Publications by authors named "Lan Yu"

761 Publications

Research and Fabrication of Broadband Ring Flextensional Underwater Transducer.

Sensors (Basel) 2021 Feb 23;21(4). Epub 2021 Feb 23.

Acoustic Science and Technology Laboratory, Harbin Engineering University, Harbin 150001, China.

At present, high-speed underwater acoustic communication requires underwater transducers with the characteristics of low frequency and broadband. The low-frequency transducers also are expected to be low-frequency directional for realization of point-to-point communication. In order to achieve the above targets, this paper proposes a new type of flextensional transducer which is constructed of double mosaic piezoelectric ceramic rings and spherical cap metal shells. The transducer realizes broadband transmission by means of the coupling between radial vibration of the piezoelectric rings and high-order flexural vibration of the spherical cap metal shells. The low-frequency directional transmission of the transducer is realized by using excitation signals with different amplitude and phase on two mosaic piezoelectric rings. The relationship between transmitting voltage response (TVR), resonance frequency and structural parameters of the transducer is analyzed by finite element software COMSOL. The broadband performance of the transducer is also optimized. On this basis, the low-frequency directivity of the transducer is further analyzed and the ratio of the excitation signals of the two piezoelectric rings is obtained. Finally, a prototype of the broadband ring flextensional underwater transducer is fabricated according to the results of simulation. The electroacoustic performance of the transducer is tested in an anechoic water tank. Experimental results show that the maximum TVR of the transducer is 147.2 dB and the operation bandwidth is 1.5-4 kHz, which means that the transducer has good low-frequency, broadband transmission capability. Meanwhile, cardioid directivity is obtained at 1.4 kHz and low-frequency directivity is realized.
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http://dx.doi.org/10.3390/s21041548DOI Listing
February 2021

The quality of life in papillary thyroid microcarcinoma patients undergoing lobectomy or total thyroidectomy: A cross-sectional study.

Cancer Med 2021 Feb 26. Epub 2021 Feb 26.

Department of Ultrasound, General Hospital of Chinese PLA, Beijing, China.

Objective: Papillary thyroid microcarcinoma (PTMC) has a good prognosis and a long survival time, surgery is the common treatment including total thyroidectomy (TT) and unilateral lobectomy (LT), but recent studies showed that TT does not show an advantage over LT for PTMC in preventing cancer recurrence and reducing mortality. Given this, the health-related quality of life (HRQoL) has become one of the important factors that physicians must consider when making treatment decisions. The aim of this study was to compare the HRQoL of patients between undergoing TT and LT.

Methods: From October 2019 to December 2019, 69 PTMC patients were enrolled in our study, including 34 in the LT group and 35 in the TT group, respectively. We used three questionnaires which included the 36-item short-form health survey (SF-36), thyroid cancer-specific quality of life (THYCA-QOL), and Fear of Progression Questionnaire-Short Form (FoP-Q-SF) for each patient to evaluate their scores of HRQoL.

Results: According to the SF-36, the scores of the domain for the role limitation due to physical problems, emotional problems, and social function (RP, RE, and SF) as well as Physical Component Summary (PCS) and Mental Component Summary (MCS) showed a significant negative linear association between the LT group and TT group: RP (coefficient [coef]: -33.953 [confidence interval (CI) -51.187 to -16.720], p < 0.001, RE (coef: -21.633 [CI -39.500 to -3.766], p = 0.018), SF (coef: -10.169 [CI -19.586 to -0.752], p = 0.035)and PCS (coef: -10.571 [CI -17.768 to -3.373], p = 0.005), MCS (coef: -10.694 [CI -19.465 to -1.923], p = 0.018). The THYCA-QOL showed that the scores of the TT group were higher than that of the LT group in the problem of scar (coef: 16.245 [CI 1.697 to 30.794], p = 0.029 according to the multivariate analysis), suggesting a higher level of complaint in the TT group. There was no statistically significant difference in the scores of FoP-Q-SF between the two groups.

Conclusions: In patients with PTMC, LT offers an advantage over TT in terms of HRQoL, which supports the role of LT as an alternative strategy to TT.
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http://dx.doi.org/10.1002/cam4.3747DOI Listing
February 2021

Evaluation of Ultrasound-Guided Radiofrequency Ablation as a Treatment Option for Papillary Thyroid Microcarcinoma in the Isthmus: A Retrospective Study.

Front Endocrinol (Lausanne) 2020 9;11:599471. Epub 2021 Feb 9.

Department of Ultrasound, First Medical Center of General Hospital of Chinese PLA, Beijing, China.

Background: About 3-9.2% of papillary thyroid carcinomas (PTC) are found in the isthmus, which has unique anatomic properties, making treatment more challenging. The aim of this study was to evaluate the treatment and undesirable effects of ultrasound-guided radiofrequency ablation (RFA) for PTC in the isthmus.

Methods: This retrospective case series study assessed 112 patients with single papillary thyroid microcarcinoma in the isthmus, pathologically diagnosed before RFA at the General Hospital of Chinese PLA in 2014-2018. Follow-up was performed by contrast-enhanced ultrasound (CEUS) and ultrasound examinations at 1, 3, and 6 months and every 6 months thereafter. The complete ablation (CAR), disappearance (DR), and volume reduction (VRR) rates of nodules, the incidence of complications, and the rate of lymph-node metastasis were recorded.

