Brain functional changes across mood states in bipolar disorder: from a large-scale network perspective.

BACKGROUND: Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis. RESULTS: A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients. CONCLUSIONS: Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.

Aberrant modular segregation of brain networks in female patients with bulimia nervosa.

OBJECTIVE: Bulimia nervosa (BN) is an eating disorder associated with the dysfunction of intrinsic brain networks. However, whether the network disruptions in BN patients manifest as dysconnectivity or imbalances of network modular segregation remains unclear. METHOD: We collected data from 41 women with BN and 41 matched healthy control (HC) women. We performed graph theory analysis based on resting-state functional magnetic resonance imaging (RS-fMRI) data; then, we computed the participation coefficient (PC) among brain modules to characterize the modular segregation for the BN and HC groups. The number of intra- and inter-modular connections was calculated to explain the PC changes. Additionally, we examined the potential associations of the measures mentioned above with clinical variables within the BN group. RESULTS: Compared with the HC group, the BN group showed significantly decreased PC in the fronto-parietal network (FPN), cingulo-opercular network (CON), and cerebellum (Cere). Additionally, the number of intra-modular connections of the default mode network (DMN) and the number of the inter-modular connections between the DMN and CON, FPN and Cere, and CON and Cere in the BN group were lower than those in the HC group. The nodal level analysis showed that the BN group had a decreased PC of the anterior prefrontal cortex (aPFC), dorsal frontal cortex (dFC), inferior parietal lobule (IPL), thalamus, and angular gyrus. Further, these metrics were significantly correlated with clinical variables in the BN group. DISCUSSION: These findings may provide novel insights to capture atypical topologies associated with pathophysiology mechanisms and clinical symptoms underlying BN.

Intrinsic functional connectivity correlates of cognitive deficits involving sustained attention and executive function in bipolar disorder.

BACKGROUND: The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs). METHODS: Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses. RESULTS: Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs). CONCLUSIONS: These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN.

Boron Derivatives Accelerate Biofilm Formation of Recombinant Escherichia coli via Increasing Quorum Sensing System Autoinducer-2 Activity.

Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. However, it is unclear how boron affects biofilm formation in E. coli, particularly recombinant E. coli with intracellular enzymes. This study screened different boron derivatives to explore their effect on biofilm formation. The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. Results showed that boron derivatives promote AI-2 activity in QS system. After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. Moreover, treatment with H3BO3 (0.6 mM) increased biomass by 88.54%. Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0−0.6 mM H3BO3 and NaBO2 (R2 > 0.8). Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli.

[Two new monoterpenoid indole alkaloids from hook-bearing branches of Uncaria sessilifructus].

The present study investigated the chemical constituents from Uncaria sessilifructus and their neuroprotective activities. The compounds were separated and purified from the 90% ethanol extract of U. sessilifructus by various chromatographic methods, including silica gel, Sephadex LH-20, and semi-preparative HPLC. Seven compounds were obtained, and their structures were identified as uncanidine J(1), uncanidine K(2), 17-O-ethylhirsutine(3), tetrahydroalstonine(4), akuammigine(5), hirsutine(6), and hirsuteine(7) by physicochemical properties and various spectral techniques, including UV, IR, MS, and NMR. Compounds 1 and 2 are two new compounds. Compound 3 is a new natural product, and compound 4 was isolated from U. sessilifructus for the first time. In addition, the isolated compounds were evaluated for their neuroprotective effects on oxygen and glucose deprivation/reoxygenation(OGD/R) injury in primary cortical neurons in rats. The results showed that compounds 1-7 had different degrees of protective effects on OGD/R injury. The EC_(50) values of compounds 2-4 were(0.17±0.03),(1.70±0.38), and(1.79±0.23) µmol·L~(-1), respectively.

Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

Uncoupled endothelial nitric oxide synthase (eNOS) produces O2- instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O2- production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O2- burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O2- releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis.

Combination of NGAL and Cystatin C for Prediction of Preeclampsia at 10-14 Weeks of Gestation.

