Objective To explore the impact of peptidylarginine deiminase 2(Padi2)-knockout on depressive-like behaviors in socially isolated mice.Methods Using CRISPR/Cas9 technology,a Padi2-knockout(Padi2-/-)mouse model with a C57BL/6J background was established,and the effect of Padi2 knockout was identified by genotyping and RT-qPCR detection.Six-week-old male Padi2-/- mice and wild-type C57BL/6J mice were selected and divided into normal rearing and social isolation groups,with 15 mice per group.The normal rearing group mice were housed with 5 mice per cage,and the social isolation group was housed with 1 mouse per cage,and weighed once a week.After 4 weeks,forced swimming and open field tests were conducted.After the behavioral experiments,brain tissues were taken from mice in each group,and changes in microglia in the brains were detected by immunofluorescence.Results We successfully established Padi2-/- mice.There was no difference in behavior between Padi2-/- mice and C57BL/6J mice in the normal rearing group.After social isolation,compared with C57BL/6J mice,Padi2-/- mice showed a significant increase in depressive symptoms,obvious weight gain,and a significant increase in the number of microglia in brain tissue.Conclusions Padi2 knockout exacerbated depressive-like behaviors and obesity in socially isolated mice,indicating that Padi2 is involved in the progression of depression and may be an effective target for the prevention and treatment of depression.

Japanese encephalitis virus(JEV)usually evades the inhibitory effect of the innate immunity factor type Ⅰ interferon(Ⅰ-IFN)when it infects human cells and tissues.The virus then causes a series of serious symptoms,such as spasticity,neurodegenerative lesions,neuroinflammation,and even death.Generally,JEV escapes innate immunity by inhibiting IFN-α/β production and the interferon Janus kinase-signal transducer and activator of transcription signaling pathway.Because of this special immune escape mechanism,various mouse infection models have been constructed for the study of the pathogenesis of and therapeutic regimens for JEV infections.In this review,based on an exposition of the IFN immune escape mechanism of JEV,we systematically introduce the concept of JEV-infected mouse models and analyze the characteristics of these models and the degree to which they simulate human symptoms.The intention is to develop various new JEV-infected mouse models based on potential new research targets and provide novel ideas for animal models for JEV research.

Objective:To evaluate the effect of value orientation brief therapy(VBT)combined with selective serotonin reuptake inhibitors(SSRIs)on clinical symptoms,rumination,decision-making ability,and cognitive func-tion in patients with mild to moderate depression.Methods:Eighty patients meeting the DSM-5 diagnostic criteria for mild to moderate depression were randomly assigned to either a medication(SSRIs)group(36 completed)or a VBT combined group(38 completed)for a 6-week intervention.Baseline and post-intervention assessments includ-ed the Hamilton Depression Scale(HAMD),Hamilton Anxious Scale(HAMA),Ruminative Response Scale-Chi-nese Version(RRS-CV),Iowa Gambling Test(IGT),number of eye fixation(NEF),responsive search score(RSS)in exploratory eye trajectory movement were used to evaluate patients'anxiety and depression symptoms,ru-minative thinking,decision-making function,and cognitive function.Results:The VBT combined group showed sig-nificantly better therapeutic effects than the medication group(P＜0.05).Compared to baseline and the medication group,the VBT combined group had significantly lower post-intervention scores in HAMD,HAMA,symptom rumi-nation,introspective reflection,compulsive meditation,and RRS-CV total scores after intervention(Ps＜0.05),and significantly higher scores in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Compared with the medica-tion group,the VBT combined group demonstrated a greater reduction in HAMD,HAMA,symptom rumination,in-trospective reflection,compulsive meditation,and RRS-CV total scores before and after intervention(Ps＜0.05),and a larger increase in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Conclusion:VBT combined with SSRIs effectively improves the symptoms of depression,anxiety,decision-making ability,rumination thinking,and cognitive function in patients with mild to moderate depression.

Objective Construction of an immune-tumor dual humanized mouse model to explore the role of targeting monoamine oxidase A(MAOA)in the immune microenvironment of prostate cancer.Methods Bioinformatics analysis was used to examine the relationship between MAOAhigh cancer associated fibroblasts(CAFs)and T cells in prostate cancer.Multiplex immunofluorescence was employed to analyze the relationship between stromal MAOA expression and CD8+T cells.An immune-tumor dual humanized mouse model was constructed for in vivo verification of the infiltration of CD8+T cells in response to the targeting of stromal MAOA.Results MAOA expression in the stroma was inversely proportional to the infiltration of CD8+T cells.Inhibiting MAOA expression in the stroma enhanced the infiltration of CD8+T cells in vivo,which may reflect suppression of the accumulation of collagen in the tumor microenvironment.Conclusions Stromal MAOA plays an important role in the immunosuppressive microenvironment of prostate cancer,and its inhibition may promote the infiltration of immune cells.MAOA inhibitors have therapeutic potential in immune combination therapy for patients with prostate cancer.

