Sunlight-powered sustained flight of an ultralight micro aerial vehicle.

Limited flight duration is a considerable obstacle to the widespread application of micro aerial vehicles (MAVs)1-3, especially for ultralightweight MAVs weighing less than 10 g, which, in general, have a flight endurance of no more than 10 min (refs. 1,4). Sunlight power5-7 is a potential alternative to improve the endurance of ultralight MAVs, but owing to the restricted payload capacity of the vehicle and low lift-to-power efficiency of traditional propulsion systems, previous studies have not achieved untethered sustained flight of MAVs fully powered by natural sunlight8,9. Here, to address these challenges, we introduce the CoulombFly, an electrostatic flyer consisting of an electrostatic-driven propulsion system with a high lift-to-power efficiency of 30.7 g W-1 and an ultralight kilovolt power system with a low power consumption of 0.568 W, to realize solar-powered sustained flight of an MAV under natural sunlight conditions (920 W m-2). The vehicle's total mass is only 4.21 g, within 1/600 of the existing lightest sunlight-powered aerial vehicle6.

Episymbiotic Saccharibacteria TM7x modulates the susceptibility of its host bacteria to phage infection and promotes their coexistence.

Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface-associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA-Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down-regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x-associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont-mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source-sink" dynamics between phage and bacteria in biofilm, promoting their long-term coexistence within the human microbiome.

Genomic structural variation contributes to evolved changes in gene expression in high-altitude Tibetan sheep.

Tibetan sheep were introduced to the Qinghai Tibet plateau roughly 3,000 B.P., making this species a good model for investigating genetic mechanisms of high-altitude adaptation over a relatively short timescale. Here, we characterize genomic structural variants (SVs) that distinguish Tibetan sheep from closely related, low-altitude Hu sheep, and we examine associated changes in tissue-specific gene expression. We document differentiation between the two sheep breeds in frequencies of SVs associated with genes involved in cardiac function and circulation. In Tibetan sheep, we identified high-frequency SVs in a total of 462 genes, including EPAS1, PAPSS2, and PTPRD. Single-cell RNA-Seq data and luciferase reporter assays revealed that the SVs had cis-acting effects on the expression levels of these three genes in specific tissues and cell types. In Tibetan sheep, we identified a high-frequency chromosomal inversion that exhibited modified chromatin architectures relative to the noninverted allele that predominates in Hu sheep. The inversion harbors several genes with altered expression patterns related to heart protection, brown adipocyte proliferation, angiogenesis, and DNA repair. These findings indicate that SVs represent an important source of genetic variation in gene expression and may have contributed to high-altitude adaptation in Tibetan sheep.

iEnhance: a multi-scale spatial projection encoding network for enhancing chromatin interaction data resolution.

Although sequencing-based high-throughput chromatin interaction data are widely used to uncover genome-wide three-dimensional chromatin architecture, their sparseness and high signal-noise-ratio greatly restrict the precision of the obtained structural elements. To improve data quality, we here present iEnhance (chromatin interaction data resolution enhancement), a multi-scale spatial projection and encoding network, to predict high-resolution chromatin interaction matrices from low-resolution and noisy input data. Specifically, iEnhance projects the input data into matrix spaces to extract multi-scale global and local feature sets, then hierarchically fused these features by attention mechanism. After that, dense channel encoding and residual channel decoding are used to effectively infer robust chromatin interaction maps. iEnhance outperforms state-of-the-art Hi-C resolution enhancement tools in both visual and quantitative evaluation. Comprehensive analysis shows that unlike other tools, iEnhance can recover both short-range structural elements and long-range interaction patterns precisely. More importantly, iEnhance can be transferred to data enhancement of other tissues or cell lines of unknown resolution. Furthermore, iEnhance performs robustly in enhancement of diverse chromatin interaction data including those from single-cell Hi-C and Micro-C experiments.

Designing efficient randstrobes for sequence similarity analyses.

