A strategy to distinguish similar traditional Chinese medicines by liquid chromatography-mass spectrometry, electronic senses, and gas chromatography-ion mobility spectrometry: Marsdeniae tenacissimae Caulis and Paederiae scandens Caulis as examples.

INTRODUCTION: Marsdeniae tenacissimae Caulis (MTC), a popular traditional Chinese medicine, has been widely used in the treatment of tumor diseases. Paederiae scandens Caulis (PSC), which is similar in appearance to MTC, is a common counterfeit product. It is difficult for traditional methods to effectively distinguish between MTC and PSC. Therefore, there is an urgent need for a rapid and accurate method to identify MTC and PSC. OBJECTIVES: The aim is to distinguish between MTC and PSC by analyzing the differences in nonvolatile organic compounds (NVOCs), taste, odor, and volatile organic compounds (VOCs). METHODS: Liquid chromatography-mass spectrometry (LC-MS) was utilized to analyze the NVOCs of MTC and PSC. Electronic tongue (E-tongue) and electronic nose (E-nose) were used to analyze their taste and odor respectively. Gas chromatography-ion mobility spectrometry (GC-IMS) was applied to analyze VOCs. Finally, multivariate statistical analyses were conducted to further investigate the differences between MTC and PSC, including principal component analysis, orthogonal partial least squares discriminant analysis, discriminant factor analysis, and soft independent modeling of class analysis. RESULTS: The results of this study indicate that the integrated strategy of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis can be effectively applied to distinguish between MTC and PSC. Using LC-MS, 25 NVOCs were identified in MTC, while 18 NVOCs were identified in PSC. The major compounds in MTC are steroids, while the major compounds in PSC are iridoid glycosides. Similarly, the distinct taste difference between MTC and PSC was precisely revealed by the E-tongue. Specifically, the pronounced bitterness in PSC was proven to stem from iridoid glycosides, whereas the bitterness evident in MTC was intimately tied to steroids. The E-nose detected eight odor components in MTC and six in PSC, respectively. The subsequent statistical analysis uncovered notable differences in their odor profiles. GC-IMS provided a visual representation of the differences in VOCs between MTC and PSC. The results indicated a relatively high relative content of 82 VOCs in MTC, contrasted with 32 VOCs exhibiting a similarly high relative content in PSC. CONCLUSION: In this study, for the first time, the combined use of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis has proven to be an effective method for distinguishing between MTC and PSC from multiple perspectives. This approach provides a valuable reference for the identification of other visually similar traditional Chinese medicines.

A strategy to comprehensively analyze the bioactivity of complex herbal prescriptions via peak-by-peak cutting and knock-out chromatography: Qiliqiangxin capsule as an example.

An herbal prescription is usually composed of several herbal medicines. The complex and diverse components bring great challenges to its bioactivity study. To comprehensively analyze the bioactivity of an herbal prescription, a new strategy based on peak-by-peak cutting and knock-out chromatography was proposed. In this strategy, active compounds were screened out via peak-by-peak cutting from an herbal extract, and the influence of a compound on the overall activity of the herbal extract was evaluated by knock-out chromatography. Qiliqiangxin capsule is an herbal prescription composed of 11 herbal medicines for the treatment of chronic heart failure. A total of 71 peaks were collected through peak-by-peak cutting, and each peak was identified by a high-resolution mass spectrum. The bioassay against 1,1-diphenyl-2-picrylhydrazyl showed that two types of compounds namely salvianolic acids and caffeoylquinic acids were potent scavengers. Knock-out chromatography suggested that the removal of one single compound had no obvious influence on the overall activity of the Qiliqiangxin capsule. After all the main peaks in the Qiliqiangxin capsule were knocked out, the remaining part still exhibited a potent activity, indicating high activity stability of the Qiliqiangxin capsule. The proposed strategy is helpful for the comprehensive analysis of the bioactivity of other herbal prescriptions.

Efficient tandem organic light-emitting diodes with non-doped structures.

Highly efficient tandem organic light-emitting diodes (TOLEDs) were achieved based on a non-doped charge generation unit (CGU) consisting of LiF/Al/C60/4,4',4"-tris(N-3-methylphenyl-N-phenyl-amino) triphenylamine (m-MTDATA) and ultrathin emitting layers. The current-voltage characteristics of the CGU devices and electron-only devices and the capacitance-voltage characteristics of the CGU-based capacitance devices were characterized to explore the charge generation and injection mechanisms. The charge generation process occurs at the interface of C60/m-MTDATA through electron transferring from the highest occupied molecular orbital of m-MTDATA to the lowest unoccupied molecular orbital of C60. It is found that the thinner C60 layer contributes to efficient electron injection. Under the optimal structure, the blue TOLEDs exhibit a maximum current efficiency (CEmax) of 43.3 cd/A. The CEmax and maximum external quantum efficiency (EQEmax) of the white TOLEDs reach 84.6 cd/A and 26.7%, respectively.

