BPI-GNN: Interpretable brain network-based psychiatric diagnosis and subtyping.

Converging evidence increasingly suggests that psychiatric disorders, such as major depressive disorder (MDD) and autism spectrum disorder (ASD), are not unitary diseases, but rather heterogeneous syndromes that involve diverse, co-occurring symptoms and divergent responses to treatment. This clinical heterogeneity has hindered the progress of precision diagnosis and treatment effectiveness in psychiatric disorders. In this study, we propose BPI-GNN, a new interpretable graph neural network (GNN) framework for analyzing functional magnetic resonance images (fMRI), by leveraging the famed prototype learning. In addition, we introduce a novel generation process of prototype subgraph to discover essential edges of distinct prototypes and employ total correlation (TC) to ensure the independence of distinct prototype subgraph patterns. BPI-GNN can effectively discriminate psychiatric patients and healthy controls (HC), and identify biological meaningful subtypes of psychiatric disorders. We evaluate the performance of BPI-GNN against 11 popular brain network classification methods on three psychiatric datasets and observe that our BPI-GNN always achieves the highest diagnosis accuracy. More importantly, we examine differences in clinical symptom profiles and gene expression profiles among identified subtypes and observe that our identified brain-based subtypes have the clinical relevance. It also discovers the subtype biomarkers that align with current neuro-scientific knowledge.

The evolutionary history of vertebrate RNA viruses.

Our understanding of the diversity and evolution of vertebrate RNA viruses is largely limited to those found in mammalian and avian hosts and associated with overt disease. Here, using a large-scale meta-transcriptomic approach, we discover 214 vertebrate-associated viruses in reptiles, amphibians, lungfish, ray-finned fish, cartilaginous fish and jawless fish. The newly discovered viruses appear in every family or genus of RNA virus associated with vertebrate infection, including those containing human pathogens such as influenza virus, the Arenaviridae and Filoviridae families, and have branching orders that broadly reflected the phylogenetic history of their hosts. We establish a long evolutionary history for most groups of vertebrate RNA virus, and support this by evaluating evolutionary timescales using dated orthologous endogenous virus elements. We also identify new vertebrate-specific RNA viruses and genome architectures, and re-evaluate the evolution of vector-borne RNA viruses. In summary, this study reveals diverse virus-host associations across the entire evolutionary history of the vertebrates.

Author Correction: The evolutionary history of vertebrate RNA viruses.

Change history: In this Article, author Li Liu should be associated with affiliation number 5 (College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong, China), rather than affiliation number 4 (Wenzhou Center for Disease Control and Prevention, Wenzhou, Zhejiang, China). This has been corrected online.

An integrated finite element method and machine learning algorithm for brain morphology prediction.

The human brain development experiences a complex evolving cortical folding from a smooth surface to a convoluted ensemble of folds. Computational modeling of brain development has played an essential role in better understanding the process of cortical folding, but still leaves many questions to be answered. A major challenge faced by computational models is how to create massive brain developmental simulations with affordable computational sources to complement neuroimaging data and provide reliable predictions for brain folding. In this study, we leveraged the power of machine learning in data augmentation and prediction to develop a machine-learning-based finite element surrogate model to expedite brain computational simulations, predict brain folding morphology, and explore the underlying folding mechanism. To do so, massive finite element method (FEM) mechanical models were run to simulate brain development using the predefined brain patch growth models with adjustable surface curvature. Then, a GAN-based machine learning model was trained and validated with these produced computational data to predict brain folding morphology given a predefined initial configuration. The results indicate that the machine learning models can predict the complex morphology of folding patterns, including 3-hinge gyral folds. The close agreement between the folding patterns observed in FEM results and those predicted by machine learning models validate the feasibility of the proposed approach, offering a promising avenue to predict the brain development with given fetal brain configurations.

An attention-based context-informed deep framework for infant brain subcortical segmentation.

