EndoQuad: a comprehensive genome-wide experimentally validated endogenous G-quadruplex database.

G-quadruplexes (G4s) are non-canonical four-stranded structures and are emerging as novel genetic regulatory elements. However, a comprehensive genomic annotation of endogenous G4s (eG4s) and systematic characterization of their regulatory network are still lacking, posing major challenges for eG4 research. Here, we present EndoQuad (https://EndoQuad.chenzxlab.cn/) to address these pressing issues by integrating high-throughput experimental data. First, based on high-quality genome-wide eG4s mapping datasets (human: 1181; mouse: 24; chicken: 2) generated by G4 ChIP-seq/CUT&Tag, we generate a reference set of genome-wide eG4s. Our multi-omics analyses show that most eG4s are identified in one or a few cell types. The eG4s with higher occurrences across samples are more structurally stable, evolutionarily conserved, enriched in promoter regions, mark highly expressed genes and associate with complex regulatory programs, demonstrating higher confidence level for further experiments. Finally, we integrate millions of functional genomic variants and prioritize eG4s with regulatory functions in disease and cancer contexts. These efforts have culminated in the comprehensive and interactive database of experimentally validated DNA eG4s. As such, EndoQuad enables users to easily access, download and repurpose these data for their own research. EndoQuad will become a one-stop resource for eG4 research and lay the foundation for future functional studies.

Integrating massive RNA-seq data to elucidate transcriptome dynamics in Drosophila melanogaster.

The volume of ribonucleic acid (RNA)-seq data has increased exponentially, providing numerous new insights into various biological processes. However, due to significant practical challenges, such as data heterogeneity, it is still difficult to ensure the quality of these data when integrated. Although some quality control methods have been developed, sample consistency is rarely considered and these methods are susceptible to artificial factors. Here, we developed MassiveQC, an unsupervised machine learning-based approach, to automatically download and filter large-scale high-throughput data. In addition to the read quality used in other tools, MassiveQC also uses the alignment and expression quality as model features. Meanwhile, it is user-friendly since the cutoff is generated from self-reporting and is applicable to multimodal data. To explore its value, we applied MassiveQC to Drosophila RNA-seq data and generated a comprehensive transcriptome atlas across 28 tissues from embryogenesis to adulthood. We systematically characterized fly gene expression dynamics and found that genes with high expression dynamics were likely to be evolutionarily young and expressed at late developmental stages, exhibiting high nonsynonymous substitution rates and low phenotypic severity, and they were involved in simple regulatory programs. We also discovered that human and Drosophila had strong positive correlations in gene expression in orthologous organs, revealing the great potential of the Drosophila system for studying human development and disease.

Synergy of Spall Strength and Toughness in Nanograined Metals.

Under shock loading, the spall strength of nanocrystals exhibits intricate grain-size effects due to the presence of abundant grain boundary and dislocation activities. However, the influence of size on spall toughness and void evolution has been largely overlooked. This study employs molecular dynamics simulations to investigate the damage accumulation characteristics of nanocrystalline aluminum across various grain sizes. Unlike the trade-off observed in quasi-static loading conditions, our study reveals a consistency in which grain size governs both nanovoid nucleation and coalescence, yielding a novel spall strength-toughness synergy. These insights highlight grain sizes that are particularly susceptible to spall fracture, offering a crucial understanding of nanocrystal failure mechanisms in extreme environments.

Controlling the Selectivity of Electrocatalytic NO Reduction through pH and Potential Regulation on Single-Atom Catalysts.

Electrocatalytic nitrogen oxide reduction (NOxRR) emerges as an effective way to bring the disrupted nitrogen cycle back into balance. However, efficient and selective NOxRR is still challenging partly due to the complex reaction mechanism, which is influenced by experimental conditions such as pH and electrode potential. Here, we have studied the enzyme-inspired iron single-atom catalysts (Fe-N4-C) and identified that the selectivity roots in the first step of the nitric oxide reduction. Combining the constrained molecular dynamics (MD) simulations with the quasi-equilibrium approximation, the effects of electrode potential and pH on the reaction free energy were considered explicitly and predicted quantitatively. Systematic heat maps for selectivity between single-N and N-N-coupled products in a wide pH-potential space are further developed, which have reproduced the experimental observations of NOxRR. The approach presented in this study allows for a realistic simulation of the electrocatalytic interfaces and a quantitative evaluation of interfacial effects. Our results in this study provide valuable and straightforward guidance for selective NOx reduction toward desired products by precisely designing the experimental conditions.

