Iron-Catalyzed Primary Amination of C(sp3)-H Bonds.

Primary amines are privileged molecules in drug development. Yet, there is a noticeable scarcity of methods for directly introducing a primary amine group into the ubiquitous C(sp3)-H bonds within organic compounds. Here, we report an iron-based catalytic system that enables direct primary amination of C(sp3)-H bonds under aqueous conditions and air. Various types of C(sp3)-H bonds, including benzylic, allylic, and aliphatic ones, can be readily functionalized with high selectivity and efficiency. The broad utility of this method has been further verified by late-stage amination of 11 complex bioactive molecules. Mechanistic studies unveil a protonated iron-nitrene complex as the key intermediate for the C-H bond activation. This work extends the toolbox for direct C(sp3)-H functionalizations, opening up new opportunities for late-stage modifications of organic molecules.

Real-world effectiveness and safety of recombinant human endostatin plus PD-1 inhibitors and chemotherapy as first-line treatment for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer.

BACKGROUND: This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. CONCLUSIONS: Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

First-principles studies on the electronic and contact properties of monolayer Ga2STe-metal contacts.

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga2STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga2STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga2STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga2STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga2STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga2STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga2STe devices.

The inoculation of Bacillus paralicheniformis and Streptomyces thermoviolaceus enhances the lignocellulose degradation and microbial communities during spent mushroom substrate composting.

The burgeoning global mushroom industry has precipitated challenges related to the efficient and sustainable utilization of spent mushroom substrate (SMS). Composting is regarded as an efficient way for the ecological utilization of SMS. The addition of microbial inoculants can promote the composting process and improve the quality of compost products. This study introduced two bacterial inoculants, Bacillus paralicheniformis HL-05 (BP) and Streptomyces thermoviolaceus LC-10 (ST), into the composting process of SMS. The impact of these inoculants was evaluated through analyses of physicochemical properties, lignocellulose degradation, and high-throughput sequencing to elucidate their ecological roles and optimize the composting process. The results suggest that inoculation with BP and ST significantly prolonged the thermophilic stage by 2-3 days, representing an increase of 22.22-33.33%. Moreover, it boosted the degradation rates of cellulose, hemicellulose, and lignin by 18.37-29.77%, 35.74-50.43%, and 40.32-40.83%, respectively, compared to the control. Furthermore, inoculation rapidly altered the microbial community structure during the rapid temperature-rising stage and strengthened interconnections among composting microorganisms. The microbial inoculation substantially enhanced the proliferation of thermophilic lignocellulose-degrading microorganisms during the thermophilic stage, thereby facilitating the utilization of lignocellulose. This study proposes a novel and effective strategy for SMS composting using microbial inoculants.

Nutritional qualities and antioxidant activity of Pleurotus floridanus grown on composted peach sawdust substrate with different composting time.

Recently, composting cultivation method is widely used in oyster mushroom production. In this study, we focused on the effects of composting processes on nutritional qualities and antioxidant activity of Pleurotus floridanus mushroom fruiting bodies. Three treatments of different composting time (2, 4, and 5 days) were performed with an atmospheric sterilization treatment as the control. The results showed that the pH value, total carbon content, and total nitrogen content of substrate were critical parameters which would significantly affect mushroom qualities and bioactivities. Fruiting bodies of the control demonstrated significantly higher crude protein content, total amino acid content, and essential amino acid content than that of composting treatments. Moreover, fruiting bodies of treatment D4 and D5 manifested significantly higher crude polysaccharide contents. Crude polysaccharide of treatment D4 represented the highest scavenging ability toward both radical 3-ethylbenzthiazoline-6-sulfonic acid (ABTS·+ ) and Hydroxyl radical (OH·). It suggests that composting processes is suitable for oyster mushroom cultivation based on nutritional and antioxidant qualities of fruiting bodies.

Continuous-Variable Assisted Thermal Quantum Simulation.

