Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

Theory and verification of moiréfringes for x-ray three-phase grating interferometer

Dual-phase and three-phase grating x-ray interference is a promising new technique for grating-based x-ray differential phase contrast imaging.Dual-phase grating interferometers have been relatively completely studied and discussed.In this paper,the corresponding imaging fringe formula of the three-phase grating interferometer is provided.At the same time,the similarities and differences between the three-phase grating interferometer and the dual-phase grating interferometer are investigated and verified,and that the three-phase grating interferometer can produce large-period moiréfringes without using the analyzing grating is demonstrated experimentally.Finally,a simple method of designing three-phase grating and multi-grating imaging systems from geometric optics based on the thin-lens theory of gratings is presented.These theoretical formulas and experimental results provide optimization tools for designing three-phase grating interferometer systems.

Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.

Relevance of Medical Imaging in the Pre-Therapeutic Evaluation of Acute Intestinal Obstruction at CIMED

Objective: We initiated this work with the aim of studying the contribution of imaging in the diagnosis of acute intestinal obstruction at CIMED. Patients and methods: This was a prospective, descriptive and analytical study involving 96 patients collected at the radiology and medical imaging department of CIMED, from January 2022 to January 2023. Result: The age of our patients varied between 11 and 86 years with an average age of 36 years. There was a male predominance of 64.6% compared to 35.4% for women, i.e. a sex ratio of 1.82. The notion of previous surgery was found in 61.5% of our patients. Pain was present in all patients. Radiography of the ASP was performed in 89.6% of patients. It showed hydro-aerial levels in 96.5% of patients. Abdominopelvic CT was performed in 12 patients and made it possible to make the diagnosis of occlusion in all patients. The results of the positive diagnosis were concordant with those intraoperatively in 92% of cases. 8% of our patients, compared to the treatment, spontaneously resumed their transit, 91% benefited from surgical treatment and 1% died before surgery. The outcome was favorable in 80 patients or 83.3%, poor with death in 16 patients or 16.7% of cases. Conclusion: Acute intestinal obstruction remains a serious pathology for which ASP radiography often remains the only radiological examination performed urgently. However, abdominopelvic CT seems widely indicated thanks to its contribution both for the positive diagnosis and for the serious and etiological diagnoses. However, this imaging technique is largely underused in our practice due to its high cost and lack of availability.

Accuracy Validation for Medical Image Registration Algorithms:a Review

Accuracy validation is essential to clinical application of medical image registration techniques. Registration validation remains a challenging problem in practice mainly due to lack of 'ground truth'. In this paper, an overview of current validation methods for medical image registration is presented with detailed discussion of their benefits and drawbacks. Special focus is on non-rigid registration validation. Promising solution is also discussed.

Fortuitous Discovery of a Multifocal Enchondromatosis in a Case at the “Luxembourg” Hospital Center in Bamako

The aim of this study was to clarify the interest of standard radiography in the management of Ollier’s disease. Observation: Enchondromas are benign lesions that may present on imaging with nonspecific features in children, and they are relatively large lesions, with frequent endosteal erosion and rare matrix mineralization. We report a case of predominantly right-sided multifocal enchondromatosis in a 5-year-old girl with no known medical history, diagnosed fortuitously on standard radiography during a trauma assessment and confirmed by histology. No sign of pain was noted after a 6-month follow-up. But the radiographic control noted signs of diffuse osteoarthritic remodeling in the surgical areas and early fusion of the growth cartilages. Conclusion: Ollier’s disease is rare, you have to know how to think about it in the face of fortuitous discoveries, especially at an early age. Enchondromas are benign lesions that may present on imaging with nonspecific features in children. In all cases, standard radiography is essential in the diagnosis and follow-up of Ollier’s disease.

Requirements for Evaluation on Drug-medical Device

The administration of combination products in U.S.Food and Drug Administration(FDA)are analyzed and summarized in this paper.Furthermore,the technical evaluation on drug-medical device in the State Food and Drug Administration of China(SFDA)is also illustrated.Meanwhile,this paper discusses how to promote the development of drug-medical device in the administration and technical evaluation.

Bacterial therapy:a promising strategy for cancer immunotherapy

Cancer immunotherapy is capable of stimulating the body's immune system to selectively attack cancer cells and has the advantages of high efficacy and low toxicity over traditional therapies.Numerous immunotherapies have been approved for clinical applications or clinical trials,including immune checkpoint blockade,adoptive cell therapy,recombinant cytokines,bispecific T-cell engagers,and cancer vaccines.