MOTIVATION: Substrings of length k, commonly referred to as k-mers, play a vital role in sequence analysis. However, k-mers are limited to exact matches between sequences leading to alternative constructs. We recently introduced a class of new constructs, strobemers, that can match across substitutions and smaller insertions and deletions. Randstrobes, the most sensitive strobemer proposed in Sahlin (Effective sequence similarity detection with strobemers. Genome Res 2021a;31:2080-94. https://doi.org/10.1101/gr.275648.121), has been used in several bioinformatics applications such as read classification, short-read mapping, and read overlap detection. Recently, we showed that the more pseudo-random the behavior of the construction (measured in entropy), the more efficient the seeds for sequence similarity analysis. The level of pseudo-randomness depends on the construction operators, but no study has investigated the efficacy. RESULTS: In this study, we introduce novel construction methods, including a Binary Search Tree-based approach that improves time complexity over previous methods. To our knowledge, we are also the first to address biases in construction and design three metrics for measuring bias. Our evaluation shows that our methods have favorable speed and sampling uniformity compared to existing approaches. Lastly, guided by our results, we change the seed construction in strobealign, a short-read mapper, and find that the results change substantially. We suggest combining the two results to improve strobealign's accuracy for the shortest reads in our evaluated datasets. Our evaluation highlights sampling biases that can occur and provides guidance on which operators to use when implementing randstrobes. AVAILABILITY AND IMPLEMENTATION: All methods and evaluation benchmarks are available in a public Github repository at https://github.com/Moein-Karami/RandStrobes. The scripts for running the strobealign analysis are found at https://github.com/NBISweden/strobealign-evaluation.

IL-37 Attenuates Platelet Activation and Thrombosis Through IL-1R8 Pathway.

BACKGROUND: IL-37 (interleukin-37), a natural suppressor of innate inflammatory and immune responses, is increased in patients with myocardial infarction. Platelets play an important role in the progress of myocardial infarction, but the direct effects of IL-37 on platelet activation and thrombosis, as well as the underlying mechanisms, still remain unclear. METHODS: We evaluated the direct effects of IL-37 on agonists-induced platelet activation and thrombus formation, as well as revealed the underlying mechanisms using platelet-specific IL-1R8 (IL-1 receptor 8)-deficient mice. Using myocardial infarct model, we explored the effects of IL-37 on microvascular obstruction and myocardial injury. RESULTS: IL-37 directly inhibited agonists-induced platelet aggregation, dense granule ATP release, P-selectin exposure, integrin αIIbß3 activation, platelet spreading, and clot retraction. IL-37 inhibited thrombus formation in vivo in a FeCl3-injured mesenteric arteriole thrombosis mouse model and ex vivo in a microfluidic whole-blood perfusion assay. Mechanistic studies using platelet-specific IL-1R8-deficient mice revealed that IL-37 bound to platelet IL-1R8 and IL-18Rα, and IL-1R8 deficiency impaired the inhibitory effects of IL-37 on platelet activation. Using PTEN (phosphatase and tensin homolog)-specific inhibitor and PTEN-deficient platelets, we found that IL-37 combined with IL-1R8 to enhance PTEN activity, inhibit Akt (protein kinase B), mitogen-activated protein kinases, and spleen tyrosine kinase pathways, as well as decrease the generation of reactive oxygen species to regulate platelet activation. Exogenous IL-37 injection suppressed microvascular thrombosis to protect against myocardial injury in wild-type mice but not in platelet-specific IL-1R8-deficient mice after permanent ligation of the left anterior descending coronary. Finally, a negative correlation between plasma IL-37 concentration and platelet aggregation was observed in patients with myocardial infarction. CONCLUSIONS: IL-37 directly attenuated platelet activation, thrombus formation, and myocardial injury via IL-1R8 receptor. Accumulated IL-37 in plasma inhibited platelet activation to ameliorate atherothrombosis and infarction expansion, and thus may have therapeutic advantages as potential antiplatelet drugs.

Targeting of ubiquitination and degradation of KLF15 by E3 ubiquitin ligase KBTBD7 regulates LPS-induced septic brain injury in microglia.

