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Phlomis brevidentata H.W.Li Radix (PbR) is a rare traditional Tibetan medicine, and it is widely used in the Chinese Tibetan region for the treatment of pharyngitis, pneumonia, and so forth. Nevertheless, there is very little research on its modern pharmacy, and the active ingredients and mechanisms against these diseases remain unknown. In this study, we employed the qualitative analysis and pharmacokinetic based on LC–MS technology and network pharmacology to explore the active ingredients and mechanisms of PbR for treatment of pneumonia. Ultraperformance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q-TOF/MS) methodology was applied to identify the chemical composition of PbR. Meanwhile, a UPLC-MS/MS method was developed to quantify three active constituents (sesamoside, shanzhiside methyl ester, and barlerin) in rat plasma for the pharmacokinetic analysis after oral administration of PbR. Finally, in order to clarify the anti-pneumonia mechanism of this rare Tibetan medicine, a comprehensive network pharmacology strategy was applied. As a result, a total of 23 compounds were identified in PbR, including 14 iridoid glycosides, 7 phenylethanoid glycosides, and 2 other kinds of compounds. Pharmacokinetic studies have shown that the three compounds exhibit extremely similar pharmacokinetic characteristics, possibly due to their highly analogous chemical structure. We speculate that the iridoid glycosides may be the main active component in PbR. Then, the three iridoid glycoside constituents absorbed into blood were subjected to network pharmacology analysis for treatment of pneumonia. Compound-target-disease, gene ontology bioanalysis, KEGG pathway, and other network pharmacology analysis methods were applied to reveal that five main targets of the three iridoid glycosides, namely, GAPDH, ALB, MAPK1, AKT1, and EGFR, were significant in the regulation of the above bioprocesses and pathways. These results provide a basis for elucidating the bioactive compounds and the pharmacological mechanisms of P. brevidentata H.W.Li radix under clinical applications.

The intestinal capillary pathway is the most common way to absorb oral drugs, but for drugs with poor solubility and permeability and high first-pass metabolism, this pathway is very inefficient. Although intestinal lymphatic transport of lipophilic drugs or prodrugs is a promising strategy to improve the oral delivery efficiency of these drugs. The prodrug strategy for modifying compounds with Log P > 5 to promote intestinal lymphatic transport is a common approach. However, transport of poor liposoluble compounds (Log P

In recent years, direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis. Several major components, such as bergenin and 11-O-galloylbergenin, have good anti-inflammatory activity. Since research on the chemical components of Bergenia purpurascens and related mechanisms for the treatment of osteoarthritis has never been performed, this study aimed to analyze the chemical components of Bergenia purpurascens through ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology and the UNIFI screening platform to predict the underlying mechanisms in treating osteoarthritis by analyzing the network pharmacology. In total, 43 chemical constituents were identified, mainly flavonoids (18), phenolic glycosides (13), and organic acids (7). Among them, 16 components were found in Bergenia purpurascens for the first time. Through the analysis of network pharmacology, several potential candidate targets and pathways were initially predicted, including AKT1, MAPK1, and MAPK3, as well as the apoptosis, estrogen, and MAPK signaling pathways. Bergenin, 11-O-galloylbergenin, arbutin, catechin-3-O-gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.

