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1.
Biosci Rep ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006257

RESUMO

Breast cancer is the most common cancer and the leading cause of cancer-related death in women. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are important biomarkers in the prognosis of breast cancer, and their expression is used to categorize breast cancer into subtypes. We aimed to analyze the concordance between ER, PR, and HER2 expression levels and breast cancer subtyping results obtained by immunohistochemistry (IHC, for protein) and reverse transcriptase-polymerase chain reaction (RT-PCR, for mRNA) and to assess the recurrence-free survival (RFS) of the different subtypes as determined by the two methods. We compared biomarker expression by IHC and RT-PCR in 397 operable breast cancer patients and categorized all patients into luminal, HER2, and triple-negative (TN) subtypes. The concordance of biomarker expression between the two methods was 81.6% (kappa = 0.4075) for ER, 87.2% (kappa = 0.5647) for PR, and 79.1% (kappa = 0.2767) for HER2. The kappa statistic was 0.3624 for the resulting luminal, HER2, and TN subtypes. The probability of a 5-year RFS was 0.78 for the luminal subtype versus 0.77 for HER2 and 0.51 for TN, when determined by IHC (p = 0.007); and 0.80, 0.71, and 0.61, respectively, when determined by the RT-PCR method (p = 0.008). Based on the current evidence, subtyping by RT-PCR performs similarly to conventional IHC with regard to the 5-year prognosis. The PCR method may thus provide a complementary means of subtyping when IHC results are ambiguous.

3.
Philos Trans A Math Phys Eng Sci ; 380(2214): 20210125, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34802278

RESUMO

The outbreak of the novel coronavirus, COVID-19, has become one of the most severe pandemics in human history. In this paper, we propose to leverage social media users as social sensors to simultaneously predict the pandemic trends and suggest potential risk factors for public health experts to understand spread situations and recommend proper interventions. More precisely, we develop novel deep learning models to recognize important entities and their relations over time, thereby establishing dynamic heterogeneous graphs to describe the observations of social media users. A dynamic graph neural network model can then forecast the trends (e.g. newly diagnosed cases and death rates) and identify high-risk events from social media. Based on the proposed computational method, we also develop a web-based system for domain experts without any computer science background to easily interact with. We conduct extensive experiments on large-scale datasets of COVID-19 related tweets provided by Twitter, which show that our method can precisely predict the new cases and death rates. We also demonstrate the robustness of our web-based pandemic surveillance system and its ability to retrieve essential knowledge and derive accurate predictions across a variety of circumstances. Our system is also available at http://scaiweb.cs.ucla.edu/covidsurveiller/. This article is part of the theme issue 'Data science approachs to infectious disease surveillance'.


Assuntos
COVID-19 , Mídias Sociais , Mineração de Dados , Humanos , Pandemias , SARS-CoV-2
4.
J Cancer Res Ther ; 17(5): 1141-1156, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34850761

RESUMO

The Expert Consensus reviews current literatures and provides clinical practice guidelines for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The main contents include the following: (1) clinical evaluation of GGN; (2) procedures, indications, contraindications, outcomes evaluation, and related complications of thermal ablation for GGN; and (3) future development directions.

5.
J Formos Med Assoc ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34865947

RESUMO

BACKGROUND/PURPOSE: To assess the relationship between gene expressions of the magnesium transporters and glucose parameters in pregnant women. METHODS: A cohort of women without ongoing or prior medical illnesses was recruited at the start of an early singleton pregnancy. Expression levels of the magnesium transporters-SLC41A1, CNNM2, MAGT1, TRPM6, and TRPM7-were assessed in the peripheral leukocytes, while total calcium and magnesium were assessed in the serum between 10 and 13 weeks gestation. Glucose parameters were assessed between 24 and 28 weeks gestation using the 75 g oral glucose tolerance test. RESULTS: A total of 208 patients were included in the study. The expressions of the magnesium transports were generally unrelated to age, body mass index (BMI), or serum levels of calcium and magnesium. The magnesium transporters were correlated with each other at baseline (correlation coefficients: 0.31 to 0.51). BMI was a strong predictor of fasting glucose levels, while both BMI and age were strong predictors of post-load glucose levels. The expression of TRPM7 was found to be predictive of 1-h post-load blood glucose after accounting for the effects of age and BMI (ß = -0.196, p = 0.020). CONCLUSION: The increased maternal expression of the magnesium transporter TRPM7 may be associated with decreased glucose tolerance in pregnant women. In particular, the association between TRPM7 and 1-h post-load glucose levels was found to be independent of the effects of age and BMI. Future studies are needed to determine whether a mechanistic relationship can be demonstrated between TRPM7 and glucose metabolism.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34882304

