Publications by authors named "Sheng Yang"

777 Publications

Programming Cells by Multicopy Chromosomal Integration Using CRISPR-Associated Transposases.

CRISPR J 2021 Jun;4(3):350-359

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China; Shanghai Institutes for Biological Sciences, Huzhou, China.

Directed evolution and targeted genome editing have been deployed to create genetic variants with usefully altered phenotypes. However, these methods are limited to high-throughput screening methods or serial manipulation of single genes. In this study, we implemented multicopy chromosomal integration using CRISPR-associated transposases (MUCICAT) to simultaneously target up to 11 sites on the chromosome for multiplex gene interruption and/or insertion, generating combinatorial genomic diversity. The MUCICAT system was improved by replacing the isopropyl-beta-D-thiogalactoside (IPTG)-dependent promoter to decouple gene editing and product synthesis and truncating the right end to reduce the leakage expression of cargo. We applied MUCICAT to engineer and optimize the N-acetylglucosamine (GlcNAc) biosynthesis pathway in to overproduce the industrially important GlcNAc in only 8 days. Two rounds of transformation, the first round for disruption of two degradation pathways related gene clusters and the second round for multiplex integration of the GlcNAc gene cassette, would generate a library with 1-11 copies of the GlcNAc cassette. We isolated a best variant with five copies of GlcNAc cassettes, producing 11.59 g/L GlcNAc, which was more than sixfold than that of the strain containing the pET-GNAc plasmid. Our multiplex approach MUCICAT has potential to become a powerful tool of cell programing and can be widely applied in many fields such as synthetic biology.
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http://dx.doi.org/10.1089/crispr.2021.0018DOI Listing
June 2021

Design and Engineering of Hypoxia and Acidic pH Dual-Stimuli-Responsive Intelligent Fluorescent Nanoprobe for Precise Tumor Imaging.

Small 2021 Jun 12:e2100243. Epub 2021 Jun 12.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Institute of Chemical Biology and Nanomedicine (ICBN), Hunan University, Changsha, 410082, China.

Stimulus-responsive fluorescence imaging modality shows great promise for detection of tumor due to the advantages of high sensitivity, simplicity and noninvasiveness. However, some non-cancer regions including nodules and inflammation may also exhibit a stimulus-related characteristic, which cause the problem of nonspecific responsiveness and then cause "false positive" results for tumor recognition. Herein, hypoxia and acidic pH, two typical features strongly associated with tumor invasion, progression and metastasis in tumor microenvironment (TME), are chosen as dual stimuli to fabricate "dual lock-and-key" fluorescent nanoprobe for highly specific and precise imaging of tumor cells. Mesoporous silica coated gold nanorods ([email protected] ) are employed as nanocarrier and nanoquencher to load the pH-sensitive fluorescent reporter (Rho-TP). Azobenzene (azo) which can be reduced to amines by the highly expressed azoreductase under hypoxic conditions, is elected as the effective gatekeeper for [email protected] by forming complex with β-cyclodextrin polymer via host-guest interaction (azo/β-CDP). By elaborately combining the hypoxia-responsive gatekeeper and pH-responsive fluorescent signal reporter into one nanoprobe, sensitive and specific imaging of tumor cells can be realized. The fabricated dual lock-and-key fluorescent nanoprobe successfully further apply in tumor-bearing mice model, which indicate potential of early diagnosis and assessment of cancer treatment.
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http://dx.doi.org/10.1002/smll.202100243DOI Listing
June 2021

Emerging perovskite monolayers.

Nat Mater 2021 Jun 10. Epub 2021 Jun 10.

Technical University of Darmstadt, Darmstadt, Germany.

The library of two-dimensional (2D) materials has been enriched over recent years with novel crystal architectures endowed with diverse exciting functionalities. Bulk perovskites, including metal-halide and oxide systems, provide access to a myriad of properties through molecular engineering. Their tunable electronic structure offers remarkable features from long carrier-diffusion lengths and high absorption coefficients in metal-halide perovskites to high-temperature superconductivity, magnetoresistance and ferroelectricity in oxide perovskites. Emboldened by the 2D materials research, perovskites down to the monolayer limit have recently emerged. Like other 2D species, perovskites with reduced dimensionality are expected to exhibit new physics and to herald next-generation multifunctional devices. In this Review, we critically assess the preliminary studies on the synthetic routes and inherent properties of monolayer perovskite materials. We also discuss how to exploit them for widespread applications and provide an outlook on the challenges and opportunities that lie ahead for this enticing class of 2D materials.
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http://dx.doi.org/10.1038/s41563-021-01029-9DOI Listing
June 2021

Incidence and Risk Factors of In-Hospital Prosthesis-Related Complications Following Total Knee Arthroplasty: A Retrospective Nationwide Inpatient Sample Database Study.

Orthop Surg 2021 Jun 9. Epub 2021 Jun 9.

Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Objective: To examine the incidence and risk factors of in-hospital prosthesis-related complications (PRCs) following total knee arthroplasty (TKA) using a large-scale national database.

Methods: A retrospective database analysis was performed based on Nationwide Inpatient Sample (NIS) from 2005-2014. Patients who underwent TKA were included. The recruited cases were divided into two groups according to the occurrence of PRCs. Patient demographics (age, sex, and race), hospital characteristics (type of admission and payer, and bedsize, teaching status, location, and region of hospital), length of stay (LOS), total charges during hospitalization, in-hospital mortality, comorbidities, and perioperative complications were analyzed.

