The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

Unraveling the link between childhood maltreatment and depression: Insights from the role of ventral striatum and middle cingulate cortex in hedonic experience and emotion regulation.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

Dapagliflozin Ameliorates Ovulation Disorders via Attenuating Activated Microglia-Mediated Hypothalamic Inflammation in HFD-Fed Mice.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation. METHODS: C57BL/6J female mice fed HFD were treated with dapagliflozin (1 mg/kg) for 22 weeks. Plasma insulin, leptin, luteinizing hormone (LH), estradiol (E2), and IL-1ß levels were also tested. Microglial morphology, cell numbers, and SGLT2 expression were evaluated using immunofluorescence. The expression of IL-1ß, NLRP3, kisspeptin, gonadotropin-releasing hormone (GnRH), SGLT2, insulin, and leptin receptors in the hypothalamus was determined using immunohistochemical staining. We also examined the effects of dapagliflozin on glucose metabolism and the release of inflammatory factor in palmitic acid (PA)-treated HMC3 cells. RESULTS: As expected, dapagliflozin improved HFD-induced metabolic disturbances, peripheral versus central insulin and leptin resistance and also restored the regular estrous cycle. Furthermore, dapagliflozin blunted microglia activation, NLRP3 inflammasome priming, hypothalamic inflammation, and increased the expression of GnRH and kisspeptin at proestrus in the hypothalamus. Additionally, dapagliflozin markedly reduced IL-6 and NO release and fat accumulation, decreased lactic acid production and glucose consumption, and inhibited mammalian target of rapamycin (mTOR) and hexokinase 2 (HK2) expression in PA-treated HMC3 cells. These effects suggest that dapagliflozin reduced the mTOR/HK2-mediated aerobic glycolysis. CONCLUSIONS: Dapagliflozin improved HFD-related ovulation disorders by regulating glucose metabolism through mTOR/HK2 signaling and attenuating microglia-mediated hypothalamic inflammation. These results validate the novel role for the neuroprotection of SGLT2i in HFD-induced obesity and ovulation disorders.

E3 ligase ATL5 positively regulates seed longevity by mediating the degradation of ABT1 in Arabidopsis.

Ubiquitination is a fundamental mechanism regulating the stability of target proteins in eukaryotes; however, the regulatory mechanism in seed longevity remains unknown. Here, we report that an uncharacterized E3 ligase, ARABIDOPSIS TÓXICOS EN LEVADURA 5 (ATL5), positively regulates seed longevity by mediating the degradation of ACTIVATOR OF BASAL TRANSCRIPTION 1 (ABT1) in Arabidopsis. Seeds in which ATL5 was disrupted showed faster accelerated aging than the wild-type, while expressing ATL5 in atl5-2 basically restored the defective phenotype. ATL5 was highly expressed in the embryos of seeds, and its expression could be induced by accelerated aging. A yeast two-hybrid screen identified ABT1 as an ATL5 interacting protein, which was further confirmed by bimolecular fluorescence complementary assay and co-immunoprecipitation analysis. In vitro and in vivo assays showed that ATL5 functions as an E3 ligase and mediates the polyubiquitination and degradation of ABT1. Disruption of ATL5 diminished the degradation of translated ABT1, and the degradation could be induced by seed ageing and occurred in a proteasome-dependent manner. Furthermore, disruption of ABT1 enhanced seed longevity. Taken together, our study reveals that ATL5 promotes the polyubiquitination and degradation of the ABT1 protein posttranslationally and positively regulates seed longevity in Arabidopsis.

Neuroimaging prognostic factors for treatment response to motor imagery training after stroke.

