Hypidone Hydrochloride (YL-0919) Produces a Fast-Onset Reversal of the Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure

Our previous study showed that hypidone hydrochloride (YL-0919), a partial serotonin 1A (5-HT1A) receptor agonist and 5-HT reuptake inhibitor, exerts a significant antidepressant effect in various animal models. The aim of the present study was to further investigate the underlying mechanisms and whether it could act as a fast-onset antidepressant. In the current study, depressive-like behavior was induced in rats by a chronic unpredictable stress (CUS) model and assessed with the Sucrose Preference Test (SPT). Treatment with YL-0919 (2.5 mg/kg, i.g.), but not with fluoxetine (Flx; 10 mg/kg, i.g.), caused a fast improvement in the SPT scores. In CUS-exposed rats, YL-0919 treatment for 5 days decreased the immobility time in a forced swimming test (FST), and a 10-day treatment decreased the latency to feed in a Novelty-Suppressed Feeding Test (NSFT). In addition to the behavioral tests, the effects of YL-0919 on synaptic protein expression were also evaluated. Western blotting showed that YL-0919 significantly enhanced the expression levels of synaptic proteins such as synapsin I, postsynaptic density protein 95 (PSD95), phosphorylated mammalian targeting of rapamycin (pmTOR) and brain-derived neurotrophic factor (BDNF) in the hippocampus. To determine how the mTOR signaling is involved in the fast-onset antidepressant-like effects of YL-0919, the mTOR-specific inhibitor rapamycin was administered intracerebroventricularly (i.c.v.) together with the YL-0919 treatment. The observed changes in behavioral tests and protein expression could be reversed by rapamycin treatment. This suggests that the fast-onset antidepressant effects of YL-0919 were partially caused by changes in synaptogenesis mediated by activation of mTOR pathways. Our data suggest that YL-0919 may be a powerful/effective antidepressant with fast-onset

The effects of tensile and compressive dwells on creep-fatigue behavior and fracture mechanism in welded joint of P92 steel

The creep-fatigue interactions on the long-term service damage of P92 welded joint were investigated on the tensile and compressive holdings with a series of applied strains, respectively. The local mechanical properties including hardness, elastic modulus and creep resistance of welded joint were uncovered using nanoindentation. The features of fracture morphology and internal defects after CF tests were studied by scanning electron mi- croscope. Based on the characteristic of microstructural evolution and the variation in local mechanical prop- erties, holding type effects of creep-fatigue interaction on the local creep behavior and fracture mechanism of the welds were systematically investigated

Genome-wide identification of the WRKY gene family in Camellia oleifera and expression analysis under phosphorus deficiency

Camellia oleifera Abel. is an economically important woody edible-oil species that is mainly cultivated in hilly areas of South China. The phosphorus (P) deficiency in the acidic soils poses severe challenges for the growth and productivity of C. oleifera. WRKY transcription factors (TFs) have been proven to play important roles in biological processes and plant responses to various biotic/abiotic stresses, including P deficiency tolerance. In this study, 89 WRKY proteins with conserved domain were identified from the C. oleifera diploid genome and divided into three groups, with group II further classified into five subgroups based on the phylogenetic relationships. WRKY variants and mutations were detected in the gene structure and conserved motifs of CoWRKYs. Segmental duplication events were considered as the primary driver in the expanding process of WRKY gene family in C. oleifera. Based on transcriptomic analysis of two C. oleifera varieties characterized with different P deficiency tolerances, 32 CoWRKY genes exhibited divergent expression patterns in response to P deficiency stress. qRT-PCR analysis demonstrated that CoWRKY11, -14, -20, -29 and -56 had higher positive impact on P-efficient CL40 variety compared with P-inefficient CL3 variety. Similar expression trends of these CoWRKY genes were further observed under P deficiency with longer treatment period of 120d. The result indicated the expression sensitivity of CoWRKYs on the P-efficient variety and the C. oleifera cultivar specificity on the P deficiency tolerance. Tissue expression difference showed CoWRKYs may play a crucial role in the transportation and recycling P in leaves by affecting diverse metabolic pathways. The available evidences in the study conclusively shed light on the evolution of the CoWRKY genes in C. oleifera genome and provided a valuable resource for further investigation of functional characterization of WRKY genes involved to enhance the P deficiency tolerance in C. oleifera

Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials

BackgroundProbiotics play a vital role in treating immune and inflammatory diseases by improving intestinal barrier function; however, a comprehensive evaluation is missing. The present study aimed to explore the impact of probiotics on the intestinal barrier and related immune function, inflammation, and microbiota composition. A systematic review and meta-analyses were conducted.MethodsFour major databases (PubMed, Science Citation Index Expanded, CENTRAL, and Embase) were thoroughly searched. Weighted mean differences were calculated for continuous outcomes with corresponding 95% confidence intervals (CIs), heterogeneity among studies was evaluated utilizing I2 statistic (Chi-Square test), and data were pooled using random effects meta-analyses.ResultsMeta-analysis of data from a total of 26 RCTs (n = 1891) indicated that probiotics significantly improved gut barrier function measured by levels of TER (MD, 5.27, 95% CI, 3.82 to 6.72, P < 0.00001), serum zonulin (SMD, -1.58, 95% CI, -2.49 to -0.66, P = 0.0007), endotoxin (SMD, -3.20, 95% CI, -5.41 to -0.98, P = 0.005), and LPS (SMD, -0.47, 95% CI, -0.85 to -0.09, P = 0.02). Furthermore, probiotic groups demonstrated better efficacy over control groups in reducing inflammatory factors, including CRP, TNF-α, and IL-6. Probiotics can also modulate the gut microbiota structure by boosting the enrichment of Bifidobacterium and Lactobacillus.ConclusionThe present work revealed that probiotics could improve intestinal barrier function, and alleviate inflammation and microbial dysbiosis. Further high-quality RCTs are warranted to achieve a more definitive conclusion.Clinical trial registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281822, identifier CRD42021281822

面向知识经济大潮的领导者素质问题 = A study on the leaders' qualities in a knowledge economy environment

Being a completely new economic form, knowledge economy is exerting more and more strikingly affects on all aspects of the society. What qualities leaders should possess to meet the challenge of knowledge economy becomes an important research topic. This thesis thoroughly discussed the essential qualities leaders (mainly the leaders of counties, cities and enterprises) should own in a knowledge economy environment. The methodologies and methods for a comprehensive improvement in the leaders' qualities have been systematically studied. Based on a thorough study of knowledge economy and the newest research results, this thesis systematically discussed the origins, concepts and characteristics of knowledge economy and their influences on various aspects of the society. Based on abundant information analysis and typical case studies, this thesis has initially revealed the five basic qualities (global brain, foresight, creativeness, alllife- study and moral quality) that leaders at every level must own to suit the corresponding characteristics of knowledge economy, i.e., network, globalization and creative ability, etc. The author objectively analyzed the current situations of the leaders at various positions from different aspects, such as moral characteristics, educational background, management ability, creative ability and global viewpoint, etc. New concepts and standards for the choice and use of leaders have been put forward. The ways and methods for the selection, examination, and training of leaders have also been presented in details.​Master of Science (Managerial Economics

PVP2005-71502 STUDY ON TUBE PULLING APART LOAD IN TUBULAR HEAT EXCHANGERS WITH FEA METHOD

ABSTRACT Tube pulling apart loads of tube-and-shell heat exchangers are very complicated, because these loads are affected by many factors, such as, tube to tubesheet joint structure, pressure, and temperatures. The tubes may break or be fouled during the service, which will result in change of tube metal temperatures and affect pulling loads. Some tubes may be pulled out from the tubesheet because of too much high tube pulling apart loads and the heat exchanger cannot be operated normally. Depending on the different flow passes of the fluid and the temperature change in the service, the tube pulling loads for several cases with different temperature distribution are calculated and analyzed for a heat exchanger using finite element (FE) method. The results show that the pulling loads of different tubes are different obviously. The pulling loads of the heat exchanger are assessed with ASME Code. The maximum pulling load is over the allowable force. FE method is a good technique to assess the distribution of the pulling loads and the location of the maximum pulling load. So it is useful and important to use FE method for forecasting the break and leak of the tubes

Numerical Simulation of Internal Flow Field, Electromagnetic Field and Temperature Field in Deep-Water Motor

In this paper, considering the heat exchange between the ends of stator&rotor and lubricating oil, the internal flow field model is established to analyse the flow state. The variation law of the pressure drops in the internal flow field and the friction loss of the rotor surface are specified. The operation characteristic of the motor and the variation law of the magnetic field loss are obtained through the analysis of motor magnetic field. Based on the results of internal flow field and magnetic field, the temperature distribution law of motor is obtained. Compared with the result of the temperature simulation in which only air gap path is considered, the stator temperature shows totally different distribution law, and the stator temperature increases from 32°C to 42°C. Compared with the result of the temperature simulation without considering heat source loss change, the maximum temperature of the motor decreases from 71°C to 49°C. The results show that the ends of stator&rotor and the variation of heat source loss can influence the temperature simulation results