Application of microbial-induced carbonate precipitation (MICP) techniques to remove heavy metal in the natural environment: A critical review.

The occurrence of imbalanced heavy metals concentration due to anthropogenic hindrances in the aquatic and terrestrial environment has become a potential risk to life after circulating through different food chains. The microbial-induced carbonate precipitation (MICP) method has gradually received great attention from global researchers but the underlying mechanism of heavy metal mineralization is not well-understood and challenging, limiting the applications in wastewater engineering. This paper reviews the metabolic pathways, mechanisms, operational factors, and mathematical/modeling approaches in the MICP process. Subsequently, the recent advancement in MICP for the remediation of heavy metal pollution is being discussed. In the follow-up, the key challenges and prospective associated with technical bottlenecks of MICP method are elaborated. The prospective study reveals that MICP technology could be efficiently used to remediate heavy metal contaminants from the natural environment in a cost-effective way and has the potential to improve soil properties while remediating heavy metal contaminated soil.

Intestinal fungi and systemic autoimmune diseases.

Nearly 20 years of studies have shown that fungi and the human immune system (non-specific immunity and specific immunity) and bacterial--fungal interactions maintain a balance that can't lead to diseases. Fungi--microorganism that lives in human intestine--may play an important role in human health and disease. Population studies and animal models in some diseases have found the changes in the diversity and composition of fungi. The dysregulation of the fungi can disrupt the normal "running" of the immune system and bacteria, which triggers the development of inflammatory diseases. The latest studies of fungi in inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and type 1 diabetes mellitus were summarized. This review considers how the healthy host protect against the potential harm of intestinal fungi through the immune system and how fungal dysregulation alters host immunity.

Unusual N-pyridinium amino acid-type alkaloids from roots and rhizomes of Sophora tonkinensis Gagnep.

Two previously undescribed amino acid-type alkaloids with unusual N-pyridinium cation (1-2) and six known alkaloids (3-8), were isolated from the roots and rhizomes of Sophora tonkinensis Gapnea. Their structures were characterized by UV, IR, NMR, and HRESIMS spectroscopic data. The absolute configurations of compounds 1 and 2 were established through comparison of their experimental ECD spectra to the theoretical spectra of 2 calculated by TDDFT method. The plausible biosynthetic pathway of pyridinium was also proposed. Moreover, compound 4 exhibited weak XOD inhibitory activity with the inhibition rate of 65.8% at concentration of 10 µM.

Aromatic diglycosides from Sophora tonkinensis and a multi-step conformer filtering procedure for TDDFT calculation of flexible glycoside.

Three previously undescribed aromatic diglycosides (1, 5, and 8) and six known analogs (2-4, 6, 7, and 9) were isolated from the roots and rhizomes of Sophora tonkinensis Gagnep. Their structures were elucidated by detailed spectroscopic analysis. The absolute configuration of compound 8 was determined by comparing the experimental and TDDFT calculated ECD spectra of 8 and aglycone 8a. Furthermore, a multistep conformer filtering procedure for TDDFT calculation of flexible glycoside was proposed, which afforded high accuracy with acceptable computing cost in determining the absolute configuration of glycosides using quantum calculated ECD.

Altered gut fungi in systemic lupus erythematosus - A pilot study.

Objective: Gut fungi, as symbiosis with the human gastrointestinal tract, may regulate physiology via multiple interactions with host cells. The plausible role of fungi in systemic lupus erythematosus (SLE) is far from clear and need to be explored. Methods: A total of 64 subjects were recruited, including SLE, rheumatoid arthritis (RA), undifferentiated connective tissue diseases (UCTDs) patients and healthy controls (HCs). Fecal samples of subjects were collected. Gut fungi and bacteria were detected by ITS sequencing and 16S rRNA gene sequencing, respectively. Alpha and beta diversities of microbiota were analyzed. Linear discriminant analysis effect size analysis was performed to identify abundance of microbiota in different groups. The correlation network between bacterial and fungal microbiota was analyzed based on Spearman correlation. Results: Gut fungal diversity and community composition exhibited significant shifts in SLE compared with UCTDs, RA and HCs. Compared with HCs, the alpha and beta diversities of fungal microbiota decreased in SLE patients. According to principal coordinates analysis results, the constitution of fungal microbiota from SLE, RA, UCTDs patients and HCs exhibited distinct differences with a clear separation between fungal microbiota. There was dysbiosis in the compositions of fungal and bacterial microbiota in the SLE patients, compared to HCs. Pezizales, Cantharellales and Pseudaleuria were enriched in SLE compared with HCs, RA and UCTDs. There was a complex relationship network between bacterial and fungal microbiota, especially Candida which was related to a variety of bacteria. Conclusion: This study presents a pilot analysis of fungal microbiota with diversity and composition in SLE, and identifies several gut fungi with different abundance patterns taxa among SLE, RA, UCTDs and HCs. Furthermore, the gut bacterial-fungal association network in SLE patients was altered compared with HCs.

