Suanzaoren decoction exerts its antidepressant effect via the CaMK signaling pathway.

Calmodulin-dependent protein kinases (CaMKs) are widely regarded as "memory molecules" due to their role in controlling numerous neuronal functions in the brain, and the CaMK signaling pathway plays a crucial role in controlling synaptic plasticity. Suanzaoren decoction (SZRD) can improve depression-like behavior and thus has potential benefits in the clinical treatment of depression; however, its mechanism of action is not fully understood. In this study, we found that key proteins in the CaMK signaling pathway were regulated by the decoction used to treat depression. The purpose of this research was to ascertain if the SZRD's therapeutic efficacy in the treatment of depression is associated with the modulation of key proteins in the CaMK signaling pathway. A rat model of depression was created by exposing the animals to chronic, unexpected, mild stress. Model rats were given intragastric administration of SZRD or fluoxetine every morning once a day. Protein and mRNA relative expression levels of CaM, CaMK I, and CaMK IV in the hippocampus were measured by Western blot, quantitative polymerase chain reaction, and immunohistochemistry in the hippocampus. Our findings demonstrated that SZRD significantly improved the mood of depressed rats. This indicates that SZRD, by modulating the CaMK signaling system, may alleviate depressive symptoms and lessen work and life-related pressures.

A double-blind, randomized, placebo and positive-controlled study in healthy volunteers to evaluate pharmacokinetic and pharmacodynamic properties of multiple oral doses of cetagliptin.

AIMS: This study investigated the pharmacokinetics and pharmacodynamics properties, safety and tolerability of cetagliptin. METHODS: Forty-eight healthy subjects were enrolled in this study. Three cohorts were investigated in sequential order: 50, 100 and 200 mg cetagliptin. Positive control (sitagliptin 100 mg) was designed as open label. Blood samples were collected and analysed for pharmacokinetic and pharmacodynamic properties. Safety and tolerability were assessed throughout the study. RESULTS: Following multiple oral doses, cetagliptin was rapidly absorbed and reached peak plasma concentrations after approximately 1.0-1.5 hours. Plasma cetagliptin concentrations increased at a rate greater than dose. Accumulation of cetagliptin was modest, and steady state was generally achieved at day 5. Doses ≥50 mg of cetagliptin administered once daily will result in sustained dipeptidyl peptidase-4 (DPP-4) inhibition (≥80%). The plasma concentration giving 50% of maximum drug effect of DPP-4 inhibition for cetagliptin (5.29 ng/mL) was lower than that of sitagliptin (7.03 ng/mL). Active glucagon-like-1 peptide (GLP-1) concentrations were significantly increased in the cetagliptin groups by 2.3- to 3.1-fold at day 1 and 3.1- to 3.6-fold at steady state compared with that of placebo, and active GLP-1 concentrations were increased with increasing dose. Compared with sitagliptin, doses ≥100 mg once daily of cetagliptin produced postprandial increases in active GLP-1 level and induced to long-lasting glucose-lowering efficacy. Cetagliptin was well tolerated across all doses studied. CONCLUSION: Cetagliptin demonstrates the great potential for treatment with type 2 diabetes patients based on the inhibition of DPP-4, the increase in GLP-1 and insulin, the decrease in glucose, and might be more effective in DPP-4 inhibition than sitagliptin.

The metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C] cetagliptin in healthy volunteers.

The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50µCi [14C] cetagliptin.The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [14C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336 h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulphate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and faeces at low levels, except that metabolite M640B was not detected in faeces. All metabolites were observed with <10% of parent compound systemic exposure after oral administration.

A Novel Method for Growing α-Ga2O3 Films Using Mist-CVD Face-to-face Heating Plates.

In this paper, the method for growing α-Ga2O3 films on c-plane sapphire substrates using an inexpensive fine-channel mist-CVD face-to-face heating plate was investigated. Because high temperatures can result in reactor deformation, expensive AlN ceramics resistant to deformation are used as the reactor fabrication material in traditional fine-channel mist-CVD equipment, which limits its use for promotion and research purposes. In this work, we used a face-to-face heating method to replace the traditional single-sided heating method which will reduce the requirement for equipment sealability. Therefore, cheap quartz can be used to replace expensive AlN ceramics to make reactors, which can greatly reduce the cost of mist-CVD equipment. We also investigated the effects of substrate temperature and carrier gas on the crystalline quality and surface morphology of α-Ga2O3 films. By optimizing the fabrication conditions, we obtained triangular grains with edges that were clearly visible in atomic force microscopy images. Using absorption spectrum analysis, we also found that the optical bandgap of the film reached 5.24 eV. Finally, we recorded a value of 508 arcsec for the full width at half maximum of the α-Ga2O3 (0006) diffraction peak in the X-ray diffraction pattern.

