Publications by authors named "Jing Yao"

382 Publications

CRISPR/Cas13d mediated efficient KDM5B mRNA knockdown in porcine cells and parthenogenetic embryos.

Reproduction 2021 Jun 1. Epub 2021 Jun 1.

J Zhao, School of Life Sciences, University of Science and Technology of China, Hefei, China.

An efficient mRNA knockdown strategy is needed to explore gene function in cells and embryos, especially to understand the process of maternal mRNA decay during early embryo development. Cas13, a novel RNA-targeting CRISPR effector protein, could bind and cleave complementary single-strand RNA, which has been employed for mRNA knockdown in mouse and human cells and RNA-virus interference in plants. Cas13 has not yet been reported to be used in pigs. In the current study, we explored the feasibility of CRISPR/Cas13d-mediated endogenous RNA knockdown in pigs. KDM5B, a histone demethylase of H3K4me3, was down-regulated at the transcriptional level by 50% with CRISPR/Cas13d in porcine fibroblast cells. Knockdown of KDM5B induced H3K4me3 expression and decreased the abundance of H3K27me3, H3K9me3, H3K4ac, H4K8ac, and H4K12ac. These changes affected cell proliferation and cell cycle. Furthermore, stable integration of the CRISPR/Cas13d system into the porcine genome resulted in the continuous expression of Cas13d and persistent knockdown of KDM5B. Finally, the RNA-targeting potential of Cas13d was further validated in porcine parthenogenetic embryos. By micro-injection of Cas13d mRNA and gRNA targeting KDM5B into porcine oocytes, the expression of KDM5B was down-regulated, the abundance of H3K4me3 increased as expected, and the expression of embryonic development-related genes was changed accordingly. These results indicate that CRISPR/Cas13d provides an easily programmable platform for spatiotemporal transcriptional manipulation in pigs.
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http://dx.doi.org/10.1530/REP-21-0053DOI Listing
June 2021

CRISPR/Cas9-mediated correction of homozygous point mutation in a Waardenburg syndrome 2A pig model.

Mol Ther Nucleic Acids 2021 Jun 16;24:986-999. Epub 2021 Apr 16.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Gene therapy for curing congenital human diseases is promising, but the feasibility and safety need to be further evaluated. In this study, based on a pig model that carries the c.740T>C (L247S) mutation in with an inheritance pattern and clinical pathology that mimics Waardenburg syndrome 2A (WS2A), we corrected the point mutation by the CRISPR-Cas9 system in the mutant fibroblast cells using single-stranded oligodeoxynucleotide (ssODN) and long donor plasmid DNA as the repair template. By using long donor DNA, precise correction of this point mutation was achieved. The corrected cells were then used as the donor cell for somatic cell nuclear transfer (SCNT) to produce piglets, which exhibited a successfully rescued phenotype of WS2A, including anophthalmia and hearing loss. Furthermore, engineered base editors (BEs) were exploited to make the correction in mutant porcine fibroblast cells and early embryos. The correction efficiency was greatly improved, whereas substantial off-targeting mutations were detected, raising a safety concern for their potential applications in gene therapy. Thus, we explored the possibility of precise correction of WS2A-causing gene mutation by the CRISPR-Cas9 system in a large-animal model, suggesting great prospects for its future applications in treating human genetic diseases.
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http://dx.doi.org/10.1016/j.omtn.2021.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141604PMC
June 2021

Prognostic Value of Baseline d-Dimer Level in Patients With Coronary Artery Disease: A Meta-Analysis.

Angiology 2021 Jun 3:33197211019805. Epub 2021 Jun 3.

Coronary Heart Disease Center, Fuwai Hospital, National Center for Cardiovascular Diseases, 34736Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

The prognostic significance of d-dimer level in patients with coronary artery disease (CAD) is not fully established. This meta-analysis aimed to examine the association between elevated d-dimer level at baseline and adverse outcomes in patients with CAD. Two independent authors comprehensively searched PubMed and Embase databases from their inception to December 31, 2020. All observational studies reporting the values of baseline d-dimer level in predicting the major adverse cardiovascular events (MACEs) or survival outcomes in patients with CAD were included. The prognostic values were calculated by pooling adjusted RR with 95% CI for the highest versus the lowest d-dimer level. Thirteen studies consisting of 25 600 patients with CAD were identified. Comparison between the highest and lowest d-dimer level showed that the pooled multivariable adjusted RR was 1.69 (95% CI, 1.53-1.86) for all-cause mortality, 2.37 (95% CI, 1.52-3.69) for cardiovascular mortality, and 1.44 (95% CI, 1.19-1.74) for MACEs, respectively. Elevated blood level of d-dimer at baseline was independently associated with higher risk of MACEs, cardiovascular death, and all-cause mortality in patients with CAD. The baseline d-dimer level may have important prognostic value in patients with CAD.
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http://dx.doi.org/10.1177/00033197211019805DOI Listing
June 2021

Endmember-Guided Unmixing Network (EGU-Net): A General Deep Learning Framework for Self-Supervised Hyperspectral Unmixing.

IEEE Trans Neural Netw Learn Syst 2021 May 28;PP. Epub 2021 May 28.

