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.
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.
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.
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.
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.
Retinal fundus diseases can lead to irreversible visual impairment without timely diagnoses and appropriate treatments. Single disease-based deep learning algorithms had been developed for the ...detection of diabetic retinopathy, age-related macular degeneration, and glaucoma. Here, we developed a deep learning platform (DLP) capable of detecting multiple common referable fundus diseases and conditions (39 classes) by using 249,620 fundus images marked with 275,543 labels from heterogenous sources. Our DLP achieved a frequency-weighted average F1 score of 0.923, sensitivity of 0.978, specificity of 0.996 and area under the receiver operating characteristic curve (AUC) of 0.9984 for multi-label classification in the primary test dataset and reached the average level of retina specialists. External multihospital test, public data test and tele-reading application also showed high efficiency for multiple retinal diseases and conditions detection. These results indicate that our DLP can be applied for retinal fundus disease triage, especially in remote areas around the world.
The Co‐based electrocatalyst is among the most promising candidates for electrochemical oxidation of 5‐hydroxymethylfurfural (HMF). However, the intrinsic active sites and detailed mechanism of this ...catalyst remains unclear. We combine experimental evidence and a theoretical study to show that electrogenerated Co3+ and Co4+ species act as chemical oxidants but with distinct roles in selective HMF oxidation. It is found that Co3+ is only capable of oxidizing formyl group to produce carboxylate while Co4+ is required for the initial oxidation of hydroxyl group with significantly faster kinetics. As a result, the product distribution shows explicit dependence on the Co oxidation states and selective production of 5‐hydroxymethyl‐2‐furancarboxylic acid (HMFCA) and 2,5‐furandicarboxylic acid (FDCA) are achieved by tuning the applied potential. This work offers essential mechanistic insight on Co‐catalyzed organic oxidation reactions and might guide the design of more efficient electrocatalysts.
A detailed mechanism for cobalt‐catalyzed electrochemical 5‐hydroxymethylfurfural (HMF) oxidation is revealed. A combined experimental and theoretical study shows that a Co3+ species is capable of oxidizing the formyl group to produce carboxylate but remains inert towards oxidation of the hydroxyl group. In contrast, a Co4+ species is required for the initial oxidation of the hydroxyl group in HMF.
The utilization of solar energy to produce hydrogen from water is showing increased importance and desirability in the field of artificial photosynthesis to produce clean and sustainable fuels. In a ...typical three‐component dye‐sensitized semiconductor system for photocatalysis, the dye sensitizer plays an essential role of energy antenna for harvesting visible light and promoting the reduction reaction to generate hydrogen. In recent decades, a lot of attention has focused on metal‐free organic sensitizers, which have the advantages of low cost, high molar extinction coefficient, good modifiability and, most importantly, ability to avoid the use of noble metal ions. This Review enumerates the design strategies, specific properties and photocatalytic performances of metal‐free sensitizers in the past 30 years and concludes their evolution process. The advantages of different types of metal‐free sensitizers are highlighted and the instructively enlightening experiences are systematic summarized.
Learning from the past: In the past 30 years diverse types of metal‐free dyes have been developed and applied in dye‐sensitized semiconductor photocatalysts for visible‐light‐driven hydrogen production from water. This Review retrospects the development history and tendency of metal‐free dyes, in which the design strategies, structures, properties and photocatalytic performances are enumerated and their structure‐activity relationships are summarized systematically.
Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Mutations in MFN2 cause the neurodegenerative disease Charcot-Marie-Tooth ...type 2A (CMT2A). The molecular basis underlying the physiological and pathological relevance of MFN2 is unclear. Here, we present crystal structures of truncated human MFN2 in different nucleotide-loading states. Unlike other dynamin superfamily members including MFN1, MFN2 forms sustained dimers even after GTP hydrolysis via the GTPase domain (G) interface, which accounts for its high membrane-tethering efficiency. The biochemical discrepancy between human MFN2 and MFN1 largely derives from a primate-only single amino acid variance. MFN2 and MFN1 can form heterodimers via the G interface in a nucleotide-dependent manner. CMT2A-related mutations, mapping to different functional zones of MFN2, lead to changes in GTP hydrolysis and homo/hetero-association ability. Our study provides fundamental insight into how mitofusins mediate mitochondrial fusion and the ways their disruptions cause disease.