DSEATM: drug set enrichment analysis uncovering disease mechanisms by biomedical text mining.

Disease pathogenesis is always a major topic in biomedical research. With the exponential growth of biomedical information, drug effect analysis for specific phenotypes has shown great promise in uncovering disease-associated pathways. However, this method has only been applied to a limited number of drugs. Here, we extracted the data of 4634 diseases, 3671 drugs, 112 809 disease-drug associations and 81 527 drug-gene associations by text mining of 29 168 919 publications. On this basis, we proposed a 'Drug Set Enrichment Analysis by Text Mining (DSEATM)' pipeline and applied it to 3250 diseases, which outperformed the state-of-the-art method. Furthermore, diseases pathways enriched by DSEATM were similar to those obtained using the TCGA cancer RNA-seq differentially expressed genes. In addition, the drug number, which showed a remarkable positive correlation of 0.73 with the AUC, plays a determining role in the performance of DSEATM. Taken together, DSEATM is an auspicious and accurate disease research tool that offers fresh insights.

Association Between Home Renovation and Sleeping Problems Among Children Aged 6-18 Years: A Nationwide Survey in China.

BACKGROUND: Although the indoor environment has been proposed to be associated with childhood sleep health, to our knowledge no study has investigated the association between home renovation and childhood sleep problems. METHODS: The study included 186,470 children aged 6-18 years from the National Chinese Children Health Study (2012-2018). We measured childhood sleeping problems via the Chinese version of the Sleep Disturbance Scale for Children (C-SDSC). Information on home renovation exposure within the recent 2 years was collected via parent report. We estimated associations between home renovation and various sleeping problems, defined using both continuous and categorized (binary) C-SDSC t-scores, using generalized mixed models. We fitted models with city as a random effect variable, and other covariates as fixed effects. RESULTS: Out of the overall participants, 89,732 (48%) were exposed to recent home renovations. Compared to the unexposed group, children exposed to home renovations had higher odds of total sleep disorder (odd ratios [OR] = 1.3; 95% confidence interval [CI] = 1.2, 1.4). Associations varied when we considered different types of home renovation materials. Children exposed to multiple types of home renovation had higher odds of sleeping problems. We observed similar findings when considering continuous C-SDSC t-scores. Additionally, sex and age of children modified the associations of home renovation exposure with some of the sleeping problem subtypes. CONCLUSIONS: We found that home renovation was associated with higher odds of having sleeping problems and that they varied when considering the type of renovation, cumulative exposure, sex, and age differences.

Solvation enhanced long-range proton transfer in aqueous phase for glycolaldehyde hydrogenation over Ru/C catalyst.

The catalytic hydrogenation of biomass-derived chemicals is essential in chemical industry due to the growing demand for sustainable and renewable energy sources. In this study, we present a comprehensive theoretical investigation regarding the hydrogenation of glycolaldehyde to ethylene glycol over a Ru/C catalyst by employing density functional theory and ab initio molecular dynamics simulations. With inclusion of explicit solvation, we have demonstrated that the glycolaldehyde hydrogenation is significantly improved due to the fast proton transfer through the hydrogen bond network. The enhanced activity could be attributed to the participation of the solvent water as the hydrogen source and the highly positively charged state of a Ru cluster in an aqueous phase, which are critical for the activation of aldehyde groups and proton-assisted hydrogenation. Overall, our findings provide valuable insights into glycolaldehyde hydrogenation over Ru/C catalysts in the aqueous phase, highlighting the importance of solvation effects in the biomass conversion.

Classify patients with Moyamoya disease according to their cognitive performance might be helpful in clinical and practical with support vector machine based on hypergraph.