Results: The CAR of the tumors was 100%. During follow-up, the volume of coagulation necrosis gradually decreased. DRs at 1, 3, 6, 12, and 18 months after RFA were 0.8% (1/112), 10.7% (12/112), 51.7% (58/112), 91.0% (102/112), and 100% (112/112), respectively. The VRR evaluated by ultrasound and CEUS gradually increased. One recurrent case (0.8%) was found at 7 months after RFA. No complications, lymph node metastasis confirmed by ultrasound, and abnormal thyroid function were observed.

Conclusions: This retrospective study shows that RFA is beneficial for the treatment of PTMC in the isthmus.
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http://dx.doi.org/10.3389/fendo.2020.599471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900160PMC
February 2021

Discovery of a Positron Emission Tomography Radiotracer Selectively Targeting the BD1 Bromodomains of BET Proteins.

ACS Med Chem Lett 2021 Feb 8;12(2):282-287. Epub 2021 Jan 8.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.

In this paper, we report the design, synthesis, and biological evaluation of the first selective bromodomain and extra-terminal domain (BET) BD1 bromodomains of the PET radiotracer [F]PB006. The standard compound PB006 showed high affinity and good selectivity toward BRD4 BD1 ( = 100 nM and 29-fold selectively for BD1 over BD2) in an binding assay. PET imaging experiments in rodents were performed to evaluate the bioactivity of [F]PB006 . A biodistribution study of [F]PB006 in mice revealed high radiotracer uptake in peripheral tissues, such as liver and kidney, and moderate radiotracer uptake in the brain. Further blocking studies demonstrated the significant radioactivity decreasing (20-30% reduction compared with baseline) by pretreating unlabeled PB006 and JQ1, suggesting the high binding selectivity and specificity of [F]PB006. Our study indicated that [F]PB006 is a potent PET probe selectively targeting BET BD1, and further structural optimization of the radiotracer is still required to improve brain uptake to support neuroepigenetic imaging.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883468PMC
February 2021

How Solvents Control the Chemoselectivity in Rh-Catalyzed Defluorinated [4 + 1] Annulation.

Org Lett 2021 Feb 10;23(4):1489-1494. Epub 2021 Feb 10.

School of Chemistry and Chemical Engineering, and Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University, Chongqing 400030, China.

Density functional theory calculations have been performed to reveal the chemoselectivity of Rh-catalyzed chiral C-F cleavage and γ-site functionalization. We found that the chemoselectivity is controlled by β-F elimination in methanol solvent, leading to formation of the alkynylic product. In isobutyronitrile solvent, the chemoselectivity is controlled by the allene insertion step, where the fluoroalkenylic product can be observed. The difference can be explained by analysis of the explicit solvent models.
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http://dx.doi.org/10.1021/acs.orglett.1c00223DOI Listing
February 2021

Degradation of 1,4-Dioxane by Xanthobacter sp. YN2.

Curr Microbiol 2021 Feb 6. Epub 2021 Feb 6.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, China.

1,4-Dioxane is a highly toxic and carcinogenic pollutant found worldwide in groundwater and soil environments. Several microorganisms have been isolated by their ability to grow on 1,4-dioxane; however, low 1,4-dioxane tolerance and slow degradation kinetics remain obstacles for their use in 1,4-dioxane bioremediation. We report here the isolation and characterization of a new strain, Xanthobacter sp. YN2, capable of highly efficient 1,4-dioxane degradation. High degradation efficiency and high tolerance to 1,4-dioxane make this new strain an ideal candidate for the biodegradation of 1,4-dioxane in various treatment facilities. The maximum degradation rate of 1,4-dioxane was found to be 1.10 mg-1,4-dioxane/h mg-protein. Furthermore, Xanthobacter sp. YN2 was shown to grow in the presence of higher than 3000 mg/L 1,4-dioxane with little to no degradation inhibition. In addition, Xanthobacter sp. YN2 could grow on and degrade 1,4-dioxane at pH ranges 5 to 8 and temperatures between 20 and 40 °C. Xanthobacter sp. YN2 was also found to be able to grow on a variety of other substrates including several analogs of 1,4-dioxane. Genome sequence analyses revealed the presence of two soluble di-iron monooxygenase (SDIMO) gene clusters, and regulation studies determined that all of the genes in these two clusters were upregulated in the presence of 1,4-dioxane. This study provides insights into the bacterial stress response and the highly efficient biodegradation of 1,4-dioxane as well as the identification of a novel Group-2 SDIMO.
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http://dx.doi.org/10.1007/s00284-021-02347-6DOI Listing
February 2021

Degradome sequencing-based identification of phasiRNAs biogenesis pathways in Oryza sativa.

BMC Genomics 2021 Jan 30;22(1):93. Epub 2021 Jan 30.

College of Life Sciences, Huzhou University, NO.1 Xueshi Road, Huzhou, 313000, P.R. China.

