Anti-oomycete ability of scopolamine against Phytophthora infestans, a terrible pathogen of potato late blight.

BACKGROUND: Phytophthora infestans causes late blight, threatening potato production. The tropane alkaloid scopolamine from some industrial plants (Datura, Atropa, etc.) has a broad-spectrum bacteriostatic effect, but its effect on P. infestans is unknown. RESULTS: In the present study, scopolamine inhibited the mycelial growth of phytopathogenic oomycete P. infestans, and the half-maximal inhibitory concentration (IC50 ) was 4.25 g L-1 . The sporangia germination rates were 61.43%, 16.16%, and 3.99% at concentrations of zero (control), 0.5 IC50 , and IC50 , respectively. The sporangia viability of P. infestans was significantly reduced after scopolamine treatment through propidium iodide and fluorescein diacetate staining, speculating that scopolamine destroyed cell membrane integrity. The detached potato tuber experiment demonstrated that scopolamine lessened the pathogenicity of P. infestans in potato tubers. Under stress conditions, scopolamine showed good inhibition of P. infestans, indicating that scopolamine could be used in multiple adverse conditions. The combination effect of scopolamine and the chemical pesticide Infinito on P. infestans was more effective than the use of scopolamine or Infinito alone. Moreover, transcriptome analysis suggested that scopolamine leaded to a downregulation of most P. infestans genes, functioning in cell growth, cell metabolism, and pathogenicity. CONCLUSION: To our knowledge, this is the first study to detect scopolamine inhibitory activity against P. infestans. Also, our findings highlight the potential of scopolamine as an eco-friendly option for controlling late blight in the future. © 2023 Society of Chemical Industry.

Global trends and prospects in research of artificial cornea over past 20 years: a bibliometric and visualized analysis.

BACKGROUND: Many studies have been focused on the area of the artificial cornea. In our study, a bibliometric analysis was performed on the artificial cornea to identify the global key research fields and trends over the past 20 years. METHODS: Publications about artificial cornea were retrieved and downloaded from the Web of Science Core Collection from 2002 to 2021. CiteSpace and VOSviewer were used to analyze countries, institutions, authors, and related research areas. RESULTS: A total of 829 eligible publications were analyzed. The USA was the most productive country for the artificial cornea, followed by China and Canada. Harvard University was the most prolific institution in this field. Cornea published most of the studies in this area and Dohlman CH was the most cited author. CONCLUSIONS: Bibliometric analysis in our study first provides a general perspective on the artificial cornea, which can be helpful to further explore the issues in the rapidly developing area.

Prevalence and Incidence of Dry Eye Disease in Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Dry eye disease (DED) is the most common ocular surface disease, which severely affects the quality of life. An overall estimate of the prevalence, incidence, and risk factors of DED in Asia would help in planning and implementing appropriate public health strategies. OBJECTIVES: The present study aimed to study the epidemiology of DED in Asia. METHODS: A comprehensive and systematic search was performed using several databases, including PubMed, Cochrane Library, and Web of Science, in January 2021. A random-effects meta-analysis was performed on logit-transformed prevalence and incidence rates to calculate pooled prevalence and incidence estimates. Meta-regression and subgroup analyses were performed to explain the heterogeneity. RESULTS: Among the 6,742 articles identified, 23 were included in the analysis, with a total sample size of 1,488,935 subjects. Twenty studies reported the prevalence of DED in Asia, two studies reported the incidence, and one study reported both prevalence and incidence. The estimated pooled prevalence of DED in any population in Asia was 20.1% (95% confidence interval [Ozdemir et al., Acta Ophthalmol. 2019;97(1):e91-6]: 13.9-28.3%), and the incidence 16.7% (95% CI: 0-34.9%). The prevalence rate of DED in males and females was 16.4% (95% CI: 10.0-25.8%) and 21.7% (95% CI: 14.7-30.8%; p < 0.001), respectively. In general, the prevalence increased with age. The risk factors considered for specific populations were not significant, and the prevalence in the general population, excluding the populations considered at risk, was similar at 20.9% (95% CI: 12.8-32.1%). CONCLUSIONS: DED is common in Asian populations and causes a significant disease burden. Its prevalence is higher in females than that in males, and it tends to increase in severity with age. Further research on additional risk factors is needed to adequately explain the epidemiology of DED in Asia.

Alterations in resting-state global brain connectivity in bipolar I disorder patients with prior suicide attempt.

BACKGROUND: Bipolar I disorder (BD-I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) allows non-invasive mapping of brain functional connectivity. The current study used an unbiased voxel-based graph theory analysis of rs-fMRI to investigate the intrinsic brain networks of BD-I patients with and without suicide attempt. METHODS: A total of 30 BD-I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non-attempter group), and 67 healthy controls underwent rs-fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. RESULTS: Compared with the non-attempter group, we found regional differences in GBC values in emotion-encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub-like regions displayed fair to good power in distinguishing attempters from non-attempters among BD-I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. CONCLUSIONS: Our results indicate that abnormal connectivity patterns in emotion-encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion-encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.

Treating Fungal Keratitis with Oral Voriconazole Only: A Case Series.

BACKGROUND: To report the clinical effect of oral voriconazole only as a treatment for fungal keratitis. HISTORY AND SIGNS: Three patients (1 female and 2 males) with culture-proven fungal keratitis (1 Mucoraceae, 1 Aspergillus, 1 Fusarium) were included in this study. The patients were treated with oral voriconazole 200 mg twice daily to observe the clinical response in the treatment of fungal keratitis. THERAPY AND OUTCOME: The mean age of the patients was 51 years and the average treatment duration was 6 weeks. The corneal inflammation in these three patients was eliminated by oral voriconazole only. CONCLUSIONS: This is the first reported case of oral voriconazole only as a treatment for fungal keratitis. We found that oral voriconazole has a significant clinical effect on the treatment of fungal keratitis.

Inflammation, brain structure and cognition interrelations among individuals with differential risks for bipolar disorder.

Neuro-inflammation might impact on clinical manifestations and cognition function via changing the volumes of key brain structures such as the anterior cingulate cortex (ACC) in bipolar disorder (BD). In this study, we investigated the interrelations among interleukin (IL)-6 cytokine level, grey matter (GM) volume of the anterior cingulated cortex (ACC), and attention function among offspring of parents diagnosed with BD. The offspring were categorized as being either asymptomatic or symptomatic based on whether they manifested pre-defined sub-threshold mood symptoms. We found that the symptomatic offspring showed significantly higher serum levels of IL-6 than the asymptomatic offspring (F(1, 59) = 67.65, p < 0.001). On the brain level, we obtained significant interactive effect of group and IL6 level on the ACC GM (PFWE = 0.017). Specifically, the GM volume of the rostral ACC was negatively associated with the levels of IL-6 in the asymptomatic offspring (PFWE = 0.021), but not the symptomatic offspring (PFWE > 0.05). Mediation analyses revealed that the GM volume of the rostral ACC significantly mediated the negative association between the IL-6 levels and attention performance in the asymptomatic offspring (bootstrapping Confidence Interval (CI) = -6.0432 to -0.0731) but not the symptomatic offspring (bootstrapping CI = -0.3197 to 1.3423). Our data suggest that the asymptomatic and symptomatic bipolar offspring may exhibit different neurocognitive-inflammatory profiles, which could be further validated as viable biosignatures for BD risk and resilience.

A preliminary study on brain developmental features of bipolar disorder familial risk and subthreshold symptoms.

BACKGROUND: Risk for Bipolar disorder (BD) is increased among individuals with family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remained unknown. METHODS: This longitudinal cohort study examined the brain grey matter volume (GMV) developmental features of familial and symptomatic risks for BD, and their associations with participants' global function levels. We recruited unaffected BD offspring with (N=26, age=14.9±2.9 years, 14 females) or without (N=35, age=15.3±2.7 years, 19 females) subthreshold manic or depressive symptoms, and unaffected non-BD offspring with (N=49, age=14.5±2.2 years, 30 females) or without (N=68, age=15.0±2.3 years, 37 females) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63±1.63 years. RESULTS: We found at baseline, significant interactive effects of familial risk and subthreshold symptoms indicated the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and non-symptomatic) displayed accelerated GMV decrease than BD non-offspring, in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and non-offspring) displayed slower GMV decrease than non-symptomatic participants, in the ventromedial prefrontal cortex. Larger GMV at baseline, and accelerated GMV decrease during follow-up, prospectively and longitudinally predicted positive global function changes. All results survived multiple-testing correction. CONCLUSIONS: These findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments, and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.

[Inhibitory effects of doxycycline on argyrophilic nucleolar organizing regions and a-smooth muscle actin expression in proliferative bovine corneal myofibroblasts in vitro].

OBJECTIVE: To investigate the effect of doxycycline on the nucleolar organizing regions and a-smooth muscle actin expression in bovine corneal myofibroblasts in vitro and assess its contribution to ocular surface repair mechanisms. METHODS: Cell culture and identification: bovine corneal fibroblasts were cultured after the stroma was incubated in 1.0 and 2.0 g/L type I collagenase in two stages.Isolated cells were plated at mantaryay culture flask in 10% of BSA RPMI-1640. Vimentin and alpha-smooth muscle actin (α-SMA) organization were evaluated by immunocytochemistry. The cells staining positive for Vimentin and α-SMA indicated the presence of corneal myofibroblasts. Bovine corneal myofibroblasts were treated with different concentrations of doxycycline (10, 20, 40, 60, 80 mg/L) , a bland control group and the dexamethasone group (120 mg/L) were set up, each group had 30 cases. The argyrophilic nucleolar organizing regions (AgNOR) staining and the immunohistochemistry for α-SMA were performed when the cells were treated for 24 hours and 48 hours. The AgNOR count (Ag-c), AgNOR area (Ag-a) and the expression of α-SMA in the bovine corneal myofibroblasts among each experiment group and control group were compared using one-way ANOVA, further pairwise comparisons using Independent-Samples t test. RESULTS: Cell culture techniques were successfully used to establish a method for the isolation and culture of bovine corneal myofibroblasts. Microscopic examination and immunohistochemical staining confirmed that the cells cultured were bovine corneal myofibroblasts. The Ag-c and Ag-a of bovine corneal myofibroblasts progressively decreased as the concentrations of doxycycline was increase. 24 h:bland control group Ag-c was 6.40 ± 0.6, 60 mg/L doxycycline group Ag-c was 2.23 ± 0.43;bland control group Ag-a was (34.80 ± 2.36) µm(2), 60 mg/L doxycycline hormone group Ag-a was (19.91 ± 2.15) µm(2). 48 h: bland control group Ag-c was 7.27 ± 0.6,60 mg/L doxycycline hormone group Ag-c was 2.80 ± 0.76, bland control group Ag-a was (36.27 ± 1.99) µm(2), 60 mg/L doxycycline group Ag-a was (13.75 ± 2.09) µm(2). The differences were statistically significant: in the same time intervention (FAg-c 24 h = 252.55, FAg-a 24 h = 202.16, P < 0.05, FAg-c 48 h = 169.38, FAg-a 48 h = 853.23, P < 0.05), in the same concentrations intervention (tAg-c = 6.98, tAg-a = 11.62, P < 0.05). And 60 mg/L of doxycycline had an obviously inhibitory action as 120 mg/L dexamethasone in the same treated hours (dexamethasone group Ag-a 24 h = 30.56 ± 3.66, dexamethasone group Ag-a 48 h = 28.35 ± 1.23 ),the differences were not statistically significant (tAg-a 24h = 1.182, P = 0.242,tAg-a 48 h = 0.21, P = 0.832). As the concentrations investigated, doxycycline can inhibit the expression of α-SMA in the bovine corneal myofibroblasts (189.90 ± 7.48, 140.20 ± 7.79, 113.20 ± 8.98, 98.00 ± 3.50, 85.50 ± 4.99), the difference was statistically significant (F = 761.79, P = 0.00). While dexamethasone had no significant role in the expression of α-SMA (bland control group was 225.10 ± 6.74, the dexamethasone group was 228.50 ± 7.12), and the statistically difference was not obvious (t = 1.096, P = 0.287). CONCLUSIONS: As the concentrations of doxycycline was increased from 10 mg/L to 80 mg/L, the AgNOR count and AgNOR area of bovine corneal myofibroblasts can be significantly reduced in vitro. Compared with dexamethasone, doxycycline significantly suppressed the expression of α-SMA in bovine corneal myofibroblasts in a dose-dependent positive trend.

Oral voriconazole monotherapy for fungal keratitis: efficacy, safety, and factors associated with outcomes.

Purpose: To provide preliminary data on the efficacy and safety of oral voriconazole (VCZ) as a primary treatment for fungal keratitis (FK). Method: We performed a retrospective histopathological analysis of data on 90 patients with FK at The First Affiliated Hospital of Guangxi Medical University between September 2018 and February 2022. We recorded three outcomes: corneal epithelial healing, visual acuity (VA) improvement, and corneal perforation. Independent predictors were identified using univariate analysis, and multivariate logistic regression analysis was used to identify independent predictive factors associated with the three outcomes. The area under the curve was used to evaluate the predictive value of these factors. Results: Ninety patients were treated with VCZ tablets as the only antifungal drug. Overall, 71.1% (n = 64) of the patients had extreme corneal epithelial healing, 56.7% (n = 51) showed an improvement in VA, and 14.4% (n = 13) developed perforation during treatment. Non-cured patients were more likely to have large ulcers (≥5 × 5 mm2) and hypopyon. Conclusion: The results indicated that oral VCZ monotherapy was successful in the patients with FK in our study. Patients with ulcers larger than 5 × 5 mm2 and hypopyon were less likely to respond to this treatment.

DivIVA Interacts with the Cell Wall Hydrolase MltG To Regulate Peptidoglycan Synthesis in Streptococcus suis.

Bacterial morphology is largely determined by the spatial and temporal regulation of peptidoglycan (PG) biosynthesis. Ovococci possess a unique pattern of PG synthesis different from the well studied Bacillus, and the mechanism of the coordination of PG synthesis remains poorly understood. Several regulatory proteins have been identified to be involved in the regulation of ovococcal morphogenesis, among which DivIVA is an important one to regulate PG synthesis in streptococci, while its mechanism is largely unknown. Here, the zoonotic pathogen Streptococcus suis was used to investigate the regulation of DivIVA on PG synthesis. Fluorescent d-amino acid probing and 3D-structured illumination microscopy found that DivIVA deletion caused abortive peripheral PG synthesis, resulting in a decreased aspect ratio. The phosphorylation-depleted mutant (DivIVA3A) cells displayed a longer nascent PG and became longer, whereas the phosphorylation-mimicking mutant (DivIVA3E) cells showed a shorter nascent PG and became shorter, suggesting that DivIVA phosphorylation is involved in regulating peripheral PG synthesis. Several DivIVA-interacting proteins were identified, and the interaction was confirmed between DivIVA and MltG, a cell wall hydrolase essential for cell elongation. DivIVA did not affect the PG hydrolysis activity of MltG, while the phosphorylation state of DivIVA affected its interaction with MltG. MltG was mislocalized in the ΔdivIVA and DivIVA3E cells, and both ΔmltG and DivIVA3E cells formed significantly rounder cells, indicating an important role of DivIVA phosphorylation in regulating PG synthesis through MltG. These findings highlight the regulatory mechanism of PG synthesis and morphogenesis of ovococci. IMPORTANCE The peptidoglycan (PG) biosynthesis pathway provides a rich source of novel antimicrobial drug targets. However, bacterial PG synthesis and its regulation is a very complex process involving dozens of proteins. Moreover, unlike the well studied Bacillus, ovococci undergo unusual PG synthesis with unique mechanisms of coordination. DivIVA is an important regulator of PG synthesis in ovococci, while its exact role in regulating PG synthesis remains poorly understood. In this study, we determined the role of DivIVA in regulating lateral PG synthesis of Streptococcus suis and identified a critical interacting partner, MltG, in which DivIVA influenced the subcellular localizations of MltG through its phosphorylation. Our study characterizes the detailed role of DivIVA in regulating bacterial PG synthesis, which is very helpful for understanding the process of PG synthesis in streptococci.

Discovery of a highly efficient TylF methyltransferase via random mutagenesis for improving tylosin production.

Macrolides are currently a class of extensively used antibiotics in human and animal medicine. Tylosin is not only one of the most important veterinary macrolides but also an indispensable material for the bio- and chemo-synthesis of new generations of macrolide antibiotics. Thus, improving its production yield is of great value. As the key rate-limiting enzyme catalyzing the terminal step of tylosin biosynthesis in Streptomyces fradiae (S. fradiae), TylF methyltransferase's catalytic activity directly affects tylosin yield. In this study, a tylF mutant library of S. fradiae SF-3 was constructed based on error-prone PCR technology. After two steps of screening in 24-well plates and conical flask fermentation and enzyme activity assay, a mutant strain was identified with higher TylF activity and tylosin yield. The mutation of tyrosine to phenylalanine is localized at the 139th amino acid residue on TylF (TylFY139F), and protein structure simulations demonstrated that this mutation changed the protein structure of TylF. Compared with wild-type protein TylF, TylFY139F exhibited higher enzymatic activity and thermostability. More importantly, the Y139 residue in TylF is a previously unidentified position required for TylF activity and tylosin production in S. fradiae, indicating the further potential to engineer the enzyme. These findings provide helpful information for the directed molecular evolution of this important enzyme and the genetic modification of tylosin-producing bacteria.

Development and Application of Two Inducible Expression Systems for Streptococcus suis.

Streptococcus suis is an important zoonotic bacterial pathogen posing a threat to the pig industry as well as public health, for which the mechanisms of growth and cell division remain largely unknown. Developing convenient genetic tools that can achieve strictly controlled gene expression is of great value for investigating these fundamental physiological processes of S. suis. In this study, we first identified three strong constitutive promoters, Pg, Pt, and Pe, in S. suis. Promoter Pg was used to drive the expression of repressor genes tetR and lacI, and the operator sequences were added within promoters Pt and Pe. By optimizing the insertion sites of the operator sequence, we successfully constructed an anhydrotetracycline (ATc)-inducible expression system and an isopropyl-ß-d-thiogalactopyranoside (IPTG)-inducible expression system in S. suis. We showed that these two systems provided inducer-concentration- and induction-time-dependent expression of the reporter gene. By using these tools, we investigated the subcellular localization of a key cell division protein, FtsZ, which showed that it could be correctly localized to the midcell region. In addition, we constructed a conditional knockout strain for the glmS gene, which is an essential gene, and showed that our ATc-inducible promoter could provide strictly controlled expression of glmS in trans, suggesting that our inducible expression systems can be used for deletion of essential genes in S. suis. Therefore, for the first time we developed two inducible expression systems in S. suis and showed their applications in the study of an important cell division protein and an essential gene. These genetic tools will further facilitate the functional study of other important genes of S. suis. IMPORTANCE Streptococcus suis is an important zoonotic bacterial pathogen. Studying the mechanisms of cell growth and division is important for the identification of novel antimicrobial drug targets. Inducible expression systems can provide strictly controlled expression of the protein of interest and are useful tools to study the functions of physiologically important proteins. However, there is a lack of convenient genetic tools that can achieve inducible protein expression in S. suis. In this study, we developed two (ATc-inducible and IPTG-inducible) inducible expression systems and showed their applications in a subcellular localization study of a cell division protein and the construction of conditional knockout of essential genes in S. suis. These systems will be useful for functional studies of important proteins of S. suis.

IPA-3: An Inhibitor of Diadenylate Cyclase of Streptococcus suis with Potent Antimicrobial Activity.

Antimicrobial resistance (AMR) poses a huge threat to public health. The development of novel antibiotics is an effective strategy to tackle AMR. Cyclic diadenylate monophosphate (c-di-AMP) has recently been identified as an essential signal molecule for some important bacterial pathogens involved in various bacterial physiological processes, leading to its synthase diadenylate cyclase becoming an attractive antimicrobial drug target. In this study, based on the enzymatic activity of diadenylate cyclase of Streptococcus suis (ssDacA), we established a high-throughput method of screening for ssDacA inhibitors. Primary screening with a compound library containing 1133 compounds identified IPA-3 (2,2'-dihydroxy-1,1'-dinapthyldisulfide) as an ssDacA inhibitor. High-performance liquid chromatography (HPLC) analysis further indicated that IPA-3 could inhibit the production of c-di-AMP by ssDacA in vitro in a dose-dependent manner. Notably, it was demonstrated that IPA-3 could significantly inhibit the growth of several Gram-positive bacteria which harbor an essential diadenylate cyclase but not E. coli, which is devoid of the enzyme, or Streptococcus mutans, in which the diadenylate cyclase is not essential. Additionally, the binding site in ssDacA for IPA-3 was predicted by molecular docking, and contains residues that are relatively conserved in diadenylate cyclase of Gram-positive bacteria. Collectively, our results illustrate the feasibility of ssDacA as an antimicrobial target and consider IPA-3 as a promising starting point for the development of a novel antibacterial.

Global hippocampus functional connectivity as a predictive neural marker for conversion to future mood disorder in unaffected offspring of bipolar disorder parents.

OBJECTIVES: Hippocampus-related functional alteration in genetically at-risk individuals may reflect an endophenotype of a mood disorder. Herein, we performed a prospective study to investigate whether baseline hippocampus functional connectivity (FC) in offspring of patients with bipolar disorder (BD) would predict subsequent conversion to mood disorder. METHODS: Eighty bipolar offspring and 40 matched normal controls (NC) underwent resting state functional MRI (rsfMRI) scanning on a 3.0 Tesla MR scanner. The offspring were subdivided into asymptomatic offspring (AO) (n = 41) and symptomatic offspring (SO) (n = 39) according to whether they manifested subthreshold mood symptoms. After identifying the different hippocampus FCs between the AO and SO, a logistic regression analysis was conducted to investigate whether the baseline hippocampus FCs predicted a future mood disorder during a 6-year follow-up. RESULTS: We identified seven baseline para/hippocampus FCs that showed differences between AO and SO, which were entered as predictive features in the logistic regressive model. Of the 80 bipolar offspring entering the analysis, the FCs between left hippocampus and left precuneus, and between right hippocampus and left posterior cingulate, showed a discriminative capacity for predicting future mood disorder (area-under-curve, or AUC=75.76 % and 75.00 % respectively), and for predicting BD onset (AUC=77.46 % and 81.63 %, respectively). CONCLUSIONS: The present findings revealed high predictive utility of the hippocampus resting state FCs for future mood disorder and BD onset in individuals at familial risk. These neural markers can potentially improve early detection of individuals carrying particularly high risk for future mood disorder.

Differential Relationships Among C-Reactive Protein, Attention Functioning, and Brain Structure in Bipolar Offspring With and Without Subthreshold Mood Symptoms.

Background: Bipolar disorder (BD) is a highly heritable mood disorder. Activated low-grade inflammation may not only play an adverse role in the pathophysiology of BD, but also contribute to a resilience process. The neuroinflammatory processes may underlie the attention deficit and alteration of gray matter volume (GMV) in the early stage and premorbid period of BD. Also, the differential inflammation-brain relationship may be identified as biological markers for BD pathology or resilience.Methods: The present data were collected between March 2013 and June 2016. Sixty-four offspring of BD patients were recruited and subdivided into asymptomatic (n = 33, mean age = 17.8 years) and symptomatic (n = 31, mean age = 16.2 years) groups according to whether they manifested subthreshold mood symptoms. The diagnosis of BD was confirmed according to DSM-IV criteria. C-reactive protein (CRP) level, attention functioning, and GMV data were measured by ELISA, the Continuous Performance Test-Identical Pair test (CPT-IP), and 3.0 T magnetic resonance imaging, respectively. Their relationships were examined with mediation and moderation analyses.Results: We observed a higher level of CRP and poorer attention in the symptomatic group than the asymptomatic group and found a significant group × CRP interactive effect on GMV in regions spanning right precentral and postcentral gyri (P = .043). CRP levels negatively mediated the relationship between the group and CPT-IP scores, and the group marginally moderated the relationship between pre/postcentral gyri volumes and CPT-IP scores (P = .05).Conclusions: Symptomatic and asymptomatic bipolar offspring manifested differential inflammation-GMV-attention relationships, which may represent, respectively, an endophenotype or a resilience process for BD.

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study.

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049-0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

Rumination network dysfunction in major depression: A brain connectome study.

BACKGROUND: Rumination is a central feature of major depressive disorder (MDD). Knowledge of the neural structures that underpin rumination offers significant insight into depressive pathophysiology and may help to develop potential intervention strategies for MDD, a mental illness that has become the leading cause of disability worldwide. METHODS: Using resting-state fMRI and graph theory, this study adopted a connectome approach to examine the functional topological organization of the neural network associated with rumination in MDD. Data from 96 participants were analyzed, including 51 patients with MDD and 45 healthy controls. RESULTS: We found altered functional integration and segregation of neural networks associated with depressive rumination as indicated by reduced global and local efficiency in MDD patients compared with controls. Interestingly, these metrics correlated positively with depression severity, as measured by the Hamilton Depression Rating Scale. Moreover, mediation analysis indicated that the association between network metrics and depression severity was mediated by the ruminative tendency of patients. Disrupted nodal centralities were located in regions associated with emotional processing, visual mental imagery, and attentional control. CONCLUSION: Our results highlight rumination as a two-edged sword that reflects a disease-specific neuropathology but also points to a functionality of depressive symptoms with evolutionary meaning.

Aerobic exercise impacts the anterior cingulate cortex in adolescents with subthreshold mood syndromes: a randomized controlled trial study.

Aerobic exercise is effective in alleviating mood symptoms while the mechanism is poorly understood. There are limited clinical trials that investigated the effect of exercise on the anterior cingulate cortex (ACC), a key brain region involved in mood regulations, in adolescents with subthreshold mood syndromes. This randomized controlled trial (RCT) of aerobic exercise was undertaken in a middle school in Guangzhou, China. Participants were adolescents aged 12-14 with subthreshold mood syndromes including depressive and manic symptoms and were randomly assigned to an aerobic exercise intervention or a psychoeducation control group. Participants in the exercise group received moderate-intensity exercise intervention, consisting of 30 mins running, 4 days per week for 3 months. The primary outcome in this study was structural changes in the ACC from baseline to post intervention. The trial was registered with ClinicalTrial.gov (NCT03300778). Of 56 participants who met the criteria for subthreshold mood syndromes, 39 (41.03% males) had complete MRI data, with 20 and 19 subjects in the exercise and control group, respectively. At baseline, demographic information (e.g., age and sex), clinical symptoms, and the gray matter volume and cortical thickness of ACC were matched between the two groups. After 12 weeks of treatment, participants in the exercise group displayed increased gray matter volume of the left rostral ACC (F1,30 = 5.73, p = 0.02) and increased cortical thickness of the right rostral ACC (F1,30 = 7.83, p = 0.01) when compared with the control group. No significant differences were found for caudal ACC cortical thickness and gray matter volume. Our data demonstrate that 12-week, moderate-intensity aerobic exercise can induce structural changes in the rostral ACC in adolescents with subthreshold mood syndromes.

CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania.

BACKGROUND: The ß2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown. METHODS: Forty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri). RESULTS: Cortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016). LIMITATIONS: Lithium treatment may influence our results, and the sample size in our study is relatively small. CONCLUSIONS: Our results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.

The Wound Healing Effect of Doxycycline after Corneal Alkali Burn in Rats.

PURPOSE: To evaluate the wound healing effect of doxycycline and its underlying mechanisms in a rat model of corneal alkali burn. METHODS: Male SD rats were administered 1.0 N NaOH in the right cornea for 25 seconds and randomly divided into the doxycycline group and the control group, with 84 rats in each group. 1.0 g·L-1 doxycycline eye drops (doxycycline group) or vehicle (control group) was topically instilled onto the rat cornea after chemical injury. Three days, 7 days, and 14 days after alkali burn, microscopy was used to observe corneal wound healing by fluorescein staining and the degree of corneal opacity. The expression of transforming growth factor-beta 1 (TGF-ß1) and matrix metalloproteinase-9 (MMP-9) was detected by RT-PCR and ELISA, alpha-smooth muscle actin (a-SMA) levels were measured by immunofluorescent staining, and Western blot assays for TGF-ß1, a-SMA, and nuclear factor-kappa B (NF-κB) were also performed. RESULTS: Corneal wound healing and corneal opacity scores were better in the doxycycline group than in the control group. Three, 7, and 14 days after corneal alkali burn, a significant increase in TGF-ß1 was observed in corneas from the control group, compared with the corneas from the doxycycline group (P < 0.05). The corneal levels of MMP-9 in the doxycycline group were lower than those in the control group 3 days and 7 days after alkali burn (P < 0.05). In addition, doxycycline inhibited α-SMA expression and suppressed NF-κB expression. CONCLUSION: Doxycycline treatment promoted corneal healing and reduced corneal opacity in SD rats. Doxycycline protected the cornea from alkali burn injury by reducing TGF-ß1, MMP-9, NF-κB, and α-SMA expression.