Massively parallel reporter assays and variant scoring identified functional variants and target genes for melanoma loci and highlighted cell-type specificity.

The most recent genome-wide association study (GWAS) of cutaneous melanoma identified 54 risk-associated loci, but functional variants and their target genes for most have not been established. Here, we performed massively parallel reporter assays (MPRAs) by using malignant melanoma and normal melanocyte cells and further integrated multi-layer annotation to systematically prioritize functional variants and susceptibility genes from these GWAS loci. Of 1,992 risk-associated variants tested in MPRAs, we identified 285 from 42 loci (78% of the known loci) displaying significant allelic transcriptional activities in either cell type (FDR < 1%). We further characterized MPRA-significant variants by motif prediction, epigenomic annotation, and statistical/functional fine-mapping to create integrative variant scores, which prioritized one to six plausible candidate variants per locus for the 42 loci and nominated a single variant for 43% of these loci. Overlaying the MPRA-significant variants with genome-wide significant expression or methylation quantitative trait loci (eQTLs or meQTLs, respectively) from melanocytes or melanomas identified candidate susceptibility genes for 60% of variants (172 of 285 variants). CRISPRi of top-scoring variants validated their cis-regulatory effect on the eQTL target genes, MAFF (22q13.1) and GPRC5A (12p13.1). Finally, we identified 36 melanoma-specific and 45 melanocyte-specific MPRA-significant variants, a subset of which are linked to cell-type-specific target genes. Analyses of transcription factor availability in MPRA datasets and variant-transcription-factor interaction in eQTL datasets highlighted the roles of transcription factors in cell-type-specific variant functionality. In conclusion, MPRAs along with variant scoring effectively prioritized plausible candidates for most melanoma GWAS loci and highlighted cellular contexts where the susceptibility variants are functional.

Functional annotation and investigation of the 10q24.33 melanoma risk locus identifies a common variant that influences transcriptional regulation of OBFC1.

The 10q24.33 locus is known to be associated with susceptibility to cutaneous malignant melanoma (CMM), but the mechanisms underlying this association have been not extensively investigated. We carried out an integrative genomic analysis of 10q24.33 using epigenomic annotations and in vitro reporter gene assays to identify regulatory variants. We found two putative functional single nucleotide polymorphisms (SNPs) in an enhancer and in the promoter of OBFC1, respectively, in neural crest and CMM cells, one, rs2995264, altering enhancer activity. The minor allele G of rs2995264 correlated with lower OBFC1 expression in 470 CMM tumors and was confirmed to increase the CMM risk in a cohort of 484 CMM cases and 1801 controls of Italian origin. Hi-C and chromosome conformation capture (3C) experiments showed the interaction between the enhancer-SNP region and the promoter of OBFC1 and an isogenic model characterized by CRISPR-Cas9 deletion of the enhancer-SNP region confirmed the potential regulatory effect of rs2995264 on OBFC1 transcription. Moreover, the presence of G-rs2995264 risk allele reduced the binding affinity of the transcription factor MEOX2. Biologic investigations showed significant cell viability upon depletion of OBFC1, specifically in CMM cells that were homozygous for the protective allele. Clinically, high levels of OBFC1 expression associated with histologically favorable CMM tumors. Finally, preliminary results suggested the potential effect of decreased OBFC1 expression on telomerase activity in tumorigenic conditions. Our results support the hypothesis that reduced expression of OBFC1 gene through functional heritable DNA variation can contribute to malignant transformation of normal melanocytes.

Cell-type-specific meQTLs extend melanoma GWAS annotation beyond eQTLs and inform melanocyte gene-regulatory mechanisms.

