Search

Near-infrared (NIR) fluorophores have promoted the development of materials for bioimaging, but traditional NIR dyes usually suffer from aggregation-caused quenching (ACQ), impeding their applications. Herein, we propose two difluoroboron β-diketonate complexes TBO and TBS, consisting a donor-acceptor (D-A) structure with triphenylamine (TPA) moiety as an electron donors and difluoroboron as well as furan or thiophene building block as an electron acceptor. The theoretical calculation and optical data shows that both of them have intramolecular charge transfer (ICT) characteristics. Such ICT characteristics endow them with both solvatochromism and dual-state emission (DSE) properties. In the solvent CH 2 Cl 2 , the emission wavelength of TBO ranges from 550 nm to 750 nm, with a low fluorescence quantum yield (Φ = 7.0 %). However, in the less polar solvent hexane, the emission wavelength blue-shifts, with an increased Φ reaching up to 18 %. Moreover, TBO and TBS exhibit mechanochromic characteristics and rare multi-channel fluorescence emission phenomena at solid-state. Their solid-state samples can emit fluorescence in four spectral bands with maximum emission wavelengths at 300 nm, 400 nm, 600 nm, and 770 nm under excitation at 240 nm. These unique optical properties are expected to be utilized for detecting polarity of system and deformation. Moreover, according to the results of cell imaging and flow cytometry, TBO molecular were easily internalized into Hela cells and distributed in the cytoplasm with strong red fluorescence. Therefore, this research inspires more insight into development of NIR luminogens for biomedical imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification" to screen potential nephrotoxic substances rapidly., Method: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened., Results: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi., Conclusions: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi., (© 2024 John Wiley & Sons Ltd.)

Background: Inner Mongolia cashmere goat (IMCG), renowned for its superior cashmere quality, is a Chinese indigenous goat breed that has been developed through natural and artificial selection over a long period. However, recently, the genetic resources of IMCGs have been significantly threatened by the introduction of cosmopolitan goat breeds and the absence of adequate breed protection systems., Results: In order to assess the conservation effectiveness of IMCGs and efficiently preserve and utilize the purebred germplasm resources, this study analyzed the genetic diversity, kinship, family structure, and inbreeding of IMCGs utilizing resequencing data from 225 randomly selected individuals analyzed using the Plink (v.1.90), GCTA (v.1.94.1), and R (v.4.2.1) software. A total of 12,700,178 high-quality SNPs were selected through quality control from 34,248,064 SNP sites obtained from 225 individuals. The average minor allele frequency (MAF), polymorphic information content (PIC), and Shannon information index (SHI) were 0.253, 0.284, and 0.530, respectively. The average observed heterozygosity (Ho) and the average expected heterozygosity (He) were 0.355 and 0.351, respectively. The analysis of the identity by state distance matrix and genomic relationship matrix has shown that most individuals' genetic distance and genetic relationship are far away, and the inbreeding coefficient is low. The family structure analysis identified 10 families among the 23 rams. A total of 14,109 runs of homozygosity (ROH) were identified in the 225 individuals, with an average ROH length of 1014.547 kb. The average inbreeding coefficient, calculated from ROH, was 0.026 for the overall population and 0.027 specifically among the 23 rams, indicating a low level of inbreeding within the conserved population., Conclusions: The IMCGs exhibited moderate polymorphism and a low level of kinship with inbreeding occurring among a limited number of individuals. Simultaneously, it is necessary to prevent the loss of bloodline to guarantee the perpetuation of the IMCGs' germplasm resources., (© 2024. The Author(s).)

The purpose of this study was to investigate the effects of non-genetic factors on the growth and development performance of Inner Mongolia white cashmere goats (Erlanghan type), such as birth weight (BW), weaning weight (WW), 6-month weight (6 WT), 12-month weight (12 WT), body height (BH), and body length (BL), and wool production performance, such as cashmere fineness (CF), cashmere thickness (CT), and cashmere yield (CY). The research objects were 4654 kids produced by 45 buck goats and 2269 doe goats in the Erlang Mountain Ranch of Beiping Textile Co., Ltd., Inner Mongolia, from 2020 to 2023. Based on the generalized linear model, ANOVA was used to analyze the effects of non-genetic factors, such as birth year (Y), birth month (M), sex (S), birth type (T), birth herd (H), assay flock (F), age at measurement (MA), and the age of doe goats at lambing (DLA), on growth and development traits and cashmere traits. The results show that the birth weight (BW), weaning weight (WW), 6-month weight (6 WT), 12-month weight (12 WT), body length (BL), body height (BH), chest depth (CD), chest width (CW), chest circumference (CC), cannon circumference (CNC), wool length (WL), and cashmere yield (CY) of buck goats were significantly higher than those of doe goats ( p < 0.01), and the fineness of the cashmere produced by doe goats was significantly finer than that produced by buck goats ( p < 0.01). The birth weight, weaning weight, and 6-month weight of single kids were significantly higher than those of multiple kids ( p < 0.01), but the effect on the 12-month weight was not significant ( p > 0.05). The age of doe goats at lambing had significant effects on birth weight, weaning weight, and 6-month weight ( p < 0.01). Assay flock and age at measurement had significant effects on cashmere fineness, cashmere thickness, and cashmere yield ( p < 0.01). This study will provide a basis for the scientific breeding and management of cashmere goats and lay a foundation for the setting of fixed effects in the genetic evaluation model of Inner Mongolia white cashmere goats (Erlangshan type).

Ethnopharmacological Relevance: The pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation., Aim of the Study: This study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases., Materials and Methods: The dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model., Results: Morphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway., Conclusions: Proper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cangjie Temple was built to commemorate Cangjie, the legendary inventor of Chinese characters. It stands as one of the few remaining temples in China dedicated to the invention and creation of writing. In this study, the material properties of wooden paintings from the Cangjie temple were characterized using Polarized Light Microscopy (PLM), Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (SEM-EDS), Micro-confocal Raman Spectroscopy, X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Pyrolysis-Gas Chromatography-Mass Spectrometry (Py-GC/MS). It was confirmed that the pigments of the paintings included cinnabar, lapis lazuli, lead white, Paris green, and carbon black. The proteinaceous glue was used as an adhesive in the pigment samples, with tung oil likely being utilized as a primer for the wooden structures before painting. This study not only provides valuable data support for the conservation and restoration of the architectural features of Cangjie Temple but also provides useful reference for the maintenance and inheritance of similar ancient buildings.

