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IntroductionScutellariae Radix (SR), derived from the root of Scutellaria baicalensis Georgi, is a traditional Chinese medicine (TCM) for clearing heat and cooling blood. It has been used as a traditional herbal medicine and is popular as a functional food in Asian countries today.MethodsIn this study, UPLC-Q-TOF-MS was first employed to identify the chemical components in the ethanol extract of SR. Then, the extraction process was optimized using star point design-response surface methodology. Fingerprints of different batches and processed products were established, and chemical markers were screened through a combination of various artificial neural network models. Finally, network pharmacology and molecular simulation techniques were utilized for verification to determine the quality markers.ResultsA total of 35 chemical components in SR were identified, and the optimal extraction process was determined as follows: ultrasonic extraction with 80% methanol at a ratio of 120:1 for 70 minutes, with a soaking time of 30 minutes. Through discriminant analysis using various artificial neural network models, the samples of SR could be classified into two categories based on their growth years: Kuqin (dried roots of older plants) and Ziqin (roots of younger plants). Moreover, the samples within each category could be further clustered according to their origins. The four different processed products of SR could also be distinguished separately. Finally, through the integration of network pharmacology and molecular simulation techniques, it was determined that baicalin, baicalein, wogonin, norwogonin, norwogonin-8-O-glucuronide, skullcapflavone II, hispidulin, 8, 8"-bibaicalein, and oroxylin A-7-O-beta-D-glucuronide could serve as quality markers for SR.DiscussionThe primary factors affecting the quality of SR were its growth years. The geographic origin of SR was identified as a secondary factor affecting its quality. Processing also had a significant impact on its quality. The selected quality markers have laid the foundation for the quality control of SR, and this research strategy also provides a research paradigm for improving the quality of TCM.

Abstract Background Panax japonicus C.A. Meyer (Zhujieshen) is widely used in traditional medicine as a tonic hemostatic and anti-inflammatory agent in China, Japan, and Korea. Furthermore, it is used as an important substitute for ginseng roots by minority ethnic groups in China. The purpose of this review is to summarize the latest research on Zhujieshen in recent years, aiming at providing a systematic overview of the current knowledge, and perspectives for future research and exploitation. Main body This review examines the research advances in botanical profile, phytochemicals, pharmacology, pharmacokinetics, and authentication of Zhujieshen. Various compounds have been reported as active components, mainly including saponins, volatile oils, and polysaccharides. Pharmacological investigations have demonstrated that Zhujieshen is an important herb with significant bioactivities, such as anti-inflammatory, hepato-protective, cardio-protective, neuro-protective, anti-tumor, anti-oxidant, anti-thrombotic and immunomodulatory activities. Conclusion Currently, research on Zhujieshen is in the preliminary stages, and further research is required to understand the active compounds present and mechanisms of action. We hope that this comprehensive review of Zhujieshen will serve as a background for future research and exploitation.

Coral reef ecosystems in the South China Sea are one of the globally important marine biodiversity hotspots. However, there are few studies on nematode biodiversity in coral reef sediments. Here, we assessed nematode biodiversity in coral reef sediments in the South China Sea using eDNA metabarcoding. Eight sampling stations were set up in the region north of the South China Sea Basin (Xisha and Zhongsha Islands) and south of it (Nansha Islands), respectively. We also compared and analysed the nematode biodiversity and community structure in different regions, as well as the effects of environmental factors on the community structure. The results showed that a total of 503 operational taxonomic units (OTUs) were detected in 16 sediment samples. The nematodes identified belong to two classes, 10 orders, 37 families, 51 genera and 61 species, and all of them were Enoplea and Chromadorea, except for the unidentified taxa, which accounted for 97.26% of the total abundance. The analyses showed that the northern region had higher nematode abundance and diversity relative to the southern region. However, there was no significant difference in the nematode community structure between the two regions, which was less affected by geographic location. Similarly, environmental factors (total nitrogen, total phosphorus, copper, zinc, cadmium, lead and arsenic) have an effect on the abundance of specific nematode groups but not on the overall community structure. In summary, this study initially reveals the composition and diversity of nematode communities in coral reef sediments in the South China Sea and provides an important reference for further in-depth study of the South China Sea ecosystem.