Background: The microRNAs(miRNA)-derived secondary phased small interfering RNAs (phasiRNAs) participate in post-transcriptional gene silencing and play important roles in various bio-processes in plants. In rice, two miRNAs, miR2118 and miR2275, were mainly responsible for triggering of 21-nt and 24-nt phasiRNAs biogenesis, respectively. However, relative fewer phasiRNA biogenesis pathways have been discovered in rice compared to other plant species, which limits the comprehensive understanding of phasiRNA biogenesis and the miRNA-derived regulatory network.

Results: In this study, we performed a systematical searching for phasiRNA biogenesis pathways in rice. As a result, five novel 21-nt phasiRNA biogenesis pathways and five novel 24-nt phasiRNA biogenesis pathways were identified. Further investigation of their regulatory function revealed that eleven novel phasiRNAs in 21-nt length recognized forty-one target genes. Most of these genes were involved in the growth and development of rice. In addition, five novel 24-nt phasiRNAs targeted to the promoter of an OsCKI1 gene and thereafter resulted in higher level of methylation in panicle, which implied their regulatory function in transcription of OsCKI1,which acted as a regulator of rice development.

Conclusions: These results substantially extended the information of phasiRNA biogenesis pathways and their regulatory function in rice.
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http://dx.doi.org/10.1186/s12864-021-07406-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847607PMC
January 2021

Lewis acid-catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides to access chiral azabicycles.

Sci Adv 2021 Jan 29;7(5). Epub 2021 Jan 29.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing, China.

[2,3]-Sigmatropic rearrangement of ammonium ylides represents a fundamental reaction for stereoselective synthesis of nitrogenous compounds. However, its applicability is limited by the scarcity of efficient, catalytic, and mild methods for generating ammonium ylides. Here, we report silver-catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides, furnishing chiral azabicycles with bridgehead quaternary stereogenic centers in high enantiomeric purity (up to 99% ). A combination of density functional theory calculations and experimental studies revealed that residual water in the reaction system is crucial for the mild reaction conditions by functioning as a proton shuttle to assist carbon-silver bond protonation and C2─H deprotonation to generate the ammonium ylide. This reaction has a broad application scope. Besides the diverse substituents, N-fused azabicycles of various ring sizes are also easily accessed. In addition to silver salts, this strategy has also been successfully implemented by using a stoichiometric amount of nonmetallic I.
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http://dx.doi.org/10.1126/sciadv.abd5290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846163PMC
January 2021

Aryne 1,2,3,5-Tetrasubstitution Enabled by 3-Silylaryne and Allyl Sulfoxide via an Aromatic 1,3-Silyl Migration.

J Am Chem Soc 2021 Feb 28;143(5):2178-2184. Epub 2021 Jan 28.

School of Chemistry and Chemical Engineering, Chongqing University, 174 Shazheng Street, Chongqing, P. R. China, 400030.

Although benzyne has been well-known to serve as a synthon that can conveniently prepare various 1,2-difunctionalized benzenes, the sites other than its formal triple bond remain silent in typical benzyne transformations. An unprecedented aryne 1,2,3,5-tetrasubstitution was realized from 3-silylbenzyne and aryl allyl sulfoxide, the mechanistic pathway of which includes a regioselective aryne insertion into the S═O bond, a [3,6]-sigmatropic rearrangement, and a thermal aromatic 1,3-silyl migration cascade.
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http://dx.doi.org/10.1021/jacs.0c11119DOI Listing
February 2021

Radiomics Analysis of MR Imaging with Gd-EOB-DTPA for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Investigation and Comparison of Different Hepatobiliary Phase Delay Times.

Biomed Res Int 2021 7;2021:6685723. Epub 2021 Jan 7.

Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Purpose: To investigate whether the radiomics analysis of MR imaging in the hepatobiliary phase (HBP) can be used to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).

Method: A total of 130 patients with HCC, including 80 MVI-positive patients and 50 MVI-negative patients, who underwent MR imaging with Gd-EOB-DTPA were enrolled. Least absolute shrinkage and selection operator (LASSO) regression was applied to select radiomics parameters derived from MR images obtained in the HBP 5 min, 10 min, and 15 min images. The selected features at each phase were adopted into support vector machine (SVM) classifiers to establish models. Multiple comparisons of the AUCs at each phase were performed by the Delong test. The decision curve analysis (DCA) was used to analyze the classification of MVI-positive and MVI-negative patients.

Results: The most predictive features between MVI-positive and MVI-negative patients included 9, 8, and 14 radiomics parameters on HBP 5 min, 10 min, and 15 min images, respectively. A model incorporating the selected features produced an AUC of 0.685, 0.718, and 0.795 on HBP 5 min, 10 min, and 15 min images, respectively. The predictive model for HBP 5 min, 10 min and 15 min showed no significant difference by the Delong test. DCA indicated that the predictive model for HBP 15 min outperformed the models for HBP 5 min and 10 min.

Conclusions: Radiomics parameters in the HBP can be used to predict MVI, with the HBP 15 min model having the best differential diagnosis ability.
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http://dx.doi.org/10.1155/2021/6685723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810556PMC
January 2021

CTCF-induced upregulation of LINC01207 promotes gastric cancer progression via miR-1301-3p/PODXL axis.