Hypoaconitine (HA), a major secondary metabolite of aconite (a plant-derived rodenticide), is a highly toxic di-ester alkaloidal constituent. The toxicity of HA is intense with a low LD 50 . However, studies on its toxicity mechanism have mainly focused on cardiotoxicity, with few reports on the mechanism of hepatotoxicity. In this study, we combined metabolomics and network toxicology to investigate the effects of HA on the liver and analyzed the mechanisms by which it causes hepatotoxicity. The results of metabolomics studies indicated diethylphosphate, sphingosine-1-phosphate, glycerophosphorylcholine, 2,8-quinolinediol, guanidinosuccinic acid, and D-proline as differential metabolites after HA exposure. These metabolites are involved in eight metabolic pathways including arginine and proline metabolism, ether lipid metabolism, β-alanine metabolism, sphingolipid metabolism, glutathione metabolism, and glycerophospholipid metabolism. Network toxicology analysis of HA may affect the HIF-1 signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and so on by regulating the targets of ALB, HSP90AA1, MMP9, CASP3, and so on. Integrating the results of metabolomics and network toxicology, it was concluded that HA may induce hepatotoxicity by triggering physiological processes such as oxidative stress, inflammatory response, and inducing apoptosis in hepatocytes., Competing Interests: Declaration of competing interest The authors declared that there are no conflicts of interest in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rechargeable aluminum battery (RAB) is expected to be a promising energy storage technique for grid-scale energy storage. However, the development of RABs is seriously plagued by the lack of suitable cathode materials. Herein, we report two p-type conjugated polymers of L-PBPz and C-PBPz with the same building blocks of diphenylphenazine but different linkage patterns of linear and crosslinked structures as the cathode materials for Al dual-ion batteries. Compared to the linear polymer skeleton in L-PBPz, the crosslinked structure endows C-PBPz with amorphous nature and low dihedral angles of the polymer chains, which severally contribute to the fast diffusion of AlCl 4 - with large size and the electron transfer during the redox reaction of diphenylphenazine. As a result, C-PBPz delivers a much better rate performance than L-PBPz. The crosslinked structure also leads to a stable cyclability with over 80000 cycles for C-PBPz. Benefiting from the fast kinetics, meanwhile, the C-PBPz cathode could realize a high redox activity of 117 mAh g -1 , corresponding to an areal capacity of 2.30 mAh cm -2 , even under a high mass loading of 19.7 mg cm -2 and a low content of 10 wt% conductive agent. These results might boost the development of polymer cathodes for RABs., (© 2024 Wiley-VCH GmbH.)

This study analyzes the pigments and binders used in the painted wooden structure of DaZhong Gate in the Confucius Temple in Qufu, Shandong Province, China. Five samples were collected from the building and analyzed using techniques such as polarized light microscopy (PLM), energy-dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy (m-RS), and Fourier-transform infrared spectroscopy (FT-IR). The findings reveal that the red, yellow, green, and blue pigments are identified as lead red, lead chromate yellow, emerald green, and ultramarine, respectively. The white pigment is determined to be a combination of chalk and lead white or anglesite. Considering the production period of the yellow and green pigments, it is inferred that architectural paintings underwent restoration or repainting during the late Qing Dynasty. The analysis of the binder in the pigment using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) reveals that the binder employed is a protein-based glue. Additionally, the detected presence of Heat-bodied tung oil suggests a potential connection to traditional Chinese painting techniques on wooden surfaces. This discovery not only contributes to the historical research of the Confucius Temple but also provides crucial data for the conservation and restoration efforts of this culturally significant heritage site.

The scroll paintings for ancestor trees have been used to inherit the spirit of ancestor worship as a historical record of family development since the late Ming Dynasty in China. A severely degraded scroll painting of an ancestor tree (made of cotton textiles) needs intervention and conservation treatment to mitigate further deterioration. On the basis of the previously reported characterization results for the painting, in this paper, a suspension that is composed of 0.6% cellulose nanofibril (CNF) and nanosized 0.15% MgO in aqueous solvent (denoted as the CNF-MgO susairpension) was prepared. Conventional characterization methods were used to assess the properties of model samples before and after treatment with the CNF-MgO suspension, as well as before and after degradation under two sets of conditions. The results show that the treated model samples are slightly alkaline, given the deposit of alkaline particles, and demonstrate good mechanical properties before and after degradation due to the increase in fiber-to-fiber bond and mitigation of acid-catalyzed hydrolysis. In spite of the non-transparency of CNF and MgO nanoparticles, they have little impact on the optical properties of textiles, as verified by transmittance data and the determination of color changes. This suspension was then used to reinforce and restore the scroll painting in a practical conservation process. The application of CNF and MgO nanoparticles on textile objects investigated in this study would expand our understanding of the conservation of such objects, especially for those that have already become acidic and degraded.

Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.

Conjugated polymers have gained considerable interest due to their unique structures and promising applications in areas such as optoelectronics, photovoltaics, and flexible electronics. This review focuses on the structure-property relationship, glass transition, and crystallization behaviors of conjugated polymers. Understanding the relationship between the molecular structure of conjugated polymers and their properties is essential for optimizing their performance. The glass transition temperature ( T g ) plays a key role in determining the processability and application of conjugated polymers. We discuss the mechanisms underlying the glass transition phenomenon and explore how side-chain interaction affects T g . The crystallization behavior of conjugated polymers significantly impacts their mechanical and electrical properties. We investigate the nucleation and growth processes, as well as the factors that influence the crystallization process. The development of the three generations of conjugated polymers in controlling the crystalline structure and enhancing polymer ordering is also discussed. This review highlights advanced characterization techniques such as X-ray diffraction, atomic force microscopy, and thermal analysis, which provide insights into molecular ordering and polymer-crystal interfaces. This review provides an insight of the structure-property relationship, glass transition, and crystallization behaviors of conjugated polymers. It serves as a foundation for further research and development of conjugated polymer-based materials with enhanced properties and performance.

Inner Mongolia Arbas white cashmere goats is a dual-purpose breed for producing cashmere and meat. In recent years, its meat has become more and more popular among consumers because of rich nutrients and delicious flavor. Therefore, it is particularly important to study the genetic and non-genetic factors affecting the early growth traits and estimate variance components of pre-weaning growth traits of Inner Mongolia Albas white cashmere goats. A total of 37487 kidding records such as birth weight (BWT), weaning weight (WWT), average daily gain from birth to weaning (ADG) and Kleiber ratio (KR) from 343 sires and 7296 dams were used in this study. The most appropriate model was chosen on the basis of likelihood ratio test by fitting six models which excluding or including maternal genetic, maternal permanent environmental effects. The parameters were estimated under the most appropriate model using AIREML method by WOMBAT software. With the best model (Model 6), heritability estimates were 0.0435, 0.0911, 0.0932 and 0.2339 for BWT, WWT, ADG and KR traits, respectively. Maternal heritability estimates were 0.0143, 0.0246, 0.0220 and 0.0186 for BWT, WWT, ADG, and KR traits respectively. The correlation between different traits was estimated with the most suitable model by using bivariate analysis method. The direct additive genetic correlation among the traits ranged from -0.026 (BWT~KR) to 0.772 (ADG~KR). The maternal permanent environment correlation is between -0.289 (BWT-KR) ~0.900 (WWT-ADG). Results indicated that maternal effects and direct-maternal genetic covariance should be considered in any program aimed at improving pre-weaning growth traits to have an accurate genetic evaluation. In addition, positive and medium to high genetic correlations generally exist among WWT, ADG and KR due to the existence of genetic variation for early growth traits. The results showed that the genetic progress of these traits could be slowly through selection except for KR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Liu, Shi, Qi, Li, Wang, Zhang, Zhao, Su and Li.)