In vitro study of the drug-drug interaction potential of cetagliptin and clinical study of pharmacokinetic interaction of cetagliptin and metformin in healthy volunteers.

Cetagliptin is an oral, potent, and newly developed selective inhibitor of dipeptidyl peptidase-4 (DPP-4). We evaluated the in vitro drug-drug interaction (DDI) potential of cetagliptin, as well as the pharmacokinetics of cetagliptin and metformin and the interaction between cetagliptin and metformin.Cetagliptin did not inhibit CYP1A2, CYP2C8, CYP2B6, CYP2C9, CYP2C19, and CYP3A4, only has a moderate inhibitory effect on CYP2D6, and did not induce CYP1A2, CYP2B6, and CYP3A4. Plasma protein binding of cetagliptin didn't have species differences or concentration dependence. Cetagliptin was a substrate for P-glycoprotein (P-gp).The 34 healthy subjects enrolled were randomly divided into two sequences (A and B) with 17 subjects in each sequence. Coadministration with metformin had no effect on cetagliptin AUC0-120 (GMR, 99.25%; 90% CI, 95.96%-102.65%). There was a slightly increase in cetagliptin Cmax (GMR, 117.33%; 90% CI, 102.54%-134.25%). Coadministration with cetagliptin did not affect the metformin's AUC0-24 (GMR, 108.54%; 90% CI, 101.41%-116.17%) or Cmax (GMR, 97.67%; 90% CI, 90.96%-104.89%).Based on in vitro study results, cetagliptin is unlikely to cause CYP-mediated, clinically relevant DDI. Although the possibility of transporter-mediated, clinically relevant DDI cannot be ruled out, there is little or no risk of side effects. Coadministration of cetagliptin and metformin had no clinically meaningful effect on the pharmacokinetics of each drug. There was no drug-drug interaction between cetagliptin and metformin. Both monotherapies and combination therapy were well tolerated. No serious AEs and hypoglycaemia was reported.

Palmatine ameliorates high fat diet induced impaired glucose tolerance.

BACKGROUND: The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. METHODS: Male Sprague-Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. RESULTS: Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased ß cell mass after the treatment of PAL. We further found out that PAL could alleviate the ß cell apoptosis that accounts for ß cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress ß cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the ß cell apoptosis and JNK signaling in vitro. CONCLUSION: In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.

The Investigation of Hybrid PEDOT:PSS/ß-Ga2O3 Deep Ultraviolet Schottky Barrier Photodetectors.

In this paper, the hybrid ß-Ga2O3 Schottky diodes were fabricated with PEDOT:PSS as the anode. The electrical characteristics were investigated when the temperature changes from 298 K to 423 K. The barrier height ϕb increases, and the ideality factor n decreases as the temperature increases, indicating the presence of barrier height inhomogeneity between the polymer and ß-Ga2O3 interface. The mean barrier height and the standard deviation are 1.57 eV and 0.212 eV, respectively, after taking the Gaussian barrier height distribution model into account. Moreover, a relatively fast response speed of less than 320 ms, high reponsivity of 0.6 A/W, and rejection ratio of R254 nm/R400 nm up to 1.26 × 103 are obtained, suggesting that the hybrid PEDOT:PSS/ß-Ga2O3 Schottky barrier diodes can be used as deep ultraviolet (DUV) optical switches or photodetectors.

Palmatine ameliorates high fat diet induced impaired glucose tolerance

BACKGROUND: The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. METHODS: Male Sprague-Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. RESULTS: Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased ß cell mass after the treatment of PAL. We further found out that PAL could alleviate the ß cell apoptosis that accounts for ß cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress ß cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the ß; cell apoptosis and JNK signaling in vitro. CONCLUSION: In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.