Simulation of a quantum many-body system at finite temperatures is crucially important but quite challenging. Here we present an experimentally feasible quantum algorithm assisted with continuous variable for simulating quantum systems at finite temperatures. Our algorithm has a time complexity scaling polynomially with the inverse temperature and the desired accuracy. We demonstrate the quantum algorithm by simulating a finite temperature phase diagram of the quantum Ising and Kitaev models. It is found that the important crossover phase diagram of the Kitaev ring can be accurately simulated by a quantum computer with only a few qubits and thus the algorithm may be implementable on current quantum processors. We further propose a protocol with superconducting or trapped ion quantum computers.

Glacieibacterium frigidum gen. nov., sp. nov., a novel member of the family Sphingosinicellaceae isolated from a glacier.

A novel Gram-stain-negative, rod-shaped, yellow bacterium, designated as LB1R16T, was isolated from the Laigu glacier on the Tibetan Plateau, PR China. Strain LB1R16T was catalase-positive, oxidase-negative and grew at 0-28 °C, pH 6.0-8.0 and in the absence of NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain LB1R16T belongs to the family Sphingosinicellaceae but formed an independent lineage. The highest level of 16S rRNA gene sequence similarities were found to Polymorphobacter arshaanensis DJ1R-1T (95.24 %), Sphingoaurantiacus capsulatus YLT33T (94.78 %) and Sandarakinorhabdus limnophila DSM 17366T (94.67 %). The genomic DNA G+C content was 68.8 mol%. The main cellular fatty acids were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), C16 : 0 and C12 : 0-OH. The respiratory quinone was ubiquinone-10. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, one sphingoglycolipid, one unidentified aminolipid, one unidentified phospholipid and two unidentified polar lipids, which were different from the type strains of Polymorphobacter arshaanensis, Sphingoaurantiacus capsulatus and Sandarakinorhabdus limnophila. Based on a polyphasic approach, a novel species of a new genus, Glacieibacterium frigidum gen. nov., sp. nov., within the family Sphingosinicellaceae is proposed. The type strain is LB1R16T (=CGMCC 1.11941T=NBRC 113873T).

Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder.

The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitters (using UHPLC-MS/MS) of 26 children with ASD and 24 normal children. All 26 children with ASD participated in the intervention stage, and we measured the gut microbiota profiles, SCFAs and neurotransmitters before and after probiotics + FOS (n = 16) or placebo supplementation (n = 10). We found that gut microbiota was in a state of dysbiosis and significantly lower levels of Bifidobacteriales and Bifidobacterium longum were observed at the discovery stage in children with ASD. An increase in beneficial bacteria (Bifidobacteriales and B. longum) and suppression of suspected pathogenic bacteria (Clostridium) emerged after probiotics + FOS intervention, with significant reduction in the severity of autism and gastrointestinal symptoms. Compared to children in the control group, significantly lower levels of acetic acid, propionic acid and butyric acid were found, and a hyperserotonergic state (increased serotonin) and dopamine metabolism disorder (decreased homovanillic acid) were observed in children with ASD. Interestingly, the above SCFAs in children with autism significantly elevated after probiotics + FOS intervention and approached those in the control group. In addition, our data demonstrated that decreased serotonin and increased homovanillic acid emerged after probiotics + FOS intervention. However, the above-mentioned changes did not appear in the placebo group for ASD children. Probiotics + FOS intervention can modulate gut microbiota, SCFAs and serotonin in association with improved ASD symptoms, including a hyper-serotonergic state and dopamine metabolism disorder.

Flavobacterium restrictum sp. nov., Flavobacterium rhamnosiphilum sp. nov., and Flavobacterium zepuense sp. nov. isolated from glaciers.