Over the past decades, enormous efforts have been made to improve the performance of linear or nonlinear mixing models for hyperspectral unmixing (HU), yet their ability to simultaneously generalize various spectral variabilities (SVs) and extract physically meaningful endmembers still remains limited due to the poor ability in data fitting and reconstruction and the sensitivity to various SVs. Inspired by the powerful learning ability of deep learning (DL), we attempt to develop a general DL approach for HU, by fully considering the properties of endmembers extracted from the hyperspectral imagery, called endmember-guided unmixing network (EGU-Net). Beyond the alone autoencoder-like architecture, EGU-Net is a two-stream Siamese deep network, which learns an additional network from the pure or nearly pure endmembers to correct the weights of another unmixing network by sharing network parameters and adding spectrally meaningful constraints (e.g., nonnegativity and sum-to-one) toward a more accurate and interpretable unmixing solution. Furthermore, the resulting general framework is not only limited to pixelwise spectral unmixing but also applicable to spatial information modeling with convolutional operators for spatial-spectral unmixing. Experimental results conducted on three different datasets with the ground truth of abundance maps corresponding to each material demonstrate the effectiveness and superiority of the EGU-Net over state-of-the-art unmixing algorithms. The codes will be available from the website: https://github.com/danfenghong/IEEE_TNNLS_EGU-Net.
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http://dx.doi.org/10.1109/TNNLS.2021.3082289DOI Listing
May 2021

Effects of dissolved oxygen on the sludge dewaterability and extracellular polymeric substances distribution by bioleaching.

Chemosphere 2021 May 17;281:130906. Epub 2021 May 17.

School of Environment, Henan Normal University, China.

Bioleaching is a biological conditioning technology for sludge, which not only improves sludge dewatering performance but also removes heavy metals from sludge. As the bioleaching process is a comprehensive biological and chemical process, it is necessary to explore the effects of dissolved oxygen (DO) concentrations on bioleaching efficiency. Three bioleaching experiments with different DO concentrations (T1: 0.8-3.1 mg/L, T2: 3.1-5.5 mg/L, T3: 5.5-7.5 mg/L) were conducted for five days. The sludge dewatering efficiency was evaluated using capillary suction time (CST) and specific resistance to filtration (SRF). The relationship between sludge dewaterability and extracellular polymeric substance (EPS) fraction distribution was investigated. In the treatment with the highest DO concentration, the minimum values of SRF and CST were 4.31 × 10 m/kg and 13.5 s, which occurred earlier than the treatment with the lower DO concentrations by approximately 24-48 h. A significant decrease (83.4-93.2%) in tightly bound EPS (TB-EPS) protein (PN) was observed in all treatments, while a positive correlation (r = 0.924, P < 0.01) was observed between SRF and PN content in TB-EPS. A relatively higher abundance of Acidithiobacillus was found with the increase in DO concentration. Additionally, other genera including Metallibacterium, Alicyclobacillus, Acidibacter, Acidocella, and Luteococcus also played important roles in EPS biodegradation. These results revealed that increasing the DO concentration could improve sludge dewatering performance and heavy metal removal by enhancing bioleaching microbial activity, the degradation of PN in TB-EPS, and sludge floc fragmentation, but only if sufficient energy sources were provided.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130906DOI Listing
May 2021

Long non-coding RNA FEZF1-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma via targeting miR-107/Wnt/β-catenin axis.

Aging (Albany NY) 2021 05 23;13(10):13726-13738. Epub 2021 May 23.

Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Hepatocellular carcinoma (HCC) is a public health problem around the world, with the molecular mechanisms being still incompletely clear. This study was carried out to explore the role and mechanism of long-noncoding RNA (lncRNA) FEZF1-AS1 in HCC progression. RNA sequencing and quantitative real time polymerase chain reaction (qRT- PCR) were applied to identify differently expressed lncRNAs in HCC tissues and adjacent normal tissues. CCK8 assay was adopted to test cell proliferation and flow cytometry was taken to detect cell apoptosis. Wound healing assay and transwell experiment were performed to determine cell migration and invasion. To validate the function of lncRNA FEZF1-AS1 , tumor-burdened models were established. The results showed that lncRNA FEZF1-AS1 level was prominently enhanced in HCC tumor specimens and overexpression of FEZF1-AS1 promoted the proliferation, migration and invasion of HCC cells. In mechanism, overexpression of FEZF1-AS1 reduced the expression of miR-107 which inhibited the activation of Wnt/β-catenin signaling. Overexpression of β-catenin promoted cell proliferation, migration and invasion which were inhibited by FEZF1-AS1 downregulation. In conclusion, our study demonstrated that FEZF1-AS1 promoted HCC progression through activating Wnt/β-catenin signaling by targeting miR-107, which provided a novel target for the therapy of HCC.
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http://dx.doi.org/10.18632/aging.202960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202841PMC
May 2021

Impurity profiling of Compound Amino Acid Injection (6AA) using ion-pair high performance liquid chromatography coupled with corona-charged aerosol detection and high resolution mass spectrometry.

J Pharm Biomed Anal 2021 Jul 24;201:114099. Epub 2021 Apr 24.