Results: A total of 1,227,244 TKAs were captured from the NIS database. There were 8484 cases of in-hospital PRCs after TKA and the overall incidence was 0.69%, with a slight downward trend annually. Periprosthetic joint infection (PJI) was the main category among PRCs (0.20%), followed by mechanical loosening (0.04%), dislocation (0.02%), and periprosthetic fracture (PPF) (0.01%). Patients suffered from in-hospital PRCs were 3 years younger (64 years vs 67 years) and 6.51% more likely to be male (43.60% vs 37.09%) compared to the nonaffected population (P < 0.0001). Additionally, patients experiencing in-hospital PRCs after TKA were 2.11% less likely through elective admission (92.07% vs 94.18%) while 2.34% more likely in teaching hospital (45.53% vs 43.19%) than those without these complications (P < 0.0001). Furthermore, the occurrence of in-hospital PRCs was associated with longer LOS (4 days vs 3 days; P < 0.0001), more total charges ($53,418 vs $41,204, P < 0.0001), and higher in-hospital mortality (0.30% vs 0.07%; P < 0.0001). Multivariate logistic regression was performed to identify independent risk factors of in-hospital PRCs after TKA which included younger age, male, non-elective admission, teaching hospital, deficiency and chronic blood loss anemia, coagulopathy, congestive heart failure, depression, diabetes with chronic complications, fluid and electrolyte disorders, pulmonary circulation disorders, metastatic cancer, and weight loss. Besides, in-hospital PRCs after TKA were associated with secondary osteoarthritis, inflammatory arthritis, prior knee arthroscopy, acute renal failure, acute myocardial infarction, deep vein thrombosis, sepsis, transfusion, and wound dehiscence.

Conclusion: It is beneficial to study the risk factors of in-hospital PRCs after TKA to ensure the appropriate management and optimize consequences although a relatively low incidence was identified.
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http://dx.doi.org/10.1111/os.13008DOI Listing
June 2021

Design and Experimental Study of Space Continuous Robots Applied to Space Non-Cooperative Target Capture.

Micromachines (Basel) 2021 May 9;12(5). Epub 2021 May 9.

State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China.

Space capture actuators face problems such as insufficient flexibility and electrical components that are vulnerable to extreme space environments. To address these problems, a centralized-driven flexible continuous robot based on a multiple scissor mechanism units is proposed in this study. The continuous robot body is composed of two scissor mechanism units coupled in series, and the base container's three motors to drive the robot. The two scissor mechanism units ensure a wide range of flexible operations and the light weight of the robot. The centralized drive with three motors not only reduces the number of driving sources, but also ensures temperature control and protection of electrical components in the space environment. The kinematics and dynamics of the robot are analyzed, and the workspace and deformation performance of the robot are verified through experiments. Compared with other continuous robots, the proposed continuous robot retains the characteristics of continuous robots in a wide range of flexible operations. At the same time, the configuration is light and a small number of driving sources are used, which is suitable for extreme temperatures, vacuum, radiation, and strict resource-constrained environments in space.
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http://dx.doi.org/10.3390/mi12050536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151530PMC
May 2021

Soil potentials to resist continuous cropping obstacle: Three field cases.

Environ Res 2021 May 28;200:111319. Epub 2021 May 28.

Tobacco Research Institute of Hunan Province, Changsha, 410004, China. Electronic address:

Continuous cropping has become the most common system in intensive, modern agricultural production; however, obstacles often appear in continuous cropping patterns after a few years of use. There have been several studies about the impacts of continuous cropping on soil microbial, but few about differences between soil experiencing continuous cropping obstacles and those where such obstacles had been resisted. Here, after ten or twenty years of continuous tobacco cropping, we collected soil samples investigating discrepancies in soil property and bacterial community between soils experiencing continuous cropping obstacles and soils where the obstacles were resisted providing insight into preventing and controlling continuous cropping obstacles. Results showed that soil organic matter (SOM), available phosphorus (AP), total nitrogen (TN), nitrate-N (NO-N), and bacterial diversity of samples where continuous cropping obstacles had been resisted were significantly higher than those where continuous cropping obstacles were present. Besides, SOM, AP, TN, and Ammonium-N (NH-N) considerably affected the bacterial community. Among all variables, NH-N explained the largest proportion of bacterial community variation. Molecular ecological networks were used to putatively identify keystone taxa, including Acidobacteria Gp1, Acidobacteria Gp2, Acidobacteria Gp16, and WPS-1_genera_incertae_sedis. Their relative abundance significantly changed between the two conditions. Overall, our results indicate that decreases in soil nutrient content and bacterial diversity, and significant changes in some keystone taxa abundances may be important factors leading to increased soil-borne diseases and reduced tobacco production potential or quality. Thus, during agricultural production, we could regulate the stability of the soil-crop-microbial ecological system via crop rotation, intercropping, or the use of specialized bio-fertilizers and soil conditioners to mitigate continuous cropping obstacles.
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http://dx.doi.org/10.1016/j.envres.2021.111319DOI Listing
May 2021

The risk of hepatitis C virus recurrence in hepatitis C virus-infected patients treated with direct-acting antivirals after achieving a sustained virological response: A comprehensive analysis.

Liver Int 2021 May 29. Epub 2021 May 29.

Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background & Aims: The risk for hepatitis C virus (HCV) recurrence persists after HCV eradication with direct-acting antivirals (DAAs), particularly in patients with ongoing high-risk behaviours. Our aim was to assess the risk of HCV recurrence (late relapse and/or reinfection) post-sustained virological response (SVR).

Methods: We searched the literature for studies reporting HCV recurrence rates post-SVR in PubMed, Web of Science and the Cochrane Library. Identified publications were divided into groups based on patient risk for HCV reinfection: low-risk HCV mono-infection, high-risk HCV mono-infection and a human immunodeficiency virus (HIV)/HCV coinfection. The HCV recurrence rate for each study was calculated by using events divided by the person-years of follow-up (PYFU). HCV recurrence was defined as confirmed, detectable HCV RNA post-SVR.

Results: In the 16 studies of low-risk patients, the pooled recurrence rate was 0.89/1000 PYFU (95% confidence interval [CI], 0.16-2.03). For the 19 studies of high-risk patients, the pooled recurrence rate was 29.37/1000 PYFU (95% CI, 15.54-46.91). For the eight studies of HIV/HCV-coinfected patients, the pooled recurrence rate was 23.25/1000 PYFU (95% CI, 4.24-53.39). The higher pooled estimates of recurrence in the high-risk and HIV/HCV-coinfected populations were predominantly driven by an increase in reinfection rather than late relapse.

Conclusions: The HCV recurrence risk after achieving SVR with all-oral DAAs therapy is low, and the risk of HCV recurrence in high-risk and HIV/HCV-coinfected populations was driven by an increase in reinfection rather than late relapse.
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http://dx.doi.org/10.1111/liv.14976DOI Listing
May 2021

Deep Learning-Based Fluence Map Prediction for Pancreas Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost.