Undescribed protolimonoids from the root bark of Dictamnus dasycarpus Turcz.

Nine undescribed protolimonoids, including two apotirucallane and seven tirucallane triterpenoids, as well as five known compounds, were isolated from the root bark of Dictamnus dasycarpus Turcz. Their structures were elucidated by extensive spectroscopic analysis. Compounds 4-8, with an undescribed 22,25-epoxytirucallene part, were established their absolute configuration by single-crystal X-ray diffraction of 4. Such compounds might provide evidence for the degradation of protolimonoids to limonoids, bridging an oxidative cleavage biogenetic pathway between these structurally diverse triterpenoids. None of them showed anti-inflammatory, hepatoprotective, or monoamine oxidase B inhibitory activity.

Cutaneous mucosa-associated lymphoid tissue lymphoma complicating Sjögren's syndrome: A case report and review of literature.

BACKGROUND: The association of Sjögren's syndrome (SS) and lymphoma is similar. Mucosa-associated lymphoid tissue (MALT) or extranodal marginal zone B-cell lymphoma was the most common lymphomatous histology in SS patients. MALT in SS patients is frequently located in the parotid gland, while MALT lymphoma of the skin with SS is an exceedingly rare entity that needs to be recognized. CASE SUMMARY: A 60-year-old woman presented with a 3-year history of progressive dry mouth associated with a 1-year history of enlarging cutaneous nodules. Physical examination revealed two hard subcutaneous nodules on her right lower leg. The results of Schirmer's test were positive, despite the absence of dry eyes. Labial salivary gland biopsy revealed lymphocytic infiltration and chronic inflammation with a focus score of 2. The patient was diagnosed with SS. She underwent resection of one cutaneous nodule, and histopathological analysis identified the nodule as MALT lymphoma. Her dry mouth symptoms improved, and the nodules decreased after 6 mo of treatment with hydroxychloroquine sulfate and chemotherapy (thalidomide, cyclophosphamide, and dexamethasone). CONCLUSION: Lymphoma is a severe complication of SS, shown by the reported unique case of cutaneous MALT lymphoma with SS.

Structures and neuroprotective activities of triterpenoids from Cynomorium coccineum subsp. songaricum (Rupr.) J. Leonard.

Cynomorium coccineum subsp. songaricum (Rupr.) J. Leonard has been widely used as a Chinese herbal remedy or a functional food for treating symptoms of aging or neurodegenerative diseases. A further investigation on the finding of active constituents led to the isolation and identification of four previously undescribed triterpenoids, together with 20 known compounds. Their structures were elucidated by extensive spectroscopic analysis (IR, NMR, HRMS, and CD). Sixteen compounds showed significant neuroprotective effects against glutamate-induced or oxygen-glucose deprivation-induced SK-N-SH cell death. Our findings revealed the active constituents of C. coccineum subsp. songaricum and indicated that both oleanane-type and ursane-type triterpenes could be valuable platforms for neurodegenerative agents based on primary structure-activity relationship analysis.

A full set of 8,4'-oxy-8'-phenylneolignan stereoisomers from Sophora tonkinensis and their absolute configurations by TDDFT.

