Maternal riboflavin deficiency causes embryonic defects by activating ER stress-induced hepatocyte apoptosis pathway.

Riboflavin deficiency (RD) induces liver damage, abnormal embryonic development, and high mortality. We hypothesized that the phenotype could be rescued by inhibiting ER stress. The objectives of the present study were to investigate the underlying molecular mechanisms of RD-induced embryonic defects using in vitro and in vivo models. Primary duck embryonic hepatocytes were treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, and cultured in RD medium and riboflavin-sufficient (CON) medium for 8 days. Laying ducks (n = 20 cages/diet, 1 bird/cage) were fed an RD diet or CON diet for 14 wk, and the eggs were collected for hatching. At day 7 of incubation, the fertilized RD eggs were injected with or without 4-PBA into the yolk. RD decreased cell number and cell viability compared to the CON group, induced oxidative stress and apoptosis in primary duck embryonic hepatocytes. However, after being treated with an ER stress inhibitor (4-PBA) or transfected with CHOP siRNA, the apoptosis rate in RD hepatocytes decreased by 60.6 % and 86.1 %, respectively, being equal to the CON. These results indicated that RD-induced hepatocyte apoptosis is mediated by ER stress and the CHOP pathway. In vivo, RD embryos showed low hatchability, abnormal development, liver damage, ER stress, and apoptosis compared to the CON group. However, 4-PBA administration, as a model of ER stress inhibition, substantially restored embryonic development and alleviated liver damage in the RD group, including ER stress and apoptosis. Notably, hatchability in the RD group increased from 21.7 % to 72.7 % after 4-PBA treatment, though it remained less than the CON group (87.7 %). These results implicated ER stress-CHOP-apoptosis pathway as molecular mechanisms underlying RD-induced abnormal embryonic development and death, this target with potential for therapy or intervention.

Distinguishing schizophrenia and bipolar disorder through a Multiclass Classification model based on multimodal neuroimaging data.

This study aimed to identify neural biomarkers for schizophrenia (SZ) and bipolar disorder (BP) by analyzing multimodal neuroimaging. Utilizing data from structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI), multiclass classification models were created for SZ, BP, and healthy controls (HC). A total of 113 participants (BP: 31, SZ: 39, and HC: 43) were recruited under strict enrollment control, from which 272, 200, and 1875 features were extracted from sMRI, DTI, and rs-fMRI data, respectively. A support vector machine (SVM) with recursive feature elimination (RFE) was employed to build the models using a one-against-one approach and leave-one-out cross-validation, achieving a classification accuracy of 70.8%. The most discriminative features were primarily from rs-fMRI, along with significant findings in sMRI and DTI. Key biomarkers identified included the increased thickness of the left cuneus cortex and decreased regional functional connectivity strength (rFCS) in the left supramarginal gyrus as shared indicators for BP and SZ. Additionally, decreased fractional anisotropy in the left superior fronto-occipital fasciculus was suggested as specific to BP, while decreased rFCS in the left inferior parietal area might serve as a specific biomarker for SZ. These findings underscore the potential of multimodal neuroimaging in distinguishing between BP and SZ and contribute to the understanding of their neural underpinnings.

Dietary riboflavin supplementation improves meat quality, antioxidant capacity, fatty acid composition, lipidomic, volatilomic, and proteomic profiles of breast muscle in Pekin ducks.

Our objective was to determine effects of supplemental dietary riboflavin on meat quality, antioxidant capacity, fatty acid composition, lipidomic, volatilomic, and proteomic profiling of duck breast muscle. The results showed that dietary riboflavin supplementation significantly increased growth performance, breast meat yield, intramuscular fat content, polyunsaturated fatty acid (PUFA), n3-PUFA, n6-PUFA, redness (a*), and pH24h, but decreased lightness (L*) and yellowness (b*). Furthermore, riboflavin supplementation significantly improved muscle antioxidant capacity based on various biochemical parameters. Lipidomic and volatilomic analyses revealed that riboflavin supplementation markedly increased breast meat phosphatidylglycerol and coenzyme Q contents and two favourable key odorants, citronellyl acetate and 3-(methylthio)-propanal. Proteomics analyses confirmed that riboflavin supplementation activated mitochondrial aerobic respiration, including fatty acid beta oxidation, the tricarboxylic acid cycle, and oxidative phosphorylation. In conclusion, supplementing duck diets with riboflavin enhanced breast meat quality, attributed to increases in antioxidant capacity and mitochondrial functions.

Risk spillover network in the supply chain system during the COVID-19 crisis: Evidence from China.

