Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective To investigate the detection of respiratory tract virus from throat swabs of patients with lower respiratory tract infection(LRTI)in a hospital,so as to provide reference for clinical diagnosis and treatment. Methods Throat swabs of hospitalized children with LRTI between May 2103 and April 2014 were detected by di-rect immunofluorescence assay,infection/carriage of respiratory syncytial virus(RSV),adenovirus(ADV),influen-za virus A(IV-A),IV-B,parainfluenza virus 1(PIV-1),PIV-2,and PIV-3 in children were surveyed.Results Of 8 425 throat swab specimens of hospitalized patients,1 879 were detected virus,the total detection rate was 22.30%,detection rate of RSV was the highest (11 .31 %),followed by PIV-3(4.37%).There was no significant difference in the total detection rate of respiratory tract virus between children of different genders (P =0.051).Of all age groups,detection rate of RSV in infants and young children was the highest,the detection rates of 7 kinds of virus from preschool children were approximate,detection rate of ADV from primary school children was the high-est (37.50%).In spring and winter,children mainly infected with RSA,accounting for 62.82% and 69.88% re-spectively;in summer,PIV-3 was the predominant virus,accounting for 41 .47%,in autumn,there was little difference in the percentage of each virus.Conclusion The detection rate of 7 kinds of virus isolated from throat swabs of hospitalized children with LRTI is related to age and season;the detection rate of 7 kinds of virus from in-fants and young children is high,RSA is the main virus.