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1.
Anal Methods ; 12(23): 2978-2984, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32930157

RESUMO

Visual detection of pH changes in lysosomes is critical because lysosomes not only play an important role in diverse cellular functions but also are closely related to various physiological and pathological processes. Herein, we disclose a donor-acceptor-donor (D-A-D) type fluorescent probe DBTD for detecting pH fluctuation in lysosomes. DBTD was rationally designed by using benzothiadiazole as the electron acceptor and N,N-diethylamino groups as the electron donor. Owing to its unique D-A-D structure, DBTD displayed a red-emission centered at 614 nm. It showed a sensitive and a linear response to pH from 4.5 to 5.2 with a pKa of 5.0, which is very suitable for lysosomal pH imaging. The response was based on the intramolecular charge transfer (ICT) effect owing to the protonation of the diethylamino group. Furthermore, DBTD could accurately monitor lysosomal pH variations in SGC-7901 cells. More importantly, it was able to image the pH change in lysosomes during the autophagy process successfully, suggesting the great potential of DBTD acting as a powerful tool for monitoring lysosomal pH-related biological processes.

2.
J Biol Chem ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913123

RESUMO

ADAMTSL2 mutations cause an autosomal recessive connective tissue disorder, geleophysic dysplasia 1 (GPHYSD1), which is characterized by short stature, small hands and feet, and cardiac defects. ADAMTSL2 is a matricellular protein previously shown to interact with latent TGF-ß binding protein 1 and influence assembly of fibrillin 1 microfibrils. ADAMTSL2 contains seven thrombospondin type-1 repeats (TSRs), six of which contain the consensus sequence for O-fucosylation by protein O-fucosyltransferase 2 (POFUT2). O-fucose modified TSRs are subsequently elongated to a Glucoseß1-3Fucose (GlcFuc) disaccharide by ß1,3-glucosyltransferase (B3GLCT). B3GLCT mutations cause Peters Plus Syndrome (PTRPLS), which is characterized by skeletal defects similar to GPHYSD1. Several ADAMTSL2 TSRs also have consensus sequences for C-mannosylation. Six reported GPHYSD1 mutations occur within the TSRs and two lie near O-fucosylation sites. To investigate the effects of TSR glycosylation on ADAMTSL2 function, we used mass spectrometry to identify glycan modifications at predicted consensus sequences on mouse ADAMTSL2. We found that most TSRs were modified with the GlcFuc disaccharide at high stoichiometry at O-fucosylation sites and variable mannose stoichiometry at C-mannosylation sites. Loss of ADAMTSL2 secretion in POFUT2-/- but not in B3GLCT-/- cells suggested that impaired ADAMTSL2 secretion is not responsible for skeletal defects in PTRPLS patients. In contrast, secretion was significantly reduced for ADAMTSL2 carrying GPHYSD1 mutations (S641L in TSR3 and G817R in TSR6), and S641L eliminated O-fucosylation of TSR3. These results provide evidence that abnormalities in GPHYSD1 patients with this mutation are caused by loss of O-fucosylation on TSR3 and impaired ADAMTSL2 secretion.

3.
G3 (Bethesda) ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32816916

RESUMO

Husk has multiple functions such as protecting ears from diseases, infection, and dehydration during development. Additionally, husks comprised of fewer, shorter, thinner, and narrower layers allow faster moisture evaporation of kernels prior to harvest. Intensive studies have been conducted to identify appropriate husk architecture by understanding the genetic basis of related traits, including husk length, husk layer number, husk thickness, and husk width. However, marker-assisted selection is inefficient because the identified quantitative trait loci and associated genetic loci could only explain a small proportion of total phenotypic variation. Genomic selection (GS) has been used successfully on many species including maize on other traits. Thus, the potential of using GS for husk traits to directly identify superior inbred lines, without knowing the specific underlying genetic loci, is well worth exploring. In this study, we compared four GS models on a maize association population with 498 inbred lines belonging to four subpopulations, including 27 lines in stiff stalk, 67 lines in non-stiff stalk, 193 lines in tropical-subtropical, and 211 lines in mixture subpopulations. Genomic Best Linear Unbiased Prediction with principal components as cofactor, performed the best and was selected to examine the impact of interaction between sampling proportions and subpopulations. We found that predictions on inbred lines in a subpopulation were benefited from excluding individuals from other subpopulations for training if the training population within the subpopulation was large enough. Husk thickness exhibited the highest prediction accuracy among all husk traits. These results gave a strategic inside to improve husk architecture.