The efficacy of motor imagery training for motor recovery is well acknowledged, but with substantial inter-individual variability in stroke patients. To help optimize motor imagery training therapy plans and screen suitable patients, this study aimed to explore neuroimaging biomarkers explaining variability in treatment response. Thirty-nine stroke patients were randomized to a motor imagery training group (n = 22, received a combination of conventional rehabilitation therapy and motor imagery training) and a control group (n = 17, received conventional rehabilitation therapy and health education) for 4 weeks of interventions. Their demography and clinical information, brain lesion from structural MRI, spontaneous brain activity and connectivity from rest fMRI, and sensorimotor brain activation from passive motor task fMRI were acquired to identify prognostic factors. We found that the variability of outcomes from sole conventional rehabilitation therapy could be explained by the reserved sensorimotor neural function, whereas the variability of outcomes from motor imagery training + conventional rehabilitation therapy was related to the spontaneous activity in the ipsilesional inferior parietal lobule and the local connectivity in the contralesional supplementary motor area. The results suggest that additional motor imagery training treatment is also efficient for severe patients with damaged sensorimotor neural function, but might be more effective for patients with impaired motor planning and reserved motor imagery.

Activity flow mapping over probabilistic functional connectivity.

Emerging evidence indicates that activity flow over resting-state network topology allows the prediction of task activations. However, previous studies have mainly adopted static, linear functional connectivity (FC) estimates as activity flow routes. It is unclear whether an intrinsic network topology that captures the dynamic nature of FC can be a better representation of activity flow routes. Moreover, the effects of between- versus within-network connections and tight versus loose (using rest baseline) task contrasts on the prediction of task-evoked activity across brain systems remain largely unknown. In this study, we first propose a probabilistic FC estimation derived from a dynamic framework as a new activity flow route. Subsequently, activity flow mapping was tested using between- and within-network connections separately for each region as well as using a set of tight task contrasts. Our results showed that probabilistic FC routes substantially improved individual-level activity flow prediction. Although it provided better group-level prediction, the multiple regression approach was more dependent on the length of data points at the individual-level prediction. Regardless of FC type, we consistently observed that between-network connections showed a relatively higher prediction performance in higher-order cognitive control than in primary sensorimotor systems. Furthermore, cognitive control systems exhibit a remarkable increase in prediction accuracy with tight task contrasts and a decrease in sensorimotor systems. This work demonstrates that probabilistic FC estimates are promising routes for activity flow mapping and also uncovers divergent influences of connectional topology and task contrasts on activity flow prediction across brain systems with different functional hierarchies.

Pathway-Specific Mediation Effect Between Structure, Function, and Motor Impairment After Subcortical Stroke.

BACKGROUND AND OBJECTIVE: To investigate the pathway-specific correspondence between structural and functional changes resulting from focal subcortical stroke and their causal influence on clinical symptom. METHODS: In this retrospective, cross-sectional study, we mainly focused on patients with unilateral subcortical chronic stroke with moderate-severe motor impairment assessed by Fugl-Meyer Assessment (upper extremity) and healthy controls. All participants underwent both resting-state fMRI and diffusion tensor imaging. To parse the pathway-specific structure-function covariation, we performed association analyses between the fine-grained corticospinal tracts (CSTs) originating from 6 subareas of the sensorimotor cortex and functional connectivity (FC) of the corresponding subarea, along with the refined corpus callosum (CC) sections and interhemispheric FC. A mediation analysis with FC as the mediator was used to further assess the pathway-specific effects of structural damage on motor impairment. RESULTS: Thirty-five patients (mean age 52.7 ± 10.2 years, 27 men) and 43 healthy controls (mean age 56.2 ± 9.3 years, 21 men) were enrolled. Among the 6 CSTs, we identified 9 structurally and functionally covaried pathways, originating from the ipsilesional primary motor area (M1), dorsal premotor area (PMd), and primary somatosensory cortex (p < 0.05, corrected). FC for the bilateral M1, PMd, and ventral premotor cortex covaried with secondary degeneration of the corresponding CC sections (p < 0.05, corrected). Moreover, these covarying structures and functions were significantly correlated with the Fugl-Meyer Assessment (upper extremity) scores (p < 0.05, uncorrected). In particular, FC between the ipsilesional PMd and contralesional cerebellum (ß = -0.141, p < 0.05, CI = [-0.319 to -0.015]) and interhemispheric FC of the PMd (ß = 0.169, p < 0.05, CI = [0.015-0.391]) showed significant mediation effects in the prediction of motor impairment with structural damage of the CST and CC. DISCUSSIONS: This study reveals causal influence of structural and functional pathways on motor impairment after subcortical stroke and provides a promising way to investigate pathway-specific structure-function coupling. Clinically, our findings may offer a circuit-based evidence for the PMd as a critical neuromodulation target in more impaired patients with stroke and also suggest the cerebellum as a potential target.

