Multiple Early Biomarkers to Predict Cognitive Decline in Dementia-Free Older Adults.

INTRODUCTION: Baseline olfactory impairment, poor performance on cognitive test, and medial temporal lobe atrophy are considered biomarkers for predicting future cognitive decline in dementia-free older adults. However, the combined effect of these predictors has not been fully investigated. METHODS: A group of 110 participants without dementia were continuously recruited into this study, and underwent olfactory, cognitive tests and MRI scanning at baseline and 5-year follow-up. Olfactory function was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). Participants were divided into the cognitive decliners and non-decliners. RESULTS: Among 87 participants who completed the 5-year follow-up, cognitive decline was present in 32 cases and 55 remained stable. Compared with non-decliners, cognitive decliners presented lower scores on both the UPSIT and the Montreal Cognitive Assessment (MoCA), and smaller hippocampal volume at baseline (all P < .001). The logistic regression analysis revealed that lower scores on UPSIT and MoCA, and smaller hippocampal volume were strongly associated with subsequent cognitive decline, respectively (all P < .001). For the prediction of cognitive decline, lower score on UPSIT performed the sensitivity of 63.6% and specificity of 81.2%, lower score on MoCA with the sensitivity of 74.5% and specificity of 65.6%, smaller hippocampal volume with the sensitivity of 70.9% and specificity of 78.1%, respectively. Combining three predictors resulted in the sensitivity of 83.6% and specificity of 93.7%. CONCLUSIONS: The combination of olfactory test, cognitive test with structural MRI may enhance the predictive ability for future cognitive decline for dementia-free older adults.

Joint effects of heat-humidity compound events on drowning mortality in Southern China.

BACKGROUND: Several previous studies have examined the association of ambient temperature with drowning. However, no study has investigated the effects of heat-humidity compound events on drowning mortality. METHODS: The drowning mortality data and meteorological data during the five hottest months (May to September) were collected from 46 cities in Southern China (2013-2018 in Guangdong, Hunan and Zhejiang provinces). Distributed lag non-linear model was first conducted to examine the association between heat-humidity compound events and drowning mortality at city level. Then, meta-analysis was employed to pool the city-specific exposure-response associations. Finally, we analysed the additive interaction of heat and humidity on drowning mortality. RESULTS: Compared with wet-non-hot days, dry-hot days had greater effects (excess rate (ER)=32.34%, 95% CI: 24.64 to 40.50) on drowning mortality than wet-hot days (ER=14.38%, 95%CI: 6.80 to 22.50). During dry-hot days, males (ER=42.40%, 95% CI: 31.92 to 53.72), adolescents aged 0-14 years (ER=45.00%, 95% CI: 21.98 to 72.35) and urban city (ER=36.91%, 95% CI: 23.87 to 51.32) showed higher drowning mortality risk than their counterparts. For wet-hot days, males, adolescents and urban city had higher ERs than their counterparts. Attributable fraction (AF) of drowning attributed to dry-hot days was 23.83% (95% CI: 21.67 to 26.99) which was significantly higher than that for wet-hot days (11.32%, 95% CI: 9.64 to 13.48%). We also observed that high temperature and low humidity had an additive interaction on drowning mortality. CONCLUSION: We found that dry-hot days had greater drowning mortality risk and burden than wet-hot days, and high temperature and low humidity might have synergy on drowning mortality.

Disrupted hypothalamic CRH neuron responsiveness contributes to diet-induced obesity.

The current obesity epidemic mainly results from high-fat high-caloric diet (HFD) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVH), a known body weight-regulating region, represent one key group of stress-responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both of which showed HFD-mimicking, blunted PVH CRH neuron responsiveness. Strikingly, both models developed rapid HFD-induced obesity, associated with HFD-mimicking, reduced diurnal rhythmicity in feeding and energy expenditure. Thus, blunted responsiveness of PVH CRH neurons, but not their absolute activity levels, underlies HFD-induced obesity and may also contribute to stress-induced obesity.

Investigating the interpretability of fetal status assessment using antepartum cardiotocographic records.

