Extraction, purification, characteristics, bioactivities, prospects, and toxicity of Lilium spp. polysaccharides.

The genus Lilium has been widely used worldwide as a food and medicinal ingredient in East Asia for over 2000 years due to its higher nutritional and medicinal value. Polysaccharide is the most important bioactive ingredient in Lilium spp. and has various health benefits. Recently, Lilium spp. polysaccharides (LSPs) have attracted significant attention from industries and researchers due to their various biological properties, such as antioxidant, immunomodulatory, antitumor, antibacterial, hypoglycaemic, and anti-radiation. However, the development and utilization of LSP-based functional biomaterials and medicines are limited by a lack of comprehensive understanding regarding the structure-activity relationships (SARs), industrial applications, and safety of LSPs. This review provides an inclusive overview of the extraction, purification, structural features, bioactivities, and mechanisms of LSPs. SARs, applications, toxicities, and influences of structural modifications on bioactivities are also highlighted, and the potential development and future study direction are scrutinized. This article aims to offer a complete understanding of LSPs and provide a foundation for further research and application of LSPs as therapeutic agents and multifunctional biomaterials.

Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION: DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

Five Gram-stain-positive, aerobic, non-motile actinobacterial strains designated as CPCC 205763T, CPCC 203386T, CPCC 205716T, CPCC 203406T, and CPCC 203407 were obtained from different ecosystems associated with four kinds of Chinese traditional medicinal plants. The 16S rRNA gene sequences of these five strains showed closely related to members of the genus Herbiconiux of the family Microbacteriaceae, with the highest similarities of 97.4-99.7% to the four validly named species of Herbiconiux. In the phylogenetic trees based on 16S rRNA gene sequences and the core genome, these isolates clustered into the clade of the genus Herbiconiux within the lineage of the family Microbacteriaceae. The overall genome relatedness indexes (values of ANI and dDDH) and the phenotypic properties (morphological, physiological and chemotaxonomic characteristics) of these isolates, readily supported to affiliate them to the genus Herbiconiux, representing four novel species, with the isolates CPCC 203406T and CPCC 203407 being classified in the same species. For which the names Herbiconiux aconitum sp. nov. (type strain CPCC 205763T = I19A-01430T = CGMCC 1.60067T), Herbiconiux daphne sp. nov. (type strain CPCC 203386T = I10A-01569T = DSM 24546T = KCTC 19839T), Herbiconiux gentiana sp. nov. (type strain CPCC 205716T = I21A-01427T = CGMCC 1.60064T), and Herbiconiux oxytropis sp. nov. (type strain CPCC 203406T = I10A-02268T = DSM 24549T = KCTC 19840T) were proposed, respectively. In the genomes of these five strains, the putative encoding genes for amidase, endoglucanase, phosphatase, and superoxidative dismutase were retrieved, which were classified as biosynthetic genes/gene-clusters regarding plant growth-promotion (PGP) functions. The positive results from IAA-producing, cellulose-degrading and anti-oxidation experiments further approved their potential PGP bio-functions. Pangenome analysis of the genus Herbiconiux supported the polyphasic taxonomy results and confirmed their bio-function potential.

Corrigendum: Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

[This corrects the article DOI: 10.3389/fmicb.2023.1119226.].

A Novel Method for Quality Evaluation of Gardeniae fructus Praeparatus during Heat Processing Based on Sensory Characteristics and Chemical Compositions.

The intrinsic chemical components and sensory characteristics of Gardeniae fructus Praeparatus (GFP) directly reflect its quality and subsequently, affect its clinical curative effect. However, there is little research on the correlation between the appearance traits and chemical compositions of GFP during heat processing. In this study, the major components of five typical processed decoction pieces of GFP were determined. With the deepening of processing, the contents of geniposidic acid and 5-HMF gradually increased, while the contents of deacetyl-asperulosidic acid methyl ester, gardenoside, and two pigments declined. Moreover, the electronic eye, electronic tongue, and electronic nose were applied to quantify GFP's sensory properties. It was found that the chroma values showed a downward trend during the processing of GFP. The results of odor showed that ammonia, alkenes, hydrogen, and aromatic compounds were the material base for aroma characteristics. Complex bitterness in GF was more obvious than that in other GFP processed products. Furthermore, one mathematical model was established to evaluate the correlation between the sensory characteristics and chemical composition of GFP during five different stages. A cluster analysis and neural network analysis contributed to recognizing the processing stage of GFP. This study provided an alternative method for the exterior and interior correlation-based quality evaluation of herbs.