Motor function and fALFF modulation in convalescent-period ischemic stroke patients after scalp acupuncture therapy: a multi-centre randomized controlled trial.

BACKGROUND: Scalp acupuncture has been found to be effective at improving motor function after ischemic stroke, but few studies examining its central mechanisms of action have been carried out. The aim of this study was to investigate the clinical effects of scalp acupuncture on motor dysfunction and changes in spontaneous brain activity in patients with ischemic stroke. METHODS: This was an evaluator- and analyst-blinded, multi-center randomized controlled trial. A total of 108 convalescent-stage ischemic stroke patients with motor dysfunction were allocated to receive either scalp acupuncture combined with rehabilitation treatment (SR group) or rehabilitation treatment alone (RE group). Patients in both groups received treatment 5 times per week for 8 weeks. The primary outcome measure was the Fugl-Meyer assessment (FMA). Secondary outcome measures included the modified Barthel index (mBI), modified Rankin scale (mRS) and values of fractional amplitude of low frequency fluctuation (fALFF) acquired using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. RESULTS: Both groups showed significant improvements in motor function, daily life ability and degree of disability, as measured by FMA, mRS and mBI (p < 0.05), and the SR group showed a significantly greater improvement (p < 0.05). Compared with the RE group, the areas where the fALFF values increased in the SR group were located in the cerebellum, praecuneus, precentral gyrus, superior frontal gyrus and parietal lobe. The improvement in FMA scores had the strongest correlation with the baseline fALFF values of the ipsilateral precentral gyrus. CONCLUSION: Scalp acupuncture improved motor function in convalescent-period ischemic stroke patients, and effects were correlated with regulation of motor-relevant brain regions. The fALFF value of the ipsilateral precentral and postcentral gyri could be potential clinical indices for prognostication of motor dysfunction. TRIAL REGISTRATION NUMBER: NCT03120650 (http://www.clinicaltrials.gov).

Motor network reorganization after motor imagery training in stroke patients with moderate to severe upper limb impairment.

BACKGROUND: Motor imagery training (MIT) has been widely used to improve hemiplegic upper limb function in stroke rehabilitation. The effectiveness of MIT is associated with the functional neuroplasticity of the motor network. Currently, brain activation and connectivity changes related to the motor recovery process after MIT are not well understood. AIM: We aimed to investigate the neural mechanisms of MIT in stroke rehabilitation through a longitudinal intervention study design with task-based functional magnetic resonance imaging (fMRI) analysis. METHODS: We recruited 39 stroke patients with moderate to severe upper limb motor impairment and randomly assigned them to either the MIT or control groups. Patients in the MIT group received 4 weeks of MIT therapy plus conventional rehabilitation, while the control group only received conventional rehabilitation. The assessment of Fugl-Meyer Upper Limb Scale (FM-UL) and Barthel Index (BI), and fMRI scanning using a passive hand movement task were conducted on all patients before and after treatment. The changes in brain activation and functional connectivity (FC) were analyzed. Pearson's correlation analysis was conducted to evaluate the association between neural functional changes and motor improvement. RESULTS: The MIT group achieved higher improvements in FM-UL and BI relative to the control group after the treatment. Passive movement of the affected hand evoked an abnormal bilateral activation pattern in both groups before intervention. A significant Group × Time interaction was found in the contralesional S1 and ipsilesional M1, showing a decrease of activation after intervention specifically in the MIT group, which was negatively correlated with the FM-UL improvement. FC analysis of the ipsilesional M1 displayed the motor network reorganization within the ipsilesional hemisphere, which correlated with the motor score changes. CONCLUSIONS: MIT could help decrease the compensatory activation at both hemispheres and reshape the FC within the ipsilesional hemisphere along with functional recovery in stroke patients.

Inflammation-activated C/EBPß mediates high-fat diet-induced depression-like behaviors in mice.