Although expression quantitative trait loci (eQTLs) have been powerful in identifying susceptibility genes from genome-wide association study (GWAS) findings, most trait-associated loci are not explained by eQTLs alone. Alternative QTLs, including DNA methylation QTLs (meQTLs), are emerging, but cell-type-specific meQTLs using cells of disease origin have been lacking. Here, we established an meQTL dataset by using primary melanocytes from 106 individuals and identified 1,497,502 significant cis-meQTLs. Multi-QTL colocalization with meQTLs, eQTLs, and mRNA splice-junction QTLs from the same individuals together with imputed methylome-wide and transcriptome-wide association studies identified candidate susceptibility genes at 63% of melanoma GWAS loci. Among the three molecular QTLs, meQTLs were the single largest contributor. To compare melanocyte meQTLs with those from malignant melanomas, we performed meQTL analysis on skin cutaneous melanomas from The Cancer Genome Atlas (n = 444). A substantial proportion of meQTL probes (45.9%) in primary melanocytes is preserved in melanomas, while a smaller fraction of eQTL genes is preserved (12.7%). Integration of melanocyte multi-QTLs and melanoma meQTLs identified candidate susceptibility genes at 72% of melanoma GWAS loci. Beyond GWAS annotation, meQTL-eQTL colocalization in melanocytes suggested that 841 unique genes potentially share a causal variant with a nearby methylation probe in melanocytes. Finally, melanocyte trans-meQTLs identified a hotspot for rs12203592, a cis-eQTL of a transcription factor, IRF4, with 131 candidate target CpGs. Motif enrichment and IRF4 ChIP-seq analysis demonstrated that these target CpGs are enriched in IRF4 binding sites, suggesting an IRF4-mediated regulatory network. Our study highlights the utility of cell-type-specific meQTLs.

A UVB-responsive common variant at chromosome band 7p21.1 confers tanning response and melanoma risk via regulation of the aryl hydrocarbon receptor, AHR.

Genome-wide association studies (GWASs) have identified a melanoma-associated locus on chromosome band 7p21.1 with rs117132860 as the lead SNP and a secondary independent signal marked by rs73069846. rs117132860 is also associated with tanning ability and cutaneous squamous cell carcinoma (cSCC). Because ultraviolet radiation (UVR) is a key environmental exposure for all three traits, we investigated the mechanisms by which this locus contributes to melanoma risk, focusing on cellular response to UVR. Fine-mapping of melanoma GWASs identified four independent sets of candidate causal variants. A GWAS region-focused Capture-C study of primary melanocytes identified physical interactions between two causal sets and the promoter of the aryl hydrocarbon receptor (AHR). Subsequent chromatin state annotation, eQTL, and luciferase assays identified rs117132860 as a functional variant and reinforced AHR as a likely causal gene. Because AHR plays critical roles in cellular response to dioxin and UVR, we explored links between this SNP and AHR expression after both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and ultraviolet B (UVB) exposure. Allele-specific AHR binding to rs117132860-G was enhanced following both, consistent with predicted weakened AHR binding to the risk/poor-tanning rs117132860-A allele, and allele-preferential AHR expression driven from the protective rs117132860-G allele was observed following UVB exposure. Small deletions surrounding rs117132860 introduced via CRISPR abrogates AHR binding, reduces melanocyte cell growth, and prolongs growth arrest following UVB exposure. These data suggest AHR is a melanoma susceptibility gene at the 7p21.1 risk locus and rs117132860 is a functional variant within a UVB-responsive element, leading to allelic AHR expression and altering melanocyte growth phenotypes upon exposure.

Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.

Development of SDS-Modified PbO2 Anode Material Based on Ti3+ Self-Doping Black TiO2NTs Substrate as a Conductive Interlayer for Enhanced Electrocatalytic Oxidation of Methylene Blue.

