Publications by authors named "Hongbo Wang"

401 Publications

Active triggering control of pneumatic rehabilitation gloves based on surface electromyography sensors.

PeerJ Comput Sci 2021 19;7:e448. Epub 2021 Apr 19.

Robotics and Mechatronics Department, Institute of Solid Mechanics of the Romanian Academy, Bucharest, Bucharest, Romania.

The portable and inexpensive hand rehabilitation robot has become a practical rehabilitation device for patients with hand dysfunction. A pneumatic rehabilitation glove with an active trigger control system is proposed, which is based on surface electromyography (sEMG) signals. It can trigger the hand movement based on the patient's hand movement trend, which may improve the enthusiasm and efficiency of patient training. Firstly, analysis of sEMG sensor installation position on human's arm and signal acquisition process were carried out. Then, according to the statistical law, three optimal eigenvalues of sEMG signals were selected as the follow-up neural network classification input. Using the back propagation (BP) neural network, the classifier of hand movement is established. Moreover, the mapping relationship between hand sEMG signals and hand actions is built by training and testing. Different patients choose the same optimal eigenvalues, and the calculation formula of eigenvalues' amplitude is unique. Due to the differences among individuals, the weights and thresholds of each node in the BP neural network model corresponding to different patients are not the same. Therefore, the BP neural network model library is established, and the corresponding network is called for operation when different patients are trained. Finally, based on sEMG signal trigger, the pneumatic glove training control algorithm was proposed. The combination of the trigger signal waveform and the motion signal waveform indicates that the pneumatic rehabilitation glove is triggered to drive the patient's hand movement. Preliminary tests have confirmed that the accuracy rate of trend recognition for hand movement is about 90%. In the future, clinical trials of patients will be conducted to prove the effectiveness of this system.
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http://dx.doi.org/10.7717/peerj-cs.448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064233PMC
April 2021

Prevention of cisplatin-induced nausea and vomiting by seabuckthorn ( L.) seed oil: Insights at the level of orexin-A in rats.

Iran J Basic Med Sci 2021 Feb;24(2):248-255

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.

Objectives: Nausea and vomiting are perennial problems in cancer patients undergoing chemotherapy. Orexin-A (OXA) has been shown to regulate feeding and gastric motility. Seabuckthorn ( L.) seed oil (SSO) has been proved to promote digestion and bowel movements. We investigated whether SSO alleviated cisplatin-induced vomiting and its possible mechanism involved in OXA.

Materials And Methods: Rats were randomly divided into normal control group (NCG), cisplatin group (CG), SSO low-dose group (SLG), SSO middle-dose group (SMG) SSO high-dose group (SHG), and ondansetron group (OG). Rats were pretreated respectively with SSO (0.850, 1.675, and 3.350 g/kg·BW) and ondansetron (2 mg/kg·BW) in SLG, SMG, SHG, and OG for 6 days, and the same volume of saline in NCG and CG groups. On the 6th day, cisplatin (6 mg/kg, IP) was administered in all groups except NCG. The cumulative food and kaolin intake, gastric emptying, plasma OXA level, OXR mRNA and protein expression in the hypothalamus and brainstem, and OXA expression in the lateral hypothalamic area (LHA) were observed, and the HPLC method was used to analyze the composition of SSO.

Results: Kaolin intake in cisplatin-induced vomiting rats was significantly reduced (<0.05) and gastric emptying delayed by cisplatin was improved (<0.05-0.01) by pretreatment with SSO. Plasma OXA concentration, OXR expression in the hypothalamus and brainstem increased significantly (<0.05-0.01). Furthermore, OXA expression in LHA also increased significantly (<0.05).

Conclusion: SSO prevents cisplatin-induced vomiting in rats, which is possibly involved in increasing peripheral and central OXA and the expression of OXR in the hypothalamus and brainstem.
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http://dx.doi.org/10.22038/ijbms.2020.47599.10973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061333PMC
February 2021

Zebularine suppressed gemcitabine-induced senescence and improved the cellular and plasma pharmacokinetics of gemcitabine, augmented by liposomal co-delivery.

Int J Pharm 2021 Apr 30;602:120659. Epub 2021 Apr 30.

School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand. Electronic address:

Chemoresistance is a major factor driving cancer recurrence. This study investigated the potential of zebularine, a dual cytidine deaminase (CDA)/epigenetic inhibitor, to circumvent gemcitabine-resistance in pancreatic cancer using a nanomedicine co-delivery approach. The mRNA expression of key metabolic enzymes, including CDA for gemcitabine deactivation in a gemcitabine-resistant cell line Gr2000 and its parental MIA PaCa-2 was compared using quantitative reverse transcription polymerase chain reaction. A highly gemcitabine-resistant population (HRP) in Gr2000 were characterised for their growth pattern, β-galactosidase activity (a hallmark of senescence) and chemosensitivity to zebularine after isolation. The CDA inhibition effects of zebularine on the intracellular gemcitabine accumulation and pharmacokinetics in rats when co-delivered with pH-sensitive liposomes (pSL) were investigated. Gr2000 had a 3-time upregulated mRNA expression and enzyme activity for CDA. The HRP (28% of bulk Gr2000) were predominately senescent cells which re-proliferated following a growth arrest for a week. Zebularine suppressed the regrowth of senescent cells, meanwhile enhanced cellular gemcitabine concentration by 2-fold. When co-delivered with pSL, zebularine increased cellular gemcitabine concentration by 4-fold, and extended the half-life of gemcitabine in plasma by 22-fold in rats. In conclusion, multiple mechanisms including therapy-induced senescence were identified with gemcitabine-resistance. Co-delivery of zebularine using liposomes could provide multifaceted benefits in gemcitabine therapy for pancreatic cancer treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120659DOI Listing
April 2021

Single-cell RNA sequencing reveals the heterogeneity of liver-resident immune cells in human.

