CRdb: a comprehensive resource for deciphering chromatin regulators in human.

Chromatin regulators (CRs) regulate epigenetic patterns on a partial or global scale, playing a critical role in affecting multi-target gene expression. As chromatin immunoprecipitation sequencing (ChIP-seq) data associated with CRs are rapidly accumulating, a comprehensive resource of CRs needs to be built urgently for collecting, integrating, and processing these data, which can provide abundant annotated information on CR upstream and downstream regulatory analyses as well as CR-related analysis functions. This study established an integrative CR resource, named CRdb (http://cr.liclab.net/crdb/), with the aim of curating a large number of available resources for CRs and providing extensive annotations and analyses of CRs to help biological researchers clarify the regulation mechanism and function of CRs. The CRdb database comprised a total of 647 CRs and 2,591 ChIP-seq samples from more than 300 human tissues and cell types. These samples have been manually curated from NCBI GEO/SRA and ENCODE. Importantly, CRdb provided the abundant and detailed genetic annotations in CR-binding regions based on ChIP-seq. Furthermore, CRdb supported various functional annotations and upstream regulatory information on CRs. In particular, it embedded four types of CR regulatory analyses: CR gene set enrichment, CR-binding genomic region annotation, CR-TF co-occupancy analysis, and CR regulatory axis analysis. CRdb is a useful and powerful resource that can help in exploring the potential functions of CRs and their regulatory mechanism in diseases and biological processes.

SEdb 2.0: a comprehensive super-enhancer database of human and mouse.

Super-enhancers (SEs) are cell-specific DNA cis-regulatory elements that can supervise the transcriptional regulation processes of downstream genes. SEdb 2.0 (http://www.licpathway.net/sedb) aims to provide a comprehensive SE resource and annotate their potential roles in gene transcriptions. Compared with SEdb 1.0, we have made the following improvements: (i) Newly added the mouse SEs and expanded the scale of human SEs. SEdb 2.0 contained 1 167 518 SEs from 1739 human H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) samples and 550 226 SEs from 931 mouse H3K27ac ChIP-seq samples, which was five times that of SEdb 1.0. (ii) Newly added transcription factor binding sites (TFBSs) in SEs identified by TF motifs and TF ChIP-seq data. (iii) Added comprehensive (epi)genetic annotations of SEs, including chromatin accessibility regions, methylation sites, chromatin interaction regions and topologically associating domains (TADs). (iv) Newly embedded and updated search and analysis tools, including 'Search SE by TF-based', 'Differential-Overlapping-SE analysis' and 'SE-based TF-Gene analysis'. (v) Newly provided quality control (QC) metrics for ChIP-seq processing. In summary, SEdb 2.0 is a comprehensive update of SEdb 1.0, which curates more SEs and annotation information than SEdb 1.0. SEdb 2.0 provides a friendly platform for researchers to more comprehensively clarify the important role of SEs in the biological process.

SEanalysis 2.0: a comprehensive super-enhancer regulatory network analysis tool for human and mouse.

Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.

TF-Marker: a comprehensive manually curated database for transcription factors and related markers in specific cell and tissue types in human.

Transcription factors (TFs) play key roles in biological processes and are usually used as cell markers. The emerging importance of TFs and related markers in identifying specific cell types in human diseases increases the need for a comprehensive collection of human TFs and related markers sets. Here, we developed the TF-Marker database (TF-Marker, http://bio.liclab.net/TF-Marker/), aiming to provide cell/tissue-specific TFs and related markers for human. By manually curating thousands of published literature, 5905 entries including information about TFs and related markers were classified into five types according to their functions: (i) TF: TFs which regulate expression of the markers; (ii) T Marker: markers which are regulated by the TF; (iii) I Marker: markers which influence the activity of TFs; (iv) TFMarker: TFs which play roles as markers and (v) TF Pmarker: TFs which play roles as potential markers. The 5905 entries of TF-Marker include 1316 TFs, 1092 T Markers, 473 I Markers, 1600 TFMarkers and 1424 TF Pmarkers, involving 383 cell types and 95 tissue types in human. TF-Marker further provides a user-friendly interface to browse, query and visualize the detailed information about TFs and related markers. We believe TF-Marker will become a valuable resource to understand the regulation patterns of different tissues and cells.

TcoFBase: a comprehensive database for decoding the regulatory transcription co-factors in human and mouse.