Precise segmentation of subcortical structures from infant brain magnetic resonance (MR) images plays an essential role in studying early subcortical structural and functional developmental patterns and diagnosis of related brain disorders. However, due to the dynamic appearance changes, low tissue contrast, and tiny subcortical size in infant brain MR images, infant subcortical segmentation is a challenging task. In this paper, we propose a context-guided, attention-based, coarse-to-fine deep framework to precisely segment the infant subcortical structures. At the coarse stage, we aim to directly predict the signed distance maps (SDMs) from multi-modal intensity images, including T1w, T2w, and the ratio of T1w and T2w images, with an SDM-Unet, which can leverage the spatial context information, including the structural position information and the shape information of the target structure, to generate high-quality SDMs. At the fine stage, the predicted SDMs, which encode spatial-context information of each subcortical structure, are integrated with the multi-modal intensity images as the input to a multi-source and multi-path attention Unet (M2A-Unet) for achieving refined segmentation. Both the 3D spatial and channel attention blocks are added to guide the M2A-Unet to focus more on the important subregions and channels. We additionally incorporate the inner and outer subcortical boundaries as extra labels to help precisely estimate the ambiguous boundaries. We validate our method on an infant MR image dataset and on an unrelated neonatal MR image dataset. Compared to eleven state-of-the-art methods, the proposed framework consistently achieves higher segmentation accuracy in both qualitative and quantitative evaluations of infant MR images and also exhibits good generalizability in the neonatal dataset.

In situgrowth strategy to construct perovskite quantum dot@covalent organic framework composites with enhanced water stability.

Metal halide perovskite quantum dots (QDs) have excellent optoelectronic properties; however, their poor stability under water or thermal conditions remains an obstacle to commercialization. Here, we used a carboxyl functional group (-COOH) to enhance the ability of a covalent organic framework (COF) to adsorb lead ions and grow CH3NH3PbBr3(MAPbBr3) QDsin situinto a mesoporous carboxyl-functionalized COF to construct MAPbBr3QDs@COF core-shell-like composites to improve the stability of perovskites. Owing to the protection of the COF, the as-prepared composites exhibited enhanced water stability, and the characteristic fluorescence was maintained for more than 15 d. These MAPbBr3QDs@COF composites can be used to fabricate white light-emitting diodes with a color comparable to natural white emission. This work demonstrates the importance of functional groups for thein situgrowth of perovskite QDs, and coating with a porous structure is an effective way to improve the stability of metal halide perovskites.

A 4D infant brain volumetric atlas based on the UNC/UMN baby connectome project (BCP) cohort.

Spatiotemporal (four-dimensional) infant-dedicated brain atlases are essential for neuroimaging analysis of early dynamic brain development. However, due to the substantial technical challenges in the acquisition and processing of infant brain MR images, 4D atlases densely covering the dynamic brain development during infancy are still scarce. Few existing ones generally have fuzzy tissue contrast and low spatiotemporal resolution, leading to degraded accuracy of atlas-based normalization and subsequent analyses. To address this issue, in this paper, we construct a 4D structural MRI atlas for infant brains based on the UNC/UMN Baby Connectome Project (BCP) dataset, which features a high spatial resolution, extensive age-range coverage, and densely sampled time points. Specifically, 542 longitudinal T1w and T2w scans from 240 typically developing infants up to 26-month of age were utilized for our atlas construction. To improve the co-registration accuracy of the infant brain images, which typically exhibit dynamic appearance with low tissue contrast, we employed the state-of-the-art registration method and leveraged our generated reliable brain tissue probability maps in addition to the intensity images to improve the alignment of individual images. To achieve consistent region labeling on both infant and adult brain images for facilitating region-based analysis across ages, we mapped the widely used Desikan cortical parcellation onto our atlas by following an age-decreasing mapping manner. Meanwhile, the typical subcortical structures were manually delineated to facilitate the studies related to the subcortex. Compared with the existing infant brain atlases, our 4D atlas has much higher spatiotemporal resolution and preserves more structural details, and thus can boost accuracy in neurodevelopmental analysis during infancy.