BACKGROUND: Cardiotocography (CTG) interpretation plays a critical role in prenatal fetal monitoring. However, the interpretation of fetal status assessment using CTG is mainly confined to clinical research. To the best of our knowledge, there is no study on data analysis of CTG records to explore the causal relationships between the important CTG features and fetal status evaluation. METHODS: For analyses, 2126 cardiotocograms were automatically processed and the respective diagnostic features measured by the Sisporto program. In this paper, we aim to explore the causal relationships between the important CTG features and fetal status evaluation. First, we utilized data visualization and Spearman correlation analysis to explore the relationship among CTG features and their importance on fetal status assessment. Second, we proposed a forward-stepwise-selection association rule analysis (ARA) to supplement the fetal status assessment rules based on sparse pathological cases. Third, we established structural equation models (SEMs) to investigate the latent causal factors and their causal coefficients to fetal status assessment. RESULTS: Data visualization and the Spearman correlation analysis found that thirteen CTG features were relevant to the fetal state evaluation. The forward-stepwise-selection ARA further validated and complemented the CTG interpretation rules in the fetal monitoring guidelines. The measurement models validated the five latent variables, which were baseline category (BCat), variability category (VCat), acceleration category (ACat), deceleration category (DCat) and uterine contraction category (UCat) based on fetal monitoring knowledge and the above analyses. Furthermore, the interpretable models discovered the cause factors of fetal status assessment and their causal coefficients to fetal status assessment. For instance, VCat could predict BCat, and UCat could predict DCat as well. ACat, BCat and DCat directly affected fetal status assessment, where ACat was the important causal factor. CONCLUSIONS: The analyses revealed the interpretation rules and discovered the causal factors and their causal coefficients for fetal status assessment. Moreover, the results are consistent with the computerized fetal monitoring and clinical knowledge. Our approaches are conducive to evidence-based medical research and realizing intelligent fetal monitoring.

Local Corticotropin-Releasing Factor Signaling in the Hypothalamic Paraventricular Nucleus.

Corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) initiate hypothalamic-pituitary-adrenal axis activity through the release of CRF into the portal system as part of a coordinated neuroendocrine, autonomic, and behavioral response to stress. The recent discovery of neurons expressing CRF receptor type 1 (CRFR1), the primary receptor for CRF, adjacent to CRF neurons within the PVN, suggests that CRF also signals within the hypothalamus to coordinate aspects of the stress response. Here, we characterize the electrophysiological and molecular properties of PVN-CRFR1 neurons and interrogate their monosynaptic connectivity using rabies virus-based tracing and optogenetic circuit mapping in male and female mice. We provide evidence that CRF neurons in the PVN form synapses on neighboring CRFR1 neurons and activate them by releasing CRF. CRFR1 neurons receive the majority of monosynaptic input from within the hypothalamus, mainly from the PVN itself. Locally, CRFR1 neurons make GABAergic synapses on parvocellular and magnocellular cells within the PVN. CRFR1 neurons resident in the PVN also make long-range glutamatergic synapses in autonomic nuclei such as the nucleus of the solitary tract. Selective ablation of PVN-CRFR1 neurons in male mice elevates corticosterone release during a stress response and slows the decrease in circulating corticosterone levels after the cessation of stress. Our experiments provide evidence for a novel intra-PVN neural circuit that is activated by local CRF release and coordinates autonomic and endocrine function during stress responses.SIGNIFICANCE STATEMENT The hypothalamic paraventricular nucleus (PVN) coordinates concomitant changes in autonomic and neuroendocrine function to organize the response to stress. This manuscript maps intra-PVN circuitry that signals via CRF, delineates CRF receptor type 1 neuron synaptic targets both within the PVN and at distal targets, and establishes the role of this microcircuit in regulating hypothalamic-pituitary-adrenal axis activity.

An excitatory projection from the basal forebrain to the ventral tegmental area that underlies anorexia-like phenotypes.

Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of anxiety, all hallmarks of typical anorexia symptoms. Importantly, activation of BF glutamatergic terminals in the VTA reduced dopamine release in the nucleus accumbens. Collectively, our results point to overactivation of the glutamatergic BF → VTA circuit as a potential cause of anorexia-like phenotypes involving reduced dopamine release.

Novel risk assessment model of food quality and safety considering physical-chemical and pollutant indexes based on coefficient of variance integrating entropy weight.