Deep learning method for cell count from transmitted-light microscope

Automatic cell counting provides an effective tool for medical research and diagnosis.Currently,cell counting can be completed by transmitted-light microscope,however,it requires expert knowledge and the counting accuracy which is unsatisfied for overlapped cells.Further,the image-translation-based detection method has been proposed and the potential has been shown to accomplish cell counting from transmitted-light microscope,automatically and effectively.In this work,a new deep-learning(DL)-based two-stage detection method(cGAN-YOLO)is designed to further enhance the performance of cell counting,which is achieved by combining a DL-based fluorescent image translation model and a DL-based cell detection model.The various results show that cGAN-YOLO can effectively detect and count some different types of cells from the acquired transmitted-light microscope images.Compared with the previously reported YOLO-based one-stage detection method,high recognition accuracy(RA)is achieved by the cGAN-YOLO method,with an improvement of 29.80%.Furthermore,we can also observe that cGAN-YOLO obtains an improvement of 12.11%in RA compared with the previously reported image-translation-based detection method.In a word,cGAN-YOLO makes it possible to implement cell counting directly from the experimental acquired transmitted-light microscopy images with high flexibility and performance,which extends the applicability in clinical research.

Exploring the potential of the metaverse medical paradigm in drug addiction treatment: a preliminary discussion and future prospects

INTRODUCTION,Drug addiction is a chronic and recurrent encephalopathy characterised by impulsive behaviour,spiritual cravings,psychological distortion and physical damage!'According to the role of molecular biology mechanisms on the central nervous system,addictive substances can be classified as inhibitors(eg,opioids,etc),stimulants(eg,methamphetamine(MA),nicotine,cocaine,etc)and hallucinogens(eg,cannabis,etc).As published by the World Drug Report 2022,over284million individualsaged 15-64 worldwide have reportedly abused drugs in the past 12 months,emphasising the international challenge of effective detox treatment.

Emerging novel targets for nonalcoholic fatty liver disease treatment: Evidence from recent basic studies

Nonalcoholic fatty liver disease(NAFLD),a leading chronic disease worldwide,affects approximately a quarter of the global population.Nonalcoholic steatohepatitis(NASH)is an advanced form of NAFLD and is more likely to progress to liver fibrosis than simple steatosis.NASH is also identified as the most rapidly growing cause of hepatocellular carcinoma.Although in the past decade,several phase II/III clinical trials have shown promising results in the use of novel drugs targeting lipid synthase,farnesoid X receptor signaling,peroxisome proliferatoractivated receptor signaling,hepatocellular injury,and inflammatory signaling,proven pharmaceutical agents to treat NASH are still lacking.Thus,continuous exploration of the mechanism underlying the pathogenesis of NAFLD and the identification of novel therapeutic targets remain urgent tasks in the field.In the current review,we summarize studies reported in recent years that not only provide new insights into the mechanisms of NAFLD development but also explore the possibility of treating NAFLD by targeting newly identified signaling pathways.We also discuss evidence focusing on the intrahepatic targets involved in the pathogenesis of NAFLD as well as extrahepatic targets affecting liver metabolism and function.

On the sampling strategies and models for measuring diffusion exchange with a double diffusion encoding sequence

Water exchange between the different compartments of a heterogeneous specimen can be characterized via diffusion magnetic resonance imaging(dMRI).Many analysis frameworks using dMRI data have been proposed to describe exchange,often using a double diffusion encoding(DDE)stimulated echo sequence.Techniques such as diffusion exchange weighted imaging(DEWI)and the filter exchange and rapid exchange models,use a specific subset of the full space DDE signal.In this work,a general representation of the DDE signal was employed with different sampling schemes(namely constant b1,diagonal and anti-diagonal)from the data reduction models to estimate exchange.A near-uniform sampling scheme was proposed and compared with the other sampling schemes.The filter exchange and rapid exchange models were also applied to estimate exchange with their own subsampling schemes.These subsampling schemes and models were compared on both simulated data and experimental data acquired with a benchtop MR scanner.In synthetic data,the diagonal and near-uniform sampling schemes performed the best due to the consistency of their estimates with the ground truth.In experimental data,the shifted diagonal and near-uniform sampling schemes outperformed the others,yielding the most consistent estimates with the full space estimation.The results suggest the feasibility of measuring exchange using a general representation of the DDE signal along with variable sampling schemes.In future studies,algorithms could be further developed for the optimization of sampling schemes,as well as incorporating additional properties,such as geometry and diffusion anisotropy,into exchange frameworks.

Recent evidence for subcutaneous drains to prevent surgical site infections after abdominal surgery:A systematic review and metaanalysis

BACKGROUND Surgical site infections(SSIs)increase mortality,hospital stays,additional medical treatment,and medical costs.Subcutaneous drains prevent SSIs in gynecological and breast surgeries;however,their clinical impact in abdominal surgery remains unclear.AIM To investigate whether subcutaneous drains were beneficial in abdominal surgery using a systematic review and meta-analysis.METHODS The database search used PubMed,MEDLINE,and the Cochrane Library.The following inclusion criteria were set for the systematic review:(1)Randomized controlled trial studies comparing SSIs after abdominal surgery with or without subcutaneous drains;and(2)Studies that described clinical outcomes,such as SSIs,seroma formation,the length of hospital stays,and mortality.RESULTS Eight studies were included in this meta-analysis.The rate of total SSIs was significantly lower in the drained group(54/771,7.0%)than in the control group(89/759,11.7%),particularly in gastrointestinal surgery.Furthermore,the rate of superficial SSIs was slightly lower in the drained group(31/517,6.0%)than in the control group(49/521,9.4%).No significant differences were observed in seroma formation between the groups.Hospital stays were shorter in the drained group than in the control group.CONCLUSION Subcutaneous drains after abdominal surgery prevented SSIs and reduced hospital stays but did not significantly affect seroma formation.The timing of drain removal needs to be reconsidered in future studies.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.