Cell Discov 2020 Apr 28;6(1):22. Epub 2020 Apr 28.

Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong, 518112, China.

The liver plays a critical role in both immune defense and tolerance in the body. The liver-resident immune cells (LrICs) determine the immune properties, but the unique composition and heterogeneity of these cells are incompletely understood. Here, we dissect the diversity of LrICs by a comprehensive transcriptomic profiling using the unbiased single-cell RNA-sequencing (scRNA-seq). A total of 70, 706 of CD45 immune cells from the paired liver perfusion, spleen and peripheral blood as references were profiled. We identified more than 30 discrete cell populations comprising 13 of T and NK cell, 7 of B cell, 4 of plasma cell, and 8 of myeloid cell subsets in human liver and donor-paired spleen and blood, and characterized their tissue distribution, gene expression and functional modules. Especially, four of CXCR6 T and NK cell subsets were found to be present preferentially in the liver, where they manifested heterogeneity, distinct function and prominent homeostatic proliferation. We propose a universal category system of T and NK cells based on distinct chemokine receptors, confirmed subsequently by phenotype, transcriptional factors and functionality. We also identified adaptive changes by the spleen and liver-derived monocyte and macrophage populations. Finally, we give a global glimpse on B cell and plasma cell subsets in human spleen and liver. We, therefore, reveal the heterogeneity and functional diversity of LrICs in human. This study presents comprehensively the landscape of LrICs and will enable further study on their roles in various human diseases.
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http://dx.doi.org/10.1038/s41421-020-0157-zDOI Listing
April 2020

Guiding-Strand-Controlled DNA Nucleases with Enhanced Specificity and Tunable Kinetics for DNA Mutation Detection.

Anal Chem 2021 May 26;93(18):7054-7062. Epub 2021 Apr 26.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Nucleases are powerful tools in various biomedical applications, such as genetic engineering, biosensing, and molecular diagnosis. However, the commonly used nucleases (endonuclease IV, apurinic/apyrimidinic endonuclease-1, and λ exonuclease) are prone to the nonspecific cleavage of single-stranded DNA, making the desired reactions extremely low-yield and unpredictable. Herein, we have developed guiding-strand-controlled nuclease systems and constructed theoretical kinetic models to explain their mechanisms of action. The models displayed excellent agreement with the experimental results, making the kinetics highly predictable and tunable. Our method inhibited the nonspecific cleavage of single-stranded probes while maintaining highly efficient cleavage of double-stranded DNA. We also demonstrated the clinical practicability of the method by detecting a low-frequency mutation in a genomic DNA sample extracted from the blood of a patient with cancer. The limit of detection could be 0.01% for PTEN rs121909219. We believe that our findings provide a powerful tool for the field and the established model provides us a deeper understanding of the enzymatic activities of DNA nucleases.
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http://dx.doi.org/10.1021/acs.analchem.1c00507DOI Listing
May 2021

Dual-triggered biomimetic vehicles enable treatment of glioblastoma through a cancer stem cell therapeutic strategy.

Nanoscale 2021 Apr 8;13(15):7202-7219. Epub 2021 Apr 8.

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Glioma stem cells (GSCs) and their complex microenvironment play a crucial role in the high invasion of cancer and therapeutic resistance and are considered to be the most likely cause of cancer relapse. We constructed a biomimetic vehicle (LDL-SAL-Ang) based on a low density lipoprotein triggered by Angiopep-2 peptide and ApoB protein, to improve the transport of an anti-GSC therapeutic agent into the brain. The LDL-SAL-Ang showed significant inhabitation for GSC microsphere formation and induced the highest apoptotic rate in two types of GSCs. LDL-SAL-Ang reduced the number of GSC-derived endothelial tubules at a lower drug concentration and inhibited endothelial cell migration and angiogenesis. The pharmacokinetic analysis showed that the brain tissue uptake rate (% ID g) for LDL-SAL-Ang was significantly enhanced at 0.45. For anti-glioblastoma activity in vivo, the median survival time of LDL-SAL-Ang plus temozolomide group was 47 days, which were significantly increased compared with the control or temozolomide only groups. The endogenous biomimetic nanomedicine that we designed provides a potential approach to improve treatments for intracranial tumors and reduced neurotoxicity of nanomedicine.
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http://dx.doi.org/10.1039/d0nr08899dDOI Listing
April 2021

Development of the Ultralight Hybrid Pneumatic Artificial Muscle: Modelling and optimization.

PLoS One 2021 22;16(4):e0250325. Epub 2021 Apr 22.

Soft BioRobotics Perception, Istituto Italiano di Tecnologia (IIT), Genova, Italy.

Pneumatic artificial muscles (PAMs) are one of the key technologies in soft robotics, and they enable actuation in mobile robots, in wearable devices and exoskeletons for assistive and rehabilitative purposes. While they recently showed relevant improvements, they still present quite low payload, limited bandwidth, and lack of repeatability, controllability and robustness. Vacuum-based actuation has been recently demonstrated as a very promising solution, and many challenges are still open, like generating at the same time a large contraction ratio, and a high blocking force with enhanced axial stiffness. In this paper, a novel Ultralight Hybrid PAM (UH-PAM), based on bellow-type elastomeric skin and vacuum actuation, is presented. In particular, open-cell foam is exploited as a structural backbone, together with plastic rings, all embedded in a thin skin. The design and optimization combine numerical, analytical, and experimental data. Both static and dynamic analysis are performed. The weight of the optimized actuator is only 20 g. Nevertheless, a contraction ratio up to 50% and a maximum payload of 3 kg can be achieved. From a dynamic point of view, a rise time of 0.5 s for the contraction phase is observed. Although hysteresis is significant when using the whole contraction span, it can be reduced (down to 11.5%) by tuning both the vacuum range and the operating frequency for cyclic movements. Finally, to demonstrate the potentiality of this soft actuation approach, a 3 DoFs Stewart platform is built. The feasibility of performing smooth movements by exploiting open-loop control is shown through simple and more complex handwriting figures projected on the XY plane.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250325PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062031PMC
April 2021

A Novel Chemiluminescence Probe for Sensitive Detection of Fibroblast Activation Protein-Alpha In Vitro and in Living Systems.