[Specification and solution of the normative elements in the development of the national standard: "Pure moxa stick"].

This paper introduced the research ideas and methods for the development of the national standard, "Pure moxa stick". According to the orientation of product standard and related documents, on the basis of extensive investigation and in consultation with manufacturers and experts, the problems encountered in this standard development were solved. The general technical requirements were specified in association with the basic experimental data. The technical requirements should not only conform to the current technological status of moxa sticks production, but also present a certain of innovation. The innovation of this standard lies in the concepts of the ratio of leaves to floss, the ratio of whole plant to floss, density, etc. Besides, the main technical requirements of "Pure moxa stick" have been specified, i.e. material, shape and structure, combustion characteristics, physical and chemical characteristics. The development of national standard "Pure moxa stick" contributes to the favorable exploration and practice of the standardization of traditional Chinese medicine and provides the effective reference for the further stan-dardization of acupuncture and moxibustion.

[Consideration on development of the national standard: Pure Moxa Stick].

The paper gives a consideration on the development of the national standard, Pure Moxa Stick. It is proposed that the principle and requirements for the development of product standard should be adhered to, while focusing on the applicability and safety of pure moxa stick. In terms of quality, the specific requirements should be developed on the ratio of moxa floss, wrapping paper and adhesives. Regarding the specifications, either the market demands or the resource waste prevention should be considered. In safety, the combustion temperature and moxa smoke control are the key issues.

Shenmai Injection Alleviates Acute Lung Injury in a Severe Acute Pancreatitis Rat Model via Heme Oxygenase-1 Upregulation.

BACKGROUND: One of the serious complications of severe acute pancreatitis (SAP) is acute lung injury (ALI). Suppressing inflammation is a feasible treatment strategy for SAP-induced ALI. Shenmai injection (SMI), which is a Traditional Chinese Medicine (TCM treatment, can suppress inflammation. Therefore, this study used an established SAP rat model to determine the effect of SMI on ALI induced by SAP. METHODS: A total of 40 male Sprague-Dawley (SD) rats were assigned to one of four groups: the SAP group, the sham surgery (SS) group, the SAP + SMI group and the SAP + SMI + zinc protoporphyrin (ZnPP) group. Rats in the SAP group were intravenously injected with 1.6 ml/kg saline 30 minutes after induction of SAP models, rats in the SAP + SMI group were intravenously injected with 1.6 ml/kg SMI, while rats in the SAP + SMI + ZnPP group were intravenously injected with 1.6 ml/kg SMI and 30 mg/kg ZnPP via intraperitoneal injection. The rates were sacrificed 24 hours after SAP induction. Excised lung tissues were histologically examined, protein concentration in bronchoalveolar lavage fluid (BALF) was measured and lung wet-to-dry (W/D) weight ratio was calculated. The protein and mRNA levels of tumor necrosis factor (TNF)-α, heme oxygenase (HO)-1 and interleukin (IL)-10 in blood and tissue samples were measured. RESULTS: SMI treatment attenuated SAP-induced ALI as evidenced by lower lung damage scores compared with the untreated SAP group (P < .05). SMI also abolished the SAP-induced rise in BALF and W/D ratio protein concentrations (P < .05). Moreover, SMI treatment increased HO-1 and IL-10 levels but decreased TNF-α levels in serum and tissue samples (P < .05). However, inhibition of HO-1 expression by ZnPP led to significant inhibition of all the changes. CONCLUSION: SMI can alleviate SAP-induced ALI through HO-1 upregulation.

[Pioneering a great undertaking, glorifying acupuncture worldwide: brief on WANG Xue-tai's academic thought].

WANG Xue-tai is a famous scholar of acupuncture-moxibustion of TCM, one of the founders of Institute of Acupuncture and Moxibusiton, China Academy of Chinese Medical Sciences, the director of the second-term leadership of Institute, as well as the representative inheritor of "acupuncture" in the national intangible cultural heritage project. The academic and administrative achievement of professor WANG Xue-tai has been systematically reviewed in this paper. His academic thought and contributions are summarized as: clarifying the source of acupuncture-moxibustion development and laying the foundation of academic history research of acupuncture-moxibustion; emphasizing moxibustion techniques and promoting new acupuncture techniques; maintaining the characteristics of acupuncture-moxibustion to improve clinical therapeutic effect; advocating the standardization of acupuncture-moxibustion to promote its internationalization; and insisting on inheritance and innovation to enhance the modernization of acupuncture-moxibusiton of TCM.

Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation.

BACKGROUND: Atherosclerosis is a progressive chronic disease characterised by aberrant lipid metabolism and a maladaptive inflammatory response. As atherosclerosis-driven cardiovascular disease remains the major cause of morbidity and mortality worldwide, more effective clinical therapies are urgently needed. Traditional Chinese Medicine (TCM) has demonstrated efficacy against atherosclerosis, with Qing-Xue-Xiao-Zhi formula (QXXZF) having been approved for clinical treatment of patients with atherosclerosis. However, the mechanisms underlying the anti-atherosclerotic activity of QXXZF remain unknown. PURPOSE: To investigate the anti-atherosclerotic effect of QXXZF and reveal its mechanisms using preclinical models. METHODS: In vivo, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-choline diet (HHD) to induce atherosclerosis. Serum metabolomic profiling was used to identify the concentration of trimethylamine N-oxide (TMAO) in mice. In vitro, RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) from WT and TLR4-/- C57BL/6 mice were used to explore the effects of QXXZF on macrophages. After confirming the therapeutic effects of QXXZF, mass spectrometry and network pharmacology analyses were used to predict and investigate the main components and the anti-atherogenic mechanisms of QXXZF in the context of atherosclerosis. RESULTS: Our results showed QXXZF significantly suppressed the development of atherosclerosis, as evidenced by the decreased atherosclerotic plaques in the aorta and aortic root, reduced plasma lipid levels and decreased serum TMAO content in HHD-fed ApoE-/- mice. Meanwhile, QXXZF effectively reduced foam cell formation in oxidized low-density lipoprotein (ox-LDL) and TMAO-stimulated RAW264.7 macrophages and BMDMs. Moreover, QXXZF facilitated reverse cholesterol transport (RCT) in macrophages by upregulating the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1. Mechanistic studies revealed that QXXZF influenced cholesterol metabolism by inhibiting the TLR4-mediated nuclear factor kappa B (NF-κB) axis. Importantly, TLR4 knockout abolished the influence of QXXZF on macrophages. CONCLUSION: QXXZF promotes lipid efflux and inhibits macrophage-mediated inflammation, producing a therapeutic effect against atherosclerosis. Our study provides new insight into the mechanism of QXXZF against atherosclerosis.

[Sample size estimation in acupuncture and moxibustion clinical trials].

The appropriate sample size estimation is very important in the design of clinical trials. However, insufficient or inappropriate sample size estimation is still a prominent problem in the currently published acupuncture and moxibustion clinical trials. At present, the superiority test, non-inferiority test and equivalence test have been widely used in acupuncture and moxibustion clinical trials. This article focuses on the application, calculation methods and PASS11 software using of these three hypothesis test types. In view of the problems in the estimation of sample size in acupuncture and moxibustion clinical trials, the particularity of sample size estimation in acupuncture and moxibustion is summarized from the aspects of parameter setting, ratio of intervention group and control group, and multi-group comparison, in order to guide acupuncture clinical researchers to correctly estimate sample size when conducting clinical trials.

[Thinking on the development direction of acupuncture-moxibustion science from the study of genres of acupuncture and moxibustion].

The paper introduces the general situation on academic school of acupuncture and moxibustion in ancient China, the status of the modern genres of acupuncture and moxibustion, as well as the existing problems in the relevant studies. It is pointed out that "academic school" and "genre" should be distinguished each other in terms of modern context. The former should refer to the school of academic theory, while the latter should be the school of clinical treatment technology. It would be best to classify the modern academic school of acupuncture and moxibustion based on the therapeutic techniques with specific characteristics for the outline, focusing on the study of the academic thought of each genre. Modern genres of acupuncture and moxibustion should be more inclusive and open, "encouraging the unique academic views", rather than "restricting access to inheritance". The development of modern genres of acupuncture and moxibustion is an important driving force for the development of acupuncture-moxibustion discipline and it is ought to contribute to the reconstruction of medical theory of acupuncture and moxibustion.

Liangxue Jiedu Formula Improves Psoriasis and Dyslipidemia Comorbidity via PI3K/Akt/mTOR Pathway.