Institute of Medicinal Biotechnology, Peking Union Medical College & Chinese Academy of Medical Sciences, No. 1, Tian Tan Xi Li, 100050, Beijing, PR China. Electronic address:

The complex industrial production process of amino acids (AAs) leads to the existence of a certain amount of impurities in Compound Amino Acid Injection (6AA). It is difficult to obtain its comprehensive and systematic impurity profile using conventional ultraviolet (UV) detectors due to lack of a suitable chromophore in the structures of AAs and their impurities. In our study, a universal ion-pair high performance liquid chromatography (HPLC) method combined with high resolution mass spectrometer (HRMS) and charged aerosol detection (CAD) was developed to identify and determine the content of impurities in Compound Amino Acid Injection (6AA), respectively. After optimizing the content of trifluoroacetic acid (TFA) and heptafluorobutyric acid (HFBA) in the mobile phase on a C18 AQ column, HPLC-CAD method was developed and nine unknown impurities were detected. These impurities were successfully identified using HPLC coupled with orbitrap mass spectrometry and confirmed with their reference substances. The CAD parameters setting was optimized to improve the sensitivity and linearity of the methods before the developed method was validated. The results of validation reflected that the limit of detection (LOD) was approximately 2 ng (corresponding to approximately 0.02 % of L-isoleucine in injection). Under the optimized power function value (PFV) of CAD, the linear range of each impurity was 1 ∼ 200 μg mL (the linear range of one of the impurities with higher content was 2 ∼ 400 μg mL) with coefficients of determination (R) greater than 0.998. The recovery rates for nine impurities were 93.37 % ∼ 110.23 %. This study made full use of the qualitative functions of HRMS and the versatility of CAD, revealing possible impurities in the 6AA injection, which could provide reference for the safety research of it.
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http://dx.doi.org/10.1016/j.jpba.2021.114099DOI Listing
July 2021

Efficient management strategy of COVID-19 patients based on cluster analysis and clinical decision tree classification.

Sci Rep 2021 05 5;11(1):9626. Epub 2021 May 5.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, National Clinical Research Center for Respiratory Diseases, Beijing, 100029, China.

Early classification and risk assessment for COVID-19 patients are critical for improving their terminal prognosis, and preventing the patients deteriorate into severe or critical situation. We performed a retrospective study on 222 COVID-19 patients in Wuhan treated between January 23rd and February 28th, 2020. A decision tree algorithm has been established including multiple factor logistic for cluster analyses that were performed to assess the predictive value of presumptive clinical diagnosis and features including characteristic signs and symptoms of COVID-19 patients. Therapeutic efficacy was evaluated by adopting Kaplan-Meier survival curve analysis and cox risk regression. The 222 patients were then clustered into two groups: cluster I (common type) and cluster II (high-risk type). High-risk cases can be judged from their clinical characteristics, including: age > 50 years, chest CT images with multiple ground glass or wetting shadows, etc. Based on the classification analysis and risk factor analysis, a decision tree algorithm and management flow chart were established, which can help well recognize individuals who needs hospitalization and improve the clinical prognosis of the COVID-19 patients. Our risk factor analysis and management process suggestions are useful for improving the overall clinical prognosis and optimize the utilization of public health resources during treatment of COVID-19 patients.
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http://dx.doi.org/10.1038/s41598-021-89187-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100107PMC
May 2021

Porcine and bovine aortic valve comparison for surgical optimization: A fluid-structure interaction modeling study.

Int J Cardiol 2021 07 28;334:88-95. Epub 2021 Apr 28.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Porcine aortic valve (PAV) and bovine aortic valve (BAV) are commonly used in aortic valve replacement (AVR) surgeries. A detailed comparison for their hemodynamic and structural stress/strain performances would help to better understand valve cardiac function and select valve type and size for AVR outcome optimizations.

Methods: Eight fluid-structure interaction models were constructed to compare hemodynamic and stress/strain behaviors of PAV and BAV with 4 sizes (19, 21, 23, and 25 mm). Blood flow velocity, systolic cross-valve pressure gradient (SCVPG), geometric orifice area (GOA), flow shear stresses (FSS), and stress/strain were obtained for comparison.

Results: Compared with PAV, BAV has better hemodynamic performance, with lower maximum flow velocity (7.17%) and pressure (9.82%), smaller pressure gradient (mean and peak SCVPG: 8.92% and 9.28%), larger GOA (9.56%) and lower FSS (6.61%). The averages of the mean and peak net pressure gradient values from 4 BAV models were 8.10% and 8.35% lower than that from PAV models. Larger valve sizes for both PAV and BAV had improved hemodynamic performance. Maximum flow velocity, pressure, mean SCVPG and maximum FSS from 25 mm BAV were 36.80%, 15.81%, 39.05% and 38.83% lower than those from 19 mm BAV. The GOA of PAV and BAV 25 mm Valve were 43.75% and 33.07% larger than 19 mm valves, respectively. BAV has lower stress on the leaflets than PAV.

Conclusions: BAV had better hemodynamic performance and lower leaflets stress than PAV. More patient studies are needed to validate our findings.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.051DOI Listing
July 2021

Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial.

Int Immunopharmacol 2021 Apr 21;97:107702. Epub 2021 Apr 21.

Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China; Department of Infectious Disease, Peking University International Hospital, Beijing, China. Electronic address:

Background: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients.

Methods: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample.

Results: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting.

Conclusion: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.
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http://dx.doi.org/10.1016/j.intimp.2021.107702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059985PMC
April 2021

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine.

Elife 2021 Apr 20;10. Epub 2021 Apr 20.

State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted syndrome in humans. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive therapeutics for skin inflammation.
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http://dx.doi.org/10.7554/eLife.68128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112869PMC
April 2021

Expert consensus of Chinese Association for the Study of Pain on the application of ozone therapy in pain medicine.