BACKGROUND: Preeclampsia (PE) is a severe pregnancy complication and is an important cause for maternal and child death, premature delivery, and limited intrauterine growth and development. The aim of this study was to investigate the role of NGAL and cystatin C, alone and in combination, for early prediction of PE at 10 - 14 weeks of gestation. METHODS: Serum levels of NGAL and cystatin C were assessed in women at 10 - 14 weeks of gestation who subsequently developed PE (n = 128) and normal pregnancy outcome (n = 183). Comparison of clinical characteristics, NGAL, and cystatin C levels between normal pregnancy and PE groups were analyzed using Mann-Whitney test. The receiver operating characteristic curve (ROC curve) was used to analyze the value of serum NGAL and cystatin C levels in predicting PE. RESULTS: The levels of cystatin C and NGAL in the serum were significantly higher in the PE group [0.64 mg/L (0.52 - 0.78)] and [34.9 ng/mL (24.4 - 55.2), respectively] than in the normal pregnancy group [0.56 mg/L (0.49 - 0.65)] and [20.2 ng/mL (13.8 - 26.9), respectively]. ROC curve analysis showed that serum NGAL levels predicted the area under the curve in the PE period 0.739 (95% CI: 0.618 to 0.860). Serum cystatin C levels predicted the area under the curve in the PE period 0.722 (95% CI: 0.592 to 0.853). The combination of serum NGAL and cystatin C levels predicted the area under the curve in the PE period 0.877 (95% CI: 0.811 to 0.943). CONCLUSIONS: NGAL and cystatin C levels in serum appear to be ideal biomarkers for PE prediction at 10 - 14 weeks. The combination of NGAL and cystatin C will also be more valuable in discriminating patients at risk of developing PE from other pregnancy complications early in gestation.

Mutational spectrum of the phenylalanine hydroxylase gene in patients with phenylketonuria in the central region of China.

Phenylketonuria (PKU, OMIM 261600) caused by phenylalanine hydroxylase (PAH) deficiency is an autosomal recessive disease that is characterized by abnormalities of phenylalanine metabolism. In this study, a total of 77 patients, originating from the central region of China and who were diagnosed with PAH deficiency at the third affiliated hospital of Zhengzhou University, were enrolled in this study. The 13 exons and 12 flanking introns of the PAH gene were analyzed by Sanger sequencing and next generation sequencing. The sequencing data were aligned to the hg19, PAHvdb and HGMD databases to characterize the genotypes of PKU patients, and genotype-phenotype correlations and BH4 responsiveness predictions were performed using BIOPKUdb. In total, 149 alleles were characterized among the 154 PKU alleles. These mutations were located in exons 2-13, and intron 12 of the PAH gene, with a relative frequency of ≥5%, for EX6-96A>G, p.R241C, p.R243Q, p.V399V and p.R53H. Additionally, a novel variant, p.D84G, was identified. The genotype correlated with clinical symptoms in 33.3-100% of the cases, depending on the disease severity, and BH4 responsiveness predictions show that only five patients with MHP-PKU and one patient with Mild-PKU were predicted to be BH4 responsive. In conclusion, we have characterized the mutational spectrum of PAH in the central region of China and have identified a novel mutation. The hotspot mutation information might be useful for screening, diagnosis and treatment of PKU.

Recombinant Escherichia coli BL21-pET28a-egfp Cultivated with Nanomaterials in a Modified Microchannel for Biofilm Formation.

The application of whole cells as catalytic biofilms in microchannels has attracted increasing scientific interest. However, the excessive biomass formation and structure of biofilms in a reactor limits their use. A microchannel reactor with surface modification was used to colonize recombinant Escherichia coil BL21-pET28a-egfp rapidly and accelerated growth of biofilms in the microchannel. The segmented flow system of 'air/culture medium containing nanomaterials' was firstly used to modulate the biofilms formation of recombinant E. coil; the inhibitory effects of nanomaterials on biofilm formation were investigated. The results indicated that the segmental flow mode has a significant impact on the structure and development of biofilms. Using the channels modified by silane reagent, the culture time of biofilms (30 h) was reduced by 6 h compared to unmodified channels. With the addition of graphene sheets (10 mg/L) in Luria-Bertani (LB) medium, the graphene sheets possessed a minimum inhibition rate of 3.23% against recombinant E. coil. The biofilms cultivated by the LB medium with added graphene sheets were stably formed in 20 h; the formation time was 33.33% shorter than that by LB medium without graphene. The developed method provides an efficient and simple approach for rapid preparation of catalytic biofilms in microchannel reactors.