Honey is a natural food often used as an auxiliary material in Traditional Chinese Medicine (TCM). Cortex Mori (CM) is a commonly used Chinese medicinal material that requires honey preparation before use. Our research discovered that various factors including honey temperature, color intensity, moisture content, viscosity, TPC, 5-HMF content, and FRAP all increased over time during the honey refining process. To systematically study the excipients that play a unique role in TCM processing, this study focuses on honey as the representative and CM as the model drug. The overall components of honey-processed CM, stir-fried CM, and raw CM were determined using the fingerprint method, resulting in 36 chromatographic peaks with significant differences. The principal component analysis (PCA) results showed significant differences among honey-fried, stir-fried, and raw CM. Orthogonal partial least squares-discriminant analysis (OPLS-DA) and artificial neural network (ANN) were used to screen the important differential components. Network pharmacology and molecular docking technology were used to correlate the efficacy of the marker components. Oxyresveratrol, kuwanon G, and morusin were identified as potential markers. This study proved that the addition of honey as an excipient can affect the chemical composition of the drug itself, thereby impacting its efficacy.

Abstract The evaluation of soil quality can provide new insights into the sustainable management of forests. This study investigated the effects of three types of forest management intensities (non-management (CK), extensive management (EM), and intensive management (IM)), and five management durations (0, 3, 8, 15, and 20 years) on the soil quality of a Carya dabieshanensis forest. Further, minimum data sets (MDS) and optimized minimum data sets (OMDS) were established to evaluate the soil quality index (SQI). A total of 20 soil indicators representing its physical, chemical, and biological properties were measured for the 0–30 cm layer. Using one-way ANOVA and principal component analysis (PCA), the total data set (TDS), the minimum data set (MDS), and optimized minimum data set (OMDS) were established. The MDS and OMDS contained three (alkali hydrolyzed nitrogen (AN), soil microbial biomass nitrogen (SMBN), and pH) and four (total phosphorus (TP), soil organic carbon (SOC), AN, and bulk density (BD)) soil indicators, respectively. The SQI derived from the OMDS and TDS exhibited a stronger correlation (r = 0.94, p

Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy. A novel dual-drug codelivery nanosystem, which combines dual-drug administration with nanotechnology, can overcome the application limitation of free drugs. Both the characteristics of nanoparticles and the synergistic effect of dual drugs contribute to circumventing various drug-resistant mechanisms in tumor cells. Therefore, developing dual-drug codelivery nanosystems with different multidrug-resistant mechanisms has an important reference value for reversing MDR and enhancing the clinical antitumor effect. In this review, the advantages, principles, and common codelivery nanocarriers in the application of dual-drug codelivery systems are summarized. The molecular mechanisms of MDR and the dual-drug codelivery nanosystems designed based on different mechanisms are mainly introduced. Meanwhile, the development prospects and challenges of codelivery nanosystems are also discussed, which provide guidelines to exploit optimized combined chemotherapy strategies in the future.

Polygoni multiflori radix (PM) is a well-known tonic herb. It has been reported that PM could cause idiosyncratic inflammatory liver injury in some individuals. In this study, we investigated the mechanism of PM-induced idiosyncratic inflammatory liver injury in zebrafish and rat models based on pharmacodynamics and pharmacokinetics. The zebrafish were administered with polygoni multiflori radix extract (PME), emodin (EMO), and 2,3,5,4′-tetrahydroxystilbene-2-Ο-β-D-glucoside (TSG) after lipopolysaccharide (LPS) treatment, to establish an idiosyncratic inflammation model. In zebrafish with idiosyncratic inflammation, PME, EMO, and TSG decreased liver area and brightness and increased the number of immune cells around the colliculi. PME+LPS produced hepatocyte damage, aggravated mitochondrial and endoplasmic reticulum damage, and increased AST and ALT activity. RT-PCR showed that PME and EMO up-regulated the expression of IL-6, IL-1β, and INF-γ, and PME down-regulated expression of FXR and SHP. In rats with idiosyncratic inflammation, AST and ALT activities increased significantly, and liver tissues showed pathological damage. An efficient and sensitive LC-MS/MS method was established for the pharmacokinetic study of EMO and TSG in rats with idiosyncratic inflammation. The AUC0−t was higher for EMO and TSG in the model group compared with the normal group. The MRT0−t was significantly prolonged in EMO, while CLz/F was significantly reduced. The present results suggested that the absorption of potentially toxic components of PM increased and metabolism slowed down under inflammatory stress, and PM induced idiosyncratic liver injury via the FXR-SHP axis.