Depression, one of the most common causes of disability, has a high prevalence rate in patients with metabolic syndrome. Type 2 diabetes patients are at an increased risk for depression. However, the molecular mechanism coupling diabetes to depressive disorder remains largely unknown. Here we found that the neuroinflammation, associated with high-fat diet (HFD)-induced diabetes and obesity, activated the transcription factor CCAAT/enhancer binding protein ß (C/EBPß) in hippocampal neurons. This factor repressed brain-derived neurotrophic factor (BDNF) expression and caused depression-like behaviors in male mice. Besides, the loss of C/EBPß expression in C/EBPß heterozygous knockout male mice attenuated HFD-induced depression-like behaviors, whereas Thy1-C/EBPß transgenic male mice (overexpressing C/EBPß) showed depressive behaviors after a short-term HFD. Furthermore, HFD impaired synaptic plasticity and decreased surface expression of glutamate receptors in the hippocampus of wild-type (WT) mice, but not in C/EBPß heterozygous knockout mice. Remarkably, the anti-inflammatory drug aspirin strongly alleviated HFD-elicited depression-like behaviors in neuronal C/EBPß transgenic mice. Finally, the genetic delivery of BDNF or the pharmacological activation of the BDNF/TrkB signaling pathway by 7,8-dihydroxyflavone reversed anhedonia in a series of behavioral tests on HFD-fed C/EBPß transgenic mice. Therefore, our findings aim to demonstrate that the inflammation-activated neuronal C/EBPß promotes HFD-induced depression by diminishing BDNF expression.

Multi-modal fMRI and TMS follow-up study of motor cortical stroke caused by hyaluronic acid filler: A case report.

Background: Blindness and stroke resulting from hyaluronic acid (HA) fillers are not frequently reported complications. Reports on stroke recovery after HA injection are limited. In the current study, the recovery process, task-based functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and neurophysiological changes of a patient with monocular blindness and ipsilateral motor cortical stroke after forehead injection of HA are explored. Case-report: The study comprised a 34-year-old female patient who presented with left eye blindness and a stroke after receiving an HA injection a month before admission. The lesion was mainly limited to the left precentral gyrus, and the patient had pure arm monoparesis. For 3 weeks, the patient received conventional rehabilitation treatments and ten sessions of repetitive transcranial magnetic stimulation (rTMS) intervention. Clinical assessments, neurophysiological evaluation, task-based fMRI, and DTI examinations were conducted to assess her motor improvement and the possible neuro mechanism. Clinical rehabilitation impact: The patient's right upper limb motor function was almost completely restored after receiving rehabilitation therapy. However, the vision in her left eye did not show significant improvement. The neurophysiological evaluation showed partial recovery of the ipsilesional motor evoked potentials (MEPs). DTI results showed that the ipsilesional corticospinal tract (CST) was intact. Task-based fMRI results indicated that the activation pattern of the affected hand movement was gradually restored to normal. Conclusion: A case of good motor recovery after stroke due to HA injection with a lesion mainly restricted to the precentral gyrus but without CST damage is presented in the current study. Further studies should be conducted to explore the efficacy and the mechanisms of rehabilitation and neuromodulation approaches to motor cortical stroke.

Modulation of Brain Activity and Functional Connectivity by Acupuncture Combined With Donepezil on Mild-to-Moderate Alzheimer's Disease: A Neuroimaging Pilot Study.

