Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn's disease.

Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.

XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7.

Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.

The lack of correlation between symptoms and signs in patients with meibomian gland dysfunction: a secondary analysis of the multicenter, randomized controlled trial.

BACKGROUND: This study was performed to investigate the association between symptoms and signs in patients with meibomian gland dysfunction (MGD). METHODS: Data were obtained from 122 MGD patients who were recruited for intense pulsed light therapy from November 2017 to April 2018 and the severity of their symptoms and signs at baseline were observed and recorded. Spearman correlation analyses were performed to analyze the relationships between SPEED score and signs. Subjects were divided into different subgroups based on possible influencing factors, and the differences in symptoms and signs were compared between different subgroups. Then influencing factors were controlled by regression analysis to explore the relationship between symptoms and signs and the strong factors affecting symptoms and signs. RESULTS: Analysis of baseline data showed that SPEED scores were not correlated with TBUT, CFSS, MGYSS or any index of eyelid margin abnormality (p > 0.05). In addition, abnormalities of lid margins, including hyperemia, thickening, rounding, hyperkeratinization, and telangiectasia around orifices, were more likely to occur in older patients, menopausal patients, and patients living in northern China. Multiple linear regression analysis indicated that there was still no correlation between symptoms and signs (p > 0.05) after adjusting for influencing factors. Further analysis suggested that each influencing factor has different effects on symptoms and signs, among which menopause affects the SPEED score (R = -4.112, p = 0.025), and age and region have significant effects on eyelid margin abnormalities. CONCLUSIONS: In conclusion, the results demonstrated a poor correlation between symptoms and signs in MGD patients. Age, hormone, and a dry environment may influence the disease, which suggests that the severity of the disease needs to be comprehensively assessed.

A Retrospective Study of Treatment Outcomes and Prognostic Factors of Intense Pulsed Light Therapy Combined With Meibomian Gland Expression in Patients With Meibomian Gland Dysfunction.

OBJECTIVES: To evaluate clinical changes after intense pulsed light and meibomian gland expression (IPL/MGX) treatment in meibomian gland dysfunction (MGD) patients, and to identify ideal candidates, and the therapeutic window, for IPL/MGX. METHODS: This retrospective study reviewed the medical records of 44 MGD patients (44 eyes). The IPL/MGX treatment was applied on the eyelids three times at intervals of 4 weeks. Age, sex, relevant ocular history, Standard Patient Evaluation of Eye Dryness (SPEED), Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), corneal fluorescein staining score (CFSS), meiboscore, meibomian gland loss score (MGLS), meibomian glands yielding secretion score (MGYSS), meibomian glands yielding clear secretion (MGYCS), and meibomian glands yielding liquid secretion (MGYLS) were analyzed. RESULTS: Standard Patient Evaluation of Eye Dryness, OSDI, TBUT, CFSS, MGYSS, MGYLS, and MGYCS were significantly improved after three IPL/MGX treatments, but the meiboscore and MGLS remained unchanged. In patients who had better treatment outcomes (improvement in MGYSS >7), younger age (36.0, 22.5 vs. 53.0, 25.0 years; P=0.012), a longer TBUT (8.0, 4.5 vs. 6.0, 3.0 sec; P=0.010), better meiboscore (1.0, 0.5 vs. 2.0, 1.0; P=0.012), and less gland loss (19.8%, 20.3% vs. 41.1%, 30.2%; P=0.008) before IPL/MGX were noted. Sex, relevant ocular history, SPEED, OSDI, MGYSS, MGYLS, and MGYCS before IPL/MGX showed no significant differences between patients with an improvement in MGYSS >7 versus those with an improvement of ≤7. Meibomian glands yielding secretion score changes in patients who had a meiboscore of 0 to 1 and MGYSS of 0 before IPL/MGX (12.0, 10.0) were significantly higher than those who had a meiboscore of 2 to 3 and MGYSS of 0 (6.5, 9.3; P=0.031), or a meiboscore of 0 to 1 and MGYSS >0 (5.0, 11.5; P=0.041). CONCLUSIONS: Improved dry eye symptoms, TBUT, corneal staining, and meibomian gland secretion were observed in MGD patients after IPL/MGX. Patients in the early stages of MGD maybe benefited most from IPL/MGX treatment.

