Atomic-Resolution Electron Microscopy Unravelling the Role of Unusual Asymmetric Twin Boundaries in the Electron-Beam-Sensitive NASICON-Type Solid Electrolyte.

An atomic-scale understanding of the role of nonperiodic features is essential to the rational design of highly Li-ion-conductive solid electrolytes. Unfortunately, most solid electrolytes are easily damaged by the intense electron beam needed for atomic-resolution electron microscopy observation, so the reported in-depth atomic-scale studies are limited to Li0.33La0.56TiO3- and Li7La3Zr2O12-based materials. Here, we observe on an atomic scale a third type of solid electrolyte, Li1.3Al0.3Ti1.7(PO4)3 (LATP), through minimization of damage induced by specimen preparation. With this capability, LATP is found to contain large amounts of twin boundaries with an unusual asymmetric atomic configuration. On the basis of the experimentally determined structure, the theoretical calculations suggest that such asymmetric twin boundaries may considerably promote Li-ion transport. This discovery identifies a new entry point for optimizing ionic conductivity, and the method presented here will also greatly benefit the mechanistic study of solid electrolytes.

Comparative efficacy and pharmacological mechanism of Chinese patent medicines against anthracycline-induced cardiotoxicity: An integrated study of network meta-analysis and network pharmacology approach.

Background: This study aimed to evaluate the efficacy of Chinese patent medicines (CPMs) combined with dexrazoxane (DEX) against anthracycline-induced cardiotoxicity (AIC) and further explore their pharmacological mechanism by integrating the network meta-analysis (NMA) and network pharmacology approach. Methods: We searched for clinical trials on the efficacy of DEX + CPMs for AIC until March 10, 2023 (Database: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, China Science and Technology Journal and China Online Journals). The evaluating outcomes were cardiac troponin I (cTnI) level, creatine kinase MB (CK-MB) level, left ventricular ejection fraction (LVEF) value, and electrocardiogram (ECG) abnormal rate. Subsequently, the results of NMA were further analyzed in combination with network pharmacology. Results: We included 14 randomized controlled trials (RCTs) and 1 retrospective cohort study (n = 1,214), containing six CPMs: Wenxinkeli (WXKL), Cinobufotalin injection (CI), Shenqifuzheng injection (SQFZ), Shenmai injection (SM), Astragalus injection (AI) and AI + CI. The NMA was implemented in Stata (16.0) using the mvmeta package. Compared with using DEX only, DEX + SM displayed the best effective for lowering cTnI level (MD = -0.44, 95%CI [-0.56, -0.33], SUCRA 93.4%) and improving LVEF value (MD = 14.64, 95%CI [9.36, 19.91], SUCRA 98.4%). DEX + SQFZ showed the most effectiveness for lowering CK-MB level (MD = -11.57, 95%CI [-15.79, -7.35], SUCRA 97.3%). And DEX + AI + CI has the highest effectiveness for alleviating ECG abnormalities (MD = -2.51, 95%CI [-4.06, -0.96], SUCRA 96.8%). So that we recommended SM + DEX, SQFZ + DEX, and DEX + AI + CI as the top three effective interventions against AIC. Then, we explored their pharmacological mechanism respectively. The CPMs' active components and AIC-related targets were screened to construct the component-target network. The potential pathways related to CPMs against AIC were determined by KEGG. For SM, we identified 118 co-targeted genes of active components and AIC, which were significantly enriched in pathways of cancer pathways, EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications. For SQFZ, 41 co-targeted genes involving pathways of microRNAs in cancer, Rap1 signaling pathway, MAPK signaling pathway, and lipid and atherosclerosis. As for AI + CI, 224 co-targeted genes were obtained, and KEGG analysis showed that the calcium signaling pathway plays an important role except for the consistent pathways of SM and SQFZ in anti-AIC. Conclusions: DEX + CPMs might be positive efficacious interventions from which patients with AIC will derive benefits. DEX + SM, DEX + SQFZ, and DEX + AI + CI might be the preferred intervention for improving LVEF value, CK-MB level, and ECG abnormalities, respectively. And these CPMs play different advantages in alleviating AIC by targeting multiple biological processes.

A bibliometric analysis of global trends in the research field of pharmaceutical care over the past 20 years.