[Clinicopathological Analysis of Autoimmune Hepatitis with Sjögren's Syndrome].

OBJECTIVE: To explore the biochemical-immune and pathological characteristics of autoimmune hepatitis (AIH) with Sjögren's syndrome (SS) . METHODS: A total of 76 cases of AIH patients were included from January 2009 to April 2017. Among them,there were 40 cases of AIH with SS and 36 cases without SS. The liver function,immunological index,histological features,length of first diagnosis and treatment costs were compared between the two groups. RESULTS: For AIH+SS group and AIH group,the proportion of women were 97.5% and 77.8%,the proportion of the first diagnosis age less than 60 years were 70% and 47.2%,the median course of disease were 30 months and 9 months,all the difference were statistically significant (P<0.05). The chief complaints in AIH+SS group and AIH group were as follows: cutaneous or scleracterus (52.5% vs. 38.9%),abnormal transaminase (17.5% vs. 44.4%),dryness of mouth and eye (15.0% vs. 2.8%),all the difference were statistically significant (P<0.05). There were no statistically significant difference in hospitalization expenses,and length of stay between the two groups (P>0.05). The median level of total bilirubin (TBIL),direct bilirubin (DBIL) and immunoglobulin (Ig) M of AIH +SS group were higher than those of AIH group,the mean level of albumin (ALB) and complement 3 (C3) of AIH +SS group were lower than those of AIH group,and the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) ,anti-Ro antibody A (SSA),anti-La antibody (SSB) and anti-soluble liver antigen antibody (SLA) of AIH+SS group were higher than those of AIH group (P<0.05). There were no statistically significant difference in histological changes of hepatocytes and bile duct injury rate (P>0.05). CONCLUSION: AIH patients in young and middle-aged women need to be vigilant with SS with main manifestation of skin sclera and high specific autoantibodies positive.

[Risk Factors for Missed Diagnosis of Esophageal Low-grade Intraepithelial Neoplasia in Endoscopic Forceps Biopsy Compared with Endoscopic Submucosal Dissection].

OBJECTIVE: To investigate the risk factors for pathological upgrading after endoscopic treatment of esophageal lesions which confirmed to be low-grade intraepithelial neoplasia (LGIN) by preoperative biopsy. METHODS: A total of 148 patients who were confirmed to be LGIN in preoperative forceps underwent further endoscopic resection between November 2013 and July 2018. According to the final pathological results after endoscopic treatment, they were divided into pathological upgrading group and pathological non-upgrading group, and their clinicopathological characteristics were analyzed and compared through univariate and multivariate analysis. RESULTS: The average age of the patients was (59.95±7.75) years old and the percent of male patients was 67.57% (100/148). Most lesions were located in the middle esophagus (99 cases) and lower esophagus (38 cases). Endoscopic gross type was mainly depressed type (72 cases). The en-bloc resection rate was 99.32% (147/148). Among the patients (77, 52.03%) who had pathological upgrading, 33 (22.3%) cases were HGIN, 25 (16.9%) cases were in-situ cancer, and 19 (12.8%) cases were superficial esophageal squamous cell carcinoma. Univariate analysis showed that circumferential extent (≥1/2), longitudinal diameter (≥3 cm), submucosa involvement found by endoscopic ultrasongraphy, depressed gross type and redness of lesion mucosa were risk factors for postoperative pathological upgrading. Multivariate analysis indicated that the redness of the lesion mucosa and longitudinal diameter (≥3 cm) of the lesion were independent risk factors for pathological upgrading. CONCLUSIONS: For esophageal lesions diagnosed by biopsy as LGIN, clinicians should be highly alert to the pathological underestimate if the lesion surface is reddened and its longitudinal diameter is greater than 3 cm.

[Endoscopic Characteristics and Pathological Analysis of Esophageal Low-grade Intraepithelial Neoplasm].