Dig Liver Dis 2021 Jan 22. Epub 2021 Jan 22.

Departments of Oncology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, 010017, China. Electronic address:

Background: Long non coding RNAs (lncRNAs) have been validated to be involved in the complicated biological processes during tumor progression. LINC01207 has been identified as an oncogene in several cancer types. However, the function of LINC01207 and its underlying molecular mechanism in gastric cancer (GC) are poorly understood.

Methods: The expression level of LINC01207, miR-1301-3p and PODXL mRNA was detected in GC tissues and cells by RT-qPCR. The level of PODXL protein was examined by western blot. Colony formation assay, EdU assay, TUNEL assay, caspase-3 activity test and transwell assays were carried out to analyze the effect of LINC01207 on GC cell proliferation, apoptosis, migration and invasion. The interaction between RNAs was confirmed by luciferase reporter assay, RNA pull-down assay and RIP assay.

Results: LINC01207 was expressed at high level in GC tissues and cells. Silencing of LINC01207 impaired GC cell proliferation, migration and invasion but promoted cell apoptosis. Mechanistically, LINC01207 acted as a ceRNA by sponging miR-1301-3p to upregulate PODXL. Besides, miR-1301-3p silencing or PODXL overexpression could abolish the inhibitory effect of LINC01207 knockdown on GC cell growth and migration. CCCTC-binding factor (CTCF) could transcriptionally activate LINC01207 in GC cells.

Conclusions: CTCF-induced activation of LINC01207 contributes to GC progression through regulating miR-1301-3p/PODXL axis.
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http://dx.doi.org/10.1016/j.dld.2020.12.006DOI Listing
January 2021

Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses.

Cell Res 2021 Jan 20. Epub 2021 Jan 20.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.

Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal-distal and anterior-posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.
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http://dx.doi.org/10.1038/s41422-021-00467-zDOI Listing
January 2021

T Cell Development: Old Tales Retold By Single-Cell RNA Sequencing.

Trends Immunol 2021 02 11;42(2):165-175. Epub 2021 Jan 11.

Department of Rheumatology and Immunology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China. Electronic address:

Mammalian T cell development initiates from the migration of hematopoietic progenitors to the thymus, which undergo cell proliferation, T-lineage specification and commitment, as well as positive and negative selection. These processes are precisely controlled at multiple levels and have been intensively studied using gene-modified animal models and in vitro coculture systems. However, several long-standing questions, including the characterization of the rare but crucial progenitors/precursors and the molecular mechanisms underlying their fate decision, have been dampened because of cell scarcity and lack of appropriate techniques. Single-cell RNA sequencing (scRNA-seq) makes it possible to investigate and resolve some of these questions, leading to new remarkable progress in identifying and characterizing early thymic progenitors and delineating the refined developmental trajectories of conventional and unconventional T cells.
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http://dx.doi.org/10.1016/j.it.2020.12.004DOI Listing
February 2021

[Short-term Outcome of T1bN0M0 Papillary Thyroid Cancer after Ultrasonography-guided Radiofrequency Ablation].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2020 Dec;42(6):771-775

School of Medicine,Nankai University,Tianjin 300071,China.

Objective To investigate the short-term outcome of T1bN0M0 papillary thyroid cancer after ultrasonography-guided radiofrequency ablation(RFA). Methods Eighty-nine patients with T1bN0M0 papillary thyroid cancer who were treated with ultrasonography-guided RFA in our center from April 2014 to January 2019 were retrospectively analyzed.Trans-isthmus approach and moving shot technique were used during the RFA procedure.Ultrasonography and contrast-enhanced ultrasonography were performed before ablation,and immediately,1,3,6 and 12 months after ablation and then every 6 months thereafter. Results RFA was performed in 89 cases of papillary thyroid cancer,and no major complications were observed during the RFA.The mean follow-up was(18.8±7.3)months.The ablation zones decreased gradually during follow-up,and 38 ablation zones(42.7%)completely disappeared.The volume reduction rate was(99.2±2.3)% 30 months after ablation.During follow-up,2 patients(2.2%)developed tumor recurrence and 1 patient(1.1%)developed cervical lymph node metastasis. Conclusion Ultrasonography-guided RFA may be a safe and effective method for patients with T1bN0M0 papillary thyroid cancer.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12731DOI Listing
December 2020

Butylphthalide enhances recovery from sudden deafness.

Am J Otolaryngol 2021 Mar-Apr;42(2):102891. Epub 2021 Jan 4.

Department of Otolaryngology Head and Neck Surgery, General Hospital of Southern Theater Command of PLA (Guangzhou Liuhuaqiao Hospital), Liuhua road 111, Guangzhou 510010, Guangdong, China.

Objectives: Cochlear microcirculation disturbance caused by vasculopathy is a common cause of sudden deafness (SD). Reactive oxygen species (ROS) plays an important role in cochlear injury during ischemia-reperfusion. Butylphthalide can improve microcirculation, reduce ROS formation and inhibit apoptosis. The aim of this study was to investigate the therapeutic effect of butylphthalide on patients with SD.