4.
Opt Lett ; 45(16): 4448-4451, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32796980

RESUMO

We designed and fabricated a Mach-Zehnder interferometer (MZI) thermo-optic switch with an inverted triangular waveguide. The inverted triangular waveguide achieves a fundamental mode in a large waveguide dimension, which can reduce the coupling loss and increase the extinction ratio. The triangular waveguide-based switch was simulated and presented higher heating efficiency and lower power consumption than that of the traditional rectangular waveguide-based switch. Compared with the traditional rectangular waveguide-based device, the power consumption of the proposed device is reduced by 60%. Spacing photobleaching was introduced to fabricate the inverted triangular waveguide and adjust the refractive index to minimize the mode number. The insertion loss of the typical fabricated device with a 2 cm length is about 7.8 dB. The device shows an extinction ratio of ∼8.1dB at 532 nm with a very low power consumption of 2.2 mW, and the switching rise time and fall time are 110 and 130 µs, respectively. The proposed single-mode waveguide and low-power-consumption optical switch have great potential applications in visible optical communication fields such as wavelength division multiplexing and mode-division multiplexing.

5.
EMBO Mol Med ; 12(9): e12050, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32657028

RESUMO

Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA-IgA-negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2-DG or blockade of INSL5 by a neutralizing antibody reversed INSL5-induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC.

6.
Theor Appl Genet ; 133(10): 2869-2879, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32607592

RESUMO

KEY MESSAGE: Genomic selection with a multiple-year training population dataset could accelerate early-stage testcross testing by skipping the first-stage yield testing, which significantly saves the time and cost of early-stage testcross testing. With the development of doubled haploid (DH) technology, the main task for a maize breeder is to estimate the breeding values of thousands of DH lines annually. In early-stage testcross testing, genomic selection (GS) offers the opportunity of replacing expensive multiple-environment phenotyping and phenotypic selection with lower-cost genotyping and genomic estimated breeding value (GEBV)-based selection. In the present study, a total of 1528 maize DH lines, phenotyped in multiple-environment trials in three consecutive years and genotyped with a low-cost per-sample genotyping platform of rAmpSeq, were used to explore how to implement GS to accelerate early-stage testcross testing. Results showed that the average prediction accuracy estimated from the cross-validation schemes was above 0.60 across all the scenarios. The average prediction accuracies estimated from the independent validation schemes ranged from 0.23 to 0.32 across all the scenarios, when the one-year datasets were used as training population (TRN) to predict the other year data as testing population (TST). The average prediction accuracies increased to a range from 0.31 to 0.42 across all the scenarios, when the two-years datasets were used as TRN. The prediction accuracies increased to a range from 0.50 to 0.56, when the TRN consisted of two-years of breeding data and 50% of third year's data converted from TST to TRN. This information showed that GS with a multiple-year TRN set offers the opportunity to accelerate early-stage testcross testing by skipping the first-stage yield testing, which significantly saves the time and cost of early-stage testcross testing.

7.
Ultrason Sonochem ; 69: 105247, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32634727

RESUMO

This work focuses on the effects of different ultrasound power densities on the microstructural changes and physicochemical properties of okara fibers, which are composed of carbohydrate-based polymers. Okara suspensions were treated with ultrasound at different power densities (0, 1, 2, 3, 4, and 5 W/mL) for 30 min, after which the ultrasound-treated okara were hydrolyzed by trypsin to obtain okara fibers. The ultrasound treatment of the okara fibers induced structural disorganization and changes, evidenced mainly in their morphological characteristics and their relative crystallinity degrees. Increasing the ultrasound power broke the okara fibers into flaky and stacked structures. When the ultrasound power density reached 4 W/mL, the parenchyma became compact and the hourglass structure fractured. The mean particle size of the okara fiber was reduced from 82.24 µm to 53.96 µm, and the homogeneity was enhanced significantly. The relative crystallinity of the okara fibers was reduced from 55.14% to 36.47%. The okara fiber surface charge decreased when the ultrasound power was increased. However, after ultrasound treatment at 4 W/mL (800 W), the okara fiber suspension exhibited the highest viscosity value and a higher swelling capacity, water-holding capacity, and oil-holding capacity. Therefore, the results indicated that the selection of processing conditions for okara fibers is critical and that okara fiber modification using a high ultrasound treatment might improve their use in potential applications.

