Microbial nitrogen cycling in Microcystis colonies and its contribution to nitrogen removal in eutrophic Lake Taihu, China.

Cyanobacterial blooms induced by excessive loadings of nitrogen (N) and other nutrients are a severe ecological problem in aquatic ecosystems. Previous studies of N removal have primarily focused on sediment-water interface, yet the role of cyanobacterial colonies has recently been attracting more research attention. In this study, N cycling processes were quantified for cyanobacterial colonies (primarily Microcystis colonies) and their contribution to N removal was estimated for a large, shallow eutrophic lake in China, Lake Taihu. Various N cycling processes were determined via stable 15N isotope, together with 16S rRNA gene sequencing and quantitative microbial element cycling (QMEC) chip. Denitrification was found to be the most prominent process, estimated to be 36.63, 9.85, 3.35, and 3.15 times higher than dissimilatory nitrate reduction to ammonium (DNRA), nitrification, ammonium (NH4+) uptake and nitrate (NO3-) uptake rates, respectively. Denitrifiers accounted for a large part of the bacterial taxa (35.50 ± 24.65%), and the nirS gene was the most abundant among N cycling-related genes, with (2.54 ± 0.51) × 109 copies g-1Microcystis colonies. A field investigation revealed a positive correlation between the potential denitrification rate and the Chl-a concentration (mostly derived from Microcystis colonies). Based on a multiple stepwise regression model and historical data from 2007 to 2015 for Lake Taihu, the total amount of N removed via denitrification by Microcystis colonies was estimated at 171.72 ± 49.74 t yr-1; this suggests that Microcystis colonies have played an important role in N removal in Lake Taihu since the drinking water crisis in 2007. Overall, this study revealed the importance of denitrification within Microcystis colonies for N removal in eutrophic lakes, like Lake Taihu.

Influence of panic disorder and paroxetine on brain functional hubs in drug-free patients.

BACKGROUND: The effects of panic disorder (PD) and pharmacotherapy on brain functional hubs in drug-free patients, and the utility of their degree centrality (DC) in diagnosing and predicting treatment response (TR) for PD, remained unclear. AIMS: This study aimed to assess the effects of PD and paroxetine on brain functional hubs in drug-free patients and to identify neuroimaging biomarkers for diagnosing and predicting TR in patients with PD. METHODS: Imaging data from 54 medication-free PD patients and 54 matched healthy controls (HCs) underwent DC and functional connectivity (FC) analyses before and after a 4-week paroxetine treatment. Diagnosis and prediction of TR models for PD were constructed using support vector machine (SVM) and support vector regression (SVR), with DC as features. RESULTS: Patients with PD showed aberrant DC and FC in the anterior cingulum, temporal, and occipital areas compared with HCs at baseline. After treatment, DC of the patients increased in the calcarine cortex, lingual gyrus, and cerebellum IV/V, along with improved clinical symptoms. Utilizing voxel-wise DC values at baseline, the SVM effectively distinguished patients with PD from HCs with an accuracy of 83.33%. In SVR, the predicted TR significantly correlated with the observed TR (correlation coefficient (r) = 0.893, Mean Squared Error = 0.009). CONCLUSION: Patients with PD exhibited abnormal DC and FC, notably in the limbic network, temporal, and occipital regions. Paroxetine ameliorated patients' symptoms while altering their brain FC. SVM and SVR models, utilizing baseline DC, effectively distinguished the patients from HCs and accurately predicted TR.

Diminished functional segregation and resilience are associated with symptomatic severity and cognitive impairments in schizophrenia: a large-scale study.