Abstract Background Ribosomal DNAs (rDNAs) are arranged in purely tandem repeats, preventing them from being reliably assembled onto chromosomes during generation of genome assembly. The uncertainty of rDNA genomic structure presents a significant barrier for studying their function and evolution. Results Here we generate ultra-long Oxford Nanopore Technologies (ONT) and short NGS reads to delineate the architecture and variation of the 5S rDNA cluster in the different strains of C. elegans and C. briggsae. We classify the individual rDNA’s repeating units into 25 types based on the unique sequence variations in each unit of C. elegans (N2). We next perform assembly of the cluster by taking advantage of the long reads that carry these units, which led to an assembly of 5S rDNA cluster consisting of up to 167 consecutive 5S rDNA units in the N2 strain. The ordering and copy number of various rDNA units are consistent with the separation time between strains. Surprisingly, we observed a drastically reduced level of variation in the unit composition in the 5S rDNA cluster in the C. elegans CB4856 and C. briggsae AF16 strains than in the C. elegans N2 strain, suggesting that N2, a widely used reference strain, is likely to be defective in maintaining the 5S rDNA cluster stability compared with other wild isolates of C. elegans or C. briggsae. Conclusions The results demonstrate that Nanopore DNA sequencing reads are capable of generating assembly of highly repetitive sequences, and rDNA units are highly dynamic both within and between population(s) of the same species in terms of sequence and copy number. The detailed structure and variation of the 5S rDNA units within the rDNA cluster pave the way for functional and evolutionary studies.

Early embryonic cell cycles usually alternate between S and M phases without any gap phase. When the gap phases are developmentally introduced in various cell types remains poorly defined especially during embryogenesis. To establish the cell-specific introduction of gap phases in embryo, we generate multiple fluorescence ubiquitin cell cycle indicators (FUCCI) in C. elegans. Time-lapse 3D imaging followed by lineal expression profiling reveals sharp and differential accumulation of the FUCCI reporters, allowing the systematic demarcation of cell cycle phases throughout embryogenesis. Accumulation of the reporters reliably identifies both G1 and G2 phases only in two embryonic cells with an extended cell cycle length, suggesting that the remaining cells divide either without a G1 phase, or with a brief G1 phase that is too short to be picked up by our reporters. In summary, we provide an initial picture of gap phase introduction in a metazoan embryo. The newly developed FUCCI reporters pave the way for further characterization of developmental control of cell cycle progression.

Cyclin-dependent kinase 1 (CDK1) plays an indispensable role in the whole cell cycle. It has become a new target for cancer therapy. According to the binding mode of a pan-CDK inhibitor, flavopiridol with CDK1, and our previous work, a new series of flavone derivatives were discovered. Among them, compound 2a showed the best CDK1 inhibitory and anti-proliferative potencies in the in vitro activity investigation. The IC50 of 2a against CDK1 was 36.42 ± 1.12 μM vs. 11.49 μM ± 0.56 of flavopiridol. In the anti-proliferation activity assays, 2a exhibited better activity toward RAW264.7 than MCF-7 cells. The results indicated that flavone derivatives, besides inhibiting the growth of tumor cells, can also antagonize inflammatory response. Molecular docking results showed that conformation of 2a can form hydrogen bonds and various hydrophobic interactions with the key amino acid residues of CDK1. It can be used as a promising lead compound for CDK1 inhibitor development.

Berberine (BBR) is a plant derived quaternary benzylisoquinoline alkaloid, which has been widely used in traditional medicines for a long term. It possesses broad pharmacological effects and is widely applied in clinical. In recent years, the anti-tumor effects of BBR have attracted more and more attention of the researchers. The canonical right-handed double-stranded helical deoxyribonucleic acid (B-DNA) and its polymorphs occur under various environmental conditions and are involved in a plethora of genetic instability-related diseases especially tumor. BBR showed differential binding effects towards various polymorphic DNA structures. But its poor lipophilicity and fast metabolism limited its clinical utility. Structural modification of BBR is an effective approach to improve its DNA binding activity and bioavailability in vivo. A large number of studies dedicated to improving the binding affinities of BBR towards different DNA structures have been carried out and achieved tremendous advancements. In this article, the main achievements of BBR derivatives in polymorphic DNA structures binding researches in recent 20 years were reviewed. The structural modification strategy of BBR, the DNA binding effects of its derivatives, and the structure activity relationship (SAR) analysis have also been discussed.