The pathological mechanism of psoriasis and dyslipidemia comorbidity is unclear, and there are few reports on therapy. By establishing an animal model of ApoE-/- mice induced by imiquimod (IMQ), we explored the effects of Liangxue Jiedu formula (LXJDF), a traditional Chinese herb medicine, on psoriasis and dyslipidemia comorbidity through PI3K/Akt/mTOR pathway. The experiment was divided into a control group, a model group, an LXJDF high-dose group, an LXJDF low-dose group, and a positive drug (atorvastatin) group. Each group of mice was given continuous oral administration once a day. After 3 weeks, the mice dorsal skins were smeared with 62.5 mg of 5% IMQ cream for five consecutive days and continued to be given the corresponding drugs. We observed the effects of LXJDF on skin lesion changes, PASI score, pathological characteristics, blood lipid levels (TC, TG, LDL, HDL, and oxLDL), liver pathology, inflammatory factors in the skin, and the protein expression of PI3K/Akt/mTOR pathway in both the skin and liver. The results showed that LXJDF could significantly improve the psoriasiform skin lesions of IMQ-induced ApoE-/- mice, including the reduction of PASI, thinning of epidermal thickness, inhibition of hyperkeratosis and parakeratosis, and inflammatory infiltration in the dermis, and reduce lipid accumulation in the epidermal. LXJDF could regulate blood lipid levels, reduce liver inflammation, and protect the liver. LXJDF could significantly decrease the gene expressions of inflammatory factors IL-17A, IL-23, IL-6, and TNF-α in the skin. LXJDF showed specific inhibition of PI3K, Akt, mTOR protein, and its phosphorylation expressions. In conclusion, LXJDF exerts an intervention effect on psoriasis and dyslipidemia comorbidity via PI3K/Akt/mTOR and its phosphorylation pathway.

Shen-Yuan-Dan Capsule Attenuates Verapamil-Induced Zebrafish Heart Failure and Exerts Antiapoptotic and Anti-Inflammatory Effects via Reactive Oxygen Species-Induced NF-κB Pathway.

Background: Heart failure (HF) is the end stage of ischemic cardiovascular diseases; nonetheless, safe and effective therapeutic agents for HF are still lacking, and their discovery remains challenging. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a hospital preparation of traditional Chinese herbal, effectively protected ischemic injury in cardiovascular diseases. However, its therapeutic effects and possible mechanisms on HF remain unclear. Methods: A zebrafish HF model treated with verapamil was developed to assess the therapeutic effect of SYDC on HF zebrafish. Zebrafish were administered with SYDC and digoxin (positive control) by direct soaking. After drug treatment, zebrafish were randomly assigned to the visual observation and image acquisition using a Zebralab Blood Flow System. The reactive oxygen species (ROS), MDA, and SOD levels were determined by fluorescence signal detection, TBA, and WST-8 methods. RT-PCR determined the mRNA expressions of Caspase-3, Caspase-1, Bcl-2, Bax, IL-1ß, NF-κB, and TNF-α. Results: SYDC significantly inhibited the levels of heart dilatation and venous congestion and markedly increased the levels of cardiac output, blood flow dynamics, and heart rates in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Moreover, SYDC also significantly decreased the levels of MDA and ROS and increased the level of SOD in HF zebrafish. The RT-PCR results revealed that SYDC decreased the expression of Caspase-1, Caspase-3, Bax, IL-1ß, NF-κB, and TNF-α but increased the expression of Bcl-2 in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Conclusions: SYDC improved the heart function in verapamil-induced HF zebrafish and alleviated inflammation and apoptosis by inhibiting the ROS-mediated NF-κB pathway.

[Study advance of depressive animal models and its application in traditional Chinese medicines].

