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1.
Science ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409524

RESUMO

Human genetic history in East Asia is poorly understood. To clarify population relationships, we obtained genome wide data from 26 ancient individuals from northern and southern East Asia spanning 9,500-300 years ago. Genetic differentiation was higher in the past than the present, reflecting a major episode of admixture involving northern East Asian ancestry spreading across southern East Asia after the Neolithic, transforming the genetic ancestry of southern China. Mainland southern East Asian and Taiwan Strait island samples from the Neolithic show clear connections with modern and ancient samples with Austronesian-related ancestry, supporting a southern China origin for proto-Austronesians. Connections among Neolithic coastal groups from Siberia and Japan to Vietnam indicate that migration and gene flow played an important role in the prehistory of coastal Asia.

2.
Comput Biol Chem ; 86: 107261, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32361585

RESUMO

Mutant isocitrate dehydrogenase 2 (mIDH2) is an emerging target for the treatment of cancer. AG-221 is the first mIDH2 inhibitor approved by the FDA for acute myeloid leukemia treatment, but its acquired resistance has recently been observed, necessitating the development of new inhibitor. In this study, a multi-step virtual screening protocol was employed for the analysis of a large database of compounds to identify potential mIDH2 inhibitors. To this end, we firstly utilized molecular dynamics (MD) simulations and binding free energy calculations to elucidate the key factors affecting ligand binding and drug resistance. Based on these findings, the receptor-ligand interaction-based pharmacophore (IBP) model and hierarchical docking-based virtual screening were sequentially carried out to assess 212,736 compounds from the Specs database. The resulting hits were finally ranked by PAINS filter and ADME prediction and the top compounds were obtained. Among them, six molecules were identified as mIDH2 putative inhibitors with high selectivity by interacting with the capping residue Asp312. Furthermore, subsequent docking and MD experiments demonstrated that compound V2 might have potential inhibitory activity against the AG-221-resistant mutants, thereby making it a promising lead for the development of novel mIDH2 inhibitors.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32375931

RESUMO

A Gram-stain-positive, non-motile, creamy-white actinobacterium, which has an elementary branching rod-coccus life cycle was isolated from the rhizosphere soil of rice (Oryza sativa L.) collected from Northeast Agricultural University in Harbin, Heilongjiang province, north-east PR China, and its taxonomic status was examined by using a polyphasic approach. Results from the 16S rRNA gene sequence study showed that the isolate, designated strain NEAU-CX67T, belonged to the genus Rhodococcus and formed a cluster with Rhodococcus maanshanensis DSM 44675T, Rhodococcus kronopolitis NEAU-ML12T and Rhodococcus tukisamuensis JCM 11308T (98.3, 98.1 and 97.7% gene sequence similarity, respectively). The major fatty acids were C16 : 0, 10-methyl C18 : 0, C18 : 1 ω9c and C16 : 1 ω7c. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major isoprenoid quinone was MK-8(H2). Whole-cell hydrolysates contained meso-diaminopimelic acid. Arabinose, galactose and ribose were detected as diagnostic sugars from whole-cell hydrolysates. Mycolic acids were detected. The genomic DNA G+C content of strain NEAU-CX67T was 64.6 mol%. Strain NEAU-CX67T exhibited low average nucleotide identity and digital DNA-DNA hybridization values with R. maanshanensis DSM 44675T (92.1 and 45.4 %) and R. tukisamuensis JCM 11308T (81.9 and 24.4 %). On the basis of results of phylogenetic, genotypic, physiological and chemotaxonomic analysis, strain NEAU-CX67T is considered to represent a novel species of the genus Rhodococcus for which the name Rhodococcus oryzae sp. nov. is proposed. The type strain is NEAU-CX67T (=DSM 107701T=CCTCC AB 2018233T).