Anal Chem 2021 04 18;93(16):6501-6507. Epub 2021 Apr 18.

Shanghai Key Laboratory of Bioactive Small Molecules & Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, Shanghai 201203, P. R. China.

Fibroblast activation protein-alpha (FAPα) is a key modulator of the microenvironment in multiple pathologies and is becoming the next pan-cancer target for cancer diagnostics and therapeutics. Chemiluminescence (CL) luminophores are considered as one of the most sensitive families of probes for detection and imaging applications due to their high signal-to-noise ratio. Until now, however, no such effective CL probe was reported for FAPα detection. Herein, we developed a novel CL probe for the detection of endogenous FAPα activity by incorporating FAPα-specific dipeptide substrates (glycine-proline) to the improved Schaap's adamantylidene-dioxetane. In this manner, we designed three CL probes (, , and ) with the dipeptide substrate blocked by N-terminal benzyloxycarbonyl, --butoxycarbonyl or -quinoline-4-carboxylic acid, respectively, which was used as the masking group to restrain the chemiexcitation energy. Probe exhibited the optimal specificity for the discrimination of FAPα from dipeptidase IV and prolyl oligopeptidase, which was elucidated by molecular docking simulation. Upon FAPα cleavage, was turned on for the highly selective and sensitive detection of FAPα with a limit of detection of 0.785 ng/mL. Furthermore, the ability of to image FAPα was effectively demonstrated in vitro, including various biological samples (plasma and tissue preparations), and in living systems (tumor cells and tumor-bearing mice). Furthermore, this newly established probe could be easily extended to evaluate FAPα inhibitors. Overall, we anticipate that probe will offer a facile and cost-effective alternative in the early detection of pathologies, individual tailoring of drug therapy, and drug screening.
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http://dx.doi.org/10.1021/acs.analchem.1c00413DOI Listing
April 2021

Biomechanical analysis of a novel clavicular hook plate for the treatment of acromioclavicular joint dislocation: A finite element analysis.

Comput Biol Med 2021 Apr 14;133:104379. Epub 2021 Apr 14.

The Second Department of Orthopedics, Xi'an Centeral Hospital, No. 161, West Fifth Road, Xincheng District, Xi'an, 710003, Shaanxi, China. Electronic address:

Background: Clavicular hook plates are frequently used in clinical orthopedics to treat acromioclavicular joint dislocation. However, patients often exhibit acromial osteolysis and peri-implant fracture after hook plate fixation. To solve the above problems, we developed a novel double-hook clavicular plate and used finite element analysis (FEA) to investigate its biomechanical properties.

Methods: A finite element (FE) model was constructed and validated. Then, a double-hook clavicular plate, a single-hook clavicular plate, and an anatomical double-hook clavicular plate was implanted into the acromioclavicular joint and fixed with screws in groups 1, 2 and 3, respectively. Finally, a load was applied, and some indicators were recorded and analyzed.

Results: For both the proximal clavicular rotation angle and the distal clavicular displacement, the range of motion in groups 1 and 3 was more than 90% lower than that in group 2. The maximum von Mises stress of the clavicle in groups 1 and 3 was more than 45% lower than that in group 2. The maximum stress of the acromion in group 2 was significantly higher than that in groups 1 and 3, and that in group 3 was less than that in group 1, for both cortical and cancellous bone.

Conclusions: The double-hook clavicular plate could immediately reconstruct the stability of the acromioclavicular joint, effectively reducing the stress of the bone around the clavicle and screws. Additionally, the double-hook clavicular plate could reduce the peak stress of the acromion and produce a more uniform stress distribution.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104379DOI Listing
April 2021

Simulation study on the indirect effect of sulfate on the summer climate over the eastern China monsoon region.

Sci Rep 2021 Apr 15;11(1):8295. Epub 2021 Apr 15.

Liaoning Weather Modification Office, Shenyang, 110166, China.

In this study, we designed a sensitivity test using the half number concentration of sulfate in the nucleation calculation process to study the aerosol-cloud interaction (ACI) of sulfate on clouds, precipitation, and monsoon intensity in the summer over the eastern China monsoon region (ECMR) with the National Center for Atmospheric Research Community Atmosphere Model version 5. Numerical experiments show that the ACI of sulfate led to an approximately 30% and 34% increase in the cloud condensation nuclei and cloud droplet number concentrations, respectively. Cloud droplet effective radius below 850 hPa decreased by approximately 4% in the southern ECMR, while the total liquid water path increased by 11%. The change in the indirect radiative forcing due to sulfate at the top of the atmosphere in the ECMR during summer was - 3.74 W·m. The decreased radiative forcing caused a surface cooling of 0.32 K and atmospheric cooling of approximately 0.3 K, as well as a 0.17 hPa increase in sea level pressure. These changes decreased the thermal difference between the land and sea and the gradient of the sea-land pressure, leading to a weakening in the East Asian summer monsoon (EASM) and a decrease in the total precipitation rate in the southern ECMR. The cloud lifetime effect has a relatively weaker contribution to summer precipitation, which is dominated by convection. The results show that the ACI of sulfate was one possible reason for the weakening of the EASM in the late 1970s.
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http://dx.doi.org/10.1038/s41598-021-87832-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050310PMC
April 2021

Region-specific Risk Factors for Pelvic Lymph Node Metastasis in Patients with Stage IB1 Cervical Cancer.