Longitudinal brain atlases of early developing cynomolgus macaques from birth to 48 months of age.

Longitudinal brain imaging atlases with densely sampled time-points and ancillary anatomical information are of fundamental importance in studying early developmental characteristics of human and non-human primate brains during infancy, which feature extremely dynamic imaging appearance, brain shape and size. However, for non-human primates, which are highly valuable animal models for understanding human brains, the existing brain atlases are mainly developed based on adults or adolescents, denoting a notable lack of temporally densely-sampled atlases covering the dynamic early brain development. To fill this critical gap, in this paper, we construct a comprehensive set of longitudinal brain atlases and associated tissue probability maps (gray matter, white matter, and cerebrospinal fluid) with totally 12 time-points from birth to 4 years of age (i.e., 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 months of age) based on 175 longitudinal structural MRI scans from 39 typically-developing cynomolgus macaques, by leveraging state-of-the-art computational techniques tailored for early developing brains. Furthermore, to facilitate region-based analysis using our atlases, we also provide two popular hierarchy parcellations, i.e., cortical hierarchy maps (6 levels) and subcortical hierarchy maps (6 levels), on our longitudinal macaque brain atlases. These early developing atlases, which have the densest time-points during infancy (to the best of our knowledge), will greatly facilitate the studies of macaque brain development.

Redefining the invertebrate RNA virosphere.

Current knowledge of RNA virus biodiversity is both biased and fragmentary, reflecting a focus on culturable or disease-causing agents. Here we profile the transcriptomes of over 220 invertebrate species sampled across nine animal phyla and report the discovery of 1,445 RNA viruses, including some that are sufficiently divergent to comprise new families. The identified viruses fill major gaps in the RNA virus phylogeny and reveal an evolutionary history that is characterized by both host switching and co-divergence. The invertebrate virome also reveals remarkable genomic flexibility that includes frequent recombination, lateral gene transfer among viruses and hosts, gene gain and loss, and complex genomic rearrangements. Together, these data present a view of the RNA virosphere that is more phylogenetically and genomically diverse than that depicted in current classification schemes and provide a more solid foundation for studies in virus ecology and evolution.

Ultrathin Covalent Organic Framework Nanosheets/Ti3C2Tx-Based Photoelectrochemical Biosensor for Efficient Detection of Prostate-Specific Antigen.

Designable and ultrathin covalent organic framework nanosheets (CONs) with good photoelectric activity are promising candidates for the construction of photoelectrochemical (PEC) biosensors for the detection of low-abundance biological substrates. However, achieving highly sensitive PEC properties by using emerging covalent organic framework nanosheets (CONs) remains a great challenge due to the polymeric nature and poor photoelectric activity of CONs. Herein, we report for the first time the preparation of novel composites and their PEC sensing properties by electrostatic self-assembly of ultrathin CONs (called TTPA-CONs) with Ti3C2Tx. The prepared TTPA-CONs/Ti3C2Tx composites can be used as photocathodes for PEC detection of prostate-specific antigen (PSA) with high sensitivity, low detection limit, and good stability. This work not only expands the application of CONs but also opens new avenues for the development of efficient PEC sensing platforms.

Synthesis and Visualization of Entangled 3D Covalent Organic Frameworks with High-Valency Stereoscopic Molecular Nodes for Gas Separation.