Transcription co-factors (TcoFs) play crucial roles in gene expression regulation by communicating regulatory cues from enhancers to promoters. With the rapid accumulation of TcoF associated chromatin immunoprecipitation sequencing (ChIP-seq) data, the comprehensive collection and integrative analyses of these data are urgently required. Here, we developed the TcoFBase database (http://tcof.liclab.net/TcoFbase), which aimed to document a large number of available resources for mammalian TcoFs and provided annotations and enrichment analyses of TcoFs. TcoFBase curated 2322 TcoFs and 6759 TcoFs associated ChIP-seq data from over 500 tissues/cell types in human and mouse. Importantly, TcoFBase provided detailed and abundant (epi) genetic annotations of ChIP-seq based TcoF binding regions. Furthermore, TcoFBase supported regulatory annotation information and various functional annotations for TcoFs. Meanwhile, TcoFBase embedded five types of TcoF regulatory analyses for users, including TcoF gene set enrichment, TcoF binding genomic region annotation, TcoF regulatory network analysis, TcoF-TF co-occupancy analysis and TcoF regulatory axis analysis. TcoFBase was designed to be a useful resource that will help reveal the potential biological effects of TcoFs and elucidate TcoF-related regulatory mechanisms.

In situ monitoring of toxic effects of algal toxin on cells by a novel microfluidic flow cytometry instrument.

Algal toxins produced by microalgae, such as domoic acid (DA)1, have toxic effects on humans. However, toxicity tests using mice only yield lethal doses of algal toxins without providing insights into the mechanism of action on cells. In this study, a fast segmentation of microfluidic flow cytometry cell images based on the bidirectional background subtraction (BBS)2 method was developed to get the visual evidence of apoptosis in both bright-field and fluorescence images. This approach enables mapping of changes in cell morphology and activity under algal toxins, allowing for fast (within 60 s) and automated biological detection. By combining microfluidics with flow cytometry, the intricate cellular-level reaction process can be observed in micro samples of 293 T cells and mouse spleen cells, offering potential for future in vitro experiments.

A film-linked electrostatic self-assembly microfluidic chip.

This article proposes a film-linked electrostatic self-assembly microfluidic chip for the first time, designed to be ready-to-use. Barrier films are used to isolate the gas/liquid path microchannels and the pre-stored reagents of the chip before use. Through the linkage design between the film materials, the motion of barrier films is linked to the structural changes inside the chip. Under the combined action of the rebound force of the elastic substrate, the electrostatic adsorption force between the substrates, and the reaction force of the elastic film, the elastic substrate and the liquid storage substrate are instantly bonded, and the self-assembly of the chip is completed within 1 s. By using six independently output programmable sequences to perform the sequential quantitative pumping of pre-stored reagents, the transfer and mixing of samples and pre-stored reagents are automatically driven in a confined space, which greatly reduces the contamination risk and loss rate of samples/reagents, and improves the accuracy and reproducibility of test results. In addition, the microfluidic multi-step reaction driven in parallel can avoid liquid reflux, accurately control the amount of reactant transfer, and realize the quantitative detection of samples. Multiple reactions can be performed synchronously without interference, saving the test time. Since each gas path is independently controllable, the chip can be extended to a variety of biochemical reactions and has the potential to detect a variety of substances.

VARAdb: a comprehensive variation annotation database for human.

With the study of human diseases and biological processes increasing, a large number of non-coding variants have been identified and facilitated. The rapid accumulation of genetic and epigenomic information has resulted in an urgent need to collect and process data to explore the regulation of non-coding variants. Here, we developed a comprehensive variation annotation database for human (VARAdb, http://www.licpathway.net/VARAdb/), which specifically considers non-coding variants. VARAdb provides annotation information for 577,283,813 variations and novel variants, prioritizes variations based on scores using nine annotation categories, and supports pathway downstream analysis. Importantly, VARAdb integrates a large amount of genetic and epigenomic data into five annotation sections, which include 'Variation information', 'Regulatory information', 'Related genes', 'Chromatin accessibility' and 'Chromatin interaction'. The detailed annotation information consists of motif changes, risk SNPs, LD SNPs, eQTLs, clinical variant-drug-gene pairs, sequence conservation, somatic mutations, enhancers, super enhancers, promoters, transcription factors, chromatin states, histone modifications, chromatin accessibility regions and chromatin interactions. This database is a user-friendly interface to query, browse and visualize variations and related annotation information. VARAdb is a useful resource for selecting potential functional variations and interpreting their effects on human diseases and biological processes.