World J Clin Cases 2021 Mar;9(9):2037-2046

Department of Algology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

This consensus was compiled by first-line clinical experts in the field of pain medicine and was organized by the Chinese Association for the Study of Pain. To reach this consensus, we consulted a wide range of opinions and conducted in-depth discussions on the mechanism, indications, contraindications, operational specifications and adverse reactions of ozone iatrotechnique in the treatment of pain disorders. We also referred to related previous preclinical and clinical studies published in recent years worldwide. The purpose of this consensus is to standardize the rational application of ozone iatrotechnique in pain treatment, to improve its efficacy and safety and to reduce and prevent adverse reactions and complications in this process.
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http://dx.doi.org/10.12998/wjcc.v9.i9.2037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017497PMC
March 2021

The relationship between SARS-COV-2 RNA positive duration and the risk of recurrent positive.

Infect Dis Poverty 2021 Mar 31;10(1):45. Epub 2021 Mar 31.

Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.

Background: The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is challenging. However, there are fewer scientific dissertations about the risk of recurrent positive. The aim of this study was to explore the relationship between SARS-COV-2 RNA positive duration (SPD) and the risk of recurrent positive.

Methods: This case-control multi-center study enrolled participants from 8 Chinese hospital including 411 participants (recurrent positive 241). Using unadjusted and multivariate-adjusted logistic regression analyses, generalized additive model with a smooth curve fitting, we evaluated the associations between SPD and risk of recurrent positive. Besides, subgroup analyses were performed to explore the potential interactions.

Results: Among recurrent positive patients, there were 121 females (50.2%), median age was 50 years old [interquartile range (IQR): 38-63]. In non-adjusted model and adjusted model, SPD was associated with an increased risk of recurrent positive (fully-adjusted model: OR = 1.05, 95% CI: 1.02-1.08, P = 0.001); the curve fitting was not significant (P = 0.286). Comparing with SPD < 14 days, the risk of recurrent positive in SPD > 28 days was risen substantially (OR = 3.09, 95% CI: 1.44-6.63, P = 0.004). Interaction and stratified analyses showed greater effect estimates of SPD and risk of recurrent positive in the hypertension, low monocyte count and percentage patients (P for interaction = 0.008, 0.002, 0.036, respectively).

Conclusion: SPD was associated with a higher risk of recurrent positive and especially SPD > 28 day had a two-fold increase in the relative risk of re-positive as compared with SPD < 14 day. What's more, the risk may be higher among those with hypertension and lower monocyte count or percentage.
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http://dx.doi.org/10.1186/s40249-021-00831-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010778PMC
March 2021

One-step synthesis of reduced graphene oxide based ceric dioxide modified with cadmium sulfide (CeO/CdS/RGO) heterojunction with enhanced sunlight-driven photocatalytic activity.

J Colloid Interface Sci 2021 Jul 15;594:621-634. Epub 2021 Mar 15.

Key Laboratory of Advanced Catalytic Materials and Technology, Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, Changzhou University, Changzhou, Jiangsu Province 213164, China. Electronic address:

Heterojunction photocatalyst with efficient photocatalytic performance can remarkably promote the separation of photogenerated charge carriers. Herein, a ternary photocatalyst, reduced graphene oxide (RGO) based CeO modified with CdS (CeO/CdS/RGO), was synthesized by a simple one-step hydrothermal method as a bifunctional catalyst for both photodegradation and photoreduction. The ternary composite exhibited a 90.04% photodegradation efficiency to ciprofloxacin (CIP) under simulated sunlight irradiation for 2 h, much higher than CeO (54%). Moreover, CeO/CdS/RGO showed broad applicability to the photodegradation of organic pollutants, including norfloxacin (NFX), tetracycline (TC), methylene blue (MB), rhodamine B (RhB), methyl violet (MV), methyl orange (MO) and reactive blue BES (RB). Besides, CeO/CdS/RGO exhibited a 100.00% photoreduction efficiency to Cr(VI) within 60 min. The improvement of the photocatalytic performance is ascribed to the modification of CeO with CdS, which improves the separation efficiency of photogenerated carriers. Also, the modification with RGO inhibits the agglomeration of CeO, improves the adsorption capacity toward pollutants and provides another nanochannel to separate photogenerated electron-hole (e-h) pairs. Additionally, the photocatalytic mechanism of CeO/CdS/RGO is explored. It is expected that this work would provide a promising way to construct efficient and versatile RGO-based photocatalysts applied to environmental remediation.
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http://dx.doi.org/10.1016/j.jcis.2021.03.034DOI Listing
July 2021

Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis.

J Inflamm Res 2021 12;14:843-858. Epub 2021 Mar 12.

Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei, 230032, People's Republic of China.

Purpose: The severity of rheumatoid arthritis (RA) in women is generally lower than that in men. RA is mediated, at least in part, by the protective effects of estradiol. However, the mechanisms underlying the protective effect of estradiol on RA are still unclear. Recent studies have demonstrated that activation of acid-sensing ion channel 1a (ASIC1a) by tissue acidosis plays an important role in the injury of cartilage in RA. Here, we assessed the effects of estradiol on acid-mediated cartilage injury both in vitro and in vivo and explored the involvement of ASIC1a in RA and its underlying mechanism.