Moyamoya disease (MMD) patients were now classified according to their cerebrovascular manifestations, with cognition and emotion ignored, which attenuated the therapy. The present study tried to classify them based on their cognitive and emotional performance and explored the neural basis underlying this classification using resting-state fMRI (rs-fMRI). Thirty-nine MMD patients were recruited, assessed mental function and MRI scanned. We adopted hierarchical analysis of their mental performance for new subtypes. Next, a three-step analysis, with each step consisting of 10 random cross validation, was conducted for robust brain regions in classifying the three subtypes of patients in a support vector machine (SVM) model with hypergraph of rs-fMRI. We found three new subtypes including high depression-high anxiety-low cognition (HE-LC, 50%), low depression-low anxiety-high cognition (LE-HC, 14%), and low depression-low anxiety-low cognition (LE-LC, 36%), and no hemorrhagic MMD patients fell into the LE-HC group. The temporal and the bilateral superior frontal cortex, and so forth were included in all 10 randomized SVM modeling. The classification accuracy of the final three-way classification model was 67.5% in average of 10 random cross validation. In addition, the S value between the frontal cortex and the angular cortex was positively correlated with the anxiety score and backward digit span (p < .05). Our results might provide a new perspective for MMD classification concerning patients' mental status, guide timely surgery and suggest angular cortex, and so forth should be protected in surgery for cognitive consideration.

Annotating functional effects of non-coding variants in neuropsychiatric cell types by deep transfer learning.

Genomewide association studies (GWAS) have identified a large number of loci associated with neuropsychiatric traits, however, understanding the molecular mechanisms underlying these loci remains difficult. To help prioritize causal variants and interpret their functions, computational methods have been developed to predict regulatory effects of non-coding variants. An emerging approach to variant annotation is deep learning models that predict regulatory functions from DNA sequences alone. While such models have been trained on large publicly available dataset such as ENCODE, neuropsychiatric trait-related cell types are under-represented in these datasets, thus there is an urgent need of better tools and resources to annotate variant functions in such cellular contexts. To fill this gap, we collected a large collection of neurodevelopment-related cell/tissue types, and trained deep Convolutional Neural Networks (ResNet) using such data. Furthermore, our model, called MetaChrom, borrows information from public epigenomic consortium to improve the accuracy via transfer learning. We show that MetaChrom is substantially better in predicting experimentally determined chromatin accessibility variants than popular variant annotation tools such as CADD and delta-SVM. By combining GWAS data with MetaChrom predictions, we prioritized 31 SNPs for Schizophrenia, suggesting potential risk genes and the biological contexts where they act. In summary, MetaChrom provides functional annotations of any DNA variants in the neuro-development context and the general method of MetaChrom can also be extended to other disease-related cell or tissue types.

Optimum substrate stiffness in coalescence-induced droplet jumping.

When droplets are brought into contact and coalesced on a superhydrophobic surface, the kinetic energy converted from the surface energy enables the merged droplet to jump. Current studies mainly focus on the microstructure of surfaces and the properties of droplets that influence the jumping dynamics. Here, by means of molecular dynamics, we investigate the coalescence-induced jumping of nanodroplets on soft substrates. The optimum stiffness of the substrate is suggested and the mechanism involved is demonstrated through the analysis of the interactions between the droplets and the substrates. The momentum of the droplet is evaluated by integrating the forces from the substrate. The optimum stiffness for jumping velocity is provided by the competition between the impact and the adhesion from the substrate during the process, which are both closely related to the stiffness. The results may inspire fundamental research and applications in a broad scope.

Higher Damping Capacities in Gradient Nanograined Metals.

The capability of damping mechanical energy in polycrystalline metals depends on the activities of defects such as dislocation and grain boundary (GB). However, operating defects has the opposite effect on strength and damping capacity. In the quest for high damping metals, maintaining the level of strength is desirable in practice. In this work, gradient nanograined structure is considered as a candidate for high-damping metals. The atomistic simulations show that the gradient nanograined models exhibit enhanced damping capacities compared with the homogeneous counterparts. The property can be attributed to the long-range order of GB orientations in gradient grains, where shear stresses facilitate GB sliding. Combined with the extraordinary mechanical properties, the gradient structure achieves a strength-ductility-damping synergy. The results provide promising solutions to the conflicts between mechanical properties and damping capacity in polycrystalline metals.