Three strains, designated as LB1R34T, LB3P52T and ZT4R6T, were isolated from glaciers located on the Tibetan Plateau, PR China. The strains were Gram-stain-negative, aerobic, rod-shaped, non-motile and yellow. Phylogenetic analysis based on the 16S rRNA gene and genomic sequences indicated that they were related to the members of the genus Flavobacterium. The 16S rRNA gene sequences similarities between the three strains were 92.31-96.93 %. The average nucleotide identity values and digital DNA-DNA hybridization values between these three strains and their closest relatives were 76.80-91.33 % and 21.3-44.2 %, respectively. LB1R34T, LB3P52T and ZT4R6T contained MK-6 as the major menaquinone, summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and iso-C15 : 0 as the major fatty acids. Phosphatidylethanolamine was present in their polar lipids profiles. On the basis of the phenotypic characteristics, he results of phylogenetic analysis and genotypic data, three novel species, Flavobacterium restrictum sp. nov. (type strain=LB1 R34T=CGMCC 1.11493T=NBRC 113650T), Flavobacterium rhamnosiphilum sp. nov. (type strain=LB3 P52T=CGMCC 1.11446T=NBRC 113776T) and Flavobacterium zepuense sp. nov. (type strain=ZT4 R6T=CGMCC 1.11919T=NBRC 113653T) are proposed.

miR-194 inhibits liver cancer stem cell expansion by regulating RAC1 pathway.

Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed low expression of miR-194 in chemoresistant HCC cells. A remarkable decrease of miR-194 was detected in EpCAM or CD133-positive liver CSCs and CSC-enriched hepatoma spheres. Interference miR-194 facilitated liver CSCs expansion by enhancing the self-renewal of liver CSCs. While up-regulating miR-194 inhibited liver CSCs expansion by suppressing the self-renewal of liver CSCs. Furthermore, hepatoma cells with miR-194 overexpression performed more sensitivity to sorafenib treatment. Mechanistically, functional studies found that Ras-related C3 botulinum toxin substrate 1 (RAC1) was a direct target of miR-194. Overexpression of miR-194 inhibited the expression of RAC1 in liver CSCs. Special RAC1 siRNA diminished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-194 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-194-inhibited liver CSCs expansion. More importantly, downregulated expression of miR-194 was a predictor of poor prognosis of HCC patients.

ARHGEF10L expression regulates cell proliferation and migration in gastric tumorigenesis.

We recently reported that Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L) activated Rho GTPases as guanine nucleotide exchange factor to stimulate liver tumorigenesis. The present study continued to explore the effect of ARHGEF10L on the tumorigenic process of gastric cancer. This study detected increased expression of ARHGEF10L in GC tissues compared to peritumoral tissue samples. SGC7901 cells with ARHGEF10L overexpression showed increased cell proliferation, cell migration, and tube-like structure formation abilities, as well as increased expression of GTP-RhoA, ROCK1, and phospho-Ezrin/Radixin/Moesin. ARHGEF10L overexpression downregulated the expression of E-cadherin and upregulated the expression of N-cadherin and Slug, indicating an activation of EMT in the transfected cells. RNA-sequencing assay detected an increased expression of Heat shock 70 kDa protein 6 in the SGC7901 cells overexpressing ARHGEF10L. The above results suggest that ARHGEF10L expression can stimulate gastric tumorigenesis by prompting RhoA-ROCK1-phospho-ERM signaling, inducing EMT and increasing HSPA6 expression.

Concordance Study Between IBM Watson for Oncology and Clinical Practice for Patients with Cancer in China.

BACKGROUND: IBM Watson for Oncology (WFO), which can use natural language processing to evaluate data in structured and unstructured formats, has begun to be used in China. It provides physicians with evidence-based treatment options and ranks them in three categories for treatment decision support. This study was designed to examine the concordance between the treatment recommendation proposed by WFO and actual clinical decisions by oncologists in our cancer center, which would reflect the differences of cancer treatment between China and the U.S. PATIENTS AND METHODS: Retrospective data from 362 patients with cancer were ingested into WFO from April 2017 to October 2017. WFO recommendations were provided in three categories: recommended, for consideration, and not recommended. Concordance was analyzed by comparing the treatment decisions proposed by WFO with those of the multidisciplinary tumor board. Concordance was achieved when the oncologists' treatment decisions were in the recommended or for consideration categories in WFO. RESULTS: Ovarian cancer showed the highest concordance, which was 96%. Lung cancer and breast cancer obtained a concordance of slightly above 80%. The concordance of rectal cancer was 74%, whereas colon cancer and cervical cancer showed the same concordance of 64%. In particular, the concordance of gastric cancer was very low, only 12%, and 88% of cases were under physicians choice. CONCLUSION: Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major cause of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. ClinicalTrials.gov Identifier: NCT03400514. IMPLICATIONS FOR PRACTICE: IBM Watson for Oncology (WFO) has begun to be used in China. In this study, concordance was examined between the treatment recommendation proposed by WFO and clinical decisions for 362 patients in our cancer center, which could reflect the differences of cancer treatment between China and the U.S. Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major causes of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. This study may have a significant effect on application of artificial intelligence systems in China.