Objective Construction of an immune-tumor dual humanized mouse model to explore the role of targeting monoamine oxidase A(MAOA)in the immune microenvironment of prostate cancer.Methods Bioinformatics analysis was used to examine the relationship between MAOAhigh cancer associated fibroblasts(CAFs)and T cells in prostate cancer.Multiplex immunofluorescence was employed to analyze the relationship between stromal MAOA expression and CD8+T cells.An immune-tumor dual humanized mouse model was constructed for in vivo verification of the infiltration of CD8+T cells in response to the targeting of stromal MAOA.Results MAOA expression in the stroma was inversely proportional to the infiltration of CD8+T cells.Inhibiting MAOA expression in the stroma enhanced the infiltration of CD8+T cells in vivo,which may reflect suppression of the accumulation of collagen in the tumor microenvironment.Conclusions Stromal MAOA plays an important role in the immunosuppressive microenvironment of prostate cancer,and its inhibition may promote the infiltration of immune cells.MAOA inhibitors have therapeutic potential in immune combination therapy for patients with prostate cancer.

Precision therapy has become an important approach in modern medicine,with the goal of providing individualized treatment according to the characteristics of individual patients.The successful development of precision medicine depends on the application of preclinical cancer models.Patient-derived organoid(PDO)xenograft models display characteristics of both PDO models and in vivo patient-derived tumor xenograft models.This type of model can not only maintain the heterogeneity of the original tumor,but also has additional advantages,such as large-scale cultivation,high-throughput drug screening in vitro and drug sensitivity testing in vivo.It is an innovative,precise preclinical disease model.In this review,we summarize the basic characteristics of the PDO xenograft model,analyze its construction method and influencing factors,further discuss its application in precision therapy,with the aim of providing a reliable preclinical experimental tool for individualized cancer treatment.

Homing pigeons and many other animals have exquisite geomagnetic sensing ability and can accurately find appropriate paths and directions during long-distance migration.Homing pigeons are the preferred animal model for studies of biological geomagnetic navigation.Despite substantial progress in research on bio-geomagnetic navigation over the past few decades,the biological mechanism is still unclear.In this paper,we review recent advancements in research on biological magnetoreception using homing pigeons.We focus on the magnetic sensing mechanisms of the magnetoreceptor models based on nanoscale ferromagnetic particles and the light-dependent radical pair model.Key directions for biological magnetoreception research are proposed.This review provides an improved theoretical basis for the study of geomagnetic navigation using homing pigeons as well as insight into the operating principles of the biological magnetic perception system.

Objective:To evaluate the effect of value orientation brief therapy(VBT)combined with selective serotonin reuptake inhibitors(SSRIs)on clinical symptoms,rumination,decision-making ability,and cognitive func-tion in patients with mild to moderate depression.Methods:Eighty patients meeting the DSM-5 diagnostic criteria for mild to moderate depression were randomly assigned to either a medication(SSRIs)group(36 completed)or a VBT combined group(38 completed)for a 6-week intervention.Baseline and post-intervention assessments includ-ed the Hamilton Depression Scale(HAMD),Hamilton Anxious Scale(HAMA),Ruminative Response Scale-Chi-nese Version(RRS-CV),Iowa Gambling Test(IGT),number of eye fixation(NEF),responsive search score(RSS)in exploratory eye trajectory movement were used to evaluate patients'anxiety and depression symptoms,ru-minative thinking,decision-making function,and cognitive function.Results:The VBT combined group showed sig-nificantly better therapeutic effects than the medication group(P＜0.05).Compared to baseline and the medication group,the VBT combined group had significantly lower post-intervention scores in HAMD,HAMA,symptom rumi-nation,introspective reflection,compulsive meditation,and RRS-CV total scores after intervention(Ps＜0.05),and significantly higher scores in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Compared with the medica-tion group,the VBT combined group demonstrated a greater reduction in HAMD,HAMA,symptom rumination,in-trospective reflection,compulsive meditation,and RRS-CV total scores before and after intervention(Ps＜0.05),and a larger increase in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Conclusion:VBT combined with SSRIs effectively improves the symptoms of depression,anxiety,decision-making ability,rumination thinking,and cognitive function in patients with mild to moderate depression.

Prostaglandin D2(PGD2)is a biologically active substance with important roles in a variety of physiological and pathological processes.PGD2 exerts its biological functions mainly through prostaglandin D2 synthase(PGDS),which is closely related to inflammation and immune regulation.Recent studies have found that PGD2 and its synthase,PGDS,are able to directly inhibit tumor cell proliferation,induce apoptosis,suppress migration and invasion,and further regulate the tumor immune microenvironment to affect the immunotherapy of tumors,demonstrating good tumor therapeutic potential.In this paper,we review the biological properties of PGD2 and its synthase,focusing on its role in the immunotherapy of tumor models.We explore the immunotherapeutic efficacy of PGD2 and its synthase,and their roles in promoting immune cell infiltration in the tumor microenvironment,and discuss their potential as new targets for tumor therapy.

Homing pigeons and many other animals have exquisite geomagnetic sensing ability and can accurately find appropriate paths and directions during long-distance migration.Homing pigeons are the preferred animal model for studies of biological geomagnetic navigation.Despite substantial progress in research on bio-geomagnetic navigation over the past few decades,the biological mechanism is still unclear.In this paper,we review recent advancements in research on biological magnetoreception using homing pigeons.We focus on the magnetic sensing mechanisms of the magnetoreceptor models based on nanoscale ferromagnetic particles and the light-dependent radical pair model.Key directions for biological magnetoreception research are proposed.This review provides an improved theoretical basis for the study of geomagnetic navigation using homing pigeons as well as insight into the operating principles of the biological magnetic perception system.