Background: Neuropathic pain is a common chronic pain caused by a lesion or diseases of somatosensory nervous system, which has a significant impact on the quality of life. It has been found that its underling pathological mechanism is related to inflammation. Daphnetin is a natural product with a variety of biological activities such as anti-inflammatory and analgesic. It has been shown to be effective in the treatment of chronic inflammatory pain, but its underlying mechanisms are not completely understood. We aimed to evaluate the effect and regulatory mechanism of daphnetin on neuropathic pain.Methods: The experimental animals were divided into 8 groups: control group, model group, sham group, positive group (0.0375mg/kg), DAPH group (0.0625mg/kg), DAPL group (0.025mg/kg), P2X4 blocker group (1mg/kg) and P38 blocker group (5mg/kg). After constructing the subdural drug delivery system in rats, the neuropathic pain model was established by chronic constrictive injury (CCI), and the pain sensitivity was evaluated by measuring mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The protein expression of inflammatory factors and related pathways was measured by Western Blot. The activation of microglia and neurons and the expression of target protein in spinal dorsal horn were measured by immunofluorescence staining.Results: Compared with the sham group, MWT and TWT decreased significantly in model group, and the expression of IL-1 β, IL-6 and TNF-α increased. After intrathecal injection of daphnetin, the MWT and TWT of rats were significantly increased, and the protein expression of IL-1 β, IL-6 and TNF- α was significantly decreased compared with the model group. Compared with sham group, the expression of P2X4, IRF8, IRF5, BDNF, p-P38 / P38, p-JNK / JNK and p-ERK1/2 / ERK1/2 in model group increased significantly. After intrathecal injection of daphnetin, the expression of the above proteins was significantly down-regulated compared with model group. Compared with sham group, microglia and neurons in the spinal dorsal horn of model group were activated, and the expression of P2X4 and P38 in microglia increased. After intrathecal injection of daphnetin, compared with the model group, the activation of microglia and neurons in the spinal dorsal horn decreased significantly, and the expression of P2X4 and P38 in microglia decreased. Importantly, daphnetin could not improve neuropathic pain in CCI rats under the action of P2X4 and P38 blocker.Conclusion: daphnetin can alleviate neuropathic pain in CCI model rats by interfering with P2X4-P38 MAPK pathway of microglia, suggesting that daphnetin is a potential drug for the treatment of neuropathic pain.

Panax notoginseng saponins (PNS) are known as clinical anti-stroke herbal medicines. The aim of this study is to describe the impact of PNS on ischemia-reperfusion-induced cerebral microvasculature barrier dysfunction which has not been investigated yet. Mice were subjected to transient middle cerebral artery occlusion and PNS were administrated to mice 3 days before and 2 days after surgery. Leukocyte adhesion, albumin leakage, tight junctions and other parameters in the cortex were measured. The PNS 45 mg/kg intervention alleviated leukocyte adhesion, inhibited endothelial barrier alterations evidenced by reduced albumin leakage and tight junction degradations, and ultimately ameliorated infarct volumes and neurological deficits subsequent to ischemia-reperfusion. Taken together, P. notoginseng saponins are able to attenuate leukocyte-mediated microvascular disturbance at the onset of ischemic stroke.

BackgroundAdipose tissue (e.g. white, brown and brite) plays a critical role in modulating energy metabolism. Activating brown adipose tissue (BAT) and inducing browning in white adipose tissue (WAT) has been proposed to be a potential molecular target for obesity treatment. Emodin is a natural anthraquinone derivative that exhibits variety of pharmacologic effects including lowering lipids and regulating glucose utilization. However, the underlying mechanism of action is still unclear. In the present study, we investigated whether emodin could alleviate obesity via promoting browning process in adipose tissue.MethodsC57BL/6J mice were fed with high fat diet to induce obesity. Emodin at the doses of 40 and 80 mg/kg were orally given to obesity mice for consecutive 6 weeks. Parameters including fasting blood glucose, oral glucose tolerance, blood lipids, and the ratios of subcutaneous white adipose tissue (scWAT) or BAT mass to body weight, and morphology of adipose tissue were observed. Besides, the protein expression of uncoupling protein 1 (UCP1) and prohibitin in BAT and scWAT was determined by immunohistochemistry method. Relative mRNA expression of Cd137, transmembrane protein 26 (Tmem26) and Tbx1 in scWAT was analyzed using qRT-PCR. And the protein expression of UCP1, CD36, fatty acid transporter 4 (FATP4), peroxisome proliferator-activated receptor alpha (PPARα) and prohibitin of scWAT and BAT were analyzed using western blotting. In addition, ultra-high-performance liquid chromatography with electrospray ionization tandem mass spectrometry was utilized to detect the small lipid metabolites of scWAT and BAT.ResultsEmodin decreased the body weight and food intake in HFD-induced obesity mice, and it also improved the glucose tolerance and reduced the blood lipids. Emodin treatment induced beiging of WAT, and more multilocular lipid droplets were found in scWAT. Also, emodin significantly increased markers of beige adipocytes, e.g. Cd137, Tmem26 and Tbx1 mRNA in scWAT, and UCP1, CD36, FATP4, PPARα and prohibitin protein expression in scWAT and BAT. Furthermore, emodin perturbed the lipidomic profiles in scWAT and BAT of obese mice. Emodin increased total ceramides (Cers), lysophosphatidylcholines (LPCs), lyso-phosphatidylcholines oxygen (LPCs-O), and phosphatidylethanolamines oxygen (PEs-O) species concentration in scWAT. Specifically, emodin significantly up-regulated levels of Cer (34:1), LPC (18:2), LPC-(O-20:2), PC (O-40:7), PE (O-36:3), PE (O-38:6), PE (O-40:6), and sphingolipid (41:0) [SM (41:0)], and down-regulated PC (O-38:0), PE (O-40:4), PE (O-40:5) in scWAT of obesity mice. In terms of lipid matabolites of BAT, the emodin remarkably increased the total PCs levels, which was driven by significant increase of PC (30:0), PC (32:1), PC (32:2), PC (33:4) and PC (38:0) species. In addition, it also increased species of LPCs, e.g. LPC (20:0), LPC (20:1), LPC (22:0), LPC (22:1), LPC (24:0), and LPC (24:1). Especially, emodin treatment could reverse the ratio of PC/PE in HFD-induced obese mice.ConclusionsThese results indicated that emodin could ameliorate adiposity and improve metabolic disorders in obese mice. Also, emodin could promote browning in scWAT and activate the BAT activities. In addition, emodin treatment-induced changes to the scWAT and BAT lipidome were highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflects selective remodeling in scWAT and BAT of both glycerophospholipids and sphingolipids in response to emodin treatment.