Methods: Cultured primary articular chondrocytes were subjected to acidosis-mediated injury in vitro. Beclin1, LC3, p62, GPER1, and ASIC1a expression was detected through Western blotting, quantitative real-time PCR, and immunofluorescence analysis. Adjuvant arthritis (AA) was induced in rats through intradermal immunization by injecting 0.25 mL heat-killed mycobacteria (10 mg/mL) suspended in complete Freund's adjuvant into the left hind metatarsal footpad. The levels of estrogen and related inflammatory factors in the serum were measured using enzyme-linked immunosorbent assay. The expression of ASIC1a and autophagy-related proteins was detected through immunohistochemical analysis and Western blot.

Results: Treatment of primary articular chondrocytes with estradiol decreased the expression of ASIC1a and autophagy level. The symptoms of cartilage damage and levels of inflammatory cytokines in the serum were reduced after estradiol treatment in the rats with AA. In addition, estradiol treatment reduced ASIC1a expression via the PI3K-AKT-mTOR pathway, among which G-protein coupled estradiol receptor 1 (GPER1) plays a regulatory role. Finally, the level of autophagy in chondrocytes was decreased by the selective ASIC1a blocker psalmotoxin-1 (PCTX-1).

Conclusion: Estradiol can protect the cartilage of rats with AA against acidosis-mediated damage and autophagy by suppressing ASIC1a expression through GPER1.
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http://dx.doi.org/10.2147/JIR.S295222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966409PMC
March 2021

Refining the concept of hydrological connectivity for large floodplain systems: Framework and implications for eco-environmental assessments.

Water Res 2021 May 3;195:117005. Epub 2021 Mar 3.

Key Laboratory of Watershed Geographic Sciences, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Postal address: 73 East Beijing Road, Nanjing, 210008, China. Electronic address:

Recent years, the hydrological connectivity has gained popularity in various research fields, however, its definition and threshold effects at a system scale have not received adequate attention. The current research proposes a promising framework to refine the concept of surface hydrological connectivity by combining hydrodynamic modeling experiments, threshold effects and geostatistical connectivity analysis, exemplified by the flood-pulse-influenced Poyang Lake floodplain system (China). To enhance the inherent linkage between hydrological connectivity and eco-environments, total connectivity (TC), general connectivity (GC), and effective connectivity (EC) were proposed to refine the metrics of hydrological connectivity. The results show that substantial differences between the three connectivity metrics are observed for all target directions, demonstrating that the joint role of water depth and flow velocity may produce more dynamic and complex influences on EC than the other two metrics of TC and GC. Topographically, the connectivity objects/areas within the flood pulse system reveal that the floodplain is a more sensitive area than the lake's main flow channels under different connectivity conditions. The modelling experimental studies show that variations in water depth thresholds are more likely to have a strong effect on connectivity for the dry, rising, and falling limbs, rather than the flooding period, while the flow velocity may exert an opposite threshold effect. The lake-floodplain system is characterized by a dynamic threshold behavior, with seasonally varying water depth and velocity thresholds. This study highlights the importance of redefined connectivity concept for facilitating scientific communication by combining hydrodynamic thresholds and offering recommendations for future connectivity assessments using our proposed metrics of TC, GC, and EC.
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http://dx.doi.org/10.1016/j.watres.2021.117005DOI Listing
May 2021

A Multiepitope Peptide, rOmp22, Encapsulated in Chitosan-PLGA Nanoparticles as a Candidate Vaccine Against Infection.

Int J Nanomedicine 2021 4;16:1819-1836. Epub 2021 Mar 4.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Background: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) () infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice.

Methods: The B-cell and T-cell epitopes of Omp22 from were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice.

Results: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22.

Conclusion: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing infection.
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http://dx.doi.org/10.2147/IJN.S296527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942956PMC
March 2021

Self-assembled nano-activator constructed ferroptosis-immunotherapy through hijacking endogenous iron to intracellular positive feedback loop.

J Control Release 2021 Apr 6;332:539-552. Epub 2021 Mar 6.

State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. Electronic address:

Ferroptosis had shown huge potential for antitumor treatment due to its capacity of improving the limited efficiency of traditional antitumor strategies. On the other hand, low confidence in clinical application prospects impeded their development as a result of use of toxic-dose iron. Herein, we prepared a nano-activator (DAR) which was assembled by doxorubicin (DOX), tannic-acid (TA) and IR820 as a photosensitizer to make full use of endogenous iron stored in endo-lysosome, realizing ferroptosis and its related oxidative stress through artificially intracellular positive feedback loop. Interestingly, this process could also promote immunogenic cell death (ICD)-associated immunotherapy through endoplasmic reticulum (ER) stress. After DAR + laser treatment, the intracellular oxidative stress response was intensified. The produced ROS could be effectively distributed in intracellular lysosomes and ERs to facilitate ferroptosis and immunotherapy respectively. The pharmacodynamics study revealed that DAR + laser had excellent antitumor combination therapy efficiency even under the adverse combined drug ratio of DOX and IR820 due to the unique synergism activation effect of DAR mediated ferroptosis-immunotherapy. In summary, our study provided an innovative solution for the development of antitumor treatment based on ferroptosis-immunotherapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.03.007DOI Listing
April 2021

Flotillin-1 Interacts With and Sustains the Surface Levels of TRPV2 Channel.