The structural diversity of three-dimensional (3D) covalent organic frameworks (COFs) are limited as there are only a few choices of building units with multiple symmetrically distributed connection sites. To date, 4 and 6-connected stereoscopic nodes with Td , D3h , D3d and C3 symmetries have been mostly reported, delivering limited 3D topologies. We propose an efficient approach to expand the 3D COF repertoire by introducing a high-valency quadrangular prism (D4h ) stereoscopic node with a connectivity of eight, based on which two isoreticular 3D imine-linked COFs can be created. Low-dose electron microscopy allows the direct visualization of their 2-fold interpenetrated bcu networks. These 3D COFs are endowed with unique pore architectures and strong molecular binding sites, and exhibit excellent performance in separating C2 H2 /CO2 and C2 H2 /CH4 gas pairs. The introduction of high-valency stereoscopic nodes would lead to an outburst of new topologies for 3D COFs.

Relationship Between Serum Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid and Organ Damage in Coronavirus 2019 Patients: A Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. METHODS: Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. RESULTS: Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. CONCLUSIONS: In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.

Substoichiometric 3D Covalent Organic Frameworks Based on Hexagonal Linkers.

Covalent organic frameworks (COFs), a fast-growing field in crystalline porous materials, have achieved tremendous success in structure development and application exploration over the past decade. The vast majority of COFs reported to date are designed according to the basic concept of reticular chemistry, which is rooted in the idea that building blocks are fully connected within the frameworks. We demonstrate here that sub-stoichiometric construction of 2D/3D COFs can be accomplished by the condensation of a hexagonal linker with 4-connected building units. It is worth noting that the partially connected frameworks were successfully reticulated for 3D COFs for the first time, representing the highest BET surface area among imine-linked 3D COFs to data. The unreacted benzaldehydes in COF frameworks can enhance C2H2 and CO2 adsorption capacity and selectivities between C2H2/CH4 and C2H2/CO2 for sub-stoichiometric 2D COFs, while the reserved benzaldehydes control the interpenetrated architectures for the 3D case, achieving a rare non-interpenetrated pts topology for 3D COFs. This work not only paves a new avenue to build new COFs and endows residual function groups with further applications but also prompts redetermination of reticular frameworks in highly connected and symmetrical COFs.

A reusable wet-transfer printing technique for manufacturing of flexible silver nanowire film-based electrodes.

To explore a simple and efficient way to fabricate thin film electrodes on flexible substrates is highly desired because of its high promising application in optoelectronics. Transfer printing technique plays a key role in the fabrication of flexible electrodes from conventional substrates to flexible substrates. Unfortunately, a simple, room temperature, environmental-friendly and reusable transfer printing technique still remains challenging. Here we demonstrated a novel water-based wet-transfer printing technique that is simple, room temperature, environmental-friendly and reusable by taking advantage of the adjustment of the intermolecular hydrogen bonding between thin film and substrates. This effective and practical transfer technique may provide an effective route to develop electronic flexible devices with high performance.

A highly sensitive strain sensor with a sandwich structure composed of two silver nanoparticles layers and one silver nanowires layer for human motion detection.

The fabrication of strain sensors with high sensitivity, large sensing range and excellent stability is highly desirable because of their promising applications in human motion detection, human-machine interface and electric skin, etc. Herein, by introducing a highly conductive silver nanowire (AgNW) layer between two serried silver nanoparticle (AgNP) layers, forming a sandwich structure, a strain sensor with high sensitivity (a large gauge factor of 2.8 × 105), large sensing range (up to 80% strain) and excellent stability (over 1000 cycles) can be achieved. A combination of experimental and mechanism studies shows that the high performance of the obtained strain sensor is ascribed to the synergy of the highly conductive AgNW layer, astatic AgNP layers and the presence of large cracks in stretching. As a proof-of-concept application, the obtained strain sensor can be used for highly effective human motion detection ranging from large scale motions, i.e. kneel bending and wrist flexion, to subtle scale motions, i.e. pulse and swallowing.

The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients.

