PBAC: A pathway-based attention convolution neural network for predicting clinical drug treatment responses.

Precise and personalized drug application is crucial in the clinical treatment of complex diseases. Although neural networks offer a new approach to improving drug strategies, their internal structure is difficult to interpret. Here, we propose PBAC (Pathway-Based Attention Convolution neural network), which integrates a deep learning framework and attention mechanism to address the complex biological pathway information, thereby provide a biology function-based robust drug responsiveness prediction model. PBAC has four layers: gene-pathway layer, attention layer, convolution layer and fully connected layer. PBAC improves the performance of predicting drug responsiveness by focusing on important pathways, helping us understand the mechanism of drug action in diseases. We validated the PBAC model using data from four chemotherapy drugs (Bortezomib, Cisplatin, Docetaxel and Paclitaxel) and 11 immunotherapy datasets. In the majority of datasets, PBAC exhibits superior performance compared to traditional machine learning methods and other research approaches (area under curve = 0.81, the area under the precision-recall curve = 0.73). Using PBAC attention layer output, we identified some pathways as potential core cancer regulators, providing good interpretability for drug treatment prediction. In summary, we presented PBAC, a powerful tool to predict drug responsiveness based on the biology pathway information and explore the potential cancer-driving pathways.

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.

Mechanically Responsive Circularly Polarized Luminescence from Cellulose-Nanocrystal-Based Shape-Memory Polymers.

Stimulus-responsive materials that display circularly polarized luminescence (CPL) have attracted great attention for application in chiral sensors and smart displays. However, due to difficulties in the regulation of chiral structures, fine control of CPL remains a challenge. Here, it is demonstrated that cellulose nanocrystal shape-memory polymers (CNC-SMPs) with luminescent components enable mechanically responsive CPL. The chiral nematic organization of CNCs in the material gives rise to a photonic bandgap. By manipulating the photonic bandgap or luminescence wavelengths of the luminescent CNC-SMPs, precise control of CPL emission with varied wavelengths and high dissymmetry factors (glum ) is achieved. Specifically, CPL emission can be switched reversibly by treating the luminescent CNC-SMPs with hot-pressing and recovery by heating. Pressure-responsive CPL with tunable glum values is ascribed to the pressure-responsive photonic bandgaps. Moreover, colorimetric and CPL-active patterns are created by imprinting desired forms into SMP samples. This study demonstrates a novel way to fabricate smart CPL systems using biomaterials.

Cellulose nanocrystals-based bio-composite optical materials for reversible colorimetric responsive films and coatings.

Photonic materials with a tunable chiral nematic structure that can selectively reflect light dynamically are valuable for applications in smart responsive materials. Here, we prepared potential photonic composites with a chiral nematic structure by forming cellulose nanocrystals (CNCs) and waterborne polyurethane (WPU) composites with different compositions on different substrates by evaporation-induced self-assembly. With increasing WPU content, the reflected wavelength increased from 400 to 680 nm, which was mainly caused by the increase of the chiral nematic pitch. In addition, the mechanical properties were better for higher WPU content. WPU was sensitive to small amounts of moisture in ethanol owing to the swollen WPU after absorbing water will increase the helical pitch. The reversible red shift induced by moisture was approximately 100 nm. When wood was used as the substrate, the CNCs still self-assembled to form chiral nematic structures and the adhesion forces of the composites to the wood substrate were strong. By using MgCl2 solution as an ink, invisible patterns can be written on the coating, which can be revealed temporarily by ethanol. In addition, the invisible pattern of photonic coating is rewritable. The easily prepared environmentally friendly photonic composite has great potential in sensors, anti-counterfeiting labels and smart decorative coatings.

Exploring the Circular Polarization Capacity from Chiral Cellulose Nanocrystal Films for a Photo-Controlled Chiral Helix of Supramolecular Polymers.

Circularly polarized light (CPL) is key to asymmetric photochemistry as it could impart the chiral organization information into chemical products. Here, we demonstrate the circular polarization capacity of chiral cellulose nanocrystal (CNC) films to trigger photo-alignment of achiral supramolecular polymers into helical structures. Right-handed transmitted (T-) CPL was generated from self-assembled CNC films, which induced amorphous azobenzene (Azo) supramolecular polymers into chiral structures. The chiral induction effect of T-CPL is enhanced on Azo polymers with longer spacers. The absorptive dissymmetry factor (gabs ) values of liquid-crystal supramolecular polymers can be amplified significantly (over 10 times) after T-CPL irradiation. Moreover, by integrating carbon dots into CNC films, CPL emission with a considerable luminescence dissymmetry factor (glum ) up to -0.66 was achieved, and it could be used for the photo-alignment of Azo polymers with high chiroptical properties. This work provides new insight for the photo modulation of supramolecular polymers by CPL-active materials.