RESUMO

BACKGROUND: Sepsis is a lethal clinical syndrome with T-cell dysregulation, imbalanced inflammatory reactions, and gastrointestinal dysfunction. Obesity coexistent with sepsis can cause more-deleterious disease outcomes. Vitamin D is a nutrient with immunomodulatory property, and it helps maintain the intestinal homeostasis. This study investigated treatment with calcitriol on mesenteric lymph node (MLN) CD4+ T cell polarization and intestinal injury in obese mice with sepsis. METHODS: A high-fat diet was provided to mice for 10 weeks, and then mice were separated into an OB group without sepsis and sepsis groups which underwent cecal ligation and puncture (CLP). Septic mice were subdivided into groups that were injected with either saline (SS) or calcitriol (SD) via a tail vein 1 h after CLP. Obese mice with sepsis were sacrificed at 12 or 24 h post-CLP. RESULTS: Sepsis resulted in increased percentages of type 2 T helper (Th2), Th17, and regulatory T (Treg) cells in MLNs. Also, inflammation-associated genes were upregulated, while tight junction genes were downregulated in the intestines after CLP. Compared to the SS group, the SD group exhibited reduced Th2, Th17, and Treg percentages in MLNs. Also, intestinal inflammatory chemokine expressions were reduced, while MUC2, ZO-1, and occludin had increased after CLP. Lower inflammatory cytokine levels in peritoneal lavage fluid in the ileum were also noted in the SD group. CONCLUSIONS: Intravenous calcitriol treatment after sepsis can elicit more-balanced CD4 T cell subsets in lymph nodes near the intestines and alleviate intestinal inflammation and injury in obese mice complicated with sepsis. This article is protected by copyright. All rights reserved.

7.
Int J Mol Sci ; 22(23)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34884807

RESUMO

This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.

8.
Surg Obes Relat Dis ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34933812

RESUMO

BACKGROUND: Limited studies have focused on diabetes relapse after metabolic surgery, especially among Asians. OBJECTIVES: To identify the predictors of diabetes relapse following initial postoperative remission in Asia. SETTING: Four tertiary hospitals METHODS: We assessed 342 patients (age, 41.0 ± 10.8 yr; body mass index [BMI], 39.6 ± 7.3 kg/m2) with complete diabetes data before and 1 and 3 years after metabolic surgery. A total of 290 (84.8%) and 277 (81.0%) patients had diabetes remission at 1 and 3 years after surgery. Logistic regressions were performed to identify the independent predictors of diabetes relapse. Two published predictive models for diabetes remission were also tested for relapse. RESULTS: Of the 290 patients with 1-year diabetes remission, 29 (10%) experienced a relapse at 3 years after surgery. The area under the receiver operating characteristic curve of the ABCD score in predicting 1-year remission, 3-year remission, and 3-year relapse were .814, .793, and .795, while those of the DiaRem2 score were .823, .774, and .701, respectively. The baseline age, BMI, and insulin use were independent predictors for relapse. The most powerful predictive model for relapse was composed of preoperative insulin use, 1-year A1C, and a change in BMI between the first and third year (C-statistic: .919). CONCLUSION: The ABCD score predicted both mid-term postoperative diabetes remission and relapse in Asians. Initial older age, lower BMI, insulin use, higher 1-year A1C, and weight regain were independent predictors of relapse. Personalized strategies should be proposed for those at risk of relapse to optimize diabetes outcomes after surgery.