In December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, and has spread globally. However, the transmission route of SARS-CoV-2 has not been fully understood. In this study, we aimed to investigate SARS-CoV-2 shedding in the excreta of COVID-19 patients. Electronical medical records, including demographics, clinical characteristics, laboratory and radiological findings of enrolled patients were extracted and analyzed. Pharyngeal swab, stool, and urine specimens were collected and tested for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Viral shedding at multiple time points in specimens was recorded, and its correlation analyzed with clinical manifestations and the severity of illness. A total of 42 laboratory-confirmed patients were enrolled, 8 (19.05%) of whom had gastrointestinal symptoms. A total of 28 (66.67%) patients tested positive for SARS-CoV-2 RNA in stool specimens, and this was not associated with the presence of gastrointestinal symptoms and the severity of illness. Among them, 18 (64.29%) patients remained positive for viral RNA in the feces after the pharyngeal swabs turned negative. The duration of viral shedding from the feces after negative conversion in pharyngeal swabs was 7 (6-10) days, regardless of COVID-19 severity. The demographics, clinical characteristics, laboratory and radiologic findings did not differ between patients who tested positive and negative for SARS-CoV-2 RNA in the feces. Viral RNA was not detectable in urine specimens from 10 patients. Our results demonstrated the presence of SARS-CoV-2 RNA in the feces of COVID-19 patients and suggested the possibility of SARS-CoV-2 transmission via the fecal-oral route.

Divergent Viruses Discovered in Arthropods and Vertebrates Revise the Evolutionary History of the Flaviviridae and Related Viruses.

UNLABELLED: Viruses of the family Flaviviridae are important pathogens of humans and other animals and are currently classified into four genera. To better understand their diversity, evolutionary history, and genomic flexibility, we used transcriptome sequencing (RNA-seq) to search for the viruses related to the Flaviviridae in a range of potential invertebrate and vertebrate hosts. Accordingly, we recovered the full genomes of five segmented jingmenviruses and 12 distant relatives of the known Flaviviridae ("flavi-like" viruses) from a range of arthropod species. Although these viruses are highly divergent, they share a similar genomic plan and common ancestry with the Flaviviridae in the NS3 and NS5 regions. Remarkably, although these viruses fill in major gaps in the phylogenetic diversity of the Flaviviridae, genomic comparisons reveal important changes in genome structure, genome size, and replication/gene regulation strategy during evolutionary history. In addition, the wide diversity of flavi-like viruses found in invertebrates, as well as their deep phylogenetic positions, suggests that they may represent the ancestral forms from which the vertebrate-infecting viruses evolved. For the vertebrate viruses, we expanded the previously mammal-only pegivirus-hepacivirus group to include a virus from the graceful catshark (Proscyllium habereri), which in turn implies that these viruses possess a larger host range than is currently known. In sum, our data show that the Flaviviridae infect a far wider range of hosts and exhibit greater diversity in genome structure than previously anticipated. IMPORTANCE: The family Flaviviridae of RNA viruses contains several notorious human pathogens, including dengue virus, West Nile virus, and hepatitis C virus. To date, however, our understanding of the biodiversity and evolution of the Flaviviridae has largely been directed toward vertebrate hosts and their blood-feeding arthropod vectors. Therefore, we investigated an expanded group of potential arthropod and vertebrate host species that have generally been ignored by surveillance programs. Remarkably, these species contained diverse flaviviruses and related viruses that are characterized by major changes in genome size and genome structure, such that these traits are more flexible than previously thought. More generally, these data suggest that arthropods may be the ultimate reservoir of the Flaviviridae and related viruses, harboring considerable genetic and phenotypic diversity. In sum, this study revises the traditional view on the evolutionary history, host range, and genomic structures of a major group of RNA viruses.

Diversity and evolution of avian influenza viruses in live poultry markets, free-range poultry and wild wetland birds in China.