Variations in the dairy wastewater properties and bacterial diversity of each unit in membrane-enclosed anaerobic lagoon treatment process in Heilongjiang Province.

In order to meet the land use requirements of the treated wastewater from high density polyethylene (HDPE) membrane-enclosed anaerobic lagoons, the physical and chemical properties of the wastewater in an HDPE membrane-enclosed anaerobic lagoon were measured. The total nitrogen content (TN) in wastewater treated in membrane-enclosed anaerobic lagoons is 3165 and 1510 mg/L in winter and summer respectively. The wastewater can be used as liquid organic fertilizer, partly replacing chemical fertilizer. The safety dosage of the wastewater was 21.48 t/ha for rice and 9.54 t/ha for corn, respectively. Meanwhile, the wastewater has the characteristics of high salt (conductivity>16.0 mS/cm) and high organic matter content (COD>16,900 mg/kg). Therefore, the potential negative effects of the wastewater on soil salinity and pH should be assessed. 16S rRNA was used to investigate the bacterial population structure and assess potential biological risks of land use of the wastewater. The wastewater from lagoon has the least and the most bacterial abundance in summer and winter, respectively. The bacterial diversity of wastewater samples from lagoon is the most. 21 and 24 phyla were detected in winter and summer samples respectively. Clostridium is the absolute dominant bacteria in the summer water samples and the absolute dominant bacteria is Trichococcus in winter water samples. Several animal and plant bacterial pathogens such as Campylobacter, Corynebacterium, Facklamia and Erysipelothrix can be detected in the wastewater samples. More than 70% of pathogenic bacteria such as Campylobacter, Facklamia, Erysipelothrix and Acholeplasma can be removed by lagoon in summer, but only about 99% of Corynebacterium is still in the lagoon (XYH). While more than 60% of Corynebacterium, Facklamia and Erysipelothrix are not removed in winter. So the biological risk of land use of anaerobic pond wastewater needs to be considered.

Deep Learning-Enabled Raman Spectroscopic Identification of Pathogen-Derived Extracellular Vesicles and the Biogenesis Process.

Pathogenic bacterial infections, exacerbated by increasing antimicrobial resistance, pose a major threat to human health worldwide. Extracellular vesicles (EVs), secreted by bacteria and acting as their "long-distance weapons", play an important role in the occurrence and development of infectious diseases. However, no efficient methods to rapidly detect and identify EVs of different bacterial origins are available. Here, label-free Raman spectroscopy in combination with a new deep learning model of the attentional neural network (aNN) was developed to identify pathogen-derived EVs at Gram±, species, strain, and even down to physiological levels. By training the aNN model with a large Raman data set from six typical pathogen-derived EVs, we achieved the identification of EVs with high accuracies at all levels: exceeding 96% at the Gram and species levels, 93% at the antibiotic-resistant and sensitive strain levels, and still above 87% at the physiological level. aNN enabled Raman spectroscopy to interrogate the bacterial origin of EVs to a much higher level than previous methods. Moreover, spectral markers underpinning EV discrimination were uncovered from subtly different EV spectra via an interpretation algorithm of the integrated gradient. A further comparative analysis of the rich Raman biochemical signatures of EVs and parental pathogens clearly revealed the biogenesis process of EVs, including the selective encapsulation of biocomponents and distinct membrane compositions from the original bacteria. This developed platform provides an accurate and versatile means to identify pathogen-derived EVs, spectral markers, and the biogenesis process. It will promote rapid diagnosis and allow the timely treatment of bacterial infections.

Family socioeconomic status and mental health in Chinese adolescents: the multiple mediating role of social relationships.