Adv Radiat Oncol 2021 Jul-Aug;6(4):100672. Epub 2021 Feb 16.

Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.

Purpose: Treatment planning for pancreas stereotactic body radiation therapy (SBRT) is a challenging task, especially with simultaneous integrated boost treatment approaches. We propose a deep learning (DL) framework to accurately predict fluence maps from patient anatomy and directly generate intensity modulated radiation therapy plans.

Methods And Materials: The framework employs 2 convolutional neural networks (CNNs) to sequentially generate beam dose prediction and fluence map prediction, creating a deliverable 9-beam intensity modulated radiation therapy plan. Within the beam dose prediction CNN, axial slices of combined structure contour masks are used to predict 3-dimensional (3D) beam doses for each beam. Each 3D beam dose is projected along its beam's-eye-view to form a 2D beam dose map, which is subsequently used by the fluence map prediction CNN to predict its fluence map. Finally, the 9 predicted fluence maps are imported into the treatment planning system to finalize the plan by leaf sequencing and dose calculation. One hundred patients receiving pancreas SBRT were retrospectively collected for this study. Benchmark plans with unified simultaneous integrated boost prescription (25/33 Gy) were manually optimized for each case. The data set was split into 80/20 cases for training and testing. We evaluated the proposed DL framework by assessing both the fluence maps and the final predicted plans. Further, clinical acceptability of the plans was evaluated by a physician specializing in gastrointestinal cancer.

Results: The DL-based planning was, on average, completed in under 2 minutes. In testing, the predicted plans achieved similar dose distribution compared with the benchmark plans (-1.5% deviation for planning target volume 33 V), with slightly higher planning target volume maximum (+1.03 Gy) and organ at risk maximum (+0.95 Gy) doses. After renormalization, the physician rated 19 cases clinically acceptable and 1 case requiring minor improvement.

Conclusions: The DL framework can effectively plan pancreas SBRT cases within 2 minutes. The predicted plans are clinically deliverable, with plan quality approaching that of manual planning.
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http://dx.doi.org/10.1016/j.adro.2021.100672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099762PMC
February 2021

Strategies for optimizing acetyl-CoA formation from glucose in bacteria.

Trends Biotechnol 2021 May 5. Epub 2021 May 5.

Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; Huzhou Center of Industrial Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Huzhou 313000, China. Electronic address:

Acetyl CoA is an important precursor for various chemicals. We provide a metabolic engineering guideline for the production of acetyl-CoA and other end products from a bacterial chassis. Among 13 pathways that produce acetyl-CoA from glucose, 11 lose carbon in the process, and two do not. The first 11 use the Embden-Meyerhof-Parnas (EMP) pathway to produce redox cofactors and gain or lose ATP. The other two pathways function via phosphoketolase with net consumption of ATP, so they must therefore be combined with one of the 11 glycolytic pathways or auxiliary pathways. Optimization of these pathways can maximize the theoretical acetyl-CoA yield, thereby minimizing the overall cost of subsequent acetyl-CoA-derived molecules. Other strategies for generating hyper-producer strains are also addressed.
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http://dx.doi.org/10.1016/j.tibtech.2021.04.004DOI Listing
May 2021

Supramolecular assembly induced chiral interface for electrochemical recognition of tryptophan enantiomers.

Anal Methods 2021 05;13(17):2011-2020

School of Chemistry, EaStCHEM, University of Edinburgh, Joseph Black Building, West Mains Road, Edinburgh, EH93JJ, UK.

The β[email protected] chiral interface was prepared based on the supramolecular host-guest interaction between ferrocene (Fc) grafted polyethyleneimine (PEI-Fc) and chiral β-cyclodextrin (β-CD). SEM results show that β[email protected] interface has a regular spatial structure, which can effectively distinguish tryptophan (Trp) enantiomers. Under the optimal conditions, differential pulse voltammetry shows that the peak current ratio (Id/Il) of Trp enantiomers can reach 2.84 at 15 °C. More interestingly, the β[email protected]/GCE exhibited chiral recognition of d-Trp and l-Trp via water contact angle measurements. There was a good linear relationship between the peak current and the concentration of Trp enantiomers in the range from 0.005 mM to 0.10 mM. Finally, the chiral interface can be applied for quick detection of the proportion of isomers in Trp racemic solution, which is very important for chiral recognition in racemic mixture of chiral compounds. Meanwhile, the β[email protected]/GCE showed good stability and reproducibility.
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http://dx.doi.org/10.1039/d1ay00222hDOI Listing
May 2021

Selective vulnerability to atrophy in sporadic Creutzfeldt-Jakob disease.

Ann Clin Transl Neurol 2021 Jun 5;8(6):1183-1199. Epub 2021 May 5.

Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco (UCSF), San Francisco, California.

Objective: Identification of brain regions susceptible to quantifiable atrophy in sporadic Creutzfeldt-Jakob disease (sCJD) should allow for improved understanding of disease pathophysiology and development of structural biomarkers that might be useful in future treatment trials. Although brain atrophy is not usually present by visual assessment of MRIs in sCJD, we assessed whether using voxel-based morphometry (VBM) can detect group-wise brain atrophy in sCJD.

Methods: 3T brain MRI data were analyzed with VBM in 22 sCJD participants and 26 age-matched controls. Analyses included relationships of regional brain volumes with major clinical variables and dichotomization of the cohort according to expected disease duration based on prion molecular classification (i.e., short-duration/Fast-progressors (MM1, MV1, and VV2) vs. long-duration/Slow-progressors (MV2, VV1, and MM2)). Structural equation modeling (SEM) was used to assess network-level interactions of atrophy between specific brain regions.

Results: sCJD showed selective atrophy in cortical and subcortical regions overlapping with all but one region of the default mode network (DMN) and the insulae, thalami, and right occipital lobe. SEM showed that the effective connectivity model fit in sCJD but not controls. The presence of visual hallucinations correlated with right fusiform, bilateral thalami, and medial orbitofrontal atrophy. Interestingly, brain atrophy was present in both Fast- and Slow-progressors. Worse cognition was associated with bilateral mesial frontal, insular, temporal pole, thalamus, and cerebellum atrophy.