8.
Chin Med Sci J ; 35(2): 186-190, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32684239

RESUMO

Acute lymphoblastic leukemia (ALL) is a common pediatric cancer. The second malignant neoplasms (SMNs) in long-term survivors of pediatric ALL are relatively rare. Herein we report a 10-year-old girl who was diagnosed as primitive neuroectodermal tumor (PNET) 5 years after the initial diagnosis of ALL with radiotherapy-free treatment. PNET is an exceedingly rare neoplasm in SMNs of survivors of childhood ALL. It is predisposed to be misdiagnosed and the pathogenesis is unclear. The outcome is poor. Long-term follow-up is necessary for the survival children of ALL.

9.
Diagn Interv Radiol ; 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: covidwho-506038

RESUMO

PURPOSE: We aimed to explore the imaging findings of computed tomography (CT) in diagnosing coronavirus disease 2019 (COVID-19) and its clinical value for further evaluation of suspected cases. METHODS: Files of 155 patients visiting the fever clinics at our hospital and affiliated hospitals from January 20th to February 9th, 2020 were searched. Among them, 140 cases (including 82 males and 58 females) were included as suspected COVID-19 cases based on clinical and epidemiological history; the CT image features of 70 cases with suggestive findings on CT, confirmed by positive nucleic acid test were analyzed and evaluated. The sensitivity and specificity of CT in diagnosing COVID-19 were evaluated in patients with epidemiological history. RESULTS: Of the 70 patients, 84.3% showed bilateral lung involvement on CT; 27 cases (38.6%) showed ground-glass opacity (GGO), which was mostly distributed in the subpleural area (55.7%), and this sign was mainly observed in early COVID-19 patients. In addition, 41 cases (58.6%) manifested GGO combined with focal consolidation opacity, 2 (2.8%) had flake-like consolidation opacity, with involvements of the periphery of lung field and the central zone (44.3%), and this sign was mostly observed in severe or critical patients. Concomitant signs such as pleural effusion and mediastinal lymph node enlargement were rare. Among patients with epidemiological history, the sensitivity of CT in diagnosing COVID-19 was 89.7% (70/78), and the specificity was 88.7% (55/62). CONCLUSION: CT shows high sensitivity and specificity in diagnosing COVID-19. CT is an important examination method in evaluation of suspected cases and assessment of disease severity.

10.
Med Eng Phys ; 81: 30-38, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32505662

RESUMO

There is a large gap between the elastic modulus of the existing femoral stem and the host bone. This gap can lead to long-term complications, such as aseptic loosening and, eventually, a need for revision surgery. The porous metallic biomimetic femoral stem can effectively reduce stress shielding and provide firm implant fixation through bone ingrowth. The purpose of this research is to investigate the application of different porous femoral stems in relieving bone resorption and promoting osseointegration by finite element analysis. We present an intuitive visualization method based on a diamond lattice structure to understand the relationship between pore size, porosity, bone ingrowth criteria and additive manufacturing constraints. We further obtain an admissible design space of diamond lattice structure for porosity selection. We evaluate the relative micromotion of bone-implant interface and bone volume with density loss for three femoral stems with diamond lattice-based homogenous porous structures in admissible design space. We also evaluate porous femoral stems with four different grading orientations along the axial and radial directions of the femoral stem. These include an axial graded femoral stem with a porosity increased distally (DAGS), an axial graded femoral stem with a porosity increased proximally (PAGS), a radial graded femoral stem with a porosity increased inwardly (IRGS), and a radial graded femoral stem with a porosity increased externally (ERGS). The results indicate that: (i) homogenous porous femoral stems with 40% porosity, (ii) DAGS and (iii) IRGS can maintain the relative micromotion of the bone-implant interface in the safety range for bone ingrowth. The calculated volumes of bone with density loss in the cases of DAGS and IRGS are 3.6% and 3.3%, respectively, which are nearly 74% lower than that of fully dense stems. Therefore, DAGS and IRGS have an evident advantage in promoting osseointegration and relieving bone resorption. Thus, the graded femoral stem is more promising than the homogeneous porous stem.