Front Cell Dev Biol 2021 9;9:634160. Epub 2021 Feb 9.

State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

Transient receptor potential vanilloid subtype 2 (TRPV2) channel is a polymodal receptor regulating neuronal development, cardiac function, immunity and oncogenesis. The activity of TRPV2 is regulated by the molecular interactions in the subplasmalemmel signaling complex. Here by yeast two-hybrid screening of a cDNA library of mouse dorsal root ganglia (DRG) and patch clamp electrophysiology, we identified that flotillin-1, the lipid raft-associated protein, interacts with TRPV2 channel and regulates its function. The interaction between TRPV2 and flotillin-1 was validated through co-immuoprecipitation using endogenous DRG neurons and the recombinant expression model in HEK 293T cells. Fluorescent imaging and bimolecular fluorescence complementation (BiFC) further revealed that flotillin-1 and TRPV2 formed a functional complex on the cell membrane. The presence of flotillin-1 enhanced the whole-cell current density of TRPV2 via increasing its surface expression levels. Using site-specific mapping, we also uncovered that the SPFH (stomatin, prohibitin, flotillin, and HflK/C) domain of flotillin-1 interacted with TRPV2 N-termini and transmembrane domains 1-4, respectively. Our findings therefore demonstrate that flotillin-1 is a key element in TRPV2 signaling complex and modulates its cellular response.
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http://dx.doi.org/10.3389/fcell.2021.634160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900159PMC
February 2021

Outcomes of modified vertical rectus belly transposition versus augmented superior rectus transposition for chronic abducens nerve palsy.

J AAPOS 2021 02 20;25(1):7.e1-7.e6. Epub 2021 Feb 20.

Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical School, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia, Fudan University, Shanghai, China; Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. Electronic address:

Purpose: To compare the surgical outcomes of modified vertical rectus belly transposition (mVRBT) and medial rectus recession (MRc) versus augmented superior rectus transposition (aSRT) and MRc in Chinese patients with chronic abducens nerve palsy.

Methods: The medical records of patients with chronic abducens nerve palsy who underwent mVRBT/MRc or aSRT/MRc were retrospectively reviewed. Pre- and postoperative deviation in primary position, pre- and postoperative abduction limitation, and complications were recorded. Follow-up was at least 6 months.

Results: A total of 26 patients (mean age, 37.9 ± 19.6 years; 16 males [62%]) were included. Fourteen patients underwent mVRBT/MRc (mVRBT group) and 12 underwent aSRT/MRc (aSRT group). Both groups had similar amounts of recession (t = 0.27; P = 0.79). After surgery, statistically significant changes of abduction limitation and esotropia were observed (both P < 0.05). However, the difference in abduction improvement between groups was not statistically significant (mVRBT vs aSRT, 2.3 ± 0.91 vs 2.3 ± 0.97; t = 0.10, P = 0.92). Of the 19 patients who underwent unilateral surgery, preoperative esotropia was similar in both groups (t = 1.3; P = 0.21), but more esotropia was corrected in the mVRBT group than in the aSRT group (mVRBT vs aSRT, 57.8 ± 14.3 vs 44.6 ± 9.8; t = 2.1; P = 0.047). There was no symptomatic vertical or torsional deviation.

Conclusions: In our patient cohort, mVRBT/MRc showed a better effect in correcting esotropia and a similar effect in improving abduction limitation compared with aSRT/MRc.
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http://dx.doi.org/10.1016/j.jaapos.2020.09.010DOI Listing
February 2021

Highly efficient Ti self-doped TiO co-modified with carbon dots and palladium nanocomposites for disinfection of bacterial and fungi.

J Hazard Mater 2021 07 4;413:125318. Epub 2021 Feb 4.

School of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002, China. Electronic address:

High efficiency photocatalysts capable of disinfecting a broad-spectrum microorganisms are needed for the practical application of photodisinfection technology. Herein, we synthesized a highly efficient photodisinfection catalyst composed of Ti self-doped TiO decorated with carbon dots (CDs) and palladium nano-photocatalyst, designated as Pd/CDs/Ti-TiO, via a facile hydrothermal-calcination approach. XPS and ESR analyses were performed to verify that the composite contained Ti, while TEM imaging and FTIR confirmed that the samples contained CDs. The as synthesized photocatalysts, particularly the 1% Pd/CDs/Ti-TiO sample, exhibited superior photocatalyzed antibacterial activity to pure TiO against E. coli (~6.5 orders of magnitude increase at 30 min). The 1% Pd/CDs/Ti-TiO photocatalyst also exhibited efficient photodisinfection of five pathogenic agricultural fungi. The dark cytotoxicity of the 1% Pd/CDs/Ti-TiO nanocomposites was evaluated on HepG2 and Chinese hamster lung (V) cells via Cell Counting Kit-8 (CCK-8) and found to be minimal. Lastly, the recycling capacity for the photodisinfective activity of the nanocomposites was evaluated and found to be unchanged after five cycles. Four active species were identified as contributing to the photoinduced antimicrobial activity of the catalyst: h, •O, •OH, and e. Together, our results indicate that Pd/CDs/Ti-TiO nanocomposites have great potential in agricultural plant pathogen disinfection.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125318DOI Listing
July 2021

[Autofluorescence combined with spectral domain optical coherence tomography for diagnosis and follow-up of acute Vogt-Koyanagi-Harada disease].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Jan;41(1):135-140

Department of Ophthalmology, Second Affiliated Hospital of Xi' an Jiaotong University, Xi'an 710000, China.

