Pulse buildup dynamics in a self-starting Mamyshev oscillator.

The Mamyshev oscillator (MO) can generate high-performance pulses. However, due to their non-resonant cavities, they usually are not self-starting, and there is almost no effort to reveal the pulse buildup dynamics of the MO. This paper investigates the dynamic of single pulse (SP) and multi-pulse formation in a self-starting MO. It indicated that both SP self-starting and multi-pulse self-starting can be obtained by adjusting the oscillator parameters. More importantly, increasing pump power could only result in bound state pulses (BSPs) if SP self-starting was formed. With the increase of the pump power, the pulse number in BSPs would increase. However, multiple pulses could not be formed only by increasing the pump power, and the BSPs obtained here underwent SP generated from noise, amplified, and then bounded, which is different from conventional passive mode-locked fiber lasers (CPMLFLs). On the other hand, if multiple pulses were self-initiated, BSPs, pulse bunch, and harmonic mode-locked pulses (HMLPs) could be obtained by adjusting the polarization state and pump power in the cavity. Furthermore, once any of the above states are formed, if the oscillator polarization state and filter interval are unchanged, only increasing the pump power from zero, the original state can still be obtained, which is consistent with the characteristics of the CPMLFLs. These findings will provide new insights into the pulse dynamics of self-starting MO, which will be significant for studying ultrafast laser technology and nonlinear optics.

Design and synthesis of 2-(2,2-diarylethyl)-cyclamine derivatives as M3 receptor antagonists and functional evaluation on COPD.

Muscarine acetylcholine receptors (mAChRs) regulate a variety of central and peripheral physiological functions and emerge as important therapeutic targets for a number of diseases including chronic obstructive pulmonary disease (COPD). Inspired by two active natural products, we designed and synthesized a series of 2-(2,2-diarylethyl)-cyclamine derivatives for screening M3 mAChR antagonists. On this skeleton, the structural units including N heterocycle, aryl groups and its substituents on aryl were examined and resulted in a clear structure-activity relationships on the M3 mAChR. In general, these 2-(2,2-diarylethyl)-cyclamine derivatives exhibited good to excellent M3 antagonistic potency and receptor selectivity. The most active 5b-C1 had an IC50 value of 3 nM and the most of compound 6 displayed inactivity against histamine H1 receptor closely related to M3. In in vitro and in vivo evaluations of tracheo-relaxation function, some compounds even showed comparable activity to tiotropium bromide, a known blockbuster drug for COPD. Such excellent properties made these novel compounds potential candidates for COPD drug development.

Chemical profiling of Ziziphi spinosae semen using on-line comprehensive two-dimensional liquid chromatography-mass spectrometry based on a novel phthalic anhydride bonded stationary phase.

Ziziphi spinosae semen has been widely used to treat insomnia and anxiety. To profile its chemical components, an online comprehensive two-dimensional liquid chromatography-mass spectrometry was developed. In this two-dimensional liquid chromatography system, a novel phthalic anhydride-bonded stationary phase column was combined with a C18 column. As a result, this new stationary phase exhibited remarkable differences in separation selectivity from C18, achieving a good orthogonality of 83.3%. Moreover, this new stationary phase with weaker hydrophobicity than C18 realized solvent compatibility in the online configuration. Coupled with tandem MS, 154 compounds were identified, including 51 unreported compounds. Compared with one-dimensional liquid chromatography-mass spectrometry, this online two-dimensional liquid chromatography-mass spectrometry system exhibited a much higher resolving power in isomer separation. This work provided an effective separation and characterization method for the material basis of Ziziphi spinosae semen. This strategy provides ideas for the material basis research of other traditional Chinese medicines.

Comparative study on the selection of drainage methods in posterior lumbar interbody fusion.

