Publications by authors named "Yuan Jin"

355 Publications

Retinal vascular geometry detection as a biomarker in diabetes mellitus.

Eur J Ophthalmol 2021 Jul 20:11206721211033488. Epub 2021 Jul 20.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China.

Objective: To compare the vessel geometry characteristics of color fundus photographs in normal control and diabetes mellitus (DM) patients and to find potential biomarkers for early diabetic retinopathy (DR) based on a neural network vessel segmentation system and automated vascular geometry parameter analysis software.

Methods: A total of 102 consecutive patients with type 2 DM (T2DM) and 132 healthy controls were recruited. All participants underwent general ophthalmic examinations, and retinal fundus photographs were taken with a digital fundus camera without mydriasis. Color fundus photographs were input into a dense-block generative adversarial network (D-GAN)-assisted retinal vascular segmentation system (http://www.gdcerc.cn:8081/#/login) to obtain binary images. These images were then analyzed by customized software (ocular microvascular analysis system V2.9.1) for automatic processing of vessel geometry parameters, including the monofractal dimension (), multifractal dimension (), vessel area ratio (), max vessel diameter (), average vessel diameter (), arc-chord ratio (A/C), and tortuosity (τ). Geometric differences between the healthy subjects and DM patients were analyzed. Then, regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic efficiency of the vascular geometry parameters.

Results: No significant differences were observed between the baseline characteristics of each group. DM patients had lower and values (1.330 ± 0.041; 1.347 ± 0.038) than healthy subjects (1.343 ± 0.048, < 0.05; 1.362 ± 0.042, < 0.05) and showed increasing values of , , A/C, and τ compared with normal controls, although only the differences in and τ between the groups were statistically significant. In the regression analysis, and τ showed a good correlation with diabetes (, OR 1.765, 95% CI 1.319-2.362, < 0.001; τ, OR 9.323, 95% CI 1.492-58.262, < 0.05).

Conclusions: We demonstrated the relationship between retinal vascular geometry and the process in DM patients, showing that , , , and τ may be indicators of morphological changes in retinal vessels in DM patients and can be early biomarkers of DR.
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http://dx.doi.org/10.1177/11206721211033488DOI Listing
July 2021

Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK.

PLoS One 2021 15;16(7):e0252048. Epub 2021 Jul 15.

Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Harvard University, Boston, Massachusetts, United States of America.

Neurofibromatosis Type 2 (NF2) is an autosomal dominant genetic syndrome caused by mutations in the NF2 tumor suppressor gene resulting in multiple schwannomas and meningiomas. There are no FDA approved therapies for these tumors and their relentless progression results in high rates of morbidity and mortality. Through a combination of high throughput screens, preclinical in vivo modeling, and evaluation of the kinome en masse, we identified actionable drug targets and efficacious experimental therapeutics for the treatment of NF2 related schwannomas and meningiomas. These efforts identified brigatinib (ALUNBRIG®), an FDA-approved inhibitor of multiple tyrosine kinases including ALK, to be a potent inhibitor of tumor growth in established NF2 deficient xenograft meningiomas and a genetically engineered murine model of spontaneous NF2 schwannomas. Surprisingly, neither meningioma nor schwannoma cells express ALK. Instead, we demonstrate that brigatinib inhibited multiple tyrosine kinases, including EphA2, Fer and focal adhesion kinase 1 (FAK1). These data demonstrate the power of the de novo unbiased approach for drug discovery and represents a major step forward in the advancement of therapeutics for the treatment of NF2 related malignancies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252048PLOS
July 2021

Multi-discriminator adversarial convolutional network for nerve fiber segmentation in confocal corneal microscopy images.

IEEE J Biomed Health Inform 2021 Jul 9;PP. Epub 2021 Jul 9.

Quantitative measurements of corneal sub-basal nerves are biomarkers for many ocular surface disorders, and are also important for early diagnosis and assessment of progression of neurodegenerative diseases. This paper aims to develop an automatic method for nerve fiber segmentation from in vivo corneal confocal microscopy (CCM) images, which is fundamental for nerve morphology quantification. A novel multi-discriminator adversarial convolutional network (MDACN) is proposed, where both the generator and the two discriminators emphasize multi-scale feature representations. The generator is a U-shaped fully convolutional network with multi-scale split and concatenate blocks, and the two discriminators have different effective receptive fields, sensitive to features of different scales. A novel loss function is also proposed which enables the network to pay more attention to thin fibers. The MDACN framework was evaluated on four datasets. Experiment results show that our method has excellent segmentation performance for corneal nerve fibers and outperforms some state-of-the-art methods.
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http://dx.doi.org/10.1109/JBHI.2021.3094520DOI Listing
July 2021

Distribution and determinants of hospital efficiency and relative productivity in county-level hospitals in rural China: an observational study.

BMJ Open 2021 Jul 2;11(7):e042326. Epub 2021 Jul 2.

Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China

Background: Cataract surgery is very important to prevent blindness, but its productivity and efficiency in China are unknown. Our study aimed to evaluate the geographical distribution of cataract surgeons and prospectively identify the factors associated with the increased productivity in cataract surgery and efficiency in outpatient ophthalmic services in rural Chinese hospitals.

Methods: Data were prospectively collated from various hospital datasets and the census registered by the geographical unit county. Prior to mapping, the geographical location data of counties were cross-linked with the equivalent ophthalmologist and service output data to create categories and map multiple data attributes. Descriptive statistical analyses were performed to characterise the data stratified by county. Linear regression analyses were used to explore the factors associated with the increased productivity/efficiency.

