Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Objective To explore the differences of the global efficiency of the brain structural networks between the male paranoid schizophrenia and male healthy and its relationship with the psychotic symptoms of the schizophrenia.Methods The diffusion tensor imaging data were obtained from 27 male paranoid schizophrenia patients and 28 male healthy controls.The whole cerebral cortex was parcellated into 90 regions by the anatomical label map.Tractography was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts of the brain using fiber assignment by continuous tracking(FACT) algorithm.And then the brain structural binary networks were constructed using the complex network theory.The average global efficiency of the brain network and the global efficiency of the nodes of both groups were examined by two sample t-test and its relationship with the psychotic symptoms in the male paranoid schizophrenia was explored by the correlation analysis.Results Compared with control group,the average global efficiency of the brain network of the patients decreased significantly (7.87±0.56,8.17±0.56,P=0.005),and the global efficiency of the nodes in the brain network of the patient decreased significantly in the left superior frontal gyrus (orbital part) (P=0.00025),the left superior parietal gyrus (P=0.00011),the left cuneus (P=0.00012) and the left putamen (P=0.00032),all survived FDR correction.Significant negative correlation was found between the global efficiency of the left putamen and the total scores (r=-0.43,P=0.03),the positive scores (r=-0.41,P=0.03) and the cognitive scores (r=-0.40,P=0.04) of PANSS.Conclusion The decreased global efficiency of the left frontal,parietal and occipital lobes and the subcortical structures lead to the occurrence of schizophrenia.And the reduced efficiency of the subcortical structures is associated with the positive symptoms and the abnormal cognitive function of the patients.

Objective To explore the differences of the degree indicating the density of the connectivity of nodes between the brain structural white matter networks in the first-episode (FD),recurrent (RD) depressed patients and the healthy control (HC) subjects.Method The diffusion tensor imaging data were obtained from 29 FD patients,20 RD patients and 57 HC subjects.The whole cerebral cortex was divided into 90 regions by the anatomical label map.Fiber tracking was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts of the brain using the fiber assignment by continuous tracking algorithm.And then the brain structural networks were constructed using the complex network theory.The nodal degree of the brain networks of FD and RD were compared with that of HC,and then the correlations between the degree of the significant nodes and the clinical features of patients were explored.Result The degree of the nodes in the networks of FD descended significantly in the left putamen (11.83 ± 2.28) when compared with HC (13.95 ± 2.33;t =-4.02;P =0.000 13,survived correction).That of RD descended significantly (the right dorsolateral superior frontal gyrus (7.80 ± 1.43);the left putamen (11.75±2.07 when compared with HC (9.70 ± 2.89,13.95 ± 2.33;t=-3.81,-3.73;P =0.000 31,0.000 37,survived correction).That of RD descended significantly in the right dorsolateral superior frontal gyrus (7.80 ± 1.43) when compared with FD (9.62 ± 1.78;t =-3.80;P =0.000 42,survived correction).The distribution of the hub regions in the patient and healthy were similar and the left putamen was the same hub region for both groups.Significant negative correlations were found between the degree of the right dorsolateral superior frontal gyrus and the number of episodes (r =-0.42,P =0.002 6) and the course of the disease (r =-0.41,P =0.003 7) in the patient.Conclusions The degree of the connectivity between the frontal region and putamen are possibly decreased in the depressed patient.The left putamen is in the importance role in the brain network and the damage of its connected fibers may be the common structural changes in both FD and RD.The damage of the fibers connected to the frontal region is related with the recurrent course of the depressed patients.

Objective To explore the differences of the degree indicating the density of the connectivity of nodes between the brain structural white matter networks in the first-episode (FD),recurrent (RD) depressed patients and the healthy control (HC) subjects.Method The diffusion tensor imaging data were obtained from 29 FD patients,20 RD patients and 57 HC subjects.The whole cerebral cortex was divided into 90 regions by the anatomical label map.Fiber tracking was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts of the brain using the fiber assignment by continuous tracking algorithm.And then the brain structural networks were constructed using the complex network theory.The nodal degree of the brain networks of FD and RD were compared with that of HC,and then the correlations between the degree of the significant nodes and the clinical features of patients were explored.Result The degree of the nodes in the networks of FD descended significantly in the left putamen (11.83 ± 2.28) when compared with HC (13.95 ± 2.33;t =-4.02;P =0.000 13,survived correction).That of RD descended significantly (the right dorsolateral superior frontal gyrus (7.80 ± 1.43);the left putamen (11.75±2.07 when compared with HC (9.70 ± 2.89,13.95 ± 2.33;t=-3.81,-3.73;P =0.000 31,0.000 37,survived correction).That of RD descended significantly in the right dorsolateral superior frontal gyrus (7.80 ± 1.43) when compared with FD (9.62 ± 1.78;t =-3.80;P =0.000 42,survived correction).The distribution of the hub regions in the patient and healthy were similar and the left putamen was the same hub region for both groups.Significant negative correlations were found between the degree of the right dorsolateral superior frontal gyrus and the number of episodes (r =-0.42,P =0.002 6) and the course of the disease (r =-0.41,P =0.003 7) in the patient.Conclusions The degree of the connectivity between the frontal region and putamen are possibly decreased in the depressed patient.The left putamen is in the importance role in the brain network and the damage of its connected fibers may be the common structural changes in both FD and RD.The damage of the fibers connected to the frontal region is related with the recurrent course of the depressed patients.

