SFINN: inferring gene regulatory network from single-cell and spatial transcriptomic data with shared factor neighborhood and integrated neural network.

MOTIVATION: The rise of single-cell RNA sequencing (scRNA-seq) technology presents new opportunities for constructing detailed cell type-specific gene regulatory networks (GRNs) to study cell heterogeneity. However, challenges caused by noises, technical errors, and dropout phenomena in scRNA-seq data pose significant obstacles to GRN inference, making the design of accurate GRN inference algorithms still essential. The recent growth of both single-cell and spatial transcriptomic sequencing data enables the development of supervised deep learning methods to infer GRNs on these diverse single-cell datasets. RESULTS: In this study, we introduce a novel deep learning framework based on shared factor neighborhood and integrated neural network (SFINN) for inferring potential interactions and causalities between transcription factors and target genes from single-cell and spatial transcriptomic data. SFINN utilizes shared factor neighborhood to construct cellular neighborhood network based on gene expression data and additionally integrates cellular network generated from spatial location information. Subsequently, the cell adjacency matrix and gene pair expression are fed into an integrated neural network framework consisting of a graph convolutional neural network and a fully-connected neural network to determine whether the genes interact. Performance evaluation in the tasks of gene interaction and causality prediction against the existing GRN reconstruction algorithms demonstrates the usability and competitiveness of SFINN across different kinds of data. SFINN can be applied to infer GRNs from conventional single-cell sequencing data and spatial transcriptomic data. AVAILABILITY AND IMPLEMENTATION: SFINN can be accessed at GitHub: https://github.com/JGuan-lab/SFINN.

Hybrid multimodal fusion for graph learning in disease prediction.

Graph neural networks (GNNs) have gained significant attention in disease prediction where the latent embeddings of patients are modeled as nodes and the similarities among patients are represented through edges. The graph structure, which determines how information is aggregated and propagated, plays a crucial role in graph learning. Recent approaches typically create graphs based on patients' latent embeddings, which may not accurately reflect their real-world closeness. Our analysis reveals that raw data, such as demographic attributes and laboratory results, offers a wealth of information for assessing patient similarities and can serve as a compensatory measure for graphs constructed exclusively from latent embeddings. In this study, we first construct adaptive graphs from both latent representations and raw data respectively, and then merge these graphs via weighted summation. Given that the graphs may contain extraneous and noisy connections, we apply degree-sensitive edge pruning and kNN sparsification techniques to selectively sparsify and prune these edges. We conducted intensive experiments on two diagnostic prediction datasets, and the results demonstrate that our proposed method surpasses current state-of-the-art techniques.

Involvement of microglia-expressed MS4A6A in the onset of glioblastoma.

Glioblastoma multiforme (GBM) represents the deadliest form of brain tumour, characterized by its low survival rate and grim prognosis. Cytokines released from glioma-associated microglia/macrophages are involved in establishing the tumour microenvironment, thereby crucially promoting GBM progression. MS4A6A polymorphism was confirmed to be associated with neurodegenerative and polymorphism disease pathobiology, but whether it participates in the regulation of GBM and the underlying mechanisms is still not elucidated. Here, we found that MS4A6A was significantly upregulated in GBM patient samples. The results from the single-cell RNA-sequencing (scRNA-seq) database and immunostaining demonstrated the specific expression of MS4A6A in microglial cells. In vitro, microglial overexpression of MS4A6A stimulated the proliferation and migration of glioblastoma cells. Moreover, high MS4A6A mRNA expression was related to poor prognosis in GBM patients. Our study highlights the potential of MS4A6A as a promising biomarker for GBM, which may provide novel strategies for its prevention, diagnosis and treatment.

Forty-nine metagenomic-assembled genomes from an aquatic virome expand Caudoviricetes by 45 potential new families and the newly uncovered Gossevirus of Bamfordvirae.