4.
Curr Opin Struct Biol ; 63: 49-57, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32389895

RESUMO

Photosystem II (PSII) catalyzes the light-driven oxygen-evolving reaction via its catalytic core and peripheral light-harvesting antennas. Oxyphototrophs have evolved diverse antenna systems, enabling them to adapt to different habitats. Recently, high-resolution structures of PSII-antenna supercomplexes from the green lineage (higher plants and green algae) and the red lineage (diatoms) were solved. The antenna complexes from the two lineages share similar protein folding, but differ in terms of the oligomeric states, pigment composition, and assembly patterns with the core. These differences result in distinct pigment-protein networks in PSII from different organisms. We herein summarize the similarities and differences in these structures and outline the molecular basis of the assembly, energy transfer, and regulation of the eukaryotic PSII-antenna supercomplexes.

5.
Magn Reson Imaging ; 70: 81-90, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32276007

RESUMO

PURPOSE: A deep neural network was developed for magnetic resonance fingerprinting (MRF) quantification. This study aimed at extending previous studies of deep learning MRF to in vivo applications, allowing sub-second computation time for large-scale data. METHODS: We applied the deep learning methodology based on our previously published multi-layer perceptron. The number of layers was four, which was optimized to balance the model capacity and noise robustness. The training sets were obtained from MRF dictionaries with 9000 to 28,000 atoms, depending on the desired T1 and T2 ranges. The simulated MRF undersampling artifact based on the k-space acquisition scheme and noise were both added to the training data to reduce the error in estimates. RESULTS: The neural network achieved high fidelity (R2 _ 0.98) as compared to the T1 and T2 values of the ISMRM standardized phantom. In brain MRF experiment, the model trained with simulated artifacts and noise showed less error compared to that without. The in vivo application of our neural network for liver and prostate were also demonstrated. For an MRF slice with 256 _ 256 image resolution, the computation time of our neural network was 0.12 s, compared with the _ 28 s-pre-slice for the conventional dictionary matching method. CONCLUSION: Our neural network achieved fast computation speed for MRF quantification. The model trained with simulated artifacts and noise showed less error and achieved optimal performance for phantom experiment and in vivo normal brain and liver, and prostate cancer patient.

6.
Magn Reson Med ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32274850

RESUMO

PURPOSE: To develop a deep learning-based Bayesian estimation for MRI reconstruction. METHODS: We modeled the MRI reconstruction problem with Bayes's theorem, following the recently proposed PixelCNN++ method. The image reconstruction from incomplete k-space measurement was obtained by maximizing the posterior possibility. A generative network was utilized as the image prior, which was computationally tractable, and the k-space data fidelity was enforced by using an equality constraint. The stochastic backpropagation was utilized to calculate the descent gradient in the process of maximum a posterior, and a projected subgradient method was used to impose the equality constraint. In contrast to the other deep learning reconstruction methods, the proposed one used the likelihood of prior as the training loss and the objective function in reconstruction to improve the image quality. RESULTS: The proposed method showed an improved performance in preserving image details and reducing aliasing artifacts, compared with GRAPPA, ℓ 1 -ESPRiT, model-based deep learning architecture for inverse problems (MODL), and variational network (VN), last two were state-of-the-art deep learning reconstruction methods. The proposed method generally achieved more than 3 dB peak signal-to-noise ratio improvement for compressed sensing and parallel imaging reconstructions compared with the other methods. CONCLUSIONS: The Bayesian estimation significantly improved the reconstruction performance, compared with the conventional ℓ 1 -sparsity prior in compressed sensing reconstruction tasks. More importantly, the proposed reconstruction framework can be generalized for most MRI reconstruction scenarios.

7.
Clin Infect Dis ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32301964

RESUMO

BACKGROUND: Since December 2019, SARS-CoV-2 virus has extended to most parts of China with more than 80 thousand cases and to at least 100 countries with more than 60 thousand international cases by March 15, 2020. Here we applied household cohort study to determine the features of household transmission of COVID-19. METHODS: Total 105 index patients and 392 household contacts were enrolled. Both index patients and household members were inspected by SARS-CoV-2 RT-PCR. The information of all recruited people was extracted from medical records and confirmed or supplemented by telephone interviews. The baseline characteristics of index cases and contact patients were described. Secondary attack rates of SARS-CoV-2 to the contact members were computed and the risk factors for transmission within household were estimated. RESULTS: Secondary transmission of SARS-CoV-2 developed in 64 of 392 household contacts (16.3%). The secondary attack rate to children was 4% comparing with 17.1% to adults. The secondary attack rate to the contacts within the households with index patients quarantined by themselves since onset of symptoms was 0% comparing with 16.9% to the contacts without index patients quarantined. The secondary attack rate to contacts who were spouses of index cases was 27.8% comparing with 17.3% to other adult members in the households. CONCLUSION: The secondary attack rate of SARS-CoV-2 in household is 16.3%. Ages of household contacts and spouse relationship with index case are risk factors for transmission of SARS-CoV-2 within household. Quarantine of index patients at home since onset of symptom is useful to prevent the transmission of SARS-Co-2 within household.