YvoA and CcpA Repress the Expression of chiB in Bacillus thuringiensis.

Bacillus thuringiensis produces chitinases, which are involved in its antifungal activity and facilitate its insecticidal activity. In our recent work, we found that a 16-bp sequence, drechiB (AGACTTCGTGATGTCT), downstream of the minimal promoter region of the chitinase B gene (chiB) was a critical site for the inducible expression of chiB in B. thuringiensis Bti75. In this work, we show that a GntR family transcriptional regulator (named YvoABt), which is homologous to YvoA of Bacillus subtilis, can specifically bind to the drechiB oligonucleotide sequences in vitro by using electrophoretic mobility shift assays (EMSAs) and isothermal titration calorimetry (ITC) assays. The results of quantitative real-time reverse transcription-PCR (qRT-PCR) and Western blotting indicated that deletion of yvoA caused an ∼7.5-fold increase in the expression level of chiB. Furthermore, binding of purified YvoABt to its target DNA could be abolished by glucosamine-6-phosphate (GlcN-6-P). We also confirmed, in the presence of the phosphoprotein Hpr-Ser45-P, that purified CcpABt bound specifically to the promoter of chiB, which contains the "crechiB" sequence (ATAAAGCGTTTACA). According to the results of qRT-PCR and Western blotting, deletion of ccpA resulted in a 39-fold increase in the chiB expression level, and glucose no longer influenced the expression of chiB. We confirm that chiB is negatively controlled by both CcpABt and YvoABt in Bti75.

Characterization of regulatory regions involved in the inducible expression of chiB in Bacillus thuringiensis.

Expression of the chiB gene from Bacillus thuringiensis Bti75 was defined as inducible by the use of transcriptional fusions with the bgaB reporter gene. The transcription start site of the chiB gene was identified as the C base located 132 base pairs upstream of the start codon. Analysis of 5' and 3' deletions of the chiB promoter region revealed that the sequence from position -192 to +36 with respect to the transcription start site was necessary for wild-type levels of inducible expression of the chiB gene. The minimal promoter region for the expression of chiB gene was identified as the sequence from position -100 to +12. Furthermore, a 16-bp sequence (designated dre) downstream of the minimal promoter region of chiB was shown to be required for chitin induction. To confirm the function of this 16-bp sequence, 25 base substitutions were introduced into the dre site. Most of the mutations resulted in constitutive expression, or the efficiency of induction decreased. All mutations identified the dre sequence as a critical site for the inducible expression of chiB. In addition, the dre site was shown to interact with a sequence-specific DNA binding factor of strain Bti75 cultured in the absence of the inducer.

Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells.

Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2α, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer's disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.

Integration of High-Resolution LC-Q-TOF Mass Spectrometry and Multidimensional Chemical-Biological Analysis to Detect Nanomolar-Level Acetylcholinesterase Inhibitors from Different Parts of Zanthoxylum nitidum.

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 µM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.

Correction: Chen et al. Multifunctional Injectable Hydrogel Loaded with Cerium-Containing Bioactive Glass Nanoparticles for Diabetic Wound Healing. Biomolecules 2021, 11, 702.

The authors would like to replace Figure 4A of the following published paper [...].

Hsp90 inhibitor BIIB021 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53-MDM2 balance.

AIM: To investigate the effects of BIIB021, an inhibitor of heat shock protein 90 (Hsp90) alone or in combination with triptolide (TPL) on T-cell acute lymphoblastic leukemia (T-ALL) and the mechanisms of action. METHODS: Human T-ALL cells line Molt-4 was examined. The cell viability was measured using MTT assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. RESULTS: Treatment of Molt-4 cells with BIIB021 (50-800 nmol/L) inhibited the cell growth in a dose-dependent manner (the IC50 value was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h). BIIB021 dose-dependently induced G0/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BIIB021 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BIIB021 (50-400 nmol/L) dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL (5-40 nmol/L) dose-dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BIIB021 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. CONCLUSION: The combination of BIIB021 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.

Combinatorics-based chemical characterization and bioactivity comparison of different parts of traditional Chinese medicinal plants through LC-Q-TOF-MS/MS, multivariate statistical analysis and bioassay: Marsdenia tenacissima as an example.