Depression is a kind of mental disease with main symptoms of low mood and lack of pleasure, which seriously endangers human health. An appropriate depressive animal model is of great significance for the study of depression and new antidepressant drugs, while the suitable selection and matching of experimental animals, modeling methods and evaluation indexes are critical to eva-luate the scientificity and effectiveness of the depressive animal model. The study advance of depressive animal models in the aspects of experimental animal selection, modeling principle and method, characteristics, evaluation indexes and their application in traditional Chinese medicine are summarized through the systematic review of relevant literatures in PubMed, CNKI and other databases. The depressive animal modeling methods utilized in recent studies include stress, glucocorticoid induction, reserpine induction, lipopolysaccharide induction, surgical modeling, gene knockout, joint application modeling methods. Stress method is better to simulate the depressive symptoms of clinical patients, whereas there are some deficiencies, such as long modeling time and large cost. The depressive animal models induced by glucocorticoid, reserpine and lipopolysaccharide have the advantages of short modeling time and good controllability, but with a poor reliability. The pathogenesis of surgical modeling is highly matched with that of clinical depressive patients, whereas it has the defect of long postoperative recovery period. Gene knockout models can be used to study the precise role of specific genes in depression. However, its applicability may be restricted in studies on depression. The joint application modeling method can improve its reliability and accuracy, and attracts more and more attention. This paper provides a reference for the selection of animal models in future studies of pathological mechanism of depression, and screening and evaluation of antidepressant drugs.

The Effect of Shen-Yuan-Dan Capsule on Autophagy-Related Gene Atg13 Promoter Methylation and Genomic Methylation Levels in Atherosclerotic Mice.

BACKGROUND: Moderate autophagy plays a positive role in the prevention of atherosclerosis. Aberrant promoter methylation of autophagic genes can affect autophagy. Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, can prevent atherosclerosis in high-fat-fed mice. However, its precise mechanism remains unclear. This study investigated the mechanism of SYDC in ameliorating atherosclerosis in a mice model. METHODS: After 6 weeks of a high-fat diet, apolipoprotein E knockout (apoE-/-) mice were randomly grouped into control, Lipitor, and SYDC groups (n = 10). The mice were intragastrically administered with the respective drugs for 6 weeks. The expressions of Beclin1 and Atg5-Atg12 complex in atherosclerotic plaques of the mice were measured. The levels of 5-mC and DNA methyltransferase 1 (DNMT1) in the plasma of the mice were determined. The average methylation rate of CpG islands in the promoter region of autophagy-related protein (Atg13) and the mRNA expression of Atg13 in the aortas of the mice were determined. RESULTS: SYDC up-regulated the expressions of Atg5-Atg12 complex and Beclin-1 in atherosclerotic plaques (p < 0.01). Moreover, SYDC decreased the 5-mC and DNMT1 levels in plasma and atherosclerotic plaques of the mice (p < 0.01), and also decreased the average methylation rate of CpG islands in the promoter region of Atg13 and increased the mRNA levels of Atg13 in the aortas of atherosclerotic mice (p < 0.01). CONCLUSIONS: SYDC attenuates atherosclerosis by promoting autophagy, probably through regulating genomic DNA methylation and Atg13 promoter demethylation.

Understanding of guidance for acupuncture and moxibustion interventions on COVID-19 (Second edition) issued by CAAM.

At present, the situation of global fight against COVID-19 is serious. WHO (World Health Organization)-China Joint Mission fully confirms the success of "China's model" against COVID-19 in the report. In fact, one particular power in "China's model" is acupuncture and moxibustion of traditional Chinese medicine. To better apply "non-pharmaceutic measures"-the external technique of traditional Chinese medicine, in the article, the main content of Guidance for acupuncture and moxibustion interventions on COVID-19 (Second edition) issued by China Association of Acupuncture-Moxibution is introduced and the discussion is stressed on the selection of moxibustion device and the duration of its exertion.

Danhong Injection Alleviates Cardiac Fibrosis via Preventing the Hypermethylation of Rasal1 and Rassf1 in TAC Mice.