8.
Sci Rep ; 10(1): 6244, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32277103

RESUMO

Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imaging target for detection of glioblastoma. The goal of our study was to assess the value of hyperpolarized (HP) γ-glutamyl-[1-13C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-13C]glycine and acquiring dynamic 13C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-13C]glycine and its product [1-13C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-13C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-13C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-13C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-13C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma.

9.
JAMA Oncol ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32271353

RESUMO

Importance: Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1-infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies. Objective: To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection. Design, Setting, and Participants: The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti-PD-1 or anti-PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy. Interventions: Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects. Main Outcomes and Measures: Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. Results: A total of 20 HIV-1-infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study. Conclusions and Relevance: Durvalumab treatment was feasible and safe in HIV-1-infected patients with cancer receiving combination antiretroviral therapy. HIV-1-infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments. Trial Registration: ClinicalTrials.gov Identifier: NCT03094286.

10.
Cell Commun Signal ; 18(1): 55, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245484

RESUMO

BACKGROUND: IDH2/R140Q mutation is frequently detected in acute myeloid leukemia (AML). It contributes to leukemia via accumulation of oncometabolite D-2-HG. Therefore, mutant IDH2 is a promising target for AML. Discovery of IDH2 mutant inhibitors is in urgent need for AML therapy. METHODS: Structure-based in silico screening and enzymatic assays were used to identify IDH2/R140Q inhibitors. Molecular docking, mutant structure building and molecular dynamics simulations were applied to investigate the inhibitory mechanism and selectivity of CP-17 on IDH2/R140Q. TF-1 cells overexpressed IDH2/R140Q mutant were used to study the effects of CP-17 on cellular proliferation and differentiation, the wild-type TF-1 cells were used as control. The intracellular D-2-HG production was measured by LC-MS. The histone methylation was evaluated with specific antibodies by western blot. RESULTS: CP-17, a heterocyclic urea amide compound, was identified as a potent inhibitor of IDH2/R140Q mutant by in silico screening and enzymatic assay. It exhibits excellent inhibitory activity with IC50 of 40.75 nM against IDH2/R140Q. More importantly, it shows poor activity against the wild-type IDH1/2, resulting in a high selectivity of over 55 folds, a dramatic improvement over previously developed inhibitors such as AGI-6780 and Enasidenib. Molecular simulations suggested that CP-17 binds to IDH2/R140Q at the allosteric site within the dimer interface through extensive polar and hydrophobic interactions, locking the enzyme active sites in open conformations with abolished activity to produce D-2-HG. Cellular assay results demonstrated that CP-17 inhibits intracellular D-2-HG production and suppresses the proliferation of TF-1 erythroleukemia cells carrying IDH2/R140Q mutant. Further, CP-17 also restores the EPO-induced differentiation that is blocked by the mutation and decreases hypermethylation of histone in the TF-1(IDH2/R140Q) cells. CONCLUSIONS: These results indicate that CP-17 can serve as a lead compound for the development of inhibitory drugs against AML with IDH2/R140Q mutant. Video abstract.

