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Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection. Nanopore reads have been advantageous for de novo genome assembly; however these reads have high error rates. Here, the authors develop an error correction and de novo assembly tool, NECAT, which produces efficient, high quality assemblies of nanopore reads.

INTRODUCTION Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood. METHODS Whole‐brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI‐ALPS) in participants with AD dementia (n = 47), mild cognitive impairment (MCI; n = 137), and normal controls (n = 235) from the Alzheimer's Disease Neuroimaging Initiative. RESULTS ALPS index was significantly lower in AD dementia than in MCI or controls. Lower ALPS index was significantly associated with faster changes in amyloid positron emission tomography (PET) burden and AD signature region of interest volume, higher risk of amyloid‐positive transition and clinical progression, and faster rates of amyloid‐ and neurodegeneration‐related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline were fully mediated by amyloid PET and brain atrophy. DISCUSSION Glymphatic failure may precede amyloid pathology, and predicts amyloid deposition, neurodegeneration, and clinical progression in AD. Highlights The analysis along the perivascular space (ALPS) index is reduced in patients with Alzheimer's disease (AD) dementia, prodromal AD, and preclinical AD. Lower ALPS index predicted accelerated amyloid beta (Aβ) positron emission tomography (PET) burden and Aβ‐positive transition. The decrease in the ALPS index occurs before cerebrospinal fluid Aβ42 reaches the positive threshold. ALPS index predicted brain atrophy, clinical progression, and cognitive decline. Aβ PET and brain atrophy mediated the link of ALPS index with cognitive decline.

Magnesium alloys have received an increasing interest in the past 12 years for potential applications in the automotive, aircraft, aerospace, and electronic industries. Many of these alloys are strong because of solid-state precipitates that are produced by an age-hardening process. Although some strength improvements of existing magnesium alloys have been made and some novel alloys with improved strength have been developed, the strength level that has been achieved so far is still substantially lower than that obtained in counterpart aluminum alloys. Further improvements in the alloy strength require a better understanding of the structure, morphology, orientation of precipitates, effects of precipitate morphology, and orientation on the strengthening and microstructural factors that are important in controlling the nucleation and growth of these precipitates. In this review, precipitation in most precipitation-hardenable magnesium alloys is reviewed, and its relationship with strengthening is examined. It is demonstrated that the precipitation phenomena in these alloys, especially in the very early stage of the precipitation process, are still far from being well understood, and many fundamental issues remain unsolved even after some extensive and concerted efforts made in the past 12 years. The challenges associated with precipitation hardening and age hardening are identified and discussed, and guidelines are outlined for the rational design and development of higher strength, and ultimately ultrahigh strength, magnesium alloys via precipitation hardening.

Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative score markedly stratified the risk for 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, and genitourinary diseases, cancers, and mortality. The discriminations witnessed high accuracies achieved by ProRS for 10 endpoints (e.g., cancer, dementia, and death), with C-indexes exceeding 0.80. Notably, ProRS produced much better or equivalent predictive performance than established clinical indicators for almost all endpoints. Incorporating clinical predictors with ProRS enhanced predictive power for most endpoints, but this combination only exhibited limited improvement when compared to ProRS alone. Some proteins, e.g., GDF15, exhibited important discriminative values for various diseases. We also showed that the good discriminative performance observed could be largely translated into practical clinical utility. Taken together, proteomic profiles may serve as a replacement for complex laboratory tests or clinical measures to refine the comprehensive risk assessments of multiple diseases and mortalities simultaneously. Our models were internally validated in the UK Biobank; thus, further independent external validations are necessary to confirm our findings before application in clinical settings. The predictive capability of future health risk using plasma proteomic profiles remains largely unexplored. Using 1461 proteins collected from 50k individuals, authors show proteins can derive much better or equivalent performance than established clinical indicators for more than 40 endpoints.