The COVID-19 crisis seriously impacted the global economy and supply chain system. Unlike previous studies, this paper examines the risk spillover effects within the supply chain system rather than between financial and other specific industries. The hypotheses are proposed by developing and simulating an agent-based model; the copula-conditional value at risk model is employed to empirically validate these hypotheses in China during the COVID-19 crisis. The findings reveal that risks are transmitted and amplified from downstream, through midstream to upstream. Additionally, the financial industry amplifies the risk spillover from the midstream to the upstream and downstream. Moreover, the risk spillovers exhibit significant time-varying characteristics, and policy interventions can potentially mitigate the effect of such spillovers. This paper provides a theoretical basis and empirical evidence for risk spillover in supply chain systems and offers suggestions for industrial practitioners and regulators.

Association between cognitive impairments and aberrant dynamism of overlapping brain sub-networks in unmedicated major depressive disorder: A resting-state MEG study.

OBJECTIVE: Little is known about the pathogenesis underlying cognitive impairment in major depressive disorder (MDD). We aimed to explore the mechanisms of cognitive impairments among patients with MDD by investigating the dynamics of overlapping brain sub-networks. METHODS: Forty unmedicated patients with MDD and 28 healthy controls (HC) were enrolled in this study. Cognitive function was measured using the Chinese versions of MATRICS Consensus Cognitive Battery (MCCB). All participants were scanned using a whole-head resting-state magnetoencephalography (MEG) machine. The dynamism of neural sub-networks was analyzed based on the detection of overlapping communities in five frequency bands of oscillatory brain signals. RESULTS: MDD demonstrated poorer cognitive performance in six domains compared to HC. The difference in community detection (functional integration mode) in MDD was frequency-dependent. MDD showed significantly decreased community dynamics in all frequency bands compared to HC. Specifically, differences in the visual network (VN) and default mode network (DMN) were detected in all frequency bands, differences in the cognitive control network (CCN) were detected in the alpha2 and beta frequency bands, and differences in the bilateral limbic network (BLN) were only detected in the beta frequency band. Moreover, community dynamics in the alpha2 frequency band were positively correlated with verbal learning and reasoning problem solving abilities in MDD. CONCLUSIONS: Our study found that decreasing in the dynamics of overlapping sub-networks may differ by frequency bands. The aberrant dynamics of overlapping neural sub-networks revealed by frequency-specific MEG signals may provide new information on the mechanism of cognitive impairments that result from MDD.

How does risk information dissemination affect risk contagion in the interbank market?

This paper distinguishes between local and global risk information and disaggregates risk information dissemination in the interbank market based on specified behavioural mechanisms: information disclosure and transmission, information acquisition and decision-making. It then explores the mechanisms whereby such dissemination affects risk contagion in the interbank market and verifies through computational simulations how risk information dissemination, banks' information acquisition capability, and information disclosure strategies affect risk contagion in the interbank market. The study shows that risk information dissemination markedly increases-and greater bank information acquisition capability reduces-the scope of contagion in the interbank market. Moreover, the greater the tendency of banks is to disclose positive information, the greater the mitigating effect of this information on contagion in the interbank market. In addition, market noise has a positive effect on contagion, while the risk information transmission rate has a U-shaped influence on contagion.

Differences in verbal and spatial working memory in patients with bipolar II and unipolar depression: an MSI study.

BACKGROUND: Depressive symptoms could be similarly expressed in bipolar and unipolar disorder. However, changes in cognition and brain networks might be quite distinct. We aimed to find out the difference in the neural mechanism of impaired working memory in patients with bipolar and unipolar disorder. METHOD: According to diagnostic criteria of bipolar II disorder of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and assessments, 13 bipolar II depression (BP II), 8 unipolar depression (UD) patients and 15 healthy controls (HC) were recruited in the study. We used 2-back tasks and magnetic source imaging (MSI) to test working memory functions and get the brain reactions of the participants. RESULTS: Compared with HC, only spatial working memory tasks accuracy was significantly worse in both UD and BP II (p = 0.001). Pearson correlation showed that the stronger the FCs' strength of MFG-IPL and IPL-preSMA, the higher accuracy of SWM task within left FPN in patients with UD (r = 0.860, p = 0.006; r = 0.752, p = 0.031). However, the FC strength of IFG-IPL was negatively correlated with the accuracy of SWM task within left FPN in patients with BP II (r = - 0.591, p = 0.033). CONCLUSIONS: Our study showed that the spatial working memory of patients with whether UD or BP II was impaired. The patterns of FCs within these two groups of patients were different when performing working memory tasks.

