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IntroductionAltered functional connectivity of resting-state functional magnetic resonance imaging (rs-fMRI) within default mode network (DMN) regions has been verified to be closely associated with cognitive decline in patients with Type 2 diabetes mellitus (T2DM), but most studies neglected the fluctuations of brain activities—the dynamic effective connectivity (DEC) within DMN of T2DM is still unknown.MethodsFor the current investigation, 40 healthy controls (HC) and 36 T2DM patients have been recruited as participants. To examine the variation of DEC between T2DM and HC, we utilized the methodologies of independent components analysis (ICA) and multivariate granger causality analysis (mGCA).ResultsWe found altered DEC within DMN only show decrease in state 1. In addition, the causal information flow of diabetic patients major affected areas which are closely associated with food craving and metabolic regulation, and T2DM patients stayed longer in low activity level and exhibited decreased transition rate between states. Moreover, these changes related negatively with the MoCA scores and positively with HbA1C level.ConclusionOur study may offer a fresh perspective on brain dynamic activities to understand the mechanisms underlying T2DM-related cognitive deficits.

AbstractBackground Although abdominal aortic aneurysm (AAA) is associated with life-threatening complications, there are still limited reliable biomarkers for diagnostic purpose. MicroRNAs (miRNAs) have been proposed as the potential diagnostic and risk stratification markers of AAA patients, and we aim to evaluate the serum level of miR-1-3p and its diagnostic value in AAA.Methods This study included 200 AAA patients and 200 controls. Demographic data and clinical information were collected from the subjects’ medical records. Individual image analyses of AAA morphology were determined based on computed tomography angiography (CTA). The levels of serum miRNA expression were detected by quantitative real-time PCR. Bioinformatics tools were used to identify the target genes of miR-1-3p and their potential biological functions were further enriched.Results Serum miR-1-3p levels in the AAA group were significantly lower when compared with those in the control group in overall and subgroup comparisons. It was negatively related to WBC, CRP, maximal aneurysm diameter, area, and volume in AAA patients. Circulating miR-1-3p levels could significantly discriminate between AAA patients and healthy individuals with an area under the curve (AUC) of 0.672 (95% CI = 0.619-0.724, p

Abstract Dyslexia is a reading and spelling disorder due to neurodevelopmental abnormalities and is occasionally found to be accompanied by hearing loss, but the reason for the associated deafness remains unclear. This study finds that knockout of the dyslexia susceptibility 1 candidate 1 gene (Dyx1c1−/−) in mice, the best gene for studying dyslexia, causes severe hearing loss, and thus it is a good model for studying the mechanism of dyslexia‐related hearing loss (DRHL). This work finds that the Dyx1c1 gene is highly expressed in the mouse cochlea and that the spontaneous electrical activity of inner hair cells and type I spiral ganglion neurons is altered in the cochleae of Dyx1c1−/− mice. In addition, primary ciliary dyskinesia‐related phenotypes such as situs inversus and disrupted ciliary structure are seen in Dyx1c1−/− mice. In conclusion, this study gives new insights into the mechanism of DRHL in detail and suggests that Dyx1c1 may serve as a potential target for the clinical diagnosis of DRHL.

Fabrication of heterojunction with specialized geometry shape could improve the photodegradation efficiency of catalysts more efficiently based on the synergistic effect of components. Herein, the BiVO4/ZnCr-LDH type-II heterojunction was successfully synthesized by the growth of two-dimensional (2D) ZnCr-LDH on 2D BiVO4, forming a unique three-dimensional (3D) hierarchical structure. The 3D hierarchical BiVO4/ZnCr-LDH type-II heterojunction with intimate 2D/2D heterointerfaces enlarges the interfacial contact areas and shortens the transfer distance of carriers simultaneously, which could promote the separation and transfer of photoinduced carriers and prolong the lifetime of carriers. Additionally, the 3D structure could enhance the photon utilization efficiency caused by the multiple reflections of incident light, and provide more active sites to promote the adsorption of pollutants. Therefore, the visible light catalytic performance of the optimal heterostructure for the removal of tetracycline hydrochloride is 3.47 times and 22.43 times higher than that of BiVO4 and ZnCr-LDH, respectively. Superoxide radical (·O2−) is confirmed as the primary active species, whereas hole (h+) is the secondary active species in the photodegradation process. This work provides a facile strategy to enhance the visible light catalytic behavior of BiVO4 through the fabrication of 3D hierarchical architecture heterojunction for the removal of organic pollutant.