Results: The ophthalmologists, surgical productivity of ophthalmologists and outpatient efficacy of ophthalmologists significantly varied across counties. During the period between 2016 and 2018, the median (IQR) change in surgical productivity of and outpatient efficacy of ophthalmologists were 31.627 (-3.33 to 29.94) and 118.08 (-132.30 to 740.89). In the simple regression analysis for predictors of a high productivity change, only the increased number of phaco machine had statistical significance (p=0.003). In addition, only the gross domestic product per capita in 2016 was associated with an increased improvement in efficiency of outpatient services (p=0.008).

Conclusions: This study demonstrated that the ophthalmologist productivity and the efficiency of outpatient services were unequally geographically distributed, and their predictors were identified. Further studies to elucidate the extent of the problem and improve the health service delivery models are required.
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http://dx.doi.org/10.1136/bmjopen-2020-042326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256740PMC
July 2021

Analysis of the misalignment effect and the characterization method for imprinting continuous phase plates.

Opt Express 2021 May;29(11):17554-17572

Continuous phase plates (CPPs) are increasingly being used to realize beam shaping and smoothing in high-power laser systems. With computer controlled optical surfacing (CCOS) technology, CPPs can be imprinted with high accuracy by a series of processing iterations, in which the characterization of the imprinted CPP surface plays a key role. However, the form accuracy evaluation is sensitive to the misalignment caused by the difference between the designed and measured coordinates. In this paper, the matching problem, which is the critical part of characterization, is first summarized as a least squares problem in accordance with the processing principle of CPPs. Then, the misalignment effect on the form error evaluation is analyzed. Necessary attention is paid to the CPP features and the sensibility analysis for different misalignments is conducted. To improve the efficiency and accuracy, an automatic characterization method based on image registration and nonlinear optimization is presented. Considering the smoothness of the CPP surface, the height difference tracing method is proposed to evaluate the matching performance and embedded into the characterization method. Finally, a series of simulations and experiments were undertaken to verify the performance of the proposed characterization method. The results demonstrated the feasibility of the proposed method, indicating that it can provide the reliable form error evaluation with sub-nanometer accuracy for imprinted CPPs.
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http://dx.doi.org/10.1364/OE.425248DOI Listing
May 2021

Deep-learning models for the detection and incidence prediction of chronic kidney disease and type 2 diabetes from retinal fundus images.

Nat Biomed Eng 2021 Jun 15;5(6):533-545. Epub 2021 Jun 15.

Peking University Third Affiliated Hospital, Beijing, China.

Regular screening for the early detection of common chronic diseases might benefit from the use of deep-learning approaches, particularly in resource-poor or remote settings. Here we show that deep-learning models can be used to identify chronic kidney disease and type 2 diabetes solely from fundus images or in combination with clinical metadata (age, sex, height, weight, body-mass index and blood pressure) with areas under the receiver operating characteristic curve of 0.85-0.93. The models were trained and validated with a total of 115,344 retinal fundus photographs from 57,672 patients and can also be used to predict estimated glomerulal filtration rates and blood-glucose levels, with mean absolute errors of 11.1-13.4 ml min per 1.73 m and 0.65-1.1 mmol l, and to stratify patients according to disease-progression risk. We evaluated the generalizability of the models for the identification of chronic kidney disease and type 2 diabetes with population-based external validation cohorts and via a prospective study with fundus images captured with smartphones, and assessed the feasibility of predicting disease progression in a longitudinal cohort.
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http://dx.doi.org/10.1038/s41551-021-00745-6DOI Listing
June 2021

HIF-1α and HIF-2α redundantly promote retinal neovascularization in patients with ischemic retinal disease.

J Clin Invest 2021 Jun;131(12)

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Therapies targeting VEGF have proven only modestly effective for the treatment of proliferative sickle cell retinopathy (PSR), the leading cause of blindness in patients with sickle cell disease. Here, we shift our attention upstream from the genes that promote retinal neovascularization (NV) to the transcription factors that regulate their expression. We demonstrated increased expression of HIF-1α and HIF-2α in the ischemic inner retina of PSR eyes. Although both HIFs participated in promoting VEGF expression by hypoxic retinal Müller cells, HIF-1 alone was sufficient to promote retinal NV in mice, suggesting that therapies targeting only HIF-2 would not be adequate to prevent PSR. Nonetheless, administration of a HIF-2-specific inhibitor currently in clinical trials (PT2385) inhibited NV in the oxygen-induced retinopathy (OIR) mouse model. To unravel these discordant observations, we examined the expression of HIFs in OIR mice and demonstrated rapid but transient accumulation of HIF-1α but delayed and sustained accumulation of HIF-2α; simultaneous expression of HIF-1α and HIF-2α was not observed. Staggered HIF expression was corroborated in hypoxic adult mouse retinal explants but not in human retinal organoids, suggesting that this phenomenon may be unique to mice. Using pharmacological inhibition or an in vivo nanoparticle-mediated RNAi approach, we demonstrated that inhibiting either HIF was effective for preventing NV in OIR mice. Collectively, these results explain why inhibition of either HIF-1α or HIF-2α is equally effective for preventing retinal NV in mice but suggest that therapies targeting both HIFs will be necessary to prevent NV in patients with PSR.
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http://dx.doi.org/10.1172/JCI139202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203455PMC
June 2021

Identification of Novel Compound Heterozygous Mutations in Two Chinese Families with Autosomal Recessive Nonsyndromic Hearing Loss.