Septic brain injury is a serious disease of the central nervous system that involves inflammation. Kelch repeat and BTB domain containing 7 (KBTBD7), an E3 ubiquitin ligase, is demonstrated to facilitate the pathological changes of various diseases, but its impact on septic brain injury is unclear. In this study, a rat model of septic brain injury was induced by cecal ligation and puncture (CLP). The neurobehavioral score and survival rate of CLP group were worse than those of sham group. In addition, CLP was found to evoke microglia activation, increase inflammation, induce the activation of NLRP3 inflammasome and NF-κB signaling pathway, and upregulate KBTBD7 expression. Immunofluorescence revealed strong positive KBTBD7 staining in CLP rat microglia. Furthermore, primary microglia were exposed to lipopolysaccharide (LPS) to explore the role and mechanism of KBTBD7. The results showed that KBTBD7 expression was increased in LPS-treated microglia. Knockdown of KBTBD7 markedly inhibited LPS-induced proinflammatory cytokine release, as well as the activation of NLRP3 inflammasome and NF-κB signaling pathway. The downstream molecular mechanism of KBTBD7 was then mined. Notably, co-immunoprecipitation (co-IP) results confirmed that KBTBD7 was a novel interacting protein of KLF transcription factor 15 (KLF15) and acted as an E3 ubiquitin ligase that catalyzed the ubiquitination degradation of KLF15 through the ubiquitin-proteasome system. Moreover, recovery experiment data suggested that KLF15 knockdown abolished the anti-inflammatory role of KBTBD7 knockdown in microglia, implying that KLF15 influenced the function of KBTBD7. Taken together, our results reveal a novel KBTBD7-KLF15 signal transduction pathway involved in septic brain injury and provide a potential therapeutic strategy for its treatment.

Dual-Modal Cellular Nanoparticles for Continuous Neurotoxin Detoxification.

Neurotoxins are known for their extreme lethality. However, due to their enormous diversity, effective and broad-spectrum countermeasures are lacking. This study presents a dual-modal cellular nanoparticle (CNP) formulation engineered for continuous neurotoxin neutralization. The formulation involves encapsulating the metabolic enzyme N-sulfotransferase (SxtN) into metal-organic framework (MOF) nanoparticle cores and coating them with a natural neuronal membrane, termed "Neuron-MOF/SxtN-NPs". The resulting nanoparticles combine membrane-enabled broad-spectrum neurotoxin neutralization with enzyme payload-enabled continuous neurotoxin neutralization. The studies confirm the protection of the enzyme payload by the MOF core and validate the continuous neutralization of saxitoxin (STX). In vivo studies conducted using a mouse model of STX intoxication reveal markedly improved survival rates compared with control groups. Furthermore, acute toxicity assessments show no adverse effects associated with the administration of Neuron-MOF/SxtN-NPs in healthy mice. Overall, Neuron-MOF/SxtN-NPs represent a unique biomimetic nanomedicine platform poised to effectively neutralize neurotoxins, marking an important advancement in the field of countermeasure nanomedicine.

Rare-Earth-Modified NiS2 Improves OH Coverage for an Industrial Alkaline Water Electrolyzer.

The low coverage rate of anode OH adsorption under high current density conditions has become an important factor restricting the development of an industrial alkaline water electrolyzer (AWE). Here, we present our rare earth modification promotion strategy on using the rare earth oxygen-friendly interface to increase the OH coverage of the NiS2 surface for efficient AWE anode catalysis. Density functional theory calculations predict that rare earths can enhance the coverage of surface OH, and the synthesis reaction mechanism is discussed in the synthesis process spectrum. Experimentally, by preparing a series of rare-earth-modified NiS2, the relationship between OH coverage, active site density, and catalytic activity was established by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, time-resolved absorption spectra, and so on. The unique oxygenophilic properties of rare earths enhance OH coverage, thereby increasing the density of active sites for efficient catalysis. Furthermore, Eu2O3/NiS2 was assembled into the AWE equipment and operated stably for over 240 h at a current density of 300 mA cm-2 under industrial conditions of 80 °C and 30% KOH. Rare-earth-modified NiS2 exhibits better catalytic activity than traditional non-noble metal anode catalysts Ni(OH)2 and NiS2, providing a new approach for rare earth promotion to solve the problem of low OH coverage in the AWE anode.

ProBDNF contributed to patrolling monocyte infiltration and renal damage in systemic lupus erythematosus.

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1+ patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1+ PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE.

Detection of Single Nucleotide Polymorphisms of Circulating Tumor DNA by Strand Displacement Amplification Coupled with Liquid Chromatography.

