[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

High-efficiency static speckle-suppression method based on a combination of beam splitting cavity and liquid-core fiber.

Current static speckle suppression methods have an extremely large system size and unsatisfactory performance. This study proposes a device called beam-splitting cavity (BSC) and establishes a model of speckle suppression based on the combination of BSC and a liquid-core fiber. Subsequently, a passive static speckle suppression system is constructed and the key factors affecting the speckle contrast are studied. Consequently, the speckle contrast was reduced from 30.2% to 3.1%, which is below the human-eye speckle-discrimination limit (<4%). The scheme consists entirely of passive optical elements, which are more applicable to projectors than the traditional static and dynamic speckle-suppression methods.

Bound states in the continuum in asymmetric one-dimensional photonic crystal systems guided by anisotropy.

Bound states in the continuum (BICs) have been widely observed in many symmetric geometries in the optical system during the last decade. Here, we consider a scenario in which the structure is designed asymmetrically with anisotropic birefringent material embedded in one-dimensional photonic crystals. This kind of new shape opens the possibility of obtaining symmetry-protected BICs (SP-BICs) and Friedrich-Wintgen BICs (FW-BICs) form in tunable anisotropy axis tilt. Interestingly, these BICs can be observed as high-Q resonances by variation of the system's parameters, such as the incident angle, which means the structure without being injected at Brewster's angle can also achieve BICs. Our findings might achieve active regulation and are easy to manufacture.

[Study on biomarkers of acteoside in treating puromycin aminonucleoside nephropathy in young rats based on non-targeted urine metabolomics technology].

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.

A Highly Conserved Circular RNA circRasGEF1B Enhances Antiviral Immunity by Regulating miR-21-3p/MITA Pathway in Lower Vertebrates.

Circular RNAs (circRNAs) represent a class of widespread, diverse, and covalently closed circRNAs that function as microRNA (miRNA) sponges and crucial regulators of gene expression in mammals. However, the regulation and function of circRNAs in lower vertebrates are still unknown. Here, we first discover a highly conserved circRNA termed circRasGEF1B, which displays a high conservation from mammals to fish and serves as key regulator in eliciting antiviral immunity in teleost fish. Results indicate that circRasGEF1B was highly expressed in Siniperca chuatsi rhabdovirus-infected tissues and cells. Functionally, miR-21-3p could inhibit cellular antiviral responses significantly, whereas circRasGEF1B counteract the effects of miR-21-3p. In mechanism, the results demonstrate that circRasGEF1B acts as a competing endogenous RNA (ceRNA) of miR-21-3p to relieve the repressive effect of miR-21-3p on its target MITA, then enhance the innate antiviral responses. Our results not only provide a novel insight into the functions of circRNAs in lower vertebrates, but broaden our understanding of circRNAs in viral infection.IMPORTANCE Siniperca chuatsi rhabdovirus (SCRV) is a typical fish RNA rhabdovirus, which is one of the most significant viral pathogens in teleost fish and can cause severe hemorrhagic septicemia in freshwater and marine fishes. Here, we discovered a highly conserved circRNAs called circRasGEF1B, which acts as a key regulator for innate antiviral responses upon SCRV infection. circRasGEF1B acts as an endogenous sponge of miR-21-3p that downregulates miR-21-3p expression levels. circRasGEF1B is able to bind to miR-21-3p directly and regulates MITA expression. To our knowledge, this report is the first to characterize circRNA-miRNA regulatory networks that exist in lower vertebrates.

Circular RNA circPIKfyve acts as a sponge of miR-21-3p to enhance antiviral immunity through regulating MAVS in teleost fish.