11.
Nat Commun ; 11(1): 1525, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251275

RESUMO

Long-chain alk(a/e)nes represent the major constituents of conventional transportation fuels. Biosynthesis of alkanes is ubiquitous in many kinds of organisms. Cyanobacteria possess two enzymes, acyl-acyl carrier protein (acyl-ACP) reductase (AAR) and aldehyde-deformylating oxygenase (ADO), which function in a two-step alkane biosynthesis pathway. These two enzymes act in series and possibly form a complex that efficiently converts long chain fatty acyl-ACP/fatty acyl-CoA into hydrocarbon. While the structure of ADO has been previously described, structures of both AAR and AAR-ADO complex have not been solved, preventing deeper understanding of this pathway. Here, we report a ligand-free AAR structure, and three AAR-ADO complex structures in which AARs bind various ligands. Our results reveal the binding pattern of AAR with its substrate/cofactor, and suggest a potential aldehyde-transferring channel from AAR to ADO. Based on our structural and biochemical data, we proposed a model for the complete catalytic cycle of AAR.

12.
Org Lett ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32233500

RESUMO

A copper-catalyzed three-component reaction of terminal alkynes, TsN3, and tertiary allylic amines is developed toward the one-pot synthesis of α-allylic amidines. The product was synthesized on gram scale under 1 mol % of catalyst loading. Transformations of products into alkenyl amine and other nitrogen-containing compounds are demonstrated without any loss of stereochemical information.

13.
Plant Dis ; : PDIS12192557RE, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32320370

RESUMO

Rice is used as a staple food in different areas of world, especially in China. In recent years, rice seedlings have been affected seriously by symptoms resembling bacterial palea browning (BPB) in Heilongjiang Province. To isolate and identify the pathogenic bacteria responsible for the disease, 40 bacterial strains were isolated from diseased rice seedlings collected from the four major accumulative-temperature zones of rice fields cultivated in Heilongjiang Province, and these were identified as 13 species based on morphological characteristics and 16S ribosomal RNA (rRNA) gene sequences. Inoculation of all the isolates on healthy rice seedlings showed that the nine Enterobacter cloacae isolates were the pathogens causing typical symptoms of BPB, including yellowing to pale browning, stunting, withering, drying, and death. Moreover, the nine E. cloacae isolates could also cause symptoms of bacterial disease on the seedlings of soybean (Glycine max), maize (Zea mays L.), and tomato (Solanum lycopersicum). Phylogenetic analysis based on the 16S rRNA gene sequences and phenotypic and biochemical characteristics indicated that these nine pathogenic isolates were E. cloacae. In addition, analysis of the sequences of four housekeeping genes (rpoB, gyrB, infB, and atpD) from the selected strain SD4L also assigned the strain to E. cloacae. Therefore, E. cloacae is the pathogen causing disease of rice seedlings in Heilongjiang Province, which we propose to classify as a form of BPB. To the best of our knowledge, this is the first study to identify E. cloacae as a causal agent of BPB in rice.

14.
Microorganisms ; 8(3)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244993

RESUMO

Cancer is a serious threat to human health. With the increasing resistance to known drugs, it is still urgent to find new drugs or pro-drugs with anti-tumor effects. Natural products produced by microorganisms have played an important role in the history of drug discovery, particularly in the anticancer and anti-infective areas. The plant rhizosphere ecosystem is a rich resource for the discovery of actinomycetes with potential applications in pharmaceutical science, especially Streptomyces. We screened Streptomyces-like strains from the rhizosphere soil of wheat (Triticum aestivum L.) in Hebei province, China, and thirty-nine strains were obtained. Among them, the extracts of 14 isolates inhibited the growth of colon tumor cell line HCT-116. Strain NEAU-wh-3-1 exhibited better inhibitory activity, and its active ingredients were further studied. Then, 16S rRNA gene sequence similarity studies showed that strain NEAU-wh3-1 with high sequence similarities to Embleya scabrispora DSM 41855T (99.65%), Embleya hyalina MB891-A1T (99.45%), and Streptomyces lasii 5H-CA11T (98.62%). Moreover, multilocus sequence analysis based on the five other house-keeping genes (atpD, gyrB, rpoB, recA, and trpB) and polyphasic taxonomic approach comprising chemotaxonomic, phylogenetic, morphological, and physiological characterization indicated that the isolate should be assigned to the genus Embleya and was different from its closely related strains, therefore, it is proposed that strain NEAU-wh3-1 may be classified as representatives of a novel species of the genus Embleya. Furthermore, active substances in the fermentation broth of strain NEAU-wh-3-1 were isolated by bioassay-guided analysis and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses. Consequently, one new Zincophorin analogue together with seven known compounds was detected. The new compound showed highest antitumor activity against three human cell lines with the 50% inhibition (IC50) values of 8.8-11.6 µg/mL and good antibacterial activity against four pathogenic bacteria, the other known compounds also exhibit certain biological activity.