Patients And Methods: The hearing gains from 32 ears treated with butylphthalide were compared with that of 32 ears treated with non-butylphthalide. Butylphthalide capsules was administrated orally on an empty stomach for 10 continuous days. There were no significant differences in audiological and clinical data between butylphthalide and non-butylphthalide groups.

Results: The hearing gain of butylphthalide group at 500, 1000, 2000, and 4000 Hz was significantly higher than that of non-butylphthalide group correspondingly (P<0.01). And, the hearing gain at PTA (pure-tone average of 500, 1000, 2000, and 4000 Hz) in butylphthalide group was significantly higher than that of non-butylphthalide group (P<0.01).

Conclusion: The recovery of hearing in butylphthalide group was significantly better than that of non-butylphthalide group. It is confirmed that butylphthalide has a definite therapeutic effect on SD.
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http://dx.doi.org/10.1016/j.amjoto.2020.102891DOI Listing
January 2021

Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome.

Bioorg Med Chem Lett 2021 Feb 6;34:127777. Epub 2021 Jan 6.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States. Electronic address:

We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy substituent amenable to labeling with carbon-11. PET/CT imaging studies indicated that [C]1 exhibited rapid blood-brain barrier (BBB) penetration and moderate brain uptake, as well as blockable uptake in the brain. [C]1, thus suggesting the potential to serve as a useful tool for imaging NLRP3 inflammasome in living brains.
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http://dx.doi.org/10.1016/j.bmcl.2021.127777DOI Listing
February 2021

DNA-PKcs inhibition impairs HDAC6-mediated HSP90 chaperone function on Aurora A and enhances HDACs inhibitor-induced cell killing by increasing mitotic aberrant spindle assembly.

Cell Cycle 2021 Jan 6;20(2):211-224. Epub 2021 Jan 6.

Department of Radiation Oncology, Simmons Comprehensive Cancer Center at UT Southwestern Medical Center , Dallas, TX, USA.

Combining targeted therapeutic agents is an attractive cancer treatment strategy associated with high efficacy and low toxicity. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is an essential factor in DNA damage repair. Studies from us and others have revealed that DNA-PKcs also plays an important role in normal mitosis progression. Histone deacetylase (HDACs) inhibitors commonly lead to mitotic aberration and have been approved for treating various cancers in the clinic. We showed that DNA-PKcs depletion or kinase activity inhibition increases cancer cells' sensitivity to HDACs inhibitors and . DNA-PKcs deficiency significantly enhances HDACs inhibitors (HDACi)-induced mitotic arrest and is followed by apoptotic cell death. Mechanistically, we found that DNA-PKcs binds to HDAC6 and facilitates its acetylase activity. HDACi is more likely to impair HDAC6-induced deacetylation of HSP90 and abrogate HSP90's chaperone function on Aurora A, a critical mitotic kinase that regulates centrosome separation and mitotic spindle assembly in DNA-PKcs-deficient cells. Our current work indicates crosstalk between DNA-PKcs and HDACs signaling pathways, and highlights that the combined targeting of DNA-PKcs and HDACs can be used in cancer therapy. DNA-PKcs, DNA-dependent protein kinase catalytic subunit, HDACs, Histone deacetylases, DSBs, DNA double-strand breaks, ATM, ataxia telangiectasia mutated, ATR, ATM-Rad3-related.
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http://dx.doi.org/10.1080/15384101.2020.1867790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889180PMC
January 2021

Nitrated Graphene Oxide Derived from Graphite Oxide: A Promising Energetic Two-Dimensional Material.

Nanomaterials (Basel) 2020 Dec 29;11(1). Epub 2020 Dec 29.

State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081, China.

In order to synthesize a novel two-dimensional energetic material, nitrated graphene oxide (NGO) was prepared by the nitrification of graphite oxide to make a functional modification. Based on the morphological characterization, the NGO has a greater degree of curl and more wrinkles on the surface. The structure characterization and density functional theory calculation prove that epoxy and hydroxyl groups on the edge of graphite oxide have reacted with nitronium cation (NO) to produce nitro and nitrate groups. Hydrophobicity of NGO implied higher stability in storage than graphene oxide. Synchronous simultaneous analysis was used to explore the decomposition mechanism of NGO preliminarily. The decomposition enthalpy of NGO is 662.0 J·g and the activation energy is 166.5 kJ·mol. The thermal stability is similar to that of general nitrate energetic materials. The hygroscopicity, thermal stability and flammability of NGO prove that it is a novel two-dimensional material with potential applications as energetic additives in the catalyst, electrode materials and energetic devices.
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http://dx.doi.org/10.3390/nano11010058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823779PMC
December 2020

sRNATargetDigger: A bioinformatics software for bidirectional identification of sRNA-target pairs with co-regulatory sRNAs information.

PLoS One 2020 28;15(12):e0244480. Epub 2020 Dec 28.

College of Life Sciences, Huzhou University, Huzhou, Zhejiang, P.R. China.