Neural Plast 2021 14;2021:9957712. Epub 2021 May 14.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Congenital deafness is one of the most common causes of disability in humans, and more than half of cases are caused by genetic factors. Mutations of the gene are the third most common cause of hereditary hearing loss. Using next-generation sequencing combined with auditory tests, two novel compound heterozygous variants c.2802_2812del/c.5681T>C and c.5681T>C/c.6340G>A in the gene were identified in probands from two irrelevant Chinese families. Auditory phenotypes of the probands are consistent with the previously reported for recessive variants in the gene. The two novel variants, c.2802_2812del and c.5681T>C, were identified as deleterious mutations by bioinformatics analysis. Our findings extend the gene mutation spectrum and provide more information for rapid and precise molecular diagnosis of congenital deafness.
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http://dx.doi.org/10.1155/2021/9957712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140830PMC
May 2021

Does Percutaneous Coronary Intervention on Off Days have an Effect on Long-term Prognosis in Patients with Coronary Artery Disease in China?

Biomed Environ Sci 2021 May;34(5):387-394

Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.

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http://dx.doi.org/10.3967/bes2021.051DOI Listing
May 2021

A toxicity pathway-based approach for modeling the mode of action framework of lead-induced neurotoxicity.

Environ Res 2021 08 15;199:111328. Epub 2021 May 15.

Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

Background: The underlying mechanisms of lead (Pb) toxicity are not fully understood, which makes challenges to the traditional risk assessment. There is growing use of the mode of action (MOA) for risk assessment by integration of experimental data and system biology. The current study aims to develop a new pathway-based MOA for assessing Pb-induced neurotoxicity.

Methods: The available Comparative Toxicogenomic Database (CTD) was used to search genes associated with Pb-induced neurotoxicity followed by developing toxicity pathways using Ingenuity Pathway Analysis (IPA). The spatiotemporal sequence of disturbing toxicity pathways and key events (KEs) were identified by upstream regulator analysis. The MOA framework was constructed by KEs in biological and chronological order.

Results: There were a total of 71 references showing the relationship between lead exposure and neurotoxicity, which contained 2331 genes. IPA analysis showed that the neuroinflammation signaling pathway was the core toxicity pathway in the enriched pathways relevant to Pb-induced neurotoxicity. The upstream regulator analysis demonstrated that the aryl hydrocarbon receptor (AHR) signaling pathway was the upstream regulator of the neuroinflammation signaling pathway (11.76% overlap with upstream regulators, |Z-score|=1.451). Therefore, AHR activation was recognized as the first key event (KE1) in the MOA framework. The following downstream molecular and cellular key events were also identified. The pathway-based MOA framework of Pb-induced neurotoxicity was built starting with AHR activation, followed by an inflammatory response and neuron apoptosis.

Conclusion: Our toxicity pathway-based approach not only advances the development of risk assessment for Pb-induced neurotoxicity but also brings new insights into constructing MOA frameworks of risk assessment for new chemicals.
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http://dx.doi.org/10.1016/j.envres.2021.111328DOI Listing
August 2021

Freeform surface generation by atmospheric pressure plasma processing using a time-variant influence function.

Opt Express 2021 Apr;29(8):11479-11493

Based on a controllable chemical reaction, atmospheric pressure plasma processing (APPP) can achieve efficient material removal even when the tool influence function (TIF) size is reduced to several millimeters, resulting in its great application potential for generating freeform surfaces. However, the TIF changes with the local dwell time, introducing nonlinearity into processing, because of the influence of the plasma thermal effect on chemical reactions. In this paper, a freeform generation method using a time-variant TIF is presented and validated. First, the time-variant removal characteristics of APPP and its nonlinear influence on freeform surface generation are analyzed. Then, the freeform surface generation concept is proposed based on controlling the local volumetric removal. Consequently, the dwell time calculation method is developed to suppress the nonlinearity induced by the time-variant TIF. Finally, the developed method is evaluated by the simulation and experimental analysis of the complex structure generation process. Results show that the proposed method can reduce the nonlinear influence of the time-variant TIF by reasonably calculating dwell time, promoting the application of APPP in freeform surface generation.
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http://dx.doi.org/10.1364/OE.421688DOI Listing
April 2021

Blood lead levels and their associated risk factors in Chinese adults from 1980 to 2018.

Ecotoxicol Environ Saf 2021 May 10;218:112294. Epub 2021 May 10.

School of Public Health, Qingdao University, Qingdao 266000, China. Electronic address:

In China, studies on lead exposure to grownup are scarce compared to children, although relevant disease burdens for adults are much severe than that in developed countries. The present study evaluated blood lead levels (BLLs) in Chinese adults by data mining using Monte Carlo simulation. A total of 115 scientific studies published between January 1980 and March 2021 reflecting 45,514 Chinese adults were included in the study. After a continuous increase in Chinese adult BLLs from 1980-1983 (GM 74.84 μg/L) to 1994-1996 (GM 92.27 μg/L), BLLs began to decline from 2000--2002 (GM 80.32 μg/L) to 2016-2018 (GM 21.57 μg/L). This decline implied that the lead phase-out policy in gasoline was effective over the past two decades. The study indicated that North, South, and Southwest China were still relatively high compared to other regions in the past decade. Statistical analysis showed that BLLs of males (GM 68.45 μg/L) were higher than females (GM 56.51 μg/L), smokers (GM 80.96 μg/L) higher than nonsmokers (GM 58.95 μg/L), and populations over 40 (GM 40.43 μg/L) higher than younger populations (GM 40.37 μg/L). The significantly positive correlation between the concentrations of PM2.5 and topsoil lead and BLLs in Chinese adults indicated that air and soil pollution affect adult BLLs. Taken together, our results showed that strict lead control strategies and regular bio-monitoring are needed to maintain low BLLs in the population.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112294DOI Listing
May 2021

Co-assembled gold [email protected] core-shell nanospheres for aqueous Hg removal.

J Colloid Interface Sci 2021 Oct 21;599:436-442. Epub 2021 Apr 21.

