Dopamine D_(3) receptor(D_(3)R)is implicated in multiple psychotic symptoms.Increasing the D_(3)R selectivity over dopamine D_2 receptor(D_2R)would facilitate the antipsychotic treatments.Herein,novel carbazole and te...Dopamine D_(3) receptor(D_(3)R)is implicated in multiple psychotic symptoms.Increasing the D_(3)R selectivity over dopamine D_2 receptor(D_2R)would facilitate the antipsychotic treatments.Herein,novel carbazole and tetrahydro-carboline derivatives were reported as D_(3)R selective ligands.Through a structure-based virtual screen,ZLG-25(D_(3)R K_i=685 nmol/L;D_2R K_i>10,000 nmol/L)was identified as a novel D_(3)R selective bitopic ligand with a carbazole scaffold.Scaffolds hopping led to the discovery of novel D_(3)R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core.Further functional studies showed that most derivatives acted as h D_(3)R-selective antagonists.Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity.Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction.Furthermore,36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests,and alleviated the MK-801-induced disruption of novel object recognition in mice.Additionally,preliminary studies confirmed the favorable PK/PD profiles,no weight gain and limited serum prolactin levels in mice.These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.展开更多
In this paper, a data-driven linear clustering(DLC) method is proposed to solve the long-term system load forecasting problem caused by load fluctuation in some developed cities. A large substation load dataset with a...In this paper, a data-driven linear clustering(DLC) method is proposed to solve the long-term system load forecasting problem caused by load fluctuation in some developed cities. A large substation load dataset with annual interval is utilized and firstly preprocessed by the proposed linear clustering method to prepare for modelling.Then optimal autoregressive integrated moving average(ARIMA) models are constructed for the sum series of each obtained cluster to forecast their respective future load. Finally, the system load forecasting result is obtained by summing up all the ARIMA forecasts. From error analysis and application results, it is both theoretically and practically proved that the proposed DLC method can reduce random forecasting errors while guaranteeing modelling accuracy, so that a more stable and precise system load forecasting result can be obtained.展开更多
The power market is a typical imperfectly competitive market where power suppliers gain higher profits through strategic bidding behaviors.Most existing studies assume that a power supplier is accessible to the suffic...The power market is a typical imperfectly competitive market where power suppliers gain higher profits through strategic bidding behaviors.Most existing studies assume that a power supplier is accessible to the sufficient market information to derive an optimal bidding strategy.However,this assumption may not be true in reality,particularly when a power market is newly launched.To help power suppliers bid with the limited information,a modified continuous action reinforcement learning automata algorithm is proposed.This algorithm introduces the discretization and Dyna structure into continuous action reinforcement learning automata algorithm for easy implementation in a repeated game.Simulation results verify the effectiveness of the proposed learning algorithm.展开更多
Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival o...Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite (HA) and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.展开更多
17β-Estradiol (E2) is an endocrine disrupting chemical of harm to both animals and human beings at a low concentration level (ng/L). It cannot be completely removed by wastewater treatments, and is often detected...17β-Estradiol (E2) is an endocrine disrupting chemical of harm to both animals and human beings at a low concentration level (ng/L). It cannot be completely removed by wastewater treatments, and is often detected in both environment and drinking waters. The purpose of this feasibility study, towards environmental engineering in the field of water analysis and treatment, was to remove E2 by extraction using non-imprinted polymer (NIP) submicron particles. Experimental results showed that 0.5 mg/L of E2 could be completely extracted by adding 10 mg of NIP particles directly into 10 mL of water. However, the extraction efficiency decreased to 64% for 100 mL of water. prefilling the NIP particles inside a membrane filter showed a potential for water treatment of a large volume, requiring no effort to distribute the particles uniformly in the water. High extraction efficiency (80 ± 10)% for E2 was achieved for 100 mL of water. A total mass of 0.29 mg E2 was extracted from 1000 mL of water containing 0.8 mg/L E2 (by using only 10 mg of NIP particles). Both efficiency and mass capacity can be increased, by scaling up the amount of NIP particles, towards environmental engineering applications.展开更多
基金supported by The National Key R&D Program (2022YFC2303700,China)the Ningxia Hui Autonomous Region Key Research and Development Project (2022BEG02042,China)+3 种基金the National Natural Science Foundation of China (82030108,81803351)Open Fund of State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University (KF-202304,China)the China Postdoctoral Science Foundation (2018M641122,China)the National Major Scientific and Technological Special Project for Significant New Drugs Development (2018ZX09711002-013-004,2018ZX09735-001,China)。
文摘Dopamine D_(3) receptor(D_(3)R)is implicated in multiple psychotic symptoms.Increasing the D_(3)R selectivity over dopamine D_2 receptor(D_2R)would facilitate the antipsychotic treatments.Herein,novel carbazole and tetrahydro-carboline derivatives were reported as D_(3)R selective ligands.Through a structure-based virtual screen,ZLG-25(D_(3)R K_i=685 nmol/L;D_2R K_i>10,000 nmol/L)was identified as a novel D_(3)R selective bitopic ligand with a carbazole scaffold.Scaffolds hopping led to the discovery of novel D_(3)R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core.Further functional studies showed that most derivatives acted as h D_(3)R-selective antagonists.Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity.Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction.Furthermore,36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests,and alleviated the MK-801-induced disruption of novel object recognition in mice.Additionally,preliminary studies confirmed the favorable PK/PD profiles,no weight gain and limited serum prolactin levels in mice.These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.