J Cancer 2021 5;12(9):2624-2632. Epub 2021 Mar 5.

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

We aimed to identify the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location in patients with stage IB1 cervical cancer. A primary cohort of 728 patients with stage IB1 cervical cancer who underwent radical hysterectomy and systematic pelvic lymphadenectomy were retrospectively studied. All removed pelvic nodes (=20,134) were pathologically examined. The risk factors for LNM in different anatomic regions (obturator, internal iliac, external iliac, and common iliac) were evaluated by multivariate logistic regression analyses. Nomograms were generated from the primary cohort and validated in another external cohort =242). The performance of the nomogram was assessed by its calibration and discrimination. Overall survival and progression-free survival in patients with different LNM patterns were compared. : LNM was found in 266 (1.3%) removed nodes and 106 (14.6%) patients. The incidences of LNM at the obturator, internal iliac, external iliac, common iliac, and parametrial regions were 8.5%, 5.4%, 4.7%, 1.9% and 1.8%, respectively. Among others, tumour size and lymph-vascular space invasion (LVSI), which are preoperatively assessable, were identified as independent risk factors of LNM in the common iliac region and the lower pelvis, respectively, and age was an additional independent risk factor of obturator LNM. The negative predictive values of tumour size <2 cm for common iliac LNM and negative LVSI combined with older age (> 50 years) for obturator LNM were 100% and 98.7%, respectively. A nomogram of these two factors showed good calibration and discrimination (concordance index, 0.761 in the primary cohort and 0.830 in validation cohort). The patients with common iliac LNM had poorer survival than those with LNM confined to the lower pelvis, while the differences in survival between patients with LNM confined to one node, one region or single side and those with more widely spreading LNM were not statistically significant. Tumour size, LVSI and age are region-specific risk factors for pelvic LNM in IB1 cervical cancer, which could be used to allocate the appropriate extent of pelvic lymphadenectomy.
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http://dx.doi.org/10.7150/jca.53215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040729PMC
March 2021

Benzothiazole Amides as TRPC3/6 Inhibitors for Gastric Cancer Treatment.

ACS Omega 2021 Apr 24;6(13):9196-9203. Epub 2021 Mar 24.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education; Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.

Transient receptor potential canonical channel 6 (TRPC6) has been implicated in many kinds of malignant tumors, but very few potent TRPC6 antagonists are available. In this study, a benzothiazole amide derivative was discovered as a TRPC6 activator in a cell-based high-throughput screening. A series of benzothiazole amide derivatives were designed and synthesized. The docking analyses indicated that the conformations of the compounds bound to TRPC6 determined the agonistic or antagonistic activity of the compounds against TRPC6, and compound with the tetrahydronaphthalene group in R position fit well into the binding pocket of the antagonist-bound conformation of TRPC6. Compound showed an inhibitory potency order of TRPC3 (IC 3.3 ± 0.13 μM) ≈ C6 (IC 4.2 ± 0.1 μM) > C7 with good anti-gastric cancer activity in a micromolecular range against AGS and MKN-45, respectively. In addition, inhibited the invasion and migration of MKN-45 cells .
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http://dx.doi.org/10.1021/acsomega.1c00514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028158PMC
April 2021

Secretomes of human pluripotent stem cell-derived smooth muscle cell progenitors upregulate extracellular matrix metabolism in the lower urinary tract and vagina.

Stem Cell Res Ther 2021 Apr 6;12(1):228. Epub 2021 Apr 6.

Department of Obstetrics/Gynecology, Stanford University School of Medicine, 300 Pasteur Drive HH-333, Stanford, CA, 94305, USA.

Background: Adult mesenchymal stem cells (MSCs) have been studied extensively for regenerative medicine; however, they have limited proliferation in vitro, and the long culture time induces cell senescence. MSCs also contribute to tissue repair through their paracrine function. In this study, we sought to examine the paracrine effects of human smooth muscle cell progenitors (pSMC) on the urethra and adjacent vagina of stress urinary incontinence rodents. We use human pluripotent stem cell (PSC) lines to derive pSMCs to overcome the issue of decreased proliferation in tissue culture and to obtain a homogenous cell population.

Method: Three human PSC lines were differentiated into pSMCs. The conditioned medium (CM) from pSMC culture, which contain pSMC secretomes, was harvested. To examine the effect of the CM on the extracellular matrix of the lower urinary tract, human bladder smooth muscle cells (bSMCs) and vaginal fibroblasts were treated with pSMC-CM in vitro. Stress urinary incontinence (SUI) was induced in rats by surgical injury of the urethra and adjacent vagina. SUI rats were treated with pSMC-CM and monitored for 5 weeks. Urethral pressure testing was performed prior to euthanasia, and tissues were harvested for PCR, Western blot, and histological staining. Kruskal-Wallis one-way ANOVA test and Student t test were used for statistical comparisons.

Results: pSMC-CM upregulated MMP-2, TIMP-2, collagen, and elastin gene expression, and MMP-9 activity in the human bladder and vaginal cells consistent with elastin metabolism modulation. pSMC-CM treatment in the SUI rat improved urethral pressure (increase in leak point pressure compared to intact controls, p < 0.05) and increased collagen and elastin expression in the urethra and the adjacent vagina.

Conclusion: Conditioned media from smooth muscle cell progenitors derived from human pluripotent stem cells improved urethral leak point pressure and collagen and elastin content in the SUI rat. These findings suggest a novel therapeutic potential for PSC-based treatments for SUI and pelvic floor disorders where tissues are affected by collagen, elastin, and smooth muscle loss.
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http://dx.doi.org/10.1186/s13287-021-02292-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025391PMC
April 2021

Identifying a melanogenesis-related candidate gene by a high-quality genome assembly and population diversity analysis in Hypsizygus marmoreus.