Key Laboratory of Colloid and Interface Chemistry & Key Laboratory of Special Aggregated Materials (Shandong University), Ministry of Education, Jinan 250100, China. Electronic address:

The construction of peptide and metal nanoparticles hybrid is attractive to explore their synergistic properties and applications extensively. However, it remains a challenge to fabricate a well-defined and size-controllable short peptide/Au nanoparticles hybrid. Here, we report a facile and flexible co-assembly strategy for the construction of tripeptide coated Au nanorods (AuNRs). The tripeptide (Phe-Phe-Cys, FFC) grows via covalently crosslinking to form spheres. The size of the [email protected] nanospheres can be controlled by modulating the amount or size of AuNRs. Especially, the concentration of AuNRs fixes the amount of seeds, which further affect the local concentration of FFC on the surface of AuNRs seed, leading to a narrower diameter of hybrid compared to FFC spheres. Moreover, owing to their synergistic effects, this hybrid exhibits a good adsorption capacity of Hg from aqueous solutions by electrostatic interaction and forming into Au/Hg amalgam. This strategy could be extended to the fabrication of other biomolecules and metal nanoparticle hybrids with diverse functions.
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http://dx.doi.org/10.1016/j.jcis.2021.04.100DOI Listing
October 2021

The role of the excitation:inhibition functional balance in the mPFC in the onset of antidepressants.

Neuropharmacology 2021 06 2;191:108573. Epub 2021 May 2.

Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China; Beijing Institute of Basic Medical Sciences, Beijing, China. Electronic address:

Currently available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), generally require weeks to months to produce a therapeutic response, but the mechanism of action underlying the delayed onset of antidepressant-like action remains to be elucidated. The balance between excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons, i.e., the excitation:inhibition functional (E:I) balance, in the medial prefrontal cortex (mPFC) is critical in regulating several behaviors and might play an important mediating role in the mechanism of rapid antidepressant-like action reported by several studies. In the present study, the multichannel electrophysiological technique was used to record the firing activities of pyramidal neurons and interneurons and investigate the effects of a single dose of fluoxetine and ketamine (both 10 mg/kg, i.p.) on the E:I functional balance in the rat mPFC after 90 min or 24 h, and the forced swimming test (FST) was used to evaluate the antidepressant-like effects of fluoxetine and ketamine. The present study also explored the effects of chronic treatment with fluoxetine (10 mg/kg, i.g.) for 7 d or 21 d on the E:I functional balance in the mPFC. The present results suggested that a single dose of ketamine could both significantly increase the firing activities of pyramidal neurons and significantly decrease the firing activities of interneurons in the mPFC and exerted significant antidepressant-like action on the FST after 90 min and 24 h, but fluoxetine had no such effects under the same conditions. However, chronic treatment with fluoxetine for 21 d (but not 7 d) could significantly affect the firing activities of pyramidal neurons and interneurons in the mPFC. Taken together, the present results indicated that rapid regulation of the E:I functional balance in the mPFC might be an important common mechanism of rapid-acting antidepressants and the delayed onset of SSRIs might be partly attributed to their inability to rapidly regulate the E:I functional balance in the mPFC. The present study provided a new entry point to the development of rapid-acting antidepressants.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108573DOI Listing
June 2021

AutoImplant 2020 -First MICCAI Challenge on Automatic Cranial Implant Design.

IEEE Trans Med Imaging 2021 May 3;PP. Epub 2021 May 3.

The aim of this paper is to provide a comprehensive overview of the MICCAI 2020 AutoImplant Challenge1. The approaches and publications submitted and accepted within the challenge will be summarized and reported, highlighting common algorithmic trends and algorithmic diversity. Furthermore, the evaluation results will be presented, compared and discussed in regard to the challenge aim: seeking for low cost, fast and fully automated solutions for cranial implant design. Based on feedback from collaborating neurosurgeons, this paper concludes by stating open issues and post-challenge requirements for intra-operative use. The codes can be found at https://github.com/Jianningli/tmi.
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http://dx.doi.org/10.1109/TMI.2021.3077047DOI Listing
May 2021

Corneal biomechanical changes in allergic conjunctivitis.

Eye Vis (Lond) 2021 May 3;8(1):17. Epub 2021 May 3.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Background: To explore corneal biomechanical changes, identify related factors and determine early indicators of keratoconus (KC) development risk in allergic conjunctivitis (AC) patients.

Methods: A total of 50 patients, including 20 eyes without AC and 30 eyes with AC were enrolled in this study. All patients underwent a complete ocular examination, including evaluations of clinical manifestations of AC, corneal tomography and densitometry by Pentacam, corneal biomechanics by Corvis ST, and corneal and epithelial thickness mapping by RTvue optical coherence tomography (OCT).

Results: The index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), index of height decentration (IHD) and Belin/Ambrosio enhanced ectasia total deviation index (BAD-D) were significantly higher in the AC group than in the non-allergic conjunctivitis (NAC) group (P < 0.05). The tomography and biomechanical index (TBI) was also significantly higher in the AC group (P = 0.04). The average epithelial thickness in the 2-7 mm annulus was significantly thinner in the AC group than in the NAC group (P < 0.05). The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group (P < 0.001). The ISV, IVA, KI, IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients (P < 0.05). The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores (P < 0.05).

Conclusions: AC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements, and the TBI could be used as an indicator of KC development risk in AC patients.

Trial Registration: Corneal Biomechanical Changes of Allergic Conjunctivitis, NCT04299399 . Registered March 3, 2020 - Retrospectively registered.
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http://dx.doi.org/10.1186/s40662-021-00241-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091662PMC
May 2021

MicroRNA-760 resists ambient PM-induced apoptosis in human bronchial epithelial cells through elevating heme-oxygenase 1 expression.