15.
Magn Reson Med ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243657

RESUMO

PURPOSE: To learn bone shape features from spherical bone map of knee MRI images using established convolutional neural networks (CNN) and use these features to diagnose and predict osteoarthritis (OA). METHODS: A bone segmentation model was trained on 25 manually annotated 3D MRI volumes to segment the femur, tibia, and patella from 47 078 3D MRI volumes. Each bone segmentation was converted to a 3D point cloud and transformed into spherical coordinates. Different fusion strategies were performed to merge spherical maps obtained by each bone. A total of 41 822 merged spherical maps with corresponding Kellgren-Lawrence grades for radiographic OA were used to train a CNN classifier model to diagnose OA using bone shape learned features. Several OA Diagnosis models were tested and the weights for each trained model were transferred to the OA Incidence models. The OA incidence task consisted of predicting OA from a healthy scan within a range of eight time points, from 1 y to 8 y. The validation performance was compared and the test set performance was reported. RESULTS: The OA Diagnosis model had an area-under-the-curve (AUC) of 0.905 on the test set with a sensitivity and specificity of 0.815 and 0.839. The OA Incidence models had an AUC ranging from 0.841 to 0.646 on the test set for the range from 1 y to 8 y. CONCLUSION: Bone shape was successfully used as a predictive imaging biomarker for OA. This approach is novel in the field of deep learning applications for musculoskeletal imaging and can be expanded to other OA biomarkers.

16.
Int Immunopharmacol ; 83: 106421, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32217462

RESUMO

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells derived from bone marrow. These cells are developed from immature myeloid cells and have strong negative immunomodulatory effects. In the context of pathology (such as tumor, autoimmune disease, trauma, and burns), MDSCs accumulate around tumor and inflammatory tissues, where their main role is to inhibit the function of effector T cells and promote the recruitment of regulatory T cells. MDSCs can be used in organ transplantation to regulate the immune responses that participate in rejection of the transplanted organ. This effect is achieved by increasing the production of MDSCs in vivo or transfusion of MDSCs induced in vitro to establish immune tolerance and prolong the survival of the graft. In this review, we discuss the efficacy of MDSCs in a variety of transplantation studies as well as the induction of immune tolerance to prevent transplant rejection through the use of common clinical immunosuppressants combined with MDSCs.

17.
Clin Spine Surg ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32149743

RESUMO

STUDY DESIGN: This was a retrospective study of the clinical and radiologic outcomes of multilevel anterior cervical discectomy and fusion (ACDF) surgery for multilevel cervical spondylosis patients. OBJECTIVE: In this retrospective study, we intended to determine the relationship of neck circumference, neck length, and body mass index (BMI) with the outcomes of multilevel ACDF surgeries for patients with multilevel cervical spondylosis. SUMMARY OF BACKGROUND DATA: Obesity has become a worldwide epidemic problem since the beginning of the 21st century. However, no study has focused on how local or whole-body obesity indexes (neck circumference, length of neck, and BMI) are related to the outcome of anterior cervical surgery. METHODS: A total of 156 consecutive patients with multilevel cervical spondylosis who underwent anterior cervical surgery in our department from 2010 to 2016 were enrolled in our study. Preoperative parameters of patients such as the neck circumference, length of neck, height and weight were measured, and the BMI was also calculated. Neck circumference and length of neck in neutral position ratio was determined as an index for evaluated the neck situation. Preoperative and postoperative neurological functions were evaluated using the neck disability index (NDI) and Japan Orthopedic Association (JOA) scores. Postoperative complications during the follow-up period were also recorded. Correlations between the obesity indexes and the various factors were analyzed. RESULTS: The mean follow-up duration was 3.9±1.4 years (2.0-7.3 y). Compared with the preoperative score, the NDI and JOA score had significantly improved. There were 46 patients (29.49%) developed complications after surgery. Patients in the obese group had the highest rate of complications. Neck circumference and length of neck in neutral position ratio, BMI, and number of operation levels were significant risk factors for the occurrence of dysphagia after multilevel ACDF. CONCLUSIONS: Patients with a higher BMI, larger neck circumference, and shorter neck length may have a longer operation duration, more blood loss, and more postoperative complications. The authors recommended that the presence of obesity and neck circumference and length should be carefully considered in the perioperative risk assessment for a multilevel ACDF surgery.