Background: The research findings on the topological properties of functional connectomes (TP-FCs) in patients with schizophrenia (SZPs) exhibit inconsistencies and contradictions, which can be attributed to limitations such as small sample sizes and heterogeneous data processing techniques. Aims: To address these limitations, we conducted a large-scale study. Uniform data processing flows were employed to investigate the aberrant TP-FCs and the associations between TP-FCs and symptoms or cognitions (A-TP-SCs) in SZPs. Methods: The large-scale study included six datasets from four sites, involving 497 SZPs and 374 healthy controls (HCs). A uniform process for imaging data preprocessing and functional connectivity matrix configuration was used. ComBat was employed for data harmonisation, and various TPs were calculated. We explored between-group differences in brain functional integration (FI) and functional segregation (FS) measured with TP-FCs, and conducted partial correlation analyses, with adjustments for age, gender and educational level, to identify A-TP-SCs. Results: Compared with random networks and HCs, SZPs maintained small-worldness and global FI capacity despite their compromised global FS capacity and resilience. A decline in nodal FI and FS capacity was observed in sensory areas, whereas an increase in nodal FI capacity was found in regions associated with cognition and information integration. In addition, associations between TP-FCs and positive symptoms, negative symptoms or cognitive functions including speed of processing, visual learning and the ability to inhibit cognitive interference were identified in SZPs. Conclusions: The identified A-TP-SCs verified that reductions in FS and resilience indicated pathological impairments in schizophrenia. The A-TP-SCs or TP-FCs, which measured the same attributes of the functional connectomes, exhibited high internal consistency, robustly reinforcing these findings.

Methylparaben changes the community composition, structure, and assembly processes of free-living bacteria, phytoplankton, and zooplankton.

Parabens are common contaminants in river and lake environments. However, few studies have been conducted to determine the effects of parabens on bacteria, phytoplankton, and zooplankton communities in aquatic environments. In this study, the effect of methylparaben (MP) on the diversity and community structure of the aquatic plankton microbiome was investigated by incubating a microcosm with MP at 0.1, 1, 10, and 100 µg/L for 7 days. The results of the Simpson index showed that MP treatment altered the α-diversity of free-living bacteria (FL), phytoplankton, and zooplankton but had no significant effect on the α-diversity of particle-attached bacteria (PA). Further, the relative abundances of the sensitive bacteria Chitinophaga and Vibrionimonas declined after MP addition. Moreover, the relative abundances of Desmodesmus sp. HSJ717 and Scenedesmus armatus, of the phylum Chlorophyta, were significantly lower in the MP treatment group than in the control group. In addition, the relative abundance of Stoeckeria sp. SSMS0806, of the Dinophyta phylum, was higher than that in the control group. MP addition also increased the relative abundance of Arthropoda but decreased the relative abundance of Rotifera and Ciliophora. The ß-diversity analysis showed that FL and phytoplankton communities were clustered separately after treatment with different MP concentrations. MP addition changed community assembly mechanisms in the microcosm, including increasing the stochastic processes for FL and the deterministic processes for PA and phytoplankton. Structural equation modeling analysis showed a significant negative relationship between bacteria richness and phytoplankton richness, and a significant positive relationship between phytoplankton (richness and community composition) and zooplankton. Overall, this study emphasizes that MP, at environmental concentrations, can change the diversity and structure of plankton microbial communities, which might have a negative effect on ecological systems.

Disrupted brain functional asymmetry at rest in patients with major depressive disorder associated with sleep disturbances.

Sleep disturbances (SD) are common in major depressive disorder (MDD) patients. Brain functional asymmetry is crucial for understanding MDD pathophysiology. Previous studies using the parameter of asymmetry (PAS) approach have found brain functional asymmetry disruption in MDD. However, this has not been explored in MDD patients with SD. This study examined 26 MDD patients with SD, 34 MDD patients without SD, and 34 healthy controls using resting-state functional magnetic resonance imaging scans. SD symptoms were quantified using the 17-item Hamilton Rating Scale for Depression. PAS approach was used to evaluate functional asymmetry. MDD patients with SD displayed increased PAS in the left middle frontal gyrus (MFG)/inferior frontal gyrus (IFG) and decreased PAS in the left parahippocampal gyrus (PHG) compared to MDD patients without SD. Increased PAS in the left MFG/IFG was positively correlated with SD severity, and a negative correlation was found between decreased PAS in the left PHG and SD scores in all MDD patients. Receiver operating characteristic analysis indicated that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may serve as potential neuroimaging markers to differentiate MDD patients with SD from those without SD with Area Under Curve values of 0.8157 and 0.8068, respectively. These results highlighted that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may be considered a prominent feature associated with SD symptoms of MDD patients, potentially serving as imaging markers to discriminate between MDD patients with and without SD.

