental validation. RESULTS: Phl relieved Dox-induced cell apoptosis in vitro and in vivo. Through network pharmacology analysis, a total of 554 co-targeted genes of Phl and Dox were identified. Enrichment analysis revealed several key pathways including the PI3K-Akt signaling pathway, Apoptosis, and the IL-17 signaling pathway. Protein-protein interaction (PPI) analysis identified 24 core co-targeted genes, such as Fos, Jun, Hif1a, which were predicted to bind well to Phl based on molecular docking. Transcriptomics analysis was performed to identify the top 20 differentially expressed genes (DEGs), and 202 transcription factors (TFs) were predicted for these DEGs. Among these TFs, 10 TFs (Fos, Jun, Hif1a, etc.) are also the co-targeted genes, and 3 TFs (Fos, Jun, Hif1a) are also the core co-targeted genes. Further experiments validated the finding that Phl reduced the elevated levels of Hif3a (one of the top 20 DEGs) and Fos (one of Hif3a's predicted TFs) induced by Dox. Moreover, the interaction between Fos protein and the Hif3a promoter was confirmed through luciferase reporter assays. CONCLUSION: Phl actively targeted and down-regulated the Fos protein to inhibit its binding to the promoter region of Hif3a, thereby providing protection against DIC.

Hyperoside prevents doxorubicin-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway.

Clinical application of doxorubicin (Dox) in cancer chemotherapy is limited by its cardiotoxicity. Present study aimed to demonstrate the effect and mechanism of hyperoside in Dox-induced cardiotoxicity. C57BL/6 mice were injected with 12 mg/kg of Dox, and 1 µM Dox was exposed to primary cardiomyocytes. Cardiac function was evaluated by echocardiographic and myocardial enzyme levels. Cardiomyocyts apoptosis was analyzed by TUNEL staining and flow cytometry. Network pharmacology and molecular docking were utilized to explore potential targets of hyperoside. Protein expressions were detected by western blot and enzyme activities were determined by colorimetry. Cardiac dysfunction and cardiomyocyte apoptosis induced by Dox were attenuated by hyperoside. Mechanism of hyperoside was mainly related to "oxidative stress" pathway. Hyperoside exhibited strong binding activities with nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs, the main source of ROS in cardiomyocytes) and cyclooxygenases (COXs). Experiments proved that hyperoside suppressed the ROS generation and the elevated activities of NOXs and COXs induced by Dox. Dox also triggered the activation of NLRP3 inflammasome, which was reversed by hyperoside. Hyperoside bound to NOXs and COXs, which prevents Dox-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway. Hyperoside holds promise as a therapeutic strategy for Dox-induced cardiotoxicity.

[Clinical management of skin necrosis after penis lengthening surgery: Report of 12 cases].

OBJECTIVE: To analyze the causes of skin necrosis after penis lengthening surgery and corresponding treatment measures, and observe the clinical effect of free skin graft repair in the treatment of penile skin defects. METHODS: We retrospectively analyzed the clinical data on 12 cases of extensive penile skin necrosis and defect after penis lengthening surgery performed in our department from January 2017 to January 2022. The patients underwent free skin graft repair with medium- or full-thickness skin grafts from the thigh after wound preparation. RESULTS: The skin grafts survived well in all the 12 patients and the incisions healed in the first stage without any complications. At 6 months after surgery, skin sensation was mostly recovered in the area of penis skin grafting, no obvious skin ulceration or edema was observed, and the appearance of the penis was satisfactory. The IIEF-5 scores, Erectile Hardness Scale (EHS) scores, and the results of penile hardness tests of the patients all indicated normal erectile function. CONCLUSION: Free skin graft repair with autologous medium- or full-thickness skin grafts is a safe and effective surgical option for extensive penile skin necrosis after penis lengthening surgery.

In situ grown hierarchical NiO nanosheet@nanowire arrays for high-performance electrochromic energy storage applications.