Pharmaceutical care is essential in building up the basics of public health and clinical care. A comprehensive understanding of global status in the field of pharmaceutical care is necessary for directing its research frontiers and future trends. Therefore, this study aims to make a bibliometric analysis to track the development of pharmaceutical care research worldwide during the past two decades. The publications regarding pharmaceutical care were culled from the Web of Science Core Collection (WoSCC). Countries, institutions, authors, journals, references, and keywords in this field were visually analyzed by using VOSviewer (version 1.6.17) and CiteSpace (Version 5.8.R3). As a result, 3,597 publications (3,177 articles and 420 reviews) were obtained. The annual yields grew more than three times in the past two decades, from 54 records in 2002 to 379 papers in 2021. The United States played the leading role in this research from multiple aspects, including publication (n = 1,208), citations (n = 28,759), funding agencies, and collaboration worldwide. The University of Sydney in Australia was the most contributed institution with the greatest number of publications (n = 112) in pharmaceutical care research. Hersberger KE from the University of Basel was the most productive author (n = 40). Chen TF from the University of Sydney was the author who owed the highest H-index of 19 and most citations (n = 1,501). They both significantly impacted this field. American Journal of Health System Pharmacy produced the most publications, while Pharmacotherapy had the highest IF (IF2020 = 4.705) in this field. Clusters networks of co-cited references and keywords suggested that clinical pharmacy is an essential theme in pharmaceutical care. Terms of medication safety and critical care recognized by burst analysis of keywords also hint at the recent attention on clinical pharmacy. The present bibliometrics analysis may provide a comprehensive overview and valuable reference for future researchers and practitioners in the research field of pharmaceutical care.

Current Status and Trends of Research on Anthracycline-Induced Cardiotoxicity from 2002 to 2021: A Twenty-Year Bibliometric and Visualization Analysis.

Anthracyclines constitute the cornerstone of numerous chemotherapy regimens for various cancers. However, the clinical application of anthracyclines is significantly limited to their dose-dependent cardiotoxicity. A comprehensive understanding of the current status of anthracycline-induced cardiotoxicity is necessary for in-depth research and optimal clinical protocols. Bibliometric analysis is widely applied in depicting development trends and tracking frontiers of a specific field. The present study is aimed at revealing the status and trends of anthracycline-induced cardiotoxicity during the past two decades by employing bibliometric software including R-bibliometric, VOSviewer, and CiteSpace. A total of 3504 publications concerning anthracycline-induced cardiotoxicity from 2002 to 2021 were collected from the Web of Science Core Collection database. Results showed significant growth in annual yields from 90 records in 2002 to 304 papers in 2021. The United States was the most productive country with the strongest collaboration worldwide in the field. Charles University in the Czech Republic was the institution that contributed the most papers, while 7 of the top 10 productive institutions were from the United States. The United States Department of Health and Human Services and the National Institutes of Health are the two agencies that provide financial support for more than 50% of sponsored publications. The research categories of included publications mainly belong to Oncology and Cardiac Cardiovascular Systems. The Journal of Clinical Oncology had a comprehensive impact on this research field with the highest IF value and many publications. Simunek Tomas from Charles University contributed the most publications, while Lipshultz Steven E. from the State University of New York possessed the highest H-index. In addition, the future research frontiers of anthracycline-induced cardiotoxicity might include early detection, pharmacogenomics, molecular mechanism, and cardiooncology. The present bibliometric analysis may provide a valuable reference for researchers and practitioners in future research directions.

Coordination modulation of iridium single-atom catalyst maximizing water oxidation activity.

Single-atom catalysts (SACs) have attracted tremendous research interests in various energy-related fields because of their high activity, selectivity and 100% atom utilization. However, it is still a challenge to enhance the intrinsic and specific activity of SACs. Herein, we present an approach to fabricate a high surface distribution density of iridium (Ir) SAC on nickel-iron sulfide nanosheet arrays substrate (Ir1/NFS), which delivers a high water oxidation activity. The Ir1/NFS catalyst offers a low overpotential of ~170 mV at a current density of 10 mA cm-2 and a high turnover frequency of 9.85 s-1 at an overpotential of 300 mV in 1.0 M KOH solution. At the same time, the Ir1/NFS catalyst exhibits a high stability performance, reaching a lifespan up to 350 hours at a current density of 100 mA cm-2. First-principles calculations reveal that the electronic structures of Ir atoms are significantly regulated by the sulfide substrate, endowing an energetically favorable reaction pathway. This work represents a promising strategy to fabricate high surface distribution density single-atom catalysts with high activity and durability for electrochemical water splitting.

Proteomics and metabolomics analyses reveal the full spectrum of inflammatory and lipid metabolic abnormalities in dyslipidemia.

Dyslipidemia is a common, chronic metabolic disease associated with cardiovascular complications. Due to the multiplicity of etiological factors, the pathogenesis of dyslipidemia is still unclear. In this study, we combined proteomics and metabolomics methods to analyze the plasma of patients with dyslipidemia and healthy subjects. isobaric tags for relative and absolute quantification (iTRAQ) markers, combined with LC-MS/MS proteomics technology and the UHPLC/Orbitfast-X Tribrid system, were used to establish the metabolite profile in clinical dyslipidemia. A total of 137 differentially expressed proteins, mainly related to biological processes such as protein activation cascades, adaptive immune responses, complement activation, acute inflammatory responses, and regulation of acute inflammatory responses, were identified. These proteins are involved in the regulation of important metabolic pathways, such as immunity and inflammation, coagulation and hemostasis, lipid metabolism, and oxidation and antioxidant defenses. The analysis of clinical metabolites showed there were 69 different metabolites in plasma, mainly related to glycerolipid, sphingolipid, porphyrin, α-linolenic acid, linoleic acid, and arachidonic acid metabolism, suggesting that the regulation of inflammation and lipid metabolism may be disturbed in patients with dyslipidemia. Among these, significant changes were observed in indole-3-propionic acid (IPA), which is considered as a potential biomarker of dyslipidemia. The combined analysis of proteins and metabolites showed that arachidonic acid, linoleic acid, and lipid metabolic pathways were closely related to dyslipidemia. IPA may be a potential biomarker. The information provided in this study may provide new insights into the pathogenesis of animal models of dyslipidemia and related disease models, as well as potential intervention targets.