The Efficacy of Intense Pulsed Light Combined With Meibomian Gland Expression for the Treatment of Dry Eye Disease Due to Meibomian Gland Dysfunction: A Multicenter, Randomized Controlled Trial.

OBJECTIVES: To compare the efficacy of intense pulsed light (IPL) combined with Meibomian gland expression (MGX), and instant warm compresses combined with MGX, for treatment of dry eye disease (DED) due to meibomian gland dysfunction (MGD). METHODS: In a prospective, multicenter, interventional study, 120 subjects with DED due to MGD were randomized 1:1 to an IPL arm or a control arm. Each subject was treated 3 times at 3-week intervals. The primary outcome measure was the tear break up time (TBUT). Tear break up time and a few additional outcome measures were evaluated at the baseline and at 3 weeks after the last treatment. RESULTS: All outcome measures improved in both arms, but in general, the improvement was significantly larger in the IPL arm. Tear break up time increased by 2.3±1.9 and 0.5±1.4 sec, in the IPL and control arms respectively (P<0.001). SPEED was reduced by 38% and 22% in the IPL and control arms, respectively (P<0.01). Meibomian Gland Yielding Secretion Score was improved by 197% in the IPL arm and 96% in the control arm. Corneal fluorescein staining also decreased by 51% and 24% in the IPL and control arms respectively, but the differences between the two arms were not statistically significant (P=0.61). A composite score of lid margin abnormalities improved in both arms, but more in the IPL arm (P<0.05). CONCLUSIONS: Intense pulsed light combined with MGX therapy was significantly more effective than instant warm compresses followed with MGX. This suggests that the IPL component has a genuine contribution to the improvement of signs and symptoms of DED.

CRL4DCAF2 is required for mature T-cell expansion via Aurora B-regulated proteasome activity.

The proliferation of T cells in peripheral lymphoid tissues requires T cell receptor (TCR)-mediated cell cycle entry. However, the underlying mechanism regulating cell cycle progression in mature T cells is incompletely understood. Here, we have identified an E3 ubiquitin ligase, CRL4DCAF2, as a critical mediator controlling M phase exit in activated T cells. DCAF2 expression is induced upon TCR stimulation and its deficiency attenuates T cell expansion. Additionally, DCAF2 T cell-specific knockout mice display impaired peripheral T cell maintenance and reduced severity of various autoimmune diseases. Continuous H4K20me1 modification caused by DCAF2 deficiency inhibits the induction of Aurkb expression, which regulates 26S proteasome activity during G2/M phase. CRL4DCAF2 deficiency causes M phase arrest through proteasome-dependent mechanisms in peripheral T cells. Our findings establish DCAF2 as a novel target for T cell-mediated autoimmunity or inflammatory diseases.

A study of corneal structure and biomechanical properties after collagen crosslinking with genipin in rabbit corneas.