Introduction Behcet’s syndrome (BS) is a complex, heterogeneous disorder. However, classification of its subgroups is still debated. The purpose of this study was to investigate the clinical features and aggregation of patients with BS in China, based on manifestations and organ involvements. Methods This was a cross-sectional study of BS patients in Huadong Hospital of Fudan University between September 2012 and January 2020. We calculated relative risks (RRs) of clinical variables according to sex. Moreover, we conducted a hierarchical cluster analysis applied according to eighteen variables to determine subgroups of patients. Results A total of 860 BS patients were included. Male sex was associated with ocular involvement (RR 2.32, 95% CI 1.67, 3.22, P  < 0.0001), vascular involvement (RR 2.00, 95% CI 1.23, 3.23, P  = 0.004), cardiac lesion (RR 5.46, 95% CI 2.33, 12.77, P  < 0.0001), and central nervous system involvement (RR 2.95, 95% CI 1.07, 6.78, P  = 0.007) and was negatively associated with genital ulcers (RR 0.84, 95% CI 0.79, 0.91, P  < 0.0001). Five clusters (C1–C5) were observed. C1 ( n  = 307) showed the skin and mucosa type. In C2 ( n  = 124), all had articular involvement, barely having major organ involvement except for 18 cases with intestinal lesions. In C3 ( n  = 156), the gastrointestinal type, 144 patients presented with intestinal involvement, and 36 patients with esophageal ulcers. In C4 ( n  = 142), all subjects presented with uveitis. C5 ( n  = 131) consisted of 44 patients with cardiac lesions, 58 with vascular involvement, and 26 cases having central nervous system involvement. Conclusion Our analysis confirmed sex differences in phenotypes of BS. Cluster analysis identified gastrointestinal, uveitis, and cardiovascular involvement cluster separately in different subsets, which represents the most commonly involved organs. Further research is required to replicate and clarify the patterns of phenotype in BS.

Identifying the clinical implications and modifiable and unmodifiable factors of aging requires the measurement of biological age (BA) and age gap. Leveraging the biomedical traits involved with physical measures, biochemical assays, genomic data, and cognitive functions from the healthy participants in the UK Biobank, we establish an integrative BA model consisting of multi‐dimensional indicators. Accelerated aging (age gap >3.2 years) at baseline is associated incident circulatory diseases, related chronic disorders, all‐cause, and cause‐specific mortality. We identify 35 modifiable factors for age gap (p < 4.81 × 10−4), where pulmonary functions, body mass, hand grip strength, basal metabolic rate, estimated glomerular filtration rate, and C‐reactive protein show the most significant associations. Genetic analyses replicate the possible associations between age gap and health‐related outcomes and further identify CST3 as an essential gene for biological aging, which is highly expressed in the brain and is associated with immune and metabolic traits. Our study profiles the landscape of biological aging and provides insights into the preventive strategies and therapeutic targets for aging. The study included 59,316 healthy participants in the UK Biobank and considered 8276 phenotypes for developing biological age model. LightGBM algorithm was conducted to identify the most important predictors for biological age and build the model and the top 20 predictors were selected. We tested the longitudinal associations of age gap with 70 common health‐related outcomes, all‐cause mortality and cause‐specific mortality, and the genetic correlations of age gap with common health‐related outcomes. We identified 34 modifiable factors and 9 genomic risk loci for age gap and profiled the pleiotropy of rs3761280 in the UK Biobank.

Quantum key distribution (QKD) uses individual light quanta in quantum superposition states to guarantee unconditional communication security between distant parties. However, the distance over which QKD is achievable has been limited to a few hundred kilometres, owing to the channel loss that occurs when using optical fibres or terrestrial free space that exponentially reduces the photon transmission rate. Satellite-based QKD has the potential to help to establish a global-scale quantum network, owing to the negligible photon loss and decoherence experienced in empty space. Here we report the development and launch of a low-Earth-orbit satellite for implementing decoy-state QKD—a form of QKD that uses weak coherent pulses at high channel loss and is secure because photon-number-splitting eavesdropping can be detected. We achieve a kilohertz key rate from the satellite to the ground over a distance of up to 1,200 kilometres. This key rate is around 20 orders of magnitudes greater than that expected using an optical fibre of the same length. The establishment of a reliable and efficient space-to-ground link for quantum-state transmission paves the way to global-scale quantum networks. Decoy-state quantum key distribution from a satellite to a ground station is achieved with much greater efficiency than is possible over the same distance using optical fibres. Quantum security in orbit The laws of quantum physics give rise to protocols for ultra-secure cryptography and quantum communications. However, to be useful in a global network, these protocols will have to function with satellites. Extending existing protocols to such long distances poses a tremendous experimental challenge. Researchers led by Jian-Wei Pan present a pair of papers in this issue that take steps toward a global quantum network, using the low-Earth-orbit satellite Micius. They demonstrate satellite-to-ground quantum key distribution, an integral part of quantum cryptosystems, at kilohertz rates over 1,200 kilometres, and report quantum teleportation of a single-photon qubit over 1,400 kilometres. Quantum teleportation is the transfer of the exact state of a quantum object from one place to another, without physical travelling of the object itself, and is a central process in many quantum communication protocols. These two experiments suggest that Micius could become the first component in a global quantum internet.