Objective To investigate the small-worldness and the betweenness centrality of the nodes in the brain structural networks and its relationship with the course and the central role of the brain regions in the transmission of information across the whole brain in depression.Methods The diffusion tensor imaging data were obtained from 27 depression patients and 33 healthy controls.The brain structural networks were constructed using the complex network theory.Results The brain structural networks had small-world properties in both groups.When compared with the healthy,the betweenness centrality of the nodes of the networks in depression significantly decreased in right superior frontal gyms (orbital part) (P=0.00035,region survived critical FDR threshold for multiple comparisons),and left putamen (P=0.00054,region survived critical FDR threshold for multiple comparisons).Significant negative correlation was found between the betweenness centrality of left hippocampus and the course in the depression(r=0.50,P=0.016).Conclusion Both of the brain structural networks in depression patients and normal people have the property of small-worldness.But the central role of orbit frontal cortex and putamen in the transmission of information across the whole brain is declined,and the betweenness centrality of hippocampus is negatively related with the course in the depression.

Objective To explore the differences of the connectivity strength,the clustering coefficient and the local efficiency of the nodes in the brain structural networks in the depression and healthy subjects and then analyze the mode of the local connections of the brain regions and their local efficiency of the transmission of information and their relationship with the severity of the disease in the depression.Methods The Diffusion Tensor Imaging data were obtained from 24 depression patients and 25 healthy controls.The whole cerebral cortex was parcellated into 90 regions by the anatomical label map.Tractography was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts of the brain using the fiber assignment by continuous tracking (FACT) algorithm.And then the brain structural networks were constructed using the complex network theory.The local topological properties of the brain structural networks of the depression and healthy were examined by two sample t-test.Results The local efficiency of the nodes of the networks in depression decreased significantly (the left middle frontal gyrus (orbital part):0.64±0.30,the left hippocampus:0.57±0.07,the right parahippocampal gyrus:0.50±0.15) compared with the healthy (0.88±0.10,0.64±0.06,0.66±0.13 respectively,P=0.00098,0.00039,0.00017,survived critical FDR threshold for multiple comparisons) ; and the clustering coefficient of the nodes of the networks in depression (the left middle frontal gyrus (orbital part):0.14±0.07) decreased significantly when compared with the healthy (0.22±0.06,P=0.000030,survived critical FDR threshold for multiple comparisons).Significant negative correlation was found between the local efficiency of the left middle frontal gyrus (orbital part) and the total scores of HAMD-17 in the depression (r=-0.48,P=0.02).Conclusion The degree of the localization and the local efficiency of the information transmission of the frontal lobe are decreased.The local efficiency in the information transmission in the hippocampal is also decreased.And the local efficiency of the frontal lobe is negatively related with the severity of the disease in the depression.

Objective To explore the differences of the degree and distribution of hub regions of the brain structural networks between the schizophrenia and healthy and then analysis the importance of brain regions in the information transmission in across the whole brain.Methods The diffusion tensor imaging data were obtained from 22 schizophrenia patients and 24 healthy controls.The whole cerebral cortex was parcellated into 90 regions by the anatonical label map.Tractography was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts of the brain using the fiber assignment by continuous tracking (FACT) algorithm.And then the brain structural binary networks were constructed using the complex network theory.The average degree of the network and the degree of the nodes in the network between the brain structural networks of both groups were examined by two sample t-tests.Results The average degree of the brain structural network in the patient group (7.82±0.56) decreased significantly when compared with the control group (8.17 ±0.56; P=0.04).The degree of the nodes in the brain structural network of the patient group (the left hippocampus:11.41 ± 1.84; the left parahippocampal gyrus:6.41± 1.33 ; the left calcarine fissure:11.50±2.97 ; the left fusiform gyrus:8.27± 1.83) decreased significantly when compared with the control group (14.43±2.26; 8.54±2.15; 14.79±2.80; 10.25± 1.36; all P＜0.01,survived critical FDR threshold for multiple comparisons).And the distribution of the hub regions in the temporal and occipital lobes of the patient group was difference from that of the control group.Conclusion The importance of the hippocampus and the brain regions in the occipital lobe is decrease for the information transmission across the whole brain.The damage of the topological properties of these brain regions maybe related to the disorder of the transmission and integration of information in the brain of the schizophrenia.