Purpose: Aim to assess the short-term effect of genipin collagen crosslinking (G-CXL) on corneal structure and biomechanical properties compared with ultraviolet A/riboflavin collagen crosslinking (UVA-CXL) in rabbit corneas. Methods: Right eyes of 40 healthy rabbits were divided into the 0.20% G-CXL group, 0.25% G-CXL group, UVA-CXL group, and control group. Anterior segment optical coherence tomography (ASOCT) and in vivo confocal microscopy (IVCM) were performed before, 7 days after, and 14 days after the CXL treatment. Corneal strips were harvested for tensile strain measurements 7 and 14 days after the CXL treatment. Results: ASOCT showed the demarcation line (DL) in the UVA-CXL group was deeper than in the 0.20% G-CXL group and the 0.25% G-CXL group on day 7 (p=0.014) and day 14 (p=0.012). Nerve and keratocyte density in all CXL groups decreased, but was more obvious in the UVA-CXL group (p<0.001). Endothelial cell loss in the 0.20% G-CXL group, 0.25% G-CXL group, UVA-CXL group, and control group was 11.7%, 6.8%, 32.8%, and 2.0% 14 days after CXL, respectively. Young's modulus and stress in the 0.25% G-CXL group and the UVA-CXL group were statistically significantly higher than in the control group (p<0.05) 7 and 14 days after CXL. No statistically significant differences were observed between the 0.25% G-CXL group and the UVA-CXL group (p>0.05). The DL depth was positively correlated with Young's modulus (r=0.426, p=0.042) and stress (r=0.469, p=0.024). Conclusions: The administration of 0.25% genipin enhances corneal biomechanical properties as long as 14 days after the CXL treatment with low toxicity. The DL exists in CXL-treated corneas, and the depth is related to the biomechanical properties.

The Short-Term Safety Evaluation of Corneal Crosslinking Agent-Genipin.

BACKGROUND: Genipin (GP) is a safe method for corneal crosslinking, even for very thin corneas. However, there have been no reports on the optimal GP concentration range to use in vivo for corneal crosslinking. OBJECTIVES: To investigate the safety of corneal crosslinking after a 24-h incubation with different concentrations of GP. METHODS: Twenty New Zealand white rabbits were divided into a phosphate-buffered saline (PBS) group, 0.2% GP crosslinking (GP-CXL) group, 0.25% GP-CXL group, and 0.3% GP-CXL group. Before and after surgery, the operated eyes of each group were characterized by confocal microscopy, and corneal buttons were excised for endothelium staining and electron microscopy. RESULTS: The keratocyte structures in each GP group appeared to be similar to those in the PBS group. Through the confocal microscopy, the changes in corneal endothelial cell density also did not significantly differ among groups. There was a significant difference in apoptosis between the 0.3% GP-CXL and PBS groups (p < 0.05) and between the 0.3% GP-CXL and 0.25% GP-CXL groups (p < 0.05), but there were no significant differences between the 0.2 and 0.25% GP-CXL groups compared to the PBS group. Transmission electron microscopy showed endothelial cell damage in the 0.3% GP-CXL group, with minimal endothelial cell damage in the other groups. CONCLUSIONS: Treatment of rabbit corneas with ≤0.25% GP resulted in minimal toxicity to keratocytes and endothelial cells, suggesting that it is a safe crosslinking agent at those concentrations.

A rabbit model of corneal Ectasia generated by treatment with collagenase type II.

BACKGROUND: To investigate use of collagenase type II for generating a rabbit model of corneal ectasia. METHODS: Ten New Zealand white rabbits were used with right eyes treated as the experimental group and left eyes treated as the control group. After epithelial debridement, a collagenase type II solution (200 µL of 5 mg/mL) was applied in the experimental group at room temperature (24 °C) for 30 min, and a 200 µL solution without collagenase was applied in the control group. Slit-lamp microscopy, the mean keratometry (Km), and central cornea thickness (CCT) were examined before and after the procedure. Corneas were obtained on day 14 for biomechanical evaluation. RESULTS: No obvious inflammatory reaction was observed in all eyes after the procedure. A statistically significant increase in Km (1.54 ± 1.29D vs - 0.82 ± 0.44D at day7 and 0.89 ± 0.89D vs - 2.11 ± 1.02D at day14) and a statistically significant decrease in CCT (- 23.10 ± 12.17 µm vs 6.20 ± 16.51 µm at day7 and - 16.10 ± 10.46 µm vs 11.60 ± 0.88 µm at day14) were observed in the experimental group compared with the control group. The mean stresses and elastic modulus at 5%, 10%, 15%, and 20% deformities in the experimental group decreased and the differences in elastic modulus between the two groups were statistically significant at 10% and 15% deformities. CONCLUSIONS: Collagenase type II treatment results in mimic KC with increased corneal keratometry and corneal thinning and a lower elastic modulus. An animal model for corneal ectasia can be generated by treatment with collagenase type II.