Efficient and stable electrode materials are urgently required for wastewater treatment in the electrocatalytic degradation of toxic and refractory organic pollutants. Ti3+ self-doping black TiO2 nanotube arrays (Ti/B-TiO2-NTs) as an interlayer were used for preparing a novel PbO2 electrode via an electrochemical reduction technology, and a sodium dodecyl sulfate (SDS)-modified PbO2 catalytic layer was successfully achieved via an electrochemical deposition technology. The physicochemical characterization tests showed that the Ti/B-TiO2-NTs/PbO2-SDS electrodes have a denser surface and finer grain size with the introduction of Ti3+ in the interlayer of Ti/TiO2-NTs and the addition of SDS in the active layer of PbO2. The electrochemical characterization results showed that the Ti3+ self-doping black Ti/TiO2-NTs/PbO2-SDS electrode had higher oxygen evolution potential (2.11 V vs. SCE), higher electrode stability, smaller charge-transfer resistance (6.74 Ω cm-2), and higher hydroxyl radical production activity, leading to it possessing better electrocatalytic properties. The above results indicated that the physicochemical and electrochemical characterization of the PbO2 electrode were all enhanced significantly with the introduction of Ti3+ and SDS. Furthermore, the Ti/B-TiO2-NTs/PbO2-SDS electrodes displayed the best performance on the degradation of methylene blue (MB) in simulated wastewater via bulk electrolysis. The removal efficiency of MB and the chemical oxygen demand (COD) could reach about 99.7% and 80.6% under the optimal conditions after 120 min, respectively. The pseudo-first-order kinetic constant of the Ti/B-TiO2-NTs/PbO2-SDS electrode was 0.03956 min-1, which was approximately 3.18 times faster than that of the Ti/TiO2-NTs/PbO2 electrode (0.01254 min-1). In addition, the Ti/B-TiO2-NTs/PbO2-SDS electrodes showed excellent stability and reusability. The degradation mechanism of MB was explored via the experimental identification of intermediates. In summary, the Ti3+ self-doping black Ti/TiO2-NTs/PbO2-SDS electrode is a promising electrode in treating wastewater.

Synthesis of Ag3PO4/Ag/g-C3N4 Composite for Enhanced Photocatalytic Degradation of Methyl Orange.

In this study, we have successfully constructed Ag3PO4/Ag/g-C3N4 heterojunctions via the hydrothermal method, which displays a wide photo-absorption range. The higher photocurrent intensity of Ag3PO4/Ag/g-C3N4 indicates that the separation efficiency of the photogenerated electron-hole pairs is higher than that of both Ag3PO4 and Ag/g-C3N4 pure substances. It is confirmed that the efficient separation of photogenerated electron-hole pairs is attributed to the heterojunction of the material. Under visible light irradiation, Ag3PO4/Ag/g-C3N4-1.6 can remove MO (~90%) at a higher rate than Ag3PO4 or Ag/g-C3N4. Its degradation rate is 0.04126 min-1, which is 4.23 and 6.53 times that of Ag/g-C3N4 and Ag3PO4, respectively. After five cycles of testing, the Ag3PO4/Ag/g-C3N4 photocatalyst still maintained high photocatalytic activity. The excellent photocatalysis of Ag3PO4/Ag/g-C3N4-1.6 under ultraviolet-visible light is due to the efficient separation of photogenerated carriers brought about by the construction of the Ag3PO4/Ag/g-C3N4 heterostructure. Additionally, Ag3PO4/Ag/g-C3N4 specimens can be easily recycled with high stability. The effects of hydroxyl and superoxide radicals on the degradation process of organic compounds were studied using electron paramagnetic resonance spectroscopy and radical quenching experiments. Therefore, the Ag3PO4/Ag/g-C3N4 composite can be used as an efficient and recyclable UV-vis spectrum-driven photocatalyst for the purification of organic pollutants.

[Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study].

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Cell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes.

Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type-specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 cis-eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0.05). Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissue types, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were unique to melanocytes compared to those of GTEx skin tissues or TCGA melanomas. The melanocyte data set also identified trans-eQTLs, including those connecting a pigmentation-associated functional SNP with four genes, likely through cis-regulation of IRF4 Melanocyte eQTLs are enriched in cis-regulatory signatures found in melanocytes as well as in melanoma-associated variants identified through genome-wide association studies. Melanocyte eQTLs also colocalized with melanoma GWAS variants in five known loci. Finally, a transcriptome-wide association study using melanocyte eQTLs uncovered four novel susceptibility loci, where imputed expression levels of five genes (ZFP90, HEBP1, MSC, CBWD1, and RP11-383H13.1) were associated with melanoma at genome-wide significant P-values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings, and present a robust database for genomic research of melanoma risk and melanocyte biology.

Cubature Information SMC-PHD for Multi-Target Tracking.