Objective: We aimed to evaluate the similarity of BAT2206 to its originator, ustekinumab, including pharmacokinetic profiles, immunogenicity, and safety in healthy Chinese male subjects., Methods: This was a double-blinded, randomized, single-dose, parallel-group clinical trial, in which 270 healthy male subjects were enrolled to receive a single subcutaneous injection (45 mg) of either BAT2206 or ustekinumab (European Union or USA) at a 1:1:1 ratio. The pairwise pharmacokinetic similarities and the safety and immunogenicity of both drugs were evaluated and compared., Results: The results showed that the 90% confidence interval of the geometric mean ratio for primary pharmacokinetic parameters (maximum plasma concentration and area under the plasma concentration-time curve from time zero to infinity) among BAT2206 and ustekinumab (USA or European Union sourced) groups were all within the predefined equivalent interval of 80-125%. Furthermore, all the groups had similar incidences of treatment-emergent adverse events, in which the majority of cases belonged to Common Terminology Criteria for the Classification of Adverse Events Grade 1 or 2. Anti-drug antibodies were detected in 54 (20.1%) subjects, namely 24 (26.7%), 13 (14.8%), and 17 (18.9%) patients in the BAT2206, ustekinumab (European Union), and ustekinumab (USA) groups, respectively. In contrast, the incidences of positive neutralizing antibodies were similar among the three groups., Conclusions: Pharmacokinetic similarity between BAT2206 and ustekinumab (USA or European Union sourced) was confirmed. The three groups had similar safety profiles, and the investigational drugs were well tolerated by subjects., Clinical Trial Registration: This study was registered with ClinicalTrials.gov (NCT04371185)., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Long non-coding RNA (lncRNA) refers to non-coding RNA longer than 200 nt, with one or more short open reading frames (sORF), which encode functional micro-peptides. These functional micro-peptides often play key roles in various biological processes, such as Ca 2+ transport, mitochondrial metabolism, myocyte fusion, cellular senescence and others. At the same time, these biological processes play a key role in the regulation of body homeostasis, diseases and cancers development and progression, embryonic development and other important physiological processes. Therefore, studying the potential regulatory mechanisms of micro-peptides encoded by lncRNA in organisms will help to further elucidate the potential regulatory processes in organisms. Furthermore, it will provide a new theoretical basis for the subsequent targeted treatment of diseases and improvement of animal growth performance. This review summarizes the latest research progress in the field of lncRNA-encoded micro-peptides, as well as the progress in the fields of muscle physiological regulation, inflammation and immunity, common human cancers, and embryonic development. Finally, the challenges of lncRNA-encoded micro-peptides are briefly described, with the aim to facilitate subsequent in-depth research on micro-peptides.

The hair follicle is a complex skin accessory organ, which determines hair growth. Long non-coding RNAs (lncRNAs) have been proven to play an important role in hair follicle development, but their specific mechanism is still unclear. In this study, high-throughput sequencing was used to obtain the expression profiles of lncRNA in the hair follicles of Inner Mongolian cashmere goats at different embryonic stages (45, 55, 65, and 75 days), and a total of 6,630 lncRNA were identified. According to the rules of hair follicle development, we combined miRNA and mRNA databases (published) and predicted lncRNA-miRNA, miRNA-mRNA, and lncRNA-mRNA interaction pairs in the 45 vs. 75 comparison group. We obtained 516 lncRNA-mRNA, 1,011 lncRNA-miRNA, and 7,411 miRNA-mRNA relationship pairs. Finally, target genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and it was found that they were mainly enriched in the Wnt signaling pathway and PI3K-Akt signaling pathway related to hair follicle development, indicating that lncRNA may interact with miRNA/mRNA to directly or indirectly regulate the expression of genes related to hair follicle development. Dual-luciferase reporter gene analysis showed that lncRNA MSTRG.1705.1 could bind to Chi-miR-1 , while lncRNA MSTRG.11809.1 had no binding site for Chi-miR-433 . In conclusion, this study aims to further analyze the molecular regulation mechanism of hair follicle development and to lay a theoretical foundation for revealing the regulation mechanism of cashmere hair follicle growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Shang, Rong, Pan, Wang, Niu, Qi, Li, Lv, Wang, Wang, Su, Liu, Zhao, Wang, Li and Zhang.)

Cashmere goat hair follicles are divided into primary hair follicles and secondary hair follicles. The primary hair follicles produce coarse hair, and the secondary hair follicles produce cashmere. The development of hair follicles is affected by a variety of signaling molecules and pathways. Studies have shown that non-coding RNAs are widely involved in the development of hair follicles of the goat, including small RNAs (miRNAs), long non-coding RNAs (lncRNA), and circular RNAs (circRNAs). In recent years, circRNAs, as a new type of circular closed non-coding RNAs, have attracted great attention due to their high stability. However, its regulatory effect on cashmere goat hair follicles mainly focuses on the periodic regulation of secondary hair follicles, and there is no report on the development of cashmere goat hair follicles during the fetal period. Therefore, this study was based on the circRNA, miRNA, and mRNA expression profiles obtained by whole-transcriptional sequencing of the skin tissue of the Inner Mongolia cashmere goats in the fetal period (days 45, 55, 65, and 75) and screening out the morphological changes of hair follicles at different periods. A total of 113 circRNAs related to the development of secondary hair follicles were present. According to the principle of the ceRNA regulatory network, a ceRNA regulatory network composed of 13 circRNAs, 21 miRNAs, and 110 mRNAs related to the development of secondary hair follicles was constructed. Then, qRT-PCR and Sanger sequencing identified circRNA2034, circRNA5712, circRNA888, and circRNA9127 were circRNAs. Next, the dual-luciferase reporter gene verified the targeting relationship of circRNA5712-miR-27b-3p-Dll4. In conclusion, this study constructed a ceRNA regulatory network for the development of cashmere goat secondary hair follicles, laying a foundation for the analysis of circRNAs regulating the morphogenesis and development of cashmere goat secondary hair follicles through the ceRNA mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shang, Ma, Rong, Pan, Wang, Niu, Qi, Li, Wang, Lv, Wang, Su, Liu, Zhao, Wang, Li and Zhang.)