The comparative safety of genipin versus UVA-riboflavin crosslinking of rabbit corneas.

PURPOSE: To investigate, after 24 h, the safety of genipin or ultraviolet A (UVA)-riboflavin crosslinking of keratocytes and endothelial cells. METHODS: Fifteen New Zealand white rabbits were selected and divided into a PBS group (five rabbits), a 0.2% genipin crosslinking (GP-CXL) group (five rabbits), and a UVA-riboflavin crosslinking (UVA-CXL) group (five rabbits). In the GP-CXL and PBS groups, 0.2% genipin or PBS was applied to the corneal surface of the right eyes. In the UVA-CXL group, a clinical crosslinking procedure was used. Before and after surgery, the operated eyes of each group were characterized with confocal microscopy, and the corneal buttons were excised for endothelium staining and electron microscopy. RESULTS: The corneal endothelial cell density of the GP-CXL, UVA-CLX, and PBS groups changed. There was a statistically significant difference in thickness and changes in corneal endothelial cell density between the UVA-CXL group and the PBS group (p<0.05), and between the UVA-CXL group and the GP-CXL group (p<0.05), but no statistically significant difference between the GP-CXL group and the PBS group. Confocal microscopy, transmission electron microscopy, and hematoxylin and eosin staining showed that there was keratocyte apoptosis in the anterior and middle stroma and endothelial cell damage in the UVA-CXL group. In the GP-CXL group, only active keratocytes were found and minimal endothelial cell damage. CONCLUSIONS: Treatment of rabbit corneas with 0.2% genipin showed minimal toxicity toward keratocytes and endothelial cells. Genipin is safer than UVA-CXL for crosslinking of thin corneas.

A comparative study of interhemispheric functional connectivity in major depression and schizophrenia.

BACKGROUND: Major depressive disorder (MDD) and schizophrenia (SZ) are serious psychiatric disorders that, despite exhibiting different diagnostic criteria, exhibit significant overlap regarding the biological and clinical features of affected patients. While prior evidence has shown that interhemispheric functional connectivity (FC) is abnormal in MDD and SZ, the particular similarities and differences that unify and characterize MDD and SZ regarding these interhemispheric FC patterns remain to be characterized. This study was thus designed to conduct an in-depth analysis of MDD- and SZ-related patterns of interhemispheric FC. METHODS: This study enrolled MDD patients, SZ patients, and normal control (NC) individuals (n = 36 each). Resting-state functional MRI (rs-fMRI) studies of these patients were conducted, after which voxel-mirrored homotopic connectivity (VMHC) was used to analyze the preprocesses rs-fMRI data. The VMHC values in these different values were then compared through one-way ANOVAs and post hoc analyses. RESULTS: Significant differences were observed in both the striatum and middle frontal gyrus (MFG) when comparing these three groups. Through pairwise comparisons, MDD patients but not SZ patients exhibited reduced MFG VMHC values relative to the NC individuals. Conversely, striatum VMHC values significantly increased in SZ patients relative to NC individuals and MDD patients. CONCLUSION: These results support the interhemispheric functional disconnection hypothesis as a basis for the pathogenesis of MDD and SZ. The observed differences in interhemispheric FC in the MFG and striatum of MDD and SZ patients will offer a neuroimaging basis that can aid in the differential diagnosis of these debilitating conditions.

Alterations in the white matter structure of major depressive disorder patients and their link to childhood trauma.