Anti-SSA/Ro antibodies, while strongly linked to fetal cardiac injury and neonatal rash, can associate with a spectrum of disease in the mother, ranging from completely asymptomatic to overt Systemic Lupus Erythematosus (SLE) or Sjögren’s Syndrome (SS). This study was initiated to test the hypothesis that the microbiome, influenced in part by genetics, contributes to disease state. The stool microbiome of healthy controls (HC) was compared to that of anti-SSA/Ro positive women whose children had neonatal lupus. At the time of sampling, these women were either asymptomatic (Asym), had minor rheumatic symptoms or signs considered as an undifferentiated autoimmune syndrome (UAS), or were diagnosed with SLE or SS. Differences in microbial relative abundances among these three groups were tested assuming an ordering in clinical severity (HC

Whether China’s coal consumption control policy (CCCP) improves air quality is controversial. This study used city-level panel data and applied a DID model to identify it. We found that 1) The CCCP has a positive effect on AQI and PM25, which decrease by 7.6327 µg/m3 and 8.4293 µg/m3, respectively, but fails to reduce O3 concentration. 2) The effect of CCCP has regional heterogeneity. The CCCP has not significantly reduced PM2.5 emissions or improved air quality in the PRD region as in the BTHS and YRD regions. Additionally, in the YRD and PRD regions, CCCP can reduce O3 significantly. But the BTHS region failed to reduce the O3, and the introduction of CCCP made the O3 in pilot cities even higher by 4.1539 µg/m3. This study recognized the effects of the CCCP and its regional heterogeneity, which were supportive for policymakers to optimize coal-related policies to ensure environmental sustainability. We suggested that policymakers should differentiate policies according to regional differences and pay attention to reducing O3 pollution to establish sustainable ecosystems.

Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) share etiological and pathophysiological characteristics. Although neuroimaging studies have reported hippocampal alterations in SZ, BD, and MDD, little is known about how different hippocampal subregions are affected in these conditions because such subregions, namely, the cornu ammonis (CA), dentate gyrus (DG), and subiculum (SUB), have different structural foundations and perform different functions. Here, we hypothesize that different hippocampal subregions may reflect some intrinsic features among the major psychiatric disorders, such as SZ, BD, and MDD. By investigating resting functional connectivity (FC) of each hippocampal subregion among 117 SZ, 103 BD, 96 MDD, and 159 healthy controls, we found similarly and distinctly changed FC of hippocampal subregions in the three disorders. The abnormal functions of middle frontal gyrus might be the core feature of the psychopathological mechanisms of SZ, BD, and MDD. Anterior cingulate cortex and inferior orbital frontal gyrus might be the shared abnormalities of SZ and BD, and inferior orbital frontal gyrus is also positively correlated with depression and anxiety symptoms in SZ and BD. Caudate might be the unique feature of SZ and showed a positive correlation with the cognitive function in SZ. Middle temporal gyrus and supplemental motor area are the differentiating features of BD. Our study provides evidence for the different functions of different hippocampal subregions in psychiatric pathology.

How to mitigate greenhouse gas emission and achieve human development remain major sustainability issues, particularly in China. Empirical research on the effects of climate warming and social change on human health and wellbeing is quite fragmented. This study examines the impact of environmental issues and social changes on health and human wellbeing using a time series data of China from 1991 to 2020. Findings show that environmental issues have a negative impact on health and human wellbeing in long run. While the internet is a form of social change that tends to improve health and human wellbeing in the long run. FDI exerts a positive effect on human health, but it does not improve wellbeing in the long run. In contrast, financial development does not improve human health but it has a significant positive impact on wellbeing in the long run. Our empirical insights have important implications for achieving human wellbeing through the pursuit of environmental sustainability and social change.