OBJECTIVE: To compare and analyze the clinical effects of bilateral natural pressure drainage and negative pressure drainage after posterior lumbar interbody fusion (PLIF) to provide a reference for selecting drainage methods after lumbar surgery. METHODS: A retrospective cohort study, 281 patients who underwent single-segment PLIF in our hospital from January 2017 to December 2020 and met the inclusion and exclusion criteria were included in the study, including 132 males and 149 females, aged 22-85 years, with an average of (53.62 ± 11.23) years. According to different postoperative incision drainage methods determined by the random number table method before surgery, they were divided into the natural pressure drainage group and negative pressure drainage group, both of which were bilateral drainage. The general observation indexes and perioperative-related indexes were recorded and analyzed. RESULTS: There were 143 cases in the natural pressure drainage group and 138 cases in the negative pressure drainage group. There was no significant difference in age, gender, body mass index, disease type, blood pressure on the day of surgery, preoperative albumin, hemoglobin, platelet, prothrombin time, and intraoperative bleeding between the two groups (P > 0.05). The albumin on the first postoperative day in the natural pressure drainage group was higher than that in the negative pressure drainage group [(33.24 ± 3.52) vs. (32.17 ± 5.03), P < 0.05]; The hemoglobin on the first postoperative day in the natural pressure drainage group was higher than that in the negative pressure drainage group [(126.01 ± 15.03) vs. (115.19 ± 16.25), P < 0.01]; The drainage volume on the first postoperative day in the natural pressure drainage group was lower than that in the negative pressure drainage group [(93.25 ± 63.58) ml vs. (119.46 ± 54.48) ml, P < 0.01]; The total postoperative drainage volume in the natural pressure drainage group was lower than that in the negative pressure drainage group [(355.60 ± 189.69) ml vs. (434.37 ± 149.12) ml, P < 0.01]; The indwelling time of drainage tube in the natural pressure drainage group was lower than that in the negative pressure drainage group [(3.29 ± 1.17) d vs. (3.45 ± 0.97) d, P < 0.05]. There was no significant difference in platelet count on the first postoperative day, postoperative hospital stays, and complications (incision infection and hematoma) between the two groups (P > 0.05). CONCLUSION: Bilateral natural pressure drainage and negative pressure drainage can achieve good drainage effects after PLIF, but patients with natural pressure drainage have less loss of albumin and hemoglobin, less drainage volume, and shorter drainage tube indwelling time, which is worthy of clinical application.

A Physical Fatigue Evaluation Method for Automotive Manual Assembly: An Experiment of Cerebral Oxygenation with ARE Platform.

Due to the complexity of the automobile manufacturing process, some flexible and delicate assembly work relies on manual operations. However, high-frequency and high-load repetitive operations make assembly workers prone to physical fatigue. This study proposes a method for evaluating human physical fatigue for the manual assembly of automobiles with methods: NIOSH (National Institute for Occupational Safety and Health), OWAS (Ovako Working Posture Analysis System) and RULA (Rapid Upper Limb Assessment). The cerebral oxygenation signal is selected as an objective physiological index reflecting the human fatigue level to verify the proposed physical fatigue evaluation method. Taking auto seat assembly and automobile manual assembly as an example, 18 group experiments were carried out with the ARE platform (Augmented Reality-based Ergonomic Platform). Furthermore, predictions of metabolic energy expenditure were performed for experiments in Tecnomatix Jack. Finally, it is concluded that the proposed physical fatigue evaluation method can reflect the human physical fatigue level and is more accurate than the evaluation of metabolic energy consumption in Tecnomatix Jack because of the immersion that comes with the AR devices and the precision that comes with motion capture devices.

Wavelength and bandwidth tunable filter and its application in a dissipative soliton fiber laser.

A wavelength and bandwidth tunable filter and its application in a dissipative soliton (DS) Yb-doped fiber laser are demonstrated. The spectral filter consisting of six cascaded temperature-sensitive long-period fiber gratings is designed and fabricated for the first time, to the best of our knowledge. The corresponding spectral characteristics of the filter are also characterized with temperature. Its 3-dB bandwidth can be adjusted from 4.84 to 11.02 nm, and the center wavelength is continuously adjustable from 1036 to 1045 nm. The sensitivity of the variation of the center wavelength and the linearity of the center wavelength variation are 32 pm/°C and 99.53%, respectively. This home-made spectral filter has two notable features: i) with regard to the tunable spectrum, the 3-dB bandwidth of the spectrum filter can be unchanged; ii) with regard to the spectral tunability, the 3-dB bandwidth of the spectral filter can also be quantitatively changed as needed by changing the heating mode. The home-made spectral filter is used in the DS fiber laser to further realize the continuous adjustment of DS with a tuning accuracy of 0.03 nm by a step size of 1°C. Such a wavelength-tunable DS fiber laser greatly enhances the design flexibility of the coherent anti-Stokes Raman scattering source.