OBJECTIVE: To explore endoscopic characteristics and pathological changes of esophageal low-grade intraepithelial neoplasm (LGIN) as well as its risk factors. METHODS: A total of 201 LGIN lesions from 169 cases were included from January 2009 to August 2017. The endoscopic characteristics and pathological changes were analysis. Logistic regression analysis was used to analyze the risk factors of LGIN. The endoscopic morphologic findings of esophageal mucosa lesions and the pathological findings of simple inflammatory lesions were enrolled as controls. RESULTS: LGIN occurred more common in elderly patients, the ratio of male to female was 2.5∶1. The maximum transverse and the maximum longitudinal diameter (MLD) were (0.9±0.8) cm,(1.4±1.3) cm, respectively. The most common location of lesion was in the middle segment of esophagus (52.2%). The morphological types of lesions were dominantly 0-Ⅱb (45.8%) and 0-Ⅱa (31.8%). There were 42 LGIN lesions with reflux esophagitis. Multiple dysplastic lesions accounted for 57.4%. After (10.3±12.1) months follow-up, 58.2% lesions were pathological reversal with 24.9% (50/201) of the lesion completely disappeared, and 28.9% lesions had no pathological changes, but 12.9% (26/201) lesions progressed to high-grade intraepithelial neoplasia and invasive cancer. Multivariate analysis indicated that age (compared to <45 years old) and longitudinal diameter of the lesion (compared to ≤0.5 cm) were independent risk factors for LGIN. The risk of esophageal LGIN in lesions with MLD > 0.5-1 cm was 1.96 times higher than that in lesions with MLD ≤ 0.5 cm. CONCLUSIONS: The MLD of esophageal mucosal lesions >0.5 cm and age >45 years old may increase the possibility of esophageal LGIN. Close follow-up is required for LGIN lesions with MLD>1 cm.

Endoscopic Submucosal Tunnel Dissection: A Feasible Solution for Large Superficial Rectal Neoplastic Lesions.

BACKGROUND: Although endoscopic submucosal tunnel dissection has been used for the resection of esophageal and stomach neoplastic lesions, there are still no reports about large superficial rectal neoplastic lesions. Compared with esophageal and stomach endoscopic submucosal dissection, the dissection of large superficial rectal neoplastic lesions is more difficult because of the flimsy bowel wall with abundant vasculature in the submucosal region, which results in poor endoscopic maneuverability and serious complications, such as bleeding and perforation. OBJECTIVE: The study aimed to assess the efficacy and safety of endoscopic submucosal tunnel dissection for large superficial rectal neoplastic lesions over 5 to 24 months in selected patients. DESIGN: This was a prospective, single-center evaluation. SETTINGS: The study was conducted at a digestive endoscopic center. PATIENTS: Patients with large superficial rectal neoplastic lesions were included. INTERVENTIONS: Endoscopic submucosal tunnel dissection was performed in all of the patients with large, superficial rectal neoplastic lesions. The submucosal tunnel was created via a submucosal incision from the anal incision to the oral incision. Next, tunnel wall resection was performed to completely remove the lesion. MAIN OUTCOME MEASURES: Dissection speed, complications, and recurrence rate were measured. RESULTS: A total of 19 patients, including 13 men and 6 women, with an average age of 60.1 ± 12.2 years (range, 34.0-75.0 y) underwent endoscopic submucosal tunnel dissection. The average size of lesions was 17.54 ± 13.47 cm. The mean operative time was 84.84 ± 53.49 minutes, and the operating speed was 21.01 ± 9.00 mm/min. En bloc resections with negative basal margins were achieved in all cases without serious intraoperative complications. No recurrence was observed in any patient within 5 to 24 months after the operations. LIMITATIONS: This was a single-center study. CONCLUSIONS: Endoscopic submucosal tunnel dissection is feasible, safe, and effective for the treatment of large, superficial rectal neoplastic lesions in selected patients. See Video Abstract at http://links.lww.com/DCR/A321.

Endoscopic submucosal multi-tunnel dissection for circumferential superficial esophageal neoplastic lesions (with videos).