J Genet Genomics 2021 Feb 15. Epub 2021 Feb 15.

Center for Genomics and Biotechnology, Haixia Institute of Science and Technology, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address:

Hypsizygus marmoreus is one of the most important edible fungi in Basidiomycete division and includes white and gray strains. However, very limited knowledge is known about the genomic structures and the genetic basis for the white/gray diversity of this mushroom. Here, we report the near-complete high-quality H. marmoreus genome at the chromosomal level. Comparative genomics analysis indicates that chromosome structures were relatively conserved, and variations in collinearity and chromosome number were mainly attributed by chromosome split/fusion events in Aragicales, whereas the fungi genome experienced many genomic chromosome fracture, fusion, and genomic replication events after the split of Aragicales from Basidiomycetes. Resequencing of 57 strains allows us to classify the population into four major groups and associate genetic variations with morphological features, indicating that white strains were not originated independently. We further generated genetic populations and identified a cytochrome P450 as the candidate causal gene for the melanogenesis in H. marmoreus based on bulked segregant analysis (BSA) and comparative transcriptome analysis. The high-quality H. marmoreus genome and diversity data compiled in this study provide new knowledge and resources for the molecular breeding of H. marmoreus as well as the evolution of Basidiomycete.
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http://dx.doi.org/10.1016/j.jgg.2021.01.002DOI Listing
February 2021

Topographic distribution of lymph node metastasis in patients with stage IB1 cervical cancer: an analysis of 8314 lymph nodes.

Radiat Oncol 2021 Mar 20;16(1):54. Epub 2021 Mar 20.

University Clinic for Medical Radiation Physics, Medical Campus Pius-Hospital, Carl von Ossietzky University Oldenburg, Georgstrasse 12, 26121, Oldenburg, Germany.

Background: Systematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment.

Methods: A total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification.

Results: Totally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases.

Conclusions: The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI.
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http://dx.doi.org/10.1186/s13014-021-01781-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981976PMC
March 2021

Pyxinol bearing amino acid residues: Easily achievable and promising modulators of P-glycoprotein-mediated multidrug resistance.

Eur J Med Chem 2021 Apr 3;216:113317. Epub 2021 Mar 3.

School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, China. Electronic address:

The P-glycoprotein (Pgp) is a major transporter involved in multidrug resistance (MDR) of cancer cells leading to chemotherapy failure. In our previous study, we demonstrated that the amide derivatives of pyxinol are promising modulators against Pgp-mediated MDR in cancer. In the present study, we designed and synthesized novel pyxinol derivatives linked to amino acid residues. We evaluated MDR (paclitaxel (Ptx) resistance) reversal potency of forty pyxinol derivatives in KBV cells and analyzed their structure-activity relationships. Half of our derivatives sensitized KBV cells to Ptx at non-toxic concentrations, among which the pyxinol compound bearing a methionine residue (3c) exhibited the best activity in MDR reversal. Compound 3c was found to possess high selectivity toward Pgp and sensitize the KBV cells to Pgp substrates by blocking the efflux function of Pgp. This manifestation may be attributed to its high binding affinity with Pgp, as suggested by docking studies. Overall, the biological profile and ease of synthesizing these pyxinol derivatives render them promising lead compounds for further development for Pgp-mediated MDR.
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http://dx.doi.org/10.1016/j.ejmech.2021.113317DOI Listing
April 2021

sensitizes ovarian cancer cells to irradiation by inhibiting and attenuating autophagy.

Mol Ther Nucleic Acids 2021 Mar 3;23:1110-1119. Epub 2020 Dec 3.

Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081 Heilongjiang Province, China.

Ovarian cancer (OC) is a type of cancer with high prevalence and shocking mortality in women around the world. Radioresistance is a major reason for OC relapse. Mounting studies have shown the significant function of dysregulated microRNAs (miRNAs) in cancer progression and the cellular response to irradiation. The present study inquired about the function and mechanism of microRNA () in regulating radiosensitivity of OC cells. Results showed that was downregulated in OC, and a low level indicated a disappointing prognosis for OC patients. Besides, in OC cells exposed to irradiation, the expression of decreased over time. Functionally, the upregulation of retarded OC cell proliferation and sensitized OC cells to irradiation. Mechanistically, targeted and inhibited fused in sarcoma (). Additionally, was upregulated in OC and its expression further elevated in OC cells under irradiation. Furthermore, targeted to inhibit autophagy, therefore sensitizing OC cells to irradiation. Collectively, our study uncovered as a novel radiosensitizer by targeting in OC cells, which may shed a new light on developing targets for treating patients with OC, particularly those with radioresistance.
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http://dx.doi.org/10.1016/j.omtn.2020.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901029PMC
March 2021

Interleukin-1 receptor-associated kinase 4 as a potential biomarker: Overexpression predicts poor prognosis in patients with glioma.

Oncol Lett 2021 Apr 3;21(4):254. Epub 2021 Feb 3.

Department of Orthopaedics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450001, P.R. China.

The undetectable onset of glioma and the difficulty of surgery lead to a poor prognosis. Appropriate biomarkers for diagnosis and treatment need to be identified. Interleukin-1 receptor-associated kinase 4 (IRAK4) is involved in the initiation and progression of cancer. However, up until now, no report has revealed the relationship between IRAK4 and glioma. The present study aimed to examine the expression of IRAK4 in glioma, and to determine if there was a relationship between IRAK4 expression and clinical outcomes or survival prognosis. Thousands of glioma tissue samples and corresponding clinical information were obtained from various databases. Then a series of bioinformatics methods were used to reveal the role of IRAK4 in glioma. Finally, reverse transcription-quantitative PCR technology was used to verify the bioinformatics results. The study found that the expression of IRAK4 was significantly increased in glioma compared with the control brain tissue samples, and IRAK4, as an independent prognostic factor, shortened the overall survival time of patients with glioma. Gene Set Enrichment Analysis showed that IRAK4 promoted the activation of cell signalling pathways, such as NOD-like and Toll-like receptor signalling pathways. Co-expression analysis showed that the expression of IRAK4 was correlated with CMTM6, MOB1A and other genes. The present study demonstrated the role of IRAK4 as an oncogene in the pathological process of glioma for the first time, and highlights the potential of IRAK4 as a biomarker for prognostic evaluation and treatment of glioma.
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http://dx.doi.org/10.3892/ol.2021.12516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882878PMC
April 2021

Metabolomics, metabolic flux analysis and cancer pharmacology.