Twenty complete genomes (29-63 kb) and 29 genomes with an estimated completeness of over 90 % (30-90 kb) were identified for novel dsDNA viruses in the Yangshan Harbor metavirome. These newly discovered viruses contribute to the expansion of viral taxonomy by introducing 46 potential new families. Except for one virus, all others belong to the class Caudoviricetes. The exception is a novel member of the recently characterized viral group known as Gossevirus. Fifteen viruses were predicted to be temperate. The predicted hosts for the viruses appear to be involved in various aspects of the nitrogen cycle, including nitrogen fixation, oxidation and denitrification. Two viruses were identified to have a host of Flavobacterium and Tepidimonas fonticaldi, respectively, by matching CRISPR spacers with viral protospacers. Our findings provide an overview for characterizing and identifying specific viruses from Yangshan Harbor. The Gossevirus-like virus uncovered emphasizes the need for further comprehensive isolation and investigation of polinton-like viruses.

Chemotherapeutic drug elemene induces pain and anxiety-like behaviors by activating GABAergic neurons in the lateral septum of mice.

Most chemotherapeutic drugs are potent and have a very narrow range of dose safety and efficacy, most of which can cause many side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and serious side effect of chemotherapy for cancer treatment. However, its mechanism of action is yet to be fully elucidated. In the present study, we found that the treatment of the chemotherapy drug elemene induced hyperalgesia accompanied by anxiety-like emotions in mice based on several pain behavioral assays, such as mechanical allodynia and thermal hyperalgesia tests. Second, immunostaining for c-fos (a marker of activated neurons) further showed that elemene treatment activated several brain regions, including the lateral septum (LS), cingulate cortex (ACC), paraventricular nucleus of the thalamus (PVT), and dorsomedial hypothalamic nucleus (DMH), most notably in the GABAergic neurons of the lateral septum (LS). Finally, we found that both chemogenetic inhibition and apoptosis of LS neurons significantly reduced pain- and anxiety-like behaviors in mice treated with elemene. Taken together, these findings suggest that LS is involved in the regulation of elemene-induced chemotherapy pain and anxiety-like behaviors, providing a new target for the treatment of chemotherapy pain induced by elemene.

Carbon Nanotube Support, Carbon Loricae and Oxygen Defect Co-Promoted Superior Activities and Excellent Durability of RuO2 Nanoparticles Towards the pH-Universal H2 Evolution.

This work reports a strategy that integrates the carbon nanotube (CNT) supporting, ultrathin carbon coating and oxygen defect generation to fabricate the RuO2 based catalysts toward the pH-universal hydrogen evolution reaction (HER) with high efficiencies. Specifically, the CNT supported RuO2 nanoparticles with ultrathin carbon loricae and rich oxygen vacancies at the surface (C@OV-RuO2/CNTs-325) have been synthesized. The C@OV-RuO2/CNTs-325 shows superior activities and excellent durability for the HER. It only requires overpotentials of 36.1, 18.0, and 19.3 mV to deliver -10 mA cm-2 in the acidic, neutral, and alkaline media, respectively. Its HER activities are comparable to that of the Pt/C in the acidic media but higher than those of the Pt/C in the neutral and alkaline media. The C@OV-RuO2/CNTs-325 shows excellent HER durability with no activity losses for > 500 h in the acidic, neutral or alkaline media at -250 mA cm-2. The density-functional-theory calculations indicate that the CNT supporting, the carbon coating, and the OVs can modulate the d-band centers of Ru, increasing the HER activities of C@OV-RuO2/CNTs-325, and stabilize the Ru atoms in the catalyst, increasing the durability of the C@OV-RuO2/CNTs-325. More interestingly, the C@OV-RuO2/CNTs-325 shows great potential for practical applications toward overall seawater splitting.

Strong Metal-Support Interaction Modulation between Pt Nanoclusters and Mn3O4 Nanosheets through Oxygen Vacancy Control to Achieve High Activities for Acidic Hydrogen Evolution.