Interpretation: Brain atrophy in sCJD preferentially affects specific cortical and subcortical regions, with an effective connectivity model showing strength and directionality between regions. Brain atrophy is present in Fast- and Slow-progressors, correlates with clinical findings, and is a potential biomarker in sCJD.
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http://dx.doi.org/10.1002/acn3.51290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164858PMC
June 2021

Engineering the oleaginous yeast Yarrowia lipolytica for β-farnesene overproduction.

Biotechnol J 2021 May 2:e2100097. Epub 2021 May 2.

Key Laboratory of Synthetic Biology, CAS Center for Excellence of Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.

β-farnesene is a sesquiterpenoid with various industrial applications which is now commercially produced by a Saccharomyces cerevisiae strain obtained by random mutagenesis and genetic engineering. We rationally designed a genetically defined Yarrowia lipolytica through recovery of L-leucine biosynthetic route, gene dosage optimization of β-farnesene synthase and disruption of the competition pathway. The resulting β-farnesene titer was improved from 8 to 345 mg L . Finally, the strategy for decreasing the lipid accumulation by individually and iteratively knocking out four acyltransferases encoding genes was adopted. The result displayed that β-farnesene titer in the engineered strain CIBT6304 in which acyltransferases (DGA1 and DGA2) were deleted increased by 45% and reached 539 mg L (88 mg g DCW). Using fed-batch fermentation, CIBT6304 could produce the highest β-farnesene titer (22.8 g L ) among the genetically defined strains. This study will provide the foundation of engineering Y. lipolytica to produce other terpenoids more cost-efficiently.
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http://dx.doi.org/10.1002/biot.202100097DOI Listing
May 2021

Analysis of the Accelerator-Driven System Fuel Assembly during the Steam Generator Tube Rupture Accident.

Materials (Basel) 2021 Apr 7;14(8). Epub 2021 Apr 7.

Institute of Modern Physics, Fudan University, Shanghai 200433, China.

China is developing an ADS (Accelerator-Driven System) research device named the China initiative accelerator-driven system (CiADS). When performing a safety analysis of this new proposed design, the core behavior during the steam generator tube rupture (SGTR) accident has to be investigated. The purpose of our research in this paper is to investigate the impact from different heating conditions and inlet steam contents on steam bubble and coolant temperature distributions in ADS fuel assemblies during a postulated SGTR accident by performing necessary computational fluid dynamics (CFD) simulations. In this research, the open source CFD calculation software OpenFOAM, together with the two-phase VOF (Volume of Fluid) model were used to simulate the steam bubble behavior in heavy liquid metal flow. The model was validated with experimental results published in the open literature. Based on our simulation results, it can be noticed that steam bubbles will accumulate at the periphery region of fuel assemblies, and the maximum temperature in fuel assembly will not overwhelm its working limit during the postulated SGTR accident when the steam content at assembly inlet is less than 15%.
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http://dx.doi.org/10.3390/ma14081818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067567PMC
April 2021

Pepper NAC-type transcription factor NAC2c Balances the Trade-off Between Growth and Defense Responses.

Plant Physiol 2021 Apr 26. Epub 2021 Apr 26.

Key Laboratory of Applied Genetics of universities in Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, Fujian, 350002, China.

Plant responses to pathogen attacks and to high temperature stress (HTS) are distinct in nature but generally share several signaling components. How plants produce specific responses through these common signaling intermediates remains elusive. With the help of reverse-genetics approaches, we describe here the mechanism underlying trade-offs in pepper (Capsicum annuum) between growth, immunity and thermotolerance. The NAC-type transcription factor CaNAC2c was induced by HTS and Ralstonia solanacearum infection (RSI). CaNAC2c inhibited pepper growth, promoted immunity against RSI by activating jasmonate-mediated immunity and H2O2 accumulation, and promoted HTS responses by activating Heat shock factor A5 (CaHSFA5) transcription and blocking H2O2 accumulation. We show that CaNAC2c physically interacts with CaHSP70 and CaNAC029 in a context-specific manner. Upon HTS, CaNAC2c-CaHSP70 interaction in the nucleus protected CaNAC2c from degradation and resulted in the activation of thermotolerance by increasing CaNAC2c binding and transcriptional activation of its target promoters. CaNAC2c did not induce immunity-related genes under HTS, likely due to the degradation of CaNAC029 by the 26S proteasome. Upon RSI, CaNAC2c interacted with CaNAC029 in the nucleus and activated jasmonate-mediated immunity but was prevented from activating thermotolerance-related genes. In non-stressed plants, CaNAC2c was tethered outside the nucleus by interaction with CaHSP70, and thus was unable to activate either immunity or thermotolerance. Our results indicate that pepper growth, immunity and thermotolerance are coordinately and tightly regulated by CaNAC2c via its inducible expression and differential interaction with CaHSP70 and CaNAC029.
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http://dx.doi.org/10.1093/plphys/kiab190DOI Listing
April 2021

Advances and Perspectives for Genome Editing Tools of .

Front Microbiol 2021 7;12:654058. Epub 2021 Apr 7.

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

has been considered a promising synthetic biological platform for biomanufacturing and bioremediation. However, there are still some challenges in genetic manipulation of . Recently, more and more genetic parts or elements (replicons, promoters, reporter genes, and selectable markers) have been mined, characterized, and applied. In addition, continuous improvement of classic molecular genetic manipulation techniques, such as allelic exchange via single/double-crossover, nuclease-mediated site-specific recombination, RecT-mediated single-chain recombination, actinophages integrase-mediated integration, and transposition mutation, has accelerated the molecular study of More importantly, emerging gene editing tools based on the CRISPR/Cas system is revolutionarily rewriting the pattern of genetic manipulation technology development for , which made gene reprogramming, such as insertion, deletion, replacement, and point mutation, much more efficient and simpler. This review summarized the recent progress in molecular genetic manipulation technology development of and discussed the bottlenecks and perspectives for future research of as a distinctive microbial chassis.
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http://dx.doi.org/10.3389/fmicb.2021.654058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058222PMC
April 2021

Nanotube-decorated hierarchical tantalum scaffold promoted early osseointegration.