Background: Obesity has become a worldwide health threat related to type 2 diabetes, hypertension, cardiovascular disease, etc. Activating brown adipocytes and inducing browning of white adipocytes has been proposed as a potential molecular target for obesity treatment. In the present study, we investigated the effects of emodin on browning in mice with high-fat diet (HFD) and explore its underlying pharmacological mechanisms. Methods: The positive effects of emodin (40, 80 mg/kg/day, i.g. for 6 weeks) on lipid metabolism were evaluated in mice model of hyperlipidemia. Hyperlipidemia mice were induced by high-fat diet (60% of kilocalories from fat, 5.24 Kcal/kg) for 8 weeks. Body weight and food intake were monitored every week. After 6 weeks of treatment, fasting blood glucose, oral glucose tolerance, Lee's index, the ratio of fat weight to body weight, blood lipids, and adipose tissues morphology were assayed. Then uncoupling protein 1 (UCP1), CD36, fatty acid transporter 4 (FATP4), peroxisome proliferator activated receptor α (PPARα) and prohibitin (PHB) protein of subcutaneous white adipose tissue (scWAT) and brown adipose tissue (BAT) were analyzed. In addition, the lipid metabolites in adipose tissues were analyzed by ultra-high- performance liquid chromatography with electrospray ionization tandem mass spectrometry.Results: Emodin treatment decreased body weight gain, fasting blood glucose, Lee's index, the ratio of scWAT weight to body weight, and the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and Leptin in serum, and increased serum adiponectin content and improved glucose tolerance. Furthermore, emodin enhanced the expression of UCP1, CD36, FATP4, PPARα and PHB protein in scWAT and BAT. Meanwhile, emodin can significantly up-regulated lipid levels in scWAT of mice fed with HFD such as PC(O-18:2/22:5), PE(O-18:1/18:2), PE(O-18:2/20:4), PE(O-20:1/20:5), Cer(d14:1/20:0) and SM(d18:0/23:0), and reduced the lipid levels such as PC(O-18:0/20:0), PE(O-18:2/22:2), PE(O-18:0/22:5). In addition, emodin significantly up-regulate lipid levels in BAT of mice fed with HFD such as PC(14:0/16:0), PC(16:0/16:1), PC(16:1/16:1), PC(15:1/18:3), PC(18:0/20:0), LysoPC(20:0), LysoPC(22:0) and LysoPC(22:1), and reduced the lipid levels PC(12:0/20:4) and PC(17:0/22:5). Conclusions: These results indicated that hyperlipidemia could be alleviated by treatment of emodin via promoting browning of white adipose tissue. In addition, the disturbance of some small lipid metabolites in adipose also could be reversed by emodin.

As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities. However, the underlying molecular mechanism is still unclear. In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected. Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion. β1,6-branching of N-linked carbohydrate as one kind of glycosylation could participate in regulating cell-cell adhesion and has been reported to be overexpressed in HCC cells and tissues. Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5. This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.