In multi-target tracking, the key problem lies in estimating the number and states of individual targets, in which the challenge is the time-varying multi-target numbers and states. Recently, several multi-target tracking approaches, based on the sequential Monte Carlo probability hypothesis density (SMC-PHD) filter, have been presented to solve such a problem. However, most of these approaches select the transition density as the importance sampling (IS) function, which is inefficient in a nonlinear scenario. To enhance the performance of the conventional SMC-PHD filter, we propose in this paper two approaches using the cubature information filter (CIF) for multi-target tracking. More specifically, we first apply the posterior intensity as the IS function. Then, we propose to utilize the CIF algorithm with a gating method to calculate the IS function, namely CISMC-PHD approach. Meanwhile, a fast implementation of the CISMC-PHD approach is proposed, which clusters the particles into several groups according to the Gaussian mixture components. With the constructed components, the IS function is approximated instead of particles. As a result, the computational complexity of the CISMC-PHD approach can be significantly reduced. The simulation results demonstrate the effectiveness of our approaches.

Telomere Length as an Indicator of the Robustness of B- and T-Cell Response to Influenza in Older Adults.

BACKGROUND: Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown. METHODS: We selected 22 HLA-A2-positive healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8(+) T-cell response against an influenza antigen. RESULTS: B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8(+) T cells. Vaccination did not increase M1-specific CD8(+) T cells in blood, but M1-specific CD8(+) T cells from the long telomere group exhibited significantly greater expansion in vitro than those from the short telomere group. Finally, M1-specific CD8(+) T cells that underwent more expansions had significantly longer telomeres than cells with fewer divisions. CONCLUSIONS: Telomere length is positively associated with a robust lymphocyte response, and telomere attrition may contribute to the age-associated decline of adaptive immunity.

Bile duct adenoma: a case report and literature review.

BACKGROUND: Bile duct adenoma (BDA) is a comparatively rare disease clinically, therefore, there are relatively few reported cases about it both in China and abroad. CASE PRESENTATION: Herein, we present a 51-year-old man, diagnosed preoperatively with enhanced-contrast abdominal computed tomography, as having a nodule in the left hepatic. The patient underwent a liver tumor resection, and the histological examination revealed bile duct adenoma (BDA). CONCLUSIONS: BDA is an extremely rare benign tumor, which is difficult to distinguish BDA from hepatocellular carcinoma definitely preoperatively, surgical resection is needed as a way of treatment.

The influence of the tibial plateau slopes on injury of the anterior cruciate ligament: a meta-analysis.

PURPOSE: The purpose of this meta-analysis was (1) to examine the effect of the tibial plateau slopes (medial and lateral) on anterior cruciate ligament (ACL) injury and (2) to investigate gender differences between ACL-injured subjects and gender-matched controls. METHODS: The PubMed database was searched through to 1 November 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. A meta-analysis was conducted, and either a fixed- or a random-effects model was used to calculate the overall weighted mean difference (WMD). RESULTS: Twelve studies (n = 1,871: 923 patients in the ACL-injured group and 938 patients in the control group) were included. The medial tibial plateau slope in the ACL group ranged from 1.8° ± 3.7° to 12.1° ± 3.3° while it ranged from 2.9° ± 2.8° to 9.5° ± 3° among the controls. The lateral tibial plateau slope in the ACL ranged from 1.8° ± 3.2° to 11.5° ± 3.5° and 0.3° ± 3.6° to 9° ± 4° in the control group. Statistically significant increased angles were observed in ACL-injured group compared to control group for medial tibial plateau slope (WMD, 1.1°; 95 % confidence interval, 0.5°-1.7°) and lateral tibial plateau slope (WMD, 1.8°; 95 % confidence interval, 1.3°-2.3°). Sensitivity analysis and subgroup analysis proved this to be a reliable result. CONCLUSIONS: The current meta-analysis suggests that both, increased medial and lateral tibial plateau slopes, are associated with increased susceptibility to ACL injury regardless of gender. In addition, this study indicates a stronger evidence for lateral tibial plateau slope to be associated with ACL injury compared with medial tibial plateau slope due to the larger increased angle value and on the basis of consistency among the included studies.

Deep M2CDL: Deep Multi-Scale Multi-Modal Convolutional Dictionary Learning Network.