The removal of the net enclosure has been used as a lake management strategy in various regions of China as ecological development is given more attention. Nevertheless, little is known about the substantive impact of this measure on fish communities in inland lakes. To this end, the fish community composition and structural features after the removal of the net enclosure in Gehu Lake were explored and evaluated in this study from 2021 to 2022 and compared to the investigation before the net enclosure removal from 2017 to 2018. Belonging to 7 orders, 10 families, and 46 species, a total of 17,151 fish were collected, with pelagic, sedentary, and omnivorous species dominating. In comparison, the number of species increased by 10 after removal, and fish alpha diversity increased. The Index of Relative Importance (IRI) revealed that the composition of dominating species remained constant, including Coilia nasus, Hypophthalmichthys molitrix, and Hypophthalmichthys nobilis; Parabramis pekinensis, Megalobrama amblycephal, and Culter mongolicus were upgraded from common species to general species. Culter alburnus, Hemiculter bleekeri, and Pseudobrama simoni were downgraded from general species to common species. Elopichthys bambusa had become a common species (IRI = 109.35), which was not discovered before removal. According to the hierarchical clustering (HC) and non-metric multidimensional sequencing (NMDS), the fish community of the northern reserve was highly aggregated. As the Abundance Biomass Comparison (ABC) curve and biodiversity index indicated, the fish community structure of the whole lake was in a state of moderate anthropogenic disturbance with reduced stability, while that of the northern reserve was in a state of light anthropogenic disturbance with greater stability. The number of fish species increased in this survey compared to the period before removal, species and dominant species composition altered dramatically, and total lake stability declined. This study demonstrates that the fish diversity in Gehu Lake increased after the removal of the net enclosure. Meanwhile, the stability of the fish community structure was decreased temporarily. Lake restoration is a long-term process, and the underlying impact of the removal of the net enclosure still requires continuous monitoring and further studies.

Physalis alkekengi L. var. franchetii (PALF) is a traditional Chinese medicine, which is well known for its antimicrobial, anti-inflammatory, antipyretic, and expectorant properties. Its fruits and fruiting calyxes are used as dietary supplements and traditional herbs in China. However, the quality of calyxes is uneven, and it is prone to getting moldy or moth-eaten during storage. High-performance liquid chromatography (HPLC) fingerprints and multivariate chemometric methods were combined to evaluate quality, and three representative compounds were chosen as the quality markers (Q-markers). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) provided a clear discrimination of PALF samples. Through further verification by partial least squares discriminant analysis (PLS-DA), backpropagation artificial neural network (BP-ANN), machine learning, and combination with the determination of the content, biology, and pharmacology effect judgment, galuteolin, rutin, and physalin O could be used as Q-markers that their contents affect the quality of PALF grade evaluation. A simple method was established to rapidly assess the quality of PALF that is important for its clinical application and storage and provide a reference for evaluating the quality of materials used in Chinese medicine.

Flavonoids are important active components of traditional Chinese medicines (TCMs) because of their many biological activities. We studied the interaction between 17 polysaccharides and eight flavonoids via high-performance liquid chromatography (HPLC) and the effect of the interactions on the solubility and stability of the flavonoids. The effect of the polysaccharides on the solubility of flavonoids was analyzed by statistical methods and showed significant solubility improvements. The constant temperature acceleration method (90°C/pH 9 buffer solution) was used to measure the degradation kinetics and half-life of flavonoids with and without polysaccharides. All the polysaccharides displayed a stabilizing effect on all eight flavonoids. The stabilizing effects varied in the order: quercetin, baicalein > baicalin > galuteolin > daidzin > rutin > luteolin > daidzien. The phase-solubility method was applied to quercetin and baicalein to study the mechanism of action of the polysaccharides. It appeared that the two flavonoids could form 1 : 1 inclusion complexes with polysaccharides, which may be one of the factors increasing solubility and stability. These findings increase our understanding of the role of endogenous polysaccharides in TCM in improving the stability and bioavailability of bioactive flavonoids.