Circular RNAs (circRNAs) are a class of widespread and diverse covalently closed circular endogenous RNAs that exert crucial functions in regulating gene expression in mammals. However, the function and regulation mechanism of circRNAs in lower vertebrates are still unknown. Here, we discovered a novel circRNA derived from PIKfyve, named circPIKfyve, that is related to the antiviral responses in teleost fish. The results showed that circPIKfyve plays essential roles in host antiviral immunity and inhibition of SCRV replication. Moreover, we also found that the antiviral effect inhibited by miR-21-3p could be reversed with the addition of circPIKfyve. In mechanism, our data revealed that circPIKfyve is a competitive endogenous RNA (ceRNA) of MAVS by sponging miR-21-3p, leading to activation of NF-κB/IRF3 pathway, which then enhance the innate antiviral responses. In addition, we firstly found that RNA binding protein QKI is involved in the formation and regulation of circPIKfyve. Our results provided a strong basis that circRNAs to play a regulatory role in antiviral immune responses in teleost fish.Importance: Here, we identified a novel circRNA, namely, circPIKfyve, that can act as a key regulator of the innate immune response in teleost fish. circPIKfyve acts as a molecular sponge by competitive adsorbing of miR-21-3p, thereby increasing the abundance of MAVS and activating the downstream NF-κB/IRF3 pathway to enhance the antiviral response. In addition, this study was the first to find that QKI protein is involved in regulating the formation of circPIKfyve in fish. The overall results of this study suggest that circPIKfyve plays an active regulatory role in the antiviral immune response of teleost fish.

MicroRNA-103 and microRNA-190 negatively regulate NF-κB-mediated immune responses by targeting IL-1R1 in Miichthys miiuy.

Accumulating evidence has demonstrated that microRNAs (miRNAs) regulate various physiological and pathological processes at the transcriptional level, thus called novel regulators in immune response. In this study, we used bioinformatics and functional experiments to determine the role of miR-103 and miR-190 in the regulation of IL-1R1 gene involved in the immune and inflammatory responses in miiuy croakers. First, we predicted the target genes of miR-103 and miR-190 through bioinformatics and found that IL-1R1 is a direct target gene of miR-103 and miR-190. This was further confirmed by the dual-luciferase reporter assay that the over-expression of miR-103, miR-190 mimics and the pre-miR-103, pre-miR-190 plasmids inhibit the luciferase levels of the wild-type of IL-1R1 3'UTR. miR-103 and miR-190 inhibitors increase the luciferase levels of IL-1R1-3'UTR. Additionally, we found that miR-103 and miR-190 could negatively regulate the mRNA expression of IL-1R1. Importantly, we demonstrated that miR-103 and miR-190 significantly inhibit the NF-κB signaling pathway by targeting IL-1R1 upon LPS stimulation. Collectively, these results provide strong evidence for an important regulatory mechanism of miR-103 and miR-190 targeting the IL-1R1 gene, thereby preventing excessive inflammatory immune responses from causing autoimmunity.

[Comprehensive evaluation system for quality of Chinese medicinal decoction pieces based on "experience-ingredients-activity-electronic sensing"].

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

[Determination and comparison of 10 active components in different parts of Loropetalum chinensis based on ultra-high performance liquid chromatography-tandem mass spectrometry].

To establish a method for the simultaneous determination of ellagic acid, quercetin, gallic acid, kaempferol, myricetin, tiliroside, salidroside, isoquercetin, chlorogenic acid, and quinic acid in the leaves, flowers, fruits, and roots of Loropetalum chinensis by ultra-performance liquid chromatography-tandem mass spectrometry, and provide references for the development and utilization of L. chinensis resources. The analysis was performed on the chromatographic column ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm) with a gradient mobile phase of acetonitrile-0.2% formic solution at the flow rate of 0.3 mL·min~(-1). Column temperature was 30 ℃ and injection volume was 2 µL. Multiple reactive ion monitoring mode(MRM) was used in the negative ion ionization mode of electrospray ion source. The 10 active components had a good linear relationship, and the established method was stable, simple, and accurate. The 10 active components existed in different parts of L. chinensis, with significant different content. The main components in different parts of L. chinensis were polyphenols, with the highest content, followed by flavonoids. The content of 10 active components was generally high in flowers. Among them, the content of quinic acid was the highest, reaching 22.539 1 mg·g~(-1). This study elucidates the differences of active components in the same part and the different parts of L. chinensis, thereby providing basis for the research on the pharmacodynamic substances of L. chinensis and references for the comprehensive development and utilization of L. chinensis resources.

microRNA-489 negatively modulates RIG-I signaling pathway via targeting TRAF6 in miiuy croaker after poly(I:C) stimulation.