BackgroundThe confounding effects of antipsychotics that led to the inconsistencies of neuroimaging findings have long been the barriers to understanding the pathophysiology of schizophrenia (SZ). Although it is widely accepted that antipsychotics can alleviate psychotic symptoms during the early most acute phase, the longer-term effects of antipsychotics on the brain have been unclear. This study aims to look at the susceptibility of different imaging measures to longer-term medicated status through real-world observation.MethodsWe compared gray matter volume (GMV) with amplitude of low-frequency fluctuations (ALFFs) in 89 medicated-schizophrenia (med-SZ), 81 unmedicated-schizophrenia (unmed-SZ), and 235 healthy controls (HC), and the differences were explored for relationships between imaging modalities and clinical variables. We also analyzed age-related effects on GMV and ALFF values in the two patient groups (med-SZ and unmed-SZ).ResultsMed-SZ demonstrated less GMV in the prefrontal cortex, temporal lobe, cingulate gyri, and left insula than unmed-SZ and HC (p < 0.05, family-wise error corrected). Additionally, GMV loss correlated with psychiatric symptom relief in all SZ. However, medicated status did not influence ALFF values: all SZ showed increased ALFF in the anterior cerebrum and decreased ALFF in posterior visual cortices compared with HC (p < 0.05, family-wise error corrected). Age-related GMV effects were seen in all regions, which showed group-level differences except fusiform gyrus. No significant correlation was found between ALFF values and psychiatric symptoms.ConclusionGMV loss appeared to be pronounced to longer-term antipsychotics, whereby imbalanced alterations in regional low-frequency fluctuations persisted unaffected by antipsychotic treatment. Our findings may help to understand the disease course of SZ and potentially identify a reliable neuroimaging feature for diagnosis.

Abstract Objective Although many studies have shown that the corpus callosum (CC) may play an important role in bipolar disorder (BD) and suicide, the pathophysiological mechanism of BD underlying suicidal behavior is still unclear. This study aimed to explore the relationship between the CC, and BD and suicidal ideation using diffusion tensor imaging (DTI). Method A total of 203 participants (47 BD patients with suicidal ideation, 59 with BD without suicidal ideation, and 97 healthy controls [HC]) underwent DTI scanning at a single site. We examined the white matter integrity of the CC in the three groups. Results A comparison among groups showed that BD patients with suicidal ideation had significant lower fractional anisotropy (FA) values than those of BD without suicidal ideation and HCs in the body and genu of the CC, and FA values of BD without suicidal ideation were significantly lower than those of HCs. However, in the splenium of corpus callosum, no difference was found between BD without suicidal ideation and HCs. Conclusions Our findings add to the evidence suggesting that the CC plays a key role in BD with suicidal ideation, especially with respect to the role of the genu and body of the CC subserving emotion regulation.

Abstract Background Cognitive impairments are prominent in schizophrenia (SZ). Imaging studies have demonstrated that functional changes of several areas of the brain exist in SZ patients. The relationships between these two indexes are largely unexplored in SZ. The MATRICS Consensus Cognitive Battery (MCCB) was used to measure cognitive impairment in multi-dimensional cognitive fields of SZ patients. This study was conducted to explore the relationship between cognitive functional impairment and the amplitude of low-frequency fluctuation (ALFF) in SZ patients. Method A total of 104 participants (44 SZ patients and 60 age- and gender-matched healthy controls (HC)) were recruited for this study. The MCCB was used to assess cognitive function of the participants, while brain activity was assessed using the ALFF. The relationship between the MCCB and the ALFF was investigated by using a correlation analysis. Results There were significant differences between SZ patients and HC in MCCB total and domain scores as well as in ALFF results. The reduction of ALFF in the bilateral postcentral gyri and paracentral lobule in SZ patients has a negative correlation with the MCCB sub-test of symbol coding. Conclusion These findings suggest that the reduction of ALFF in bilateral postcentral gyri and paracentral lobule may be related to cognitive impairment in SZ patients.