9.
Life (Basel) ; 11(12)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34947850

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide and its incidence is increasing; therefore, an understanding of its oncogenic mechanisms is critical for improving its treatment and management. Methylglyoxal (MGO) has a highly reactive aldehyde group and has been suggested to play a role in oncogenesis. However, no standardized data are currently available on MGO levels in colorectal precancerous and cancerous lesions. We collected 40 matched colorectal tumor and peritumor tissues from patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive cancer (IC). MGO levels increased between LGD, HGD, and IC tumor tissues (215.25 ± 39.69, 267.45 ± 100.61, and 587.36 ± 123.19 µg/g protein, respectively; p = 0.014). The MGO levels in peritumor tissue increased and were significantly higher than MGO levels in tumor tissue (197.99 ± 49.40, 738.09 ± 247.87, 933.41 ± 164.83 µg/g protein, respectively; p = 0.002). Tumor tissue MGO levels did not correlate with age, sex, underlying disease, or smoking status. These results suggest that MGO levels fluctuate in progression of CRC and warrants further research into its underlying mechanisms and function in tumor biology.

11.
Macromol Rapid Commun ; : e2100736, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837422

RESUMO

Nano- and microscale morphology endows surfaces that play conspicuous roles in natural or artificial objects with unique functions. Surfaces with dynamic regulating features capable of switching the structures, patterns, and even dimensions of their surface profiles can control friction and wettability, thus having potential applications in antibacterial, haptics, and fluid dynamics. Here, a freestanding film with light-switchable surface based on cholesteric liquid crystal networks is presented to translate 2D flat plane into a 3D nanometer-scale topography. The wettability of the interface can be controlled by hiding or revealing the geometrical features of the surfaces with light. This reversible dynamic actuation is obtained through the order parameter change of the periodic cholesteric organization under a photoalignment procedure and lithography-free mode. Complex tailored structures can be used to encrypt tactile information and improve wettability by predesigning the orientation distribution of liquid crystal director. This rapid switching nanoprecision smart surface provides a novel platform for artificial skin, optics, and functional coatings.

12.
EBioMedicine ; 74: 103712, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34839261

RESUMO

BACKGROUND: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. METHODS: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. FINDINGS: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. INTERPRETATION: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

13.
Opt Express ; 29(23): 37245-37252, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808801

RESUMO

We propose and demonstrate a green semipolar (20-21) micro-light emitting diode (LED) acting as a high speed visible light communication (VLC) photodiode (PD). The micro-LED PD has the optical-to-electrical (OE) response of 228 MHz. A record data rate of 540 Mbit/s in on-off-keying (OOK) format with free-space transmission distance of 1.1 m was achieved, fulfilling the pre-forward error correction (FEC) limit. Many transmitters (Txs) and receivers (Rxs) is required to support the high density pico/femto-cells in future wireless networks, as well as the Internet-of-Things (IOT) networks. The proposed work could allow the realization of a low-cost, small-footprint and a high level of integration of VLC Txs and Rxs on the same platform.

14.
BMC Bioinformatics ; 22(Suppl 5): 92, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749632

RESUMO

BACKGROUND: Heart sound measurement is crucial for analyzing and diagnosing patients with heart diseases. This study employed phonocardiogram signals as the input signal for heart disease analysis due to the accessibility of the respective method. This study referenced preprocessing techniques proposed by other researchers for the conversion of phonocardiogram signals into characteristic images composed using frequency subband. Image recognition was then conducted through the use of convolutional neural networks (CNNs), in order to classify the predicted of phonocardiogram signals as normal or abnormal. However, CNN requires the tuning of multiple hyperparameters, which entails an optimization problem for the hyperparameters in the model. To maximize CNN robustness, the uniform experiment design method and a science-based methodical experiment design were used to optimize CNN hyperparameters in this study. RESULTS: An artificial intelligence prediction model was constructed using CNN, and the uniform experiment design method was proposed to acquire hyperparameters for optimal CNN robustness. The results indicate Filters ([Formula: see text]), Stride ([Formula: see text]), Activation functions ([Formula: see text]), and Dropout ([Formula: see text]) to be significant factors considerably influencing the ability of CNN to distinguish among heart sound states. Finally, the confirmation experiment was conducted, and the hyperparameter combination for optimal model robustness was Filters ([Formula: see text]) = 32, Kernel Size ([Formula: see text] = 3 × 3, Stride ([Formula: see text]) = (1,1), Padding ([Formula: see text] as same, Optimizer ([Formula: see text] as the stochastic gradient descent, Activation functions ([Formula: see text]) as relu, and Dropout ([Formula: see text]) = 0.544. With this combination of parameters, the model had an average prediction accuracy rate of 0.787 and standard deviation of 0. CONCLUSION: In this study, phonocardiogram signals were used for the early prediction of heart diseases. The science-based and methodical uniform experiment design was used for the optimization of CNN hyperparameters to construct a CNN with optimal robustness. The results revealed that the constructed model exhibited robustness and an acceptable accuracy rate. Other literature has failed to address hyperparameter optimization problems in CNN; a method is subsequently proposed for robust CNN optimization, thereby solving this problem.