Food safety is important for sustainable social and economic development and people's health. The traditional single risk assessment model is one-sided to the weight distribution of food safety factors including physical-chemical and pollutant indexes, which cannot comprehensively assess food safety risks. Therefore, a novel food safety risk assessment model combining the coefficient of variation (CV) integrating the entropy weight (EWM) (CV-EWM) is proposed in this paper. The CV and the EWM are used to calculate the objective weight of each index with physical-chemical and pollutant indexes effecting food safety, respectively. Then, the weights determined by the EWM and the CV are coupled by the Lagrange multiplier method. The ratio of the square root of the product of two weights and the weighted sum of the square root of the product are regarded as the combined weight. Thus, the CV-EWM risk assessment model is constructed to comprehensively assess the food safety risk. Moreover, the Spearman rank correlation coefficient method is used to test the compatibility of the risk assessment model. Finally, the proposed risk assessment model is applied to evaluate the quality and safety risk of sterilized milk. By analyzing the attribute weight and comprehensive risk value of physical-chemical and pollutant indexes effecting the sterilized milk quality, the results show that this proposed model can scientifically obtain the weight of physical-chemical and pollutant indexes to objectively and reasonably evaluate the overall risk of food, which has certain practical value for discovering the influencing factors of risk occurrence to risk prevention and control of food quality and safety.

Lateral septum as a melanocortin downstream site in obesity development.

The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVHMc4R) preferably project to the ventral part of the lateral septum (LSv), a brain region known to be involved in emotional behaviors. Photostimulation of PVHMc4R neuron terminals in the LSv reduces feeding and causes aversion, whereas deletion of Mc4Rs or disruption of glutamate release from LSv-projecting PVH neurons causes obesity. In addition, disruption of AMPA receptor function in PVH-projected LSv neurons causes obesity. Importantly, chronic inhibition of PVH- or PVHMc4R-projected LSv neurons causes obesity associated with reduced energy expenditure. Thus, the LSv functions as an important node in mediating melanocortin action on body-weight regulation.

The melanocortin action is biased toward protection from weight loss in mice.

The melanocortin action is well perceived for its ability to regulate body weight bidirectionally with its gain of function reducing body weight and loss of function promoting obesity. However, this notion cannot explain the difficulty in identifying effective therapeutics toward treating general obesity via activation of the melanocortin action. Here, we provide evidence that altered melanocortin action is only able to cause one-directional obesity development. We demonstrate that chronic inhibition of arcuate neurons expressing proopiomelanocortin (POMC) or paraventricular hypothalamic neurons expressing melanocortin receptor 4 (MC4R) causes massive obesity. However, chronic activation of these neuronal populations failed to reduce body weight. Furthermore, gain of function of the melanocortin action through overexpression of MC4R, POMC or its derived peptides had little effect on obesity prevention or reversal. These results reveal a bias of the melanocortin action towards protection of weight loss and provide a neural basis behind the well-known, but mechanistically ill-defined, predisposition to obesity development.

Twin Adversarial Contrastive Learning for Underwater Image Enhancement and Beyond.

Underwater images suffer from severe distortion, which degrades the accuracy of object detection performed in an underwater environment. Existing underwater image enhancement algorithms focus on the restoration of contrast and scene reflection. In practice, the enhanced images may not benefit the effectiveness of detection and even lead to a severe performance drop. In this paper, we propose an object-guided twin adversarial contrastive learning based underwater enhancement method to achieve both visual-friendly and task-orientated enhancement. Concretely, we first develop a bilateral constrained closed-loop adversarial enhancement module, which eases the requirement of paired data with the unsupervised manner and preserves more informative features by coupling with the twin inverse mapping. In addition, to confer the restored images with a more realistic appearance, we also adopt the contrastive cues in the training phase. To narrow the gap between visually-oriented and detection-favorable target images, a task-aware feedback module is embedded in the enhancement process, where the coherent gradient information of the detector is incorporated to guide the enhancement towards the detection-pleasing direction. To validate the performance, we allocate a series of prolific detectors into our framework. Extensive experiments demonstrate that the enhanced results of our method show remarkable amelioration in visual quality, the accuracy of different detectors conducted on our enhanced images has been promoted notably. Moreover, we also conduct a study on semantic segmentation to illustrate how object guidance improves high-level tasks. Code and models are available at https://github.com/Jzy2017/TACL.

A subpopulation of oxytocin neurons initiate expression of CRF receptor 1 (CRFR1) in females post parturition.