Marsdenia tenacissima is a traditional Chinese medicinal plant used for treating cancer, and its main medicinal part is the stem. Considering the resource shortage of M. tenacissima, it is of great significance to improve its utilization efficiency. Steroids and caffeoylquinic acids, the two main components of M. tenacissima, are composed of several basic structures. Based on this rule, a novel strategy of combinatorics-based chemical characterization was proposed to analyze the constituents of roots, stems and leaves of M. tenacissima. Combinatorics was used to generate a compound library for structure alignment, which has the advantages of wide coverage and high specificity. Steroids are composed of four basic parts: core skeleton (C), substituent at position 11 (A), substituent at position 12 (B) and sugar moiety (S). Based on combinatorics, a compound library consisting of 1080 steroids was generated. Diagnostic neutral loss has been used to effectively predict the substituents at position 11 and 12 of steroids, including acetyl, 2-methylpropionyl, tigloyl, 2-methylbutyryl and benzoyl. As a result, 131, 131 and 99 components were detected from the roots, stems and leaves of M. tenacissima, respectively. Principal component analysis (PCA) was used to analyze the differences of roots, stems and leaves, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was further applied to find differential components. Tenacissoside H, a critical indicator component for quality evaluation of the stem, has been proved to be a differential component between roots and stems. Notably, the relative content of tenacissoside H in the roots was significantly higher than that in the stems. The bioactivity comparison showed that roots, stems and leaves of M. tenacissima had similar scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. However, their α-glucosidase inhibitory activity was ranked as leaves > stems > roots. Therefore, besides stems, the other parts of M. tenacissima have potential medicinal value. This study not only helps to develop the resource of M. tenacissima, but also provides a paradigm for the research of other similar medicinal plants.

Construction of a promoter-probe vector for Bacillus thuringiensis: the identification of cis-acting elements of the chiA locus.

The expression and application of Bacillus thuringiensis (Bt) chitinase genes have been extensively investigated. However, little information is available regarding the regulation of chitinase gene expression in Bt. In this study, a shuttle promoter-probe vector was constructed incorporating the thermostable ß-galactosidase gene bgaB of B. stearothermophilus as the reporter for the study of Bt promoters. Using this plasmid, the activity of the chiA gene promoter in Bt was investigated. Deletion analysis of the putative chiA promoter region revealed that the sequence located ~75 bp DNA from positions -116 to -42, with respect to the translation start site, is the core promoter of chiA gene. Furthermore, a site for chitin induction was identified near position -36. This site for negative regulation was indicated downstream of the RNA polymerase binding sites of the promoter of chiA. The expression of chiA started in cell grown for about 6 h and reached the maximum after 60 h of incubation. Induction of chiA expression by chitin was demonstrated by an increase in ß-galactosidase activity of ~2.5-fold.

[Comparison of the therapeutic effects of electroacupuncture and probiotics combined with deanxit in treating diarrhea-predominant irritable bowel syndrome].

OBJECTIVE: To study and compare the therapeutic effects of electroacupuncture and probiotics combine Deanxit in treating diarrhea predominant irritable bowel syndrome (D-IBS). METHODS: Totally 64 D-IBS patients accompanied with anxiety and/or depression were randomly assigned to the Western medicine group (Group A) and the electroacupuncture (EA) group (Group B), 30 patients in Group A and 34 patients in Group B. Patients in Group A took Bacillus licheniformis and Deanxit, while those in Group B received EA. Four weeks consisted of one therapeutic course. Three-month follow-up was carried out. The scoring for the digestive tract symptoms, HAMA score, and HAMD score were evaluated before and after treatment. The recurrence in the 3-month follow-up was also observed. RESULTS: The total effect rate was 86.67% in Group A and 88.24% in Group B with no statistical difference between the two groups (P > 0.05). There was statistical difference in the scoring for the digestive tract symptoms, HAMA score, and HAMD score (P < 0.05, P < 0.01). There was no statistical difference in the improvement of defecation frequency score, HAMA score, HAMD score between the two groups after treatment (P > 0.05). Better effects on improving abdominal pain score and abdominal distention score was obtained in Group B (P < 0.01), while better effects on improving the stool form score and mucus score were obtained in Group A (P < 0.01). There was no statistical difference in the recurrence rate between the two groups within the two-month follow-up (P > 0.05). The recurrence rate within the 3-month follow-up was obviously lower in Group B than in Group A (P < 0.05). CONCLUSIONS: EA and Western medicine (probiotics combined Deanxit) could effectively treat D-IBS patients accompanied with anxiety and/or depression. Both of them had different superiorities in improving symptoms. But EA had better long-term therapeutic effects.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

[Regulation of chitinase genes expression in bacteria].