Background: Functional brain imaging changes have been proven as potential pathophysiological targets in early-stage AD. Current longitudinal neuroimaging studies of AD treated by acupuncture, which is one of the growingly acknowledged non-pharmacological interventions, have neither adopted comprehensive acupuncture protocols, nor explored the changes after a complete treatment duration. Thus, the mechanisms of acupuncture effects remain not fully investigated. Objective: This study aimed to investigate the changes in spontaneous brain activity and functional connectivity and provide evidence for central mechanism of a 12-week acupuncture program on mild-to-moderate AD. Methods: A total of forty-four patients with mild-to-moderate AD and twenty-two age- and education-level-matched healthy subjects were enrolled in this study. The forty-four patients with AD received a 12-week intervention of either acupuncture combined with Donepezil (the treatment group) or Donepezil alone (the control group). The two groups received two functional magnetic resonance imaging (fMRI) scans before and after treatment. The healthy subject group underwent no intervention, and only one fMRI scan was performed after enrollment. The fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) were applied to analyze the imaging data. The correlations between the imaging indicators and the changed score of Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-cog) were also explored. Results: After the 12-week intervention, compared to those in the control group, patients with AD in the treatment group scored significantly lower on ADAS-cog value. Moreover, compared to healthy subjects, the areas where the fALFF value decreased in patients with AD were mainly located in the right inferior temporal gyrus, middle/inferior frontal gyrus, middle occipital gyrus, left precuneus, and bilateral superior temporal gyrus. Compared with the control group, the right precuneus demonstrated the greatest changed value of fALFF after the intervention in the treatment group. The difference in ADAS-cog after interventions was positively correlated with the difference in fALFF value in the left temporal lobe. Right precuneus-based FC analysis showed that the altered FC by the treatment group compared to the control group was mainly located in the bilateral middle temporal gyrus. Conclusion: The study revealed the key role of precuneus in the effect of the combination of acupuncture and Donepezil on mild-to-moderate AD for cognitive function, as well as its connection with middle temporal gyrus, which provided a potential treating target for AD. Trial Registration Number: NCT03810794 (http://www.clinicaltrials.gov).

Effects of high frequency rTMS of contralesional dorsal premotor cortex in severe subcortical chronic stroke: protocol of a randomized controlled trial with multimodal neuroimaging assessments.

BACKGROUND: Previous studies have revealed that low frequency repeated transcranial magnetic stimulation (rTMS) on the contralesional primary motor cortex (cM1) is less effective in severe stroke patients with poor neural structural reserve than in patients with highly reserved descending motor pathway. This may be attributed to the fact that secondary motor cortex, especially contralesional dorsal premotor cortex (cPMd), might play an important compensatory role in the motor function recovery of severely affected upper extremity. The main purpose of this study is to compare the effectiveness of low frequency rTMS on cM1 and high frequency rTMS on cPMd in subcortical chronic stroke patients with severe hemiplegia. By longitudinal analysis of multimodal neuroimaging data, we hope to elucidate the possible mechanism of brain reorganization following different treatment regimens of rTMS therapy, and to determine the cut-off of stimulation strategy selection based on the degree of neural structural reserve. METHODS/DESIGN: The study will be a single-blinded randomized controlled trial involving a total of 60 subcortical chronic stroke patients with severe upper limb motor impairments. All patients will receive 3 weeks of conventional rehabilitation treatment, while they will be divided into three groups and receive different rTMS treatments: cM1 low frequency rTMS (n = 20), cPMd high frequency rTMS (n = 20), and sham stimulation group (n = 20). Clinical functional assessment, multimodal functional MRI (fMRI) scanning, and electrophysiological measurement will be performed before intervention, 3 weeks after intervention, and 4 weeks after the treatment, respectively. DISCUSSION: This will be the first study to compare the effects of low-frequency rTMS of cM1 and high-frequency rTMS of cPMd. The outcome of this study will provide a theoretical basis for clarifying the bimodal balance-recovery model of stroke, and provide a strategy for individualized rTMS treatment for stroke in future studies and clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027399. Registered on 12 Nov 2019, http://www.chictr.org.cn/showproj.aspx?proj=43686 .

Decreased Interhemispheric Functional Connectivity and Its Associations with Clinical Correlates following Traumatic Brain Injury.

Objective: To explore the interhemispheric functional coordination following traumatic brain injury (TBI) and its association with posttraumatic anxiety and depressive symptoms. Methods: This was a combination of a retrospective cohort study and a cross-sectional observational study. We investigated the functional coordination between hemispheres by voxel-mirrored homotopic connectivity (VMHC). Grey matter volumes were examined by voxel-based morphometry (VBM), and microstructural integrity of the corpus callosum (CC) was assessed by diffusion tension imaging (DTI). The anxiety and depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale. Results: The VMHC values of the bilateral middle temporal gyrus (MTG) and orbital middle frontal gyrus (MFG) were significantly decreased in TBI patients versus the healthy controls. Weakened homotopic functional connectivity (FC) in the bilateral orbital MFG is moderate positively correlated with anxiety and depressive symptoms. The white matter integrity in the CC was extensively reduced in TBI patients. In the receiver operating characteristic analysis, the VMHC value of the orbital MFG could distinguish TBI from HC with an area under the curve of 0.939 (sensitivity of 1 and specificity of 0.867). Conclusion: TBI disrupts the interhemispheric functional and structural connection, which is correlated with posttraumatic mood disorders. These findings may serve as a clinical indicator for diagnosis.