Reversible Controlling the Supramolecular Chirality of Side Chain Azobenzene Polymers: Chiral Induction and Modulation.

Chirality represents a fundamental structure in nature and the induction and reversible modulation of supramolecular chirality with feasible techniques is of great value in the design of new chiroptical smart materials. Herein, two kinds of azobenzene side-chain polymers (without spacer: Azo-PMA0; with 6 spacers: Azo-PMA6) are synthesized, the length of spacer and azobenzene chromophores play a vital role in chirality transfer and modulation. The supramolecular chiral arrangement of Azo-PMA0 (amorphous phase) can be completely controlled and reversibly modulated over multiple cycles by 450 nm circularly polarized light driven by the supramolecular interaction between azo groups of polymer chains, with an absorption dissymmetry factor (g) value of 0.0019. The chiroptical properties of Azo-PMA6 (liquid crystal state) can also be reversibly modulated by UV light and thermal annealing treatment during trans-cis isomerization of azo chromophore, with the g-value changes from 0-0.038. The successful construction of reversible chiral induction and modulation based on side chain azobenzene polymers may pave the way for designing photo-switchable functional materials.

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.

Cancer CRC: A Comprehensive Cancer Core Transcriptional Regulatory Circuit Resource and Analysis Platform.

A core transcriptional regulatory circuit (CRC) is a group of interconnected auto-regulating transcription factors (TFs) that form loops and can be identified by super-enhancers (SEs). Studies have indicated that CRCs play an important role in defining cellular identity and determining cellular fate. Additionally, core TFs in CRCs are regulators of cell-type-specific transcriptional regulation. However, a global view of CRC properties across various cancer types has not been generated. Thus, we integrated paired cancer ATAC-seq and H3K27ac ChIP-seq data for specific cell lines to develop the Cancer CRC (http://bio.liclab.net/Cancer_crc/index.html). This platform documented 94,108 cancer CRCs, including 325 core TFs. The cancer CRC also provided the "SE active core TFs analysis" and "TF enrichment analysis" tools to identify potentially key TFs in cancer. In addition, we performed a comprehensive analysis of core TFs in various cancer types to reveal conserved and cancer-specific TFs.

Hydrothermal synthesis of nitrogen-doped carbon quantum dots from lignin for formaldehyde determination.

This work assessed the fabrication of nitrogen-doped CQDs (NCQDs) from alkali lignin (AL) obtained from spruce, representing a green, low-cost biomass generated by the pulp and biorefinery industries. The AL was found to retain its original lignin skeleton and could be used to produce NCQDs with excellent photoluminescence properties by one-pot hydrothermal treatment of AL and m-phenylenediamine. These NCQDs exhibited blue-green fluorescence (FL) with excitation/emission of 390/490 nm under optimal conditions. The NCQDs showed pH and excitation wavelength-dependent FL emission behaviors. On the basis of the exceptional selective response of these NCQDs to specific solvents, we developed a FL probe for the detection of formaldehyde (FA). The FL intensity of NCQDs was found to be directly proportional to the concentration of FA in the range of 0.05 to 2 mM (R 2 = 0.993), with a detection limit of 4.64 µM (based on 3σ/K). A composite film comprising NCQDs with poly(vinyl alcohol) was found to act as a sensor with a good FL response to FA gas. When exposed to gaseous FA, this film exhibited increased FL intensity and transitioned from blue-green to blue. A mechanism is proposed in which the NCQDs react rapidly with FA to generate Schiff bases that result in enhanced FL emission and the observed blue shift in color.

Compressible, anisotropic lamellar cellulose-based carbon aerogels enhanced by carbon dots for superior energy storage and water deionization.

Heteroatom-doped carbon materials have received great attention for applications in electrode materials. However, conventional heteroatom-doping methods sacrifice conductivity, stability, and specific surface area (SSA). Here, the carbon quantum dots (CDs) are used as carriers of N, P, O to form electron-rich regions promoting electron transport without decreasing stability and SSA. The CDs promote the formation of graphitic nitrogen in the composite, which effectively reduces their internal resistance by increasing the dielectric constant. Moreover, the orderly growth of ice crystals generates a unique bridged layer structure under bidirectional freeze-casting in a mixture of GO/CDs/microfibrillated cellulose, which gives the composite super-compressibility. Notably, the optimal sample has a 117% increase in specific capacitance. The CDs also improve wettability and thus reduce the charge transfer resistance giving a large desalination capacity of 32.59 mg g-1 (504 mg L-1 NaCl). This work illustrates the unique role of CDs in improving the electrochemical performance of composites.