Summary Background Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a ...cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. Methods For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18–70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0–1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov , number NCT01287624. Findings From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4–26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7–25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523–0·915; pnon-inferiority <0·0001, psuperiority =0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16–9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76–7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight 7% vs one <1%), vomiting (13 11% vs one <1%), musculoskeletal pain (none vs ten 8%), anaemia (39 33% vs six 5%), and thrombocytopenia (38 32% vs three 3%), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1–4 alopecia (12 10% vs 42 36%) and peripheral neuropathy (27 23% vs 60 51%), but more grade 1–4 anorexia (33 28% vs 10 8%), constipation (29 25% vs 11 9%), hypomagnesaemia (27 23% vs five 4%), and hypokalaemia (10 8% vs two 2%). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. Interpretation Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. Funding Shanghai Natural Science Foundation.
Herein, we present a stable water‐soluble cobalt complex supported by a dianionic 2,2′‐(2,2′‐bipyridine‐6,6′‐diyl)bis(propan‐2‐ol) ligand scaffold, which is a rare example of a high‐oxidation ...species, as demonstrated by structural, spectroscopic and theoretical data. Electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements revealed that the CoIV center of the mononuclear complex in the solid state resides in the high spin state (sextet, S=5/2). The complex can effectively catalyze water oxidation via a single‐site water nucleophilic attack pathway with an overpotential of only 360 mV in a phosphate buffer with a pH of 6. The key intermediate toward water oxidation was speculated based on theoretical calculations and was identified by in situ spectroelectrochemical experiments. The results are important regarding the accessibility of high‐oxidation state metal species in synthetic models for achieving robust and reactive oxidation catalysis.
A stable water‐soluble cobalt(IV) complex supported by a dianionic 2,2′‐(2,2′‐bipyridine‐6,6′‐diyl)bis(propan‐2‐ol) ligand scaffold is very active in the catalysis of water oxidation at an overpotential of only 360 mV at pH=6.
The progress of plasmon-based technologies relies on an understanding of the properties of the enhanced electromagnetic fields generated by the coupling nanostrucutres
. Plasmon-enhanced applications ...include advanced spectroscopies
, optomechanics
, optomagnetics
and biosensing
. However, precise determination of plasmon field intensity distribution within a nanogap remains challenging. Here, we demonstrate a molecular ruler made from a set of viologen-based, self-assembly monolayers with which we precisely measures field distribution within a plasmon nanocavity with ~2-Å spatial resolution. We observed an unusually large plasmon field intensity inhomogeneity that we attribute to the formation of a plasmonic comb in the nanocavity. As a consequence, we posit that the generally adopted continuous media approximation for molecular monolayers should be used carefully.
High porosity with well‐defined molecular reticulation along with strong stability is desired for natural gas delivery. The catalyzed Yamamoto‐type Ullmann cross‐coupling route with efficient ...terminal halogen removal capability is currently used to prepare porous organic materials with high specific surface area as well as ultrahigh hydrothermal stability. As a typical fast coupling reaction, the traditional stirred solvothermal approach shows the limitation of macroscopic reaction kinetics due to the increasing viscosity of the reaction mixture with the molecular network growth until it turns to a jelly‐like consistency. Herein, a high‐gravity chemical synthetic strategy to achieve rapid and economical preparation of a class of, but not limited to, covalent organic polymers (COPs) with high hydrothermal stability using the Ullman cross‐coupling route is described. The viscous fluid is vigorously split into homogeneous microdroplets through the rotating packed bed (RPB) under the HiGee environment. The HiGee approach shortens the traditional reaction time from 600 to 15 min as well as reduces the usage of high‐cost nickel (0) catalyst by 40 wt%. Specially, the COP‐10 obtained with the HiGee approach displays an excellent deliverable methane capacity of 415 cm3 STP g−1 at 298 K with working pressures 5–65 bar, which is higher than that of most reported porous organic materials.
Covalent organic polymers are efficiently synthesized by the HiGee approach, shortening the reaction time from 600 to 15 min and reducing usage of high‐cost nickel (0) catalyst by 40% with a space–time yield of 150–360 kg m−3 day−1. The synthesized COP‐10 through the HiGee approach displays an excellent deliverable methane capacity of 415 cm3STP g−1 at 298 K during working pressures 5–65 bar.
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