Environ Pollut 2021 Sep 23;284:117213. Epub 2021 Apr 23.

School of Public Health, Qingdao University, Qingdao, China. Electronic address:

PM (particles matter smaller aerodynamic diameter of 2.5 μm) exposure, a major environmental risk factor for the global burden of diseases, is associated with high risks of respiratory diseases. Heme-oxygenase 1 (HMOX1) is one of the major molecular antioxidant defenses to mediate cytoprotective effects against diverse stressors, including PM-induced toxicity; however, the regulatory mechanism of HMOX1 expression still needs to be elucidated. In this study, using PM as a typical stressor, we explored whether microRNAs (miRNAs) might modulate HMOX1 expression in lung cells. Systematic bioinformatics analysis showed that seven miRNAs have the potentials to target HMOX1 gene. Among these, hsa-miR-760 was identified as the most responsive miRNA to PM exposure. More importantly, we revealed a "non-conventional" miRNA function in hsa-miR-760 upregulating HMOX1 expression, by targeting the coding region and interacting with YBX1 protein. In addition, we observed that exogenous hsa-miR-760 effectively elevated HMOX1 expression, reduced the reactive oxygen agents (ROS) levels, and rescued the lung cells from PM-induced apoptosis. Our results revealed that hsa-miR-760 might play an important role in protecting lung cells against PM-induced toxicity, by elevating HMOX1 expression, and offered new clues to elucidate the diverse functions of miRNAs.
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http://dx.doi.org/10.1016/j.envpol.2021.117213DOI Listing
September 2021

A novel epigenetic mechanism unravels hsa-miR-148a-3p-mediated CYP2B6 downregulation in alcoholic hepatitis disease.

Biochem Pharmacol 2021 Jun 23;188:114582. Epub 2021 Apr 23.

Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China. Electronic address:

Cytochrome P450 (CYP) enzymes play critical roles in drug transformation, and the total CYPs are markedly decreased in alcoholic hepatitis (AH), a fatal alcoholic liver disease. miRNAs are endogenous small noncoding RNAs that regulate many essential biological processes. Knowledge concerning miRNA regulation of CYPs in AH disease is limited. Here we presented the changes of key CYPs in liver samples of AH patients retrieved from GEO database, performed in silico prediction of miRNAs potentially targeting the dysregulated CYP transcripts, and deciphered a novel mechanism underlying miRNA mediated CYPs expression in liver cells. Nine miRNAs were predicted to regulate CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2J2, and CYP3A4, among which hsa-miR-148a-3p was selected as a case study. Biochemical and molecular evidences demonstrated that miR-148a promoted CYP2B6 expression by increasing mRNA stability via directly binding to the 3'UTR sequence, and that this positive posttranscriptional regulation was AGO1/2-dependent. Further, luciferase reporter gene assay and RNA secondary structure analysis illustrated that the seedless target site, not the seed target site, controlled miR-148a-mediated CYP2B6 upregulation. Moreover, we identified HNF4A as a liver-specific transcription factor of MIR-148A through EMSA and chromatin immunoprecipitation experiments. In conclusion, ethanol downregulated miR-148a in hepatocytes through HNF4A regulation, which eventually decreased CYP2B6 expression. Our finding will benefit the understanding of dysregulated drug metabolism in AH patients and highlight an unconventional mechanism for epigenetic regulation of CYP gene expression.
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http://dx.doi.org/10.1016/j.bcp.2021.114582DOI Listing
June 2021

Nanoemulsion fluorescent inks for anti-counterfeiting encryption with dual-mode, full-color, and long-term stability.

Chem Commun (Camb) 2021 May;57(40):4894-4897

Key Laboratory of Colloid and Interface Chemistry (Ministry of Education), Shandong University, Jinan 250100, China.

An oil-in-water nanoemulsion (O/W NE) is selected as the carrier to encapsulate hydrophobic dual-mode luminescent upconversion nanoparticles (UC NPs) and downconversion (DC) carbon quantum dots (CQDs) inside the oil droplets for forming water-based fluorescent inks. The NE inks conform well to the requirements of inkjet printing for anti-counterfeiting encryption applications.
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http://dx.doi.org/10.1039/d1cc00555cDOI Listing
May 2021

Self-Assembly of Amphiphilic Copper Nanoclusters Driven by Cationic Surfactants.

Langmuir 2021 Jun 22;37(22):6613-6622. Epub 2021 Apr 22.

Key Laboratory of Colloid and Interface Chemistry & Key Laboratory of Special Aggregated Materials, Shandong University, Ministry of Education, Jinan 250100, China.

Amphiphilicity is an excellent physicochemical property, which is yet to be explored from traditional surfactants to nanoparticles. This article shows that the amphiphilicity of copper nanoclusters (CuNCs) can be readily tuned by electrostatic interactions with cationic surfactants and cetyltrimethylammonium cations (CTA) with counterions Br, Cl, and CHOS. Due to the role of surface ligands, the complexes of glutathione-capped CuNCs (GSH-CuNCs) and the surfactants exhibit good amphiphilicity, which enables them to self-assemble like a molecular amphiphile. This could significantly increase the utility of metal nanoclusters in basic and applied research. As the concentration of the surfactant changes, the aggregates change from nanoparticles to network-like structures. After the formation of supramolecular self-assemblies by hydrophobic interactions, the enhancement of fluorescence intensity was observed, which can be ascribed to the suppression of intramolecular vibrations based on aggregation-induced emission (AIE) and combined with the compactness of GSH-CuNCs in self-assemblies. Our study provides a facile way to generate solid fluorescent materials with excellent fluorescence performance, which may find applications in light-emitting diodes (LEDs).
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http://dx.doi.org/10.1021/acs.langmuir.1c00022DOI Listing
June 2021

KenDTI: an ensemble model based on network integration and CNN for drug-target interaction prediction.