For multi-modal image processing, network interpretability is essential due to the complicated dependency across modalities. Recently, a promising research direction for interpretable network is to incorporate dictionary learning into deep learning through unfolding strategy. However, the existing multi-modal dictionary learning models are both single-layer and single-scale, which restricts the representation ability. In this paper, we first introduce a multi-scale multi-modal convolutional dictionary learning ( M2CDL) model, which is performed in a multi-layer strategy, to associate different image modalities in a coarse-to-fine manner. Then, we propose a unified framework namely Deep M2CDL derived from the M2CDL model for both multi-modal image restoration (MIR) and multi-modal image fusion (MIF) tasks. The network architecture of Deep M2CDL fully matches the optimization steps of the M2CDL model, which makes each network module with good interpretability. Different from handcrafted priors, both the dictionary and sparse feature priors are learned through the network. The performance of the proposed Deep M2CDL is evaluated on a wide variety of MIR and MIF tasks, which shows the superiority of it over many state-of-the-art methods both quantitatively and qualitatively. In addition, we also visualize the multi-modal sparse features and dictionary filters learned from the network, which demonstrates the good interpretability of the Deep M2CDL network.

Assessing Face Image Quality: A Large-Scale Database and a Transformer Method.

The amount of face images has been witnessing an explosive increase in the last decade, where various distortions inevitably exist on transmitted or stored face images. The distortions lead to visible and undesirable degradation on face images, affecting their quality of experience (QoE). To address this issue, this paper proposes a novel Transformer-based method for quality assessment on face images (named as TransFQA). Specifically, we first establish a large-scale face image quality assessment (FIQA) database, which includes 42,125 face images with diversifying content at different distortion types. Through an extensive crowdsource study, we obtain 712,808 subjective scores, which to the best of our knowledge contribute to the largest database for assessing the quality of face images. Furthermore, by investigating the established database, we comprehensively analyze the impacts of distortion types and facial components (FCs) on the overall image quality. Accordingly, we propose the TransFQA method, in which the FC-guided Transformer network (FT-Net) is developed to integrate the global context, face region and FC detailed features via a new progressive attention mechanism. Then, a distortion-specific prediction network (DP-Net) is designed to weight different distortions and accurately predict final quality scores. Finally, the experiments comprehensively verify that our TransFQA method significantly outperforms other state-of-the-art methods for quality assessment on face images.

Chemical Speciation, Leaching Behavior, and Environmental Risk Assessment of Trace Elements in the Bottom Ash from Biomass Power Plant.

Biomass combustion for power generation stands as a pivotal method in energy utilization, offering a promising approach for renewable energy utilization. However, the substantial volume of slag produced by biomass burning plants poses environmental challenges, impeding sustainable energy practices. This article systematically studies the characteristics of ash generated from typical biomass direct combustion power plant ash and analyzes the chemical composition, trace element content characteristics, leaching characteristics, and chemical forms of biomass bottom ash. Furthermore, it assesses the environmental ecology and bioavailability of trace elements in bottom ash using the ecological risk assessment method and RAC method. The results demonstrate that the biomass bottom ash contains plant nutrients, such as K, Ca, Mg, and P, while the content of harmful trace elements is lower than the relevant Chinese standards. In dissolution experiments, the leaching rate of nearly all elements remains exceptionally low, primarily due to the distribution of trace elements within the lattice structure of stable minerals. Trace elements predominantly exist in the residual phase, Cu and Zn primarily found in organic compounds and sulfide bound states, while other elements mostly exist in the form of iron manganese oxide bound states. Ecological risk assessment indicates a significant risk level for Cd, contrasting with the slight risk associated with other elements. RAC results indicated no ecological risk of all of the trace elements. Consequently, the utilization of bottom ash in agricultural and forestry soils is deemed to be viable. These findings serve as a crucial foundation for biomass bottom ash resource utilization and underpin the sustainable utilization of biomass energy.

CrossHomo: Cross-Modality and Cross-Resolution Homography Estimation.