Preparation, characterization, and in-vitro cytotoxicity of nanoliposomes loaded with anti-tubercular drugs and TGF-ß1 siRNA for improving spinal tuberculosis therapy.

BACKGROUND: Tuberculosis (TB) represents a bacterial infection affecting many individuals each year and potentially leading to death. Overexpression of transforming growth factor (TGF)-ß1 has a primary immunomodulatory function in human tuberculosis. This work aimed to develop nanoliposomes to facilitate the delivery of anti-tubercular products to THP-1-derived human macrophages as Mycobacterium host cells and to evaluate drug efficiencies as well as the effects of a TGF-ß1-specific short interfering RNA (siRNA) delivery system employing nanoliposomes. METHODS: In the current study, siTGF-ß1 nanoliposomes loaded with the anti-TB drugs HRZ (isoniazid, rifampicin, and pyrazinamide) were prepared and characterized in vitro, determining the size, zeta potential, morphology, drug encapsulation efficiency (EE), cytotoxicity, and gene silencing efficiency of TGF-ß1 siRNA. RESULTS: HRZ/siTGF-ß1 nanoliposomes appeared as smooth spheres showing the size and positive zeta potential of 168.135 ± 0.5444 nm and + 4.03 ± 1.32 mV, respectively. Drug EEs were 90%, 88%, and 37% for INH, RIF, and PZA, respectively. Meanwhile, the nanoliposomes were weakly cytotoxic towards human macrophages as assessed by the MTT assay. Nanoliposomal siTGF-ß1 could significantly downregulate TGF-ß1 in THP-1-derived human macrophages in vitro. CONCLUSION: These findings suggested that HRZ-loaded nanoliposomes with siTGF-ß1 have the potential for improving spinal tuberculosis chemotherapy via nano-encapsulation of anti-TB drugs.

[Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs].

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,ß-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 µmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.

Symbiotic coexistence of noise-like pulses.

Noise-like pulse (NLP) can split and then self-assemble into dynamic bound states, named NLP polymer. Here, we reported the first observation, to the best of our knowledge, of the buildup process of bound NLPs in all-normal-dispersion Yb-doped fiber lasers. By designing two NLP fiber lasers, the distinct autocorrelation trace property for the bound NLPs with a short time interval (around 30 ps), and the high-speed oscilloscope trace characterization for the bound NLPs with a relatively broad time interval (∼500 ps) have all been exhibited. Also, we have demonstrated that it was the Raman effect that mediated the NLP bound states. The experiment results showed that though the inter-interval between the NLPs and the NLP width in the bound states are constantly changing, the envelope of each NLP remained localized and the bound NLPs could maintain within a wide pump range. The dynamics of the experimentally observed bound NLPs have also been discussed with fitting models and numerical simulations. In addition, the experimental test results for the coherence of the NLPs and their bound states further indicated that the NLPs had low temporal coherence characteristics.

Spectral filtering effect-induced temporal rogue waves in a Tm-doped fiber laser.

We have experimentally and theoretically investigated optical rogue waves (ORWs) in a net negative dispersion Tm-doped fiber laser with a long cavity, adopting nonlinear polarization evolution as a mode-locker as well as a spectral filter. We obtained a state with numerous pulses bunched in a burst accompanied by perturbation within the burst, in which the spectrum was partially perturbed. After statistical analysis, we found that ORWs have existed in this bunching state. By adjusting the intra-cavity polarization controllers, the perturbed pulse bunching turned into a chaotic pulse bunching state, which gave rise to giant pulses with ultra-high amplitudes, and the giant pulses were a precursor of a broad-spectrum noise-like pulse. The probability of occurrence of ORWs was increased in the chaotic state, which is caused by multi-pulse instability induced by the spectral filtering effect. Simulation results confirm the experimental results and demonstrate that the spectral filter bandwidth (SFB) is directly related to the probability of the emergence of ORWs. When increasing the SFB across the range of multi-pulse instability at a fixed pump power, the frequency with which ORWs appear increases.

Identification and target-pathway deconvolution of FFA4 agonists with anti-diabetic activity from Arnebia euchroma (Royle) Johnst.