Objectives: Major Depressive Disorder (MDD) is significantly influenced by childhood trauma (CT), affecting brain anatomy and functionality. Despite the unique disease trajectory in MDD patients with CT, the underlying neurobiological mechanisms remain unclear. Our objective is to investigate CT's impact on the white matter structure of the brain in patients with MDD. Methods: This research employed tract-based spatial statistics (TBSS) to detect variations between groups in Fractional Anisotropy (FA) throughout the whole brain in 71 medication-free MDD patients and 97 HCs. Participants filled out the Childhood Trauma Questionnaire (CTQ) and assessments for depression and anxiety symptoms. The relationship between FA and CTQ scores was explored with partial correlation analysis, adjusting for factors such as age, gender, educational background, and length of illness. Results: Compared to HCs, the MDD group showed decreased FA values in the right posterior limb of the internal capsule (PLIC), the inferior fronto-occipital fasciculus (IFOF), and bilateral superior longitudinal fasciculus (SLF). Simple effects analysis revealed that compared to HC-CT, the MDD-CT group demonstrated decreased FA values in right PLIC, IFOF, and bilateral SLF. The MDD-nCT group showed decreased FA values in right PLIC and IFOF compared to HC-nCT. The total scores and subscale scores of CTQ were negatively correlated with the FA in the right SLF. Conclusion: The right SLF may potentially be influenced by CT during the brain development of individuals with MDD. These results enhance our knowledge of the role of the SLF in the pathophysiology of MDD and the neurobiological mechanisms by which CT influences MDD.

Distinct resting-state functional connectivity of the anterior cingulate cortex subregions in first-episode schizophrenia.

The anterior cingulate cortex (ACC) is a heterogeneous region of the brain's limbic system that regulates cognitive and emotional processing, and is frequently implicated in schizophrenia. This study aims to characterize resting-state functional connectivity (rsFC) profiles of three subregions of ACC in patients with first-episode schizophrenia and healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were collected from 60 first-episode schizophrenia (FES) patients and 60 healthy controls (HC), and the subgenual ACC (sgACC), pregenual ACC (pgACC), and dorsal ACC (dACC) were selected as seed regions from the newest automated anatomical labeling atlas 3 (AAL3). Seed-based rsFC maps for each ACC subregion were generated and compared between the two groups. The results revealed that compared to the HC group, the FES group showed higher rsFC between the pgACC and bilateral lateral orbitofrontal cortex (lOFC), and lower rsFC between the dACC and right posterior OFC (pOFC), the medial prefrontal gyrus (MPFC), and the precuneus cortex (PCu). These findings point to a selective functional dysconnectivity of pgACC and dACC in schizophrenia and provide more accurate information about the functional role of the ACC in this disorder.

Sex differences of neural connectivity in internet gaming disorder and its association with sleep quality: an exploratory fMRI study.

Objectives: Sex-specific differences in internet gaming disorder (IGD) neurophysiology remain underexplored. Here we investigated sex-related variability in regional homogeneity (ReHo) and functional connectivity (FC) in IGD and their correlations with sleep quality. Methods: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 52 subjects with IGD and 50 healthy controls (HCs). Two-way ANOVA was used to examine sex and diagnosis interactions in ReHo and FC, followed by post-hoc analyses to explore FC biomarkers for different sexes. Results: In ReHo analysis, the four groups showed significant sex and diagnosis interactions in the right middle frontal gyrus (rMFG). FC analysis with rMFG as the seed region revealed a significant sex and diagnosis interaction effect in FC of the rMFG with the bilateral postcentral gyrus (PoCG). In male IGD group, FC between the rMFG and the bilateral PoCG correlates strongly with daytime dysfunction score and the Pittsburgh sleep quality inventory (PSQI) total score. Conclusion: These findings emphasize the importance of considering sexual dimorphism in the neurobiology of IGD, which might influence subsequent treatment strategies.

Common and Distinct Functional Connectivity of the Orbitofrontal Cortex in Depression and Schizophrenia.