Multi-modal homography estimation aims to spatially align the images from different modalities, which is quite challenging since both the image content and resolution are variant across modalities. In this paper, we introduce a novel framework namely CrossHomo to tackle this challenging problem. Our framework is motivated by two interesting findings which demonstrate the mutual benefits between image super-resolution and homography estimation. Based on these findings, we design a flexible multi-level homography estimation network to align the multi-modal images in a coarse-to-fine manner. Each level is composed of a multi-modal image super-resolution (MISR) module to shrink the resolution gap between different modalities, followed by a multi-modal homography estimation (MHE) module to predict the homography matrix. To the best of our knowledge, CrossHomo is the first attempt to address the homography estimation problem with both modality and resolution discrepancy. Extensive experimental results show that our CrossHomo can achieve high registration accuracy on various multi-modal datasets with different resolution gaps. In addition, the network has high efficiency in terms of both model complexity and running speed.

HyperSOR: Context-Aware Graph Hypernetwork for Salient Object Ranking.

Salient object ranking (SOR) aims to segment salient objects in an image and simultaneously predict their saliency rankings, according to the shifted human attention over different objects. The existing SOR approaches mainly focus on object-based attention, e.g., the semantic and appearance of object. However, we find that the scene context plays a vital role in SOR, in which the saliency ranking of the same object varies a lot at different scenes. In this paper, we thus make the first attempt towards explicitly learning scene context for SOR. Specifically, we establish a large-scale SOR dataset of 24,373 images with rich context annotations, i.e., scene graphs, segmentation, and saliency rankings. Inspired by the data analysis on our dataset, we propose a novel graph hypernetwork, named HyperSOR, for context-aware SOR. In HyperSOR, an initial graph module is developed to segment objects and construct an initial graph by considering both geometry and semantic information. Then, a scene graph generation module with multi-path graph attention mechanism is designed to learn semantic relationships among objects based on the initial graph. Finally, a saliency ranking prediction module dynamically adopts the learned scene context through a novel graph hypernetwork, for inferring the saliency rankings. Experimental results show that our HyperSOR can significantly improve the performance of SOR.

Facilitating charge transfer via a Semi-Coherent Fe(PO3)2-Co2P2O7 heterointerface for highly efficient Zn-Air batteries.

Developing reversible oxygen electrodes for both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is crucial for achieving high-performance rechargeable Zn-air batteries (ZABs). This study introduced an nitrogen-doped carbon confined with a semi-coherent Fe(PO3)2-Co2P2O7 heterojunction for bifunctional oxygen electrocatalysis. This nanocomposite yielded an ORR half-wave potential of 0.908 V and an OER overpotential of 291 mV at 10 mA/cm2. ZABs incorporating this catalyst yielded impressive performance, including a peak power density of 203 mW/cm2, a specific capacity of 737 mAh/gZn, and promoted stability. Both experimental and theoretical simulations demonstrated that the unique electric field between Fe(PO3)2 and Co2P2O7 promoted efficient charge transport across the heterointerface. This interaction likely modulated the d-band center of the heterojunction, expedite the desorption of oxygen intermediates, thus improving oxygen catalysis and, consequently, ZAB performance. This work illustrates a significant design principle for creating efficient bifunctional catalysts in energy conversion technologies.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts. Integrating childhood obesity GWAS summary statistics with our existing 3D genomic datasets for 57 human cell types, consisting of high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, and RNA-seq, we applied stratified LD score regression and calculated the proportion of genome-wide SNP heritability attributable to cell type-specific features, revealing pancreatic alpha cell enrichment as the most statistically significant. Subsequent chromatin contact-based fine-mapping was carried out for genome-wide significant childhood obesity loci and their linkage disequilibrium proxies to implicate effector genes, yielded the most abundant number of candidate variants and target genes at the BDNF, ADCY3, TMEM18 and FTO loci in skeletal muscle myotubes and the pancreatic beta-cell line, EndoC-BH1. One novel implicated effector gene, ALKAL2 - an inflammation-responsive gene in nerve nociceptors - was observed at the key TMEM18 locus across multiple immune cell types. Interestingly, this observation was also supported through colocalization analysis using expression quantitative trait loci (eQTL) derived from the Genotype-Tissue Expression (GTEx) dataset, supporting an inflammatory and neurologic component to the pathogenesis of childhood obesity. Our comprehensive appraisal of 3D genomic datasets generated in a myriad of different cell types provides genomic insights into pediatric obesity pathogenesis.