Nocardioides zhouii sp. nov., isolated from the Hailuogou Glacier in China.

A novel Gram-stain-positive, non-motile, rod-shaped, non-spore-forming bacterium, designated HLT2-9T, was isolated from the ice tongue surface of Hailuogou Glacier in Sichuan Province, PR China. Colonies of cells were cream yellow, convex and round. Growth occurred at 0-27 °C (optimum, 20 °C), pH 7.0-10.0 (pH 7.0) and in the presence of 0-2.0 % (w/v) NaCl (0 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain HLT2-9T belonged to the genus Nocardioides. The highest level of sequence similarities were found to Nocardioides glacieisoli CGMCC1.11097T (99.24 %), Nocardioides oleivorans CGMCC 4.6882T (98.54 %) and Nocardioides ganghwensis CGMCC 4.6875T (98.54 %). However, the low average nucleotide identity (85.6-87.9 %) and digital DNA-DNA hybridization values (26.4-30.2 %) of strain HLT2-9T to its three closest relatives demonstrated that it represents a novel species of the genus Nocardioides. The major cellular fatty acids of strain HLT2-9T were C17 : 1ω8c and iso-C16 : 0. Strain HLT2-9T contained ll-2,6-diaminopimelic acid as the diamino acid in the cell-wall peptidoglycan. The predominant menaquinone is MK-8(H4). The G+C content of the genomic DNA was 70.65 mol%. Based on evidence collected from the phenotypic, genotypic and phylogenetic analyses, a novel species Nocardioideszhouii sp. nov. is proposed, with HLT2-9T (=CGMCC 1.11084T=NBRC 109783T) as the type strain.

Flavobacterium ranwuense sp. nov., isolated from glacier.

A Gram-stain-negative, aerobic, rod-shaped, devoid of flagella, orange-yellow-coloured bacterium (strain LB2P22T) was isolated from an ice sample collected from the Laigu glacier on the Tibetan Plateau, PR China. The results of 16S rRNA gene sequence analysis indicated that strain LB2P22T belongs to the genus Flavobacterium with highest similarity to Flavobacterium laiguense LB2P30T (98.14 %), Flavobacterium glaciei CGMCC 1.5380T (98.02 %), Flavobacterium psychroterrae CCM 8827T (97.94 %) and Flavobacterium granuli CGMCC 1.10125T (97.91 %). Strain LB2P22T had 77.99-84.99 % average nucleotide identity and 22.3-29.3 % digital DNA-DNA hybridization values with its closest relatives, indicating that it represents a novel species of the genus Flavobacterium. Strain LB2P22T grew at 0-25 °C, pH 7.0-8.0 and up to 1.0 % (w/v) NaCl. The main cellular fatty acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1ω7c/C16 : 1ω6c) and anteiso-C15 : 0. The genomic DNA G+C content is 34.3 mol%. The predominant menaquinone was MK-6 and the polar lipids were phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. Based on these data, a novel species, Flavobacteriumranwuense sp. nov., is proposed, with LB2P22T (=CGMCC 1.11361T=NBRC 113777T) as the type strain.

Basiliximab application on liver recipients: a meta-analysis of randomized controlled trials.