The physiological and pathological roles of RNA modifications in T cells.

RNA molecules undergo dynamic chemical modifications in response to various external or cellular stimuli. Some of those modifications have been demonstrated to post-transcriptionally modulate the RNA transcription, localization, stability, translation, and degradation, ultimately tuning the fate decisions and function of mammalian cells, particularly T cells. As a crucial part of adaptive immunity, T cells play fundamental roles in defending against infections and tumor cells. Recent findings have illuminated the importance of RNA modifications in modulating T cell survival, proliferation, differentiation, and functional activities. Therefore, understanding the epi-transcriptomic control of T cell biology enables a potential avenue for manipulating T cell immunity. This review aims to elucidate the physiological and pathological roles of internal RNA modifications in T cell development, differentiation, and functionality drawn from current literature, with the goal of inspiring new insights for future investigations and providing novel prospects for T cell-based immunotherapy.

Neural substrates of predicting anhedonia symptoms in major depressive disorder via connectome-based modeling.

MAIN PROBLEM: Anhedonia is a critical diagnostic symptom of major depressive disorder (MDD), being associated with poor prognosis. Understanding the neural mechanisms underlying anhedonia is of great significance for individuals with MDD, and it encourages the search for objective indicators that can reliably identify anhedonia. METHODS: A predictive model used connectome-based predictive modeling (CPM) for anhedonia symptoms was developed by utilizing pre-treatment functional connectivity (FC) data from 59 patients with MDD. Node-based FC analysis was employed to compare differences in FC patterns between melancholic and non-melancholic MDD patients. The support vector machines (SVM) method was then applied for classifying these two subtypes of MDD patients. RESULTS: CPM could successfully predict anhedonia symptoms in MDD patients (positive network: r = 0.4719, p < 0.0020, mean squared error = 23.5125, 5000 iterations). Compared to non-melancholic MDD patients, melancholic MDD patients showed decreased FC between the left cingulate gyrus and the right parahippocampus gyrus (p_bonferroni = 0.0303). This distinct FC pattern effectively discriminated between melancholic and non-melancholic MDD patients, achieving a sensitivity of 93.54%, specificity of 67.86%, and an overall accuracy of 81.36% using the SVM method. CONCLUSIONS: This study successfully established a network model for predicting anhedonia symptoms in MDD based on FC, as well as a classification model to differentiate between melancholic and non-melancholic MDD patients. These findings provide guidance for clinical treatment.

Cerebellar functional connectivity and its associated genes: A longitudinal study in drug-naive patients with obsessive-compulsive disorder.

The role of cerebellar-cerebral functional connectivity (CC-FC) in obsessive-compulsive disorder (OCD), its trajectory post-pharmacotherapy, and its potential as a prognostic biomarker and genetic mechanism remain uncertain. To address these gaps, this study included 37 drug-naive OCD patients and 37 healthy controls (HCs). Participants underwent baseline functional magnetic resonance imaging (fMRI), followed by four weeks of paroxetine treatment for patients with OCD, and another fMRI scan post-treatment. We examined seed-based CC-FC differences between the patients and HCs, and pre- and post-treatment patients. Support vector regression (SVR) based on CC-FC was performed to predict treatment response. Correlation analysis explored associations between CC-FC and clinical features, as well as gene profiles. Compared to HCs, drug-naive OCD patients exhibited reduced CC-FC in executive, affective-limbic, and sensorimotor networks, with specific genetic profiles associated with altered CC-FC. Gene enrichment analyses highlighted the involvement of these genes in various biological processes, molecular functions, and pathways. Post-treatment, the patients showed partial clinical improvement and partial restoration of the previously decreased CC-FC. Abnormal CC-FC at baseline correlated negatively with compulsions severity and social functional impairment, while changes in CC-FC correlated with cognitive function changes post-treatment. CC-FC emerged as a potential predictor of symptom severity in patients following paroxetine treatment. This longitudinal resting-state fMRI study underscores the crucial role of CC-FC in the neuropsychological mechanisms of OCD and its pharmacological treatment. Transcriptome-neuroimaging spatial correlation analyses provide insight into the neurobiological mechanisms underlying OCD pathology. Furthermore, SVR analyses hold promise for advancing precision medicine approaches in treating patients with OCD.