Identification of the target genes of microRNAs (miRNAs), trans-acting small interfering RNAs (ta-siRNAs), and small interfering RNAs (siRNAs) is an important step for understanding their regulatory roles in plants. In recent years, many bioinformatics software packages based on small RNA (sRNA) high-throughput sequencing (HTS) and degradome sequencing data analysis have provided strong technical support for large-scale mining of sRNA-target pairs. However, sRNA-target regulation is achieved using a complex network of interactions since one transcript might be co-regulated by multiple sRNAs and one sRNA may also affect multiple targets. Currently used mining software can realize the mining of multiple unknown targets using known sRNA, but it cannot rule out the possibility of co-regulation of the same target by other unknown sRNAs. Hence, the obtained regulatory network may be incomplete. We have developed a new mining software, sRNATargetDigger, that includes two function modules, "Forward Digger" and "Reverse Digger", which can identify regulatory sRNA-target pairs bidirectionally. Moreover, it has the ability to identify unknown sRNAs co-regulating the same target, in order to obtain a more authentic and reliable sRNA-target regulatory network. Upon re-examination of the published sRNA-target pairs in Arabidopsis thaliana, sRNATargetDigger found 170 novel co-regulatory sRNA-target pairs. This software can be downloaded from http://www.bioinfolab.cn/sRNATD.html.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244480PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769420PMC
December 2020

Deletion of pksA attenuates the melanogenesis, growth and sporulation ability and causes increased sensitivity to stress response and antifungal drugs in the human pathogenic fungus Fonsecaea monophora.

Microbiol Res 2021 Mar 5;244:126668. Epub 2020 Dec 5.

Department of Dermatology and Venerology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

Fonsecaea monophora, which is very similar to Fonsecaea pedrosoi in morphological features, has been commonly misdiagnosed as F. pedrosoi. Like F. pedrosoi, F. monophora has been also identified as a predominant pathogen of Chromoblastomycosis (CBM). Melanin has been recognized as a virulence factor in several fungi, however, it is still largely unknown about the biological role of melanin and how melanin is synthesized in F. monophora. In this study, we identified two putative polyketide synthase genes (pks), AYO21_03016 (pksA) and AYO21_10638, by searching against the genome of F. monophora. AYO21_03016 and AYO21_10638 were further targeted disrupted by Agrobacterium tumefaciens-mediated transformation (ATMT). We discovered that pksA gene was the major polyketide synthase required for melanin synthesis in F. monophora, rather than AYO21_10638. Phenotypic analysis showed that, knocking out of the pksA gene attenuated melanogenesis, growth rate, sporulation ability and virulence of F. monophora, as compared with wild-type and complementation strain (pksA-C). Furthermore, the ΔpksA mutant was confirmed to be more sensitive to the oxidative stress, extreme pH environment, and antifungal drugs including itraconazole (ITC), terbinafine (TER), and amphotericin B (AMB). Taken together, these findings enabled us to comprehend the role of pksA in regulating DHN-melanin pathway and its effect on the biological function of F. monophora.
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http://dx.doi.org/10.1016/j.micres.2020.126668DOI Listing
March 2021

Effect of corn straw biochar on corn straw composting by affecting effective bacterial community.

Prep Biochem Biotechnol 2020 Dec 25:1-11. Epub 2020 Dec 25.

Agricultural College, Shenyang Agricultural University, Shenyang, China.

This study investigated the effect of corn straw biochar on the decomposition, nutrient transformation, and bacterial community characteristics in the corn straw decomposition process. A 90-day microcosm incubation experiment was performed to assess the effects of corn straw biochar (500 °C, 1 h) on the corn straw decomposition process and the resulting product. Four biochar amendment rates (0%, 5, 10, and 15%, as mass fractions of biochar) and three different addition times (1st day, 30th day, and 60th day) were set in total. The results showed that corn straw biochar significantly increased the pH of the corn straw decomposition process by 0.71-0.73 and increased the electrical conductivity value by 0.64-1.07 μS/cm over that of the controls. In addition, biochar was shown to increase the temperature rise rate and temperature peak of the straw maturation system, and advance the process of straw maturation by 10 days. Thus, treatment with corn straw biochar could accelerate the corn straw decomposition process and change the conditions for microorganisms involved in the process. Furthermore, biochar additions significantly decreased the organic matter content by 9.67% under B3 and T treatment, and enhanced the N, PO, and KO contents of the straw decomposition product by 0.36, 0.19, and 0.88% under B3 and T treatment. Biochar additions could increase the abundance of several effective bacteria closely related to the N, PO, and KO contents of the straw maturation product. The growth of these bacteria was likely to be affected by the increase in pH with biochar addition, which enabled the improvement of the nutrient mineralization process.
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http://dx.doi.org/10.1080/10826068.2020.1858428DOI Listing
December 2020

Is the reaction sequence in phosphine-catalyzed [8+2] cycloaddition controlled by electrophilicity?

Chem Commun (Camb) 2021 Jan;57(6):761-764

Green Catalysis Center, and College of Chemistry, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450001, P. R. China. and School of Chemistry and Chemical Engineering, and Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University, Chongqing 400030, P. R. China.

In the presence of multiple electrophiles, the reaction sequence is a critical mechanistic problem. Here, we report a theoretical study on the mechanism of phosphine-catalyzed [8+2] cycloaddition of heptafulvenes and allenoate. DFT calculations showed that electrophilicity is the barrier for nucleophilic attack, while it fails in the prediction of priority.
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http://dx.doi.org/10.1039/d0cc07370aDOI Listing
January 2021

Decoding Human Megakaryocyte Development.