The optimization of metal-support interactions is used to fabricate noble metal-based nanoclusters with high activity for hydrogen evolution reaction (HER) in acid media. Specifically, the oxygen-defective Mn3O4 nanosheets supported Pt nanoclusters of ≈1.71 nm in diameter (Pt/V·-Mn3O4 NSs) are synthesized through the controlled solvothermal reaction. The Pt/V·-Mn3O4 NSs show a superior activity and excellent stability for the HER in the acidic media. They only require an overpotential of 19 mV to drive -10 mA cm-2 and show negligible activity loss at -10 and -250 mA cm-2 for >200 and >60 h, respectively. Their Pt mass activity is 12.4 times higher than that of the Pt/C and even higher than those of many single-atom based Pt catalysts. DFT calculations show that their high HER activity arises mainly from the strong metal-support interaction between Pt and Mn3O4. It can facilitate the charge transfer from Mn3O4 to Pt, optimizing the H adsorption on the catalyst surface and promoting the evolution of H2 through the Volmer-Tafel mechanism. The oxygen vacancies in the V·-Mn3O4 NSs are found to be inconducive to the high activity of the Pt/V·-Mn3O4 NSs, highlighting the great importance to reduce the vacancy levels in V·-Mn3O4 NSs.

Efficient Carrier Transport in 2D Bi2O2Se/CsBi3I10 Perovskite Heterojunction Enables Highly-Sensitive Broadband Photodetection.

2D Bi2O2Se has recently garnered significant attention in the electronics and optoelectronics fields due to its remarkable photosensitivity, broad spectral absorption, and excellent long-term environmental stability. However, the development of integrated Bi2O2Se photodetector with high performance and low-power consumption is limited by material synthesis method and the inherent high carrier concentration of Bi2O2Se. Here, a type-I heterojunction is presented, comprising 2D Bi2O2Se and lead-free bismuth perovskite CsBi3I10, for fast response and broadband detection. Through effective charge transfer and strong coupling effect at the interfaces of Bi2O2Se and CsBi3I10, the response time is accelerated to 4.1 µs, and the detection range is expanded from ultraviolet to near-infrared spectral regions (365-1500 nm). The as-fabricated photodetector exhibits a responsivity of 48.63 AW-1 and a detectivity of 1.22×1012 Jones at 808 nm. Moreover, efficient modulation of the dominant photocurrent generation mechanism from photoconductive to photogating effect leads to sensitive response exceeding 103 AW-1 for heterojunction-based photo field effect transistor (photo-FETs). Utilizing the large-scale growth of both Bi2O2Se and CsBi3I10, the as-fabricated integrated photodetector array demonstrates outstanding homogeneity and stability of photo-response performance. The proposed 2D Bi2O2Se/CsBi3I10 perovskite heterojunction holds promising prospects for the future-generation photodetector arrays and integrated optoelectronic systems.

Middle Jurassic insect mines on gymnosperms provide missing links to early mining evolution.

We investigated the mining mode of insect feeding, involving larval consumption of a plant's internal tissues, from the Middle Jurassic (165 million years ago) Daohugou locality of Northeastern China. Documentation of mining from the Jurassic Period is virtually unknown, and results from this time interval would address mining evolution during the temporal gap of mine-seed plant diversifications from the previous Late Triassic to the subsequent Early Cretaceous. Plant fossils were examined with standard microscopic procedures for herbivory and used the standard functional feeding group-damage-type system of categorizing damage. All fossil mines were photographed and databased. We examined 2014 plant specimens, of which 27 occurrences on 14 specimens resulted in eight, new, mine damage types (DTs) present on six genera of bennettitalean, ginkgoalean, and pinalean gymnosperms. Three conclusions emerge from this study. First, these mid-Mesozoic mines are morphologically conservative and track plant host anatomical structure rather than plant phylogeny. Second, likely insect fabricators of these mines were three basal lineages of polyphagan beetles, four basal lineages of monotrysian moths, and a basal lineage tenthredinoid sawflies. Third, the nutrition hypothesis, indicating that miners had greater access to nutritious, inner tissues of new plant lineages, best explains mine evolution during the mid-Mesozoic.