Fluid dynamics and leukocyte transit in the lymphatic system.

The lymphatic system plays a vital role in maintaining fluid balance in living tissue and serves as a pathway for the transport of antigen, immune cells, and metastatic cancer cells. In this study, we investigate how the movement of cells through a contracting lymphatic vessel differs from steady flow, using a lattice Boltzmann-based computational model. Our model consists of cells carried by flow in a 2D vessel with regularly spaced, bi-leaflet valves that ensure net downstream flow as the vessel walls contract autonomously in response to calcium and nitric oxide levels regulated by stretch and shear stress levels. The orientation of the vessel with respect to gravity, which may oppose or assist fluid flow, significantly modulates cellular motion due to its effect on the contraction dynamics of the vessel, even when the cells themselves are neutrally buoyant. Additionally, our model shows that cells are carried along with the flow, but when the vessel is actively contracting, they move faster than the average fluid velocity. We also find that the fluid forces cause significant deformation of the compliant cells, especially in the vicinity of the valves. Our study highlights the importance of considering the complex, transient flows near the valves in understanding cellular motion in lymphatic vessels.

Association between abnormal default mode network homogeneity and sleep disturbances in major depressive disorder.

Background: Sleep disturbance is a common comorbidity of major depressive disorder (MDD). However, network homogeneity (NH) changes of the default mode network (DMN) in MDD with sleep disturbances are unclear. Aims: The purpose of this study was to probe the abnormal NH in the DMN in MDD with sleep disturbances and to reveal the differences between MDD with or without sleep disturbances. Methods: Twenty-four patients with MDD and sleep disturbances (Pa_s), 33 patients with MDD without sleep disturbances (Pa_ns) and 32 healthy controls (HCs) were recruited in this study. Resting-state functional imaging data were analysed using NH. Results: Compared with Pa_ns and HCs, Pa_s showed decreased NH in the left superior medial prefrontal cortex and increased NH in the right precuneus. There was a negative correlation between NH in the left superior medial prefrontal cortex and sleep disturbances (r=-0.42, p=0.001) as well as a positive correlation between NH in the right precuneus and sleep disturbances (r=0.41, p=0.002) in patients with MDD. Conclusions: MDD with sleep disturbances is associated with abnormal NH in the DMN, which could differentiate pa_s from pa_ns. The DMN may play a crucial role in the neurobiological mechanisms of MDD with sleep disturbances.

Similar imaging changes and their relations to genetic profiles in bipolar disorder across different clinical stages.

Bipolar disorder (BD) across different clinical stages may present shared and distinct changes in brain activity. We aimed to reveal the neuroimaging homogeneity and heterogeneity of BD and its relationship with clinical variables and genetic variations. In present study, we conducted fractional amplitude of low-frequency fluctuations (fALFF), functional connectivity (FC) and genetic neuroimaging association analyses with 32 depressed, 26 manic, 35 euthymic BD patients and 87 healthy controls (HCs). Significant differences were found in the bilateral pre/subgenual anterior cingulate cortex (ACC) across the four groups, and all bipolar patients exhibited decreased fALFF values in the ACC when compared to HCs. Furthermore, positive associations were significantly observed between fALFF values in the pre/subgenual ACC and participants' cognitive functioning. No significant changes were found in ACC-based FC. We identified fALFF-alteration-related genes in BD, with enrichment in biological progress including synaptic and ion transmission. Taken together, abnormal activity in ACC is a characteristic change associated with BD, regardless of specific mood stages, serving as a potential neuroimaging feature in BD patients. Our genetic neuroimaging association analysis highlights possible heterogeneity in biological processes that could be responsible for different clinical stages in BD.

Arginine-methylated c-Myc affects mitochondrial mitophagy in mouse acute kidney injury via Slc25a24.