Chitinases, which can hydrolyze chitin, occur in a wide range of microorganisms including viruses, bacteria, and fungi. The derivatives of chitin are potentially useful in several areas such as food processing, medicines, and biological control in agriculture. Some bacteria can uptake and utilize chitin as carbon source by secreting chitinase. The chitin is degraded into chito-oligosaccharides [(GlcNAc)n] or N-acetylglucosamine (GlcNAc) by chitinases, and then the chitin derivatives are transferred into cells by specific transport systems of bacteria. The intracellular chitin derivatives activate or suppress the transcription of a series of chi genes and affect the amount of chitinase. The expression of chitinase genes are strictly regulated by various regulatory factors and responsive cis-acting elements. The present review will focus on the transport system and the regulation of chitinase genes expression in bacteria.

Inhibition of MDA-MB-231 cell proliferation by pHLIP(Var7)-P1AP and SPECT imaging of MDA-MB-231 breast cancer-bearing nude mice using 125I-pHLIP(Var7)-P1AP.

AIM: To observe the effect of pHLIP(Var7)-P1AP on the proliferation of MDA-MB-231 triple-negative breast cancer cells and the small-animal single-photon-emission computed tomography (SPECT) imaging of breast cancer-bearing mice carrying MDA-MB-231 cells. METHODS: Peptide pHLIP(Var7)-P1AP was synthesized by solid-phase peptide synthesis. The binding of fluorescently labeled pHLIP(Var7)-P1AP to MDA-MB-231 cells under various pH conditions and its effect on MDA-MB-231 cell proliferation were analyzed. pHLIP(Var7)-P1AP was labeled with 125I, and the biological distribution of 125I-pHLIP(Var7)-P1AP in the breast cancer mouse model carrying MDA-MB-231 cells as well as the outcome of small-animal SPECT imaging were evaluated. RESULTS: pHLIP(Var7)-P1AP was successfully synthesized. Under pH 6.0, fluorescently labeled pHLIP(Var7)-P1AP had a higher binding ability to MDA-MB-231 cells and significantly inhibited the proliferation of MDA-MB-231 cells. The labeling efficiency of pHLIP(Var7)-P1AP with 125I was 33.1 ±â€Š2.7 %, and the radiochemical purity was 98.5 ±â€Š1.8 %. 125I-pHLIP(Var7)-P1AP showed a high concentration in tumors. Small-animal SPECT imaging showed clearly visible tumors at 4 h after injection. CONCLUSIONS: In the acidic environment, pHLIP(Var7)-P1AP can efficiently target MDA-MB-231 cells and inhibit their growth. Small-animal SPECT of 125I-pHLIP(Var7)-P1AP can clearly image tumors.

A strategy to discover selective α-glucosidase/acetylcholinesterase inhibitors from five function-similar citrus herbs through LC-Q-TOF-MS, bioassay and virtual screening.

The lack of direct connection between traditional herbal medicines and multiple biological targets is a bottleneck in herbal research and quality evaluation. To solve this problem, a strategy for the discovery of active ingredients from function-similar herbal medicines based on multiple biological targets was proposed in this article. The technical route includes chromatographic separation, mass spectrometry analysis, enzymatic activity detection, pharmacophore analysis and molecular docking. Five citrus herbs of Citri Reticulatae Pericarpium (CRP), Citri Exocarpium Rubrum (CER), Citri Grandis Exocarpium (CGE), Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) were used as the research objects. A total of 136 chemical components were identified from above five herbs based on LC-Q-TOF-MS/MS and database matching. The extracts of the five herbs showed obvious inhibitory effects on α-glucosidase and acetylcholinesterase in a concentration-dependent manner. Interestingly, the different types of components in the herbs exhibited selectivity for different targets: flavanone glycosides are effective on α-glucosidase but ineffective on acetylcholinesterase; polymethoxyflavonoids are effective on acetylcholinesterase but ineffective on α-glucosidase. Furthermore, we found for the first time that the components in citrus herbs exhibit opposite structure-activity relationships on the above two targets. For example, the methoxy group can enhance the activity of compounds on acetylcholinesterase but weaken the activity of compounds on α-glucosidase. The selective action is a supplement to the "multi-components, multi-targets" system of herbal medicines. Pharmacophore analysis and molecular docking were applied to explore the interaction between active ingredients and biological targets from the perspective of ligands and receptors, respectively. By combining the above multiple technologies, a strong connection among herbal medicines, chemical components and multiple biological targets was established. This work not only helps to understand the similar function of citrus herbs for the treatment of diabetes and Alzheimer's disease, but also provides selective lead compounds for the development of related drugs. This strategy is also helpful to improve the quality evaluation of citrus herbs from the perspective of biological activity.