Specific white matter connectomic changes in schizophrenia compared with psychotic bipolar disorder.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder with psychosis (BDP) can be clinically confusing. The specific connectomic changes in SZ compared with BDP may lead to a deeper comprehension of the pathophysiological core of SZ. Therefore, this study explored the common and distinct white matter (WM) structural connectomic alterations between these two diseases. METHOD: Diffusion tensor imaging data were collected from 19 drug-naïve patients with first episode SZ, 19 drug-naïve patients with BDP, and 19 healthy controls (HC). A graph theoretical approach was used to assess the brain WM network properties. RESULTS: Except for the clustering coefficients, no significant differences in the global parameters was found between SZ and BDP. Five brain regions, the right precentral, right post-cingulum, right insula, left superior occipital, and left inferior temporal gyri, showed specific differences in the nodal parameters in SZ compared with BDP and HC. Nine brain regions, the left rectus, left lingual, right inferior parietal, left superior temporal, right precentral, right postcentral, bilateral middle frontal, and right post-cingulum gyri, showed specific differences in the nodal parameters in BDP. Significant correlations between clinical symptoms and connectomic changes were detected in the right insula and left superior occipital gyrus in patients with SZ but in the left lingual gyrus in patients with BDP. CONCLUSIONS: Identifying shared and distinct WM structural networks between SZ and BDP may improve the understanding of the neuroanatomy of mental diseases. Specifically, the insula, the inferior temporal, superior temporal, and the lingual gyri may help to distinguish between SZ and BDP.

The characteristic of cognitive impairments in patients with bipolar II depression and its association with N-acetyl aspartate of the prefrontal white matter.

BACKGROUND: Cognitive deficit is acknowledged as a core feature of clinical manifestations of bipolar disorder (BD). However, the underlying mechanism of cognitive impairment in bipolar II depression has remained uncertain. We aim to determine the association of cognitive impairments with biochemical metabolism using proton magnetic resonance spectroscopy (1H-MRS) and a battery of neuropsychological testing. METHODS: The current study was designed to assess four cognitive domains in a sample of 110 patients with bipolar II depression and 110 healthy controls, using a battery of 6 cognitive tests, including the Digit Symbol Substitution Test (DSST), Wisconsin Cart Sorting Test (WCST), Trail Making Test Part B (TMT-B), Digit Span Test (DST), TMT-part A (TMT-A) and Verbal Fluency Test (VFT). Metabolite levels were obtained in the following brain regions of interest: bilateral prefrontal white matter (PWM), bilateral anterior cingulate cortex (ACC), bilateral lenticular nucleus (LN), and bilateral thalamus. N-acetyl aspartate (NAA)/creatine (Cr) and choline-containing compounds (Cho)/Cr ratios are analyzed. RESULTS: Patients with bipolar II depression performed significantly worse on DSST (score), TMT (completion time), DSB (score), and VFT (valid word number) when compared with healthy controls. In the bilateral PWM, NAA/Cr ratios in the PWM were significantly reduced (bilaterally) than those in healthy controls. Correlation analysis was conducted with data from patients with bipolar II depression, we found that the NAA/Cr ratio of the left PWM was positively correlated with the score of DS and DSB, and the NAA/Cr ratio of the right PWM was negatively correlated with the completion time of TMT-B. CONCLUSIONS: Our findings suggested that psychomotor speed, executive function, working memory, and verbal fluency are impaired in patients with BD II depression. Hypoactivity NAA/Cr in bilateral PWM may be associated with BD II depression's pathophysiology and results in cognitive dysfunction.

Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model.

BACKGROUND: Major depressive disorder (MDD) is frequently associated with cognitive deficits and high copper levels. Dysfunction of N-methyl-d-aspartate (NMDA) receptors has been postulated to underlie MDD pathogenesis. This study sought to investigate the curative effect of the NMDA receptor antagonist memantine on cognitive deficits in depression and the underlying mechanisms. METHODS: Adult male Sprague-Dawley rats received corticosterone (CORT) (20 mg/kg) bi-weekly via subcutaneous injection and/or copper gluconate (7 mg/kg) via daily intragastric administration. After 3 weeks, sucrose preference tests and open field tests showed anhedonia and high anxiety in both the CORT and CORT+Cu groups. Memantine intervention (20 mg/kg daily via intragastric administration for 14 days) led to recovery of anhedonia and anxiety behaviors. Memantine also remarkably suppressed serum copper ion levels. Moreover, memantine treatment effectively rescued depression-related spatial memory deficits as shown by the Morris water maze task. RESULTS: Compared to the pre-memantine treatment results, the results of behavioral tests and cognitive function after memantine treatment were significantly normalized, and the copper concentration was decreased in all groups. CONCLUSIONS: Collectively, our findings suggest that the NMDA receptor antagonist memantine may improve symptoms of anhedonia and anxiety and the cognitive deficits associated with depression, likely be related to suppress serum copper ion levels.