The innate immune response is first line of host defense against pathogen invasion. However, excessive activation of immune responses may cause autoimmune diseases and excessive inflammation. Retinoic acid-inducible gene I (RIG-I) is an important cytoplasmic pathogen recognition receptor that is activated on virus infection. TNF-receptor-associated factor 6 (TRAF6) plays an essential role in the RIG-I-mediated signaling pathway. MicroRNAs (miRNAs) are noncoding RNAs that are emerging as important regulators of immune responses. In this study, we found that the overexpression of miR-489 mimics and pre-miR-489 significantly suppressed the luciferase activity of the wild-type TRAF6 3'UTR, whereas mutant-type led to a complete abrogation of the negative effect. In addition, we also observed that miR-489 can negatively regulate TRAF6 at the level of translation. More importantly, we demonstrated that miR-489 is a negative regulator of TRAF6 involved in the immune response to poly(I:C) stimulation. These common findings indicated that miR-489 plays a regulatory role in host-virus interactions by targeting TRAF6. Overall, all of the present results provide direct evidence that miR-489 is involved in the regulation of TRAF6 expression in miiuy croaker, which will help to better understand the complex regulatory networks of teleost fish.

microRNA-148 is involved in NF-κB signaling pathway regulation after LPS stimulation by targeting IL-1ß in miiuy croaker.

The inflammatory response is a protective process to clear detrimental stimuli, constitutes the defense against infectious pathogens. Clearing pathogen infection requires appropriate immune and inflammatory response, but excessive inflammatory response can lead to uncontrolled inflammation, autoimmune disease, or pathogen transmission. Accumulating evidences show that miRNAs are important and multifunctional regulators of innate immunity and inflammation. However, in the inflammatory response of lower vertebrates, the miRNAs regulatory networks are largely unknown. In this study, a combination of bioinformatics and experimental techniques were used to investigate the functions of miR-148. IL-1ß is a hypothetical target gene of miR-148 predicted by bioinformatics. In addition, dual-luciferase reporter gene experiment was used to verify the targeting effect of miR-148 on IL-1ß-3'UTR. miR-148 inhibits IL-1ß expression in a dose-dependent manner at protein and mRNA levels. It is important that miR-148 participates in regulation of LPS-induced the NF-κB signaling pathway by inhibiting IL-1ß. These results will improve our understanding of the regulation of miRNAs in fish on the immune response.

[Identification of chemical constituents of Xiaoer Chiqiao Qingre Granules based on UHPLC-LTQ-Orbitrap-MS/MS and network pharmacology analysis].

This study aimed to qualitatively analyze the chemical components in Xiaoer Chiqiao Qingre Granules(XRCQ) by UHPLC-LTQ-Orbitrap-MS/MS and identify its material basis. The absorbed components in plasma were combined for exploring the potential action mechanism by integrated network pharmacology. ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm) column and mobile phase system of 0.1% formic acid solution(A)-acetonitrile(B) were used for gradient elution, followed by high resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning modes. According to the precise relative molecular mass and MS/MS fragment ions, a total of 124 chemical components were identified in XRCQ by the comparison with references and literature reports, among which 29 compounds were completely confirmed by comparison with reference substances. Then, the main absorbed components of XRCQ in plasma were also analyzed and clarified by UHPLC-LTQ-Orbitrap-MS/MS. BATMAN-TCM and SwissTargetPrediction were used for target prediction of absorbed components in plasma. Following the plotting of association network with Cytoscape 3.8.2, the core targets were subjected to GO and KEGG pathway enrichment analysis and a component-target-pathway network was constructed. A total of eight main targets of XRCQ against fever in children were obtained together with eight absorbed components in plasma, including glycyrhydinic acid, hesperidin, emodin, reticuline, daidzein, magnolignan C, magnolignan A, and magnolaldehyde D. It was inferred that XRCQ might improve alimentary system abnormality, inflammatory response, oxidative stress, and endocrine disorder through tumor necrosis factor, PI3 K-AKT, and other signaling pathways. The present study comprehensively expounded the chemical profiles of XRCQ and the main absorbed components in plasma and predicted the potential mechanism of XRCQ based on integrated network pharmacology, which has provided certain theoretical reference for the clinical application of XRCQ.

Integrated Phytochemical Analysis Based on UPLC-MS and Network Pharmacology Approaches to Explore the Quality Control Markers for the Quality Assessment of Trifolium pratense L.