BACKGROUND/AIM: Danhong injection (DHI) is a Chinese patent drug used for relieving cardiovascular diseases. Recent studies have suggested that DNA methylation plays a pivotal role in the maintenance of cardiac fibrosis (CF) in cardiovascular diseases. This study was aimed at identifying the effect and the underlying mechanism of DHI on CF, especially the DNA methylation. METHODS: A CF murine model was established by thoracic aortic constriction (TAC). A 28-day daily treatment with or without DHI via intraperitoneal injection was carried out immediately following TAC surgery. The changes in cardiac function, pathology, and fibrosis following TAC were measured by echocardiography and immunostaining. We used methyl-seq analysis to assess the DNA methylation changes in whole genes and identified the methylation changes of two Ras signaling-related genes in TAC mice, including Ras protein activator like-1 (Rasal1) and Ras-association domain family 1 (Rassf1). Next, the methylation status and expression levels of Rasal1 and Rassf1 genes were consolidated by bisulfite sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting, respectively. To determine the underlying molecular mechanism, the expressions of DNA methyltransferases (DNMTs), Tet methylcytosine dioxygenase 3 (TET3), fibrosis-related genes, and the activity of Ras/ERK were measured by RT-qPCR and Western blotting. RESULTS: DHI treatment alleviated CF and significantly improved cardiac function on day 28 of TAC. The methyl-seq analysis identified 42,606 differential methylated sites (DMSs), including 19,618 hypermethylated DMSs and 22,988 hypomethylated DMSs between TAC and sham-operated mice. The enrichment analysis of these DMSs suggested that the methylated regulation of Ras signal transduction and focal adhesion-related genes would be involved in the TAC-induced CF development. The results of bisulfite sequencing revealed that the TAC-induced methylation affected the CpG site in both of Rasal1 and Rassf1 genes, and DHI treatment remarkably downregulated the promoter methylation of Rasal1 and Rassf1 in CF hearts. Furthermore, DHI treatment upregulated the expressions of Rasal1 and Rassf1, inhibited the hyperactivity of Ras/ERK, and decreased the expressions of fibrosis-related genes. Notably, we found that DHI treatment markedly downregulated the expression of DNMT3B in CF hearts, while it did not affect the expressions of DNMT1, DNMT3A, and TET3. CONCLUSION: Aberrant DNA methylation of Rasal1 and Rassf1 genes was involved in the CF development. DHI treatment alleviated CF, prevented the hypermethylation of Rasal1 and Rassf1, and downregulated DNMT3B expression in CF hearts.

All Two-Dimensional Pseudocapacitive Sheet Materials for Flexible Asymmetric Solid-State Planar Microsupercapacitors with High Energy Density.

With the rapid development of portable devices and wireless protocols, miniaturized energy storage units have become an important prerequisite. Although in-plane microsupercapacitors are emerging as competitive candidate devices, their practical applications have been severely hindered by their low energy density. Here, employing pseudocapacitive active materials working in complementary voltage windows, namely, manganese oxide (MnO2) and titanium carbide (Ti3C2), both in the two-dimensional sheet morphology, a flexible asymmetric interdigitated solid-state microsupercapacitor was assembled. Profiting from the perfect voltage complementarity of the two types of sheets, the high exposure of electrochemically active sites and the maximized utilization of the sheets due to the planar ion transport, the designed device achieved excellent electrochemical performance even when using a gel electrolyte. In particular, the device obtained a high specific capacitance of 106 F g-1 (295 mF cm-2), a wide potential window (2 V), an ultrahigh rate performance (retaining 83% even with a 20-fold in current density to 20 A g-1), an excellent cycling stability (87% retention after 104 cycles at 10 A g-1), and a competitive energy density of 58 W h kg-1 (162 µW h cm-2) that are even comparable to those of some microbatteries, while maintaining a high power density of 985 W kg-1 (2.7 mW cm-2). Importantly, this outstanding electrochemical performance was also stably maintained under various bending conditions. These results indicate that two-dimensional pseudocapacitive sheet materials have a plethora of possibilities for constructing flexible and wearable devices.

[Questionnaire survey and analysis of implementability of clinical practice guidelines for acupuncture-moxibustion].

The current usage and the existing problems in the implementability of clinical practice guidelines for acupuncture-moxibustion were investigated by questionnaire survey, aiming to provide reference for the development or update of clinical practice guidelines for acupuncture-moxibustion in the future. The results showed most of the acupuncture-moxibustion clinicians did not have a deep understanding of the guidelines, but they had a strong will of uniform standards and related guidelines. Although the published clinical practice guidelines for acupuncture-moxibustion achieved some success, they still had not got rid of the shackles of the previous textbook. The main existing problems in the guidelines included insufficient promotion, poor credibility, no evaluation criteria for curative effect, and lack of consideration for patients' will, etc. As the guidelines for acupuncture-moxibustion were based on the latest evidence of current clinical research, it reflected the low quality of current clinical research on acupuncture-moxibustion and lacking of evidence-based concept among acupuncture-moxibustion clinicians. The implementability of clinical practice guidelines is a key step in evidence-based translational medicine, while the research on the implementability of acupuncture-moxibustion guidelines is still blank. More attention should be paid to this field in the future.