The transcription factor methylated c-Myc heterodimerizes with MAX to modulate gene expression, and plays an important role in energy metabolism in kidney injury but the exact mechanism remains unclear. Mitochondrial solute transporter Slc25a24 imports ATP into mitochondria and is central to energy metabolism. Gene Expression Omnibus data analysis reveals Slc25a24 and c-Myc are consistently upregulated in all the acute kidney injury (AKI) cells. Pearson correlation analysis also shows that Slc25a24 and c-Myc are strongly correlated (⍴ > 0.9). Mutant arginine methylated c-Myc (R299A and R346A) reduced its combination with MAX when compared with the wild type of c-Myc. On the other hand, the Slc25a24 levels were also correspondingly reduced, which induced the downregulation of ATP production. The results promoted reactive oxygen species (ROS) production and mitophagy generation. The study revealed that the c-Myc overexpression manifested the most pronounced mitochondrial DNA depletion. Additionally, the varied levels of mitochondrial proteins like TIM23, TOM20, and PINK1 in each group, particularly the elevated levels of PINK1 in AKI model groups and lower levels of TIM23 and TOM20 in the c-Myc overexpression group, suggest potential disruptions in mitochondrial dynamics and homeostasis, indicating enhanced mitophagy or mitochondrial loss. Therefore, arginine-methylated c-Myc affects mouse kidney injury by regulating mitochondrial ATP and ROS, and mitophagy via Slc25a24.

FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity.

Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. On the contrary, the decreased IFITM3 expression in STAT1-deficient Tregs indicates that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of tumor-infiltrating Tregs in the tumor model. Overall, our study demonstrates that the perturbation of tumor-infiltrating Tregs through the IFNγ-IFITM3-STAT1 feedback loop is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy.

Altered interhemispheric functional connectivity in patients with obsessive-compulsive disorder and its potential in therapeutic response prediction.

The trajectory of voxel-mirrored homotopic connectivity (VMHC) after medical treatment in obsessive-compulsive disorder (OCD) and its value in prediction of treatment response remains unclear. This study aimed to investigate the pathophysiological mechanism of OCD, as well as biomarkers for prediction of pharmacological efficacy. Medication-free patients with OCD and healthy controls (HCs) underwent magnetic resonance imaging. The patients were scanned again after a 4-week treatment with paroxetine. The acquired data were subjected to VMHC, support vector regression (SVR), and correlation analyses. Compared with HCs (36 subjects), patients with OCD (34 subjects after excluding two subjects with excessive head movement) exhibited significantly lower VMHC in the bilateral superior parietal lobule (SPL), postcentral gyrus, and calcarine cortex, and VMHC in the postcentral gyrus was positively correlated with cognitive function. After treatment, the patients showed increased VMHC in the bilateral posterior cingulate cortex/precuneus (PCC/PCu) with the improvement of symptoms. SVR results showed that VMHC in the postcentral gyrus at baseline could aid to predict a change in the scores of OCD scales. This study revealed that SPL, postcentral gyrus, and calcarine cortex participate in the pathophysiological mechanism of OCD while PCC/PCu participate in the pharmacological mechanism. VMHC in the postcentral gyrus is a potential predictive biomarker of the treatment effects in OCD.

The crosstalk between enteric nervous system and immune system in intestinal development, homeostasis and diseases.

The gut is the largest digestive and absorptive organ, which is essential for induction of mucosal and systemic immune responses, and maintenance of metabolic-immune homeostasis. The intestinal components contain the epithelium, stromal cells, immune cells, and enteric nervous system (ENS), as well as the outers, such as gut microbiota, metabolites, and nutrients. The dyshomeostasis of intestinal microenvironment induces abnormal intestinal development and functions, even colon diseases including dysplasia, inflammation and tumor. Several recent studies have identified that ENS plays a crucial role in maintaining the immune homeostasis of gastrointestinal (GI) microenvironment. The crosstalk between ENS and immune cells, mainly macrophages, T cells, and innate lymphoid cells (ILCs), has been found to exert important regulatory roles in intestinal tissue programming, homeostasis, function, and inflammation. In this review, we mainly summarize the critical roles of the interactions between ENS and immune cells in intestinal homeostasis during intestinal development and diseases progression, to provide theoretical bases and ideas for the exploration of immunotherapy for gastrointestinal diseases with the ENS as potential novel targets.