BACKGROUND: The purpose of this study is to explore whether social relationships of family and school contexts mediate the influence of socioeconomic status (SES) on Chinese adolescents' mental health. METHODS: A school-based study was conducted among a sample aged 13-18 in East China (n = 6902). We used scales for measuring social relationships and self-rated mental health. Family SES was computed from subjective socioeconomic status, education and occupation of parents.The mediation model was tested by using Path Analysis in IBM SPSS-Amos. RESULTS: The results showed that SES can significantly influence adolescent mental health through parent-child relationship, student-teacher relationship and student-student relationship. The total effect, direct effect and total indirect effect were -0.209 (95% CI = -0.299, -0.136), -0.090 (95% CI = -0.174, -0.007), -0.119 (95% CI = -0.187, -0.078) for boys, and -0.337 (95% CI = -0.478, -0.230), -0.132 (95% CI = -0.283, 0.010), -0.205 (95% CI = -0.351, -0.085) for girls. CONCLUSION: The link between SES and adolescent mental health can be explained by social relationships. Focusing on the parent-child, student-student and student-teacher relationship interventions may contribute to improving the mental health of Chinese adolescents, especially in low socioeconomic groups, as well as female students.

Surgical revascularization vs. conservative treatment for adult hemorrhagic moyamoya disease: analysis of rebleeding in 322 consecutive patients.

Whether surgical revascularization can prevent recurrent hemorrhage in hemorrhagic moyamoya disease (HMD) patients remains a matter of debate. This study mainly aims at the comparison of treatment effect between surgical revascularization and conservative treatment of adult HMD patients. We retrospectively enrolled 322 adult HMD patients, including 133 in revascularization group and 189 in conservative group. The revascularization group included patients who underwent combined (n = 97) or indirect revascularization alone (n = 36). Ninety-two and forty-one patients underwent unilateral and bilateral revascularization respectively. The modified Rankin scale (mRS) was used to assess the functional status. The comparison was made based on initial treatment paradigm among two categories: (1) revascularization vs. conservative, (2) unilateral vs. bilateral revascularization. The rebleeding rate was significantly lower in revascularization group than that in conservative group (14.3% vs. 27.0%, P = 0.007). As for the functional outcomes, the average mRS was significantly better in revascularization group (1.7 ± 1.5) than that in conservative group (2.8 ± 1.9) (P < 0.001). The death rate in revascularization group was 8.3% (11/133), comparing to 20.1% (38/189) in conservative group (P = 0.004). While comparing between unilateral and bilateral revascularization within the revascularization group, the result demonstrated lower annual rebleeding rate in bilateral group (0.5%/side-year) than that in unilateral group (3.3%/side-year) (P = 0.001). This study proved the better treatment efficacy of surgical revascularization than that of conservative treatment in HMD patients, regarding both in rebleeding rate and mortality rate. Furthermore, bilateral revascularization seems more effective in preventing rebleeding than unilateral revascularization.

Meaning of socioeconomic status for mental health of adolescents in East China.

There is limited evidence on the association between different dimensions of socioeconomic status and mental health on adolescents in developing nations. The aim of this study was to examine this association among adolescents in East China. A school-based study that recruited 6902 adolescents aged 13 to 18 years was conducted in Suzhou, Hefei and Hangzhou. Multiple of indicators of socioeconomic status and mental health in adolescents were examined. Results revealed that girls showed significantly higher score of the global severity index, obsessive-compulsive, depression, anxiety, hostility, and phobic anxiety symptoms than boys. As expected, there was a slightly negative correlation between different dimensions of socioeconomic status to different domains of mental health problems (r ranged from -0.044 to 0.124). Furthermore, we found that maternal education and occupation were significantly associated with mental health for both boys and girls, while subjective socioeconomic status only was significantly associated with girls. In conclusion, adolescents in families with socioeconomic disadvantage, in the form of lower educational level and occupational prestige of mothers, had greater risk of mental health problem. Meanwhile, higher subjective socioeconomic status positively affects the mental health of female adolescents.

Phytochemicals and Allelopathy of Induced Water Hyacinth against Microcystis aeruginosa.