Objective: Suicide is the leading cause of death from bipolar disorder (BD). At least 25–50% of the patients with BD will attempt suicide, with suicide rates much higher in women patients than in men. It is crucial to explore the potential neural mechanism underlying suicidality in women with BD, which will lead to understanding and detection of suicidality and prevent death and injury from suicide.Methods: Brain function and structure were measured by amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) in 155 women [30 women with BD and a history of suicidality, 50 women with BD without suicidality, and 75 healthy controls (HC)]. The differences in ALFF and GMV across the BD with suicidality, BD without suicidality, and HC groups were investigated.Results: BD with suicidality showed significantly increased ALFF in the left and right cuneus compared with BD without suicidality and HC groups. Moreover, the GMV in the left lateral prefrontal cortex and left cuneus in BD with suicidality were significantly lower than those in BD without suicidality and HC groups, while the GMV of the right ventral prefrontal cortex was significantly decreased in both BD with and without suicidality groups.Conclusions: This study, combining functional and structural neuroimaging techniques, may help to identify specific pathophysiological changes in women with BD and suicidality. Increased ALFF and less GMV in cuneus might represent the neuroimaging features of suicidality in women with BD. Investigating this potential neuromarker for suicidality in women with BD may lead to the ability to prevent suicidality.

Background: Previous studies of atypical antipsychotic effects on cortical structures in schizophrenia (SZ) and bipolar disorder (BD) have findings that vary between the short and long term. In particular, there has not been a study exploring the effects of atypical antipsychotics on age-related cortical structural changes in SZ and BD. This study aimed to determine whether mid- to long-term atypical antipsychotic treatment (mean duration = 20 months) is associated with cortical structural changes and whether age-related cortical structural changes are affected by atypical antipsychotics.Methods: Structural magnetic resonance imaging images were obtained from 445 participants consisting of 88 medicated patients (67 with SZ, 21 with BD), 84 unmedicated patients (50 with SZ, 34 with BD), and 273 healthy controls (HC). Surface-based analyses were employed to detect differences in thickness and area among the three groups. We examined the age-related effects of atypical antipsychotics after excluding the potential effects of illness duration.Results: Significant differences in cortical thickness were observed in the frontal, temporal, parietal, and insular areas and the isthmus of the cingulate gyrus. The medicated group showed greater cortical thinning in these regions than the unmediated group and HC; furthermore, there were age-related differences in the effects of atypical antipsychotics, and these effects did not relate to illness duration. Moreover, cortical thinning was significantly correlated with lower symptom scores and Wisconsin Card Sorting Test (WCST) deficits in patients. After false discovery rate correction, cortical thinning in the right middle temporal gyrus in patients was significantly positively correlated with lower HAMD scores. The unmedicated group showed only greater frontotemporal thickness than the HC group.Conclusion: Mid- to long-term atypical antipsychotic use may adversely affect cortical thickness over the course of treatment and ageing and may also result in worsening cognitive function.

The hippocampus is an important candidate region in the study of functional connectivity alterations in schizophrenia (SZ) given its role as a functional hub for multiple brain networks. Although studies have implicated the hippocampus in SZ, no studies have compared hippocampal functional connectivity in healthy participants, patients with SZ, and unaffected family members (UAFMs). Patients and UAFM likely share biomarkers associated with susceptibility to SZ; the study of UAFM may also reveal compensatory markers. Patients with SZ, UAFM, and healthy control (HC) participants underwent resting state magnetic resonance imagingty and completed the Wisconsin Card Sort Task (WCST) as a measure of general cognitive function. We compared functional coupling with a hippocampus seed across the three groups. SZ and UAFM groups shared reductions in connectivity between the hippocampus and the striatum relative to HC. We also identified a significant positive correlation between WCST errors and hippocampal-striatal connectivity in the UAFM group. Hippocampal-striatal rsFC may be associated with familial susceptibility to SZ and with subtle cognitive deficits in the UAFM of individuals with SZ.

BackgroundAlterations of white matter integrity during adolescence/young adulthood may contribute to the neurodevelopmental pathophysiology of bipolar disorder (BD), but it remains unknown how white matter integrity changes in BD patients during this critical period of brain development. In the present study, we aimed to identify possible age-associated alterations of white matter integrity in adolescents and young adults with BD across the age range of 13–30 years.MethodsWe divided the participants into two groups by age as follows: adolescent group involving individuals of 13–21 years old (39 patients with BD and 39 healthy controls) and young adult group involving individuals of 22–30 years old (47 patients with BD and 47 healthy controls). Diffusion tensor imaging (DTI) was performed in all participants to assess white matter integrity.ResultsIn the adolescent group, compared to those of healthy controls, fractional anisotropy (FA) values were significantly lower in BD patients in the left inferior longitudinal fasciculus, splenium of the corpus callosum and posterior thalamic radiation. In the young adult group, BD patients showed significantly decreased FA values in the bilateral uncinate fasciculus, genu of the corpus callosum, right anterior limb of internal capsule and fornix compared to healthy controls. White matter impairments changed from the posterior brain to the anterior brain representing a back-to-front spatiotemporal directionality in an age-related pattern.ConclusionsOur findings provide neuroimaging evidence supporting a back-to-front spatiotemporal directionality of the altered development of white matter integrity associated with age in BD patients during adolescence/young adulthood.