Cell Stem Cell 2021 Mar 18;28(3):535-549.e8. Epub 2020 Dec 18.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China; CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin 300020, China. Electronic address:

Despite our growing understanding of embryonic immune development, rare early megakaryocytes (MKs) remain relatively understudied. Here we used single-cell RNA sequencing of human MKs from embryonic yolk sac (YS) and fetal liver (FL) to characterize the transcriptome, cellular heterogeneity, and developmental trajectories of early megakaryopoiesis. In the YS and FL, we found heterogeneous MK subpopulations with distinct developmental routes and patterns of gene expression that could reflect early functional specialization. Intriguingly, we identified a subpopulation of CD42bCD14 MKs in vivo that exhibit high expression of genes associated with immune responses and can also be derived from human embryonic stem cells (hESCs) in vitro. Furthermore, we identified THBS1 as an early marker for MK-biased embryonic endothelial cells. Overall, we provide important insights and invaluable resources for dissection of the molecular and cellular programs underlying early human megakaryopoiesis.
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http://dx.doi.org/10.1016/j.stem.2020.11.006DOI Listing
March 2021

Rhodium-Catalyzed Atroposelective Construction of Indoles via C-H Bond Activation.

Angew Chem Int Ed Engl 2020 Dec 16. Epub 2020 Dec 16.

School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, China.

Reported herein is the rhodium(III)-catalyzed C-H activation of anilines bearing an N-isoquinolyl directing group for oxidative [3+2] annulation with four classes of internal alkynes, leading to atroposelective indole synthesis via dynamic kinetic annulation with C-N reductive elimination constituting the stereo-determining step. This reaction proceeds under mild conditions with high regio- and enantioselectivity and functional group compatibility.
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http://dx.doi.org/10.1002/anie.202012932DOI Listing
December 2020

Chemoselective Union of Olefins, Organohalides, and Redox-Active Esters Enables Regioselective Alkene Dialkylation.

J Am Chem Soc 2020 12 11;142(51):21410-21419. Epub 2020 Dec 11.

Department of Chemistry, National University of Singapore, 12 Science Drive 2, Singapore 117549, Republic of Singapore.

Multicomponent catalytic processes that can generate multiple C(sp)-C(sp) bonds in a single step under mild conditions, particularly those that employ inexpensive catalysts and substrates, are highly sought-after in chemistry research for complex molecule synthesis. Here, we disclose an efficient Ni-catalyzed reductive protocol that chemoselectively merges alkenyl amides with two different aliphatic electrophiles. Starting materials are readily accessible from stable and abundant feedstock, and products are furnished in up to >98:2 regioisomeric ratios. The present strategy eliminates the use of sensitive organometallic reagents, tolerates a wide array of complex functionalities, and enables regiodivergent addition of two primary alkyl groups bearing similar electronic and steric attributes across aliphatic C═C bonds with exquisite control of site selectivity. Utility is underscored by the concise synthesis of bioactive compounds and postreaction functionalizations leading to structurally diverse scaffolds. DFT studies revealed that the regiochemical outcome originates from the orthogonal reactivity and chemoselectivity profiles of in situ generated organonickel species.
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http://dx.doi.org/10.1021/jacs.0c09922DOI Listing
December 2020

Insight into the organocatalytic arylation of azonaphthalenes with α-chloroaldehydes: the general mechanism and origin of selectivities.

Chem Commun (Camb) 2021 Jan 10;57(2):219-222. Epub 2020 Dec 10.

Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, China.

A systemical computational study was performed to explore the mechanism and origin of selectivities on the organocatalytic arylation of azonaphthalenes with α-chloroaldehydes. The calculated results reveal that the nucleophilicity of active sites and the hydrogen bonds respectively regulate chemo- and stereoselectivities and, for the first time, N-heterocyclic carbene (NHC) can act as a multiple functional base (MFB) catalyst in one system.
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http://dx.doi.org/10.1039/d0cc07260eDOI Listing
January 2021

Deep whole-genome sequencing of multiple proband tissues and parental blood reveals the complex genetic etiology of congenital diaphragmatic hernias.

HGG Adv 2020 Oct 25;1(1). Epub 2020 Aug 25.

Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

The diaphragm is critical for respiration and separation of the thoracic and abdominal cavities, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDH), a common and often lethal birth defect. The genetic etiology of CDH is complex. Single-nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs) in more than 150 genes have been associated with CDH, although few genes are recurrently mutated in multiple individuals and mutated genes are incompletely penetrant. This suggests that multiple genetic variants in combination, other not-yet-investigated classes of variants, and/or nongenetic factors contribute to CDH etiology. However, no studies have comprehensively investigated in affected individuals the contribution of all possible classes of variants throughout the genome to CDH etiology. In our study, we used a unique cohort of four individuals with isolated CDH with samples from blood, skin, and diaphragm connective tissue and parental blood and deep whole-genome sequencing to assess germline and somatic and inherited SNVs, indels, and SVs. In each individual we found a different mutational landscape that included germline and inherited SNVs and indels in multiple genes. We also found in two individuals a 343 bp deletion interrupting an annotated enhancer of the CDH-associated gene , and we hypothesize that this common SV (found in 1%-2% of the population) acts as a sensitizing allele for CDH. Overall, our comprehensive reconstruction of the genetic architecture of four CDH individuals demonstrates that the etiology of CDH is heterogeneous and multifactorial.
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http://dx.doi.org/10.1016/j.xhgg.2020.100008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703690PMC
October 2020

Manganese-Catalyzed Asymmetric Hydrogenation of Quinolines Enabled by π-π Interaction*.