BACKGROUND AND AIMS: Endoscopic submucosal tunnel dissection (ESTD) has been used for dissection of large esophageal neoplastic lesions, but there are still some technical problems in treating circumferential superficial esophageal neoplastic lesions. This study aimed to assess the efficacy and safety of endoscopic submucosal multi-tunnel dissection (ESMTD) for circumferential superficial esophageal neoplastic lesions in selected patients followed up for 1 to 12 months. METHODS: From July 2014 to February 2015, the first series of 7 consecutive patients with circumferential superficial esophageal neoplastic lesions underwent ESMTD at our endoscopic center. The macroscopic types were classified according to the Paris endoscopic classification of superficial neoplastic lesions. RESULTS: The average length of lesions was 6.1 cm in 7 selected patients. The operative time ranged from 69 to 169 minutes (mean 121 minutes). En bloc dissection with negative basal margins was achieved in all lesions without serious intraoperative adverse events. Esophageal stricture was observed in all patients 1 to 3 months after the operation and was relieved after a retrievable metal stent was placed or esophageal water balloon dilatation was performed; however, one patient died of cerebral infarction 2 months after ESMTD. CONCLUSIONS: ESMTD is feasible, safe, and effective for the treatment of circumferential superficial esophageal neoplastic lesions in select patients.

[Expression Difference of MicroRNAs in Colorectal Adenoma and Colorectal Cancer].

OBJECTIVE: To investigate the expression difference of microRNAs in colorectal tubular adenoma, tubulovillous adenoma and colorectal cancer. METHODS: Real time-polymerase chain reaction was used to analysis the expression level of miR-1, miR-9, miR-31, miR-135a, miR-137 and miR-145 between colorectal tubular adenoma (n=44), tubulovillous adenoma (n=16), colorectal cancer (n=20) and paired paracancerous normal colorectal tissues. RESULTS: Compared with paired paracancerous normal colorectal tissues, colorectal tubular adenoma had decreased expression of miR-1, miR-9, miR-137 and miR-145 as well as increased expression of miR-31 and miR-135a. Colorectal tubulovillous adenoma had decreased levels of miR-1, miR-137, miR-145, as well as increased levels of miR-9, miR-135a, and miR-31. Colorectal cancer had the expressions of miR-1, miR-9, miR-137 and miR-145 decreased while the expression of miR-135a and miR-31 increased. CONCLUSION: The differential expressions of microRNAs suggested that miRNAs participate in the development of colorectal adenoma and cancer.

[Risk Factors of Lymph Node Metastasis in Superficial Esophageal Squamous Cell Carcinoma].

OBJECTIVE: To analysis the risk factors of lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (SESCC). METHODS: The clinical data and pathological results of 344 SESCC patients, who underwent surgical treatments between January 2009 and December 2013 in West China Hospital, Sichuan University, were analyzed retrospectively. Clinicopathologic characteristics were compared between different histological types, and their possible relationships with LNM were explored by univariate and multivariate analysis. RESULTS: There were no LNM found in the patients with tumor limited to the mucous, tumor diameter <3 cm, highly and moderate differentiated SESCC. Univariate analysis showed that tumor diameter (P=0.004), depth of tumor invasion (P=0.009), histological type (P=0.030) and lymphatic involvement (P=0.002) were correlated with LNM. Multivariate analysis revealed that tumor diameter (P=0.007), depth of tumor invasion (P=0.003), histological type (P=0.010) and lymphatic involvement (P<0.001) were independent risk factors of LNM. CONCLUSION: To the patients with low risk of LNM, such as tumor limited to the mucous, tumor diameter <3 cm, and highly and moderate differentiation, endoscopic excision may be considered as an absolute indications.

Quantitative analysis of microglia morphological changes in the hypothalamus of chronically stressed rats.