Abstract Background Major depressive disorder (MDD) is a known major risk factor for suicide and is one of the most common mental disorders. Meanwhile, gender differences in suicidal behavior have long been recognized including the finding that women have higher rates of suicidal ideation and/or suicidal behavior than men. The mechanism underlying suicide ideation in female patients with MDD remains poorly understood. The aim of the present study was to examine possible suicidal behavior-related neural circuitry in female MDD. Methods In this study, 15 female participants with the first-episode MDD with suicidal ideation and 24 participants with the first-episode MDD without suicidal ideation as well as 39 female participants in a healthy control (HC) group, ranging in age from 18 to 50 years, underwent resting-state functional magnetic resonance imaging. The whole-brain amygdala resting-state functional connectivity (rsFC) was compared among these three groups. Results Compared with female participants with the first-episode MDD without suicidal ideation and those in the HC group, female participants with the first-episode MDD with suicidal ideation showed a significant difference in rsFC between the amygdala and precuneus/cuneus (p

Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD.Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS).Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and “noncooperation”) and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD.Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD.

Summary: There is a considerable need to identify those individuals with prostate cancer who have indolent disease. We propose that genes that control adult stem cell homeostasis in organs with slow turnover, such as the prostate, control cancer fate. One such gene, KLF4, overexpressed in murine prostate stem cells, regulates their homeostasis, blocks malignant transformation, and controls the self-renewal of tumor-initiating cells. KLF4 loss induces the molecular features of aggressive cancer and converts PIN lesions to invasive sarcomatoid carcinomas; its re-expression in vivo reverses this process. Bioinformatic analysis links these changes to human cancer. KLF4 and its downstream targets make up a gene signature that identifies indolent tumors and predicts recurrence-free survival. This approach may improve prognosis and identify therapeutic targets for advanced cancer. : Available criteria for segregating prostate cancer patients into those requiring therapeutic intervention and those who can be followed are inadequate. Xiong et al. show that KLF4 and its downstream targets make up a gene signature that identifies indolent tumors. This approach may improve prognosis and identify therapeutic targets for advanced cancer. Keywords: Klf4, adult prostate stem cells, stem cell homeostasis, malignant transformation, EMT, prostate cancer, gene signature, prognosis

Objective: Clinically, it is very difficult to distinguish between major depressive disorder (MDD) and bipolar disorder (BD) in the period of depression. Increasing evidence shows that the insula plays an important role in depression. We aimed to compare the resting-state functional connectivity (rsFC) of insular subregions in patients with MDD and BD in depressive episodes (BDD), who had never experienced manic or hypomanic episodes when they were scanned to identify biomarkers for the identification of two diseases.Methods: We recruited 21 BDD patients, 40 MDD patients and 70 healthy controls (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) was performed. BDD patients had never had manic or hypomanic episodes when they were scanned, and the diagnoses were determined by follow-up. We divided the insula into three parts including the ventral anterior insular cortex (v-AIN), dorsal anterior insular cortex (d-AIN), and posterior insula (PI). The insular-based rsFC was compared among the three groups, and an analysis of the correlation between the rsFC value and Hamilton depression and anxiety scales was carried out.Results: BDD and MDD patients demonstrated decreased rsFC from the v-AIN to the left superior/middle frontal gyrus compared with the HC group. Versus MDD and HC groups, BDD patients exhibited decreased rsFC from the v-AIN to the area in the left orbital frontal gyrus and left superior temporal gyrus (included temporal pole), from the PI to the right lateral postcentral gyrus and from all three insular subregions to the somatosensory and motor cortex. Meanwhile, a correlation between the rsFC value of the PI-right lateral postcentral gyrus and anxiety score was observed in patients.Conclusion: Our findings show BDD and MDD patients have similar decreases in insular connectivity in the dorsal lateral frontal regions, and BDD patients have specific decreased insular connectivity, especially in the somatosensory and motor cortex, which may be used as imaging evidence for clinical identification.