The detection of multiple single nucleotide polymorphisms (SNPs) of circulating tumor DNA (ctDNA) is still a great challenge. In this study, we designed enzyme-assisted nucleic acid strand displacement amplification combined with high-performance liquid chromatography (HPLC) for the simultaneous detection of three ctDNA SNPs. First, the trace ctDNA could be hybridized to the specially designed template strand, which initiated the strand displacement nucleic acid amplification process under the synergistic action of DNA polymerase and restriction endonuclease. Then, the targets would be replaced with G-quadruplex fluorescent probes with different tail lengths. Finally, the HPLC-fluorescence assay enabled the separation and quantification of multiple signals. Notably, this method can simultaneously detect both the wild type (WT) and mutant type (MT) of multiple ctDNA SNPs. Within a linear range of 0.1 fM-0.1 nM, the detection limits of BRAF V600E-WT, EGFR T790M-WT, and KRAS 134A-WT and BRAF V600E-MT, EGFR T790M-MT, and KRAS 134A-MT were 29, 31, and 11 aM and 22, 29, and 33 aM, respectively. By using this method, the mutation rates of multiple ctDNA SNPs in blood samples from patients with lung or breast cancer can be obtained in a simple way, providing a convenient and highly sensitive analytical assay for the early screening and monitoring of lung cancer.

Multiplex Detection of Single Nucleotide Polymorphisms by Liquid Chromatography for Nonsmall Cell Lung Cancer Staging.

In this work, an integrated strategy with excellent accuracy and high throughput is proposed for the precise indication of single nucleotide polymorphism (SNP) in nonsmall cell lung cancer diseases. Two types of point mutations (L858R and T790M) and the corresponding wild types could be identified together in a single high-performance liquid chromatographic run. Signal amplification was achieved through a series of enzyme ligation, primer extension, and enzyme cleavage strategies, and a large number of DNA probes with different fluorescence signals were finally generated. The factors affecting the spatiotemporal separation efficiency of four DNA probes were systematically investigated. The limits of detection of wild types (WTs) or mutant types (MTs) abbreviated as L858R-MT, L858R-WT, T790M-MT, and T790M-WT were 26, 24, 19, and 22 aM, respectively. In addition, the levels of mutant types and wild types in the serum of 40 nonsmall cell lung cancer patients at different stages were detected using the method, and the correlation between the mutation ratios and cancer stages was preliminarily verified. The proposed highly selective and sensitive method may serve as an alternative approach for early diagnosis and staging of nonsmall cell lung cancer.

Metabolic engineering of Candida tropicalis for efficient 1,2,4-butanetriol production.

1,2,4-Butanetriol serves as a precursor in the manufacture of diverse pharmaceuticals and the energetic plasticizer 1,2,4-butanetriol trinitrate. The study involved further modifications to an engineered Candida tropicalis strain, aimed at improving the production efficiency of 1,2,4-butanetriol. Faced with the issue of xylonate accumulation due to the low activity of heterologous xylonate dehydratase, we modulated iron metabolism at the transcriptional level to boost intracellular iron ion availability, thus enhancing the enzyme activity by 2.2-fold. Addressing the NADPH shortfall encountered during 1,2,4-butanetriol biosynthesis, we overexpressed pivotal genes in the NADPH regeneration pathway, achieving a 1,2,4-butanetriol yield of 3.2 g/L. The introduction of calcium carbonate to maintain pH balance led to an increased yield of 4 g/L, marking a 111% improvement over the baseline strain. Finally, the use of corncob hydrolysate as a substrate culminated in 1,2,4-butanetriol production of 3.42 g/L, thereby identifying a novel host for the conversion of corncob hydrolysate to 1,2,4-butanetriol.

Development of a gene-coded biosensor to establish a high-throughput screening platform for salidroside production.

Metabolic engineering reconfigures cellular networks to produce value-added compounds from renewable substrates efficiently. However, identifying strains with desired phenotypes from large libraries through rational or random mutagenesis remains challenging. To overcome this bottleneck, an effective high-throughput screening (HTS) method must be developed to detect and analyze target candidates rapidly. Salidroside is an aromatic compound with broad applications in food, healthcare, medicine, and daily chemicals. However, there currently needs to be HTS methods available to monitor salidroside levels or to screen enzyme variants and strains for high-yield salidroside biosynthesis, which severely limits the development of microbial cell factories capable of efficiently producing salidroside on an industrial scale. This study developed a gene-encoded whole-cell biosensor that is specifically responsive to salidroside. The biosensor was created by screening a site-saturated mutagenic library of uric acid response regulatory protein binding bags. This work demonstrates the feasibility of monitoring metabolic flux with whole-cell biosensors for critical metabolites. It provides a promising tool for building salidroside high-yielding strains for high-throughput screening and metabolic regulation to meet industrial needs.