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.

MiRNA-Mediated Subpathway Identification and Network Module Analysis to Reveal Prognostic Markers in Human Pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) remains one of the most lethal cancers. In contrast to the steady increase in survival for most cancers, the 5-year survival remains low for PC patients. METHODS: We describe a new pipeline that can be used to identify prognostic molecular biomarkers by identifying miRNA-mediated subpathways associated with PC. These modules were then further extracted from a comprehensive miRNA-gene network (CMGN). An exhaustive survival analysis was performed to estimate the prognostic value of these modules. RESULTS: We identified 105 miRNA-mediated subpathways associated with PC. Two subpathways within the MAPK signaling and cell cycle pathways were found to be highly related to PC. Of the miRNA-mRNA modules extracted from CMGN, six modules showed good prognostic performance in both independent validated datasets. CONCLUSIONS: Our study provides novel insight into the mechanisms of PC. We inferred that six miRNA-mRNA modules could serve as potential prognostic molecular biomarkers in PC based on the pipeline we proposed.

Designing Hybrid Chiral Photonic Films with Circularly Polarized Room-Temperature Phosphorescence.

Circular polarized luminescence (CPL) is essential to chiral sciences and photonic technologies, but the achievement of circular polarized room-temperature phosphorescence (CPRTP) remains a great challenge due to the instability of triplet state excitons. Herein, we found that dual CPL and CPRTP were demonstrated by hybrid chiral photonic films designed by the coassembly of cellulose nanocrystals (CNCs), poly(vinyl alcohol) (PVA), and carbon dots (CDs). Tunable photonic band gaps were achieved by regulating the ratio of CNC/PVA in the hybrid films, leading to tunable CPL with invertible handedness, tunable wavelengths, and considerable dissymmetric factors (glum) up to -0.27. In particularly, triplet excitons produced by CDs were stable in the chiral photonic crystal environment, resulting in tunable right-handed CPRTP with long lifetimes up to 103 ms and large RTP dissymmetric factors (gRTP) up to -0.47. Moreover, patterned films with multiple polarized features were demonstrated by a mold technique.

Luminescent Transparent Wood Based on Lignin-Derived Carbon Dots as a Building Material for Dual-Channel, Real-Time, and Visual Detection of Formaldehyde Gas.

Formaldehyde (FA) is a widespread indoor air pollutant, and its efficient detection is a major industrial challenge. The development of a building material with real-time and visual self-detection of FA gas is highly desirable for meeting both construction and human health demands. Herein, a luminescent transparent wood (LTW) as the building material was developed for dual-channel, real-time, and visual detection of FA gas. It was fabricated by encapsulating multicolor lignin-derived carbon dots (CDs) and poly(vinyl alcohol) (PVA) into a delignified wood framework. It exhibited 85% optical transmittance, tunable room-temperature phosphorescence (RTP), and ratiometric fluorescence (FL) emission. The tunable luminescence was attributed to different CD graphitization and surface functionalization. The color-responsive ratiometric FL and delayed RTP detections of FA were displayed over the range of 20-1500 µM (R2 = 0.966, LOD = 1.08 nM) and 20-2000 µM (R2 = 0.977, LOD = 45.8 nM), respectively. The LTW was also used as an encapsulation film on a UV-emitting InGaN chip to form white light-emitting diodes, indicating the feasibility as an FA-responsive planar light source. The operational notion of functional LTW can expand its applications to new fields such as a stimuli-responsive light-transmitting window or planar light sources while monitoring indoor air pollutants, temperature, and humidity.

Nitrogen and copper (II) co-doped carbon dots for applications in ascorbic acid determination by non-oxidation reduction strategy and cellular imaging.