Neurophysiological mechanisms of white matter abnormalities in the earlier onset major depressive disorder (eoMDD, onset age ≤25 years old) differ from that in the later onset MDD (loMDD, onset age >25 years old). Myelin oligodendrocyte glycoprotein (MOG) is an important factor influencing white matter development. The influence of MOG on white matter in MDD of different age onset need to be explored. We compared MOG plasma concentrations and diffusion tensor imaging (DTI) data in 35 first-episode medication-naïve MDD patients (23 eoMDD, 12 loMDD), and 32 healthy controls (HC, 17 younger, 15 older). MOG was significantly higher in eoMDD and lower in loMDD compared with HC. Mean diffusivity (MD) values were significantly increased in inferior fronto-occipital fasciculus (IFOF) in eoMDD, and decreased in loMDD. In both younger and older groups, MOG correlated positively with IFOF MD values. Abnormal MOG has different influence in MDD of different age onset, which is linked to MOG's overly active effect on abnormal white matter in eoMDD and markedly weak effect in loMDD cases. Abnormal MOG would be an important factor in white matter damage in MDD; the influence of MOG differs with onset age.

[This corrects the article DOI: 10.1371/journal.pone.0163749.].

Most worldwide industrial wastewater, including in China, is still directly discharged to aquatic environments without adequate treatment. Because of a lack of data and few methods, the relationships between pollutants discharged in wastewater and those in surface water have not been fully revealed and unsupervised machine learning techniques, such as clustering algorithms, have been neglected in related research fields. In this study, real-time monitoring data for chemical oxygen demand (COD), ammonia nitrogen (NH3-N), pH, and dissolved oxygen in the wastewater discharged from 2213 factories and in the surface water at 18 monitoring sections (sites) in 7 administrative regions in the Yangtze River Basin from 2016 to 2017 were collected and analyzed by the partitioning around medoids (PAM) and expectation−maximization (EM) clustering algorithms, Welch t-test, Wilcoxon test, and Spearman correlation. The results showed that compared with the spatial cluster comprising unpolluted sites, the spatial cluster comprised heavily polluted sites where more wastewater was discharged had relatively high COD (>100 mg L−1) and NH3-N (>6 mg L−1) concentrations and relatively low pH (

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the potential immunomudualtory effect of APOL1 variants in auto-antigen activated myeloid cells by assessing lysosomal integrity in activated cells expressing APOL1. The primary stimuli were: 1. ssRNA hY3 as a proxy for the Ro immune complex; 2. in an bulk RNA seq model, interferon-response gene, Siglec 1, as a read out of interferon activity. The primary outcomes were: 1. Myeloid cell APOL1 expression both in primary macrophage cultures and ex-vivo patient derived macrophages; 2. Lysosome integrity as measured by fluorescence intensity of lysotracker dye on light microscopy. METHODS/STUDY POPULATION: All recruited subjects provided written informed consent as per the NEW YORK UNIVERSITY Division of Rheumatology-wide Specimen and Matched Phenotype Linked Examination (SAMPLE) protocol. Subjects were African American; SLE subjects met 4 American College of Rheumatology criteria for SLE. Healthy donor monocytes representing each genotype in duplicate (reference allele: G0/G0; heterozygote variant: RV/G0; and homozygote variant RV/RV) were cultured with GM-CSF to yield macrophages which were incubated in serum free media or with hY3 ssRNA (TLR 7/8 agonist) to yield inflammatory M1 macrophages. Fold increase of APOL1 in untreated vs hY3 treated macrophages was measured using qPCR. Live cells were then cultured on glass chamber slides with DNA dye, DAPI, and Lysotracker red, a fluorescent dye that stains acidic lysosomes. As a proof of concept, interferon response gene, Signlec1, and APOL1 transcriptional activity in peripheral blood monocytes (PBMCs) were measured and correlated in 17 SLE patients by RNA seq. RESULTS/ANTICIPATED RESULTS: Regardless of genotype, hY3 increased APOL1 expression by 29 (+/−18.4) fold (P = 0.007 vs no treatment). Genotyping of the qPCR product showed concordance with the chromosomal DNA with the RV heterozygotes expressing both alleles. To examine lysosomal membrane integrity, live hY3-treated macrophages were stained with lysosotracker dye and fluorescence intensity was measured. Compared to reference allele carrying macrophages, each additional variant allele corresponded with a lesser degree of lysosome compartment staining. In SLE PBMCs, we found that APOL1 was highly expressed, and significantly correlated with Siglec1 (F=10.5; P = 0.005) supporting an association between circulating interferons and APOL1 accumulation in monocytes. DISCUSSION/SIGNIFICANCE OF IMPACT: Given that the “cytokine milieu” in SLE elicits APOL1 expression, induces inflammatory cell metabolic rewiring, and stimulates autophagy thereby exposing defects in autophagic flux, this gene-environment interaction may underpin the relationship between chronic inflammation and heightened APOL1 polymorphism-attributed cardiovascular risk. These data support further inquiry into the intersection between chronic autoimmunity and APOL1’s functional role in the vascular microenvironment. The in vitro studies herein extend our prior work by demonstrating a mechanistic link between SLE-associated inflammation, APOL1 risk variant status and CVD via a lysosomal defect which converges on common autophagic and metabolic pathways in mononuclear cells.