MET fusions are targetable genomic variants in the treatment of advanced malignancies.

Targeted therapy for malignancies has developed rapidly in recent years, benefiting patients harboring genetic mutations sensitive to relevant tyrosine kinase inhibitors (TKIs). With the development of targeted sequencing techniques, an increasing number of detectable genomic alterations in malignancies, including MET fusions, have been revealed. MET fusions, although rare among malignancies, might be functional driver genes that participate in activating downstream signaling pathways and promoting cell proliferation. Therefore, it is believed that MET fusions could be targetable genomic variants of MET, and inhibition of MET is considered an optionable therapeutic choice for patients harboring MET fusions. According to the summary presented in this review, we recommend MET-TKIs as suitable treatment agents for patients harboring primary MET fusions. For patients harboring acquired MET fusions after the development of resistance to TKIs targeting primary genomic alterations, such as sensitive EGFR mutations, treatment with a MET-TKI alone or in combination with TKIs targeting primary genomic alterations, such as EGFR-TKIs, is hypothesized to be a reasonable option for salvage treatment. In summary, MET fusions, despite their low incidence, should be taken into consideration when developing treatment strategies for cancer patients.

Metatranscriptomic data mining together with microfluidic card uncovered the potential pathogens and seasonal RNA viral ecology in a drinking water source.

AIMS: Despite metatranscriptomics becoming an emerging tool for pathogen surveillance, very little is known about the feasibility of this approach for understanding the fate of human-derived pathogens in drinking water sources. METHODS AND RESULTS: We conducted multiplexed microfluidic cards and metatranscriptomic sequencing of the drinking water source in a border city of North Korea in four seasons. Microfluidic card detected norovirus, hepatitis B virus (HBV), enterovirus, and Vibrio cholerae in the water. Phylogenetic analyses showed that environmental-derived sequences from norovirus GII.17, genotype C of HBV, and coxsackievirus A6 (CA6) were genetically related to the local clinical isolates. Meanwhile, metatranscriptomic assembly suggested that several bacterial pathogens, including Acinetobacter johnsonii and V. cholerae might be prevalent in the studied region. Metatranscriptomic analysis recovered 349 species-level groups with substantial viral diversity without detection of norovirus, HBV, and CA6. Seasonally distinct virus communities were also found. Specifically, 126, 73, 126, and 457 types of viruses were identified in spring, summer, autumn, and winter, respectively. The viromes were dominated by the Pisuviricota phylum, including members from Marnaviridae, Dicistroviridae, Luteoviridae, Potyviridae, Picornaviridae, Astroviridae, and Picobirnaviridae families. Further phylogenetic analyses of RNA (Ribonucleic Acid)-dependent RNA polymerase (RdRp) sequences showed a diverse set of picorna-like viruses associated with shellfish, of which several novel picorna-like viruses were also identified. Additionally, potential animal pathogens, including infectious bronchitis virus, Bat dicibavirus, Bat nodavirus, Bat picornavirus 2, infectious bursal disease virus, and Macrobrachium rosenbergii nodavirus were also identified. CONCLUSIONS: Our data illustrate the divergence between microfluidic cards and metatranscriptomics, highlighting that the combination of both methods facilitates the source tracking of human viruses in challenging settings without sufficient clinical surveillance.

The virulence plasmid associated with AHPND in shrimp appears to have originated from Vibrio owensii through a process of homologous recombination of parental plasmids and the transposable insertion of two large fragments.