Oxytocin (OT) is essential for successful reproduction, particularly during parturition and lactation. During the postpartum period, OT also influences maternal behavior to promote bonding between mothers and their newborns, and increases stress resilience. However, the mechanism by which stress influences OT neuron activity and OT release has remained unclear. Here, we provide evidence that a subpopulation of OT neurons initiate expression of the receptor for the stress neuropeptide Corticotropin Releasing Factor (CRF), CRFR1, in reproductive females. OT neuron expression of CRFR1 begins at the first parturition and increases during the postpartum period until weaning. The percentage of OT neurons that express CRFR1 increases with successive breeding cycles until it reaches a plateau of 20-25% of OT neurons. OT neuron expression of CRFR1 in reproductive females is maintained after they are no longer actively breeding. CRFR1 expression leads to activation of OT neurons when animals are stressed. We propose a model in which direct CRF signaling to OT neurons selectively in reproductive females potentiates OT release to promote stress resilience in mothers.

Generation of a CRF1-Cre transgenic rat and the role of central amygdala CRF1 cells in nociception and anxiety-like behavior.

Corticotropin-releasing factor type-1 (CRF1) receptors are critical to stress responses because they allow neurons to respond to CRF released in response to stress. Our understanding of the role of CRF1-expressing neurons in CRF-mediated behaviors has been largely limited to mouse experiments due to the lack of genetic tools available to selectively visualize and manipulate CRF1+ cells in rats. Here, we describe the generation and validation of a transgenic CRF1-Cre-tdTomato rat. We report that Crhr1 and Cre mRNA expression are highly colocalized in both the central amygdala (CeA), composed of mostly GABAergic neurons, and in the basolateral amygdala (BLA), composed of mostly glutamatergic neurons. In the CeA, membrane properties, inhibitory synaptic transmission, and responses to CRF bath application in tdTomato+ neurons are similar to those previously reported in GFP+ cells in CRFR1-GFP mice. We show that stimulatory DREADD receptors can be targeted to CeA CRF1+ cells via virally delivered Cre-dependent transgenes, that transfected Cre/tdTomato+ cells are activated by clozapine-n-oxide in vitro and in vivo, and that activation of these cells in vivo increases anxiety-like and nocifensive behaviors. Outside the amygdala, we show that Cre-tdTomato is expressed in several brain areas across the brain, and that the expression pattern of Cre-tdTomato cells is similar to the known expression pattern of CRF1 cells. Given the accuracy of expression in the CRF1-Cre rat, modern genetic techniques used to investigate the anatomy, physiology, and behavioral function of CRF1+ neurons can now be performed in assays that require the use of rats as the model organism.

Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice.

Noradrenergic afferents to hypothalamic corticotropin releasing hormone (CRH) neurons provide a major excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis via α1 adrenoreceptor activation. Noradrenergic afferents are recruited preferentially by somatic, rather than psychological, stress stimuli. Stress-induced glucocorticoids feed back onto the hypothalamus to negatively regulate the HPA axis, providing a critical autoregulatory constraint that prevents glucocorticoid overexposure and neuropathology. Whether negative feedback mechanisms target stress modality-specific HPA activation is not known. Here, we describe a desensitization of the α1 adrenoreceptor activation of the HPA axis following acute stress in male mice that is mediated by rapid glucocorticoid regulation of adrenoreceptor trafficking in CRH neurons. Glucocorticoid-induced α1 receptor trafficking desensitizes the HPA axis to a somatic but not a psychological stressor. Our findings demonstrate a rapid glucocorticoid suppression of adrenergic signaling in CRH neurons that is specific to somatic stress activation, and they reveal a rapid, stress modality-selective glucocorticoid negative feedback mechanism.

A Bilevel Integrated Model With Data-Driven Layer Ensemble for Multi-Modality Image Fusion.

Image fusion plays a critical role in a variety of vision and learning applications. Current fusion approaches are designed to characterize source images, focusing on a certain type of fusion task while limited in a wide scenario. Moreover, other fusion strategies (i.e., weighted averaging, choose-max) cannot undertake the challenging fusion tasks, which furthermore leads to undesirable artifacts facilely emerged in their fused results. In this paper, we propose a generic image fusion method with a bilevel optimization paradigm, targeting on multi-modality image fusion tasks. Corresponding alternation optimization is conducted on certain components decoupled from source images. Via adaptive integration weight maps, we are able to get the flexible fusion strategy across multi-modality images. We successfully applied it to three types of image fusion tasks, including infrared and visible, computed tomography and magnetic resonance imaging, and magnetic resonance imaging and single-photon emission computed tomography image fusion. Results highlight the performance and versatility of our approach from both quantitative and qualitative aspects.