11.
Diagn Interv Radiol ; 26(5): 437-442, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32490829

RESUMO

PURPOSE: We aimed to explore the imaging findings of computed tomography (CT) in diagnosing coronavirus disease 2019 (COVID-19) and its clinical value for further evaluation of suspected cases. METHODS: Files of 155 patients visiting the fever clinics at our hospital and affiliated hospitals from January 20th to February 9th, 2020 were searched. Among them, 140 cases (including 82 males and 58 females) were included as suspected COVID-19 cases based on clinical and epidemiological history; the CT image features of 70 cases with suggestive findings on CT, confirmed by positive nucleic acid test were analyzed and evaluated. The sensitivity and specificity of CT in diagnosing COVID-19 were evaluated in patients with epidemiological history. RESULTS: Of the 70 patients, 84.3% showed bilateral lung involvement on CT; 27 cases (38.6%) showed ground-glass opacity (GGO), which was mostly distributed in the subpleural area (55.7%), and this sign was mainly observed in early COVID-19 patients. In addition, 41 cases (58.6%) manifested GGO combined with focal consolidation opacity, 2 (2.8%) had flake-like consolidation opacity, with involvements of the periphery of lung field and the central zone (44.3%), and this sign was mostly observed in severe or critical patients. Concomitant signs such as pleural effusion and mediastinal lymph node enlargement were rare. Among patients with epidemiological history, the sensitivity of CT in diagnosing COVID-19 was 89.7% (70/78), and the specificity was 88.7% (55/62). CONCLUSION: CT shows high sensitivity and specificity in diagnosing COVID-19. CT is an important examination method in evaluation of suspected cases and assessment of disease severity.

12.
Talanta ; 217: 121066, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32498855

RESUMO

Intracellular pH is a key physiological factor for controlling the activities and functions of cells and lysosome is a vital subcellular organelle. Thus, developing a novel lysosome-targeting fluorescence probe for selective and sensitive detection of lysosomal pH in living cells is very important. In this work, we synthesized a series of fluorescence probes based on imidazole-fused benzothiadiazole. The optical properties of these probes were easily adjusted by modifying the substituents with different electron-withdrawing/donating ability in imidazole moiety. All of them showed acid-response and decreased fluorescence intensity during pH values changing from 4.0 to 8.5. The introduction of morpholine group allowed them to specifically respond to the changes of lysosomal pH. Among them, probe MIBTAA possessed a suitable pKa value (5.3) and showed good linear response to pH (R2 = 0.9918) with red emission when pH changed from 4.4 to 5.6. The probe was successfully applied for monitoring pH variation in living cells induced by proton-pump inhibitor Baf-A1 and chloroquine, indicating its great potential for pH imaging in biological applications.

15.
Sci Rep ; 10(1): 8165, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424146

RESUMO

The husk-the leaf-like outer covering of maize ear-has multiple functions, including protecting the ear from diseases infection and dehydration. In previous studies, we genotyped an association panel of 508 inbred lines genotyped with a total of ~550,000 SNPs (Illumina 50 K SNP Chip and RNA-seq). Genome-Wide Association Studies (GWAS) were conducted on four husk traits: husk length (HL), husk layer number (HN), husk thickness (HT), and husk width (HW). Minimal associations were identified and none of them passed the P-value threshold after a Bonferroni multiple-test correction using a single locus test in framework of mixed linear model. In this study, we doubled the number of SNPs (~1,250,000 in total) by adding GBS and 600 K SNP Chip. GWAS, performed with the recently developed multiple loci model (BLINK), revealed six genetic loci associated with HN and HT above the Bonferroni multiple-test threshold. Five candidate genes were identified based on the linkage disequilibrium with these loci, including GRMZM2G381691 and GRMZM2G012416. These two genes were up-regulation and down-regulation in all husk related tissues, respectively. GRMZM2G381691 associated with HT encoded a CCT domain protein, which expressed higher in tropical than temperate maize. GRMZM2G012416 associated with HN encoded an Armadillo (ARM) repeat protein, which regulated GA signal pathway. These associated SNPs and candidate genes paved a path to understand the genetic architecture of husk in maize.

16.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(5): 466-472, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32434642

RESUMO

OBJECTIVE: To compare the efficacy of the CAMS-2005 and CAMS-2009 regimens in treating children with non-core binding factor acute myeloid leukemia (non-CBF AML) and to study the prognosis factors. METHODS: A total of 161 children who were initially diagnosed with non-CBF AML from April 2005 to December 2015 were enrolled as study subjects, and were divided into a CAMS-2005 regimen group (n=52) and a CAMS-2009 regimen group (n=109) according to the chemotherapy regimen provided. The efficacy was retrospectively compared between the two groups. RESULTS: The complete remission (CR) rate at the first course of treatment was higher in the CAMS-2009 regimen group than that in the CMAS-2005 regimen group (63.3% vs 46.2%; P<0.05). There were no significant differences between the two groups in treatment-related mortality rate (11.9% vs 17.3%), recurrence rate (27.5% vs 28.8%), and three-year overall survival (OS) rate (44%±5% vs 28%±6%) (P>0.05). Children who achieved CR at the first course of treatment had significantly higher OS and event-free survival rates than those who did not achieved CR (P<0.01). CONCLUSIONS: The CAMS-2009 regimen is superior to the CAMS-2005 regimen in improving the CR rate in children with non-CBF AML after induction treatment. Whether CR is achieved at the first course of treatment can affect the OS rate of children with non-CBF AML.