Structural and Functional Alterations of Substantia Nigra and Associations With Anxiety and Depressive Symptoms Following Traumatic Brain Injury.

Backgrounds: Although there are a certain number of studies dedicated to the disturbances of the dopaminergic system induced by traumatic brain injury (TBI), the associations of abnormal dopaminergic systems with post-traumatic anxiety and depressive disorders and their underlying mechanisms have not been clarified yet. In the midbrain, dopaminergic neurons are mainly situated in the substantia nigra (SN) and the ventral tegmental area (VTA). Thus, we selected SN and VTA as regions of interest and performed a seed-based global correlation to evaluate the altered functional connectivity throughout the dopaminergic system post-TBI. Methods: Thirty-three individuals with TBI and 21 healthy controls were recruited in the study. Anxiety and depressive symptoms were examined by the Hospital Anxiety and Depression Scale. All MRI data were collected using a Siemens Prisma 3.0 Tesla MRI system. The volume of SN and the global functional connectivity of the SN and VTA were analyzed. Results: In the present study, patients with TBI reported more anxiety and depressive symptoms. More importantly, some structural and functional alterations, such as smaller SN and reduced functional connectivity in the left SN, were seen in individuals with TBI. Patients with TBI had smaller substantia nigra on both right and left sides, and the left substantia nigra was relatively small in contrast with the right one. Among these findings, functional connectivity between left SN and left angular gyrus was positively associated with post-traumatic anxiety symptoms and negatively associated with depressive symptoms. Conclusions: The TBI causes leftward lateralization of structural and functional alterations in the substantia nigra. An impaired mesocortical functional connectivity might be implicated in post-traumatic anxiety and depression.

Improved magnetic resonance myelin water imaging using multi-channel denoising convolutional neural networks (MCDnCNN).

Background: Myelin water imaging (MWI) is powerful and important for studying and diagnosing neurological and psychiatric diseases. In particular, myelin water fraction (MWF) is derived from MWI data for quantifying myelination. However, MWF estimation is typically sensitive to noise. Improving the accuracy of MWF estimation based on WMI data acquired using a magnetic resonance (MR) multiple gradient recalled echo (mGRE) imaging sequence is desired. Methods: The proposed method employs a recently introduced the multi-channel denoising convolutional neural networks (MCDnCNN). Five different MCDnCNN models, denoted as Delevel1, Delevel2, Delevel3, Delevel4 and DelevelMix corresponding to five noise levels (Level1, Level2, Level3, Level4 and LevelMix), were trained using the data of the first echo of the mGRE brain images acquired from 15 healthy human subjects. Using simulated noisy data that employed a hollow cylinder model, we first evaluated the improvement in estimating MWF based on data denoised by the five different MCDnCNNs, by comparing the MWF maps calculated from the denoised data with ground truth. Next, we again evaluated the improvement using real-world in vivo datasets of 11 human participants acquired using the mGRE sequence. The datasets were first denoised by five different MCDnCNNs (Delevel1, 2, 3, 4 and DelevelMix), and subsequently their MWF maps were calculated and compared with the MWF maps directly calculated from the raw mGRE images without being denoised. Results: Experiments using the simulation data denoised by the appropriate MCDnCNN models showed that the standard deviation (SD) of the absolute error (AE) of the derived MWF results was significantly reduced (maximal reduction =15.5%, Level3 simulated noisy data, orientation angle =0, all the five MCDnCNN models). In the test using in vivo data, estimating MWF based on data particularly denoised by the appropriate MCDnCNN models was found to be the best, compared to otherwise not using the appropriate models. The results demonstrated that the appropriate MCDnCNN models may permit high-quality MWF mapping, i.e., substantial reduction of random variation in estimating MWF-maps while preserving accuracy and structural details. Conclusions: Appropriate MCDnCNN models as proposed may improve both the accuracy and precision in estimating MWF maps, thereby making it a more clinically feasible alternative.