Electrodes with hierarchical nanoarchitectures could promote electrochemical properties due to their largely exposed active sites and quick charge transfer. Herein, in situ grown hierarchical NiO nanosheet@nanowire films are reported by a one-step hydrothermal process followed by heat treatment. The unique NiO hierarchical nanostructures, which are composed of NiO nanowires grown on the surface of a nanosheet array, show improved electrochromic properties such as large optical modulation in different light regions (95% at 550 nm and 50.6% at 1000 nm), fast color change (9.8/5.4 s) and better coloring efficiency (91.2 cm2 C-1) with long-term cycling properties (82.2% after 700 cycles). Simultaneously, the hierarchical nanostructures possess optimal areal capacitance (117.2 mF cm-2), rate performance and cycling properties. The enhanced electrochemical properties are due to the pretreated seed layer and the synergistic effect between the unique in situ grown ultrathin nanowire and the underlying vertical nanosheet layer which can strengthen the mechanical adhesion of the nanoarray film to the substrate and make both nanosheets and nanowires more exposed to the electrolyte, enhancing charge transfer and mass diffusion. This work provides a promising pathway towards developing high quality electrochromic energy storage devices.

TiO2 nanotubular arrays decorated with ultrafine Ag nanoseeds enabling a stable and dendrite-free lithium metal anode.

To exploit next-generation high-energy Li metal batteries, it is vitally important to settle the issue of dendrite growth accompanied by interfacial instability of the Li anode. Applying 3D current collectors as hosts for Li deposition emerges as a prospective strategy to achieve uniform Li nucleation and suppress Li dendrites. Herein, well-aligned and spaced TiO2 nanotube arrays grown on Ti foil and surface decorated with dispersed Ag nanocrystals (Ag@TNTAs/Ti) were constructed and employed as a 3D host for regulating Li stripping/plating behaviors and suppressing Li dendrites, and also relieving volume fluctuation during repetitive Li plating/stripping. Uniform TiO2 nanotubular structures with a large surface allow fast electron/ion transport and uniform local current density distribution, leading to homogeneous Li growth on the nanotube surface. Moreover, Ag nanocrystals and TiO2 nanotubes have good Li affinity, which facilitates Li+ capture and reduces the Li nucleation barrier, achieving uniform nucleation and growth of Li metal over the 3D Ag@TNTAs/Ti host. As a result, the as-fabricated Ag@TNTAs/Ti electrode exhibits dendrite-free plating morphology and long-term cycle stability with coulombic efficiency maintained over 98.5% even after 1000 cycles at a current density of 1 mA cm-2 and cycling capacity of 1 mA h cm-2. In symmetric cells, the Ag@TNTAs/Ti-Li electrode shows a much lower hysteresis of 40 mV over an ultralong cycle period of 2600 h at a current density of 1 mA cm-2 and cycling capacity of 1 mA h cm-2. Moreover, the full cell with the Ag@TNTAs/Ti-Li anode and LiFePO4 cathode achieves a high capacity of 155.2 mA h g-1 at 0.5C and retains 77.9% capacity with an average CE of ≈99.7% over 200 cycles.

Dissecting the molecular mechanism of cepharanthine against COVID-19, based on a network pharmacology strategy combined with RNA-sequencing analysis, molecular docking, and molecular dynamics simulation.

OBJECTIVES: Recently, it has been reported that cepharanthine (CEP) is highly likely to be an agent against Coronavirus disease 2019 (COVID-19). In the present study, a network pharmacology-based approach combined with RNA-sequencing (RNA-seq), molecular docking, and molecular dynamics (MD) simulation was performed to determine hub targets and potential pharmacological mechanism of CEP against COVID-19. METHODS: Targets of CEP were retrieved from public databases. COVID-19-related targets were acquired from databases and RNA-seq datasets GSE157103 and GSE155249. The potential targets of CEP and COVID-19 were then validated by GSE158050. Hub targets and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI) network analysis and enrichment analysis. Subsequently, molecular docking was carried out to predict the combination of CEP with hub targets. Lastly, MD simulation was conducted to further verify the findings. RESULTS: A total of 700 proteins were identified as CEP-COVID-19-related targets. After the validation by GSE158050, 97 validated targets were retained. Enrichment results indicated that CEP acts on COVID-19 through multiple pathways, multiple targets, and overall cooperation. Specifically, PI3K-Akt signaling pathway is the most important pathway. Based on PPI network analysis, 9 central hub genes were obtained (ACE2, STAT1, SRC, PIK3R1, HIF1A, ESR1, ERBB2, CDC42, and BCL2L1). Molecular docking suggested that the combination between CEP and 9 central hub genes is extremely strong. Noteworthy, ACE2, considered the most important gene in CEP against COVID-19, binds to CEP most stably, which was further validated by MD simulation. CONCLUSION: Our study comprehensively illustrated the potential targets and underlying molecular mechanism of CEP against COVID-19, which further provided the theoretical basis for exploring the potential protective mechanism of CEP against COVID-19.