Red clover consists of the overground parts and inflorescence of Trifolium pratense L., a leguminous plant belonging to the genus Trifolium. It is widely distributed worldwide and has long been used in traditional medicine. In this study, a combination approach using UPLC-MS and network pharmacology was applied to explore the quality control markers for the quality assessments of red clover. Firstly, UPLC-MS was used to identify the compounds in different parts of red clover. Twenty-eight compounds were totally identified. According to the traditional clinical efficacy of red clover, a compound-target-function network was constructed by network pharmacology to discover the main active compounds based on the identified compounds. Nine compounds of chlorogenic acid, daidzin, calycosin-7-O-ß-d-glucoside, genistin, ononin, daidzein, genistein, formononetin, and biochanin A were filtrated and further confirmed in rat plasma in view of the blood-absorbed components taking effects. Finally, a novel method for simultaneously detecting the nine quality control markers was developed by UPLC-QQQ-MS in an effort to assess the quality of red clover. For all samples, the average contents of the nine compounds measured from high to low consist of formononetin, ononin, biochanin A, genistin, daidzin, calycosin-7-O-ß-d-glucoside, genistein, daidzein, and chlorogenic acid. The samples from Gansu province showed the best quality in the three producing areas This study provides new strategies to explore the quality control markers and develops a novel method for the quality assessment of red clover.

[Identification and attribution of chemical constituents of Qingfei Paidu Decoction based on UHPLC-LTQ-Orbitrap-MS technology].

UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 µm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.

[Identification and attribution of chemical compounds of Pudilan Antiphlogistic Oral Liquid].

UPLC-ESI-Orbitrap-MS/MS was used to analyze,identify and attribute the chemical constituents in Pudilan Antiphlogistic Oral Liquid. The analysis was performed on an Agilent Eclipse XDB-C18(4.6 mm × 150 mm,3.5 µm) with a gradient mobile phase of methanol-0.1% formic solution system at the flow rate of 0.5 m L·min-1. The sample volume was 2 µL. The column temperature was30 ℃. The high-resolution orbitrap mass spectrometry was used as detector,with electrospray ion source in both positive and negative models,and the MS scanning ranged between m/z 50 and 2 000. Based on the analysis of mass spectrometry and literature reports,79 compounds were confirmed,including 30 alkaloids,28 organic acids,18 flavonoids and 3 coumarins. Finally,39 compounds,such as rutin,esculetin,gallic acid,caffeic acid,cichoric acid,were identified from Taraxacum mongolicum; 11 compounds,such as baicalin,baicalein,apigenin,chrysin,oroxylin A,were identified from Scutellaria baicalensis; 13 compounds,such as arginine,proline,hypoxanthine,epigoitrin,indirubin,were identified from Isatis indigotica; and 18 compounds,such as dehydrocheilanthifoline,oxysanguinarine,corynoline,protopine,spallidamine,were identified from Corydalis bungeana. After the analysis of chemical model and attribution,the contents of some compounds were high in Pudilan Antiphlogistic Oral Liquid,such as baicalin,wogonoside,baicalein,wogonin,apigenin,chrysin,skullcapflavonⅡ,oroxylin A,cichoric acid,chlorogenic acid,caffeic acid,esculetin,dehydrocheilanthifoline,dihydrosanguinarine,protopine,corynoline and indirubin. The established method is simple,accurate,rapid,sensitive and reproducible,and thus suitable for the qualitative identification and quantitative determination of Pudilan Antiphlogistic Oral Liquid,which lays a foundation for the systematic quality control and the establishment of whole-course traceability system of active ingredients.

Identification of characteristic genes and herbal compounds for the treatment of psoriasis based on machine learning and molecular dynamics simulation.