Classification-based strategies to simplify complex traditional Chinese medicine (TCM) researches through liquid chromatography-mass spectrometry in the last decade (2011-2020): Theory, technical route and difficulty.

The difficulty of traditional Chinese medicine (TCM) researches lies in the complexity of components, metabolites, and bioactivities. For a long time, there has been a lack of connections among the three parts, which is not conducive to the systematic elucidation of TCM effectiveness. To overcome this problem, a classification-based methodology for simplifying TCM researches was refined from literature in the past 10 years (2011-2020). The theoretical basis of this methodology is set theory, and its core concept is classification. Its starting point is that "although TCM may contain hundreds of compounds, the vast majority of these compounds are structurally similar". The methodology is composed by research strategies for components, metabolites and bioactivities of TCM, which are the three main parts of the review. Technical route, key steps and difficulty are introduced in each part. Two perspectives are highlighted in this review: set theory is a theoretical basis for all strategies from a conceptual perspective, and liquid chromatography-mass spectrometry (LC-MS) is a common tool for all strategies from a technical perspective. The significance of these strategies is to simplify complex TCM researches, integrate isolated TCM researches, and build a bridge between traditional medicines and modern medicines. Potential research hotspots in the future, such as discovery of bioactive ingredients from TCM metabolites, are also discussed. The classification-based methodology is a summary of research experience in the past 10 years. We believe it will definitely provide support and reference for the following TCM researches.

Evaluation of the clinical application of the Postpartum Depression Predictors Inventory-Revised for postpartum women in China.

AIM: This study was designed to assess the clinical applicability of the Postpartum Depression Predictors Inventory-Revised (PDPI-R) during the 1st month following delivery among women in China and to survey the prevalence of postpartum depression (PPD)-related risk factors included in the PDPI-R in this population. METHODS: This was a cross-sectional study which recruited 447 women from the People's Liberation Army Hospital in Hefei of Anhui province. All participants completed the Chinese version of the PDPI-R (PDPI-R-C) and the Chinese version of the Edinburgh Postnatal Depression Scale (C-EPDS) within 1 month of delivery. The predictive ability of the PDPI-R was then evaluated through receiver operating characteristic (ROC) curve analyses. RESULTS: The PDPI-R-C was able to accurately predict 73.2% of PPD cases (area under the ROC curve = 0.732; 95% CI 0.69-0.78) using a cut-off score of 5.5, as defined by a C-EPDS score of ≥10 (sensitivity = 62.8%; specificity = 73.5%; positive predictive value = 74.5%; negative predictive value = 61.5%). All 13 risk factors in the PDPI-R-C other than socioeconomic status and marital status were associated with the risk of PPD. CONCLUSIONS: The PDPI-R-C was found to be an effective and easy-to-implement tool that has promise as a means of screening for PPD in Chinese populations.

Multifunctional Injectable Hydrogel Loaded with Cerium-Containing Bioactive Glass Nanoparticles for Diabetic Wound Healing.

Diabetic foot wound healing is a major clinical problem due to impaired angiogenesis and bacterial infection. Therefore, an effective regenerative dressing is desiderated with the function of promoting revascularization and anti-bacteria. Herein, a multifunctional injectable composite hydrogel was prepared by incorporation of the cerium-containing bioactive glass (Ce-BG) into Gelatin methacryloyl (GelMA) hydrogel. The Ce-BG was synthesized by combining sol-gel method with template method, which maintained spherical shape, chemical structure and phase constitution of bioactive glass (BG). The Ce-BG/GelMA hydrogels had good cytocompatibility, promoted endothelial cells migration and tube formation by releasing Si ion. In vitro antibacterial tests showed that 5 mol % CeO2-containing bioactive glass/GelMA (5/G) composite hydrogel exhibited excellent antibacterial properties. In vivo study demonstrated that the 5/G hydrogel could significantly improve wound healing in diabetic rats by accelerating the formation of granulation tissue, collagen deposition and angiogenesis. All in all, these results indicate that the 5/G hydrogel could enhance diabetic wound healing. Therefore, the development of multifunctional materials with antibacterial and angiogenic functions is of great significance to promote the repair of diabetic wound healing.

A strategy to discover lead chemome from traditional Chinese medicines based on natural chromatogram-effect correlation (NCEC) and natural structure-effect correlation (NSEC): Mahonia bealei and Mahonia fortunei as a case study.

Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC50 values. The structure-activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of "stem is the medicinal part of Mahonia bealei and Mahonia fortunei". Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants.