Acute stress impairs intentional memory suppression through aberrant prefrontal cortex activation in high trait ruminators.

Objective: Research shows that the effect of acute stress on intentional memory suppression could be modulated by individual differences in psychological traits. However, whether acute stress distinctly affects intentional memory suppression in high trait ruminators, a high at-risk group of stress-related disorders, and the neural correlations, remains unclear. Method: 55 healthy college students were divided into high and low trait ruminators (HTR and LTR), Following stress manipulation, a Think/No Think task assessed the memory suppression performance. Functional near-infrared spectroscopy was applied to explore the neural correlates. Psychophysiological interaction analyses were used to assess how the functional connectivity between a seed region and another brain region was modulated by tasks during memory suppression, further mediating memory suppression performance and state rumination. Results: The HTR exhibited poorer memory suppression performance than the LTR under the stress condition. Aberrant activation patterns and task-modulated functional connectivity in the dorsal prefrontal cortex (DLPFC) and superior temporal gyrus (STG) were observed only in the HTR during memory suppression under the stress condition. The effect of memory suppression performance on the state rumination of individuals was significantly mediated by the task-modulated functional connectivity between the DLPFC and STG. Conclusions: The findings could provide insights for prevention or early intervention in the development of stress-related disorders in HTR.

Cell death dependent on holins LrgAB repressed by a novel ArsR family regulator CdsR.

The cell death and survival paradox in various biological processes requires clarification. While spore development causes maternal cell death in Bacillus species, the involvement of other cell death pathways in sporulation remains unknown. Here, we identified a novel ArsR family transcriptional regulator, CdsR, and found that the deletion of its encoding gene cdsR causes cell lysis and inhibits sporulation. To our knowledge, this is the first report of an ArsR family transcriptional regulator governing cell death. We found that CdsR directly repressed lrgAB expression. Furthermore, lrgAB overexpression resulted in cell lysis without sporulation, akin to the cdsR mutant, suggesting that LrgAB, a holin-like protein, induces cell death in Bacillus spp. The lrgAB mutation increases abnormal cell numbers during spore development. In conclusion, we propose that a novel repressor is vital for inhibiting LrgAB-dependent cell lysis.

High-level production of chitinase by multi-strategy combination optimization in Bacillus licheniformis.

In view of the extensive potential applications of chitinase (ChiA) in various fields such as agriculture, environmental protection, medicine, and biotechnology, the development of a high-yielding strain capable of producing chitinase with enhanced activity holds significant importance. The objective of this study was to utilize the extracellular chitinase from Bacillus thuringiensis as the target, and Bacillus licheniformis as the expression host to achieve heterologous expression of ChiA with enhanced activity. Initially, through structural analysis and molecular dynamics simulation, we identified key amino acids to improve the enzymatic performance of chitinase, and the specific activity of chitinase mutant D116N/E118N was 48% higher than that of the natural enzyme, with concomitant enhancements in thermostability and pH stability. Subsequently, the expression elements of ChiA(D116N/E118N) were screened and modified in Bacillus licheniformis, resulting in extracellular ChiA activity reached 89.31 U/mL. Further efforts involved the successful knockout of extracellular protease genes aprE, bprA and epr, along with the gene clusters involved in the synthesis of by-products such as bacitracin and lichenin from Bacillus licheniformis. This led to the development of a recombinant strain, DW2△abelA, which exhibited a remarkable improvement in chitinase activity, reaching 145.56 U/mL. To further improve chitinase activity, a chitinase expression frame was integrated into the genome of DW2△abelA, resulting in a significant increas to 180.26 U/mL. Optimization of fermentation conditions and medium components further boosted shake flask enzyme activity shake flask enzyme activity, achieving 200.28 U/mL, while scale-up fermentation experiments yielded an impressive enzyme activity of 338.79 U/mL. Through host genetic modification, expression optimization and fermentation optimization, a high-yielding ChiA strain was successfully constructed, which will provide a solid foundation for the extracellular production of ChiA.

Systemic lupus erythematosus-related brain abnormalities in the default mode network and the limbic system: A resting-state fMRI meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an immune-mediated and multi-systemic disease which may affect the nervous system, causing neuropsychiatric SLE (NPSLE). Recent neuroimaging studies have examined brain functional alterations in SLE. However, discrepant findings were reported. This meta-analysis aims to identify consistent resting-state functional abnormalities in SLE. METHODS: PubMed and Web of Science were searched to identify candidate resting-state functional MRI studies assessing SLE. A voxel-based meta-analysis was performed using the anisotropic effect-size version of the seed-based d mapping (AES-SDM). The abnormal intrinsic functional patterns extracted from SDM were mapped onto the brain functional network atlas to determine brain abnormalities at a network level. RESULTS: Twelve studies evaluating fifteen datasets were included in this meta-analysis, comprising 572 SLE patients and 436 healthy controls (HCs). Compared with HCs, SLE patients showed increased brain activity in the bilateral hippocampus and right superior temporal gyrus, and decreased brain activity in the left superior frontal gyrus, left middle temporal gyrus, bilateral thalamus, left inferior frontal gyrus and right cerebellum. Mapping the abnormal patterns to the network atlas revealed the default mode network and the limbic system as core neural systems commonly affected in SLE. LIMITATIONS: The number of included studies is relatively small, with heterogeneous analytic methods and a risk of publication bias. CONCLUSIONS: Brain functional alterations in SLE are predominantly found in the default mode network and the limbic system. These findings uncovered a consistent pattern of resting-state functional network abnormalities in SLE which may serve as a potential objective neuroimaging biomarker.

Age-related positive emotional reactivity decline associated with the anterior insula based resting-state functional connectivity.

Recent studies have suggested that emotional reactivity changes with age, but the neural basis is still unclear. The insula may be critical for the emotional reactivity. The current study examined how ageing affects emotional reactivity using the emotional reactivity task data from a human sample (Cambridge Center for Age and Neuroscience, N = 243, age 18-88 years). The resting-state magnetic resonance measurements from the same sample were used to investigate the potential mechanisms of the insula. In the initial analysis, we conducted partial correlation assessments to examine the associations between emotional reactivity and age, as well as between the gray matter volume (GMV) of the insula and age. Our results revealed that emotional reactivity, especially positive emotional reactivity, decreased with age and that the GMV of the insula was negatively correlated with age. Subsequently, the bilateral insula was divided into six subregions to calculate the whole brain resting-state functional connectivity (rsFC). The mediating effect of the rsFC on age and emotional reactivity was then calculated. The results showed that the rsFC of the left anterior insula (AI) with the right hippocampus, and the rsFCs of the right AI with the striatum and the thalamus were mediated the relationship between positive emotional reactivity and age. Our findings suggest that attenuating emotional reactivity with age may be a strategic adaptation fostering emotional stability and diminishing emotional vulnerability. Meanwhile, the findings implicate a key role for the AI in the changes in positive emotional reactivity with age.

Aberrant positive affect dynamics in individuals with subthreshold depression: Evidence from laboratory and real-world assessments.

Background/Objective: Reduced positive affect (PA) is a core feature of major depressive disorder (MDD). However, the precursor of MDD, subthreshold depression (StD), has received less attention in this regard. Therefore, we examined PA dynamics in StD, integrating laboratory-based and ecological momentary assessment (EMA) approaches. Method: Participants were college students recruited from Chinese universities (31 with StD, and 39 healthy controls (HC)). Positive mood was induced in the laboratory by an eight-minute comedy clip used to assess PA reactivity and maintenance. To extend findings to the real world and explore mechanisms of PA maintenance, 53 participants with StD and 64 HC reported their emotional states 14 times daily for one week via EMA. Multilevel models were used to test for predictors of PA inertia. Results: In the laboratory, participants with StD achieved the same PA reactivity as HC when facing positive stimuli, yet the curve-fitting revealed difficulties for the StD group in maintaining PA over time. Such reduced capacity was further observed in real-world settings, manifesting in significantly greater PA inertia. Conclusions: High PA inertia in daily life may reflect resistance to mood change in StD, explaining anhedonia and difficulties with emotional maintenance, and highlighting the need for early identification.

Comparison of Lower and Upper Extremity Arteriovenous Graft: A Retrospective Clinical Analysis with 5-Year Follow-Up.

BACKGROUND: For patients in whom an upper extremity (UE) vascular access cannot be established, the lower extremity (LE) arteriovenous graft (AVG) could be selected. However, the application of LE AVG is limited owing to its high infection rate, uncertain patency time, and technical difficulties. This study aimed to compare the long-term patency rates and the incidence of vascular access complications of AVG in the LE and UE to provide a reference for the applications of AVG, especially in the LEs. METHODS: This was a retrospective analysis of patients who successfully underwent LE or UE AVG placement from March 2016 to October 2021. Patient characteristics were collected and compared using parameter or nonparameter tests according to data type. Postoperative patency was evaluated using Kaplan-Meier test. Postoperative complication incidence density and intergroup comparison were estimated using the Poisson distribution. RESULTS: Twenty-two patients with LE AVG and 120 patients with UE AVG were included. The 1-year primary patency rate was 67.4% (±11.0% standard error [SE]) in the LE group and 30.1% (±4.5% SE) in the UE group (P = 0.031). The assisted primary patency rate at postoperative months 12, 24, and 36 was respectively 78.6% (±9.6% SE), 65.5% (±14.4% SE), and 49.1% (±17.8% SE) in the LE group and 63.3% (±4.6% SE), 47.5% (±5.4% SE), and 30.4% (±6.1% SE) in the UE group (P = 0.137). The secondary patency rate at postoperative months 12, 24, and 36 remains 95.5% (±4.4% SE) in the LE group and 89.3% (±2.9% SE), 83.7% (±3.9% SE), and 73.0% (±6.2% SE), respectively, in the UE group (P = 0.200). Postoperative complications included stenosis, occlusion/thrombosis, infection, steal syndrome, pseudoaneurysm, severe postoperative serum swelling, and AVG exposure. The total incidence rates of postoperative complications were 0.87 (95% confidence interval [CI] 0.59-1.23) versus 1.61 (95% CI 1.45-1.79) (P = 0.001) cases/person-year, the incidence rates of stenosis were 0.45 (95% CI 0.26-0.73) versus 0.92 (95% CI 0.80-1.06) (P = 0.005) cases/person-year and the incidence rates of occlusion/thrombosis were 0.34 (95% CI 0.17-0.59) versus 0.62 (95% CI 0.52-0.74) cases/person-year in the LE group compared to those in the UE group (P = 0.041). CONCLUSIONS: LE AVG had higher primary patency rate and lower postoperative complication incidence than UE AVG. With the development of interventional technology, both LE AVG and UE AVG exhibited high secondary patency rates. LE AVG can be a reliable and long-term alternative for appropriately selected patients with unusable UE vessels.

Global-brain functional connectivity related with trait anxiety and its association with neurotransmitters and gene expression profiles.

BACKGROUND: Numerous studies have explored the neural correlates of trait anxiety, a predisposing factor for several stress-related disorders. However, the findings from previous studies are inconsistent, which might be due to the limited regions of interest (ROI). A recent approach, named global-brain functional connectivity (GBC), has been demonstrated to address the shortcomings of ROI-based analysis. Furthermore, research on the transcriptome-connectome association has provided an approach to link the microlevel transcriptome profile with the macroscale brain network. In this paper, we aim to explore the neurobiology of trait anxiety with an imaging transcriptomic approach using GBC, biological neurotransmitters, and transcriptome profiles. METHODS: Using a sample of resting-state fMRI data, we investigated trait anxiety-related alteration in GBC. We further used behavioral analysis, spatial correlation analysis, and postmortem gene expression to separately assess the cognitive functions, neurotransmitters, and transcriptional profiles related to alteration in GBC in individuals with trait anxiety. RESULTS: GBC values in the ventromedial prefrontal cortex and the precuneus were negatively correlated with levels of trait anxiety. This alteration was correlated with behavioral terms including social cognition, emotion, and memory. A strong association was revealed between trait anxiety-related alteration in GBC and neurotransmitters, including dopaminergic, serotonergic, GABAergic, and glutamatergic systems in the ventromedial prefrontal cortex and the precuneus. The transcriptional profiles explained the functional connectivity, with correlated genes enriched in transmembrane signaling. LIMITATIONS: Several limitations should be taken into account in this research. For example, future research should consider using some different approaches based on dynamic or task-based functional connectivity analysis, include more neurotransmitter receptors, additional gene expression data from different samples or more genes related to other stress-related disorders. Meanwhile, it is of great significance to include a larger sample size of individuals with a diagnosis of major depression disorder or other disorders for analysis and comparison and apply stricter multiple-comparison correction and threshold settings in future research. CONCLUSIONS: Our research employed multimodal data to investigate GBC in the context of trait anxiety and to establish its associations with neurotransmitters and transcriptome profiles. This approach may improve understanding of the neural mechanism, together with the biological and molecular genetic foundations of GBC in trait anxiety.

Continuous Spectrum of Morphologies and Phase Behavior across the Contact Zone from Poly(l-lactide) to Poly(d-lactide): Stereocomplex, Homocrystal, and Between.

The enantiomeric ratio is a key factor affecting the crystallization behavior and morphology of poly-l-lactide/poly-d-lactide (PLLA/PDLA) blends. Despite a number of studies on crystallization of nonequimolar PLLA/PDLA blends, a full picture of the effect of the L/D ratio is still lacking. Here, we put the two enantiomers in contact and allow interdiffusion above the melting point of the stereocomplex crystal (SC) to prepare samples with a continuously changing L/D ratio from enantiopure PLLA (ratio 0/100) to enantiopure PDLA (100/0). Using polarized optical microscopy, atomic force microscopy, and microbeam X-ray diffraction, the continuous spectrum of morphologies and phase behaviors across the contact zone is investigated. The blend morphology shows clear evidence of "poisoning by purity" of SC crystallization at all blend compositions. The low birefringence of the 50/50 SC is found to be due to the meandering of broken edge-on lamellae. Its further decrease to near zero as L/D deviates further away from 50/50 is explained by transition from radial edge-on lamellae to fully random meandering lamellae, then to mixed flat-on lamellae, and finally to submicron-sized axialites. In comparison with the smooth and straight homocrystal (HC) lamellae of pure enantiomers, the lamellae in the blends often have serrated edges caused by pinning by rejected excess enantiomer acting as an impurity during lamellar growth. A feature of the binary phase diagram is pure enantiomers acting as an impurity to the SC and counter-enantiomer acting as an impurity to homocrystallization of the enantiomers. Crystallization was found to be most suppressed at 99% enantiomeric purity, where the amount of the counter-enantiomer is insufficient for creation of SC nuclei and HC growth is inhibited by the small amount of the enantio-impurity. These and other intriguing results are less likely to be noticed without the continuous composition gradient of the contact sample.

The robust reciprocal relationship between loneliness and depressive symptoms among the general population: Evidence from a quantitative analysis of 37 studies.

BACKGROUND: Loneliness has long been associated with depressive symptoms, but there is no evidence on the question of "which comes first". To help us to answer this question, this study conducted a meta-analysis using a cross-lagged formula to examine the reciprocal relations between loneliness and depressive symptoms, as well as potential moderators. METHODS: The meta-analytic dataset consisted of 37 studies with sample sizes ranging from 52 to 5991. Effect sizes (including autoregressive effects and lagged coefficients) were included. We computed weighted mean effect sizes for the correlation effect and cross-lagged effect between loneliness and depressive symptoms. We also performed a meta-regression to investigate potential moderators. RESULTS: The results showed that loneliness and depressive symptoms reciprocally predicted each other over time with similar effect sizes. There was no moderation of our overall effect size in either direction by time interval between measurements, the proportion of female participants, mean age of the sample, or type of measurement. LIMITATIONS: Caution should be taken in drawing final conclusions about the relative strength of reciprocal effects between loneliness and depressive symptoms due to the potential influence of varied research focus in the included studies, which could affect the effect size. CONCLUSIONS: These findings advance the study of the relationship between loneliness and depressive symptoms by providing evidence that the link between them is symmetrically reciprocal and robust, which may help clinicians to develop effective intervention methods.

Electroacupuncture alleviates ulcerative colitis by targeting CXCL1: evidence from the transcriptome and validation.

Background: We aimed to use transcriptomics, bioinformatics analysis, and core gene validation to identify the core gene and potential mechanisms for electroacupuncture (EA) treatment of ulcerative colitis (UC). Materials and methods: EA was performed in mice after induction of UC via dextran sodium sulfate. Body weight, disease activity index (DAI), colon length, and hematoxylin-eosin of the colon tissue were used to evaluate the effects of EA. Mice transcriptome samples were analyzed to identify the core genes, and further verified with human transcriptome database; the ImmuCellAI database was used to analyze the relationship between the core gene and immune infiltrating cells (IICs); and immunofluorescence was used to verify the results. Results: EA could reduce DAI and histological colitis scores, increase bodyweight and colon length, and improve the expression of local and systemic proinflammatory factors in the serum and colon of UC mice. Eighteen co-differentially expressed genes were identified by joint bioinformatics analyses of mouse and human transcriptional data; Cxcl1 was the core gene. EA affected IICs by inhibiting Cxcl1 expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1. Conclusions: CXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ.

Low mindfulness is related to poor sleep quality from middle adolescents to emerging adults: a process model involving resilience and emotional dysfunction.

OBJECTIVES: Transitions from middle adolescence into merging adulthood, a life stage between age 15-25, has a high prevalence of sleep problems. Mindfulness is a trait defined as being attentive to the present moment which positively relates to sleep quality. In this study, we aimed to investigate how resilience and emotional dysfunction may influence the relationship between trait mindfulness and sleep quality. METHODS: The Five Facet Mindfulness Questionnaire, Connor-Davidson Resilience Scale, Pittsburgh Sleep Quality Index and Depression Anxiety Stress Scales were used to measure the key variables through an online survey of 497 participants between middle adolescence and emerging adults (317 females, mean age 18.27 ± 0.76 years). A process model was built to investigate the mediating roles of resilience and emotional dysfunction in the impact of trait mindfulness on sleep quality, together with the relationships between their specific components. RESULTS: We found a positive association between mindfulness and sleep quality through resilience and through emotional dysfunction, and through the sequential pathway from resilience to emotional dysfunction. Of note, acting with awareness (mindfulness facet) showed significant indirect effects on sleep quality, mediated by resilience and emotional dysfunction. CONCLUSIONS: Our findings may unveil the underlying mechanisms of how low mindfulness induces poor sleep quality. The findings indicate that conceiving mindfulness as a multifaceted construct facilitates comprehension of its components, relationships with other variables, and underscores its potential clinical significance given its critical implications for mental health.

Matrix metalloproteinases are key targets of acupuncture in the treatment of ulcerative colitis.

The aim of this study was to elucidate the key targets of acupuncture in the colon of ulcerative colitis (UC) mice model using full-length transcriptome sequencing. 2.5% dextran sodium sulfate (DSS)-induced colitis mice were treated with or without acupuncture. Intestinal pathology was observed, and full transcriptome sequencing and bioinformatic analysis were performed. The results demonstrated that acupuncture treatment reduced the UC symptoms, disease activity index score, and histological colitis score and increased body weight, colon length, and the number of intestinal goblet cells. In addition, acupuncture can also decrease the expression of necrotic biomarker phosphorylates mixed lineage kinase domain-like pseudo kinase (p-MLKL). Full-length transcriptome analysis indicated that acupuncture reversed the expression of 987 of the 1918 upregulated differentially expressed genes (DEGs), and 632 of the 1351 downregulated DEGs induced by DSS. DEGs regulated by acupuncture were mainly involved in inflammatory responses and intestinal barrier pathways. The protein-protein interaction network analysis revealed that matrix metalloproteinases (MMPs) are important genes regulated by acupuncture. Gene set enrichment analysis revealed that extracellular matrix (ECM)-receptor interaction was an important target of acupuncture. In addition, alternative splicing analysis suggested that acupuncture improved signaling pathways related to intestinal permeability, the biological processes of xenobiotics, sulfur compounds, and that monocarboxylic acids are closely associated with MMPs. Overall, our transcriptome analysis results indicate that acupuncture improves intestinal barrier function in UC through negative regulation of MMPs expression.

Intercultural sensitivity as a mediator in the relationship between implicit intercultural identification and emotional disturbance-An exploratory study of international high school students.