FFA4 is a novel therapeutic target for the treatment of metabolic diseases, such as type II diabetes. However, there are still few ligands with structural diversity, selectivity and high potency, and the signaling pathway downstream of FFA4 remains to be poorly characterized. In this study, a high performance liquid chromatography-corona charged aerosol detector (HPLC-CAD) combined with label-free dynamic mass redistribution (DMR) method was introduced to guide the discovery of FFA4 agonists from Arnebia euchroma (Royle) Johnst. Ten compounds were identified as FFA4 agonists and structure-activity relationship was obtained. Among them, shikonin displayed the most potent activity with pEC50 value of 6.02 ± 0.19. The activity of shikonin was confirmed by FLIPR (fluorometric imaging plate reader) assay. Signaling pathways of FFA4 were explored in HT-29 cells endogenously expressing FFA4 using shikonin and known FFA4 agonists α-linolenic acid (ALA) and TUG891. Multiple pathways included Gq/11-PLC-Ca2+-PKC, RohA, JNK, p38 MAPK, Gi/o and PI3K signaling but may not involve Gs signaling triggered by shikonin, ALA and TUG891. Besides, shikonin, TUG891 and ALA could induce ERK1/2 and AKT phosphorylation in HT-29 cells. Moreover, anti-diabetes effects of shikonin were evaluated on the glucose intolerance in diabetic db/db mice. Shikonin reduced plasma glucose level, suggesting that it had the potential in treatment of type II diabetes. The agonists identified in this study provided structure guidance for FFA4 drug design. This study was also useful for understanding FFA4 pharmacology and its biological function.

Aromatic rosane diterpenoids from the roots of Euphorbia ebracteolata and their inhibitory effects against lipase.

The bioactive chemical constituents of Euphorbia ebracteolata have been investigated in the present work using various techniques. On the basis of chromatographic methods, such as silica gel, RP C-18 column chromatography, five novel rosane type diterpenoids with an aromatic A-ring (1-5) have been isolated from the roots of Euphorbia ebracteolata. Their structures were elucidated by widely spectroscopic data, including HRESI-MS, 1D and 2D NMR. Additionally, the inhibitory effects on lipase of these isolated diterpenoids were evaluated in vitro. Compound 1 as a new diterpenoid displayed significant inhibitory effect on lipase (IC50 = 1.0 µM). And, the inhibitory kinetics has been studied fully, which determined a competitive inhibition model for compound 1 on the enzymatic activity of lipase (Ki = 1.8 µM).

[Investigation of modulating effect of Qingfei Paidu Decoction on host metabolism and gut microbiome in rats].

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.

Dexmedetomidine ameliorates lipopolysaccharide-induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK-3ß/Nrf2 signaling pathway.

Acute kidney injury (AKI) is a frequent and serious complication of sepsis; however, there are currently no effective therapies. Inflammation and oxidative stress are the major mechanisms implicated in lipopolysaccharide (LPS)-induced AKI. Dexmedetomidine (DEX) has been reported to have remarkable anti-inflammatory and antioxidant effects. Here, we examined the renoprotective effects of DEX and potential underlying mechanisms in rats with LPS-induced AKI. We analyzed renal function and structure; serum inflammatory cytokine; renal oxidant and antioxidant levels; and renal expression of glycogen synthase kinase-3ß (GSK-3ß)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins in rats 4 hr after administration of LPS. Pretreatment with DEX improved renal function and significantly reduced the levels of inflammatory cytokines and oxidative stress markers. Treatment with DEX and the GSK-3ß inhibitor SB216367 promoted phosphorylation of GSK-3ß, induced Nrf2 nuclear translocation, and increased transcription of the Nrf2 target genes heme oxygenase-1 and NAD(P)H quinone oxidoreductase-1, primarily in renal tubules. Alpha-2-adrenergic receptor (α2-AR) antagonist atipamezole and imidazoline I 2 receptor (I 2 R) antagonist idazoxan reversed the effects of DEX. These results suggest that the renoprotective effects of DEX are mediated via α2-AR and I 2 R-dependent pathways that reduce inflammation and oxidative stress through GSK-3ß/Nrf2 signaling.

Dexmedetomidine alleviates lipopolysaccharide-induced acute kidney injury by inhibiting the NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway.