Assuntos
Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Humanos , Prognóstico , Indução de Remissão , Estudos Retrospectivos
17.
Traffic ; 21(7): 488-502, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32378292

RESUMO

Lipid droplets (LDs) are cytosolic fat storage organelles that play roles in lipid metabolism, trafficking and signaling. Breakdown of LDs in Saccharomyces cerevisiae is mainly achieved by lipolysis and lipophagy. In this study, we found that the endosomal sorting complex required for transport (ESCRT) in S. cerevisiae negatively regulated the turnover of a LD marker, Erg6, under both simplified glucose restriction (GR) and acute glucose restriction (AGR) conditions by monitoring the localization and degradation of Erg6. Loss of Vps27, Snf7 or Vps4, representative subunits of the ESCRT machinery, facilitated the delivery of Erg6-GFP to vacuoles and its degradation depending on the lipophagy protein Atg15 under simplified GR. Additionally, the lipolysis proteins Tgl3 and Tgl4 were also involved in the enhanced vacuolar localization and degradation of Erg6-GFP in vps4Δ cells. Furthermore, we found that Atg14, which is required for the formation of putatively liquid-ordered (Lo) membrane domains on the vacuole that act as preferential internalization sites for LDs, abundantly localized to vacuolar membranes in ESCRT mutants. Most importantly, the depletion or overexpression of Atg14 correspondingly abolished or promoted the observed Erg6 degradation in ESCRT mutant cells. We propose that Atg14 together with other proteins promotes Erg6 degradation in ESCRT mutant cells under specific glucose restriction conditions. These results shed new light on the regulation of ESCRT on LD turnover.

18.
EMBO Rep ; 21(7): e49666, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32352641

RESUMO

Inflammasomes are intracellular complexes that form in the cytosol of inflammatory cells. NLRP3 is one of the sensor proteins in the complex that can recognize a wide variety of stimuli ranging from microbial components to environmental particulates. Here, we report that in mouse airway epithelial cells (AECs), inflammasome activation is inhibited by EphA2, a member of the transmembrane tyrosine kinase receptor family, via tyrosine phosphorylation of NLRP3 in a model of reovirus infection. We find that EphA2 depletion markedly enhances interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) production in response to the virus. EphA2-/- mice show stronger inflammatory infiltration and enhanced inflammasome activation upon viral infection, and aggravated asthma symptoms upon ovalbumin (ova) induction. Mechanistically, EphA2 binds to NLRP3 and induces its phosphorylation at Tyr132, thereby interfering with ASC speck formation and blocking the activation of the NLRP3-inflammasome. These data demonstrate that reovirus employs EphA2 to suppress inflammasome activation in AECs and that EphA2 deficiency causes a pathological exacerbation of asthma in an ova-induced asthma model.

19.
Nanoscale ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32363363

RESUMO

The search for a one-dimensional (1D) system with purely 1D bands and strong Rashba spin splitting is essential for the realization of Majorana fermions and spin transport but presents a fundamental challenge to date. Herein, using first-principles calculations, we demonstrated that atomic Tellurium (Te) chains exhibit purely 1D bands and giant Rashba spin splitting, and their splitting parameters depend strongly on strain and structure distortion. This phenomenon stems from the helical structure of atomic Te chains, which can not only sustain significant strain but also realize the synergy of orbital angular momentum and in-chain potential gradient in enhancing spin splitting. The structure distortion of stretched helical Te chains is critical to execute this synergy, generating a large Rashba spin splitting among the known systems. Our findings proposed a potential 1D giant Rashba splitting system for exploring spintronics and Majorana fermions, and provide routes for engineering spin splitting in other materials.

20.
Acta Pharmacol Sin ; 41(4): 471-482, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32112042

RESUMO

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease worldwide. However, there is no available therapy reversing the neurodegenerative process of PD. Based on the loss of dopamine or dopaminergic dysfunction in PD patients, most of the current therapies focus on symptomatic relief to improve patient quality of life. As dopamine replacement treatment remains the most effective symptomatic pharmacotherapy for PD, herein we provide an overview of the current pharmacotherapies, summarize the clinical development status of novel dopaminergic agents, and highlight the challenge and opportunity of emerging preclinical dopaminergic approaches aimed at managing the features and progression of PD.

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