Non-coding RNAs in exercise immunology:A systematic review

Regular physical exercise has been recognized as a potent modulator of immune function,with its effects including enhanced immune surveillance,reduced inflammation,and improved overall health.While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs(ncRNAs)also involved in immune system regulation,heterogeneity in individual study designs and analyzed exercise protocols exists,and a condensed list of functional,exercise-dependent ncRNAs with known targets in the immune system is missing from the literature.A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise.Two combined approaches were used:(a)a systematic literature search for“ncRNA and exercise immunology”,(b)and a database search for microRNAs(miRNAs)(miRTarBase and DIANA-Tarbase v8)aligned with known target genes in the immune system based on the Reactome database,combined with a systematic literature search for“ncRNA and exercise”.Literature searches were based on PubMed,Web of Science,and SPORTDiscus;and miRNA databases were filtered for targets validated by in vitro experimental data.Studies were eligible if they reported on exercise-based interventions in healthy humans.After duplicate removal,95 studies were included reporting on 164 miRNAs,which were used for the qualitative synthesis.Six studies reporting on long-noncoding RNAs(lncRNAs)or circular RNAs were also identified.Results were analyzed using ordering tables that included exercise modality(endurance/resistance exercise),acute or chronic interventions,as well as the consistency in reported change between studies.Evaluation criteria were defined as“validated”with 100%of≥3 independent studies showing identical direction of regulation,“plausible”(≥80%),or“suggestive”(≥70%).For resistance exercise,upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible.For endurance exercise,15 miRNAs were categorized as validated,with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated,most of them after acute exercise training.In conclusion,our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution,function,and trafficking as well as production of(anti-)inflammatory cytokines.miRNAs miR-15,miR-29c,miR-30a,miR-142/3,miR-181a,and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.

Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis

Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.

In vivo pilot study into superficial microcirculatory characteristics of colorectal adenomas using novel high-resolution magnifying endoscopy with blue laser imaging

BACKGROUND No studies have yet been conducted on changes in microcirculatory hemody-namics of colorectal adenomas in vivo under endoscopy.The microcirculation of the colorectal adenoma could be observed in vivo by a novel high-resolution magnification endoscopy with blue laser imaging(BLI),thus providing a new insight into the microcirculation of early colon tumors.AIM To observe the superficial microcirculation of colorectal adenomas using the novel magnifying colonoscope with BLI and quantitatively analyzed the changes in hemodynamic parameters.METHODS From October 2019 to January 2020,11 patients were screened for colon adenomas with the novel high-resolution magnification endoscope with BLI.Video images were recorded and processed with Adobe Premiere,Adobe Photoshop and Image-pro Plus software.Four microcirculation parameters:Microcirculation vessel density(MVD),mean vessel width(MVW)with width standard deviation(WSD),and blood flow velocity(BFV),were calculated for adenomas and the surrounding normal mucosa.RESULTS A total of 16 adenomas were identified.Compared with the normal surrounding mucosa,the superficial vessel density in the adenomas was decreased(MVD:0.95±0.18 vs 1.17±0.28μm/μm2,P<0.05).MVW(5.11±1.19 vs 4.16±0.76μm,P<0.05)and WSD(11.94±3.44 vs 9.04±3.74,P<0.05)were both increased.BFV slowed in the adenomas(709.74±213.28 vs 1256.51±383.31μm/s,P<0.05).CONCLUSION The novel high-resolution magnification endoscope with BLI can be used for in vivo study of adenoma superficial microcirculation.Superficial vessel density was decreased,more irregular,with slower blood flow.

Developing a diagnostic model for predicting prostate cancer: a retrospective study based on Chinese multicenter clinical data

The overdiagnosis of prostate cancer(PCa)caused by nonspecific elevation serum prostate-specific antigen(PSA)and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently.We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies.In this retrospective study,clinical data of 1807 patients from three Chinese hospitals were used.The final model was built using stepwise logistic regression analysis.The apparent performance of the model was assessed by receiver operating characteristic curves,calibration plots,and decision curve analysis.Finally,a risk stratification system of clinically significant prostate cancer(csPCa)was created,and diagnosis-free survival analyses were performed.Following multivariable screening and evaluation of the diagnostic performances,a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System(PI-RADS)score was established.Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration.Finally,we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values.The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7%and 99.4%,respectively,for patients with a risk threshold below O.05 after the initial negative prostate biopsy,which was significantly better than patients with higher risk.Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa.It provides a standardized tool for Chinese patients and physicians when considering thenecessity of prostatebiopsy.

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.