Abstract Caenorhabditis briggsae has emerged as a model for comparative biology against model organism C. elegans. Most of its cell fate specifications are completed during embryogenesis whereas its cell growth is achieved mainly in larval stages. The molecular mechanism underlying the drastic developmental changes is poorly understood. To gain insights into the molecular changes between the two stages, we compared the proteomes between the two stages using iTRAQ. We identified a total of 2,791 proteins in the C. briggsae embryos and larvae, 247 of which undergo up- or down-regulation between the two stages. The proteins that are upregulated in the larval stages are enriched in the Gene Ontology categories of energy production, protein translation, and cytoskeleton; whereas those upregulated in the embryonic stage are enriched in the categories of chromatin dynamics and posttranslational modification, suggesting a more active chromatin modification in the embryos than in the larva. Perturbation of a subset of chromatin modifiers followed by cell lineage analysis suggests their roles in controlling cell division pace. Taken together, we demonstrate a general molecular switch from chromatin modification to metabolism during the transition from C. briggsae embryonic to its larval stages using iTRAQ approach. The switch might be conserved across metazoans.

Abstract Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems‐level genetic architecture coordinating division timing, we performed a high‐content screening for genes whose depletion produced a significant reduction in the asynchrony of division between sister cells (ADS) compared to that of wild‐type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time‐lapse imaging followed by computer‐aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development.

Scutellaria baicalensis Georgi (SBG) is not just as a traditional herbal medicine but also a popular functional food in China and other Asian countries. A sensitive simple strategy was developed for the first time to analyze SBG from eight different geographical sources using high-performance liquid chromatography (HPLC) coupled with multivariate chemometric methods. Two unsupervised pattern recognition models, hierarchical cluster analysis (HCA) and principal components analysis (PCA), and a supervised pattern recognition model, partial least squares discriminant analysis (PLS-DA), were used to analyze the chemical compositions and physical traits of SBG. The important chemical markers baicalin, baicalein, and wogonoside were analyzed quantitatively and with PLS-DA. These methods distinguished rotten xylem (kuqin) and strip types (tiaoqin) of SBG and found that the thickness of the slice had a significant impact on the classification of SBG. Two classes of strip types were identified: one as the uncut pharmaceutical, which was sectioned with a thickness >3 mm; the other as a thin-sectioned strip type, with a thickness of

Puerariae Lobatae Radix (PLR), a well-known herbal medicine, is the root of Pueraria lobata (Willd.) Ohwi and has been employed for the treatment and prevention of cardiovascular and cerebrovascular diseases. The purpose of this study was to compare the associated-extraction efficiency of six cyclodextrins (CDs) on five flavonoids in PLR, namely puerarin, daidzein, daidzin, genistein and genistin, which are the major secondary metabolites, and exhibit low water solubility. The six CDs applied were β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropyl-γ-cyclodextrin (HP-γ-CD), carboxymethyl-β-cyclodextrin (CM-β-CD), and sulfobutyl ether β-cyclodextrin (SBE-β-CD). They can be grouped into one of the following three categories: traditional cyclodextrins (β-CD and γ-CD), water-soluble cyclodextrin derivatives (HP-β-CD and HP-γ-CD) and ionic cyclodextrin derivatives (SBE-β-CD and CM-β-CD). High-performance liquid chromatography (HPLC) was used to analyze the five flavonoids in the original aqueous extracts (OAE) in the presence or absence of various CDs. The associated-extraction efficiency of the various CDs followed the ranking: SBE-β-CD > HP-β-CD > CM-β-CD > HP-γ-CD > γ-CD > β-CD. It was clear that SBE-β-CD presented the highest associated-extraction capability, and it was used to extract the four flavonoids from three PLR products, including raw product, stir- fried product, and product simmered with wheat bran. The results showed that SBE-β-CD could improve the extraction capability of flavonoids, both from the raw product and in processed products of PLR. In conclusion, CDs, especially SBE-β-CD, have a promising application for the associated-extraction of flavonoids from PLR.

Phellodendri Chinensis Cortex (PCC) and Phellodendri Amurensis Cortex (PAC) are increasingly being used as traditional herbal medicines, but they are often mistaken for each other. In this study, the fingerprints of PCC from six different geographical sources were obtained by high-performance liquid chromatography, and multivariate chemometric methods were used for comprehensive analysis. Two unsupervised pattern recognition models (principal component analysis and hierarchical cluster analysis) and a supervised pattern recognition model (partial least squares discriminant analysis) were established on the basis of the chemical composition and physical traits of PCC and PAC. PCC and PAC were found to be distinguishable by these methods. The PCC category was divisible into two categories, one with more crude cork and a maximum thickness of ~1.5 mm, and the other with less net crude cork and a maximum thickness of 0.5 mm. According to the model established by partial least squares discriminant analysis (PLS-DA), the important chemical marker berberine hydrochloride was obtained and analyzed quantitatively. From these results combined with chemometric and content analyses, the preliminary classification standards for phellodendron were established as three grades: superior, first-order and mixed. Compared with the traditional identification methods of thin layer chromatography identification and microscopic identification, our method for quality evaluation is relatively simple. It provides a basis and reference for identification of PCC and enables establishment of grade standards. It also could be applied in quality control for compound preparations containing PCC.

Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of XBJ injection. At first, the stability of HSYA in solution and in a Xuebijing injection was investigated, then the mechanisms of the increased stability of HSYA in the XBJ injection were investigated to provide useful information on clinical safety. HSYA stability was investigated as a function of pH and temperature in aqueous solution and an XBJ injection, following the guidelines from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Products were identified by UPLC-MS/MS. HSYA reaction followed first-order kinetics under all conditions. The half-life of HSYA in XBJ was almost 40 times longer than in aqueous solution. The activation energies of HSYA reaction in aqueous solution and XBJ were calculated to be 78.53 and 92.90 kJ∙mol−1 by using Arrhenius equation. The results indicated that HSYA was more stable in XBJ than in aqueous solution. Two products were identified and the mechanism was intra-molecular nucleophilic substitution. The excellent stability of HSYA in XBJ injection partly due to the micelles formed in the injection. The study may provide clues for compatibility in TCM prescription and also provide useful information for further preparation technology research of HSYA and assessment of clinical safety of XBJ.

JinQi Jiangtang (JQJT) tablets, a Chinese patent medicine approved by the State Food and Drug Administration, are composed of Coptidis Rhizoma, Astragali Radix, and Lonicerae Japonicae Flos, and have a significant effect on diabetes. Coptidis Rhizoma is monarch drug in the prescription. The aim of the present study was to investigate and compare the pharmacokinetics of multiple ingredients from JQJT tablets and Coptidis Rhizoma extract (CRE) following oral administration in rats. Five alkaloids: coptisine chloride, epiberberine chloride, berberine chloride, jatrorrhizine chloride, and palmatine chloride, were simultaneously determined in rat plasma using established and validated ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS). Significant pharmacokinetic differences were observed for the five alkaloids after a single administration of CRE and JQJT tablets. Compared with CRE, the Cmax values of palmatine chloride and jatrorrhizine chloride were decreased significantly, the AUC0–t values of four alkaloids (all except jatrorrhizine chloride) were notably decreased, and the mean residence times of all five alkaloids were significantly decreased after administration of JQJT tablets. The results indicated that the absorption characteristics of the five alkaloids from Coptidis Rhizoma would be influenced by the compatibility of Astragali Radix or Lonicerae Japonicae Flos from JQJT tablets, such that absorption was inhibited and elimination was accelerated. In conclusion, the developed strategy was suitable for the comparison of five alkaloids from JinQi Jiangtang tablets and its monarch drug, which could be valuable for compatibility studies of traditional Chinese medicines.

Systematic characterization of ẖybrid incompatibility (HI) between related species remains the key to understanding speciation. The genetic basis of HI has been intensively studied in Drosophila species, but remains largely unknown in other species, including nematodes, which is mainly due to the lack of a sister species with which C. elegans can mate and produce viable progeny. The recent discovery of a C. briggsae sister species, C. nigoni, has opened up the possibility of dissecting the genetic basis of HI in nematode species. However, the paucity of dominant and visible marker prevents the efficient mapping of HI loci between the two species. To elucidate the genetic basis of speciation in nematode species, we first generated 96 chromosomally integrated GFP markers in the C. briggsae genome and mapped them into the defined locations by PCR and Next-Generation Sequencing (NGS). Aided by the marker, we backcrossed the GFP-associated C. briggsae genomic fragments into C. nigoni for at least 15 generations and produced 111 independent introgressions. The introgression fragments cover most of the C. briggsae genome. We finally dissected the patterns of HI by scoring the embryonic lethality, larval arrest, sex ratio and male sterility for each introgression line, through which we identified pervasive HI loci and produced a genome-wide landscape of HI between the two nematode species, the first of its type for any non-Drosophila species. The HI data not only provided insights into the genetic basis of speciation, but also established a framework for the possible cloning of HI loci between the two nematode species. Furthermore, the data on hybrids confirmed Haldane's rule and suggested the presence of a large X effect in terms of fertility between the two species. Importantly, this work opens a new avenue for studying speciation genetics between nematode species and allows parallel comparison of the HI with that in Drosophila and other species.