Aedes albopictus is the only vector that can transmit the dengue virus in Zhejiang Province, central China, and it can develop insecticide resistance due to long-term exposure to pyrethroids. The presence of knockdown resistance ( kdr ) mutations is one of the mechanisms responsible for pyrethroid resistance, and has been reported in some Ae. albopictus populations in southern China. However, little is known about the DNA diversity of the voltage-gated sodium channel (VGSC) gene in Ae. albopictus populations in central China. Four Ae. albopictus field populations were collected, in Yiwu (YW), Quzhou (QZ), Wenzhou (WZ), and Jiaxing (JX) from Zhejiang Province, central China. The susceptibility of Ae. albopictus adults to three pyrethroids (beta-cypermethrin, deltamethrin, and permethrin) was tested using the WHO tube assay, and Kdr mutations were identified via PCR and sequencing. The relationship between kdr mutations and pyrethroid phenotypes was also analyzed. Of the four populations, none was sensitive to any pyrethroid tested, and the YW population showed the strongest pyrethroid resistance. Non-synonymous kdr mutations were detected in codons 1532 and 1534, domain III. At codon 1534, one mutant allele, TCC(S), was detected in the four populations with a frequency of 42.08%, while at codon 1532, one mutant allele, ACC(T), was detected in the JX and QZ populations, with frequencies of 4.22 and 3.03%, respectively. The F1534S mutant allele was positively correlated with both beta-cypermethrin and deltamethrin resistance phenotypes (OR > 1, P < 0.05), whereas the I1532T mutant allele was possibly negatively correlated with beta-cypermethrin, deltamethrin, and permethrin resistance phenotypes (OR < 1, P > 0.05). In conclusion, resistance and resistance mutations regarding to three pyrethroids are already present in the Ae. Albopictus populations from Zhejiang, central China, which prompts the need to use non-insecticide-based methods of insect control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Liu, Qi, Wu, Ni, Chen, Wang, Li, Luo, Hou, Gong and Sun.)

In China, alum-gelatin aqueous solution is historically used to prevent falling off of mineral pigments from paintings and to enhance strength of their paper matrices in the restoration process. However, after a long period of time of preservation, alum-gelatin aqueous solution applied to paintings will hydrolyze and produce free acid, which accelerates aging. To resolve this issue, instead of using alum-gelatin aqueous solution, here we report a new method of using a water-borne fluoropolymer coating to protect paintings. This coating is applied to simulated paintings, and their influences are systematically examined on the antipeeling property of pigment, mechanical properties, thermal stability, chromaticity, surface morphology, and water contact angle. Our results show that the applied coating slightly affects the appearance of the painting without falling off of pigment observed. Moreover, the coating increases the tensile strength and folding endurance of the paper because the polymer fills into the porous structure of paper fibers and covers pigment particles from SEM analysis. The treated painting retains moderate hydrophilicity, which facilitates removal of degradation substances from the paintings by water cleaning and the subsequent mounting procedure. Moreover, this coating is successfully applied to repairing a set of real ancient Chinese paintings of Yuan Dynasty (1271∼1368 A.D.), with practical acceptance. Our work provides a facile yet effective solution to conservation of ancient paintings by applying the modern fluoropolymers., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Objectives: Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD., Methods: Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis., Results: A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender., Conclusions: The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

In this paper, we introduced a new strategy for converting aggregation-induced emission (AIE) to fluorescence emission in solution into the rational design of new fluorescent probes. Two fluorescent probes based on this strategy, namely, PDAM-Lyso and PDAM-Me, have been synthesized and tested both in vitro and in vivo. The fluorophores of the two probes are both phenothiazine molecules, which link to the diaminomaleonitrile (DAMN) moiety through imine bonds. In the presence of imine bonds, the probes emit red fluorescence in an aqueous solution caused by the AIE effect. As the imine bonds are selectively cut-off by HClO, the DAMN moiety gets removed, inducing blue fluorescence of the reaction product. In this way, the selectivity of the DAMN-based probes toward HClO against metal ions and other reactive oxygen species (ROS) was successfully improved. The imaging of endogenous and exogenous HClO with these two probes reveals that lysosome-targeting probes are of great advantage in the detection of natively generated HClO. Furthermore, the imaging of endogenous HClO in zebrafish suggests that PDAM-Lyso is capable of monitoring the generation of HClO in vivo, illustrating that this strategy is of great significance in designing new probes.

Background: Golgi protein 73 (GP73) is a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, the diagnostic value of GP73 for HCC remains controversy, and little is known about the relationship between serum GP73 concentration and clinical characteristics of HCC. This study was designed to analyze the clinical values of GP73 in diagnosing HCC and the relationship between GP73 level and clinical characteristics in HCC patients., Materials and Methods: In this study, a total of 443 serum samples including 180 patients with HCC, 61 patients with liver cirrhosis (LC), 99 chronic hepatitis patients, and 103 healthy individuals were enrolled from November 2011 to April 2013. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect the serum level of GP73 and other biomarkers., Results: GP73 level in HCC group was significantly higher than LC group, chronic hepatitis B group, and healthy control group. In HCC group, GP73 level significantly increased in patients with lymphatic metastasis; moreover, GP73 level in Child-Pugh Class B and C groups was statistically significantly higher than that in Child-Pugh Class A group (P < 0.05). The area under the receiver operating characteristic (AUROC) curve of GP73 and alpha-fetoprotein (AFP) was 0.840 and 0.718, respectively, when diagnosing HCC. Moreover, the AUROC curve by use of the combination of GP73 and AFP was 0.903. The differences among these three aspects were statistically significant (P < 0.05)., Conclusion: GP73 was better than AFP for the diagnosis of HCC, and the expression of serum GP73 is related with the clinical characteristics of HCC patients., Competing Interests: There are no conflicts of interest

Ticks and tick-borne pathogens threaten the health of both domestic animals and humans, and are associated with a high economic burden in many countries. Tick control can be achieved with chemical acaricides, but issues remain regarding their safety as well as emerging tick resistance. Propylene glycol alginate (PGA) is a food additive commonly used in China. It has been used to kill whiteflies in agriculture as an environmentally friendly insecticide. The aims of this study were to (i) explore the efficacy of PGA to kill Haemaphysalis longicornis ticks and (ii) assess the potential to develop a new tick control acaricide containing PGA and a reduced amount of synthetic pyrethroid. Beta-cypermethrin was chosen as the reference pyrethroid in this study. PGA, beta-cypermethrin and mixes (PGA and beta-cypermethrin formulated in proportions of A = 2:1, B = 1:1, and C = 1:2) were compared for efficacy to kill larval and adult H. longicornis ticks. Overall, we found no statistically significant differences in the killing efficacy of PGA as compared to beta-cypermethrin across examined time-points post-tick exposure. At 24 h post-tick exposure, similar killing efficacy for H. longicornis larvae was recorded for beta-cypermethrin alone, PGA alone, and mixed formulations B and C. Mixed formulation C had the strongest killing effect when compared to PGA alone or mixed formulation B. Similar outcomes were observed in experiments with adult H. longicornis ticks. Based on these findings, we propose that PGA can be useful as a tick control acaricide, either as a single active ingredient or formulated together with a pyrethroid., (Copyright © 2018. Published by Elsevier GmbH.)