Objective To explore the differences in the strength of the nodes in the brain white matter weighted networks between the male patients with paranoid schizophrenia and male healthy controls, and to analysis the integrity of the white matter fiber tracts that connected to the different brain regions and its relationship with the course of disease. Methods Diffusion tensor imaging (DTI) data were obtained from 25 male patients with paranoid schizophrenia and 26 male healthy controls. The whole brain was parcellated into 90 regions by using the anatomical label map. Tractography was performed in the whole brain of each subject to reconstruct white matter tracts using the FACT algorithm. The brain white matter weighted networks were then constructed using the complex network theory. Results The strength of the nodes in the networks of schizophrenia significantly decreased in the right thalamus (P=0.03, corrected) and the right hes?chl gyrus (P=0.04, corrected). Negative correlation was found between the strength of the right thalamus and the course of disease (r=-0.45, P=0.03). Conclusion The integrity of the white matter fiber tracts connected to the thalamus and tem?poral lobes in the male paranoid schizophrenia is impaired. The lesion of fiber tracts connected to the thalamus is related with the course of disease.

Objective To explore the differences of the efficiency of the networks and the nodes between the depression and the healthy,the changes of the model of information processing across the whole brain and the efficiency of information integrating across brain regions of the depression and the relationship between the global efficiency of the nodes and the severity of the disease.Methods The diffusion tensor imaging data were obtained from 27 depressive patients and 36 healthy controls.The whole cerebral cortex was divided into 90 regions by the anatomical tabel map.Fiber tracking was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts of the brain using the fiber assignment by continuous tracking algorithm.And then the brain structural binary networks were constructed using the complex network theory.The efficiency of the brain structural networks of the depression and healthy were examined by two sample t-tests.Results The brain structural networks of both the depression and the healthy exhibited a higher local efficiency and a similar global efficiency when compared with the matched random networks.But the global efficiency of the brain structural networks of the depression (0.86 ± 0.01) decreased significantly when compared with the healthy (0.87 ± 0.01 ; t =-2.31 ; P =0.02).And the global efficiency of the nodes in the networks of depression (the right superior frontal gyrus (orbital part):0.41 ± 0.04 ; the left middle temporal gyrus (temporal pole):0.31 ± 0.02) decreased significantly when compared with the healthy (0.44 ± 0.02,0.33 ± 0.03 ; t =-3.52,-3.84 ; P =0.0008,0.0003,survived critical false discorery rate threshold for multiple comparisons).Significant negative correlation was found between the global efficiency of the right superior frontal gyrus (orbital part) and the total scores of HAMD-17 (r =-0.46,P =0.02).Conclusion Efficient small-world properties when processing information across the whole brain could exhibit in both the depressive patients and the healthy persons.But the efficiency of information integrating across brain regions may be decreased in the depressive patients and be negatively related with the severity of depression.

Objective To explore the differences of the efficiency of the networks and the nodes between the depression and the healthy,the changes of the model of information processing across the whole brain and the efficiency of information integrating across brain regions of the depression and the relationship between the global efficiency of the nodes and the severity of the disease.Methods The diffusion tensor imaging data were obtained from 27 depressive patients and 36 healthy controls.The whole cerebral cortex was divided into 90 regions by the anatomical tabel map.Fiber tracking was performed in the whole cerebral cortex of each subject to reconstruct white matter tracts of the brain using the fiber assignment by continuous tracking algorithm.And then the brain structural binary networks were constructed using the complex network theory.The efficiency of the brain structural networks of the depression and healthy were examined by two sample t-tests.Results The brain structural networks of both the depression and the healthy exhibited a higher local efficiency and a similar global efficiency when compared with the matched random networks.But the global efficiency of the brain structural networks of the depression (0.86 ± 0.01) decreased significantly when compared with the healthy (0.87 ± 0.01 ; t =-2.31 ; P =0.02).And the global efficiency of the nodes in the networks of depression (the right superior frontal gyrus (orbital part):0.41 ± 0.04 ; the left middle temporal gyrus (temporal pole):0.31 ± 0.02) decreased significantly when compared with the healthy (0.44 ± 0.02,0.33 ± 0.03 ; t =-3.52,-3.84 ; P =0.0008,0.0003,survived critical false discorery rate threshold for multiple comparisons).Significant negative correlation was found between the global efficiency of the right superior frontal gyrus (orbital part) and the total scores of HAMD-17 (r =-0.46,P =0.02).Conclusion Efficient small-world properties when processing information across the whole brain could exhibit in both the depressive patients and the healthy persons.But the efficiency of information integrating across brain regions may be decreased in the depressive patients and be negatively related with the severity of depression.