Background: Intercultural adaptation is always associated with emotional disturbances. Intercultural communication competence, as an important competence of intercultural adaptation, involves implicit intercultural identification and intercultural sensitivity. Competence in these areas promotes the process of intercultural adaptation. Little is known about the relationship between intercultural communication competence and emotional disturbances in new students attending international high schools. The intercultural adaptation process of this population requires attention because of the increasing number of high school students attending international schools, and the fact that most of these teenagers are immersed in intercultural contexts for the first time. Objective: This study aimed to investigate the prevalence of emotional disturbance in new students in an international high school and confirm the relationship among implicit intercultural identification, intercultural sensitivity, and emotional disturbances. Methods: Study 1 was an investigation of the prevalence of emotional disturbance in 105 students in their 1st year at an international high school using the Self-rating Depression Scale and Self-rating Anxiety Scale. Of these students, 34 were invited to participate in Study 2 to further explore the relationship between intercultural sensitivity, implicit intercultural identification, and emotional disturbances using the Intercultural Sensitivity Scale and Single Category Implicit Association procedure. Results: Study 1 indicated that 15.24% of students were affected by apparent depression and 10.48% had anxiety symptoms. Study 2 revealed that emotional disturbances significantly correlated with intercultural sensitivity (p < 0.01) and implicit intercultural identification (p < 0.01). The openness factor from intercultural sensitivity mediated the relationship between implicit intercultural identification and depression (ratio of indirect effect = 41.04%, p < 0.05) and anxiety symptoms (ratio of indirect effect = 34.65%, p < 0.05). Conclusion: The study revealed that a significant proportion of students in the 1st year of international high school are affected by emotional difficulties. However, intercultural communication competence is a protective factor. Enhancing the international communication competence of senior students in international high schools is important to mitigate mental health challenges.

Habenula functional connectivity variability increases with disease severity in individuals with major depression.

BACKGROUND: Increasing evidence has suggested the significant relationships between major depressive disorder (MDD) and the neural abnormalities of the Habenula (Hb). Yet, previous research on the relationships between Hb and MDD mainly focuses on the static descriptions of their functional connectivity. However, recent work suggests that the connectivity patterns are indeed dynamic, though related analysis and interpretation remain scarce. METHODS: Using seed-based resting-state fMRI, the static (sFC) and dynamic functional connectivity (dFC) between the Hb and whole-brain were calculated, including 51 clinical participants (MDDs) and 45 healthy controls (HCs). Association between the aberrant connectivity patterns and depressive symptomatology was also analyzed. RESULTS: Compared with the HCs, MDDs exhibited increased sFC from the left Hb to the right inferior temporal gyrus and left superior frontal gyrus (SFG), while sFC to the right calcarine gyrus decreased. Notably, we observed that dFC between the left Hb and the right supplementary motor area, right postcentral gyrus (PoCG), left inferior frontal gyrus as well as left occipital gyrus was weak in MDDs. Furthermore, sFC between the Hb and SFG correlated positively with the measured attention-related cognitive deficits. Importantly, there was a positive correlation between dFC between the Hb and PoCG and depressive severity. CONCLUSIONS: The findings indicate that the anomalous neural circuitry of Hb may underpin impaired attention disengagement, emotional modulation and motor inhibition associated with depressive symptoms such as rumination disposition and psychomotor retardation. This may open new avenues for studying the neuropathology mechanisms and guiding new treatment strategies for MDD.

[Effect of electroacupuncture on Notch/NF-κB signaling pathway in colonic mucosa of mice with ulcerative colitis].

OBJECTIVE: To observe the protective effect of electroacupuncture (EA) on the intestinal mucosal barrier and its relationship with the Notch/NF-κB signaling pathway in mice with ulcerative colitis (UC), so as to explore its mechanism of treating UC. METHODS: Male C57BL/6J mice were randomized into control, model and EA groups, with 6 mice in each group. The UC model was established by giving the mice with 2% Dextran Sulfate Sodium (DSS) for 7 days. EA (2 Hz/15 Hz, 0.2 mA) was applied at bilateral "Zusanli" (ST36) for 30 min, once a day for 7 days. The disease activity indexes ï¼»DAI=(body weight index score+stool score+bleeding score)/3; 0-4 pointsï¼½ of mice were calculated. The morphological changes of colonic tissues of mice in each group were observed by HE staining, and serum contents of TNF-α and IL-6 were detected by ELISA. Claudin-1 protein expression in colon tissue was detected by immunofluorescence, while the protein expression levels of Muc-2, Notch-1, MMP-9 in colon tissue were detected by immunohistochemistry. The real-time PCR method was used to detect the expression levels of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA in colon tissues. RESULTS: After modeling, the DAI, serum TNF-α and IL-6 contents, Notch-1 and MMP-9 protein expression, the relative expression levels of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA in the colonic tissue were significantly increased (P<0.001, P<0.01) in the model group relevant to the control group. At the same time, Claudin-1 and Muc-2 protein expression were significantly reduced (P<0.01). After the EA intervention, the increased DAI score, TNF-α and IL-6 contents, Notch-1 and MMP-9 protein expression, the relative expressions of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA, and the decreased Claudin-1 and Muc-2 protein expression were all reversed compared with the model group (P<0.05, P<0.01, P<0.001). H.E. staining of the colonic tissue showed damage and infiltration of inflammatory cells in the model group, and those were significantly improved in the EA group. CONCLUSION: EA can promote the recovery of intestinal mucosal barrier function and reduce inflammatory reaction in UC mice, which may be associated with its effects in inhibiting the excessive activation of the Notch/NF-κB signaling pathway.