Comorbidities and functional impairments in children with attention deficit hyperactivity disorder in China: a hospital-based retrospective cross-sectional study.

OBJECTIVES: The aim of this study was to assess comorbidity patterns and functional impairment in children with and without attention deficit hyperactivity disorder (ADHD). DESIGN: Hospital-based retrospective cross-sectional study; data collection occurred between 2016 and 2019. SETTINGS AND PATIENTS: A total of 8256 children and adolescents, 6-17 years of age, with suspected ADHD agreed to participate in this hospital-based cross-sectional study over a 4-year period in China. Comorbidities and social functions were assessed according to the scales Vanderbilt ADHD Diagnostic Parent Rating Scale and Weiss Functional Impairment Rating Scale-Parent Form, which were completed by the parents of the study participants. RESULTS: Of the 8256 children, 5640 were diagnosed with ADHD. Other 2616 children who did not meet the ADHD diagnostic criteria were classified as the N-ADHD group . The proportion of comorbidities (47.4%) and functional impairments (84.5%) in the ADHD group were higher than the N-ADHD group (p≤0.001). The functional impairment scores in all of the six domains, including family, academic, life skills, self-concept, social activities and risky activities, were significantly higher in the ADHD group than the N-ADHD group (p≤0.001). The functional impairment in ADHD group with comorbidities was more severe than those without comorbidities (p≤0.001). Comorbidities and core symptoms both can affect the functions of children with ADHD. Logistics regression analysis indicated that in all of the six functional domains, the effect of comorbidities on functional impairment exceeded the effects of ADHD core symptoms. CONCLUSIONS: Comorbidities had the greatest influence on different areas of adaptive functioning in children with ADHD. Clinical management of children suspected to have ADHD should address multiple comorbidities and functional impairments assessment, as well as core symptom analysis.

Centrally circulating α-klotho inversely correlates with human obesity and modulates arcuate cell populations in mice.

OBJECTIVE: Our laboratory recently identified the centrally circulating α-klotho protein as a novel hypothalamic regulator of food intake and glucose metabolism in mice. The current study aimed to investigate novel molecular effectors of central α-klotho in the arcuate nucleus of the hypothalamus (ARC), while further deciphering its role regulating energy balance in both humans and mice. METHODS: Cerebrospinal fluid (CSF) was collected from 22 adults undergoing lower limb orthopedic surgeries, and correlations between body weight and α-klotho were determined using an α-klotho enzyme-linked immunosorbent assay (ELISA) kit. To investigate the effects of α-klotho on energy expenditure (EE), 2-day intracerebroventricular (ICV) treatment was performed in diet-induced obesity (DIO) mice housed in TSE Phenomaster indirect calorimetry metabolic cages. Immunohistochemical staining for cFOS and patch clamp electrophysiology were used to determine the effects of central α-klotho on proopiomelanocortin (POMC) and tyrosine hydroxylase (TH) neurons. Additional stainings were performed to determine novel roles for central α-klotho to regulate non-neuronal cell populations in the ARC. Lastly, ICV pretreatment with fibroblast growth factor receptor (FGFR) or PI3kinase inhibitors was performed to determine the intracellular signaling involved in α-klotho-mediated regulation of ARC nuclei. RESULTS: Obese/overweight human subjects had significantly lower CSF α-klotho concentrations compared to lean counterparts (1,044 ± 251 vs. 1616 ± 218 pmol/L, respectively). Additionally, 2 days of ICV α-klotho treatment increased EE in DIO mice. α-Klotho had no effects on TH neuron activity but elicited varied responses in POMC neurons, with 44% experiencing excitatory and 56% experiencing inhibitory effects. Inhibitor experiments identified an α-klotho→FGFR→PI3kinase signaling mechanism in the regulation of ARC POMC and NPY/AgRP neurons. Acute ICV α-klotho treatment also increased phosphorylated ERK in ARC astrocytes via FGFR signaling. CONCLUSION: Our human CSF data provide the first evidence that impaired central α-klotho function may be involved in the pathophysiology of obesity. Furthermore, results in mouse models identify ARC POMC neurons and astrocytes as novel molecular effectors of central α-klotho. Overall, the current study highlights prominent roles of α-klotho→FGFR→PI3kinase signaling in the homeostatic regulation of ARC neurons and whole-body energy balance.

A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia.