Strong Interface Coupling Enables Stability of Amorphous Meta-Stable State in CoS/Ni3S2 for Efficient Oxygen Evolution.

Rational design of heterostructure catalysts through phase engineering strategy plays a critical role in heightening the electrocatalytic performance of catalysts. Herein, a novel amorphous/crystalline (a/c) heterostructure (a-CoS/Ni3S2) is manufactured by a facile hydrothermal sulfurization method. Strikingly, the interface coupling between amorphous phase (a-CoS) and crystalline phase (Ni3S2) in a-CoS/Ni3S2 is much stronger than that between crystalline phase (c-CoS) and crystalline phase (Ni3S2) in crystalline/crystalline (c/c) heterostructure (c-CoS/Ni3S2) as control sample, which makes the meta-stable amorphous structure more stable. Meanwhile, a-CoS/Ni3S2 has more S vacancies (Sv) than c-CoS/Ni3S2 because of the presence of an amorphous phase. Eventually, for the oxygen evolution reaction (OER), the a-CoS/Ni3S2 exhibits a significantly lower overpotential of 192 mV at 10 mA cm-2 compared to the c-CoS/Ni3S2 (242 mV). An exceptionally low cell voltage of 1.51 V is required to achieve a current density of 50 mA cm-2 for overall water splitting in the assembled cell (a-CoS/Ni3S2 || Pt/C). Theoretical calculations reveal that more charges transfer from a-CoS to Ni3S2 in a-CoS/Ni3S2 than in c-CoS/Ni3S2, which promotes the enhancement of OER activity. This work will bring into play a fabrication strategy of a/c catalysts and the understanding of the catalytic mechanism of a/c heterostructures.

Protein-Loaded Cellular Nanosponges for Dual-Biomimicry Neurotoxin Countermeasure.

Neurotoxins present a substantial threat to human health and security as they disrupt and damage the nervous system. Their potent and structurally diverse nature poses challenges in developing effective countermeasures. In this study, a unique nanoparticle design that combines dual-biomimicry mechanisms to enhance the detoxification efficacy of neurotoxins is introduced. Using saxitoxin (STX), one of the deadliest neurotoxins, and its natural binding protein saxiphilin (Sxph) as a model system, human neuronal membrane-coated and Sxph-loaded metal-organic framework (MOF) nanosponges (denoted "Neuron-MOF/Sxph-NS") are successfully developed. The resulting Neuron-MOF/Sxph-NS exhibit a biomimetic design that not only emulates host neurons for function-based detoxification through the neuronal membrane coating, but also mimics toxin-resistant organisms by encapsulating the Sxph protein within the nanoparticle core. The comprehensive in vitro assays, including cell osmotic swelling, calcium flux, and cytotoxicity assays, demonstrate the improved detoxification efficacy of Neuron-MOF/Sxph-NS. Furthermore, in mouse models of STX intoxication, the application of Neuron-MOF/Sxph-NS shows significant survival benefits in both therapeutic and prophylactic regimens, without any apparent acute toxicity. Overall, the development of Neuron-MOF/Sxph-NS represents an important advancement in neurotoxin detoxification, offering promising potential for treating injuries and diseases caused by neurotoxins and addressing the current limitations in neurotoxin countermeasures.

Improvement of Perovskite Solar Cells Efficiency by Management of the Electron Withdrawing Groups in Hole Transport Materials: Theoretical Calculation and Experimental Verification.

Management of functional groups in hole transporting materials (HTMs) is a feasible strategy to improve perovskite solar cells (PSCs) efficiency. Therefore, starting from the carbazole-diphenylamine-based JY7 molecule, JY8 and JY9 molecules are incorporated into the different electron-withdrawing groups of fluorine and cyano groups on the side chains. The theoretical results reveal that the introduction of electron-withdrawing groups of JY8 and JY9 can improve these highest occupied molecular orbital (HOMO) energy levels, intermolecular stacking arrangements, and stronger interface adsorption on the perovskite. Especially, the results of molecular dynamics (MD) indicate that the fluorinated JY8 molecule can yield a preferred surface orientation, which exhibits stronger interface adsorption on the perovskite. To validate the computational model, the JY7-JY9 are synthesized and assembled into PSC devices. Experimental results confirm that the HTMs of JY8 exhibit outstanding performance, such as high hole mobility, low defect density, and efficient hole extraction. Consequently, the PSC devices based on JY8 achieve a higher PCE than those of JY7 and JY9. This work highlights the management of the electron-withdrawing groups in HTMs to realize the goal of designing HTMs for the improvement of PSC efficiency.