Dexmedetomidine (DEX) prevents kidney damage caused by sepsis, but the mechanism of this effect remains unclear. In this study, the protective molecular mechanism of DEX in lipopolysaccharide (LPS)-induced acute kidney injury was investigated and its potential pharmacological targets from the perspective of inhibiting oxidative stress damage and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Intraperitoneal injection of DEX (30 µg/kg) significantly improved LPS (10 mg/kg) induced renal pathological damage and renal dysfunction. DEX also ameliorated oxidative stress damage by reducing the contents of reactive oxygen species, malondialdehyde and hydrogen peroxide, and increasing the level of glutathione, as well as the activity of superoxide dismutase and catalase. In addition, DEX prevented nuclear factor-kappa B (NF-κB) activation and I-kappa B (IκB) phosphorylation, as well as the expressions of NLRP3 inflammasome-associated protein and downstream IL-18 and IL-1ß. The messengerRNA (mRNA) and protein expressions of toll-like receptor 4 (TLR4), NADPH oxidase-4 (NOX4), NF-κB, and NLRP3 were also significantly reduced by DEX. Their expressions were further evaluated by immunohistochemistry, yielding results were consistent with the results of mRNA and protein detection. Interestingly, the protective effects of DEX were reversed by atipamezole-an alpha 2 adrenal receptor (α2 AR) inhibitor, whereas idazoxan-an imidazoline receptor (IR) inhibitor failed to reverse this change. In conclusion, DEX attenuated LPS-induced AKI by inhibiting oxidative stress damage and NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway, mainly acting on the α2 AR rather than IR.

Dexmedetomidine attenuates lipopolysaccharide-induced liver oxidative stress and cell apoptosis in rats by increasing GSK-3ß/MKP-1/Nrf2 pathway activity via the α2 adrenergic receptor.

Dexmedetomidine (DEX) protects against liver damage caused by sepsis. The purpose of this study was to confirm the regulatory effects of DEX on glycogen synthase kinase 3 beta (GSK-3ß) via the α2 adrenergic receptor (α2AR) and evaluate the role of GSK-3ß in lipopolysaccharide (LPS)-induced liver injury. Sprague-Dawley (SD) rats were administered an intraperitoneal injection of DEX (30 µg/kg) 30 min before an intraperitoneal injection of LPS (10 mg/kg). HE staining and serum biochemical test results indicated that DEX significantly improved liver histopathological damage and liver function indices. Furthermore, DEX increased super oxide dismutase (SOD) activity and L-glutathione (GSH) levels, and inhibited malondialdehyde (MDA) production. Western blot (WB) analysis demonstrated that treatment with the GSK-3ß inhibitor SB216763 increased antioxidant-related protein mitogen-activated protein kinase phosphatase 1 (MKP-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. In addition, anti-apoptosis-related proteins were up-regulated and pro-apoptosis-related proteins were down-regulated by SB21676 administration. WB analysis also showed that DEX increased anti-apoptosis-related protein levels and decreased pro-apoptotic protein levels in LPS-induced liver injury. Nrf2, p53, and activated caspase-3 levels were further evaluated using immunohistochemistry (IHC), producing results consistent with WB results. The α2AR antagonist atipamezole (AT) significantly reversed the protective effects of DEX, as shown by WB analysis. Our data suggested that α2AR plays an important role in reversing the effects of liver oxidative stress and apoptosis via DEX, and that DEX exerts antioxidant and anti-apoptosis effects through regulation of the GSK-3ß/MKP-1/Nrf2 pathway.

A Natural Product with High Affinity to Sigma and 5-HT7 Receptors as Novel Therapeutic Drug for Negative and Cognitive Symptoms of Schizophrenia.

Dehydrocorybulbine (DHCB), an alkaloid from Corydalis yanhusuo. W.T, has been identified as a dopamine receptor antagonist. We extended our assessment of its pharmacological profile and found that DHCB exhibits high to moderate binding affinities to sigma 1 and 2 receptors, serotonin 5-HT7 receptor, and histamine H2 receptors. This led us to evaluate DHCB properties in pharmacological (apomorphine and MK-801) animal models of schizophrenia in mice. The pharmacological profile of DHCB was screened through radioligand receptor binding assays. Single dose of DHCB reversed the locomotor hyperactivity, stereotypy, and prepulse inhibition deficits induced by the dopaminergic agonist apomorphine. DHCB also reversed the depressive-like behavior and memory deficit induced by the glutamatergic antagonist MK-801 in the forced swim and the novel object recognition assays, respectively. These results indicate that DHCB effectively improves schizophrenia-like behavioral deficits that are induced by the disruption of dopaminergic and glutamatergic systems. The effectiveness of DHCB in reversing responses that mimic negative and cognitive deficits of schizophrenia might suggest that its anti-schizophrenia effects are mediated through modulating the activities of several receptor particularly sigma 1, sigma 2, 5-HT7 and dopamine receptors. Our study casts DHCB as a promising lead for therapeutic treatment of schizophrenia.