ATACdb: a comprehensive human chromatin accessibility database.

Accessible chromatin is a highly informative structural feature for identifying regulatory elements, which provides a large amount of information about transcriptional activity and gene regulatory mechanisms. Human ATAC-seq datasets are accumulating rapidly, prompting an urgent need to comprehensively collect and effectively process these data. We developed a comprehensive human chromatin accessibility database (ATACdb, http://www.licpathway.net/ATACdb), with the aim of providing a large amount of publicly available resources on human chromatin accessibility data, and to annotate and illustrate potential roles in a tissue/cell type-specific manner. The current version of ATACdb documented a total of 52 078 883 regions from over 1400 ATAC-seq samples. These samples have been manually curated from over 2200 chromatin accessibility samples from NCBI GEO/SRA. To make these datasets more accessible to the research community, ATACdb provides a quality assurance process including four quality control (QC) metrics. ATACdb provides detailed (epi)genetic annotations in chromatin accessibility regions, including super-enhancers, typical enhancers, transcription factors (TFs), common single-nucleotide polymorphisms (SNPs), risk SNPs, eQTLs, LD SNPs, methylations, chromatin interactions and TADs. Especially, ATACdb provides accurate inference of TF footprints within chromatin accessibility regions. ATACdb is a powerful platform that provides the most comprehensive accessible chromatin data, QC, TF footprint and various other annotations.

Characteristics of the Gut Microbiota in Young Adults with Autism Spectrum Disorder.

BACKGROUND: Although the characteristics of the gut microbiota of children with autism spectrum disorder (ASD) have been well studied, those of young adults with ASD have seldom been reported. METHODS: Using 16S rRNA gene sequencing, we characterized the gut microbiota of 19 young adults with ASD and compared them with that of 19 healthy adults. A random forest prediction model was used to distinguish between the two groups at the genus level. RESULTS: The abundance levels of one phylum, seven families, and 18 genera in adults with ASD were significantly different from those of controls. The genus Phascolarctobacterium was significantly enriched in adults with ASD, which might elicit ASD-like behavior through production of propionate. In addition, a random forest model identified 15 genera that could distinguish adults with ASD from healthy controls with areas under the receiver operating curve of 92.86%, and ten of them were biomarkers identified by LEfSe. CONCLUSIONS: Our results identified specific gut bacteria associated with ASD, and the successful application of certain genera in the prediction model further supports the association between gut microbiota and ASD.

Single image dehazing algorithm based on optical diffraction deep neural networks.

Single image dehazing is a challenging task because of the hue and brightness distortion problems due to the atmospheric scattering. These problems limit the perceptual fidelity, as well as information integrity, of a given image. In this paper, we propose an image dehazing method based on the optical neural networks dehazing by simulating optical diffraction. The algorithm is trained from a large number of hazy images and their corresponding clean images. The experimental results demonstrate that the proposed method has reached an advanced level in both PSNR and SSIM dehazing performance indicators, and the amount of calculation is less than most artificial neural networks.

The pathogens of secondary infection in septic patients share a similar genotype to those that predominate in the gut.

BACKGROUND: Secondary nosocomial infections, which are commonly caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and vancomycin-resistant Enterococcus faecium (VRE), often develop in septic patients. This study aimed to identify the origin of secondary systemic pathogens and reveal the underlying mechanism of infection. METHODS: In this prospective, observational case-control study, a total of 34 septic patients, 33 non-septic intensive care unit (ICU) patients and 10 healthy individuals serving as controls were enrolled. Three hundred and twelve fecal samples were collected and subjected to 16S rRNA gene amplicon sequencing. Metagenome sequencing was performed to identify the homology between dominant CRKP or VRE in the intestine and pathogens isolated from secondary infectious sites. C57/BL mice were established as pseudo germ-free animal model by pretreatment with broad-spectrum antibiotics for two weeks. RESULTS: The abundance and diversity of the gut microbiota in septic patients was drastically decreased one week after ICU admission, potentially leading to the enrichment of antibiotic-resistant bacteria, such as CRKP. Furthermore, secondary bloodstream and abdominal infections caused by CRKP or VRE in septic patients occurred after intestinal colonization with the predominant bacterial species. Genomic analysis showed that bacteria isolated from secondary infection had high homology with the corresponding predominant intestinal opportunistic pathogens. In addition, animal model experiments validated the hypothesis that the administration of antibiotics caused the enrichment of CRKP and VRE among the intestinal microbiota, increasing the likelihood of permeation of other tissues and potentially causing subsequent systemic infection in pseudo germ-free mice. CONCLUSION: Our study indicated that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens following broad-spectrum antibiotic treatment.