A full set of 8,4'-oxy-8'-phenylneolignans with four chiral carbons, named (+)/(-)-leptolepisols D1‒D2 and (+)/(-)-sophorols A‒F, were isolated from the roots and rhizomes of Sophora tonkinensis Gagnep., including 14 previously undescribed stereoisomers, along with 2 known leptolepisol D diastereomers. Their planar structures and relative configurations were elucidated by detailed spectroscopic analysis (HRESIMS and NMR). Based on a highly accurate conformer filtering protocol at low computational cost, the absolute configurations of full set 8,4'-oxy-8'-phenylneolignans were completely assigned by TDDFT calculations of ECD spectra for the first time. Furthermore, (+)/(-)-sophorol A, (-)-sophorol B, and (-)-sophorol E could moderately suppress the lipopolysaccharide-induced nitric oxide production in murine macrophages at 10 µM, with inhibitory ratios of 48.4-52.9%.

Antimicrobial alkaloids from the root bark of Dictamnus dasycarpus.

Two new furoquinoline alkaloids, named 1'-oxo-isoplatydesmine (1) and demethoxyacrophylline (2), as well as 11 known alkaloids (3-13) were isolated from the root bark of Dictamnus dasycarpus Turcz. The structures of 1 and 2 were established by detailed spectroscopic elucidation, such as 1 D & 2 D NMR and HRMS, etc. The unexpected autoracemization of 1 was discussed based on the stereochemistry of reported dihydrofuroquinolines. Compounds 3-5 exhibited moderate inhibitory activities against Bacillus subtilis, Candida albicans, and Pseudomonas aeruginosa with MICs 32-64 µg/ml, revealing the active principles of D. dasycarpus for treating skin diseases in its traditional usage.

Machine learning prediction of antiviral-HPV protein interactions for anti-HPV pharmacotherapy.

Persistent infection with high-risk types Human Papillomavirus could cause diseases including cervical cancers and oropharyngeal cancers. Nonetheless, so far there is no effective pharmacotherapy for treating the infection from high-risk HPV types, and hence it remains to be a severe threat to the health of female. Based on drug repositioning strategy, we trained and benchmarked multiple machine learning models so as to predict potential effective antiviral drugs for HPV infection in this work. Through optimizing models, measuring models' predictive performance using 182 pairs of antiviral-target interaction dataset which were all approved by the United States Food and Drug Administration, and benchmarking different models' predictive performance, we identified the optimized Support Vector Machine and K-Nearest Neighbor classifier with high precision score were the best two predictors (0.80 and 0.85 respectively) amongst classifiers of Support Vector Machine, Random forest, Adaboost, Naïve Bayes, K-Nearest Neighbors, and Logistic regression classifier. We applied these two predictors together and successfully predicted 57 pairs of antiviral-HPV protein interactions from 864 pairs of antiviral-HPV protein associations. Our work provided good drug candidates for anti-HPV drug discovery. So far as we know, we are the first one to conduct such HPV-oriented computational drug repositioning study.

Modular prosthesis fracture in a patient with developmental dysplasia of the hip: a case report and literature review.

BACKGROUND: Modular prosthesis fracture, especially distal femoral fracture, is a rare complication of total hip arthroplasty (THA). However, it is catastrophic, and may have a serious impact on the patients. A distal femoral prosthesis fracture in a patient with developmental dysplasia of the hip (DDH) with nonunion at the subtrochanteric osteotomy site has not yet been reported in any literature. This report presents the first such case, with a purpose of analyzing the causes of modular prosthesis fractures and nonunion of the osteotomy area, so as to provide orthopedic surgeons with experience and lessons. CASE PRESENTATION: We report the case of a 52-year-old woman with the distal femoral prosthesis fracture after THA and subtrochanteric osteotomy for Crowe type IV DDH. The patient had severe pain in the left thigh and her activities were limited. Plain radiographs revealed fracture of the left distal femoral prosthesis and nonunion in the subtrochanteric osteotomy region of the left femur. After a revision of the THA, the patient's symptoms were resolved. CONCLUSIONS: A prosthesis fracture combined with nonunion at the subtrochanteric osteotomy site is a rare complication. Modular THA combined with a subtrochanteric osteotomy in the treatment of Crowe type IV DDH should reduce the damage to blood supply and avoid further nonunion of the osteotomy area, which may otherwise lead to modular prosthesis fractures. A detailed preoperative plan and suitable rehabilitation program may help minimize the occurrence of subtrochanteric osteotomy nonunion and reduce complications, including femoral prosthesis fractures, in patients with DDH.

Molecular evidence of herbal formula: a network-based analysis of Si-Wu decoction.