Dexmedetomidine protects against lipopolysaccharide-induced early acute kidney injury by inhibiting the iNOS/NO signaling pathway in rats.

Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early acute kidney injury (AKI) from the perspective of antioxidant stress. We found that DEX (30 µg/kg, i.p.) ameliorated the renal dysfunction and histopathological damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory cells and cast formation) induced by LPS (10 mg/kg). DEX also attenuated renal oxidative stress remarkably in LPS-induced early AKI, as evidenced by reduction in production of reactive nitrogen species, decreasing malondialdehyde levels, as well as increasing superoxide dismutase activity and glutathione content. DEX prevented activator protein-1 translocation, inhibited phosphorylation of I-kappa B (IκB) and activation of nuclear factor kappa B (NF-κB) in LPS-induced early AKI, as assessed by real-time quantitative polymerase chain reaction and protein levels of c-Jun, c-Fos, IκB and NF-κB. Notably, DEX pretreatment had the same effect as intraperitoneal injection of an inhibitor of inducible nitric oxide synthase inhibitor (1400W; 15 mg/kg), and inhibited the activity of renal inducible nitric oxide synthase (iNOS) and decreased the expression of iNOS mRNA and NO production. However, the protective effect of DEX on LPS-induced early AKI was reversed by the alpha 2 adrenal receptor (α2-AR) inhibitor atipamezole, whereas the imidazoline receptor inhibitor idazoxan did not. Taken together, DEX protects against LPS-induced early AKI in rats by inhibiting the iNOS/NO signaling pathway, mainly by acting on α2-ARs instead of IRs.

Identification of Alkaloids from Corydalis yanhusuo W. T. Wang as Dopamine D1 Receptor Antagonists by Using CRE-Luciferase Reporter Gene Assay.

Corydalis yanhusuo W. T. Wang (C. yanhusuo) has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of C. yanhusuo blocks dopamine receptors, demonstrating that its pharmacological activities are mostly due to the antagonistic effects of some of its components at dopamine receptors. As part of our ongoing project on C. yanhusuo, the aim of the present study is to establish a high-throughput and low-cost screening assay system and test the abilities of the isolated alkaloids from C. yanhusuo to inhibit dopamine-induced dopamine D1 receptor activity. By using our established cyclic adenosine monophosphate (cAMP)-response element (CRE)-luciferase reporter gene assay system, we identified eight alkaloids from C. yanhusuo with D1 receptor antagonistic activities. We next validated the activities of these compounds using fluorometric imaging plate reader (FLIPR) assay by measuring the intracellular Ca2+ change. Six out of eight compounds, including tetrahydropalmatine, corydaline, 13-methyldehydrocorydalmine, dehydrocorybubine, dehydrocorydaline, and columbamine, can be confirmed for their inhibitory activities. The dopamine-receptor-antagonistic effects of four compounds, including 13-methyldehydrocorydalmine, dehydrocorydaline, columbamine, and corydaline, are reported for the first time. The present study provides an important pharmacological basis to support the traditional use of C. yanhusuo in China.

Practical method for the definition of chromatographic peak parameters in preparative liquid chromatography.

A practical method was established for the definition of chromatographic parameters in preparative liquid chromatography. The parameters contained both the peak broadening level under different amounts of sample loading and the concentration distribution of the target compound in the elution. The parameters of the peak broadening level were defined and expressed as a matrix, which consisted of sample loading, the forward broadening and the backward broadening levels. The concentration distribution of the target compound was described by the heat map of the elution profile. The most suitable stationary phase should exhibit the narrower peak broadening and it was best to broaden to both sides to compare to the peak under analytical conditions. Besides, the concentration distribution of the target compounds should be focused on the middle of the elution. The guiding principles were validated by purification of amitriptyline from the mixture of desipramine and amitriptyline. On the selected column, when the content of the impurity desipramine was lower than 0.1%, the recovery of target compound was much higher than the other columns even when the sample loading was as high as 8.03 mg/cm3 . The parameters and methods could be used for the evaluation and selection of stationary phases in preparative chromatography.