The Resting State Central Auditory Network: a Potential Marker of HIV-Related Central Nervous System Alterations.

OBJECTIVE: HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. DESIGN: Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. RESULTS: Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. CONCLUSIONS: The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.

Characteristics and mechanisms of ciprofloxacin degradation by black soldier fly larvae combined with associated intestinal microorganisms.

Antibiotics are challenging to degrade and are excreted by livestock which results in environmental pollution. In this paper, we demonstrated that environmentally friendly manure bioremediation performed by black soldier fly larvae (BSFL) is a wise alternative, which could effectively degrade ciprofloxacin (CIP) by approached 85.48% in artificial diet and 84.22% in poultry manure within 12 days. They are up to 2.5-4.0 fold more than that achieved by natural fermentation. The five CIP-degrading strains were isolated from the larval gut, two of which, named by Klebsiella pneumoniae BSFLG-CIP1 and Proteus mirabilis BSFLG-CIP5, could degraded CIP by nearly 98.22% and 97.83% in vitro, respectively. When the intestinal isolates were re-inoculated to sterile BSFL system, the degradation level significantly increased up to 82.38%, comparing with the sterile BSFL system (21.76%). It is proved that the larvae intestinal microbiota might carry out this highly-efficient CIP-degradation. Furthermore, seven possible metabolites were identified for CIP-degradation in vitro, and they were referring three main potential degrading mechanisms of hydroxylize, piperazine ring substitute and cleavage, and quinoline ring cleavage. In conclusion, the present study may provide a strategy to reduce antibiotics pollution in animal waste through bioremediation with BSFL and adjusted intestinal microbes.

Enhanced protein degradation by black soldier fly larvae (Hermetia illucens L.) and its gut microbes.

Black soldier fly larvae (BSFL) can convert a variety of organic wastes into biomass, and its gut microbiota are involved in this process. However, the role of gut microbes in the nutrient metabolism of BSFL is unclear. In this study, germ-free BSFL (GF) and gnotobiotic BSFL (GB) were evaluated in a high-protein artificial diet model. We used 16S rDNA sequencing, ITS1 sequencing, and network analysis to study gut microbiota in BSFL that degrade proteins. The protein reduction rate of the GB BSFL group was significantly higher (increased by 73.44%) than that of the GF BSFL group. The activity of gut proteinases, such as trypsin and peptidase, in the GB group was significantly higher than the GF group. The abundances of different gut microbes, including Pseudomonas spp., Orbus spp. and Campylobacter spp., were strongly correlated with amino acid metabolic pathways. Dysgonomonas spp. were strongly correlated with protein digestion and absorption. Issatchenkia spp. had a strong correlation with pepsin activity. Campylobacter spp., Pediococcus spp. and Lactobacillus spp. were strongly correlated with trypsin activity. Lactobacillus spp. and Bacillus spp. were strongly correlated with peptidase activity. Gut microbes such as Issatchenkia spp. may promote the gut proteolytic enzyme activity of BSFL and improve the degradation rate of proteins. BSFL protein digestion and absorption involves gut microbiota that have a variety of functions. In BSFL the core gut microbiota help complete protein degradation. These results demonstrate that core gut microbes in BSFL are important in protein degradation.

Mouse strain-specific responses of mitochondrial respiratory function and cardiac hypertrophy to isoproterenol treatment.

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O2 consumption at state III with either complex I substrates or complex II substrate, compared with those from FVB/nJ mice. ISO treatment did not affect mitochondrial respiratory control rate (RCR), but significantly suppressed the ADP/O ratio generated from the complex II substrate in both strains. The ADP/O ratio generated from the complex I substrates in A/J mice declined by 50% after ISO treatment, whereas FVB/nJ mice were not affected. These results suggest that, compared with FVB/nJ mice, A/J mice possesses a poor integrity of mitochondrial respiratory chain that might contribute to its vulnerability to ISO-induced cardiac hypertrophy.