Assuntos
Inteligência Artificial , Cardiopatias , Cardiopatias/diagnóstico por imagem , Humanos , Redes Neurais de Computação
15.
BMC Bioinformatics ; 22(Suppl 5): 148, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749637

RESUMO

BACKGROUND: The prevalence of chronic disease is growing in aging societies, and artificial-intelligence-assisted interpretation of macular degeneration images is a topic that merits research. This study proposes a residual neural network (ResNet) model constructed using uniform design. The ResNet model is an artificial intelligence model that classifies macular degeneration images and can assist medical professionals in related tests and classification tasks, enhance confidence in making diagnoses, and reassure patients. However, the various hyperparameters in a ResNet lead to the problem of hyperparameter optimization in the model. This study employed uniform design-a systematic, scientific experimental design-to optimize the hyperparameters of the ResNet and establish a ResNet with optimal robustness. RESULTS: An open dataset of macular degeneration images ( https://data.mendeley.com/datasets/rscbjbr9sj/3 ) was divided into training, validation, and test datasets. According to accuracy, false negative rate, and signal-to-noise ratio, this study used uniform design to determine the optimal combination of ResNet hyperparameters. The ResNet model was tested and the results compared with results obtained in a previous study using the same dataset. The ResNet model achieved higher optimal accuracy (0.9907), higher mean accuracy (0.9848), and a lower mean false negative rate (0.015) than did the model previously reported. The optimal ResNet hyperparameter combination identified using the uniform design method exhibited excellent performance. CONCLUSION: The high stability of the ResNet model established using uniform design is attributable to the study's strict focus on achieving both high accuracy and low standard deviation. This study optimized the hyperparameters of the ResNet model by using uniform design because the design features uniform distribution of experimental points and facilitates effective determination of the representative parameter combination, reducing the time required for parameter design and fulfilling the requirements of a systematic parameter design process.


Assuntos
Inteligência Artificial , Degeneração Macular , Progressão da Doença , Humanos , Degeneração Macular/diagnóstico por imagem , Redes Neurais de Computação , Razão Sinal-Ruído
16.
Artigo em Inglês | MEDLINE | ID: mdl-34714744

RESUMO

Acoustic levitation is considered one of the most effective non-contact particle manipulation methods, along with aerodynamic, ferromagnetic, and optical levitation techniques. It is not restricted by the material properties of the target. However, existing acoustic levitation techniques have some drawbacks that limit their potential applications. Therefore, in this paper, an innovative approach is proposed to manipulate objects more intuitively and freely. By taking advantage of the transition periods between the acoustic pulse trains and electrical driving signals, acoustic traps can be created by switching the acoustic focal spots rapidly. Since the high-energy-density points are not formed simultaneously, the computation of the acoustic field distribution with complicated mutual interference can be eliminated. Therefore, comparing to the existing approaches that created acoustic traps by solving pressure distributions using iterative methods, the proposed method simplifies the computation of time delay and makes it possible to be solved even with a microcontroller. In this work, three experiments have been demonstrated successfully to prove the capability of the proposed method including lifting a Styrofoam sphere, transportation of a single target, and suspending two objects. Besides, simulations of the distributions of acoustic pressure, radiation force, and Gor'kov potential were conducted to confirm the presence of acoustic traps in the scenarios of lifting one and two objects. The proposed tactic should be considered effective since the results of the practical experiments and simulations support each other.