18.
ACS Nano ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32149493

RESUMO

Wearable and stretchable electronics including various conductors and sensors are featured with their lightweight, high flexibility, and easy integration into functional devices or textiles. However, most flexible electronic materials are still unsatisfactory due to their poor recoverability under large strain. Herein, we fabricated a carbon nanotubes (CNTs) and polyurethane (PU) nanofibers composite helical yarn with electrical conductivity, ultrastretchability, and high stretch sensitivity. The synergy of elastic PU molecules and spring-like microgeometry enable the helical yarn excellent stretchability, while CNTs are stably winding-locked into the yarn through a simple twisting strategy, making good conductivity. By virtue of the interlaced conductive network of CNTs in microlevel and the helical structure in macrolevel, the CNTs/PU helical yarn achieves good recoverability within 900% and maximum tensile elongation up to 1700%. With these features, it can be used as a superelastic and highly stable conductive wire. Moreover, it also can monitor the human motion as a rapid-response strain sensor by adjusting the content of the CNTs simply. This general and low-cost strategy is of great promise for ultrastretchable wearable electronics and multifunctional devices.

19.
J Agric Food Chem ; 68(15): 4528-4537, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32207934

RESUMO

Ryanodine receptors (RyRs) are homotetrameric intracellular calcium (Ca2+) release channels responsible for excitation-contraction coupling of muscle cells. Diamide insecticides specifically act on RyRs of Lepidoptera and Coleoptera pests and are safe for nontargeted organisms, generating big worldwide sales. Despite their popularity, several devastating agricultural pests have been reported to be resistant to them because of mutations in a small transmembrane region of their RyRs, hinting a binding pocket nearby. A potential solution to overcome resistance is to develop new insecticides targeting different binding sites in pest RyRs. Based on a high-resolution crystal structure of diamondback moth (DBM) RyR N-terminal domain (NTD) determined by our group, we carried out extensive structure-based insecticide screening targeting the intersubunit interface. We identified eight lead compounds that selectively target the open conformation of DBM RyR, which are predicted to act as channel activators similar to diamide insecticides. Binding mode analysis shows selective binding to a hydrophobic pocket of DBM NTD-A but not to the pocket of its mammalian counterpart. We tested three available compounds on the HEK293 cell lines stably expressing DBM or mammalian RyR, one of which shows good potency and selectivity against DBM RyR. The insecticidal effect of the compound was also confirmed using fruit flies. The detailed binding mode, toxicity, absorption, distribution, metabolism, and excretion, and reactivity of the compound were predicted by bioinformatic methods. Together, our study lays a foundation for developing a new class of selective RyR-targeting insecticides to control both wild-type and resistant pests.

20.
Proc Biol Sci ; 287(1923): 20192968, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32183622

RESUMO

The clarification of the genetic origins of present-day Tibetans requires an understanding of their past relationships with the ancient populations of the Tibetan Plateau. Here we successfully sequenced 67 complete mitochondrial DNA genomes of 5200 to 300-year-old humans from the plateau. Apart from identifying two ancient plateau lineages (haplogroups D4j1b and M9a1a1c1b1a) that suggest some ancestors of Tibetans came from low-altitude areas 4750 to 2775 years ago and that some were involved in an expansion of people moving between high-altitude areas 2125 to 1100 years ago, we found limited evidence of recent matrilineal continuity on the plateau. Furthermore, deep learning of the ancient data incorporated into simulation models with an accuracy of 97% supports that present-day Tibetan matrilineal ancestry received partial contribution rather than complete continuity from the plateau populations of the last 5200 years.

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