Acute hepatopancreatic necrosis disease (AHPND) is a highly contagious and lethal disease of shrimp caused by Vibrio strains carrying the virulence plasmid (pAHPND) containing the pirAB virulence genes. Through analysis of plasmid sequence similarity, clustering, and phylogeny, a horizontal transfer element similar to IS91 was discovered within the pAHPND plasmid. Additionally, two distinct clades of plasmids related to pAHPND (designated as pAHPND-r1 and pAHPND-r2) were identified, which may serve as potential parental plasmids for pAHPND. The available evidence, including the difference in G+C content between the plasmid and its host, codon usage preference, and plasmid recombination event prediction, suggests that the formation of the pAHPND plasmid in the Vibrio owensii strain was likely due to the synergistic effect of the recombinase RecA and the associated proteins RecBCD on the pAHPND-r1 and pAHPND-r2, resulting in the recombination and formation of the precursor plasmid for pAHPND (pre-pAHPND). The emergence of pAHPND was found to be a result of successive insertions of the horizontal transfer elements of pirAB-Tn903 and IS91-like segment, which led to the deletion of one third of the pre-pAHPND. This plasmid was then able to spread horizontally to other Vibrio strains, contributing to the epidemics of AHPND. These findings shed light on previously unknown mechanisms involved in the emergence of pAHPND and improve our understanding of the disease's spread.

Neoadjuvant PD-(L)1 blockade plus platinum-based chemotherapy for potentially resectable oncogene-positive non-small cell lung cancer.

BACKGROUND: Whether programmed cell death-1/ligand-1 (PD-1/PD-L1) blockade-based neoadjuvant treatment may benefit locally advanced oncogene-mutant non-small cell lung cancer (NSCLC) patients remains controversial. This retrospective study was designed to observe the efficacy and safety of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy versus chemotherapy and corresponding tyrosine kinase inhibitors (TKIs) in patients with resectable oncogene-positive NSCLC. METHODS: Patients with potential resectable NSCLC harbouring oncogene alterations who had received neoadjuvant treatment were retrospectively recruited, and an oncogene-negative cohort of patients who received neoadjuvant PD-(L)1 blockade-based neoadjuvant treatment was reviewed for comparison during the same period. The primary aim was to observe the treatment efficacy and event-free survival (EFS) of these agents. Safety profile, molecular target, and immunologic factor data, including PD-L1 expression and tumour mutational burden (TMB), were also obtained. RESULTS: A total of 46 patients were recruited. Thirty-one of them harboured oncogene alterations, including EGFR, KRAS, ERBB2, ROS1, MET, RET, ALK, and FGFR3 alterations. Among the oncogene-positive patients, 18 patients received neoadjuvant PD-(L)1 blockade immunotherapy plus chemotherapy (oncogene-positive IO group), 13 patients were treated with neoadjuvant chemotherapy and/or corresponding TKIs or TKIs alone (oncogene-positive chemo/TKIs group), and the other 15 patients were oncogene negative and received neoadjuvant PD-(L)1 blockade plus chemotherapy (oncogene-negative IO group). The pathological complete response (pCR) and major pathological response (MPR) rates were 22.2% (4 of 18) and 44.4% (8 of 18) in the oncogene-positive IO group, 0% (P = 0.120) and 23.1% (3 of 13) (P = 0.276) in the oncogene-positive chemo/TKIs group, and 46.7% (7 of 15) (P = 0.163) and 80.0% (12 of 15) (P = 0.072) in the oncogene-negative IO group, respectively. By the last follow-up, the median EFS time had not reached in the oncogene-positive IO group, and was 29.5 months in the oncogene-positive chemo/TKIs group and 38.4 months in the oncogene-negative IO group. CONCLUSION: Compared with chemotherapy/TKIs treatment, neoadjuvant treatment with PD-(L)1 blockade plus platinum-based chemotherapy was associated with higher pCR/MPR rates in patients with partially resectable oncogene-mutant NSCLC, while the pCR/MPR rates were lower than their oncogene-negative counterparts treated with PD-(L)1 blockade-based treatment. Specifically, oncogene alteration types and other predictors of response to immunotherapy should be taken into account in clinical practice.

Superior petrosal vein sacrifice in translabyrinthine approach for resection of vestibule schwannoma.