The genus Phasmarhabditis is an economically important group of rhabditid nematodes, to which the well-known slug-parasite P. hermaphrodita belongs. Despite the commercial use of Phasmarhabditis species as an attractive and promising approach for pest control, the taxonomy and systematics of this group of rhabditids are poorly understood, largely because of the lack of diagnostic morphological features and DNA sequences for distinguishing species or inferring phylogenetic relationship. During a nematode sampling effort for identifying free-living relatives of Caenorhabditis elegans in Huizhou City, Guangdong, China, a novel species belonging to the genus Phasmarhabditis was isolated from rotting leaves. Detailed morphology of the gonochoristic P. huizhouensis sp. nov. was described and illustrated. The adult female has a robust body, a relatively short and wide buccal capsule conjoined by a rhabditiform pharynx. Females are characterized by a short cupola-shaped tail end bearing a slender pointed tip, with the junction flanked by a pair of 'rod-like' phasmids. Males have an open peloderan bursa that is supported by 9 pairs of genital papillae and 1 terminal pair of phasmids. P. huizhouensis sp. nov. is morphologically very similar to the type species Phasmarhabditis papillosa but is distinguishable by its male caudal traits. The new species is readily differentiated from other taxa in the genus by its female tail shape. Molecular phylogenetic inferences based on small subunit (SSU) and the D2-D3 domain of large subunit (LSU) ribosomal DNA genes reveal that P. huizhouensis sp. nov. forms a unique branch in both phylogenies which is genetically related to P. hermaphrodita and other parasites such as Angiostoma spp. The host associations of P. huizhouensis sp. nov. and its ability to parasitize slugs are unknown.

We re-isolated in China a relative of the nematode model Caenorhabditis elegans that was previously referred to informally as C. sp. 5. In spite of its importance for comparative biology, C. sp. 5 has remained morphologically uncharacterized. Therefore, we now provide detailed description of morphology and anatomy, assigning the name of Caenorhabditis sinica sp. n. to this nematode that is found frequently in China. C. sinica sp. n. belongs to the Elegans group in the genus Caenorhabditis, being phylogenetically close to C. briggsae although differing in reproductive mode. The gonochoristic C. sinica sp. n. displays two significantly larger distal parts of uteri filled with sperms in the female/hermaphroditic gonad than does the androdioecious C. briggsae. The new species can be differentiated morphologically from all known Caenorhabditis species within the Elegans group by presenting a uniquely shaped, three-pointed hook structure on the male precloacal lip. The lateral field of C. sinica sp. n. is marked by three ridges that are flanked by two additional incisures, sometimes appearing as five ridges in total. This study ends the prolonged period of the 'undescribed' anonymity for C. sinica sp. n. since its discovery and use in comparative biological research. Significant and crossing-direction dependent hybrid incompatibilities in F1 and F2 crossing progeny make C. sinica sp. n. an excellent model for studies of population and speciation genetics. The abundance of nematode species lacking detailed taxonomic characterization deserves renewed attention to address the species description gap for this important yet morphologically 'difficult' group of animals.

Caenorhabditis briggsae as a companion species for Caenorhabditis elegans has played an increasingly important role in study of evolution of development and genome and gene regulation. Aided by the isolation of its sister spices, it has recently been established as a model for speciation study. To take full advantage of the species for comparative study, an effective transgenesis method especially those with single-copy insertion is important for functional comparison. Here, we improved a transposon-based transgenesis methodology that had been originally developed in C. elegans but worked marginally in C. briggsae. By incorporation of a heat shock step, the transgenesis efficiency in C. briggsae with a single-copy insertion is comparable to that in C. elegans. We used the method to generate 54 independent insertions mostly consisting of a mCherry tag over the C. briggsae genome. We demonstrated the use of the tags in identifying interacting loci responsible for hybrid male sterility between C. briggsae and Caenorhabditis nigoni when combined with the GFP tags we generated previously. Finally, we demonstrated that C. briggsae tolerates the C. elegans toxin, PEEL-1, but not SUP-35, making the latter a potential negative selection marker against extrachromosomal array. [ABSTRACT FROM AUTHOR]