Celastrol is well known for its anti-cancer effects, yet its specific mechanisms against colon cancer are still not fully elucidated. In this study, cytotoxic effect of celastrol against HCT116 colon cancer cells was investigated based on cell viability assay and flow cytometry assay, and the possible mechanism was explored using a strategy combining metabolic profiling and targeted metabolite analysis based on ultra performance liquid chromatography (UPLC)/MS. Celastrol was found to inhibit the growth of colon cancer cells and induce apoptosis. Metabolomics analysis revealed characteristic changes in metabolic profiles of the colon cancer cells, revealing altered levels of amino acids, carnitine, and lipid markers. Most interestingly, with the assistance of targeted metabolite analysis, tryptophan (Trp) level was significantly increased whereas kynurenine (Kyn) level was decreased in colon cancer cells after celastrol treatment, together with markedly declined Kyn/Trp ratios. Western blot analysis revealed that expression of indoleamine 2,3-dioxygenase (IDO), the enzyme catalyzing Trp to generate Kyn, was dramatically inhibited in colon cancer cells after celastrol treatment, with a dose-dependent manner. These results suggest that suppression of IDO expression and tryptophan catabolism may be part of the mechanisms of celastrol in its cytotoxic effect against HCT116 colon cancer cells. This study provided scientific basis for further development of celastrol on treating colon cancer.

Inflammatory bowel disease (IBD) is a refractory illness with remarkably increasing incidence rate all over the world. However, no desirable treatment scheme is available. Therefore, research and development of new drugs for treating IBD are urgently needed. Histone deacetylase 6 (HDAC6) is considered to be a pro-inflammatory factor, thus the inhibitors specifically-targeting HDAC6 may find their way in IBD treatment. In this study, we evaluated the anti-inflammatory activity of a novel potent and selective HDAC6 inhibitor, LTB2, in dextran sulfate sodium (DSS)-induced colitis mouse model. It was found that LTB2 treatment significantly alleviated DSS-induced colitis in mice, as evidenced by body weight, colon length, histological examination, and the disease activity index (DAI) scores of rectal bleeding and diarrhea. More importantly, it showed a better protective effect on the DSS-induced colitis mice than the commonly used mesalazine in the clinic. Our results demonstrated that selective HDAC6 inhibitors may have a good prospect for IBD treatment.

Two-dimensional correlation spectroscopy (2DCOS) was employed for the identification of ephedrine (Ep) and pseudoephedrine (Ps) present in illegally adulterated slimming herbal products (SHPs). Second derivative (SD) spectral pretreatment was used prior to 2DCOS analysis to highlight specific features not readily observable by Fourier transform infrared spectroscopy (FTIR), SD-FTIR, or original 2DCOS, leading to enhanced resolution and a reduced lower limit of detection (<1% in this study). After examining the power spectra of suspicious SHPs, bands containing characteristic peaks for Ep (701, 747, 1042, 1363, 1375, 1451, 1478 cm -1 etc) and/or Ps (703, 767, 1037, 1375, 1428, 1455, 1590 cm - 1, etc.) were selected to construct synchronous and asynchronous maps for further analysis, while the latter was applied to discriminate positive SHPs adulterated simultaneously with Ep and Ps. The proposed method is simple and economical and has the potential to identify other chemicals in illegally adulterated herbal products. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Celastrol is well known for its anti-inflammatory and anti-cancer effects. In this study, the efficacy of celastrol against dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice was established and the mechanism was investigated using lipidomics. Celastrol treatment significantly alleviated DSS-induced colitis in mice, as revealed by the body weight, colon length, scores of rectal bleeding and diarrhea, serum TNF-α level, and histological analysis results. Lipidomics analysis based on UPLC/MS revealed characteristic changes in the metabolic profiles of the colitis mice, with altered levels of lipid markers associated with IBD, including LPC18 : 0, LPC18 : 1, LPC18 : 2, sphingomyelin (SM), and increased LPC18 : 0/LPC18 : 1 and LPC18 : 0/LPC18 : 2 ratios. For the celastrol-treated colitis mice, however, levels of the above lipid markers were restored, together with recovered saturated LPC/unsaturated LPC ratios. Accordingly, using GC-MS analysis, increased stearic acid (C18 : 0)/oleic acid (C18 : 1) and stearic acid (C18 : 0)/linoleic acid (C18 : 2) ratios were observed in colitis mice, which were later recovered after celastrol treatment. Quantitative real-time PCR analysis revealed that the liver expression of stearoyl-coenzyme A desaturase 1 (SCD1), the key enzyme controlling the desaturation of saturated fatty acid, was dramatically inhibited in IBD mice, and was obviously recovered after celastrol treatment. These results suggest that the increased saturated LPC/unsaturated LPC (and saturated fatty acid/unsaturated fatty acid) ratios associated with SCD1 down-regulation could be regarded as biomarkers of colitis, and celastrol alleviates DSS-induced colitis partially via up-regulation of SCD1, restoring the altered balance between stearic acid- and oleic acid-derived lipid species, which plays an important role in alleviating colitis. In all, this study provided the scientific basis for further development of celastrol in treating IBD.

The phenomenon of botanical dietary supplements (BDS) doped with illegal adulterants has become a serious problem all over the world, which could cause great threat to human's health. Therefore, it is of great value to identify BDS. Herein, we put forward a highly sensitive method for on-site detection of antitussive and antiasthmatic drugs adulterated in BDS using thin layer chromatography (TLC) combined with dynamic surface enhanced Raman spectroscopy (DSERS). Adulterants in BDS were separated on a TLC plate and located under UV illumination. Then DSERS detection was performed using a portable Raman spectrometer with 50% glycerol silver colloid serving as DSERS active substrate. Here, the effects of different solvents on detection efficacy were evaluated using phenformin hydrochloride (PHE) as a probe. It was shown that 50% glycerol resulted in higher SERS enhancement and relatively higher stability. Moreover, practical application of this novel TLC-DSERS method was demonstrated with rapid analysis of real BDS samples and one sample adulterated with benproperine phosphate (BEN) was found. Furthermore, the obtained result was verified by ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF/MS). The sensitivity of the TLC-DSERS technique is 1-2 orders of magnitude higher than that of TLC-SERS technique. The results turned out that this combined method would have good prospects for on-site and sensitive detection of adulterated BDS., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, was found to exacerbate inflammation and tissue injury in experimental acute colitis mice. Through lipidomics analysis, bioactive sphingolipids were significantly up-regulated in the colitis group. In this study, to provide further insight into the PPARα-dependent exacerbation of colitis, gas chromatography-mass spectrometry (GC/MS) based metabolomics was employed to investigate the serum and colon of dextran sulfate sodium (DSS)-induced colitis mice treated with fenofibrate, with particular emphasis on changes in low-molecular-weight metabolites. With the aid of multivariate analysis and metabolic pathway analysis, potential metabolite markers in the amino acid metabolism, urea cycle, purine metabolism, and citrate cycle were highlighted, such as glycine, serine, threonine, malic acid, isocitric acid, uric acid, and urea. The level changes of these metabolites in either serum or colons of colitis mice were further potentiated following fenofibrate treatment. Accordingly, the expression of threonine aldolase and phosphoserine aminotransferase 1 was significantly up-regulated in colitis mice and further potentiated in fenofibrate/DSS-treated mice. It was revealed that beyond the control of lipid metabolism, PPARα also shows effects on the above pathways, resulting in enhanced protein catabolism and energy expenditure, increased bioactive sphingolipid metabolism and proinflammatory state, which were possibly related to the exacerbated colitis.