Pharmacol Ther 2021 Mar 1;224:107827. Epub 2021 Mar 1.

School of Pharmaceutical Sciences; Tsinghua-Peking Joint Center for Life Sciences; Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing 100084, China. Electronic address:

Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression, metastasis and drug resistance. Understanding metabolic dysregulation may provide therapeutic targets and facilitate drug research and development for cancer therapy. Metabolomics enables the high-throughput characterization of a large scale of small molecule metabolites in cells, tissues and biofluids, while metabolic flux analysis (MFA) tracks dynamic metabolic activities using stable isotope tracer methods. Recent advances in metabolomics and MFA technologies make them powerful tools for metabolic profiling and characterizing metabolic activities in health and disease, especially in cancer research. In this review, we introduce recent advances in metabolomics and MFA analytical technologies, and provide the first comprehensive summary of the most commonly used isotope tracing methods. In addition, we highlight how metabolomics and MFA are applied in cancer pharmacology studies particularly for discovering targetable metabolic vulnerabilities, understanding the mechanisms of drug action and drug resistance, exploring potential strategies with dietary intervention, identifying cancer biomarkers, as well as enabling precision treatment with pharmacometabolomics.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107827DOI Listing
March 2021

Contributions of prelimbic cortex, dorsal and ventral hippocampus, and basolateral amygdala to fear return induced by elevated platform stress in rats.

Brain Res 2021 Mar 2;1761:147398. Epub 2021 Mar 2.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, PR China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address:

Fear relapse is a major challenge in the treatment of stress-related mental disorders. Most investigations have focused on fear return induced by stimuli associated with the initial fear learning, while little attention has been paid to fear return evoked after exposure to an unconditioned stressor. This study explored the neural mechanisms of fear return induced by elevated platform (EP) stressor in Sprague-Dawley rats initially subjected to auditory fear conditioning. The contributions of the prelimbic cortex (PL), dorsal hippocampus (DH), ventral hippocampus (VH), and basolateral amygdala (BLA) were examined by targeted bilateral intracerebral injection of the GABA agonist muscimol after elevated platform (EP) stressor. Muscimol-induced inactivation of PL or BLA significantly impaired the return of conditioning fear, while inactivation of the DH or VH had no effect. These results suggest that fear return induced by non-associative stressor may depend on the PL and BLA but not on the hippocampus.
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http://dx.doi.org/10.1016/j.brainres.2021.147398DOI Listing
March 2021

Are CT and MRI useful tools to distinguish between micropapillary type and typical type of ovarian serous borderline tumors?

Abdom Radiol (NY) 2021 Mar 3. Epub 2021 Mar 3.

Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan, People's Republic of China.

Purpose: To investigate the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of ovarian serous borderline tumors (SBTs), and evaluate whether CT and MRI can be used to distinguish micropapillary from typical subtypes.

Materials And Methods: We retrospectively reviewed the clinical features and CT and MR imaging findings of 47 patients with SBTs encountered at our institute from September 2013 to December 2019. 30 patients with 58 histologically proven typical SBT and 17 patients with 26 micropapillary SBT were reviewed. Preoperative CT and MR images were evaluated, by two observers in consensus for the laterality, maximum diameter (MD), morphology patterns, internal architecture, attenuation or signal intensity, ADC value, enhancement patterns of solid portions (SP), and extra-ovarian imaging features.

Results: The median age were similar between typical SBT and SBT-MP (32.5 years, 36 years, respectively, P>0.05). Morphology patterns between two subtypes were significantly different on CT and MR images (P < 0.001). Irregular solid tumor (21/37, 56.76%) was the major morphology pattern of typical SBT tumor, while unilocular cyst with mural nodules (14/20, 70%) was the major morphology pattern of SBT-MP on CT images. Similarly, papillary architecture with internal branching (PA&IB) (17/21, 80.95%) was the major morphology pattern of typical SBT tumor, while unilocular cyst with mural nodules (4/6, 66.67%) was the major pattern of SBT-MP on MR images. PA&IB all showed slightly hyperintense papillary architecture with hypointense internal branching on T2-weighted MRI. More calcifications were found in typical SBT (24/37, 64.86%) than SBT-MP mass lesion (6/20, 30%) (P < 0.05). Hemorrhage was less frequently visible in (20/37, 54.05%) typical SBT lessons than SBT-MP mass lesion (18/20, 90%) (P < 0.05). The ovarian preservation is more seen in typical SBT (38/58, 65.52%) than SBT-MP (12/28, 42.86%) in our series (P < 0.05). Mean ADC value of solid portions (papillary architecture and mural nodules) was 1.68 (range from 1.44 to 1.85) × 10 mm/s for typical SBT and 1.62 (range from 1.45 to 1.7) × 10 mm/s for that of SBT-MP. The solid components of the two SBT subtypes showed wash-in appearance enhancements after contrast injection both in CT and MR images except 2 of SBT-MP with no enhancement as complete focal hemorrhage on MR images.