PURPOSE: The aim of this study was to evaluate the safety and surgical outcome of superior petrosal vein (SPV, Dandy's vein) sacrifice in translabyrinthine approach (TLA) for resection of vestibule schwannoma (VS) as compared with SPV preservation, with further investigation of preoperational factors associated with the implement of SPV sacrifice. METHODS: The authors prospectively collected data from patients surgically treated for VS through TLA between June 2021 and April 2022 at the Gruppo Otologico. RESULTS: There were 30 and 49 patients in SPV sacrifice and preservation groups, respectively. SPV sacrifice group had significantly larger tumor size (2.46 vs. 1.40 cm), less percentage of solid tumor (26.7% vs. 83.7%), higher incidence of brainstem compression (80% vs. 26.5%), and higher percentage of facial numbness (20.0% vs. 4.1%) than SPV preservation group. Gross total resection (GTR) rates were 73.3% after SPV sacrifice and 87.8% after SPV preservation. Facial nerve preservation rates were similar. No complication related with SPV sacrifice was observed. Logistic regression analysis showed tumor size and complete solid consistency as significant risk factors associated with SPV sacrifice. ROC curve further demonstrated tumor size as a fair predictor (AUC = 0.833), with optimum cutoff value of 1.68 cm. CONCLUSION: SPV sacrifice via TLA as needed is a safe and effective maneuver for removal of relatively large VS. Tumor size and consistency can be used as a guidance in preoperational decision-making, with cutoff value of 1.68 cm and cystic formation as predictive indicators.

Ultrafast Cascade Charge Transfer in Multibandgap Colloidal Quantum Dot Solids Enables Threshold Reduction for Optical Gain and Stimulated Emission.

Achieving low-threshold infrared stimulated emission in solution-processed quantum dots is critical to enable real-life applications including photonic integrated circuits (PICs), LIDAR application, and optical telecommunication. However, realization of low threshold infrared gain is fundamentally challenging due to high degeneracy of the first emissive state (e.g., 8-fold) and fast Auger recombination. In this Letter, we demonstrate ultra-low-threshold infrared stimulated emission with an onset of 110 µJ cm-2 employing cascade charge transfer (CT) in Pb-chalcogenide colloidal quantum dot (CQD) solids. In doing so, we investigate this idea in two different architectures including a mixture of multiband gap CQDs and a layer-by-layer (LBL) configuration. Using transient absorption spectroscopy, we show ultrafast cascade CT from large band gap PbS CQD to small band gap PbS/PbSSe core/shell CQDs in LBL (∼2 ps) and mixture (∼9 ps) configurations. These results indicate the feasibility of using cascade CT as an efficient method to reduce the optical gain threshold in CQD solid films.

Characteristics of Gaseous Elemental Mercury in a Suburban Area of Shanghai, China.

To clarify gaseous elemental mercury (GEM) in suburban megacities in the Yangtze River Delta region, China, we observed GEM concentrations from December 2019 to November 2020 in Wujing town, a suburban area of Shanghai. The annual mean GEM concentration was 1.44 ± 0.88 ng m-3. Compared with the historical monitoring data of GEM in Shanghai over the past 10 years, the concentration of GEM showed a decreasing trend. The monthly mean concentrations of GEM showed clear seasonal variation, with higher values in the spring and winter. In spring and winter, typical Hg pollution events were observed, which could be mostly associated with increased local anthropogenic activity and temperature inversion. The results of the correlation analysis of the daily mean GEM concentrations with the AQI and backward trajectory calculations indicate that mercury pollution at monitoring sites can be affected by local, regional and interregional influences.

CircABCA13 acts as a miR-4429 sponge to facilitate esophageal squamous cell carcinoma development by stabilizing SRXN1.