基金supported by the National Energy(Shanghai)Smart Grid Research Centerthe National Natural Science Foundation of China(No.51377103)
文摘In this paper, a data-driven linear clustering(DLC) method is proposed to solve the long-term system load forecasting problem caused by load fluctuation in some developed cities. A large substation load dataset with annual interval is utilized and firstly preprocessed by the proposed linear clustering method to prepare for modelling.Then optimal autoregressive integrated moving average(ARIMA) models are constructed for the sum series of each obtained cluster to forecast their respective future load. Finally, the system load forecasting result is obtained by summing up all the ARIMA forecasts. From error analysis and application results, it is both theoretically and practically proved that the proposed DLC method can reduce random forecasting errors while guaranteeing modelling accuracy, so that a more stable and precise system load forecasting result can be obtained.
基金This work was supported by the National Natural Science Foundation of China(No.U1866206).
文摘The power market is a typical imperfectly competitive market where power suppliers gain higher profits through strategic bidding behaviors.Most existing studies assume that a power supplier is accessible to the sufficient market information to derive an optimal bidding strategy.However,this assumption may not be true in reality,particularly when a power market is newly launched.To help power suppliers bid with the limited information,a modified continuous action reinforcement learning automata algorithm is proposed.This algorithm introduces the discretization and Dyna structure into continuous action reinforcement learning automata algorithm for easy implementation in a repeated game.Simulation results verify the effectiveness of the proposed learning algorithm.
基金financially supported by the National Natural Science Foundation of China (Nos. 31600811, 81573154, 81773432)the Application Fundamental Research Foundation of Sichuan Province Science and Technology Department, China (Nos. 2016JY0157, 2017JY0123)Scientific Research Foundation of the Health and Family Planning Commission of Sichuan Province, China (Nos. 17PJ556, 17PJ563)
文摘Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite (HA) and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.
基金supported by the Natural Sciences and Engineering Research Council of Canada(Fund 315574)
文摘17β-Estradiol (E2) is an endocrine disrupting chemical of harm to both animals and human beings at a low concentration level (ng/L). It cannot be completely removed by wastewater treatments, and is often detected in both environment and drinking waters. The purpose of this feasibility study, towards environmental engineering in the field of water analysis and treatment, was to remove E2 by extraction using non-imprinted polymer (NIP) submicron particles. Experimental results showed that 0.5 mg/L of E2 could be completely extracted by adding 10 mg of NIP particles directly into 10 mL of water. However, the extraction efficiency decreased to 64% for 100 mL of water. prefilling the NIP particles inside a membrane filter showed a potential for water treatment of a large volume, requiring no effort to distribute the particles uniformly in the water. High extraction efficiency (80 ± 10)% for E2 was achieved for 100 mL of water. A total mass of 0.29 mg E2 was extracted from 1000 mL of water containing 0.8 mg/L E2 (by using only 10 mg of NIP particles). Both efficiency and mass capacity can be increased, by scaling up the amount of NIP particles, towards environmental engineering applications.