CharID: a two-step model for universal prediction of interactions between chromatin accessible regions.

Open chromatin regions (OCRs) allow direct interaction between cis-regulatory elements and trans-acting factors. Therefore, predicting all potential OCR-mediated loops is essential for deciphering the regulation mechanism of gene expression. However, existing loop prediction tools are restricted to specific anchor types. Here, we present CharID (Chromatin Accessible Region Interaction Detector), a two-step model that combines neural network and ensemble learning to predict OCR-mediated loops. In the first step, CharID-Anchor, an attention-based hybrid CNN-BiGRU network is constructed to discriminate between the anchor and nonanchor OCRs. In the second step, CharID-Loop uses gradient boosting decision tree with chromosome-split strategy to predict the interactions between anchor OCRs. The performance was assessed in three human cell lines, and CharID showed superior prediction performance compared with other algorithms. In contrast to the methods designed to predict a particular type of loops, CharID can detect varieties of chromatin loops not limited to enhancer-promoter loops or architectural protein-mediated loops. We constructed the OCR-mediated interaction network using the predicted loops and identified hub anchors, which are highlighted by their proximity to housekeeping genes. By analyzing loops containing SNPs associated with cardiovascular disease, we identified an SNP-gene loop indicating the regulation mechanism of the GFOD1. Taken together, CharID universally predicts diverse chromatin loops beyond other state-of-the-art methods, which are limited by anchor types, and experimental techniques, which are limited by sensitivities drastically decaying with the genomic distance of anchors. Finally, we hosted Peaksniffer, a user-friendly web server that provides online prediction, query and visualization of OCRs and associated loops.

Characterization of gastric cancer stem-like molecular features, immune and pharmacogenomic landscapes.

Cancer stem cells (CSCs) actively reprogram their tumor microenvironment (TME) to sustain a supportive niche, which may have a dramatic impact on prognosis and immunotherapy. However, our knowledge of the landscape of the gastric cancer stem-like cell (GCSC) microenvironment needs to be further improved. A multi-step process of machine learning approaches was performed to develop and validate the prognostic and predictive potential of the GCSC-related score (GCScore). The high GCScore subgroup was not only associated with stem cell characteristics, but also with a potential immune escape mechanism. Furthermore, we experimentally demonstrated the upregulated infiltration of CD206+ tumor-associated macrophages (TAMs) in the invasive margin region, which in turn maintained the stem cell properties of tumor cells. Finally, we proposed that the GCScore showed a robust capacity for prediction for immunotherapy, and investigated potential therapeutic targets and compounds for patients with a high GCScore. The results indicate that the proposed GCScore can be a promising predictor of prognosis and responses to immunotherapy, which provides new strategies for the precision treatment of GCSCs.

KMCP: accurate metagenomic profiling of both prokaryotic and viral populations by pseudo-mapping.

MOTIVATION: The growing number of microbial reference genomes enables the improvement of metagenomic profiling accuracy but also imposes greater requirements on the indexing efficiency, database size and runtime of taxonomic profilers. Additionally, most profilers focus mainly on bacterial, archaeal and fungal populations, while less attention is paid to viral communities. RESULTS: We present KMCP (K-mer-based Metagenomic Classification and Profiling), a novel k-mer-based metagenomic profiling tool that utilizes genome coverage information by splitting the reference genomes into chunks and stores k-mers in a modified and optimized Compact Bit-Sliced Signature Index for fast alignment-free sequence searching. KMCP combines k-mer similarity and genome coverage information to reduce the false positive rate of k-mer-based taxonomic classification and profiling methods. Benchmarking results based on simulated and real data demonstrate that KMCP, despite a longer running time than all other methods, not only allows the accurate taxonomic profiling of prokaryotic and viral populations but also provides more confident pathogen detection in clinical samples of low depth. AVAILABILITY AND IMPLEMENTATION: The software is open-source under the MIT license and available at https://github.com/shenwei356/kmcp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.