Induced water hyacinth with purple roots (PRWH) exerts a significant inhibitory effect on the growth of blue-green algae. Interestingly, its chemical constituents differ from those of wild-type water hyacinth and have not yet been reported. This study aimed to explore the chemical constituents of PRWH and its bioactive components serving as allelopathic agents against blue-green algae. Phytochemical investigation of the bioactive ethyl acetate fraction of a crude methanol extract from PRWH led to the isolation of 56 compounds, including 11 new phenylphenalene derivatives. The structures of these compounds were elucidated by comprehensive analyses through NMR, HRMS, and X-ray techniques. Bioactivity evaluation against Microcystis aeruginosa indicated that compounds 7, 12, 15, 37, 39, 45, and 47 potently inhibited blue-green algae growth.

Effectiveness comparisons of various psychosocial therapies for children and adolescents with depression: a Bayesian network meta-analysis.

The existence of depression among children or adolescents can trigger a sequence of burdens on themselves, their families and even the whole society, which cause both physical and economic impacts. Our network meta-analysis (NMA) was aimed at comparing them with each other for evaluating the optimal psychosocial therapy to help children and adolescents with depression to improve their mental health. Based on several biomedical databases, a system of search strategies was conducted for searching randomized controlled trials (RCTs) which published from their inception on October, 1st 2018 without language restriction. We carried out an expression analysis for comparing the efficacy of various psychosocial therapies using Bayesian NMA. A battery of analyses and assessments, such as conventional meta-analysis and risk of bias, were performed concurrently. Only 32 of RCTs which involved 2677 participants were eventually included in our analyses from the 19,176 of initial citation screening. In addition, in terms of various valid assessment instruments, interpersonal psychotherapy [standard mean difference (SMD) = -1.38, Credible interval (CrI) - 2.5, - 0.20)], computer cognitive-behavioral therapy (SMD = -1.36, CrI - 2.59, - 0.14), cognitive-behavioral therapy (SMD = -1.16, CrI - 2.15, - 0.18), had significantly better effects than the named control group. All together, these results suggest that interpersonal psychotherapy might be the best approach to improve the depressive state among children and adolescents. This study may provide an excellent resource for future endeavors to utilize psychosocial interventions and may also serve as a springboard for creative undertakings as yet unknown.

In silico production of relative correction factor for the quantitative analysis of multi-components by single marker method.

INTRODUCTION: Traditional methods to derive experimentally-generated relative correction factors (RCFs) for the quantitative analysis of herbal multi-components by single marker (QAMS) method require reference standards and multiple validations with different instruments and columns, which hampers high throughput implementation. OBJECTIVES: To effectively reduce the application amounts of raw material and provide higher and more stable accuracy, this study aimed to develop a method to computationally generate RCFs of herbal components. MATERIALS AND METHODS: This strategy included the published data collection, calibration curves screening, computer algorithm-based RCFs generation and accuracy validation. RESULTS: Using the in silico approach, we have successfully produced 133 RCFs for the multi-component quantitative analysis of 63 widely used herbs. CONCLUSION: Compared with conventional RCFs, this in silico method would be a low cost and highly efficient way to produce practical RCFs for the QAMS method.

PoMet3 and PoMet14 associated with sulfate assimilation are essential for conidiogenesis and pathogenicity in Pyricularia oryzae.

Pyricularia oryzae is the causal agent of blast disease on staple gramineous crops. Sulphur is an essential element for the biosynthesis of cysteine and methionine in fungi. Here, we targeted the P. oryzae PoMET3 encoding the enzyme ATP sulfurylase, and PoMET14 encoding the APS (adenosine-5'-phosphosulphate) kinase that are involved in sulfate assimilation and sulphur-containing amino acids biosynthesis. In P. oryzae, deletion of PoMET3 or PoMET14 separately results in defects of conidiophore formation, significant impairments in conidiation, methionine and cysteine auxotrophy, limited invasive hypha extension, and remarkably reduced virulence on rice and barley. Furthermore, the defects of the null mutants could be restored by supplementing with exogenous cysteine or methionine. Our study explored the biological functions of sulfur assimilation and sulphur-containing amino acids biosynthesis in P. oryzae.