Radix Polygoni Multiflori (RPM) has been widely used to treat various diseases in Asian countries for many centuries. Although, stilbenes and anthraquinones, two major components of RPM, show various bioactive effects, it has been speculated that the idiosyncratic hepatotoxicity induced by RPM may be related to these constituents. However, information on the pharmacokinetics of stilbenes and anthraquinones at a subtoxic dose of RPM is limited. A simple and sensitive UPLC-MS/MS bioanalytical method for the simultaneous determination of 13 ingredients of RPM, including chrysophanol, emodin, aloe-emodin, rhein, physcion, questin, citreorosein, questinol, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, torachrysone-8-O-glucoside, chrysophanol-8-O-β-D-glucoside, emodin-8-O-β-D-glucoside, and physcion-8-O-β-D-glucoside, in rat plasma was established. Acetonitrile was employed to precipitate the plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a waters HSS C18 column with a gradient elution using water and acetonitrile both containing 0.025% formic acid within a run time of 9 min. The constituents were detected in negative ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects, and stability. The lower limit of quantitation of the analytes was 0.1–1 ng/mL. The intrabatch and interbatch accuracies were 87.1–109%, and the precision was within the acceptable limits. The method was applied to a pharmacokinetic study after oral administration of RPM extract to rats at a subtoxic dose of 36 g/kg.

In recent years, direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis. Several major components, such as bergenin and 11-O-galloylbergenin, have good anti-inflammatory activity. Since research on the chemical components of Bergenia purpurascens and related mechanisms for the treatment of osteoarthritis has never been performed, this study aimed to analyze the chemical components of Bergenia purpurascens through ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology and the UNIFI screening platform to predict the underlying mechanisms in treating osteoarthritis by analyzing the network pharmacology. In total, 43 chemical constituents were identified, mainly flavonoids (18), phenolic glycosides (13), and organic acids (7). Among them, 16 components were found in Bergenia purpurascens for the first time. Through the analysis of network pharmacology, several potential candidate targets and pathways were initially predicted, including AKT1, MAPK1, and MAPK3, as well as the apoptosis, estrogen, and MAPK signaling pathways. Bergenin, 11-O-galloylbergenin, arbutin, catechin-3-O-gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.

Ethnopharmacological relevance Fufang-Yinhua-Jiedu Granules (FFYH) optimized from a Yin-Qiao-San, as traditional Chinese medicine (TCM), was used to treat influenza and upper respiratory tract infection and was recommended for the prevention and treatment of SARS in 2003 and current COVID-19 in Anhui Province in 2020. Aim of study In the clinical studies, FFYH was very effective for the treatment of influenza, but the mechanism of action against influenza A virus remains unclear. In the present study, we investigated the antiviral effect of FFYH against influenza A virus in vitro and vivo. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was investigated for the first time. Materials and methods CPE inhibition assay and HA assay were used to evaluate the in vitro antiviral effects of FFYH against influenza A virus H1N1, H3N2, H5N1, H7N9 and H9N2. Mice were used to evaluate the antiviral effect of FFYH in vivo with ribavirin and lianhuaqingwen as positive controls. RT-PCR was used to quantify the mRNA transcription of TNF-α, IL-6, IFN-γ, IP10, and IL-1β mRNA. ELISA was used to examine the expression of inflammatory factors such as TNF-α, IL-6, IFN-γ, IP10, and IL-1β in sera. The blood parameters were analyzed with auto hematology analyzer. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was also investigated. Results FFYH showed a broad-spectrum of antiviral activity against H1N1, H3N2, H5N1, H7N9, and H9N2 influenza A viruses. Furthermore, FFYH dose-dependently increased the survival rate, significantly prolonged the median survival time of mice, and markedly reduced lung injury caused by influenza A virus. Also, FFYH significantly improve the sick signs, food taken, weight loss, blood parameters, lung index, and lung pathological changes. Moreover, FFYH could markedly inhibit the inflammatory cytokine expression of TNF-α, IL-6, IFN-γ, IP10, IL-10, and IL-1β mRNA or protein via inhibition of the TLR7/MyD88/NF-κB signaling pathway in vivo. Conclusion FFYH not only showed a broad-spectrum of anti-influenza virus activity in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. Furthermore, our results indicated that the in vivo antiviral effect of FFYH against influenza virus may be attributed to suppressing the expression of inflammatory cytokines via regulating the TLR7/MyD88/NF-κB signaling pathway. These findings provide evidence for the clinical treatment of influenza A virus infection with FFYH.