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin's rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin's rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are both restored by leptin, whereas nutrient deprivation reverses the leptin action. Our results identify aberrant activation of LepRArc neurons owing to energy deprivation as the neural basis for T1D hyperglycemia and that leptin action is mediated by inhibiting LepRArc neurons through reversing energy deprivation.

Knowledge-Driven Deep Unrolling for Robust Image Layer Separation.

Single-image layer separation targets to decompose the observed image into two independent components in terms of different application demands. It is known that many vision and multimedia applications can be (re)formulated as a separation problem. Due to the fundamentally ill-posed natural of these separations, existing methods are inclined to investigate model priors on the separated components elaborately. Nevertheless, it is knotty to optimize the cost function with complicated model regularizations. Effectiveness is greatly conceded by the settled iteration mechanism, and the adaption cannot be guaranteed due to the poor data fitting. What is more, for a universal framework, the most taxing point is that one type of visual cue cannot be shared with different tasks. To partly overcome the weaknesses mentioned earlier, we delve into a generic optimization unrolling technique to incorporate deep architectures into iterations for adaptive image layer separation. First, we propose a general energy model with implicit priors, which is based on maximum a posterior, and employ the extensively accepted alternating direction method of multiplier to determine our elementary iteration mechanism. By unrolling with one general residual architecture prior and one task-specific prior, we attain a straightforward, flexible, and data-dependent image separation framework successfully. We apply our method to four different tasks, including single-image-rain streak removal, high-dynamic-range tone mapping, low-light image enhancement, and single-image reflection removal. Extensive experiments demonstrate that the proposed method is applicable to multiple tasks and outperforms the state of the arts by a large margin qualitatively and quantitatively.

Diagnostic value of circulating cell-free mtDNA in patients with suspected thyroid cancer: ND4/ND1 ratio as a new potential plasma marker.

Thyroid cancer is the most common endocrine malignancy, and its incidence continues to rise. For clinicians with cancer patients, choosing and interpreting diagnostic laboratory studies has become increasingly important. Previously, changes in plasma free mitochondrial DNA levels have been found in colorectal, breast, lung, and urinary cancers, and have demonstrated diagnostic value. In this study, we investigated whether the occurrence and development of thyroid cancer might be predicted using mtDNA copy number (ND1), mtDNA integrity (ND4/ND1) and levels of cell-free nDNA (GAPDH). We analyzed ND1, ND4, and GAPDH levels in plasma and blood cells from 75 patients with thyroid cancer, 40 patients with nodular goiter, and 107 normal controls using real-time PCR. Although both the thyroid nodule and thyroid cancer patients had significantly increased ND1 levels, the ND4/ND1 ratio in the thyroid cancer group was higher than the thyroid nodule group (P < 0.05), and significantly higher than the normal control group (P < 0.01). Plasma levels of nuclear DNA (GAPDH) in the thyroid cancer group were also higher compared to normal (P < 0.05). These results indicate that increased intactness of plasma free mtDNA is associated with increased levels of plasma cell-free nDNA, and that the ND4/ND1 ratio has the potential to be a new detection indicator in thyroid cancer. Furthermore, we classified thyroid cancer patients according to clinical data including age, tumor size, and metastasis. We found significantly higher levels of GAPDH in malignant tissues. Because ND4/ND1 correlated with plasma GAPDH in the plasma studies, this also suggests a potential relationship between ND4 intactness and thyroid tumor tissue size. Taken together, our findings suggest a tumor-specific process involving increased release of intact mtDNA, detectable in the plasma, which differentiates normal patients from patients with thyroid cancer.

BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition.

Epstein-Barr virus (EBV) is a major contributor to nasopharyngeal carcinoma (NPC) tumorigenesis. Mitochondria have been shown to be a target for tumor viral invasion, and to mediate viral tumorigenesis. In this study, we detected that mitochondrial morphological changes in tumor tissues of NPC patients infected with EBV were accompanied by an elevated expression of BHRF1, an EBV encoded protein homologue to Bcl-2. High expression of BHRF1 in human NPC cell lines enhanced tumorigenesis and metastasis features. With BHRF1 localized to mitochondria, its expression induced cyclophlin D dependent mitochondrial membrane permeabilization transition (MMPT). The MMPT further modulated mitochondrial function, increased ROS production and activated mitophagy, leading to enhanced tumorigenesis. Altogether, our results indicated that EBV-encoded BHRF1 plays an important role in NPC tumorigenesis through regulating cyclophlin D dependent MMPT.