INTRODUCTION: Emerging network pharmacology (NP) combines phytochemical information with bioinformatics tools allowing herbal formulae to be illustrated holistically in the context of phytochemical basis and therapeutic mechanisms. OBJECTIVE: This study attempted to explore the holistic molecular evidence of herbal formula Si-Wu decoction (SWD) by using the method of NP. MATERIAL AND METHOD: Databases of traditional medicines combined with PubChem, SciFinder, SEA, STRING, and KEGG were employed to gather information for establishing the "compound similarity" (CS) network and the "target-(pathway)-target" (TPT) network. Gephi software was applied to visualise the networks, with further module-based and node-based network topological analysis. Moreover, the approved drugs and shortest path analysis were used to validate the TPT network. RESULTS: The CS network presented the phytochemical profile of SWD, including the major compound groups of iridoid glycosides, glycosides, phthalide lactones, phenylpropanoids, and monoterpenoids. Furthermore, the topological analysis of TPT network depicted the holistic property of SWD in interpretable neuroendocrine immunomodulation (NIM) perspective, and the node degree analysis indicated a closer connection of SWD with endocrine or metabolism system. Moreover, by combing the analysis of the CS network and TPT network, potential active ingredients could be primarily identified. CONCLUSION: The phytochemical profile and molecular target profile, which might pave the way for an understanding of SWD in modern science and provide a reference for relevant quality research and evaluation, were demonstrated by network analysis. Moreover, the methods could be further applied to discover the phytochemical or biomolecular evidence with distinct advantages in dealing with the tremendous separated information.

Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic analysis.

Yinchenhao decoction (YCHD) is a classical Traditional Chinese Medicine (TCM) formula that has been widely used in the treatment of liver fibrosis caused by chronic hepatitis B and jaundice for more than 1800 years. The purpose of this study was to investigate the apoptosis regulation mechanisms of YCHD and its active components suppresses liver fibrosis. The active components and putative targets of YCHD were predicted by network pharmacology approach. Functional and pathway enrichment analysis were presented in the present study by using clusterProfiler. Further, experimental validation was done by using terminal deoxynucleotidyl transferase (TDT) dUTP nick end labelling (TUNEL) assay and western blotting in dimethylnitrosamine (DMN)-induced liver fibrosis rats, and cell proliferation assay, apoptosis assay, and western blotting in human hepatic L02 cells and LX2 cells. 45 active compounds in YCHD formula, 592 potential target proteins and 1191 liver fibrosis-related human genes were identified. Functional and pathway enrichment analysis indicated that YCHD obviously influenced TNF, PI3K-Akt signaling pathways. Further, In vivo experiment indicated that YCHD treatment not only attenuated the symptoms of liver fibrosis, but also decrease the apoptosis of hepatic parenchyma cells. Moreover, in vitro experiments showed that rhein, kaempferol and quercetin treatments remarkably decreased the protein levels of cleaved caspase-3 and increased p-ERK1/2, PI3K and Bcl-XL protein expression in TNF-α-stimulated L02 cells. On the contrary, rhein, kaempferol, aloe-emodin and quercetin inhibited the proliferation of LX2 cells and up-regulated the protein levels of Bax and cleaved caspase-8. In conclusion, 45 active components and 296 potential targets of YCHD against liver fibrosis were identified by the analysis of network pharmacology and transcriptomics combination. The mechanisms of YCHD against liver fibrosis were involved in the regulation of multiple targets, especially affecting the apoptosis-related signaling pathways.

Comparative comprehension on the anti-rheumatic Chinese herbal medicine Siegesbeckiae Herba: Combined computational predictions and experimental investigations.