Shared Genes of PPARG and NOS2 in Alzheimer's Disease and Ulcerative Colitis Drive Macrophages and Microglia Polarization: Evidence from Bioinformatics Analysis and Following Validation.

Emerging evidence shows that peripheral systemic inflammation, such as inflammatory bowel disease (IBD), has a close even interaction with central nervous disorders such as Alzheimer's disease (AD). This study is designed to further clarify the relationship between AD and ulcerative colitis (UC, a subclass of IBD). The GEO database was used to download gene expression profiles for AD (GSE5281) and UC (GSE47908). Bioinformatics analysis included GSEA, KEGG pathway, Gene Ontology (GO), WikiPathways, PPI network, and hub gene identification. After screening the shared genes, qRT-PCR, Western blot, and immunofluorescence were used to verify the reliability of the dataset and further confirm the shared genes. GSEA, KEGG, GO, and WikiPathways suggested that PPARG and NOS2 were identified as shared genes and hub genes by cytoHubba in AD and UC and further validated via qRT-PCR and Western blot. Our work identified PPARG and NOS2 are shared genes of AD and UC. They drive macrophages and microglia heterogeneous polarization, which may be potential targets for treating neural dysfunction induced by systemic inflammation and vice versa.

Key amino acids residues enhance the ability of CpcR to activate cry gene expression in Bacillus thuringiensis.

Typical Bacillus thuringiensis (Bt) produces one or more parasporal crystals composed of insecticidal Cry proteins during the sporulation, and the parasporal crystals and spores are produced from the same cell. Strain Bt LM1212 is different from typical Bt strains in that its crystals and spores are produced in different cells. Previous studies have found that the cell differentiation process of Bt LM1212 is related to the transcription factor CpcR which activates the cry-gene promoters. In addition, CpcR could activate the Bt LM1212 cry35-like gene promoter (P35) when introduced in the heterologous HD73- strain. It was shown that P35 was only activated in non-sporulating cells. In this study, the peptidic sequences of CpcR homologous proteins found in other strains of the Bacillus cereus group were used as references to identify two key amino acid sites for CpcR activity. The function of these amino acids was investigated by measuring P35 activation by CpcR in strain HD73-. These results will lay a foundation for the optimization of the insecticidal protein expression system in non-sporulating cells.

The prevalence and risk of developing major depression among individuals with subthreshold depression in the general population.

BACKGROUND: Subthreshold depression could be a significant precursor to and a risk factor for major depression. However, reliable estimates of the prevalence and its contribution to developing major depression under different terminologies depicting subthreshold depression have to be established. METHODS: By searching PubMed and Web of Science using predefined inclusion criteria, we included 1 129 969 individuals from 113 studies conducted. The prevalence estimates were calculated using the random effect model. The incidence risk ratio (IRR) was estimated by measuring the ratio of individuals with subthreshold depression who developed major depression compared to that of non-depressed individuals from 19 studies (88, 882 individuals). RESULTS: No significant difference in the prevalence among the different terminologies depicting subthreshold depression (Q = 1.96, p = 0.5801) was found. By pooling the prevalence estimates of subthreshold depression in 113 studies, we obtained a summary prevalence of 11.02% [95% confidence interval (CI) 9.78-12.33%]. The youth group had the highest prevalence (14.17%, 95% CI 8.82-20.55%), followed by the elderly group (12.95%, 95% CI 11.41-14.58%) and the adult group (8.92%, 95% CI 7.51-10.45%). Further analysis of 19 studies' incidence rates showed individuals with subthreshold depression had an increased risk of developing major depression (IRR = 2.95, 95% CI 2.33-3.73), and the term minor depression showed the highest IRR compared with other terms (IRR = 3.97, 95% CI 3.17-4.96). CONCLUSIONS: Depression could be a spectrum disorder, with subthreshold depression being a significant precursor to and a risk factor for major depression. Proactive management of subthreshold depression could be effective for managing the increasing prevalence of major depression.