Abnormal regional activity in the prefrontal-limbic circuit at rest: Potential imaging markers and treatment predictors in drug-naive anxiety disorders.

BACKGROUND: Previous research has identified functional impairments within the prefrontal-limbic circuit in individuals with anxiety disorders. However, the link between these deficiencies, clinical symptoms, and responses to antipsychotic treatment is still not fully understood. This study aimed to investigate abnormal regional activity within the prefrontal-limbic circuit among drug-naive individuals diagnosed with generalized anxiety disorder (GAD) and panic disorder (PD) and to analyze changes following treatment. METHODS: Resting-state magnetic resonance imaging was performed on a cohort of 118 anxiety disorder patients (64 GAD, 54 PD) and 61 healthy controls (HCs) at baseline. Among them, 52 patients with GAD and 44 patients with PD underwent a 4-week treatment regimen of paroxetine. Fractional amplitude of low-frequency fluctuation (fALFF) measurements and pattern classification techniques were employed to analyze the data in accordance with the human Brainnetome atlas. RESULTS: Both patients with GAD and PD demonstrated decreased fALFF in the right cHipp subregion of the hippocampus and increased fALFF in specified subregions of the cingulate and orbitofrontal lobe. Notably, patients with PD exhibited significantly higher fALFF in the left A24cd subregion compared to patients with GAD, while other ROI subregions showed no significant variations between the two patient groups. Whole-brain analysis revealed abnormal fALFF in both patient groups, primarily in specific areas of the cingulate and parasingulate gyrus, as well as the inferior and medial orbitofrontal gyrus (OFG). Following a 4-week treatment period, specific subregions in the GAD and PD groups showed a significant decrease in fALFF. Further analysis using support vector regression indicated that fALFF measurements in the right A13 and right A24cd subregions may be predictive of treatment response among anxiety disorder patients. CONCLUSIONS: Aberrant functional activity in certain subregions of the prefrontal-limbic circuit appears to be linked to the manifestation of anxiety disorders. These findings suggest potential imaging indicators for individual responses to antipsychotic treatment.

Enhanced interhemispheric resting-state functional connectivity of the visual network is an early treatment response of paroxetine in patients with panic disorder.

This study aimed to detect alterations in interhemispheric interactions in patients with panic disorder (PD), determine whether such alterations could serve as biomarkers for the diagnosis and prediction of therapeutic outcomes, and map dynamic changes in interhemispheric interactions in patients with PD after treatment. Fifty-four patients with PD and 54 healthy controls (HCs) were enrolled in this study. All participants underwent clinical assessment and a resting-state functional magnetic resonance imaging scan at (i) baseline and (ii) after paroxetine treatment for 4 weeks. A voxel-mirrored homotopic connectivity (VMHC) indicator, support vector machine (SVM), and support vector regression (SVR) were used in this study. Patients with PD showed reduced VMHC in the fusiform, middle temporal/occipital, and postcentral/precentral gyri, relative to those of HCs. After treatment, the patients exhibited enhanced VMHC in the lingual gyrus, relative to the baseline data. The VMHC of the fusiform and postcentral/precentral gyri contributed most to the classification (accuracy = 87.04%). The predicted changes were accessed from the SVR using the aberrant VMHC as features. Positive correlations (p < 0.001) were indicated between the actual and predicted changes in the severity of anxiety. These findings suggest that impaired interhemispheric coordination in the cognitive-sensory network characterized PD and that VMHC can serve as biomarkers and predictors of the efficiency of PD treatment. Enhanced VMHC in the lingual gyrus of patients with PD after treatment implied that pharmacotherapy recruited the visual network in the early stages.

Microcystis blooms caused the decreasing richness of and interactions between free-living microbial functional genes in Lake Taihu, China.