Nanomedicine 2021 Apr 20;35:102390. Epub 2021 Apr 20.

College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. Electronic address:

This study aimed to fabricate a hierarchical tantalum scaffold mimicking natural bone structure to enhance osseointegration. Porous tantalum scaffolds (p-Ta) with microgradients were fabricated by selective laser melting according to a computer-aided design model. Electrochemical anodization produced nanotubes on the p-Ta surface (p-Ta-nt). SEM verified the construction of a unique nanostructure on p-Ta-nt. Contact angle and protein adsorption measurements demonstrated that p-Ta-nt have enhanced hydrophilicity and protein absorption. MC3T3-E1 preosteoblasts showed increased filamentous pseudopods and comparable cell proliferation when cultured on p-Ta-nt. Osteogenic marker gene (Osterix, Runx2, COL-I) transcription was significantly upregulated in MC3T3-E1 cells cultured on p-Ta-nt after 7 days. After implantation into the femurs of New Zealand white rabbits for 2 weeks, histological examination found improved early osseointegration in the p-Ta-nt group. This study showed that a hierarchical tantalum structure could enhance early osteogenic effects in vitro and in vivo.
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http://dx.doi.org/10.1016/j.nano.2021.102390DOI Listing
April 2021

Simple and efficient registration of 3D point cloud and image data for an indoor mobile mapping system.

J Opt Soc Am A Opt Image Sci Vis 2021 Apr;38(4):579-586

Registration of 3D lidar point clouds with optical images is critical in the combination of multisource data. Geometric misalignment originally exists in the pose data between lidar point clouds and optical images. To improve the accuracy of the initial pose and the applicability of the integration of 3D points and image data, we develop a simple but efficient registration method. We first extract point features from lidar point clouds and images: point features are extracted from single-frame lidar and point features are extracted from images using a classical Canny operator. The cost map is subsequently built based on Canny image edge detection. The optimization direction is guided by the cost map, where low cost represents the desired direction, and loss function is also considered to improve the robustness of the proposed method. Experiments show positive results.
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http://dx.doi.org/10.1364/JOSAA.414042DOI Listing
April 2021

A modified pCas/pTargetF system for CRISPR-Cas9-assisted genome editing in Escherichia coli.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr;53(5):620-627

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China.

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (Cas9)-based genome editing tool pCas/pTargetF system that we established previously has been widely used in Escherichia coli MG1655. However, this system failed to manipulate the genome of E. coli BL21(DE3), owing to the potential higher leaky transcription of the gRNA-pMB1 specific to pTargetF in this strain. In this study, we modified the pCas/pTargetF system by replacing the promoter of gRNA-pMB1 with a tightly regulated promoter PrhaB, changing the replicon of pCas to a nontemperature-sensitive replicon, adding the sacB gene into pCas, and replacing the original N20-specific sequence of pTargetF with ccdB gene. We call this updated system as pEcCas/pEcgRNA. We found that gRNA-pMB1 indeed showed a slightly higher leaky expression in the pCas/pTargetF system compared with pEcCas/pEcgRNA. We also confirmed that genome editing can successfully be performed in BL21(DE3) by pEcCas/pEcgRNA with high efficiency. The application of pEcCas/pEcgRNA was then expanded to the E. coli B strain BL21 StarTM (DE3), K-12 strains MG1655, DH5α, CGMCC3705, Nissle1917, W strain ATCC9637, and also another species of Enterobacteriaceae, Tatumella citrea DSM13699, without any specific modifications. Finally, the plasmid curing process was optimized to shorten the time from $\sim$60 h to $\sim$32 h. The entire protocol (including plasmid construction, editing, electroporation and mutant verification, and plasmid elimination) took only $\sim$5.5 days per round in the pEcCas/pEcgRNA system, whereas it took $\sim$7.5 days in the pCas/pTargetF system. This study established a faster-acting genome editing tool that can be used in a wider range of E. coli strains and will also be useful for other Enterobacteriaceae species.
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http://dx.doi.org/10.1093/abbs/gmab036DOI Listing
April 2021

Dual-Stimulus Responsive Near-Infrared Reversible Ratiometric Fluorescent and Photoacoustic Probe for Tumor Imaging.

Anal Chem 2021 04 22;93(13):5420-5429. Epub 2021 Mar 22.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.

Tumor-specific imaging is a major challenge in clinical tumor resection. To overcome this problem, several activatable probes have been developed for use in tumor imaging. However, most of these probes are activated based on a single-factor stimulation and are irreversible. Therefore, false signals that make tumor-specific imaging difficult are easily generated. We have developed a new dual-stimulus responsive near-infrared (NIR) reversible adenosine 5'-triphosphate (ATP)-pH probe for fluorescence and photoacoustic ratiometric imaging of tumors. Since the H and ATP content is significantly higher in the tumor microenvironment than that in normal tissues, the Förster resonance energy transfer-based probe ATP-pH was constructed with silicon rhodamine as the donor, CS dye as the acceptor, and ATP/H recognition units that could only be activated when both H and ATP were connected to the acceptor. The ATP-pH probe is reversibly activated by both the H and ATP, which effectively reduces the cumulative response of the probe in circulation after intravenous injection. Further, the NIR ratiometric property of the probe makes it suitable for imaging. Finally, our probe was successfully utilized in ratiometric photoacoustic and fluorescence tumor imaging and ratiometric fluorescence imaging-guided tumor resection.
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http://dx.doi.org/10.1021/acs.analchem.0c04804DOI Listing
April 2021

Clinical Experience With Machine Learning-Based Automated Treatment Planning for Whole Breast Radiation Therapy.

Adv Radiat Oncol 2021 Mar-Apr;6(2):100656. Epub 2021 Jan 22.

Duke University Medical Center, Durham, North Carolina.

Purpose: The machine learning-based automated treatment planning (MLAP) tool has been developed and evaluated for breast radiation therapy planning at our institution. We implemented MLAP for patient treatment and assessed our clinical experience for its performance.

Methods And Materials: A total of 102 patients of breast or chest wall treatment plans were prospectively evaluated with institutional review board approval. A human planner executed MLAP to create an auto-plan via automation of fluence maps generation. If judged necessary, a planner further fine-tuned the fluence maps to reach a final plan. Planners recorded the time required for auto-planning and manual modification. Target (ie, breast or chest wall and nodes) coverage and dose homogeneity were compared between the auto-plan and final plan.

Results: Cases without nodes (n = 71) showed negligible (<1%) differences for target coverage and dose homogeneity between the auto-plan and final plan. Cases with nodes (n = 31) also showed negligible difference for target coverage. However, mean ± standard deviation of volume receiving 105% of the prescribed dose and maximum dose were reduced from 43.0% ± 26.3% to 39.4% ± 23.7% and 119.7% ± 9.5% to 114.4% ± 8.8% from auto-plan to final plan, respectively, all with ≤ .01 for cases with nodes (n = 31). Mean ± standard deviation time spent for auto-plans and additional fluence modification for final plans were 12.1 ± 9.3 and 13.1 ± 12.9 minutes, respectively, for cases without nodes, and 16.4 ± 9.7 and 26.4 ± 16.4 minutes, respectively, for cases with nodes.

Conclusions: The MLAP tool has been successfully implemented for routine clinical practice and has significantly improved planning efficiency. Clinical experience indicates that auto-plans are sufficient for target coverage, but improvement is warranted to reduce high dose volume for cases with nodal irradiation. This study demonstrates the clinical implementation of auto-planning for patient treatment and the significant importance of integrating human experience and feedback to improve MLAP for better clinical translation.
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http://dx.doi.org/10.1016/j.adro.2021.100656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966969PMC
January 2021

Tackling the Selectivity Dilemma of Benzopyrylium-Coumarin Dyes in Fluorescence Sensing of HClO and SO.

Anal Chem 2021 03 19;93(12):5194-5200. Epub 2021 Mar 19.

College of Chemistry & Chemical Engineering, Central South University, Changsha, Hunan 410083, China.

Benzopyrylium-coumarin fluorescent probes for sensing hypochlorous acid (HClO) or sulfur dioxide (SO) are unable to distinguish between HClO and SO because the two compounds can react with the 4-position of benzopyrylium-coumarin dyes through the nucleophilic attack. In the current work, we introduced a phenoxazine moiety to the benzopyrylium-coumarin dye to synthesize a new fluorescent probe , which can dually sense HClO and SO and generate distinct fluorescence signals with rapid response time and high sensitivity and selectivity. Moreover, probe was also successfully utilized to detect intracellular HClO and SO in HeLa cells and zebrafish.
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http://dx.doi.org/10.1021/acs.analchem.0c05266DOI Listing
March 2021

Fluence Map Prediction Using Deep Learning Models - Direct Plan Generation for Pancreas Stereotactic Body Radiation Therapy.

Front Artif Intell 2020 8;3:68. Epub 2020 Sep 8.

Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States.

Treatment planning for pancreas stereotactic body radiation therapy (SBRT) is a difficult and time-consuming task. In this study, we aim to develop a novel deep learning framework to generate clinical-quality plans by direct prediction of fluence maps from patient anatomy using convolutional neural networks (CNNs). Our proposed framework utilizes two CNNs to predict intensity-modulated radiation therapy fluence maps and generate deliverable plans: (1) Field-dose CNN predicts field-dose distributions in the region of interest using planning images and structure contours; (2) a fluence map CNN predicts the final fluence map per beam using the predicted field dose projected onto the beam's eye view. The predicted fluence maps were subsequently imported into the treatment planning system for leaf sequencing and final dose calculation (model-predicted plans). One hundred patients previously treated with pancreas SBRT were included in this retrospective study, and they were split into 85 training cases and 15 test cases. For each network, 10% of training data were randomly selected for model validation. Nine-beam benchmark plans with standardized target prescription and organ-at-risk constraints were planned by experienced clinical physicists and used as the gold standard to train the model. Model-predicted plans were compared with benchmark plans in terms of dosimetric endpoints, fluence map deliverability, and total monitor units. The average time for fluence-map prediction per patient was 7.1 s. Comparing model-predicted plans with benchmark plans, target mean dose, maximum dose (0.1 cc), and D absolute differences in percentages of prescription were 0.1, 3.9, and 2.1%, respectively; organ-at-risk mean dose and maximum dose (0.1 cc) absolute differences were 0.2 and 4.4%, respectively. The predicted plans had fluence map gamma indices (97.69 ± 0.96% vs. 98.14 ± 0.74%) and total monitor units (2,122 ± 281 vs. 2,265 ± 373) that were comparable to the benchmark plans. We develop a novel deep learning framework for pancreas SBRT planning, which predicts a fluence map for each beam and can, therefore, bypass the lengthy inverse optimization process. The proposed framework could potentially change the paradigm of treatment planning by harnessing the power of deep learning to generate clinically deliverable plans in seconds.
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http://dx.doi.org/10.3389/frai.2020.00068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861344PMC
September 2020

Knowledge Models as Teaching Aid for Training Intensity Modulated Radiation Therapy Planning: A Lung Cancer Case Study.

Front Artif Intell 2020 28;3:66. Epub 2020 Aug 28.

Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States.

Artificial intelligence (AI) employs knowledge models that often behave as a black-box to the majority of users and are not designed to improve the skill level of users. In this study, we aim to demonstrate the feasibility that AI can serve as an effective teaching aid to train individuals to develop optimal intensity modulated radiation therapy (IMRT) plans. The training program is composed of a host of training cases and a tutoring system that consists of a front-end visualization module powered by knowledge models and a scoring system. The current tutoring system includes a beam angle prediction model and a dose-volume histogram (DVH) prediction model. The scoring system consists of physician chosen criteria for clinical plan evaluation as well as specially designed criteria for learning guidance. The training program includes six lung/mediastinum IMRT patients: one benchmark case and five training cases. A plan for the benchmark case is completed by each trainee entirely independently pre- and post-training. Five training cases cover a wide spectrum of complexity from easy (2), intermediate (1) to hard (2). Five trainees completed the training program with the help of one trainer. Plans designed by the trainees were evaluated by both the scoring system and a radiation oncologist to quantify planning quality. For the benchmark case, trainees scored an average of 21.6% of the total max points pre-training and improved to an average of 51.8% post-training. In comparison, the benchmark case's clinical plans score an average of 54.1% of the total max points. Two of the five trainees' post-training plans on the benchmark case were rated as comparable to the clinically delivered plans by the physician and all five were noticeably improved by the physician's standards. The total training time for each trainee ranged between 9 and 12 h. This first attempt at a knowledge model based training program brought unexperienced planners to a level close to experienced planners in fewer than 2 days. The proposed tutoring system can serve as an important component in an AI ecosystem that will enable clinical practitioners to effectively and confidently use KBP.
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http://dx.doi.org/10.3389/frai.2020.00066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861316PMC
August 2020

A novel Huntington's disease mouse model to assess the role of neuroinflammation on disease progression and to develop human cell therapies.