The wide circulation of novel avian influenza viruses (AIVs) highlights the risk of pandemic influenza emergence in China. To investigate the prevalence and genetic diversity of AIVs in different ecological contexts, we surveyed AIVs in live poultry markets (LPMs), free-range poultry and the wetland habitats of wild birds in Zhejiang and Hubei provinces. Notably, LPMs contained the highest frequency of AIV infection, and the greatest number of subtypes (n = 9) and subtype co-infections (n = 14), as well as frequent reassortment, suggesting that they play an active role in fuelling AIV transmission. AIV-positive samples were also identified in wild birds in both provinces and free-range poultry in one sampling site close to a wetland region in Hubei. H9N2, H7N9 and H5N1 were the most commonly sampled subtypes in the LPMs from Zhejiang, whilst H5N6 and H9N2 were the dominant subtypes in the LPMs from Hubei. Phylogenetic analyses of the whole-genome sequences of 43 AIVs revealed that three reassortant H5 subtypes were circulating in LMPs in both geographical regions. Notably, the viruses sampled from the wetland regions and free-range poultry contained complex reassortants, for which the origins of some segments were unclear. Overall, our study highlights the extent of AIV genetic diversity in two highly populated parts of central and south-eastern China, particularly in LPMs, and emphasizes the need for continual surveillance.

Specific interference shRNA-expressing plasmids inhibit Hantaan virus infection in vitro and in vivo.

AIM: To investigate the antiviral effects of vectors expressing specific short hairpin RNAs (shRNAs) against Hantaan virus (HTNV) infection in vitro and in vivo. METHODS: Based on the effects of 4 shRNAs targeting different regions of HTNV genomic RNA on viral replication, the most effective RNA interference fragments of the S and M genes were constructed in pSilencer-3.0-H1 vectors, and designated pSilencer-S and pSilencer-M, respectively. The antiviral effect of pSilencer-S/M against HTNV was evaluated in both HTNV-infected Vero-E6 cells and mice. RESULTS: In HTNV-infected Vero-E6 cells, pSilencer-S and pSilencer-M targeted the viral nucleocapsid proteins and envelope glycoproteins, respectively, as revealed in the immunofluorescence assay. Transfection with pSilencer-S or pSilencer-M (1, 2, 4 µg) markedly inhibited the viral antigen expression in dose- and time-dependent manners. Transfection with either plasmid (2 µg) significantly decreased HTNV-RNA level at 3 day postinfectin (dpi) and the progeny virus titer at 5 dpi. In mice infected with lethal doses of HTNV, intraperitoneal injection of pSilencer-S or pSilencer-M (30 µg) considerably increased the survival rates and mean time to death, and significantly reduced the mean virus yields and viral RNA level, and alleviated virus-induced pathological lesions in lungs, brains and kidneys. CONCLUSION: Plasmid-based shRNAs potently inhibit HTNV replication in vitro and in vivo. Our results provide a basis for development of shRNA as therapeutics for HTNV infections in humans.

Disseminated Acanthamoeba castellanii infection in a patient with AIDS: a case report and literature review.

Background: Acanthamoeba castellanii infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this condition, and successful treatment reports are scarce. Case presentation: We present a case of Acanthamoeba castellanii infection in a 63-year-old female patient with AIDS, who was admitted to our hospital with symptoms of fever, skin ulcers, subcutaneous nodules, and food regurgitation from the nose while eating. After initial empirical treatment failed, a biopsy of the subcutaneous nodule was performed, and metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microorganisms in both the biopsy specimen and blood samples. The results revealed Acanthamoeba castellanii infection. Additionally, histopathological examination of the biopsy specimen and cytological examination of the secretions from the ulcer surface also confirmed this pathogenic infection. The patient's symptoms significantly improved upon discharge after adjusting the treatment regimen to a combination of anti-amebic therapy. Conclusion: Immunocompromised patients presenting with unexplained fever and skin or sinus lesions should be evaluated for Acanthamoeba castellanii infection. Multi-drug combination therapy is required for this organism infection, and a standard treatment protocol still needs further research. Metagenomic next-generation sequencing is a valuable tool for early diagnosis of unknown pathogen infections.