Easy processing and flexibility of polymer electrolytes make them very promising in developing all-solid-state lithium batteries. However, their low room-temperature conductivity and poor mechanical and thermal properties still hinder their applications. Here, we use Li6.75La3Zr1.75Ta0.25O12 (LLZTO) ceramics to trigger structural modification of poly(vinylidene fluoride) (PVDF) polymer electrolyte. By combining experiments and first-principle calculations, we find that La atom of LLZTO could complex with the N atom and C═O group of solvent molecules such as N,N-dimethylformamide along with electrons enriching at the N atom, which behaves like a Lewis base and induces the chemical dehydrofluorination of the PVDF skeleton. Partially modified PVDF chains activate the interactions between the PVDF matrix, lithium salt, and LLZTO fillers, hence leading to significantly improved performance of the flexible electrolyte membrane (e.g., a high ionic conductivity of about 5 × 10–4 S cm–1 at 25 °C, high mechanical s...

Background: Diabetic cardiomyopathy (DCM) is considered to be a distinct clinical entity independent of concomitant macro- and microvascular disorders, which is initiated partly by disturbances in energy substrates. This study was to observe the dynamic modulations of berberine in DCM rats and explore the changes of lipidomic profiles of myocardial tissue. Methods: Sprague-Dawley (SD) rats were fed high-sucrose and high-fat diet (HSHFD) for totally 22 weeks and intraperitoneally (i.p.) injected with 30 mg/kg of streptozotocin (STZ) at the fifth week to induce DCM. Seventy-two hours after STZ injection, the rats were orally given with berberine at 10, 30 mg/kg and metformin at 200 mg/kg, respectively. Dynamic changes of cardiac function, heart mass ratios and blood lipids were observed at f 4, 10, 16, and 22, respectively. Furthermore, lipid metabolites in myocardial tissue at week 16 were profiled by the ultra-high-performance liquid chromatography coupled to a quadruple time of flight mass spectrometer (UPLC/Q-TOF/MS) approach. Results: Berberine could protect against cardiac diastolic and systolic dysfunctions, as well as cardiac hypertrophy, and the most effective duration is with 16-week of administration. Meanwhile, 17 potential biomarkers of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and sphingolipids (SMs) of DCM induced by HSFD/STZ were identified. The perturbations of lipidomic profiles could be partly reversed with berberine intervention, i.e., PC (16:0/20:4), PC (18:2/0:0), PC (18:0/18:2), PC (18:0/22:5), PC (20:4/0:0), PC (20:4/18:0), PC (20:4/18:1), PC (20:4/20:2), PE (18:2/0:0), and SM (d18:0/16:0). Conclusions: These results indicated a close relationship between PCs, PEs and SMs and cardiac damage mechanisms during development of DCM. The therapeutic effects of berberine on DCM are partly caused by interferences with PCs, PEs, and SMs metabolisms.

Panax notoginseng saponins (PNS) are known as clinical anti-stroke herbal medicines. The aim of this study is to describe the impact of PNS on ischemia-reperfusion-induced cerebral microvasculature barrier dysfunction which has not been investigated yet. Mice were subjected to transient middle cerebral artery occlusion and PNS were administrated to mice 3 days before and 2 days after surgery. Leukocyte adhesion, albumin leakage, tight junctions and other parameters in the cortex were measured. The PNS 45 mg/kg intervention alleviated leukocyte adhesion, inhibited endothelial barrier alterations evidenced by reduced albumin leakage and tight junction degradations, and ultimately ameliorated infarct volumes and neurological deficits subsequent to ischemia-reperfusion. Taken together, P. notoginseng saponins are able to attenuate leukocyte-mediated microvascular disturbance at the onset of ischemic stroke.

In this study, we investigated the effects of ethanol extracts of Ophiocordyceps sinensis (EEOS) on neuroprotective efficacy in a rat model of focal cerebral ischemia/reperfusion (IR). The effects of EEOS on mortality rate, neurobehavior, grip strength, polymorphonuclear (PMN) cells, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, intracellular adhesion molecule 1 (ICAM-1), and cyclooxygenase-2 (COX-2) were determined by enzyme-linked immunosorbent assay and immunohistochemistry. The cerebral infarction was examined through tetrazolium chloride staining. EEOS significantly inhibited IR-induced brain production of IL-1β, TNF-α, iNOS, ICAM-1, and COX-2. Moreover, EEOS suppressed infiltration of PMN cells. EEOS caused a significant reduction in the infarct size compared with the middle cerebral artery occlusion group. The study demonstrates the neuroprotective potential of EEOS inhibition of IR through anti-inflammatory activity in a rat model of IR.