Investigation and identification of the multiple components of Rheum officinale Baill. using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry and data mining strategy.

Rheum officinale Baill. is a traditional Chinese medicine that has long been used for eliminating body heat, cooling and detoxifying blood, removing blood stasis and promoting menstruation, and clearing away heat-dampness to eliminate jaundice. Comprehensive and systematic structural identification of the components of Rheum officinale Baill. remains a challenge. An appropriate analytical method needs to be established for the comprehensive investigation and identification of the chemical constituents in Rheum officinale Baill. extract. In this study, a new systematic approach using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry in conjunction with a data mining strategy was developed to screen the targeted and nontargeted components of Rheum officinale Baill. A total of 124 compounds were identified in the Rheum officinale Baill. extract including 31 acylglucosides, 9 phenolic acids, 26 tannins, 53 anthraquinones, and 5 other compounds. Note that 55 of these compounds were reported for the first time here. In conclusion, in this study, we devised an efficient and systematic method for detecting complex compounds and have used it here to provide a foundation for future research into bioactive ingredients and quality control of Rheum officinale Baill. extract.

PL-S2, a homogeneous polysaccharide from Radix Puerariae lobatae, attenuates hyperlipidemia via farnesoid X receptor (FXR) pathway-modulated bile acid metabolism.

Polysaccharides are important active constituents of Radix Puerariae lobatae (RPL). In this study, a novel homogeneous polysaccharide from RPL was successfully obtained by HP-20 macroporous resin and purified by Sepharose G-100 column chromatography. Nuclear magnetic resonance (NMR) analysis showed that the main glycosidic bonds were composed of α-1,3-linked and α-1,4-linked glucose. The molecular weight of PL-S2 was 18.73 kDa. The hypolipidemic effect of PL-S2 on hyperlipidemic rats was evaluated in histopathology and metabolomics analyses. PL-S2 significantly reduced plasma lipid levels and inhibited bile acid metabolism. We also demonstrated that treatment with PL-S2 activated FXR, CYP7A1, BESP, and MRP2 in rat liver. Our findings first indicate that PL-S2 decreases plasma lipid levels in hyperlipidemic rats by activating the FXR signaling pathway and promoting bile acid excretion. Therefore, PL-S2 derived from RPL is implicated as a functional food factor with lipid-regulating activity, and highlighted as a potential food supplement for the treatment of hyperlipidemia.

Metabolomics and 16S rRNA Gene Sequencing Analyses of Changes in the Intestinal Flora and Biomarkers Induced by Gastrodia-Uncaria Treatment in a Rat Model of Chronic Migraine.

Accumulating evidence suggests that natural medicines have notable curative effects on neurological conditions, such as migraine, that are mediated by regulating the gut microbial flora. A natural medicine pair used in traditional Chinese medicine, Gastrodia elata Blume and Uncaria rhynchophylla (Miq.) Miq. ex Havil. (GU), have shown excellent effect in treating migraine, yet the role of gut microbes in the therapeutic effect of GU in chronic migraine (CMG) is unknown. Here, we performed a 16S rRNA gene sequencing and metabolomics study of the effects of GU in a nitroglycerin (NTG)-induced rat model of CMG. Our results showed that the gut microbial community structure changed significantly and was similar to that of control rats after GU administration in CMG rats. Specifically, GU increased the relative abundance of Bacteroides and Coprococcus and reduced the abundance of Prevotella_1 and Escherichia-Shigella in CMG rats. The metabolomics profiles of the plasma and ileum contents of CMG rats obtained with an ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) revealed similar biomarkers in both samples, and GU treatment reduced 3-indoxyl sulfate, glutamic acid, L-tyrosine, and L-arginine levels, and increased 5-HIAA, L-tryptophan, and linoleic acid levels in plasma. Correlation analysis showed that the affected bacteria were closely related to amino acid metabolism. Most importantly, GU treatment hardly affected biomarkers in feces samples after inhibiting the activity of gut microbes. Collectively, these findings indicate that structural changes in gut flora are closely related to host metabolism and that regulating the gut microbial community structure and function may be one of the important mechanisms underlying the therapeutic effects of GU in migraine.