Stem Cells Transl Med 2021 Mar 12. Epub 2021 Mar 12.

Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health, Sacramento, California, USA.

Huntington's disease (HD) is a fatal autosomal-dominant neurodegenerative disease caused by a trinucleotide CAG repeat expansion of the huntingtin gene (HTT) that affects 1 in every 10 000 individuals in the United States. Our lab developed a novel immune deficient HD mouse strain, the YACNSG, from a commonly used line, the YAC128 mouse, to enable transplantation studies using engineered human cells in addition to studying the impact of the immune system on disease progression. The primary goal of this project was to characterize this novel immune deQficient HD mouse model, using behavioral assays and histology to compare this new model to the immune competent YAC128 and immune deficient mice that had engraftment of a human immune system. Flow cytometry was used to confirm that the YACNSG strain lacked immune cells, and in vivo imaging was used to assess human mesenchymal stem/stromal cell (MSC) retention compared with a commonly used immune deficient line, the NSG mouse. We found that YACNSG were able to retain human MSCs longer than the immune competent YAC128 mice. We performed behavioral assessments starting at 4 months of age and continued testing monthly until 12 months on the accelerod and in the open field. At 12 months, brains were isolated and evaluated using immunohistochemistry for striatal volume. Results from these studies suggest that the novel immune deficient YACNSG strain of mice could provide a good model for human stem-cell based therapies and that the immune system appears to play an important role in the pathology of HD.
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http://dx.doi.org/10.1002/sctm.20-0431DOI Listing
March 2021

An oligopeptide/aptamer-conjugated dendrimer-based nanocarrier for dual-targeting delivery to bone.

J Mater Chem B 2021 03 11;9(12):2831-2844. Epub 2021 Mar 11.

College of Stomatology, Chongqing Medical University, 426 Songshibei Road, Yubei District, Chongqing, 401147, China.

Bone targeting is one of the most potentially valuable therapeutic methods for medically treating bone diseases, such as osteoarthritis, osteoporosis, nonunion bone defects, bone cancer, and myeloma-related bone disease, but its efficacy remains a challenge due to unfavorable bone biodistribution, off-target effects, and the lack of cell specificity. To address these problems, we synthesized a new dual-targeting nanocarrier for delivery to bone by covalently modifying the G4.0 PAMAM dendrimer with the C11 peptide and the CH6 aptamer (CH6-PAMAM-C11). The molecular structure was confirmed using H-NMR and FT-IR spectroscopy. CLSM results showed that the novel nanocarrier could successfully accumulate in the targeted cells, mineralized areas and tissues. DLS and TEM demonstrated that CH6-PAMAM-C11 was approximately 40-50 nm in diameter. In vitro targeting experiments confirmed that the C11 ligand had a high affinity for HAP, while the CH6 aptamer had a high affinity for osteoblasts. The in vivo biodistribution analysis showed that CH6-PAMAM-C11 could rapidly accumulate in bone within 4 h and 12 h and then deliver drugs to sites of osteoblast activity. The components of CH6-PAMAM-C11 were well excreted via the kidneys. The accumulation of many more CH6-PAMAM-C11 dual-targeting nanocarriers than single-targeting nanocarriers was observed in the periosteal layer of the rat skull, along with aggregation at sites of osteoblast activity. All of these results indicate that CH6-PAMAM-C11 may be a promising nanocarrier for the delivery of drugs to bone, particularly for the treatment of osteoporosis, and our research strategy may serve as a reference for research in targeted drug, small molecule drug and nucleic acid delivery.
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http://dx.doi.org/10.1039/d0tb02926bDOI Listing
March 2021

as a pET-Compatible Expression Host Complementary to .

Front Microbiol 2021 19;12:627181. Epub 2021 Feb 19.

Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.

Efficient and novel recombinant protein expression systems can further reduce the production cost of enzymes. is the fastest growing free-living bacterium with a doubling time of less than 10 min, which makes it highly attractive as a protein expression host. Here, 196 pET plasmids with different genes of interest (GOIs) were electroporated into the strain VnDX, which carries an integrated T7 RNA polymerase expression cassette. As a result, 65 and 75% of the tested GOIs obtained soluble expression in and , respectively, 20 GOIs of which showed better expression in the former. Furthermore, we have adapted a consensus "what to try first" protocol for based on Terrific Broth medium. Six sampled GOIs encoding biocatalysts enzymes thus achieved 50-128% higher catalytic efficiency under the optimized expression conditions. Our study demonstrated as a pET-compatible expression host with a spectrum of highly expressed GOIs distinct from and an easy-to-use consensus protocol, solving the problem that some GOIs cannot be expressed well in .
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http://dx.doi.org/10.3389/fmicb.2021.627181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933001PMC
February 2021

ADP ribosylation factor guanylate kinase 1 promotes the malignant phenotype of gastric cancer by regulating focal adhesion kinase activation.

Life Sci 2021 May 24;273:119264. Epub 2021 Feb 24.

Departments of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, PR China. Electronic address:

Aims: ADP ribosylation factor guanylate kinase 1 (ASAP1), a phospholipid-dependent guanosine triphosphate (GTP)ase activating protein, has been reported to be involved in the development of various malignant tumors. However, the biological function of ASAP1 in gastric cancer (GC) remains unclear. This study was to investigate its effect and the underlying mechanism for the malignant phenotype of GC.