Angew Chem Int Ed Engl 2021 Mar 15;60(10):5108-5113. Epub 2021 Jan 15.

Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing, 100084, China.

The non-noble metal-catalyzed asymmetric hydrogenation of N-heteroaromatics, quinolines, is reported. A new chiral pincer manganese catalyst showed outstanding catalytic activity in the asymmetric hydrogenation of quinolines, affording high yields and enantioselectivities (up to 97 % ee). A turnover number of 3840 was reached at a low catalyst loading (S/C=4000), which is competitive with the activity of most effective noble metal catalysts for this reaction. The precise regulation of the enantioselectivity were ensured by a π-π interaction.
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http://dx.doi.org/10.1002/anie.202013540DOI Listing
March 2021

Quadruple C-H activation coupled to hydrofunctionalization and C-H silylation/borylation enabled by weakly coordinated palladium catalyst.

Nat Commun 2020 11 9;11(1):5662. Epub 2020 Nov 9.

Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, PR China.

Unlike the well-reported 1,2-difunctionalization of alkenes that is directed by classic pyridine and imine-containing directing groups, oxo-palladacycle intermediates featuring weak Pd-O coordination have been less demonstrated in C-H activated cascade transformations. Here we report a quadruple C-H activation cascade as well as hydro-functionalization, C-H silylation/borylation sequence based on weakly coordinated palladium catalyst. The hydroxyl group modulates the intrinsic direction of the Heck reaction, and then acts as an interrupter that biases the reaction away from the classic β-H elimination and toward C-H functionalization. Mechanistically, density functional theory calculation provides important insights into the key six-membered oxo-palladacycle intermediates, and indicates that the β-H elimination is unfavorable both thermodynamically and kinetically. In this article, we focus on the versatility of this approach, which is a strategic expansion of the Heck reaction.
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http://dx.doi.org/10.1038/s41467-020-19508-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652853PMC
November 2020

Combinatory Effect of ALA-PDT and Itraconazole Treatment for Trichosporon asahii.

Lasers Surg Med 2020 Nov 8. Epub 2020 Nov 8.

Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 West Yanjiang Road, Guangzhou, 510120, China.

Background And Objectives: Trichosporiosis is an opportunistic infection that includes superficial infections, white piedra, hypersensitivity pneumonitis, and invasive trichosporonosis. The effect of antifungal agents against these infections is largely weakened by drug resistance and biofilms-related virulence. Photodynamic therapy (PDT) is a new therapeutic approach developed not only to combat cancerous lesions but also to treat infectious diseases such as fungal infections. However, there are few studies on the antimicrobial mechanism of 5-aminolevulinic acid PDT (ALA-PDT) in treating Trichosporon. In this work, we explored the possibility of combining ALA-PDT with an antifungal agent to enhance the therapeutic efficacy of Trichosporon asahii (T. asahii) in a clinical setting and in vitro.

Study Design/materials And Methods: The biofilms of T. asahii were constructed by a 96-well plate-based method in vitro. The planktonic and adherent T. asahii were exposed to different concentrations of photosensitizers and different light doses. After PDT treatment, counting colony-forming units and tetrazolium (XTT) reduction assay were used to estimate the antifungal efficacy. The minimal inhibitory concentration of itraconazole before and after PDT treatment was determined by the broth dilution method, and XTT viability assay was used to detect and evaluate the synergistic potential of ALA-PDT and itraconazole combinations in inhibiting biofilms. Scanning electron microscopy (SEM) was performed to assess the disruption of biofilms.

Results: Using combination therapy, we have successfully treated a patient who had a T. asahii skin infection. Further in vitro studies showed that the antifungal effect of ALA-PDT on planktonic and adherent T. asahii was dependent on the concentration of ALA and light dosages used. We also found that the sensitivity of both planktonic and biofilm cells to itraconazole were increased after ALA-PDT. Synergistic effect were observed for biofilms in ALA-PDT and itraconazole-combined treatment. The disruption of biofilms was confirmed by SEM, suggesting that ALA-PDT effectively damaged the biofilms and the destruction was further enhanced by ALA-PDT combination of antifungal agents.

Conclusions: In conclusion, these data suggest that ALA-PDT could be an alternative strategy for controlling infections caused by Trichosporon. The combination therapy of ALA-PDT with itraconazole could result in increased elimination of planktonic cells and biofilms compared with single therapy. All these findings indicate that it could be a promising treatment against trichosporonosis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
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http://dx.doi.org/10.1002/lsm.23343DOI Listing
November 2020