Rhizoma Smilacis Glabrae (RSG) is a well-known herbal medicine with the homology of medicine and food. In this study, simultaneous chemical fingerprint and quantitative analysis of the bioactive flavonoid components of RSG were developed using accelerated solvent extraction and high-performance liquid chromatography coupled with ion trap tandem mass spectrometry. The operational parameters of accelerated solvent extraction including extraction solvent, extraction temperature, static extraction time, solid-to-liquid ratio, and extraction cycles were optimized. Hierarchical cluster analysis, similarity analysis, and principal component analysis were performed to evaluate the similarity and variation of the samples collected from several provinces in China. Subsequently, high-performance liquid chromatography fingerprints were established for the discrimination of 16 batches of RSG samples, and the major six flavonoids, namely, toxifolin, neoastilbin, astilbin, neoisoastilbin, isoastilbin, and engeletin were then quantitatively determined. The calibration curves for all the six analytes showed good linearity (r(2) > 0.999), and the limits of detection and quantification were less than 0.10 and 0.27 μg·mL(-1) , respectively. Therefore, the proposed extraction and determination methods were proved to be robust and reliable for the quality control of RSG., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and diabetes. However the mechanism of resistance to HFD-induced obesity of CYP7A1-tg mice has not been determined. In this study, metabolomic and lipidomic profiles of CYP7A1-tg mice were analyzed to explore the metabolic alterations in CYP7A1-tg mice that govern the protection against obesity and insulin resistance by using ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry combined with multivariate analyses. Lipidomics analysis identified seven lipid markers including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides that were significantly decreased in serum of HFD-fed CYP7A1-tg mice. Metabolomics analysis identified 13 metabolites in bile acid synthesis including taurochenodeoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, taurocholic acid, and tauro-β-muricholic acid (T-β-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-β-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12α-hydroxylated bile acids and increasing intestinal T-β-MCA may reduce high fat diet-induced increase of phospholipids, sphingomyelins and ceramides, and ameliorate diabetes and obesity. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a major worldwide health problem. Recent studies suggest that the gut microbiota influences NAFLD pathogenesis. Here, a murine model of high-fat diet-induced (HFD-induced) NAFLD was used, and the effects of alterations in the gut microbiota on NAFLD were determined. Mice treated with antibiotics or tempol exhibited altered bile acid composition, with a notable increase in conjugated bile acid metabolites that inhibited intestinal farnesoid X receptor (FXR) signaling. Compared with control mice, animals with intestine-specific Fxr disruption had reduced hepatic triglyceride accumulation in response to a HFD. The decrease in hepatic triglyceride accumulation was mainly due to fewer circulating ceramides, which was in part the result of lower expression of ceramide synthesis genes. The reduction of ceramide levels in the ileum and serum in tempol- or antibiotic-treated mice fed a HFD resulted in downregulation of hepatic SREBP1C and decreased de novo lipogenesis. Administration of C16:0 ceramide to antibiotic-treated mice fed a HFD reversed hepatic steatosis. These studies demonstrate that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota-associated NAFLD development, linking the microbiome, nuclear receptor signaling, and NAFLD. This work suggests that inhibition of intestinal FXR is a potential therapeutic target for NAFLD treatment.

Bile acids play a pivotal role in the pathological development of inflammatory bowel disease (IBD). However, the mechanism of bile acid dysregulation in IBD remains unanswered. Here we show that intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferases (UGTs) signalling is an important determinant of bile acid homeostasis. Dextran sulphate sodium (DSS)-induced colitis leads to accumulation of bile acids in inflamed colon tissues via activation of the intestinal peroxisome PPARα-UGTs pathway. UGTs accelerate the metabolic elimination of bile acids, and thereby decrease their intracellular levels in the small intestine. Reduced intracellular bile acids results in repressed farnesoid X receptor (FXR)-FGF15 signalling, leading to upregulation of hepatic CYP7A1, thus promoting the de novo bile acid synthesis. Both knockout of PPARα and treatment with recombinant FGF19 markedly attenuate DSS-induced colitis. Thus, we propose that intestinal PPARα-UGTs and downstream FXR-FGF15 signalling play vital roles in control of bile acid homeostasis and the pathological development of colitis.

Silymarin extracted from Silybum marianum (L.) Gaertn consists of a large number of flavonolignans, of which diastereoisomeric flavonolignans including silybin A and silybin B, and isosilybin A and isosilybin B are the main bioactive components, whose preparation from the crude extracts is still a difficult task. In this work, binary-column recycling preparative high-performance liquid chromatography systems without sample loop trapping, where two columns were switched alternately via one or two six-port switching valves, were established and successfully applied to the isolation and purification of the four diastereoisomeric flavonolignans from silymarin. The proposed system showed significant advantages over conventional preparative high-performance liquid chromatography with a single column in increasing efficiency and reducing the cost. To obtain the same amounts of products, the proposed system spends only one tenth of the time that the conventional system spends, and needs only one eleventh of the solvent that the conventional system consumes. Using the proposed system, the four diastereoisomers were successfully isolated from silymarin with purities over 98%., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fibrates, such as fenofibrate, are peroxisome proliferator-activated receptor-α (PPARα) agonists and have been used for several decades as hypolipidemic agents in the clinic. However, contradictory observations exist on the role of fibrates in host response to acute inflammation, with unclear mechanisms. The role of PPARα in colitis was assessed using fenofibrate and Ppara-null mice. Wild-type or Ppara-null mice were subjected to acute colitis under three distinct protocols, dextran sulfate sodium, trinitrobenzenesulfonic acid, and Salmonella Typhi. Serum and colon lipidomics were analyzed to characterize the metabolic profiles by ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Messenger RNAs of PPARα target genes and genes involved in inflammation were determined by qunatitative PCR analysis. Fenofibrate treatment exacerbated inflammation and tissue injury in acute colitis, and this was dependent on PPARα activation. Lipidomics analysis revealed that bioactive sphingolipids, including sphingomyelins (SM) and ceramides, were significantly increased in the colitis group compared with the control group; this was further potentiated following fenofibrate treatment. In the colon, fenofibrate did not reduce the markedly increased expression of mRNA encoding TNFα found in the acute colitis model, while it decreased hydrolysis and increased synthesis of SM, upregulated RIPK3-dependent necrosis, and elevated mitochondrial fatty acid β-oxidation, which were possibly related to the exacerbated colitis., (Copyright © 2014 the American Physiological Society.)