Circular RNAs (circRNAs) play a pivotal role in the tumorigenesis and progression of various cancers. However, the role and mechanisms of circABCA13 in esophageal squamous cell carcinoma (ESCC) are largely unknown. Here, we reported that circABCA13, a novel circular RNA generated by back-splicing of the intron of the ABCA13 gene, is highly expressed in ESCC tumor tissues and cell lines. Upregulation of circABCA13 correlated with TNM stage and a poor prognosis in ESCC patients. While knockdown of circABCA13 in ESCC cells significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth, overexpression of circABCA13 facilitated tumor growth both in vitro and in vivo. In addition, circABCA13 directly binds to miR-4429 and sequesters miR-4429 from its endogenous target, SRXN1 mRNA, which subsequently upregulates SRXN1 and promotes ESCC progression. Consistently, overexpression of miR-4429 or knockdown of SRXN1 abolished malignant behavior promotion of ESCC results from circABCA13 overexpression in vitro and in vivo. Collectively, our study uncovered the oncogenic role of circABCA13 and its mechanism in ESCC, suggesting that circABCA13 could be a potential therapeutic target and a predictive biomarker for ESCC patients.

ICTV Virus Taxonomy Profile: Aoguangviridae 2023.

The family Aoguangviridae includes dsDNA viruses that have been associated with marine archaea. Currently, members of this virus family are known through metagenomics. Virions are predicted to consist of an icosahedral capsid and a helical tail, characteristic of members in the class Caudoviricetes. Aoguangviruses have some of the largest genomes among archaeal viruses and possess most of the components of the DNA replication machinery as well as auxiliary functions. The family Aoguangviridae includes the species Aobingvirus yangshanense. Many unclassified relatives of this virus group, referred to as 'magroviruses', have been discovered by metagenomics in globally distributed marine samples. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Aoguangviridae, which is available at ictv.global/report/aoguangviridae.

Diverse viruses of marine archaea discovered using metagenomics.

During the past decade, metagenomics became a method of choice for the discovery of novel viruses. However, host assignment for uncultured viruses remains challenging, especially for archaeal viruses, which are grossly undersampled compared to viruses of bacteria and eukaryotes. Here, we assessed the utility of CRISPR spacer targeting, tRNA gene matching and homology searches for viral signature proteins, such as major capsid proteins, for the assignment of archaeal hosts and validated these approaches on metaviromes from Yangshan Harbor (YSH). We report 35 new genomes of viruses which could be confidently assigned to hosts representing diverse lineages of marine archaea. We show that the archaeal YSH virome is highly diverse, with some viruses enriching the previously described virus groups, such as magroviruses of Marine Group II Archaea (Poseidoniales), and others representing novel groups of marine archaeal viruses. Metagenomic recruitment of Tara Oceans datasets on the YSH viral genomes demonstrated the presence of YSH Poseidoniales and Nitrososphaeria viruses in the global oceans, but also revealed the endemic YSH-specific viral lineages. Furthermore, our results highlight the relationship between the soil and marine thaumarchaeal viruses. We propose three new families within the class Caudoviricetes for the classification of the five complete viral genomes predicted to replicate in marine Poseidoniales and Nitrososphaeria, two ecologically important and widespread archaeal groups. This study illustrates the utility of viral metagenomics in exploring the archaeal virome and provides new insights into the diversity, distribution and evolution of marine archaeal viruses.

A combined diagnostic model based on circulating tumor cell in patients with solitary pulmonary nodules.

BACKGROUND: Although many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor-positive circulating tumor cells (FR+ CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model. METHODS: A total of 898 patients with a solitary pulmonary nodule who received FR+ CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model. RESULTS: The positive rate of FR+ CTC between patients with non-small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+ CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+ CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07-1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01-1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01-1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+ CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587-0.713) in the training set and 0.700 (95% CI, 0.603-0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659-0.791) in the training set and 0.828 (95% CI, 0.754-0.902) in the validation set, respectively. CONCLUSIONS: We confirmed the value of FR+ CTC in diagnosing SPNs and developed a prediction model based on FR+ CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.