Psoriasis brings economic and mental burdens to patients, the exact etiology and pathogenesis of psoriasis are still unclear. Compounds of herbal medicine have the potential for psoriasis treatment. This study aims to explore the characteristic genes for psoriasis, which herbal compounds may target. Four differential gene expression datasets, with 181 healthy skin and 181 psoriasis skin lesion samples, were used for analysis. This study employed random forest, neural network, and support vector machine algorithms to identify the characteristic genes associated with psoriasis. The identified genes were validated using external datasets. Then, the main compounds were identified. The targets of compounds were collected through SwissTargetPrediction, Super-PRED, HERB databases, and so on. Finally, a batch virtual screening of compounds with the identified characteristic genes was conducted. Open Babel and AutoDock Tools 1.5.6 were used for molecular docking, and Desmond was used to evaluate molecular dynamics simulations. Twelve characteristic genes, successfully validated in external datasets genes, were identified from 1270 differential genes. The 59 compounds identified contained 1795 targets. There are 143 intersections between differential genes and compound targets. Two-hundred and ninety-four compound-target combinations were selected for molecular docking screening. It was finally found that 8 protein-ligand combinations are highly critical for treating psoriasis, namely AKR1B10-Astilbin, AKR1B10-Ferulic acid, AKR1B10-Cianidanol, IL36G-Astilbin, MMP9-Ferulic acid, OASL-Astilbin, PPARG-Astilbin, SERPINB3-Astilbin, molecular dynamics simulations also indicate that these eight pairs of combinations are stable. This research brings a new perspective to the treatment of psoriasis, these characteristic genes and compounds deserve the attention of clinical researchers.Communicated by Ramaswamy H. Sarma.

High Levels of Erucic Acid Cause Lipid Deposition, Decreased Antioxidant and Immune Abilities via Inhibiting Lipid Catabolism and Increasing Lipogenesis in Black Carp (Mylopharyngodon piceus).

This study investigated the effects of dietary erucic acid (EA) on growth, lipid accumulation, antioxidant and immune abilities, and lipid metabolism in black carp fed six diets containing varying levels of EA (0.00%, 0.44%, 0.81%, 1.83%, 2.74%, and 3.49%), for 8 weeks. Results showed that fish fed the 3.49% EA diet exhibited lower weight gain, compared to those fed the 0.81% EA diet. In a dose-dependent manner, the serum triglycerides and total cholesterol were significantly elevated in the EA groups. The 1.83%, 2.74%, and 3.49% levels of EA increased alanine aminotransferase and aspartate aminotransferase activities, as well as decreased acid phosphatase and alkaline phosphatase values compared to the EA-deficient group. The hepatic catalase activity and transcriptional level were notably reduced, accompanied by increased hydrogen peroxide contents in the EA groups. Furthermore, dietary EA primarily increased the C22:1n-9 and C20:1n-9 levels, while decreasing the C18:0 and C18:1n-9 contents. In the EA groups, expressions of genes, including hsl, cpt1a, cpt1b, and ppara were downregulated, whereas the fas and gpat expressions were enhanced. Additionally, dietary EA elevated the mRNA level of il-1ß and reduced the expression of il-10. Collectively, high levels of EA (2.74% and 3.49%) induced lipid accumulation, reduced antioxidative and immune abilities in black carp by inhibiting lipid catabolism and increasing lipogenesis. These findings provide valuable insights for optimizing the use of rapeseed oil rich in EA for black carp and other carnivorous fish species.

Engineering the electronic structure of sub-nanometric Ru clusters via Pt single-atom modification for highly efficient electrocatalytic hydrogen evolution.

Developing electrocatalysts with high activity toward the hydrogen evolution reaction (HER) is a prerequisite for hydrogen fuel generation and sustainable development, but current Pt-based catalysts usually suffer from high cost and unsatisfactory performance in non-acidic media. In this work, we report an environmentally friendly and pyrolysis-free synthesis strategy to prepare an efficient catalyst, CNT-NPA-PtRu, with Pt single-atom engineered sub-nanometric Ru clusters anchored at phytic acid-modified carbon nanotubes for electrochemical HER at all pH conditions. The electronic structure of active sub-nanometric Ru clusters was optimized, which further enhanced the HER activity. The synthesized CNT-NPA-PtRu catalyst presents superior performance, reaching the current density of 10 mA cm-2 with only 18.3, 18.7 and 15 mV overpotential in alkaline, acidic and neutral electrolyte, respectively. Experimental results and theoretical calculations reveal that the single Pt atom on the sub-nanometric Ru cluster surface could modulate the electronic structure of Ru and subsequently optimize the adsorption of reaction intermediates, thus promoting HER performance. These findings underscore the importance of engineering the electronic structure of sub-nanometric clusters and offer an effective approach for the generation of high-performance electrocatalysts for HER.

Study on the potential mechanism of Qingxin Lianzi Yin Decoction on renoprotection in db/db mice via network pharmacology and metabolomics.

BACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-ß-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.