17.
J Formos Med Assoc ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34696938

RESUMO

BACKGROUND/PURPOSE: Various microRNAs (miRs) have been found to be associated with the development of the precancerous condition of the oral cavity, oral submucous fibrosis (OSF). The expression of miR-29c is dysregulated in oral cancer, but its role in OSF has not been investigated. The purpose of the study is to investigate the functional role of miR-29c and its target in OSF. METHODS: The expression levels of miR-29c in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were assessed using next-generation sequencing and real-time Polymerase Chain Reaction (PCR) analysis. MiR-29c mimic and inhibitors were employed to examine its functional role of myofibroblast transdifferentiation. In addition, several myofibroblast phenotypes, such as collagen gel contraction and migration were tested, and a luciferase reporter assay was conducted to confirm the relationship between miR-29c and its predicted target, tropomyosin-1 (TPM1). RESULTS: We observed that miR-29c expression was downregulated in fBMFs. fBMFs transfected with miR-29c mimics exhibited reduced migration ability and collagen gel contractility, whereas inhibition of miR-29c in normal BMFs induced the myofibroblast phenotypes. Results from the luciferase reporter assay showed that TPM1 was a direct target of miR-29c and the expression of TPM1 was suppressed in the fBMFs transfected with miR-29c mimics. Besides, we confirmed that the expression of miR-29c was indeed downregulated in OSF specimens. CONCLUSION: MiR-29c seems to exert an inhibitory effect on myofibroblast activation, such as collagen gel contractility and migration ability, via suppressing TPM1. These results suggested that approaches to upregulate miR-29c may be able to ameliorate the progression of OSF.

18.
Sensors (Basel) ; 21(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502599

RESUMO

To track moving targets undergoing unknown translational and rotational motions, a tracking controller is developed for unmanned aerial vehicles (UAVs). The main challenges are to control both the relative position and orientation between the target and the UAV to within desired values, and to guarantee that the generated control input to the UAV is feasible (i.e., below its motion capability). Moreover, the UAV is controlled to ensure that the target always remains within the field of view of the onboard camera. These control objectives were achieved by developing a nonlinear-model predictive controller, in which the future motion of the target is predicted by quadratic programming (QP). Since constraints of the feature vector and the control input are considered when solving the optimal control problem, the control inputs can be bounded and the target can remain inside the image. Three simulations were performed to compare the efficacy and performance of the developed controller with a traditional image-based visual servoing controller.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34342786

RESUMO

In Taiwan, the outcomes of acute limb ischemia have yet to be investigated in a standardized manner. In this study, we compared the safety, feasibility and outcomes of acute limb ischemia after surgical embolectomy or catheter-directed therapy in Taiwan. This study used data collected from the Taiwan's National Health Insurance Database (NHID) and Cause of Death Data between the years 2000 and 2015. The rate ratio of all-cause in-hospital mortality and risk of amputation during the same period of hospital stay were estimated using Generalized linear models (GLM). There was no significant difference in mortality risk between CDT and surgical intervention (9.5% vs. 10.68%, adjusted rate ratio (95% CI): regression 1.0 [0.79-1.27], PS matching 0.92 [0.69-1.23]). The risk of amputation was also comparable between the two groups. (13.59% vs. 14.81%, adjusted rate ratio (95% CI): regression 0.84 [0.68-1.02], PS matching 0.92 [0.72-1.17]). Age (p < 0.001) and liver disease (p = 0.01) were associated with higher mortality risks. Heart failure (p = 0.03) and chronic or end-stage renal disease (p = 0.03) were associated with higher amputation risks. Prior antithrombotic agent use (p = 0.03) was associated with a reduced risk of amputation. Both surgical intervention and CDT are effective and feasible procedures for patients with ALI in Taiwan.

20.
ACS Synth Biol ; 10(8): 1830-1836, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34374512

RESUMO

Protein-level regulations have gained importance in building synthetic circuits, as they offer a potential advantage in the speed of operation compared to gene regulation circuits. In nature, localized protein degradation is prevalent in polarizing cellular signaling. We, therefore, set out to systematically investigate whether localized proteolysis can be employed to construct intracellular asymmetry in Escherichia coli. We demonstrate that, by inserting a cognate cleavage site between the reporter and C-terminal degron, the unstable reporter can be stabilized in the presence of the tobacco etch virus protease. Furthermore, the split protease can be functionally reconstituted by the PopZ-based polarity system to exert localized proteolysis. Selective stabilization of the unstable reporter at the PopZ pole can lead to intracellular asymmetry in E. coli. Our study provides complementary evidence to support that localized proteolysis may be a strategy for polarization in developmental cell biology. Circuits designed in this study may also help to expand the synthetic biology repository for the engineering of synthetic morphogenesis, particularly for processes that require rapid control of local protein abundance.

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