Schizophrenia and depression are psychiatric disorders with overlapping clinical and biological features. This study aimed to identify common and distinct neuropathological mechanisms in schizophrenia and depression patients using resting-state functional magnetic resonance imaging (fMRI). The study included 28 patients with depression (DEP), 29 patients with schizophrenia (SCH), and 30 healthy control subjects (HC). Intrinsic connectivity contrast (ICC) was used to identify functional connectivity (FC) changes at the whole-brain level, and significant ICC differences were found in the bilateral orbitofrontal cortex (OFC) across all three groups. Further seed-based FC analysis indicated that compared to the DEP and HC groups, the FC between bilateral OFC and medial prefrontal cortex (MPFC), right anterior insula, and right middle frontal gyrus were significantly lower in the SCH group. Additionally, the FC between right OFC and left thalamus was decreased in both patient groups compared to the HC group. Correlation analysis showed that the FC between OFC and MPFC was positively correlated with cognitive function in the SCH group. These findings suggest that OFC connectivity plays a critical role in the pathophysiology of schizophrenia and depression and may provide new insights into the potential neural mechanisms underlying these two disorders.

Widespread Intra- and Inter-Network Dysconnectivity among Large-Scale Resting State Networks in Schizophrenia.

Schizophrenia is characterized by the distributed dysconnectivity of resting-state multiple brain networks. However, the abnormalities of intra- and inter-network functional connectivity (FC) in schizophrenia and its relationship to symptoms remain unknown. The aim of the present study is to compare the intra- and inter-connectivity of the intrinsic networks between a large sample of patients with schizophrenia and healthy controls. Using the Region of interest (ROI) to ROI FC analyses, the intra- and inter-network FC of the eight resting state networks [default mode network (DMN); salience network (SN); frontoparietal network (FPN); dorsal attention network (DAN); language network (LN); visual network (VN); sensorimotor network (SMN); and cerebellar network (CN)] were investigated in 196 schizophrenia and 169-healthy controls. Compared to the healthy control group, the schizophrenia group exhibited increased intra-network FC in the DMN and decreased intra-network FC in the CN. Additionally, the schizophrenia group showed the decreased inter-network FC mainly involved the SN-DMN, SN-LN and SN-CN while increased inter-network FC in the SN-SMN and SN-DAN (p < 0.05, FDR-corrected). Our study suggests widespread intra- and inter-network dysconnectivity among large-scale RSNs in schizophrenia, mainly involving the DMN, SN and SMN, which may further contribute to the dysconnectivity hypothesis of schizophrenia.

Preliminary findings on the effect of childhood trauma on the functional connectivity of the anterior cingulate cortex subregions in major depressive disorder.

Objectives: Childhood trauma (CT) is a known risk factor for major depressive disorder (MDD), but the mechanisms linking CT and MDD remain unknown. The purpose of this study was to examine the influence of CT and depression diagnosis on the subregions of the anterior cingulate cortex (ACC) in MDD patients. Methods: The functional connectivity (FC) of ACC subregions was evaluated in 60 first-episode, drug-naïve MDD patients (40 with moderate-to-severe and 20 with no or low CT), and 78 healthy controls (HC) (19 with moderate-to-severe and 59 with no or low CT). The correlations between the anomalous FC of ACC subregions and the severity of depressive symptoms and CT were investigated. Results: Individuals with moderate-to severe CT exhibited increased FC between the caudal ACC and the middle frontal gyrus (MFG) than individuals with no or low CT, regardless of MDD diagnosis. MDD patients showed lower FC between the dorsal ACC and the superior frontal gyrus (SFG) and MFG. They also showed lower FC between the subgenual/perigenual ACC and the middle temporal gyrus (MTG) and angular gyrus (ANG) than the HCs, regardless of CT severity. The FC between the left caudal ACC and the left MFG mediated the correlation between the Childhood Trauma Questionnaire (CTQ) total score and HAMD-cognitive factor score in MDD patients. Conclusion: Functional changes of caudal ACC mediated the correlation between CT and MDD. These findings contribute to our understanding of the neuroimaging mechanisms of CT in MDD.

Amygdala connectivity related to subsequent stress responses during the COVID-19 outbreak.

Introduction: The amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak. Methods: Data collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity. Results: We found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic. Discussion: Our findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

[An experimental study on the fate of the amniotic membrane after amniotic membrane transplantation for acute alkaline burn of rat cornea].