Conclusion: Morphology and internal architecture are two major imaging features that can help to distinguish between SBT-MP and typical SBT.
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http://dx.doi.org/10.1007/s00261-021-03000-3DOI Listing
March 2021

Effect of DLT-SML on Chronic Stable Angina Through Ameliorating Inflammation, Correcting Dyslipidemia, and Regulating Gut Microbiota.

J Cardiovasc Pharmacol 2021 Feb 19;77(4):458-469. Epub 2021 Feb 19.

Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Abstract: Chronic stable angina (CSA) is caused by coronary atherosclerosis. The gut microbiota (GM) and their metabolite trimethylamine-N-oxide (TMAO) levels are associated with atherosclerosis. Danlou tablet (DLT) combined with Salvia miltiorrhiza ligustrazine (SML) injection has been used to treat CSA. This study aims to investigate how DLT combined with SML (DLT-SML) regulates serum lipids, inflammatory cytokines, GM community, and microbial metabolite in patients with CSA. In this study, 30 patients with CSA were enrolled in the DLT-SML group, and 10 healthy volunteers were included in the healthy control group. The patients in the DLT-SML group were subdivided as the normal total cholesterol (TC) group and high-TC group according to their serum TC level before treatment. Blood samples were collected to investigate the (1) lipid content, including triglyceride (TG), TC, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, (2) fasting blood glucose (Glu), (3) inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α), and (4) gut-derived metabolite, including lipopolysaccharides and TMAO level. GM composition was analyzed by sequencing 16S rRNA of fecal samples. Results showed that DLT-SML significantly decreased serum TG, TC, low-density lipoprotein cholesterol, IL-1β, TNF-α, and TMAO levels of patients with CSA. DLT-SML increased the abundance of Firmicutes and decreased Proteobacteria, which were significantly lower or higher in patients with CSA, respectively, compared with the healthy control group. In particular, DLT-SML increased the microbial diversity and decreased Firmicutes/Bacteroidetes ratio of patients with high-TC. The abundance of Sarcina, Anaerostipes, Streptococcus, Weissella, and Erysipelatoclostridium was decreased, whereas Romboutsia, Faecalibacterium, and Subdoligranulum were increased by DLT-SML treatment in patients with CSA. These findings indicated that DLT-SML improved patients with CSA by ameliorating dyslipidemia profile, decreasing the circulating inflammatory cytokines, and regulating the GM composition and their metabolites.
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http://dx.doi.org/10.1097/FJC.0000000000000970DOI Listing
February 2021

Design and synthesis of novel glycyrrhetin ureas as anti-inflammatory agents for the treatment of acute kidney injury.

Bioorg Chem 2021 May 19;110:104755. Epub 2021 Feb 19.

First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China. Electronic address:

To develop new anti-inflammatory drugs for the prevention and treatment of acute kidney injury, a series of novel glycyrrhetic ureas were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. Compounds 5r-5u (2.04, 2.50, 3.25 and 2.48 μM, respectively) with acidic or neutral amino acid showed potent anti-inflammatory activity (IC = 2-3 μM for NO inhibition), amongst them, compound 5r also inhibited tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner. In cisplatin-induced AKI mice model, compound 5r significantly reduced the level of pro-inflammatory factors, ameliorated the pathological damage of kidney tissue, and maintained the normal metabolic capacity.
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http://dx.doi.org/10.1016/j.bioorg.2021.104755DOI Listing
May 2021

mA RNA Methylation Regulators Act as Potential Prognostic Biomarkers in Lung Adenocarcinoma.

Front Genet 2021 10;12:622233. Epub 2021 Feb 10.

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.

N-methyladenosine [m(6)A/mA] methylation is one of the most common RNA modifications in eukaryotic cell mRNA and plays an important regulatory role in mRNA metabolism, splicing, translocation, stability, and translation. Previous studies have demonstrated that the mA modification is highly associated with tumor cell proliferation, migration, and invasion. In the present study, five mA regulatory factors have been revealed, namely heterogeneous nuclear ribonucleoprotein A2/B1(HNRNPA2B1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), Vir like mA methyltransferase associated protein (KIAA1429/VIRMA), RNA binding motif protein 15 (RBM15) and methyltransferase like 3 (METTL3), which are closely related to the overall survival (OS) of patients with lung adenocarcinoma (LUAD). These five mA regulatory factors exhibited potential prognostic value for the 1, 3, and 5-years survival outcomes of LUAD patients. Our findings revealed that several signaling pathways, such as cell cycle, DNA replication, RNA degradation, RNA polymerase, nucleotide excision repair and basal transcription factors, are activated in the high-risk group of LUAD patients.
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http://dx.doi.org/10.3389/fgene.2021.622233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902930PMC
February 2021

Abnormal expression of promotes the malignant behavior of glioma cells and leads to poor prognosis of glioma patients.

PeerJ 2021 8;9:e10820. Epub 2021 Feb 8.

Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China.

Background: Homeobox D11 () plays an important role in a variety of cancers, but its precise role in gliomas remains unclear. This study aimed to explore the relationship between and gliomas by combining bioinformatics methods with basic experimental validation.

Materials And Methods: Obtain gene expression information and clinical information of glioma and non-tumor brain tissue samples from multiple public databases such as TCGA (666 glioma samples), CGGA (749 glioma samples), GEPIA(163 glioblastoma samples and 207 normal control samples), GEO (GSE4290 and GSE15824). Nine cases of glioma tissue and five cases of normal control brain tissue were collected from the clinical department of Henan Provincial People's Hospital for further verification. A series of bioinformatic analysis methods were used to confirm the relationship between expression and overall survival and clinical molecular characteristics of patients with glioma. RT-qPCR was used to verify the change of expression level of in glioma cells and tissues. MTT assay, colony formation assay, wound-healing assay, immunofluorescence staining, flow cytometry and western blotting were used to detect the effect of on the biological behavior of glioma cell line U251.