Interface segregation of solute atoms has a profound effect on properties of engineering alloys. The occurrence of solute segregation in coherent twin boundaries (CTBs) in Mg alloys is commonly considered to be induced by atomic size effect where solute atoms larger than Mg take extension sites and those smaller ones take compression sites in CTBs. Here we report an unusual solute segregation phenomenon in a group of Mg alloys—solute atoms larger than Mg unexpectedly segregate to compression sites of {10 1 ¯ 1} fully coherent twin boundary and do not segregate to the extension or compression site of {10 1 ¯ 2} fully coherent twin boundary. We propose that such segregation is dominated by chemical bonding (coordination and solute electronic configuration) rather than elastic strain minimization. We further demonstrate that the chemical bonding factor can also predict the solute segregation phenomena reported previously. Our findings advance the atomic-level understanding of the role of electronic structure in solute segregation in fully coherent twin boundaries, and more broadly grain boundaries, in Mg alloys. They are likely to provide insights into interface boundaries in other metals and alloys of different structures. Segregation of solute atoms at interfaces affects the properties of alloys and needs to be understood to allow their rational design. Here the authors report an unusual solute segregation phenomenon in a group of Mg alloys, driven by chemical bonding, where solute atoms larger than Mg segregate to compression sites of specific fully coherent twin boundary.

• Ammonium is a preferential nitrogen form for rice (Oryza sativa) grown in paddy field, but the molecular mechanisms for ammonium uptake have not been well understood. • We functionally characterized three members belonging to ammonium transporter 1 (AMT1) and investigated their contributions to ammonium uptake. • Spatial expression analysis showed that the upregulated expression of OsAMT1;1 and OsAMT1;2 and downregulated expression of OsAMT1;3 by ammonium were higher in the root mature region than in the root tips. All OsAMT1 members were polarly localized at the distal side of exodermis in the mature region of crown roots and lateral roots. Upon exposure to ammonium, localization of OsAMT1;1 and OsAMT1;2 was also observed in the endoplasmic reticulum, but their abundance in the plasma membrane was not changed. Single knockout of either gene did not affect ammonium uptake, but knockout of all three genes resulted in 95% reduction of ammonium uptake. However, the nitrogen uptake did not differ between the wild-type rice and triple mutants at high ammonium and nitrate supply. • Our results indicate that three OsAMT1 members are cooperatively required for uptake of low ammonium in rice roots and that they undergo a distinct regulatory mechanism in response to ammonium.

Solid/liquid interfaces are ubiquitous in nature and knowledge of their atomic-level structure is essential in elucidating many phenomena in chemistry, physics, materials science and Earth science1. In electrochemistry, in particular, the detailed structure of interfacial water, such as the orientation and hydrogen-bonding network in electric double layers under bias potentials, has a significant impact on the electrochemical performances of electrode materials2–4. To elucidate the structures of electric double layers at electrochemical interfaces, we combine in situ Raman spectroscopy and ab initio molecular dynamics and distinguish two structural transitions of interfacial water at electrified Au single-crystal electrode surfaces. Towards negative potentials, the interfacial water molecules evolve from structurally ‘parallel’ to ‘one-H-down’ and then to ‘two-H-down’. Concurrently, the number of hydrogen bonds in the interfacial water also undergoes two transitions. Our findings shed light on the fundamental understanding of electric double layers and electrochemical processes at the interfaces.Interfacial water structures in electric double layers under bias potentials can impact the electrochemical performance of electrodes. Two structural transitions of interfacial water at electrified Au single-crystal electrode surfaces have now been identified.