OBJECTIVE: Use three different methods of amniotic membrane transplantation for acute alkaline burn of rat cornea, to investigate the difference on operation time, reabsorption time of amniotic membrane, integration patterns of amniotic membrane into the cornea among the three amniotic membrane transplantation methods. METHODS: SD rats were randomly assigned into five groups. Group A: simply alkaline burn of cornea; Group B: inlay method; Group C: overlay method; Group D: sutureless method; Group E: normal. Prepared the model of corneal alkaline burn of the right eyes of group A-D rats, performed three different methods of amniotic membrane transplantation on Group B-D rats respectively within 24 hours after alkaline burn. The operation time was recorded. Observed the eyes with slit-lamp microscopy after transplantation, recorded the reabsorption time of amniotic membrane. HE staining and immunohistochemical staining against human collagen IV were performed for pathological study. The results were analysed with Image-Pro Plus 6.0 software. The integration patterns of amniotic membrane into the cornea after amniotic membrane reabsorbed were observed. RESULTS: (1) Operation time: Group B was (35.500 ± 2.878) minutes; Group C was (33.375 ± 2.973) minutes; Group D was (9.875 ± 1.246) minutes. There was statistical significance between group B and group D (P < 0.001), group C and group D (P < 0.001). There was no statistical significance between group B and group C (P = 0.102). (2) Reabsorption time of amniotic membrane: Group B was (16.625 ± 3.662) days; Group C was (9.250 ± 2.188) days; Group D was (12.833 ± 2.483) days. There was statistical significance among group B, C, D (P < 0.001). (3) There was significant inflammatory reaction around the suture in Group B and Group C, and there was inconspicuous inflammatory reaction in Group D. (4) There were three integration patterns of amniotic membrane into the cornea after amniotic membrane reabsorption: superficial localization, intraepithelial and intrastromal. We could find one or more integration patterns in same method of amniotic membrane transplantation, there was no statistical significance among group B, C, D (P = 0.86). CONCLUSIONS: Amniotic membrane can integrate into the cornea after amniotic membrane reabsorption. Sutureless amniotic membrane transplantation which has short operation time and inconspicuous inflammatory reaction is better than traditional amniotic membrane transplantation, and it will be used extensively in the ophthalmology field in future.

Reduced inter-hemispheric auditory and memory-related network interactions in patients with schizophrenia experiencing auditory verbal hallucinations.

Background: Inter-hemispheric disconnection is a primary pathological finding in schizophrenia. However, given the inherent complexity of this disease and its development, it remains unclear as to whether associated inter-hemispheric changes play an important role in auditory verbal hallucination (AVH) development. As such, this study was developed to explore inter-hemispheric connectivity in the context of schizophrenia with AVH while excluding positive symptoms and other factors with the potential to confound these results. Method: In total, resting-state functional magnetic resonance imaging (fMRI) was used to assess 42 patients with AVH (APG), 26 without AVH (NPG), and 82 normal control (NC) individuals. Inter-hemispheric connectivity in these subjects was then assessed through the use of voxel-mirrored homotopic connectivity (VMHC) and Pearson correlation analyses. Result: Relative to HC and NPG subjects, APG individuals exhibited a decrease in VMHC in the superior temporal gyrus (STG) extending into Heschl's gyrus, the insula, and the Rolandic operculum as well as in the fusiform gyrus extending into the para-hippocampus (Corrected p < 0.005, cluster size = 52). Among APG individuals, these observed impairments of inter-hemispheric connectivity were negatively correlated with Hoffman auditory hallucination scores. Conclusion: These results support the schizophrenia hemitropic disconnection hypothesis, and provide novel evidence suggesting that there may be a relationship between reductions in inter-hemispheric connectivity in auditory and memory-related networks and the pathogenesis of AVH in patients with schizophrenia following the exclusion of confounding factors from other positive symptoms.