Layer-structured materials are often considered to be good candidates for thermoelectric materials, because they tend to exhibit intrinsically low thermal conductivity as a result of atomic interlayer interactions. The electrical properties of layer-structured materials can be easily tuned using various methods, such as band modification and intercalation. We report TiNBr, as a member of the layer-structured metal nitride halide system MNX (M = Ti, Zr, Hf; X = Cl, Br, I), and it exhibits an ultrahigh Seebeck coefficient of 2215 $\mu V/K$ at 300K. The value of the dimensionless figure of merit, ZT, along A axis can be as high as 0.661 at 800K, corresponding to a lattice thermal conductivity as low as 1.34 W/(m K). The low ${\kappa_l}$ of TiNBr is associated with a collectively low phonon group velocity ($2.05\times 10^3 $ m/s on average) and large phonon anharmonicity that can be quantified using the Gr\"uneisen parameter and three-phonon processes. Animation of the atomic motion in highly anharmonic modes mainly involves the motion of N atoms, and the charge density difference reveals that the N atoms become polarized with the merging of anharmonicity. Moreover, the fitting procedure of the energy-displacement curve verifies that in addition to the three-phonon processes, the fourth-order anharmonic effect is also important in the integral anharmonicity of TiNBr. Our work is the first study of the thermoelectric properties of TiNBr and may help establish a connection between the low lattice thermal conductivity and the behavior of phonon vibrational modes.

Easy processing and flexibility of polymer electrolytes make them very promising in developing all-solid-state lithium batteries. However, their low room-temperature conductivity and poor mechanical and thermal properties still hinder their applications. Here, we use Li

The human bitter taste receptors (TAS2Rs) belong to the GPCR family, while the activation mechanism and how TAS2Rs recognise bitter ligands are poorly understood. In this study, 3D structure of TAS2R16 was constructed using homology modelling complemented with molecular dynamics method. Salicin and probenecid were docked to TAS2R16 receptor to investigate the possible activation mechanism of TAS2R16. The results show that salicin and probenecid locate at the binding pocket made up of transmembrane helices TM3, TM5 and TM7, and the second and third extracellular loops ECL2 and ECL3. Structural analysis reveals that the network interactions at the third intracellular loop ICL3 may play a crucial role in stabilising the inactive state of TAS2R16, and structural change in the intracellular region is correlated with the activation of TAS2R16. The binding energies of salicin and probenecid to TAS2R16 are −152.81 ± 15.09 and −271.90 ± 26.97 kJ/mol, respectively, indicating that a potential antagonist should have obviously stronger binding affinity.

Toxicity of Chinese materia medica (CMM) is an important part of Chinese herbal nature theory. In clinical application, the dosage, time limitation and compatibility of CMM is mainly determined by toxicity. At present, there is no uniform toxicity classification standard for the evaluation of Chinese herbal toxicity. Therefore, it is significant to research toxicity classification of CMM. The current situation of toxicity classification of CMM is reviewed in this paper, and proposed research thoughts are as follows: the measurement of toxicity parameters, the confirmation of poisoning target organs, the investigation on toxic mechanism by serum pharmacology and toxicokinetics, the comprehensive evaluation on toxicity based on quantitative theory. Language: zh

To study the correlation between content changes of Diester diterpenoid alkaloids (DDAs) content and safety of the processed Fuzi.Sequential and Bliss methods were used to evaluate the safety of 7 kinds of Fuzi processed with different processing time. The relationship between ED50, TD50, TI and content changes of DDAs of those processed Fuzi was studied, the correlation between the content changes and effect of different processed Fuzi was analyzed, and the toxicity of those processed Fuzi with multiple linear regression was tested.Fuzi with good efficiency and safety contains proper hypaconitine (HA) and mesaconitine (MA). Aconitine (AC) interfered efficacy of Fuzi (negative correlation), HA showed positive correlation with toxicity and efficacy of Fuzi.HA and MA kept in determinate proportion are very important for the safety and effectivity of processed Fuzi.