IEEE/ACM Trans Comput Biol Bioinform 2021 Apr 20;PP. Epub 2021 Apr 20.

The identification of drug-target interactions (DTIs) is an essential step in the process of drug discovery. As experimental validation suffers from high cost and low success rate, various computational models have been exploited to infer potential DTIs. The performance of DTI prediction depends heavily on the features extracted from drugs and target proteins. The existing predictors vary in input information and each has its own advantages. Therefore, combining the advantages of individual models and generating high-quality representations for drug-target pairs are effective ways to improve the performance of DTI prediction. In this study, we exploit both biochemical characteristics of drugs via network integration and molecular sequences via word embeddings, then we develop an ensemble model, KenDTI, based on two types of methods, i.e. network-based and classification-based. We assess the performance of KenDTI on two large-scale datasets, The experimental results show that KenDTI outperm the state-of-the-art DTI predictors by a large margin. Moreover, KenDTI is robust against missing data in input networks and lack of prior knowledge. It is able to predict for drug-candidate chemical compounds with scarce information.
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http://dx.doi.org/10.1109/TCBB.2021.3074401DOI Listing
April 2021

Wavelength beam-combining of terahertz quantum-cascade laser arrays.

Opt Lett 2021 Apr;46(8):1864-1867

Wavelength beam-combining of four terahertz (THz) distributed-feedback quantum-cascade lasers (QCLs) is demonstrated using low-cost THz components that include a lens carved out of a plastic ball and a mechanically fabricated blazed grating. Single-lobed beams from predominantly single-mode QCLs radiating peak power in the range of 50-170 are overlapped in the far field at frequencies ranging from 3.31-3.54. Collinear propagation with a maximum angular deviation of 0.3 is realized for the four beams. The total power efficiency for the focused and beam-combined radiation is as high as 25. This result could pave the way for future commercialization of beam-combined monolithic THz QCL arrays for multi-spectral THz sensing and spectroscopy at standoff distances.
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http://dx.doi.org/10.1364/OL.420398DOI Listing
April 2021

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress.

Front Cell Dev Biol 2021 18;9:659486. Epub 2021 Mar 18.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Sudden sensorineural hearing loss (SSNHL) is a common emergency in the world. Increasing evidence of imbalance of oxidant-antioxidant were found in SSNHL patients. Steroids combined with antioxidants may be a potential strategy for the treatment of SSNHL. In cochlear explant experiment, we found that N-acetylcysteine (NAC) combined with dexamethasone can effectively protect hair cells from oxidative stress when they were both at ineffective concentrations alone. A clinic trial was designed to explore whether oral NAC combined with intratympanic dexamethasone (ITD) as a salvage treatment has a better therapeutic effect. 41 patients with SSNHL were randomized to two groups. 23 patients in control group received ITD therapy alone, while 18 patient s in NAC group were treated with oral NAC and ITD. The patients were followed-up on day 1st (initiation of treatment) and day 14th. Overall, there was no statistical difference in final pure-tone threshold average (PTA) improvement between those two groups. However, a significant hearing gain at 8,000 Hz was observed in NAC group. Moreover, the hearing recovery rates of NAC group is much higher than that in control group. These results demonstrated that oral NAC in combination with ITD therapy is a more effective therapy for SSNHL than ITD alone.
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http://dx.doi.org/10.3389/fcell.2021.659486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014036PMC
March 2021

An automated and multiparametric algorithm for objective analysis of meibography images.

Quant Imaging Med Surg 2021 Apr;11(4):1586-1599

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Meibography is a non-contact imaging technique used by ophthalmologists and eye care practitioners to acquire information on the characteristics of meibomian glands. One of its most important applications is to assist in the evaluation and diagnosis of meibomian gland dysfunction (MGD). As the artificial qualitative analysis of meibography images can lead to low repeatability and efficiency, automated and quantitative evaluation would greatly benefit the image analysis process. Moreover, since the morphology and function of meibomian glands varies at different stages of MGD, multiparametric analysis offering more comprehensive information could help in discovering subtle changes to glands during MGD progression. Therefore, an automated and multiparametric objective analysis of meibography images is urgently needed.

Methods: An algorithm was developed to perform multiparametric analysis of meibography images with fully automatic and repeatable segmentation based on image contrast enhancement and noise reduction. The full architecture can be divided into three steps: (I) segmentation of the tarsal conjunctiva area as the region of interest (ROI); (II) segmentation and identification of glands within the ROI; and (III) quantitative multiparametric analysis including a newly defined gland diameter deformation index (), gland tortuosity index (), and gland signal index (). To evaluate the performance of this automated algorithm, the similarity index () and the segmentation error including the false-positive rate ( ) and the false-negative rate ( ) were calculated between the manually defined ground truth and the automatic segmentations of both the ROI and meibomian glands of 15 typical meibography images.

Results: The results of the performance evaluation between the manually defined ground truth and automatic segmentations were as follows: for ROI segmentation, the similarity index ()=0.94±0.02, the false-positive rate ( )=6.02%±2.41%, and the false-negative rate ( )=6.43%±1.98%; for meibomian gland segmentation, the similarity index ()=0.87±0.01, the false-positive rate ( )=4.35%±1.50%, and the-false negative rate ( )=18.61%±1.54%. The algorithm was successfully applied to process typical meibography images acquired from subjects of different meibomian gland health statuses, by providing the gland area ratio (), the gland length (), gland width (), gland diameter deformation index (), gland tortuosity index (), and gland signal index ().