ETHNOPHARMACOLOGICAL RELEVANCE: Siegesbeckiae Herba (SH) is a traditional anti-rheumatic herbal medicine in China. The SH-derived product is the first licensed traditional herbal medicinal product for the management of rheumatism-induced joint and muscle pain in United Kingdom. The authenticated plant origins listed in the official Chinese Pharmacopeia for SH include Siegesbeckia orientalis L. (SO), S. pubescens Markino (SP) and S. glabrescens Markino (SG). Although the therapeutic effects of these SH species in treating rheumatoid arthritis (RA) are similar, their difference in chemical profiles suggested their anti-rheumatisms mechanisms and effects may be different. AIM OF THE STUDY: This study was designed to comparatively comprehend the chemical and biological similarity and difference of SO, SP and SG for treating rheumatoid arthritis based on the combination of computational predictions and biological experiment investigations. MATERIALS AND METHODS: The reported compounds for SO, SP and SG were obtained from four chemical databases (SciFinder, Combined Chemical Dictionary v2009, Dictionary of Natural Products and Chinese academy of sciences Chemistry Database). The RA-relevant proteins involved in nuclear factor-kappa B (NF-κB), oxidative stress and autophagy signaling pathways were collected from the databases of Kyoto Encyclopedia of Genes and Genomes and Biocarta. The comparative comprehension of SH plants was performed using similarity analysis, molecular docking and compounds-protein network analysis. The chemical characterization of different SH extracts were qualitatively and quantitatively analyzed, and their effects on specific RA-relevant protein expressions were investigated using Western blotting analysis. RESULTS: Chemical analysis revealed that SO contains mainly sequiterpenes and pimarenoids; SP contains mainly pimarenoids, sequiterpenes, and kaurenoids; and SG contains mainly pimarenoids, flavonoids and alkaloids. Moreover, coincided with the predicted results from computational analysis, different SH species were observed to present different chemical constituents, and diverse effects on RA-relevant proteins at the biological level. CONCLUSIONS: The chemical and biological properties of SO, SP and SG were different and distinctive. The systematic comparison between these three confusing Chinese herbs provides reliable characterization profiles to clarify the pharmacological substances in SH for the precise management of rheumatism/-related diseases in clinics.

[Gene cloning and expression analysis of an inducible heat shock protein 70 gene from the polychaete Perinereis aibuhitensis under Cu2+ stress.] / åŒé½¿å›´æ²™èš•è¯±å¯¼åž‹çƒ­ä¼‘å ‹è›‹ç™½70åŸºå› çš„å ‹éš†åŠCu胁迫下的表达分析.

The objective of this study was to evaluate the molecular characteristics of heat shock protein 70 (HSP70) gene, and document changes in HSP70 gene expression upon exposure of Perinereis aibuhitensis to aqueous Cu2+. Full length cDNA of HSP70 was sequenced and the characteristics of the translated protein were determined and compared both with other ragworms species and other invertebrates. The results showed that the cDNA was 2161 bp and consisted of a 5'-terminal untranslated region (UTR) of 48 bp, a 3'-termianl UTR of 142 bp with a canonical polyadenylation signal sequence AATAAA and a poly A tail, and an open reading frame (ORF) of 1971 bp. The HSP70 protein was 656 amino acids with a calculated molecular weight of 71.43 kD and theore-tical isoelectric point of 5.15. Sequence analysis of the protein showed that HSP70 of P. aibuhitensis contained three signature sequences IDLGTTYS, IFDLGGGTFDVSIL and IVLVGGSTRIPKIQK all belonging to the HSP70 family, a cytoplasm characteristic motif of EEVD, and the C-terminal repeats of GGMP. The molecular characteristics of P. aibuhitensis shared 94% identity with other ragworms and 79% identity with other invertebrates. In ragworms exposed to Cu2+, expression of HSP70 mRNA increased significantly with Cu2+ concentration (0.2-5.0 mg·L-1), and it reached the peak on 1-day exposure. In summary, the molecular characteristics of HSP70 of P. aibuhitensis were described, and its gene expression was inducible by exposure to aqueous Cu2+, suggesting HSP70 has potential to become a useful molecular biomarker of environmental pollution.

[Effect of Drought and Subsequent Re-wetting Cycles on Transferable Nitrogen and Its Form Distribution in the Sediment of Water Level Fluctuating Zone in the Tributary of Three Gorge Reservoir Areas].