Potential mechanisms underlying the therapeutic roles of sinisan formula in depression: Based on network pharmacology and molecular docking study.

Background: The incidence of depression has been increasing globally, which has brought a serious burden to society. Sinisan Formula (SNSF), a well-known formula of traditional Chinese medicine (TCM), has been found to demonstrate an antidepressant effect. However, the therapeutic mechanism of this formula remains unclear. Thus, the present study aimed to explore the mechanism of SNSF in depression through network pharmacology combined with molecular docking methods. Materials and methods: Bioactive compounds, potential targets of SNSF, and related genes of depression were obtained from public databases. Essential ingredients, potential targets, and signaling pathways were identified using bioinformatics analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, Autodock software was further performed for conducting molecular docking to verify the binding ability of active ingredients to targets. Results: A total of 91 active compounds were successfully identified in SNSF with the use of the comprehensive network pharmacology approach, and they were found to be closely connected to 112 depression-related targets, among which CREB1, NOS3, CASP3, TP53, ESR1, and SLC6A4 might be the main potential targets for the treatment of depression. GO analysis revealed 801 biological processes, 123 molecular functions, and 67 cellular components. KEGG pathway enrichment analysis indicated that neuroactive ligand-receptor interaction, serotonergic synapse pathways, dopaminergic synapse pathways, and GABAergic synapse pathways might have played a role in treating depression. Molecular docking suggested that beta-sitosterol, nobiletin, and 7-methoxy-2-methyl isoflavone bound well to the main potential targets. Conclusion: This study comprehensively illuminated the active ingredients, potential targets, primary pharmacological effects, and relevant mechanism of the SNSF in the treatment of depression. SNSF might exert its antidepressant effects by regulating the signaling pathway of 5-hydroxytryptamine, dopamine, GABA, and neuroactive ligand receptor interactions. Still, more pharmacological experiments are needed for verification.

Recent Advances in W-Containing Refractory High-Entropy Alloys-An Overview.

During the past decade, refractory high-entropy alloys (RHEA) have attracted great attention of scientists, engineers and scholars due to their excellent mechanical and functional properties. The W-containing RHEAs are favored by researchers because of their great application potential in aerospace, marine and nuclear equipment and other high-temperature, corrosive and irradiated fields. In this review, more than 150 W-containing RHEAs are summarized and compared. The preparation techniques, microstructure and mechanical properties of the W-containing RHEAs are systematically outlined. In addition, the functional properties of W-containing RHEAs, such as oxidation, corrosion, irradiation and wear resistance have been elaborated and analyzed. Finally, the key issues faced by the development of W-containing RHEAs in terms of design and fabrication techniques, strengthening and deformation mechanisms, and potential functional applications are proposed and discussed. Future directions for the investigation and application of W-containing RHEAs are also suggested. The present work provides useful guidance for the development, processing and application of W-containing RHEAs and the RHEA components.

Artificially Layered CoSe2 Nanosheets by a Dual-Templating Strategy for High-Performance Lithium-Sulfur Batteries.

Owing to the attractive merits of layered transition metal dichalcogenides (LTMDs) with van der Waals interactions, it is significant to modulate electronic structures and endow them with fascinating physiochemical properties by converting a nonlayered metal dichalcogenide into an atomic layered one. Herein, a dual-templating strategy is designed to prepare artificially layered CoSe2 nanosheets on carbon fiber cloth (L-CoSe2/CFC). It is found that not only the nanosheet morphology but also the layered structure is well inherited from the precursor of layered Co(OH)2 nanosheets through a wet-solution ion-exchange approach. The as-prepared L-CoSe2/CFC serves as an efficient multifunctional interlayer to solve the challenges of "shuttling effect" and slow multistep reaction kinetics in lithium-sulfur batteries (LSBs), thus dramatically improving their electrochemical performance. Benefiting from the L-CoSe2 nanosheets with large interlayer spacing, strong chemical adsorption, and superior catalytic activity, L-CoSe2/CFC promotes the anchoring of lithium polysulfides (LiPSs) and their catalytic conversion. Consequently, the L-CoSe2/CFC cell yields a large reversible capacity of 1584 mAh g-1 at 0.2C and a high rate capability of 987 mAh g-1 at 4C. A high areal capacity of 4.38 mAh cm-2 after 100 cycles at 0.2C is achieved for the high-S-loading LSB (4.6 mg cm-2) using the L-CoSe2/CFC interlayer.

Circ_001042 Inhibits TGF-ß1/P38 MAPK Signaling Axis-Mediated Epithelial-Mesenchymal Transition and Metastasis in Lung Adenocarcinoma.

Objective: To explore the role and molecular mechanism of circ_001042 in lung adenocarcinoma (LUAD). Methods: The expression level of circ_001042 and linear RNA MRPS35 in cells and clinical tissues was detected by real-time PCR (qRT-PCR). The expression of circ_001042 and transforming growth factor ß1 (TGF-ß1) in LUAD cells was elevated by the respective transfection of overexpression vectors OE-circ_001042 and TGF-ß1; MTT and transwell assays were applied to test the proliferation, migration, and invasion abilities of cells, respectively. The E-cadherin expression level in the cells was assessed by immunofluorescence staining, and western blot was utilized to determine the expression level of epithelial-mesenchymal transition (EMT) and TGF-ß1/P38 MAPK signaling axis-related proteins in the cells. Results: Circ_001042 was significantly downregulated in LUAD tissues and cells, and high circ_001042 expression could inhibit the proliferation, invasion, and migration of LUAD cells. In addition, circ_001042 also inhibited the EMT process (the E-cadherin level was upregulated; and the levels of N-cadherin, vimentin, and Snail were downregulated) and TGF-ß1/P38 MAPK signaling axis activity in LUAD cells. Moreover, circ_001042 could suppress the promotion of TGF-ß1 on the proliferation, invasion, migration, and EMT process of LUAD cells and the activation of TGF-ß1/P38 MAPK signaling axis. Conclusion: By inhibiting TGF-ß1, circ_001042 not only suppresses the proliferation, migration, invasion, and EMT of LUAD but also inhibits the activation of TGF-ß1/P38 MAPK signaling axis. Therefore, circ_001042 can act as a potential target for early diagnosis and targeted therapy of LUAD.

Calycosin Inhibits the Malignant Behaviors of Lung Adenocarcinoma Cells by Regulating the circ_0001946/miR-21/GPD1L/HIF-1α Signaling Axis.

Objective: To clarify the potential function and molecular mechanism of calycosin in lung adenocarcinoma (LUAD) cells. Methods: LUAD cells (A549 and H1299) were treated with calycosin at different concentrations (25 nM, 50 nM, and 100 nM) for 24 h. The colony formation, invasion, and migration of the cells were assessed by colony formation, transwell, and scratch assays, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the mRNA expression level of circ_0001946, miR-21, glycerol-3-phosphate dehydrogenase 1 like (GPD1L), and hypoxia-inducible factor-1α (HIF-1α) in clinical tissue samples and LUAD cells. RNA pull-down assay and dual-luciferase reporter assay were performed to verify the relationship among circ_0001946, miR-21, GPD1L, and HIF-1α. Western blot was performed to detect the protein expression of epithelial-mesenchymal transition (EMT) process-related genes (E-cadherin, N-cadherin, and snail) and GPD1L as well as HIF-1α. Results: Calycosin inhibited colony formation, invasion, migration, and EMT progression in A549 and H1299 cells. Besides, calycosin was able to regulate the expression of circ_0001946, miR-21, GPD1L, and HIF-1α in LUAD cells. According to the findings of QRT-PCR, the expression level of circ_0001946 and GPD1L in LUAD tissues was significantly lower than that in adjacent noncancerous normal tissues, and the expression of miR-21 and HIF-1α was also significantly increased in clinical tissue samples. In addition, there was a targeted regulatory relationship among the above four expressions. Knockdown of circ_0001946 expression in A549 cells treated with calycosin enhanced the malignant behavior of A549 cells and inhibited the anticancer effect of calycosin. However, the knockdown of miR-21 promoted the anticancer effect of calycosin and inhibited the malignant behavior of A549. Conclusion: Calycosin can inhibit colony formation, invasion, migration, and EMT process of LUAD cells via regulating the circ_0001946/miR-21/GPD1L/HIF-1α signaling axis and could be a promising therapeutic drug for LUAD.

Functional Characteristics of Lactic Acid Bacteria In Vitro Isolated from Spontaneously Fermented Sour Porridge with Broomcorn Millet in Northwestern Shanxi Province of China.

Eighteen strains of lactic acid bacteria were isolated from spontaneously fermented sour porridge with broomcorn millet in Northwestern Shanxi Province of China, and their probiotic characteristics were investigated in vitro. Survival rates under gastrointestinal conditions, cholesterol reduction, antibacterial capabilities, antioxidant activities, and safety assessments were examined. Results showed that five strains were selected as probiotics and identified as Levilactobacillusbrevis. Strain L10 exhibited excellent probiotic characteristics, with an 86% survival rate under pH 2.0 for 2 h, 80% survival rate in 0.3% bile salt for 6 h, the highest survival rate (78%) in simulated gastrointestinal juice for 3 h, the highest hydrophobicity (42% to xylene and 39% to hexadecane), the highest aggregation (39% auto-aggregation and 10.4-18.13% co-aggregation), relative higher cholesterol reduction rate (80%), the highest antibacterial activities, the highest antioxidant activity, sensitive to most antibiotics tested, without hemolytic and hydrolyze gelatinase activity and could not produce biogenic amine. Therefore, strain L10 could be applied to functional foods.

Network Pharmacology-Based Strategy Combined with Molecular Docking and in vitro Validation Study to Explore the Underlying Mechanism of Huo Luo Xiao Ling Dan in Treating Atherosclerosis.

Background: Huo Luo Xiao Ling Dan (HLXLD), a famous Traditional Chinese Medicine (TCM) classical formula, possesses anti-atherosclerosis (AS) activity. However, the underlying molecular mechanisms remain obscure. Aim: The network pharmacology approach, molecular docking strategy, and in vitro validation experiment were performed to explore the potential active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. Methods: Several public databases were used to search for active components and targets of HLXLD, as well as AS-related targets. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis. Subsequently, the molecular docking strategy and molecular dynamics simulation were carried out to predict the affinity and stability of active compounds and key targets. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. Results: A total of 108 candidate compounds and 321 predicted target genes were screened. Bioinformatics analysis suggested that quercetin, dihydrotanshinone I, pelargonidin, luteolin, guggulsterone, and ß-sitosterol may be the main ingredients. STAT3, HSP90AA1, TP53, and AKT1 could be the key targets. MAPK signaling pathway might play an important role in HLXLD against AS. Molecular docking and molecular dynamics simulation results suggested that the active compounds bound well and stably to their targets. Cell experiments showed that the intracellular accumulation of lipid and increased secretory of TNF-α, IL-1ß, and MCP-1 in ox-LDL treated RAW264.7 cells, which can be significantly suppressed by pretreating with dihydrotanshinone I. The up-regulation of STAT3, ERK, JNK, and p38 phosphorylation induced by ox-LDL can be inhibited by pretreating with dihydrotanshinone I. Conclusion: Our findings comprehensively demonstrated the active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. These findings would provide a scientific basis for the study of the complex mechanisms underlying disease and drug action.

Noncoding RNA-Associated Competing Endogenous RNA Networks in Doxorubicin-Induced Cardiotoxicity.

Accumulating evidence has indicated that noncoding RNAs (ncRNAs) are involved in doxorubicin-induced cardiotoxicity (DIC). However, the ncRNA-associated competing endogenous RNA (ceRNA)-mediated regulatory mechanisms in DIC remain unclear. In this study, we aimed to systematically investigate the alterations in expression levels of long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and mRNA in a DIC mouse model through deep RNA sequencing (RNA-seq). The results showed that 217 lncRNAs, 41 circRNAs, 11 miRNAs and 3633 mRNAs were aberrantly expressed. Moreover, the expression of 12 randomly selected transcripts was determined by real-time quantitative polymerase chain reaction to test the reliability of RNA-seq data. Based on the interaction between miRNAs and mRNAs, as well as lncRNAs/circRNAs and miRNAs, we constructed comprehensive lncRNA or circRNA-associated ceRNA networks in DIC mice. Moreover, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for differentially expressed genes. In conclusion, these identified ceRNA interactions provide new insight into the underlying mechanism and may be crucial therapeutic targets of DIC.

Layer-by-Layer Assembly of CeO2-x@C-rGO Nanocomposites and CNTs as a Multifunctional Separator Coating for Highly Stable Lithium-Sulfur Batteries.

Commercialization of high-energy Li-S batteries is greatly restricted by their unsatisfactory cycle retention and poor cycling life originated from the notorious "shuttling effect" of lithium polysulfides. Modification of a commercial separator with a functional coating layer is a facile and efficient strategy beyond nanostructured composite cathodes for suppressing polysulfide shuttling. Herein, a multilayered functional CeO2-x@C-rGO/CNT separator was successfully achieved by alternately depositing conductive carbon nanotubes (CNTs) and synthetic CeO2-x@C-rGO onto the surface of the commercial separator. The cooperation of multiple components including Ce-MOF-derived CeO2-x@C, rGO, and CNTs enables the as-built CeO2-x@C-rGO/CNT separator to perform multifunctions from the separator surface: (i) to hinder the diffusion of polysulfide species through physical blocking or chemical adsorption, (ii) to accelerate the sluggish redox reactions of sulfur species, and (iii) to enhance the conductivity for sulfur re-activation and efficient utilization. Serving as a multilayer and powerful barrier, the CeO2-x@C-rGO/CNT separator greatly constrains and reutilizes the polysulfide species. Thus, the Li-S battery assembled with the CeO2-x@C-rGO/CNT separator demonstrates an excellent combination of capacity, rate capability, and cycling performances (an initial capacity of 1107 mA h g-1 with a low decay rate of 0.060% per cycle over 500 cycles at 1 C, 651 mA h g-1 at 5 C) together with remarkably mitigated self-discharge and anode corrosion. This work provides guidelines for functional separator design as well as rare-earth material applications for Li-S batteries and other energy storage systems.

High-yielding preparation of hierarchically branched carbon nanotubes derived from zeolitic imidazolate frameworks for enhanced electrochemical K+ storage.

Branched carbon nanotubes are regarded as very promising anode materials of K-ion batteries, while the high-yielding preparation still remains challenging. We here demonstrate a facile approach for synthesizing N-doped branched carbon nanotubes (br-CNTs) in macroscopic quantity, via one-step carbonization of ZnCo-containing zeolitic imidazolate framework (ZnCo-ZIF) nanotubes. At a high current density of 2 A g-1, the as-synthesized br-CNTs could exhibit 147.2 mA h g-1 specific capacity and retain 84.5% of the initial value after 1300 cycles for electrochemical K+ storage, which is better than commercial carbon nanotubes and other carbon counterparts derived from ZnCo-ZIF particles and ZnCo-BTC nanowires. The excellent K+ storage performance of ZnCo-ZIF-derived br-CNTs actually results from the unique branched architecture and N doping, by taking advantage of more active sites and desired electrochemical kinetics as well as structural integrity. Our proposed approach would give a significant example for the scalable preparation of other complex nanostructures, and the prepared br-CNT is expected to be a very competitive candidate for high-efficiency electrochemical K+ storage.