ENdb: a manually curated database of experimentally supported enhancers for human and mouse.

Enhancers are a class of cis-regulatory elements that can increase gene transcription by forming loops in intergenic regions, introns and exons. Enhancers, as well as their associated target genes, and transcription factors (TFs) that bind to them, are highly associated with human disease and biological processes. Although some enhancer databases have been published, most only focus on enhancers identified by high-throughput experimental techniques. Therefore, it is highly desirable to construct a comprehensive resource of manually curated enhancers and their related information based on low-throughput experimental evidences. Here, we established a comprehensive manually-curated enhancer database for human and mouse, which provides a resource for experimentally supported enhancers, and to annotate the detailed information of enhancers. The current release of ENdb documents 737 experimentally validated enhancers and their related information, including 384 target genes, 263 TFs, 110 diseases and 153 functions in human and mouse. Moreover, the enhancer-related information was supported by experimental evidences, such as RNAi, in vitro knockdown, western blotting, qRT-PCR, luciferase reporter assay, chromatin conformation capture (3C) and chromosome conformation capture-on-chip (4C) assays. ENdb provides a user-friendly interface to query, browse and visualize the detailed information of enhancers. The database is available at http://www.licpathway.net/ENdb.

SEdb: a comprehensive human super-enhancer database.

Super-enhancers are important for controlling and defining the expression of cell-specific genes. With research on human disease and biological processes, human H3K27ac ChIP-seq datasets are accumulating rapidly, creating the urgent need to collect and process these data comprehensively and efficiently. More importantly, many studies showed that super-enhancer-associated single nucleotide polymorphisms (SNPs) and transcription factors (TFs) strongly influence human disease and biological processes. Here, we developed a comprehensive human super-enhancer database (SEdb, http://www.licpathway.net/sedb) that aimed to provide a large number of available resources on human super-enhancers. The database was annotated with potential functions of super-enhancers in the gene regulation. The current version of SEdb documented a total of 331 601 super-enhancers from 542 samples. Especially, unlike existing super-enhancer databases, we manually curated and classified 410 available H3K27ac samples from >2000 ChIP-seq samples from NCBI GEO/SRA. Furthermore, SEdb provides detailed genetic and epigenetic annotation information on super-enhancers. Information includes common SNPs, motif changes, expression quantitative trait locus (eQTL), risk SNPs, transcription factor binding sites (TFBSs), CRISPR/Cas9 target sites and Dnase I hypersensitivity sites (DHSs) for in-depth analyses of super-enhancers. SEdb will help elucidate super-enhancer-related functions and find potential biological effects.

High repetition rate 102 W middle infrared ZnGeP2 master oscillator power amplifier system with thermal lens compensation.

We demonstrate a 102 W middle infrared ZnGeP2 (ZGP) optical parametric amplifier (OPA) pumped by a 2097-nm Q-switched Ho:YAG laser at a pulse repetition frequency of 10 kHz. The seed middle infrared laser was produced by a ZGP optical parametric oscillator. Its average power was 28.4 W pumped by a 50 W 2097-nm laser. By thermal lens compensation, the beam factor M2 reduced from 3.1 to 2.1. When the incident Ho pump power was 120 W, the middle infrared ZGP OPA yielded the maximum average output power of 102 W and slope efficiency of 61.7%. The overall optical conversion efficiency of 60% from Ho to middle infrared was obtained for the whole middle infrared laser system. In addition, at the maximum average output power, the beam quality factors of the middle infrared ZGP OPA were measured to be about 2.7 and 2.8 for horizontal and vertical directions, respectively.

110.4 mJ, 1 kHz repetition rate, Ho:YAG master oscillator power amplifier.