Based on the successful establishment of a rat model of chronic restraint stress, we used multiple algorithms to quantify the morphological changes of rat hypothalamic microglia from various perspectives, providing a pathomorphological basis for the subsequent study of molecular mechanisms of hypothalamic stress injury, such as neuroinflammation. To verify the successful establishment of the chronic stress model, an enzyme-linked immunosorbent assay was performed to detect serum glucocorticoid levels. Microglia labeled with Iba1 in frozen sections of rat hypothalamus were scanned and photographed at multiple levels using confocal microscopy. Subsequently, images were processed for external contouring and skeletonization, and morphological indices of microglia were calculated and analyzed using fractal, skeleton, and Sholl analysis. In addition, the co-expression of CD68 (a marker that can reflect phagocytic activity) and Iba1 was observed by immunofluorescence technique. Compared with the control group, microglia in the chronic stress group displayed reduced fractal dimension and lacunarity, increased density and circularity, enlarged soma areas, and shortened and reduced branches. Sholl analysis confirmed the reduced complexity of microglia following chronic stress. Meanwhile, microglia CD68 increased significantly, indicating that the microglia in the chronic stress group have greater phagocytosis activity. In summary, chronic restraint stress promoted the conversion of microglia in the rat hypothalamus to a less complex form, manifested as larger soma, shorter and fewer branches, more uniform and dense texture, and increased circularity; indeed, the shape of these microglia resembled that of amoeba and they displayed strong phagocytosis activity.

A distinctive subcortical functional connectivity pattern linking negative affect and treatment outcome in major depressive disorder.

Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) correlation analysis to explore the association between subcortical FC and mood symptom profiles. FC score, reflecting the weighted representation of each individual in this association, was computed. Replication analysis was undertaken in an independent sample (n = 74). We also investigated the relationship between FC score and treatment outcome in the main sample. A distinctive subcortical connectivity pattern was found to be associated with negative affect. In general, higher FC between the caudate, putamen and thalamus was associated with greater negative affect. This association was partly replicated in the independent sample (similarity between the two samples: r = 0.66 for subcortical connectivity, r = 0.75 for mood symptom profile). Lower FC score predicted both remission and response to treatment after 8 weeks of antidepressant monotherapy. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical FC with negative affect. However, while the FC score significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.

Four new diastereoisomeric neolignan glycosides from the root bark of Lycium chinense Miller. and their α-glucosidase inhibitory activity.

Four new diastereoisomeric neolignan glycosides (1-4) along with nine known lignan glycosides (5-13) were isolated from the root bark of Lycium chinense Mill. Their structures with absolute configurations were elucidated on the basis of NMR spectroscopy, ECD, Mo2(OAc)4-induced ECD spectra, enzymatic hydrolysis and acid hydrolysis. The isolated compounds were evaluated for their α-glucosidase inhibitory activity. Compounds 8 and 13 exhibited moderate inhibitory activities against α-glucosidase with IC50 values of 26.82 ± 2.71 and 43.14 ± 2.81 µg/mL.

Maternal anxiety during pregnancy and children's asthma in preschool age: The Ma'anshan birth cohort study.

BACKGROUND: The fetal immune system and consequent elevated risk of asthma in childhood may be impacted by maternal anxiety during pregnancy. Limited studies have evaluated whether there was a sensitive period and cumulative effect of the relationship between prenatal anxiety and children's asthma. METHODS: 3131 mother-child pairs made up the study's sample from the Ma'anshan Birth Cohort Study in China. Maternal anxiety status was repeated three times using the pregnancy-related anxiety questionnaire in the 1st, 2nd and 3rd trimesters of pregnancy. Diagnostic information on asthma was collected three times at 24, 36, and 48 months of age. RESULTS: After adjusting for confounders, children born to mothers with anxiety in the 1st, 2nd and 3rd trimesters of pregnancy all had an elevated risk of total asthma from 12 to 48 months of age. After further adjusting prenatal anxiety in the other trimesters, no association was observed between prenatal anxiety in any trimester and preschoolers' asthma. Children of mothers with persistently high anxiety score trajectory during pregnancy had an elevated risk of total asthma and high prevalence trajectory of asthma. Cumulative effects analysis showed that the more frequent the mother's anxiety, the higher the risk of her offspring developing a high prevalence trajectory of asthma from 12 to 48 months of age. The results of the subgroup analysis by age showed similar associations overall. CONCLUSIONS: Maternal antenatal anxiety was associated with an elevated risk of preschool children's asthma, and a possible cumulative effect was observed. Maternal mental health conditions during pregnancy should receive constant attention throughout pregnancy, not just during one period.