Nitrogen is the most comment source of eutrophication in freshwater systems. In current study, we investigated the various forms of transferable nitrogen in sediments, which potentially contributed to the nitrogen output into waters. Sediments samples were collected in the water level fluctuating zone of Pengxi River crossing three hydrological sections, e. g. upstream, midstream and downstream and two water level altitudes, 160 m and 170 m, with multiple depths for each site, 0-20, 20-40, 40-60, 60-80, 80-100 cm. To characterize the response of transformation of nitrogen in sediment of the water level fluctuating zone towards cycles of drought and re-wetting processes, we analyzed the content and distribution of transferable nitrogen (TF-N) and its forms. The result showed that the changing of the amount of total nitrogen followed the pattern of upstream > midstream > downstream, the mean value was in the range of 313.02-3 255.53 mg. kg-1, while the content of total transferable nitrogen was on an average of 639.40 mg . kg-1 and coincided with the pattern of total nitrogen. In addition, TF-N followed the pattern of OSF-N > IMOF-N > OSF-N > IEF-N. It indicated that both OSF-N and IMOF-N dominated the form of TF-N in sediments by proportions of 50. 9% and 33. 3%, respectively. Since the transformation rate of OSF-N into dissolved phase was relatively slow, its contribution as a source of nitrogen to eutrophication was limited. We, thus, concluded that IMOF-N was the most important fraction which could be potentially affected by water fluctuation and contributed as dissolved nitrogen into water phase. This study indicated that the manner of manipulating water resource in the Three Gorges Reservoir area has raised the potential risk of transforming IMOF-N from sediment into water phase.

Highly functionalized pyridines synthesis from N-sulfonyl ketimines and alkynes using the N-S bond as an internal oxidant.

The N-S bond-based internal oxidant offers a distinct approach for the synthesis of highly functionalized pyridines. A novel Rh(III)-catalyzed one-pot process undergoes an efficient C-C/C-N bond formation along with desulfonylation under very mild conditions. The method is quite simple, general, and efficient.

[Influences of petroleum hydrocarbons on accumulation of cadmium and induction of metallothionein in the polychaete Perinereis aibuhitensis].

Ragworm (Polychaeta) is an ecologically important species in intertidal mudflats and estuaries and is recognized as a sentinel species for environmental monitoring. In the intertidal belt of China, the ragworm Perinereis aibuhitensis is frequently exposed to various toxicants including cadmium (Cd) and petroleum hydrocarbons (PHCs). The present study investigated the influence of PHCs on accumulation of Cd and the induction of metallothionein (MT) in P. aibuhitensis by means of chronic microcosm experiment in which the ragworms were exposed to Cd or combinations of Cd and PHCs. The accumulation of Cd in P. aibuhitensis increased significantly with the Cd exposure concentration when exposed to Cd alone. Further, the bioconcentration factors (BCFs) for Cd in P. aibuhitensis increased with the duration of exposure. The addition of PHCs in Cd exposure solutions significantly increased the accumulation of Cd in P. aibuhitensis, compared with the control. Exposure to Cd induced the expression of MT, and the expression increased with the concen- tration up to 180 mg · kg(-1) DM Cd at which point the level of induction did not increase. PHCs without Cd did not significantly induce MT in P. aibuhitensis, but the addition of PHCs with Cd did influence the induction of MT compared to Cd without PHCs. Results indicated that PHCs could modulate the expression of MT during co-exposure with Cd. The potential substances other than metals influencing the interpretation of MT expression in wild P. aibuhitensis must be recognized when MT is used as a monitoring index.

[Mechanism study on preventive and curative effects of buyang huanwu decoction in Qi deficiency and blood stasis diseases based on network analysis].

In this study, researchers adopted the network analysis method to study Buyang Huanwu decoction at three levels, namely chemical ingredients, targets and diseases, and discovered the potential effect of Buyang Huanwu decoction in cancer treatment. Besides, they analyzed the "target-target" network of Buyang Huanwu decoction based on diseases, calculated four network indexes, namely node centrality, closeness centrality, betweenness centrality and eigenvector centrality for a comprehensive evaluation on the importance and significance of each target in the network. Afterwards, key targets of Buyang Huanwu decoction were excavated to obtain two important targets--COX-2 and PPAR-gamma, which may be important targets involved in the qi deficiency and blood stasis diseases. Meanwhile, the two targets were the basis to build the core network of "chemical component-target-disease" of Buyang Huanwu decoction, which provided reference for further studies on the effect of Buyang Huanwu decoction in treating qi deficiency and blood stasis diseases. According to the study, the network analysis method was helpful to excavate potential targets Buyang Huanwu decoction in treating qi deficiency and blood stasis diseases, and could provide methodological reference for revealing the mechanism of Buyang Huanwu decoction at multiple levels, with a guiding significance for interpreting mechanisms of traditional Chinese medicinal formulae and developing new drugs.