Objective: To evaluate the value of fundus autofluorescence (FAF) imaging combined with spectral domain optical coherence tomography (SD-OCT) in diagnosis, prognostic assessment and follow-up observation of acute Vogt-KoyanagiHarada (VKH) disease.

Methods: Clinical data were collected from 12 patients (23 eyes) with acute VKH disease treated in our hospital from May, 2018 to November, 2019, including detailed medical history, best corrected visual acuity (BCVA), and results of slit lamp biomicroscopy, fundus photography, SD-OCT, fundus fluorescein angiography (FFA) and FAF imaging.SDOCT and FAF imaging were repeated after a course of treatment and in follow-up examination, and the results were compared with those at the time of admission.

Results: VKH disease involved both eyes in 11 patients (91.7%).Fundus photography showed optic disc edema in 16 eyes (69.6%), and multiple retinal neuroepithelial detachment was detected by SD-OCT in all the involved eyes (100%).IN all the eyes, FFA revealed small and dense fluorescein leakage in the early stage and fluorescein accumulation in advanced stages of VHK disease to form multiple dye pooling in the areas of serous detachment.Hyperauto fluorescence was a common finding in FAF imaging (100%), and the area involved was consistent with that of fluorescein accumulation shown by FAF imaging.Ten eyes (43.5%) showed patches of relative hypoautofluorescence in the hyperauto fl uorescence areas, and granular hyperauto fl uorescence was found in the lesions in 4 eyes (17.4%).During the remission period of VKH disease, FAF imaging showed normal finding in 8 eyes (34.8%) and reduced areas (by 55.2%) and intensity (by 46.5%) of hyperautofluorescence in 9 eyes (39.1%).In 6 eyes (26.1%), only a few hyperautofluorescent spots scattered in the macula were observed.SD-OCT demonstrated significantly reduced (by 69.5% on average) or even disappearance of subretinal fluid in the eyes.The fluorescence intensity in FAF imaging showed a significant positive correlation with the volume of subretinal fluid detected by SD-OCT (=0.626, < 0.05).

Conclusions: The combination of fluorescein angiography, FAF imaging and SD-OCT can significantly improve the diagnostic accuracy of VKH disease.FAF imaging combined with SD-OCT provides an effective and noninvasive modality for evaluation of remission and monitoring the changes in VKH disease.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2021.01.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867480PMC
January 2021

Endovascular In Situ Fenestration Technique of Aortic Arch Pathology: A Systematic Review and Meta Analysis.

Ann Vasc Surg 2021 Jan 25. Epub 2021 Jan 25.

Department of Cardio-Vascular Surgery, Air Force Medical Center of People's Liberation Army, Beijing, China. Electronic address:

Objective: The aim of this study was to evaluate the safety, applicability and outcomes of the endovascular in situ fenestration (ISF) technique for patients with aortic arch pathologies by performing a systematic review.

Methods: We conducted a systematic search using the PubMed, Embase, and Cochrane databases to identify English language articles between January 2004 and March 2019 on the management of aortic arch pathologies using an in situ fenestration technique. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The studies included all investigated the clinical outcomes and postprocedural complications of using ISF techniques.

Results: Seven studies reported on a total of 117 aortic arch pathologies patients. Including fifty-two dissection patients, forty-seven aneurysm patients, eighteen intramural hematomas and penetrating ulcers patients. Needle fenestration and laser fenestration were performed in sixty-two and forty-five patients respectively, and the rest ten patients received radiofrequency fenestration. The follow-up period ranged from 1 to 55 months. The pooled technical success rates were 94% (95% confidence interval [CI]: 79-98%). The stroke rate was 6% (95% CI: 3-13%). The 30-day MAE was 11% (95% CI: 6-18%).

Conclusion: The results of the study showed that using the in-situ fenestration technique for treating patients with aortic arch pathologies produced encouraging mid-outcomes. Long-term outcomes remain undefined.
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http://dx.doi.org/10.1016/j.avsg.2020.12.021DOI Listing
January 2021

Impact of binocular visual field loss on driving performance in glaucoma patients.

Int J Ophthalmol 2021 18;14(1):112-119. Epub 2021 Jan 18.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.

Aim: To evaluate the driving performance in young and middle-aged Chinese glaucoma patients with mild to severe visual field loss compared to those without glaucoma by using a driving simulation test.

Methods: Twenty-nine participants were included in this study: nine patients with glaucoma but pass the binocular Esterman visual field test, ten patients with glaucoma and fail the binocular Esterman visual field test, and ten age-matched healthy controls. A driving simulation test was designed as a frequency-based analysis of a lane-keeping task. The total performance error, the control-response amplitude and delay were calculated.

Results: Esterman visual field test fail group showed the longest delay of control-response among three groups (=0.02). And the delay in lane-keeping task was significantly associated with inferior field of better-eye (=0.51, =0.004) and integrated visual field (=0.55, =0.002).

Conclusion: Young and middle-aged glaucoma patients with binocular visual field loss suffered from a longer delay of response in driving simulation test, while inferior visual field having more impact than superior visual field.
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http://dx.doi.org/10.18240/ijo.2021.01.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790684PMC
January 2021

The usefulness of contrast-enhanced echocardiography in the diagnosis and management of intramural hematoma and aortic dissection: A case report.