Serum copper and zinc levels correlate with biochemical metabolite ratios in the prefrontal cortex and lentiform nucleus of patients with major depressive disorder.

BACKGROUND: Previous studies have demonstrated that copper and zinc metabolism are associated with the development of major depressive disorder (MDD). Abnormal copper and zinc levels may be related to neurotransmission and biochemical metabolism in the brains of MDD patients, especially in the prefrontal cortex (PFC) and lentiform nucleus (LN). However, the mechanism of how copper and zinc levels contribute to neural metabolism in MDD patients remains to be deciphered. This study aimed to correlate copper and zinc levels with biochemical metabolite ratios in the PFC and LN of MDD patients. METHOD: Twenty-nine MDD patients and thirty-two healthy control (HC) volunteers were enrolled in this study. Proton magnetic resonance spectroscopy (1H-MRS) was used to determine the levels of the N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) in the brain, and specifically in the PFC and LN regions. Serum copper and zinc levels were measured using atomic emission spectrometry (AES). Afterwards, copper and zinc levels were correlated with biochemical metabolite ratios in the PFC and LN regions of the brain. RESULTS: Higher serum copper and lower serum zinc levels with higher copper/zinc ratios were observed in MDD patients. NAA/Cr ratios in the PFC of MDD patients were lower compared to HC volunteers. In MDD patients, serum copper levels were negatively correlated with NAA/Cr ratios in the right PFC and right LN, while copper/zinc ratios were negatively correlated with NAA/Cr ratios in the right LN. No significant differences in serum copper and zinc levels with NAA/Cr ratios in the left PFC and left LN were observed in MDD patients. CONCLUSION: Our findings suggest that higher serum copper and lower serum zinc levels may contribute to neuronal impairment by affecting neuronal biochemical metabolite ratios in the right PFC and right LN of MDD patients. Abnormal copper and zinc levels may play an important role in the pathophysiology of MDD.

Correlations between working memory impairment and neurometabolites of prefrontal cortex and lenticular nucleus in patients with major depressive disorder.

BACKGROUND: The mechanism of working memory (WM) impairment in MDD remains unclear. We aimed to find out the mechanism by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS). METHODS: 31 MDD patients and 31 healthy controls were recruited in our study. The WM performance and neurometabolite ratios of prefrontal cortex (PFC) and lenticular nucleus (LN) between two groups were evaluated and compared. And the correlations between abnormal neurometabolite ratios and WM dysfunction were computed. RESULTS: Scores of SDMT, DST(forwards), VRS and 2-back Task(accuracy rate) in MDD were lower than HCs. NAA/Cr ratios of bilateral PFC in MDD were significantly lower than HCs, while no significant differences showed in NAA/Cr ratios of LN and Cho/Cr, mI/Cr values of the bilateral PFC and LN between two groups. And for MDD patients, NAA/Cr ratios in the right PFC were positively correlated with scores of DST (Forwards). CONCLUSIONS: Our findings suggest that depressed patients may have impairments in working memory, including phonological loop, visual-spatial sketchpad, episodic buffer and central executive. And the impairment of verbal WM and WM capacity may be associated with the abnormal neurometabolites in the right PFC.

System light-loading technology for mHealth: Manifold-learning-based medical data cleansing and clinical trials in WE-CARE Project.

Cardiovascular disease (CVD) is a major issue to public health. It contributes 41% to the Chinese death rate each year. This huge loss encouraged us to develop a Wearable Efficient teleCARdiology systEm (WE-CARE) for early warning and prevention of CVD risks in real time. WE-CARE is expected to work 24/7 online for mobile health (mHealth) applications. Unfortunately, this purpose is often disrupted in system experiments and clinical trials, even if related enabling technologies work properly. This phenomenon is rooted in the overload issue of complex Electrocardiogram (ECG) data in terms of system integration. In this study, our main objective is to get a system light-loading technology to enable mHealth with a benchmarked ECG anomaly recognition rate. To achieve this objective, we propose an approach to purify clinical features from ECG raw data based on manifold learning, called the Manifold-based ECG-feature Purification algorithm. Our clinical trials verify that our proposal can detect anomalies with a recognition rate of up to 94% which is highly valuable in daily public health-risk alert applications based on clinical criteria. Most importantly, the experiment results demonstrate that the WE-CARE system enabled by our proposal can enhance system reliability by at least two times and reduce false negative rates to 0.76%, and extend the battery life by 40.54%, in the system integration level.