[Effects of electroacupuncture on synaptic plasticity in hippocampal CA3 area of rats with chronic stress depression].

OBJECTIVE: To explore the effects of electroacupuncture (EA) on behavioral function and synaptic plasticity in hippocampal CA3 area in rats with chronic stress depression. METHODS: According to the random number table method, 144 SD male rats were assigned into a blank group, a model group, an EA group and a fluoxetine group, then each group was divided into a 7 d subgroup, a 14 d subgroup and a 21 d subgroup, 12 rats in each subgroup. The chronic mild unpredictable stress stimulus combined with lonely breeding were applied to establish the depression model of rats, which was performed simultaneously with intervention treatment. The rats in the EA group were treated with EA (dilatational wave) at "Shenting" (GV 24) and "Baihui" (GV 20), while the rats in fluoxetine group were treated with intragastric administration of fluoxetine, once daily. With open-field test, sugar consumption experiment and transmission electron microscope, the changes of behavior and neuronal synapse inhippocampal CA3 area were observed. RESULTS: On 7 d, 14 d and 21 d, compared with the blank group, the open-field test score, sugar consumption and body mass were significantly lower in the model group (all P<0.01); compared with the model group, the open-field test score, sugar consumption and body mass were significantly higher in the EA group and the fluoxetine group on 14 d and 21 d (P<0.01, P<0.05). On 14 d and 21 d, compared with the blank group, the synapse in hippocampal CA3 area was significantly lower in the model group (both P<0.01); compared with the model group, the synapse in hippocampal CA3 area was significantly higher in the EA group and the fluoxetine group (P<0.01, P<0.05). The neurons cells in hippocampal CA3 area in the model group showed pyknosis and deformation from 7 d with fusion structure and unclear boundary of synapse, which were significantly improved on 21 d; the neurons cells in hippocampal CA3 area in the EA group and the fluoxetine group were significantly improved from 14 d and restored to normal level on 21 d, in addition, the structure of synapse restored to normal level. CONCLUSIONS: EA is involved in the regulation of synaptic plasticity in hippocampal CA3 area, and promotes the recovery of depression symptoms.

Simultaneously precise frequency transfer and time synchronization using feed-forward compensation technique via 120 km fiber link.

Precision time synchronization between two remote sites is desired in many applications such as global positioning satellite systems, long-baseline interferometry, coherent radar detection and fundamental physics constant measurements. The recently developed frequency dissemination technologies based on optical fiber link have improved the transfer instability to the level of 10(-19)/day at remote location. Therefore it is possible to keep clock oscillation at remote locations continuously corrected, or to reproduce a "virtual" clock on the remote location. However the initial alignment and the correction of 1 pps timing signal from time to time are still required, besides the highly stabilized clock frequency transfer between distant locations. Here we demonstrate a time synchronization based on an ultra-stable frequency transfer system via 120-km commercial fiber link by transferring an optical frequency comb. Both the phase noise compensation in frequency dissemination and temporal basis alignment in time synchronization were implemented by a feed-forward digital compensation (FFDC) technique. The fractional frequency instability was measured to be 6.18 × 10(-20) at 2000 s. The timing deviation of time synchronization was measured to be 0.6 ps in 1500 s. This technique also can be applied in multi-node fiber network topology.

Feed-forward digital phase compensation for long-distance precise frequency dissemination via fiber network.

We demonstrate precise microwave frequency dissemination of a hydrogen maser synchronized frequency comb over a 120 km commercial fiber link. The phase noise was compensated by a feed-forward digital compensation scheme, where the value of locally detected phase noise was first transmitted to the remote user end via a wavelength division multiplexing channel in the same fiber link and then compensated directly at the user end. The fractional frequency instability was measured to be at 5.28×10(-16)/s.

[Research on psychiatry in the integration of Chinese and Western medicine in 1950's].

In 1950's, the studies on psychiatry in the integration of Chinese and Western medicine was in its primary stage, which can be further divided into two periods, viz. the preparative stage, covering 1950 to 1954, during which doctors of traditional Chinese medicine were absorbed into the group of psychiatry research; and the preliminary development period, covering 1954 to 1958, during which there were more development of the clinical research on psychiatry in the integration of Chinese and Western medicine and in the Chinese herbal medicine, thus offering some effective new methods and drugs.