Unlike developed countries, China has a nationally unified water environment standard and a specific watershed protection bureau to perform water quality evaluation. It is a major challenge to assess the water quality of a large watershed at a wide spatial scale and to make decisions in a scientific way. In 2016, weekly and real-time data for four monitoring indicators (pH, dissolved oxygen, permanganate index, and ammonia nitrogen) were collected at 21 surface water sections (sites) of the Yangtze River Basin, China. Results showed that one site had a relatively low Site Water Quality Index and was polluted for 12 weeks meanwhile. By using expectation-maximization clustering and hierarchical clustering algorithms, the 21 sites were classified. Variable spatiotemporal distribution characteristics for water quality and pollutants were found; some sites exhibited similar water quality variations on the weekly scale, but had different yearly grades. The results revealed polluted water quality for short periods and abrupt anomalies, which imply potential pollution sources and negative effects on water ecosystems. Potential spatio-temporal water quality characteristics, explored by machine learning methods and evidenced by time series and statistical models, could be applied in environmental decision support systems to make watershed management more objective, reliable, and powerful.

Understanding morphologic changes in vulnerable and early disease state of schizophrenia (SZ) may provide further insight into the development of psychosis.Whole brain voxel-based morphometry was performed to identify gray matter (GM) regional differences in 60 individuals with SZ during their first psychotic episode (FE-SZ), 31 individuals at genetic high risk for SZ (GHR-SZ) individuals, and 71 healthy controls.Significant differences were found in several regions including the prefrontal cortex, parietal lobe, temporal lobe, hippocampus, occipital lobe, and cerebellum among the three groups (p

BACKGROUND:Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD). This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure. METHODS:Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC). Fractional anisotropy (FA) values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC) region showing significant differences between the two groups was identified. RESULTS:Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group. CONCLUSIONS:First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

A single-nucleotide polymorphism at the LHPP gene (rs35936514) has been reported in genome-wide association studies to be associated with major depressive disorder (MDD). However, the neural system effects of rs35936514 that mediate the association are unknown. The present work explores whether the LHPP rs35936514 polymorphism moderates brain regional activity in MDD. A total of 160 subjects were studied: a CC group homozygous for the C allele (23 individuals with MDD and 57 controls) and a T-carrier group carrying the high risk T allele (CT/TT genotypes; 22 MDD and 58 controls). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Brain activity was assessed using the amplitudes of low-frequency fluctuations (ALFF). MDD patients showed a significant increased ALFF in the left middle temporal gyrus and occipital cortex. The T-carrier group showed increased ALFF in the left superior temporal gyrus. Significant diagnosis × genotype interaction was noted in the bilateral lingual gyri, bilateral dorsal lateral prefrontal cortex (dlPFC), and left medial prefrontal cortex (mPFC) (P