The X-ray repair cross-complementing group 1 (XRCC1) gene, one of over 20 genes that participate in the base excision repair pathway, is thought to account for differences in susceptibility to hepatocellular carcinoma. To assess the relationship between the XRCC1 Arg399Gln polymorphism and the risk of hepatocellular carcinoma (HCC), we performed a meta-analysis. All the relevant studies were extracted from PubMed, Embase, the Chinese biomedicine databases, the Chinese national knowledge infrastructure, and the Wanfang databases (prior to August 2012). The meta-analysis was performed using all eligible studies, which covered a total of 2,554 cases and 3,320 controls, to examine the association between XRCC1 Arg399Gln polymorphism and the risk of HCC. Our analysis suggested that the variant genotypes of the XRCC1 Arg399Gln gene were associated with a significantly increased risk of HCC in a co-dominant model (Arg/Gln vs. Arg/Arg, odd ratios [OR] 1.39, 95 % confidence interval [CI] 1.08-1.79; Gln/Gln vs. Arg/Arg, OR 1.26, 95 % CI 1.04-1.52) and a dominant model (Arg/Gln + Gln/Gln vs. Arg/Arg OR 1.36, 95 % CI 1.07-1.72), whereas no association was observed in the recessive model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.05, 95 % CI 0.91-1.21). The results of the subgroup analysis by ethnicity indicated that the XRCC1 Arg399Gln polymorphism was associated with increased risk of HCC in Asian populations using the co-dominant model (Arg/Gln vs. Arg/Arg, OR 1.41, 95 % CI 1.06-1.87) and the dominant model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.35, 95 % CI 1.03-1.76). Our analysis provides evidence that the XRCC1 Arg399Gln polymorphism may be associated with a higher risk of HCC, especially among Asian populations.

Currently, liquid chromatography-mass spectrometry (LC-MS) is one of the most important analytical technologies for detecting hundreds of metabolites in the field of metabolomics. A recent advance in LC that has impacted metabolomics is the development of UPLC (ultra-performance liquid chromatography). In this chapter, we describe the analytical methodologies for the global metabolic profiling of serum, urine, and tissue samples using UPLC-Q-TOF (quadrupole-time-of-flight)-MS. Aqueous metabolites are extracted after adding methanol/acetonitrile/acetone and then analyzed by UPLC-MS under positive and/or negative ionization mode. With the aid of multivariate statistical analysis, separation between various groups can be observed in the score plots, and biomarkers are screened in the loading/weight/VIP (variable importance in the projection) scatterplots. Furthermore, putative markers can be identified through comparison with the authentic standards based on tandem mass spectrometry (MS/MS) fragmentation pattern and LC retention. We expect that our protocol, with modifications if necessary, can be useful in many metabolomics studies and a wide range of research areas related to small molecules and LC-MS.

The combined use of the state-of-the-art hybrid mass spectrometer (MS) together with high efficient liquid chromatography may prove to be a useful tool for neutral saccharide analysis. In the present work, we used hydrophilic interaction liquid chromatography (HILIC) to separate selected saccharides (fructose, glucose, galactose, sucrose, melibiose, raffinose, manninotriose, stachyose and verbascose). Influences of the column type, additive type, temperature, pH and other separation factors on analyte retention were evaluated. The new method did not require reduction, derivatization or postcolumn addition of reagents, which are commonly used in conventional saccharide analysis. Our results demonstrate the potential of HILIC-MS for sensitive and robust determination of saccharides in crude and processed Radix Rehmanniae, and may promote new perspectives in the research of other medicinal herbs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Increased levels of bile acids (BAs) due to the various hepatic diseases could interfere with the metabolism of xenobiotics, such as drugs, and endobiotics including steroid hormones. UDP-glucuronosyltransferases (UGTs) are involved in the conjugation and elimination of many xenobiotics and endogenous compounds. The present study sought to investigate the potential for inhibition of UGT enzymes by BAs. The results showed that taurolithocholic acid (TLCA) exhibited the strongest inhibition toward UGTs, followed by lithocholic acid. Structure-UGT inhibition relationships of BAs were examined and in vitro-in vivo extrapolation performed by using in vitro inhibition kinetic parameters (Ki) in combination with calculated in vivo levels of TLCA. Substitution of a hydrogen with a hydroxyl group in the R1, R3, R4, R5 sites of BAs significantly weakens their inhibition ability toward most UGTs. The in vivo inhibition by TLCA toward UGT forms was determined with following orders of potency: UGT1A4 > UGT2B7 > UGT1A3 > UGT1A1 ∼ UGT1A7 ∼ UGT1A10 ∼ UGT2B15. In conclusion, these studies suggest that disrupted homeostasis of BAs, notably taurolithocholic acid, found in various diseases such as cholestasis, could lead to altered metabolism of xenobiotics and endobiotics through inhibition of UGT enzymes.

β-Caryophyllene (BCP), a natural sesquiterpene existing in the essential oil of many plants, has exhibited a wide range of biological activities. However, its volatility and poor water-solubility limit its application in pharmaceutical field. β-Cyclodextrin (β-CD) has intrinsic ability to form specific inclusion complexes with different drugs to enhance their stability, solubility and bioavailability. The aim of this study is to investigate and compare the oral bioavailability and the pharmacokinetics of free BCP and BCP/β-CD inclusion complex after a single oral dose of 50mg/kg on rats. A simple, rapid, and sensitive gas chromatography-mass spectrometry method in selected ion monitoring (GC-MS/SIM) mode was developed on determination of BCP in rat plasma. The in vivo data showed that BCP/β-CD inclusion complex displayed earlier Tmax, higher Cmax and the AUC0-12h was approximately 2.6 times increase than those of free BCP. These results demonstrated that BCP/β-CD inclusion complex has significantly increased the oral bioavailability of the drug in rats than free BCP., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Although various techniques have been employed to analyze drug metabolites, the metabolism of multicomponent herbal medicine has seldom been fully addressed. In contrast to chemical drugs, a number of compounds in herbal medicine could get into circulation and then be metabolized. Metabolism study on active constituents in herbal medicine is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of herbal medicine. The present work aims to elucidate the multicomponent metabolic characteristics of a herbal medicine by the combination of plasma pharmacochemistry and microdialysis sampling. Anemarrhena asphodeloides, a well-known traditional Chinese medicine, was chosen as a model. After oral administration of A. asphodeloides saponin extract to rats, microdialysis samples were collected continuously in the jugular vein and analyzed by ultrahigh-performance LC/quadrupole-TOF MS. The identification of compounds in biosamples was achieved by accurate mass measurement and detailed fragmentation pathway analysis. The results showed that unbound constituents in blood circulation of the rat included seven parent saponins and six metabolites, which might be the potential active components in vivo. Among which, three metabolites have not been previously reported and were identified in this study. It is the first report on systemic metabolism of total saponins of A. asphodeloides in mammalian plasma., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Celastrol, a quinine methide triterpene extracted from a Chinese medicine (Trypterygium wilfordii Hook F.), has the potential to become an anticancer drug with promising prospects. Cell culture metabolomics has been a powerful method to study metabolic profiles in cell line after drug treatment, which can be used for discovery of drug targets and investigation of drug effects., Methods: We analyzed the metabolic modifications induced by celastrol treatment in human cervical cancer cells, using an ion-trap gas chromatography-mass spectrometry based metabolomics combined with multivariate statistical analysis, which allows simultaneous screening of multiple characteristic metabolic pathways related to celastrol treatment. Three representative apoptosis-inducing cytotoxic agents, namely cisplatin, doxorubicin hydrochloride and paclitaxel, were selected as positive control drugs to validate reasonableness and accuracy of our metabolomic investigation on celastrol., Results: Anti-proliferation and apoptotic effects of celastrol were demonstrated by CCK-8 assay, Annexin-V/PI staining method, mitochondrial membrane potential (deltapsim) assay and caspase-3 assay. Several significant metabolites involved in energy, amino acid and nucleic acid metabolism in HeLa cells induced by celastrol and positive drugs were reported. Our method is proved to be effective and robust to provide new evidence of pharmacological mechanism of celastrol., Conclusions: The metabolic alterations induced by drug treatment showed the impaired physiological activity of HeLa cells, which also indicated anti-proliferative and apoptotic effects of celastrol and these positive drugs., General Significance: GC/MS-based metabolomic approach applied to cell culture could give valuable information on the systemic effects of celastrol in vitro and help us to further study its anticancer mechanism.

Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD) has been clinically used for treatment of myocardial ischemia (MI) for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

In the work presented here, a novel approach to comprehensive two-dimensional liquid chromatography is evaluated. Reversed-phase liquid chromatography was employed for the first-dimension separation and polyamine chromatography was chosen for the second-dimension separation mode. The two dimensions are highly orthogonal and the separation efficacy of the developed octadecylsilica × polyamine was tested by separating an extract from Anemarrhena asphodeloides. The steroid glycosides identified by comprehensive two-dimensional liquid chromatography in this experiment were compared to those obtained for monodimensional liquid chromatography. The comprehensive two-dimensional liquid chromatography system, thanks to the complementary separation selectivity and enhanced peak capacity provided by the two columns, allowed to distribute five compounds of low amounts otherwise unachievable by monodimensional liquid chromatography. In addition, four steroid isomers with similar fragmentation characteristics in MS/MS spectra, were newly separated based on their different chemical structures., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ethnopharmacological Relevance: The dried flower buds of Magnolia biondii Pamp (Magnoliaceae) possesses significant anti-inflammatory activities., Aim of the Study: Volatile oil in Magnolia biondii Pamp (VOMbP) is considered to be important pharmacologically active individuals against acute inflammation, but its exact anti-inflammatory mechanism remains elusive. In this study, we aimed to investigate the intervention of VOMbP on rats with acute inflammation and explore the possible anti-inflammatory mechanisms of VOMbP with metabonomic strategy., Materials and Methods: Acute inflammation was induced by subcutaneously injection of carrageenan in the rats. Plasma was analyzed using gas chromatography-mass spectrometry (GC-MS), based on which the principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) models were established for metabonomic analysis., Results: It was revealed that the pretreatment of VOMbP in acute inflammatory rats induces a substantial and characteristic change in their metabolic profiles. Some significantly changed metabolites, including hexadecanoic acid, linoleic acid, oleic acid, stearic acid, and cholesterol, were found to be reasonable in explaining the anti-inflammatory mechanism of VOMbP., Conclusions: In all, it is likely that VOMbP intervenes the metabolic process of inflammatory rats by affecting the fatty acid and cholesterol metabolism. Our work also indicated that the metabonomics method is a promising tool for performing intervention and mechanism research of traditional Chinese medicines., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Slice-scan method (SS) scans the two-way chromatographic data at each retention time point, and hence obtains the corresponding spectral "slice"s. Then, the spectral slices are transformed into new spectral profiles by spectral transformation, based on which qualitative and quantitative analysis of the overlapping chromatographic peaks could be done. In this work, a new strategy for directly determining the component of interest in the overlapping chromatographic peak is presented, which takes advantage of the selective spectral slices of the determined component and establishes the best calibration curve by applying the new generated spectral profiles after spectral transformation. Meanwhile, the contents of four bioactive lignans, schisandrin, schisantherin, deoxyschizandrin and gamma-schizandrin in Schisandra chinensis Baill., a famous herb in China were determined using SS together with the new quantitative strategy, and satisfactory results have been obtained.

A 96-well protein precipitation, liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and fully validated for the determination of fudosteine in human plasma. After protein precipitation of the plasma samples (50 microL) by the methanol (150 microL) containing the internal standard (IS), erdosteine, the 96-well plate was vortexed for 5 min and centrifuged for 15 min. The 100 microL supernatant and 100 microL mobile phase were added to another plate and mixed and then the mixture was directly injected into the LC-MS/MS system in the negative ionization mode. The separation was performed on a XB-CN column for 3.0 min per sample using an eluent of methanol-water (60:40, v/v) containing 0.005% formic acid. Multiple reaction monitoring (MRM) using the precursor-product ion transitions m/z 178-->91 and m/z 284-->91 was performed to quantify fudosteine and erdosteine, respectively. The method was sensitive with a lower limit of quantification (LLOQ) of 0.02 microg mL(-1), with good linearity (r>0.999) over the linear range of 0.02-10 microg mL(-1). The within- and between-run precision was less than 5.5% and accuracy ranged from 94.2 to 106.7% for quality control (QC) samples at three concentrations of 0.05, 1 and 8 microg mL(-1). The method was employed in the clinical pharmacokinetic study of fudosteine formulation product after oral administration to healthy volunteers.

Developing a simple and fast method to analyze possibly adulterated synthetic drugs in suspected herbal medicines (HM) is both methodologically and commercially significant. This paper constructs a new approach named local straight-line screening (LSLS), to the solution of the problem, after carefully observing the characteristics of the spectral line shapes. LSLS can be applied to both the qualitative and quantitative analysis of suspected HM, based solely on infrared spectrum of the possible synthetic drug and the suspected HM without any sample pretreatment. The concept and the application of the method are exemplified by analysis of sibutramine hydrochloride (SH), an anti-obesity medicine, adulterated in some commercially available HM-based diet pills, and compared with MSFDSS, and SNICA methods. The results show that, despite highly overlapping spectra and unresolved data, it is possible with LSLS to obtain an accurate discrimination and determination of SH in the HM-based diet pills. This allows the method to be potentially used in the primary screening of other synthetic drugs suspiciously adulterated in HM, with high rapidity, accuracy and cost-effectiveness.

A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method was established for the determination of oleanolic acid and ursolic acid in cornel. The two components were separated in the running buffer of 40 mmol/L sodium borate containing 5% methanol, 25 mmol/L SDS and 15 mmol/L hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The applied voltage was 24 kV. The wavelength of detection was 200 nm. The temperature was kept at 25 C. Cinnamic acid was used as the internal standard. The analytical performance of the method was tested with respect to linearity, precision and recovery. The calibration curves were linear in the range of 10.15-243.6 microg/mL, r=0.9993 (oleanolic acid) and 10.07-241.7 microg/mL, r=0.9994 (ursolic acid); the intra-day precision (RSD) was less than 3.7% (oleanolic acid) and 4.1% (ursolic acid); the inter-day precision (RSD) was less than 4.2% (oleanolic acid) and 4.9% (ursolic acid). The limits of detection were 1.6 microg/mL for both components. The method proved to be sensitive, rapid, accurate and suitable for the determination of oleanolic acid and ursolic acid in cornel., (Copyright (c) 2005 John Wiley & Sons, Ltd.)