Nitrogen and copper co-doped carbon dots (Cu-NCDs) were prepared by solvothermal carbonization of folic acid and CuCl2. The N-containing groups including sp2-hybridized CN, porphyrin C-N-C and amino N in N-(C) 3 or H-N-(C) 2, and the Cu-containing group, N-Cu-N, have formed on the surface and framework of Cu-NCDs. The Cu-NCDs were monodisperse with the average particle diameter of 3.57 nm and exhibited dual fluorescence emission peaks at 410 and 470 nm with the excitation wavelength of 340 nm. The new emission center of 410 nm might originate from the Cu doping which changed the structural network and surface state of the carbon dots. The Cu-NCDs exhibited good fluorescence quenching response towards ascorbic acid (AA) from 0.02 to 40 µM (R2 = 0.992), and the limit of detection was 17.8 nM. The mechanism of the quenching process is non-oxidation reduction strategy based static quenching (SQE). Cu doping can improve the selectivity and sensitivity for Cu-NCDs towards AA benefiting from its chelation effect towards multi-hydroxyl in AA. Cu and N doping cause positively charged surface of Cu-NCDs, improving the interaction towards AA and then the stable Cu-NCD-based non-luminescent compounds formed, which resulted SQE. The Cu-NCDs possessed low cellular toxicity and showed good uptake by HepG2 cells.

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.

Hydrothermal synthesis of green fluorescent nitrogen doped carbon dots for the detection of nitrite and multicolor cellular imaging.

A fluorescent probe for the determination of nitrite (NO2-) was fabricated by using green fluorescent nitrogen doped carbon dots (NCDs). The NCDs were synthesized via a one-pot hydrothermal carbonization of citric acid in the presence of p-phenylenediamine as the nitrogen source. The N content of the NCDs was high to 17.09% and consisted of a variety of functional groups on the NCDs surface, including sp2-hybridized CN, porphyrin C-N-C and amino N in N-(C) 3 or H-N-(C) 2 et al. N atoms were also doped within the framework of the NCDs. The almost monodisperse NCDs (average particle diameter = 3.67 nm) exhibited green photoluminescence (PL) with excitation/emission maxima of 360/505 nm. The PL of the NCDs was dependent on both excitation wavelength and solution pH. The NCDs showed a strong PL quenching response to NO2- under acidic conditions (pH = 2.5). The PL intensity of the NCDs was inversely proportional to the concentration of NO2- between 0.02 and 40 µM (R2 = 0.992), with a detection limit of 21.2 nM. The practical use of the nanoprobe for NO2- determination in food samples was also demonstrated, successfully. NCD-nitroso compounds formed because of reaction between the abundant amide groups on the surface of NCDs with the NO2-, which caused an inner filter effect and static PL quenching. Importantly, the NCDs had low cellular toxicity and were successfully used as a multicolor cellular imaging agent for Hepg2 cells.

A facile hydrothermal method-fabricated robust and ultralight weight cellulose nanocrystal-based hydro/aerogels for metal ion removal.

Heavy metal ion contamination, in particular that associated with Pb2+, Cd2+, and Cu2+, poses a considerable threat to aquatic environments and human health. To obtain a highly efficient adsorbent, in this work, a facile hydrothermal method was applied to prepare acrylic acid grafted onto cellulose nanocrystal (AA-g-CNC) hydro/aerogel as an adsorbent for Pb2+, Cd2+, and Cu2+ removal. The obtained AA-g-CNC hydrogels withstood up to 0.821 MPa of compression and showed good reciprocating performance when the deformation reached 40%. The as-formed AA-g-CNC aerogels had highly porous honeycomb structure, with many functional groups and a high zeta potential, all of which are essential features for an effective adsorbent. The maximum Pb2+, Cd2+, and Cu2+ removal capacities of AA-g-CNC aerogels reached 1026, 898.8, and 872.4 mg/g respectively. Their adsorption followed the Freundlich isotherm model and fitted well with pseudo-second-order kinetic models. The adsorption mechanism mainly attributed to electrostatic chelation between metal ions with sulfonate and carboxylate groups.

Tunable Upconverted Circularly Polarized Luminescence in Cellulose Nanocrystal Based Chiral Photonic Films.

Integrating chromophores into chiral photonic crystals to fabricate materials that exhibit circularly polarized luminescence (CPL) is promising as this method allows efficient manipulation of the spontaneous emission within photonic bandgaps (PBGs). However, tuning the wavelength of CPL and the dissymmetry factor ( glum) in a convenient and accurate manner remains a significant challenge. Here, right-handed, tunable upconverted CPL (UC-CPL) emission was achieved by integrating multiple emissive, upconverting nanoparticles into cellulose nanocrystal based chiral photonic films that had tunable PBGs. Glycerol was used to tune the PBGs of the chiral photonic films, which yielded tunable UC-CPL emission at 450 and 620 nm with a tailored glum. Moreover, humidity responsive UC-CPL at blue wavelength was obtained from glycerol-composite photonic film, with a glum that ranged from -0.156 to -0.033. It was possible because the PBG and chirality of photonic composite was responded to the relative humidity. This work gives valuable insight into tunable and stimuli-responsive CPL photonic systems.