Materials And Methods: The Cell Counting Kit-8 assay, flow cytometry, Transwell invasion assay, and wound-healing assay were used to assess the malignant biological behavior of GC cells with ASAP1 overexpression and knockdown. In addition, co-immunoprecipitation was used to analyze the interaction between ASAP1 and FAK in BGC823 cells, and western blotting was used to determine the effects of overexpression and knockdown of ASAP1 on FAK activity in BGC823 cells. Subsequently, functional recovery experiments were used to observe the effect of ASAP1 and FAK on the malignant phenotype of GC cells.

Key Findings: ASAP1 overexpression strongly promoted the malignant biological behavior of SGC7901 cells. Knockdown of ASAP1 effectively weakened the malignant biological behavior of SGC7901 and BGC823 cells. ASAP1 directly interacted with FAK to potentiate FAK activation. In addition, knockdown of FAK combined with ASAP1 overexpression significantly weakened the malignant biological behavior of GC cells, whereas overexpression of FAK combined with knockdown of ASAP1 significantly enhanced the malignant biological behavior of GC cells.

Significance: ASAP1 interacted with FAK, and ASAP1 promoted the malignant phenotype of GC cells by regulating FAK activity. The specific underlying mechanism is worth further investigation.
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http://dx.doi.org/10.1016/j.lfs.2021.119264DOI Listing
May 2021

Long-Lasting Bioluminescence Imaging of the Fibroblast Activation Protein by an Amphiphilic Block Copolymer-Based Probe.

Anal Chem 2021 03 18;93(8):3726-3732. Epub 2021 Feb 18.

Hunan Provincial Key Laboratory of Cytochemistry, School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410114, P. R. China.

Long-term specific tracing of the fibroblast activation protein (FAP) has been of great importance because it is heavily expressed by stromal fibroblasts of multiple diseases, and several disorders associated with FAP are chronical. Bioluminescence (BL) imaging has its advantages to detect FAP since no external excitation is required, but the current FAP-responsive BL probe was constructed by covalently masking the firefly luciferase substrate and easily secreted out from the animal, resulting in transient BL imaging of FAP. To circumvent this problem, a peptide-linked amphiphilic block copolymer-based probe (PABC) was developed and applied to the long-lasting BL image of FAP . For this purpose, an amphiphilic block copolymer containing an FAP-responsive peptide was fabricated to self-assemble into micelles, which act as a depot to load amounts of d-luciferin for constructing the BL probe. Upon reaction with FAP, the micelle would be destroyed to release the internal d-luciferin for BL emission by a luciferase-catalyzed reaction. By virtue of the high loading capability of micelles, the FAP was determined from 0.5 to 10 ng/mL with a detection limit of 0.105 ng/mL, and the high sensitivity makes the PABC capable of distinguishing cancer cells from normal ones. Importantly, compared with free d-luciferin, PABC can be used to persistently image the FAP in living cells and . This characteristic of long-lasting specific tracing of the FAP makes us envision that this BL probe could be used for screening of FAP inhibitors and diagnosing various FAP-related diseases in future.
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http://dx.doi.org/10.1021/acs.analchem.0c03638DOI Listing
March 2021

The Therapeutic Effects of Dihydroartemisinin on Cisplatin-Resistant Gastric Cancer Cells.

Curr Pharm Biotechnol 2021 Feb 16. Epub 2021 Feb 16.

Departments of Oncology, Fujian Medical University Union Hospital, Fujian Medical University Fuzhou, Fujian. China.

Background: Dihydroartemisinin (DHA) exhibited anti-tumor effect in a variety of cancer cells but its mechanism of action is unclear.

Objective: To investigate the therapeutic effects of DHA on Cisplatin (DDP)-resistant gastric cancer cell strain SGC7901/DDP and the possible molecular mechanism.

Methods: Cells were treated with DHA in dose- and time-dependent manners, after which their proliferation, apoptosis, invasion and migration abilities were evaluated. We further evaluated autophagy with mRFP-GFP-LC3 adenovirus transfection and transmission electron microscopy, and also detected the expression levels of proteins (related to autophagy and apoptosis) via western blot. Meanwhile, the influence of DHA on cisplatin resistance was detected through a sensitization test and the evaluation of P-gp expression levels.

Results: DHA effectively inhibited the proliferation, invasion, and migration of SGC7901/DDP cells and induced cell apoptosis which was accompanied by caspase-8/9/3 activation. Furthermore, exposure of DHA resulted in a pronounced increase in autophagy proteins including Beclin-1 and LC3 II with PI3K/AKT/mTOR pathway inhibition. Additionally, enhancement of cisplatin sensitivity occurred in SGC7901/DDP cells treated with DHA, which was accompanied by P-gp downregulation.

Conclusion: DHA exerts an anti-cancer effect on SGC7901/DDP cells and the mechanisms possibly include enhancement of autophagy via PI3K/AKT/mTOR inhibition, inducement of apoptosis through caspase-dependent and mitochondrial pathway, and enhancement of cisplatin sensitivity through P-gp inhibition.
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http://dx.doi.org/10.2174/1389201022666210217114825DOI Listing
February 2021

Insight-HXMT observations of jet-like corona in a black hole X-ray binary MAXI J1820+070.

Nat Commun 2021 Feb 15;12(1):1025. Epub 2021 Feb 15.

Department of Physics, Tsinghua University, Beijing, PR China.

A black hole X-ray binary produces hard X-ray radiation from its corona and disk when the accreting matter heats up. During an outburst, the disk and corona co-evolves with each other. However, such an evolution is still unclear in both its geometry and dynamics. Here we report the unusual decrease of the reflection fraction in MAXI J1820+070, which is the ratio of the coronal intensity illuminating the disk to the coronal intensity reaching the observer, as the corona is observed to contrast during the decay phase. We postulate a jet-like corona model, in which the corona can be understood as a standing shock where the material flowing through. In this dynamical scenario, the decrease of the reflection fraction is a signature of the corona's bulk velocity. Our findings suggest that as the corona is observed to get closer to the black hole, the coronal material might be outflowing faster.
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http://dx.doi.org/10.1038/s41467-021-21169-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884741PMC
February 2021