Microcystis blooms have a marked effect on microbial taxonomical diversity in eutrophic lakes, but their influence on the composition of microbial functional genes is still unclear. In this study, the free-living microbial functional genes (FMFG) composition was investigated in the period before Microcystis blooms (March) and during Microcystis blooms (July) using a comprehensive functional gene array (GeoChip 5.0). The composition and richness of FMFG in the water column was significantly different between these two periods. The FMFG in March was enriched in the functional categories of nitrogen, sulfur, and phosphorus cycling, whereas the FMFG in July was enriched in carbon cycling, organic remediation, and metal homeostasis. Molecular ecological network analysis further demonstrated fewer functional gene interactions and reduced complexity in July than in March. Module hubs of the March network were mediated by functional genes associated with carbon, nitrogen, sulfur, and phosphorus, whereas those in July by a metal homeostasis functional gene. We also observed stronger deterministic processes in the FMFG assembly in July than in March. Collectively, this study demonstrated that Microcystis blooms induced significant changes in FMFG composition and metabolic potential, and abundance-information, which can support the understanding and management of biogeochemical cycling in eutrophic lake ecosystems.

Shared and distinctive dysconnectivity patterns underlying pure generalized anxiety disorder (GAD) and comorbid GAD and depressive symptoms.

The resting-state connectivity features underlying pure generalized anxiety disorder (GAD, G1) and comorbid GAD and depressive symptoms (G2) have not been directly compared. Furthermore, it is unclear whether these features might serve as potential prognostic biomarkers and change with treatment. Degree centrality (DC) in G1 (40 subjects), G2 (58 subjects), and healthy controls (HCs, 54 subjects) was compared before treatment, and the DC of G1 or G2 at baseline was compared with that after 4 weeks of paroxetine treatment. Using support vector regression (SVR), voxel-wise DC across the entire brain and abnormal DC at baseline were employed to predict treatment response. At baseline, G1 and G2 exhibited lower DC in the left mid-cingulate cortex and vermis IV/V compared to HCs. Additionally, compared to HCs, G1 had lower DC in the left middle temporal gyrus, while G2 showed higher DC in the right inferior temporal/fusiform gyrus. However, there was no significant difference in DC between G1 and G2. The SVR based on abnormal DC at baseline could successfully predict treatment response in responders in G2 or in G1 and G2. Notably, the predictive performance based on abnormal DC at baseline surpassed that based on DC across the entire brain. After treatment, G2 responders showed lower DC in the right medial orbital frontal gyrus, while no change in DC was identified in G1 responders. The G1 and G2 showed common and distinct dysconnectivity patterns and they could potentially serve as prognostic biomarkers. Furthermore, DC in patients with GAD could change with treatment.

Shared and distinctive neural substrates of generalized anxiety disorder with or without depressive symptoms and their roles in prognostic prediction.

BACKGROUND: The neurophysiological mechanisms underlying generalized anxiety disorder (GAD) with or without depressive symptoms are obscure. This study aimed to uncover them and assess their predictive value for treatment response. METHODS: We enrolled 98 GAD patients [58 (age: 33.22 ± 10.23 years old, males/females: 25/33) with and 40 (age: 33.65 ± 10.49 years old, males/females: 14/26) without depressive symptoms] and 54 healthy controls (HCs, age: 32.28 ± 10.56 years old, males/females: 21/33). Patients underwent clinical assessments and resting-state functional MRI (rs-fMRI) at baseline and after 4-week treatment with paroxetine, while HCs underwent rs-fMRI at baseline only. Regional homogeneity (ReHo) was employed to measure intrinsic brain activity. We compared ReHo in patients to HCs and examined changes in ReHo within the patient groups after treatment. Support vector regression (SVR) analyses were conducted separately for each patient group to predict the patients' treatment response. RESULTS: Both patient groups exhibited higher ReHo in the middle/superior frontal gyrus decreased ReHo in different brain regions compared to HCs. Furthermore, differences in ReHo were detected between the two patient groups. After treatment, the patient groups displayed distinct ReHo change patterns. By utilizing SVR based on baseline abnormal ReHo, we effectively predicted treatment response of patients (p-value for correlation < 0.05). LIMITATIONS: The dropout rate was relatively high. CONCLUSIONS: This study identified shared and unique neural substrates in GAD patients with or without depressive symptoms, potentially serving as biomarkers for treatment response prediction. Comorbid depressive symptoms were associated with differences in disease manifestation and treatment response compared to pure GAD cases.