Echocardiography 2020 08 27;37(8):1304-1307. Epub 2020 Jul 27.

Department of Cardiovascular Surgery, Air Force Medical Center, Beijing, China.

Contrast-enhanced transthoracic echocardiography (cTTE) plays an important role in the diagnosis of intramural hematoma (IMH) and aortic dissection (AD), and is also necessary for the adequate management from the assessment of findings. We hereby present an interesting case in which cTTE provides additional value over contrast-enhanced computed tomography (CT) in the diagnosis and the morphological characterization of IMH and AD. A 58-year-old man presented to the emergency department with intermittent chest pain. After emergency consultation, an enhanced CT scan showed an acute aortic intramural hematoma involving aortic arch and descending aorta. Nevertheless, the entry tear and false lumen flow direction were identified by cTTE, which suggested an acute type B AD.
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http://dx.doi.org/10.1111/echo.14689DOI Listing
August 2020

Nanomedicines: Redefining traditional medicine.

Biomed Pharmacother 2021 Feb 15;134:111103. Epub 2020 Dec 15.

Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China. Electronic address:

Nanomedicines offer nanoscale drug delivery system. They offer ways of promising drug transportation, and address the issues of lack of targeting and permeability of traditional drugs. The physical and chemical properties in the domain of nanomedicine applications in vivo have not been sufficiently delivered. What's more, the metabolic of nanomedicines is not clear enough. Those factors which mentioned above determine that many nanomedicines have not yet realized clinical application due to their safety problems and in vivo efficacy. For example, they may cause immune response and cytotoxicity, as well as the ability to clear organs in vivo, the penetration ability of them and the lack of targeting ability may also cause poor efficacy of drugs in vivo. In this review, the new progresses of different kinds of nanomedicines (including gold nanoparticles, nanorobots, black phosphorus nanoparticles, brain diseases, gene editing and immunotherapy etc.) in anti-tumor, antibacterial, ocular diseases and arteriosclerosis in recent years were summarized. Their shortcomings were pointed out, and the new methods to improve the biosafety and efficacy were summarized.
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http://dx.doi.org/10.1016/j.biopha.2020.111103DOI Listing
February 2021

Cytosine Base Editor (hA3A-BE3-NG)-Mediated Multiple Gene Editing for Pyramid Breeding in Pigs.

Front Genet 2020 16;11:592623. Epub 2020 Nov 16.

State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Pig is an important agricultural economic animal, providing large amount of meat products. With the development of functional genomics and bioinformatics, lots of genes and functional single nucleotide polymorphisms (SNPs) related to disease resistance and (or) economic traits in pigs have been identified, which provides the targets for genetic improvement by genome editing. Base editors (BEs), combining Cas9 nickase and cytidine or adenine deaminase, achieve all four possible transition mutations (C-to-T, A-to-G, T-to-C, and G-to-A) efficiently and accurately without double strand breaks (DSBs) under the protospacer adjacent motif (PAM) sequence of NGG. However, the NGG PAM in canonical CRISPR-Cas9 can only cover approximately 8.27% in the whole genome which limits its broad application. In the current study, hA3A-BE3-NG system was constructed with the fusion of SpCas9-NG variant and hA3A-BE3 to create C-to-T conversion at NGN PAM sites efficiently. The editing efficiency and scope of hA3A-BE3-NG were confirmed in HEK293T cells and porcine fetal fibroblast (PFF) cells. Results showed that the efficiency of hA3A-BE3-NG was much higher than that of hA3A-BE3 on NGH (H = A, C, or T) PAM sites (21.27 vs. 2.81% at average). Further, nonsense and missense mutations were introduced efficiently and precisely hA3A-BE3-NG in multiple pig economic trait-related genes (, , , and ) in PFF cells by one transfection. The current work indicates the potential applications of hA3A-BE3-NG for pyramid breeding studies in livestock.
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http://dx.doi.org/10.3389/fgene.2020.592623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701296PMC
November 2020

Axial resolution improvement of two-photon microscopy by multi-frame reconstruction and adaptive optics.

Biomed Opt Express 2020 Nov 22;11(11):6634-6648. Epub 2020 Oct 22.

Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

Two-photon microscopy (TPM) has been widely used in biological imaging owing to its intrinsic optical sectioning and deep penetration abilities. However, the conventional TPM suffers from poor axial resolution, which makes it difficult to recognize some three-dimensional fine features. We present multi-frame reconstruction two-photon microscopy (MR-TPM) using a liquid lens as a fast axial scanning engine. A sensorless adaptive optics (AO) approach is adopted to correct the aberrations caused by both the liquid lens and the optical system. By overcoming the effect of optical aberrations, inadequate sampling, and poor focusing capability of a conventional TPM, the axial resolution can be improved by a factor of 3 with a high signal-to-noise ratio. The proposed technology is compatible with the conventional TPM and requires no optical post-processing. We demonstrate the proposed method by imaging fluorescent beads, imaging of the neural circuit of mouse brain slice, and time-lapse imaging of the morphological changes of microglial cells in septic mice model. The results suggest that the axon of the neural circuit and the process of microglia along the axial direction, which cannot be resolved using conventional TPM, become distinguishable using the proposed AO MR-TPM.
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http://dx.doi.org/10.1364/BOE.409651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687969PMC
November 2020