BACKGROUND: The benefits of the application of basiliximab induction therapy in liver transplantation are not clear. The present meta-analysis was to evaluate the pros and cons of basiliximab use in liver transplantation. DATA SOURCES: We searched the associated publications in English from July 1998 to December 2015 in the following databases: MEDLINE, PubMed, Ovid, EMBASE, Web of Science and Cochrane Library. RESULTS: Basiliximab significantly decreased the incidence of de novo diabetes mellitus after liver transplantation (RR=0.56; 95% CI: 0.34-0.91; P=0.02). Subgroup analysis showed that basiliximab in combination with steroids-free immunosuppressant significantly decreased the incidence of biopsy-proven acute rejection (RR=0.62; 95% CI: 0.39-0.97; P=0.04) and new-onset hypertension (RR=0.62; 95% CI: 0.42-0.93; P=0.02). CONCLUSIONS: Basiliximab may be effective in reducing de novo diabetes mellitus. What is more, basiliximab in combination with steroids-free immunosuppressant shows statistical benefit to reduce biopsy-proven acute rejection and de novo hypertension.

[Characteristics of Raman Spectra of Polyethylene Terephthalate].

Raman spectrometry was employed to study the characteristics of Raman spectra of polyethylene terephthalate (PET), which were treated with sodium hydroxide, sulfuric acid and copper sulfate, respectively. Raman spectra under different conditions were obtained and the characteristics of the Raman spectra were analyzed. The morphology structures were observed under different conditions using Atomic Force Microscope. The results show that the spectral intensity of PET treated with sodium hydroxide is higher than that untreated between 200-1 750 cm(-1), while the intensity of PET treated with sodium hydroxide is lower than that untreated beyond 1 750 cm(-1) and the fluorescence background of Raman spectra is decreased. The spectral intensity of PET treated with sulfuric acid is remarkably reduced than that untreated, and the intensity of PET treated with copper sulphate is much higher than that untreated. The research results obtained by Atomic Force Microscopy show that the variations of the Raman spectra of PET fibers are closely related to. the chemical bonds and molecular structures of PET fibers. The surface of the PET treated with sodium hydroxide is rougher than that untreated, the surface roughness of the PET treated with sulfuric acid is reduced as compared to that untreated, while the surface roughness of the PET treated with copper sulphate is increased. The results obtained by Raman spectroscopy are consistent with those by Atomic Force Microscopy, indicating that the combination of Raman spectroscopy and Atomic Force Microscopy is expected to be a promising characterization technology for polymer characteristics.

Characterization of Full-Length Genomes of Hepatitis B Virus Quasispecies in Sera of Patients at Different Phases of Infection.

Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.

Distributed parameter model for characterizing magnetic crosstalk in a fiber optic current sensor.

The effects of magnetic crosstalk on a fiber optic current sensor are studied using the distributed parameter model. A new method to enhance the immunity to magnetic crosstalk is proposed. The experimental results show that magnetic crosstalk changes periodically with the azimuth angle and decreases as the distance between the conductors increases. When the sensing coil is placed at the optimal azimuth angle, the ratio error from magnetic crosstalk decreases from -0.32% to -0.02%, demonstrating the effectiveness of the proposed method.

Comparative pharmacokinetics of hypaconitine after oral administration of pure hypaconitine, Aconitum carmichaelii extract and Sini Decoction to rats.

Hypaconitine (HC) is one of the main aconitum alkaloids in Aconitum carmichaelii (AC), which is considered to be effective on cardiovascular disease, although it also has high toxicity. Sini Decoction (SND), composed of Aconitum carmichaelii, Glycyrrhiza uralensis and Zingiber officinale, is a traditional Chinese multi-herbal formula for recuperating the depleted yang. The aim of this study was to compare the pharmacokinetics of HC in rat plasma after oral administration of HC, AC extract and SND, and investigate the effect of other two herbal ingredients on absorption, metabolism and elimination of HC. A sensitive and specific LC-MS/MS method was developed to determine HC in rat plasma. Eighteen male Sprague-Dawley rats were randomly assigned to three groups: HC, AC and SND group. Plasma concentrations of HC were determined at designated points after oral administration, and main pharmacokinetic parameters were estimated. It was found that there was obvious difference (p < 0.05) on the pharmacokinetic parameters among three groups. Compared with AC group, Tmax, Cmax, k, AUC(0-24) and AUC(0-∞) decreased in SND group, while t1/2 and MRT had been lengthened, which indicated that the ingredients in other two herbs could influence the pharmacokinetic behavior of HC.