Conclusions: A fully automated algorithm was developed which demonstrated high similarity with moderate segmentation errors for meibography image segmentation compared with the manual approach, offering multiple parameters to quantify the morphology and function of meibomian glands for the objective evaluation of meibography images.
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http://dx.doi.org/10.21037/qims-20-611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930676PMC
April 2021

Meridian-Specific and Post-Optical Deficits of Spatial Vision in Human Astigmatism: Evidences From Psycho-Physical and EEG Scalings.

Front Psychol 2021 17;12:595536. Epub 2021 Mar 17.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Previous studies have demonstrated that orientation-specific deprivation in early life can lead to neural deficits of spatial vision in certain space, and can even result in meridional amblyopia (MA). Individuals with astigmatism are the optimal and natural models for exploring this asymmetric development of spatial vision in the human visual system. This study aims to assess the contrast sensitivity function (CSF) and EEG signals along two principal meridians in participants with regular astigmatism when being optimal optical corrected. Twelve participants with astigmatism (AST group, 20 eyes) and thirteen participants with (MA group, 19 eyes) were recruited in the current study. CSFs and spatial sweep visual evoked potentials (sVEP) were measured with vertical and horizontal sinewave gratings along two principal meridians monocularly. Area under log CSF (AULCSF), spatial frequency threshold corresponding to 80% contrast gratings (SF threshold at 80% ctr), and CSF acuity were calculated from CSF test. In addition, sVEP amplitudes and thresholds were calculated with the recursive least square method. Participants with astigmatism exhibited marked vertical-horizontal resolution disparities even after they were corrected with optimal optical corrections. CSF tests showed that AULCSF along weak meridian (measured with horizontal gratings) was lower than that along strong meridian (measured with vertical gratings) in both groups. Significant meridional disparity of CSF acuity was also found in both groups. In addition, the MA group showed larger meridional disparity compared to the AST group. Spatial sVEP thresholds also supported the existence of marked meridional disparity. Our results suggest that meridian-specific partial deprivation in early life might lead to monocularly asymmetric development of spatial vision in the human visual system. In terms of application, we tested the feasibility and reliability of adopting psychophysical and EEG scalings to investigate the asymmetric development of spatial vision related to astigmatism. These paradigms are potentially applicable to reduce and even eliminate the meridional disparity in the primary visual cortex by adopting perceptual learning or other vision-related interventions.
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http://dx.doi.org/10.3389/fpsyg.2021.595536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010696PMC
March 2021

A Study on Traditional Teaching Method Transferring to E-Learning Under the Covid-19 Pandemic: From Chinese Students' Perspectives.

Front Psychol 2021 11;12:632787. Epub 2021 Mar 11.

Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung City, Taiwan.

In response to the Covid-19 pandemic, online learning has been carried out in many countries with different types of online learning models being promoted and implemented. In the global pandemic continues, the education environment is forced to change from traditional classroom or blended teaching mode to online learning teaching model. With the outbreak of COVID-19, China was the first to announce that online courses are to be implemented in February 2020. In China, whether online learning can replace traditional offline teaching has become a topic worth discussing. Therefore, this study investigates university students in China by questionnaires and discussions of this topic. The study is based on the Push-Pull Mooring model. Based on 854 valid responses collected from an online survey questionnaire, structural equation modeling was employed to examine the research model. The results show that push effects (Perceived security risk, Learning convenience, and Service quality), pull effects (Usefulness, Ease of use, Teacher's Teaching Attitude, Task-technology Fit), and mooring effects (habit) all significantly influence users' switching intentions from offline to online learning platform. Finally, this study explores whether push-pull-mooring can be a reference for promoting and implementing online learning courses in Chinese colleges and universities in the future after the pandemic.
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http://dx.doi.org/10.3389/fpsyg.2021.632787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991594PMC
March 2021

SIRT6‑specific inhibitor OSS‑128167 exacerbates diabetic cardiomyopathy by aggravating inflammation and oxidative stress.

Mol Med Rep 2021 05 24;23(5). Epub 2021 Mar 24.

Department of Pain Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes, which importantly contributes to the increased mortality of patients with diabetes. The development of DCM is accompanied by numerous pathological mechanisms, including oxidative stress and chronic inflammation. Accordingly, the present study aimed to determine the effects of the sirtuin 6 (SIRT6) inhibitor OSS‑128167 on DCM using a mouse model of streptozotocin (STZ)‑induced diabetes and high glucose (HG)‑treated cardiomyocytes. C57BL/6 mice were intraperitoneally injected with STZ for 5 days to simulate the diabetic cardiomyopathy model. Mice with STZ‑induced diabetes (STZ‑DM1) were orally administered OSS‑128167 (20 or 50 mg/kg) through gavage every other day. The expression of SIRT6 in myocardial tissue was detected using western blotting. Tissue staining (hematoxylin and eosin and Masson's trichrome) was used to characterize myocardial structure, TUNEL fluorescent staining was used to detect myocardial apoptosis, and immunohistochemical staining was used to detect the expression of inflammatory factors in myocardial tissue. Dihydroethidium staining and a malondialdehyde (MDA) detection kit were used to detect the oxidative stress levels in myocardial tissues. , H9c2 cells were pre‑incubated with OSS‑128167 for 1 h and then stimulated with HG (33 mM) for various durations. Expression levels of fibrosis markers, collagen‑1 and transforming growth factor (TGF)‑β, apoptosis‑related proteins, Bax, Bcl‑2 and cleaved‑poly ADP‑ribose polymerase, tumor necrosis factor‑α and the oxidative stress metabolite, 3‑nitrotyrosine were analyzed using western blotting and reverse transcription‑quantitative PCR. Commercially available kits were used to detect the activity of caspase‑3 and the content of MDA in the H9c2 cell line. The corresponding results demonstrated that OSS‑128167 aggravated diabetes‑induced cardiomyocyte apoptosis and fibrosis in mice. Mechanistically, OSS‑128167 was revealed to increase the levels of inflammatory factors and reactive oxygen species (ROS) and . In conclusion, OSS‑128167 facilitated the inflammatory response and promoted the production of ROS while aggravating DCM development. These findings indicated that SIRT6 may target two closely combined and interacting pathological processes, the inflammatory response and oxidative stress, and may serve as a potentially advantageous therapeutic target.
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http://dx.doi.org/10.3892/mmr.2021.12006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986000PMC
May 2021