We reported a high-energy, high-pulse-repetition-frequency Ho:YAG master oscillator and power amplifier (MOPA), which was resonantly dual-end pumped by Tm:YLF lasers at room temperature. At a pulse repetition frequency of 1 kHz, the Ho:YAG MOPA laser system produced a maximum pulse energy of 110.4 mJ with a 28 ns pulse width, corresponding to a peak power of approximately 3.94 MW. The output wavelength of the Ho:YAG MOPA laser system was 2090.9 nm. In addition, a beam quality factor M2 of about 1.7 was achieved at maximum output level.

Comparison of mid-infrared ZnGeP2 rectangle ring optical parametric oscillators of three types of resonant regimes.

We experimentally demonstrated doubly resonant oscillator (DRO), signal singly resonant oscillator (SSRO), and idler singly resonant oscillator (ISRO) ZnGeP2 (ZGP) optical parametric oscillators (OPOs), respectively, pumped by a 1 kHz Q-switched Ho:YAG laser. At the full incident pump energy, the ISRO got the highest output pulse energy of 8.38 mJ and the best beam quality factors Mx2 of 2.3 for idler (4.6 µm) and 2.7 for signal (3.8 µm) but got the highest threshold of 3.97 MW/cm2. The DRO had the lowest threshold of 3.12 MW/cm2 but had the lowest output energy of 8.29 mJ and the worst Mx2 of 3.9 for idler and 4.1 for signal. The output laser characteristics of the SSRO were slightly worse than those of the ISRO. The experimental results show that the ISRO is the most suitable resonant regime for high brightness mid-infrared ZGP planar ring OPOs pumped by 2 µm nanosecond lasers.

Wavelength-locked continuous-wave and Q-switched Ho:CaF2 laser at 2100.5 nm.

In this paper, we demonstrated a linewidth-narrowed continuous-wave (CW) and acousto-optical Q-switched Ho:CaF2 laser for the first time. With a volume Bragg grating, a maximum CW output power of 6.94 W at 2100.5 nm, and slope efficiency of 57.9%, an FWHM linewidth of 0.31 nm was obtained. When absorbed pump power was 13.2 W, the maximum average output powers of 6.08 W, 5.9 W, and 5.71 W were achieved in a Q-switched Ho:CaF2 laser under pulse repetition frequencies of 10 kHz, 5 kHz, and 3 kHz, corresponding to the slope efficiencies of 51.2%, 49.6%, and 48.5%, respectively. The minimum pulse width of 54 ns was achieved at pulse repetition frequency of 3 kHz.

11.4 W long-wave infrared source based on ZnGeP2 optical parametric amplifier.

In this paper we present a high power long-wave infrared ZnGeP2 (ZGP) optical parametric amplifier (OPA) pumped by a 2097-nm Q-switched Ho:YAG laser with pulse repetition frequency of 20 kHz. When the incident Ho pump power was 116.0 W, the maximum average output power of 11.4 W at 8.3 µm was achieved in the ZGP OPA. The optical conversion efficiency from Ho to long-wave infrared was about 9.8%. The ZGP OPA produced 30.4 ns long-wave infrared laser pulse. The beam quality factor (M2) of ZGP OPA was measured to be about 2.9 at the maximum average output power.

Efficient middle-infrared ZGP-OPO pumped by a Q-switched Ho:LuAG laser with the orthogonally polarized pump recycling scheme.

We describe an efficient middle-infrared laser source based on the Tm:YLF-Ho:LuAG-ZnGeP2 system in this paper. A new orthogonally polarized recycling pump scheme with a simple thin-film polarizer and a half-wave plate are used in a Ho:LuAG laser. Under an incident pump power of 63.8 W, we achieve a maximum continuous wave output power of 35.7 W in the Ho:LuAG laser, corresponding to a slope efficiency of 60.4% and an optical-to-optical efficiency of 56.0%. With the Q-switched mode, maximum average output powers of 34.1 W, 34.9 W, and 35.2 W were achieved in the Ho:LuAG laser with pulse repetition frequencies of 10 kHz, 15 kHz, and 20 kHz, respectively. With a Ho pump power of 34.1 W, maximum average output powers of 16.7 W, 15.3 W, and 12.6 W were achieved in a middle-infrared zinc germanium phosphide optical parametric oscillator (ZGP-OPO) under pulse repetition frequencies of 10 kHz, 15 kHz, and 20 kHz, respectively. The evaluated beam quality factor M2 of the ZGP-OPO was 2.2 for the signal and 1.9 for the idler. To the authors' best knowledge, this is the best performance reported for a middle-infrared ZGP-OPO pumped by a Ho:LuAG laser.