Blood lead levels of Chinese children from 1991 to 2020: Based on Monte Carlo simulation.

Environ Pollut 2021 Jun 8;278:116823. Epub 2021 Mar 8.

School of Public Health, Qingdao University, Qingdao, China. Electronic address:

Chinese children have been exposed to high level of lead due to polluted air, dust, contaminated foods and water, etc. In this research, we investigated published blood lead levels (BLLs) reflecting 1,057,832 Chinese children aged at 0-12 and teenagers aged at 13-18 in the past 30 years (1991-2020). The data mining and estimation were performed innovatively by Monte Carlo simulation to remedy the skewed distribution-induced bias. The temporal trend of Chinese children's BLLs showed an obvious decrease in the past decades from 88.74 μg/L (Geometric SD = 4.09) during 1991-1995 to 27.32 μg/L (Geometric SD = 4.18) during 2016-2020. This study also indicated that children's BLLs of Yunnan, Guizhou, Shanxi were at relatively high levels and most provinces showed a downward trend. Chinese boys aged at 1-18 years old had higher BLLs (GM: 44.03 μg/L) compared to girls (GM: 41.32 μg/L) (p < 0.001). At different age groups, Chinese children's BLLs were 42.04 μg/L (1-3 years old), 52.88 μg/L (4-6 years old), 50.49 μg/L (7 and above years old), respectively. Although the BLLs of Chinese children exhibited a continuous declined trend in the past 30 years, it was still higher than that in developed countries, which indicated that more efforts are needed in children's BLLs control.
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http://dx.doi.org/10.1016/j.envpol.2021.116823DOI Listing
June 2021

Bulbar Conjunctival Microvascular Alterations in Thyroid-Associated Ophthalmopathy Patients with Different Activities.

Curr Eye Res 2021 Jul 15;46(7):943-948. Epub 2021 Mar 15.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

: To evaluate the morphologic and hemodynamic changes of bulbar conjunctival vessels in thyroid-associated ophthalmopathy (TAO) patients and the correlations with the activity.: Patients diagnosed as TAO with different clinical activity scores (CAS) and healthy participants were recruited. All subjects underwent a complete ophthalmic examination and functional slit-lamp biomicroscope. Vascular variables including the vessel density, vessel complexity, average diameter, blood flow velocity and blood flow rate in microvascular networks were measured. The correlations among microvascular parameters, CAS and exophthalmos were analyzed. Areas under the receiver operating characteristic curves (AUROCs) were applied to evaluate the diagnostic accuracy of microvascular alterations for active TAO.: A total of 46 eyes were enrolled in our study. The vessel complexity and blood flow velocity increased in the active TAO group significantly compared with the inactive group and healthy controls ( < .05). Meanwhile, the vessel complexity and blood flow rate were positively correlated with CAS (r = 0.641 and r = 0.526). Bulbar conjunctival microvascular parameters performed a good ability in distinguishing the active stage of TAO (AUROC = 0.793).: Increasing bulbar conjunctival vessel complexity and blood flow were evident in TAO with severe inflammation. The measurements of bulbar conjunctival microvasculature could be a reference to evaluate activity in TAO.
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http://dx.doi.org/10.1080/02713683.2020.1849729DOI Listing
July 2021

Genetic disruption of the small GTPase RAC1 prevents plexiform neurofibroma formation in mice with neurofibromatosis type 17.

J Biol Chem 2020 07 12;295(29):9948-9958. Epub 2020 Nov 12.

Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address:

Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome caused by mutations in the NF1 tumor suppressor gene. NF1 encodes neurofibromin, a GTPase-activating protein for RAS proto-oncogene GTPase (RAS). Plexiform neurofibromas are a hallmark of NF1 and result from loss of heterozygosity of NF1 in Schwann cells, leading to constitutively activated p21RAS. Given the inability to target p21RAS directly, here we performed an shRNA library screen of all human kinases and Rho-GTPases in a patient-derived NF1 Schwann cell line to identify novel therapeutic targets to disrupt PN formation and progression. Rho family members, including Rac family small GTPase 1 (RAC1), were identified as candidates. Corroborating these findings, we observed that shRNA-mediated knockdown of RAC1 reduces cell proliferation and phosphorylation of extracellular signal-regulated kinase (ERK) in NF1 Schwann cells. Genetically engineered Nf1;PostnCre mice, which develop multiple PNs, also exhibited increased RAC1-GTP and phospho-ERK levels compared with Nf1;PostnCre littermates. Notably, mice in which both Nf1 and Rac1 loci were disrupted (Nf1Rac1;PostnCre) were completely free of tumors and had normal phospho-ERK activity compared with Nf1;PostnCre mice. We conclude that the RAC1-GTPase is a key downstream node of RAS and that genetic disruption of the Rac1 allele completely prevents PN tumor formation in vivo in mice.
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http://dx.doi.org/10.1074/jbc.RA119.010981DOI Listing
July 2020