Results: The high expression of was significantly related to age, World Health Organization (WHO) grade, chemotherapy status, histological type, and even 1p19q codeletion data and isocitrate dehydrogenase (IDH) mutation. , as an independent risk factor, reduces the overall survival of glioma patients and has diagnostic value for the prognosis of glioma. Gene Set Enrichment Analysis (GSEA) showed that was significantly enriched in cell signaling pathway such as cell cycle, DNA replication and so on. Finally, we confirmed that the knockout of can inhibit the proliferation and invasion of U251 glioma cells, and change the biological behavior of tumor cells by preventing the progression of cell cycle.

Conclusions: may be used as a candidate biomarker for the clinical application of targeted drug and prognostic assessment treatment of glioma. In addition, This study will help to explore the pathological mechanism of glioma.
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http://dx.doi.org/10.7717/peerj.10820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877241PMC
February 2021

Discovery of a novel 53BP1 inhibitor through AlphaScreen-based high-throughput screening.

Bioorg Med Chem 2021 Mar 2;34:116054. Epub 2021 Feb 2.

Drug Discovery and Design Center, the Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address:

Tumor suppressor p53-binding protein 1 (53BP1), a tantem tudor domain (TTD) protein, takes part in DNA Damage Repair (DDR) pathways through the specific recognition of lysine methylation on histones. The dysregulation of 53BP1 is closely related to the development of many diseases including cancer. Moreover, recent studies found that deficiency of 53BP1 could increase the efficiency of precise CRISPR/Cas9 genome editing. Thus, discovery of inhibitor is beneficial to the study of biological functions of 53BP1 and the application of CRISPR/Cas9 genome editing. UNC2170 and its derivatives have been reported as 53BP1 targeted small molecular inhibitors with modest activities. Hence, to discover better 53BP1 inhibitors, we conducted an AlphaScreen assay based high-throughput screening (HTS) and identified a novel and effective 53BP1-TTD inhibitor DP308 which disrupts the binding between 53BP1 and H4K20me2 peptide with an IC value of 1.69 ± 0.73 μM. Both Microscale Themophoresis (MST) and Surface Plasmon Resonance (SPR) assays confirmed the direct binding between DP308 and 53BP1-TTD protein with binding affinity (K) of about 2.7 μM. Molecular docking studies further suggested that DP308 possibly occupies the H4K20me2 binding pocket of the 53BP1-TTD aromatic cage. These results demonstrated that DP308 is a promising small molecule inhibitor for further optimization towards a more potent chemical probe of 53BP1. Additionally, it could be a potential valuable tool for applying to gene editing therapy by increasing the efficiency of CRISPR/Cas9 genome editing.
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http://dx.doi.org/10.1016/j.bmc.2021.116054DOI Listing
March 2021

Self-awareness buffers the consequences of negative feedback: Evidence from an ERP study.

Int J Psychophysiol 2021 Jun 5;164:9-16. Epub 2021 Feb 5.

Institute of Cognition, Brain and Health, Henan University, Kaifeng 475004, China; Institute of Psychology and Behavior, Henan University, Kaifeng 475004, China. Electronic address:

Previous studies have found that self-awareness can help people to recruit more cognitive resources, while people with more cognitive resources can better buffer the detrimental effects of negative events. However, it is not clear whether self-awareness can directly buffer the consequences of negative feedback (i.e., reducing neural sensitivity to negative feedback). To explore this issue, we used a scrambled sentence task (SST) to manipulate participants' self-awareness (self vs. other) and investigated whether outcome evaluations in a gambling task are modulated by the self-awareness priming. Event-related brain potentials (ERPs) were recorded while 27 normal adults performed a gambling task. The ERP analysis focused on the feedback-related negativity (FRN), reward positivity (RewP) and P300 component. We found that the self-awareness priming resulted in a smaller FRN response to the losses compared with the other-awareness priming. There was no significant difference in the RewP response to wins between the self-awareness condition and the other-awareness condition. We also found that the self-awareness condition evoked larger P300 amplitude than the other-awareness condition. The present findings suggest that self-awareness can help people to cope with negative feedback in the early semiautomatic outcome evaluation stage (i.e., reducing neural sensitivity to negative feedback) and enhance top-down evaluation to both positive and negative feedback in the late and deliberate stage, providing direct evidence of the adaptive function of self-awareness on outcome experience.
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http://dx.doi.org/10.1016/j.ijpsycho.2021.02.004DOI Listing
June 2021

Assessment of the toxicity and toxicokinetics of the novel potent tropomyosin receptor kinase (Trk) inhibitor LPM4870108 in rhesus monkeys.

Regul Toxicol Pharmacol 2021 Jun 6;122:104886. Epub 2021 Feb 6.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. Electronic address:

LPM4870108 is a tropomyosin receptor kinase (Trk) inhibitor that is currently under consideration for human clinical trials. We characterized the toxicity and toxicokinetic properties of LPM4870108 following its oral administration to rhesus monkeys (5, 10, or 20 mg/kg/day for 4 weeks with a 4-week recovery period). No evidence of LPM4870108 toxicity was observed over this study as reflected by an absence of difference in body weight, ophthalmoscopy, urinalysis, gross, or histopathology findings. No significant differences in toxicity-related outcomes were detected when comparing LPM4870108 and control groups, and no significant treatment-related changes in food consumption, electrocardiogram results, blood pressure, hematological parameters, biochemical values, organ weight, or bone marrow parameters were observed. Treatment caused dose-dependent effects of gait disturbance, impaired balance, poor coordination, and decreased grip strength in all LPM4870108-treated animals, with these effects being attributable to excessive on-target Trk receptor inhibition. After the 4-week recovery period, all these abnormal treatment-related findings had fully or partially resolved. The toxicokinetic study of monkeys revealed that the LPM4870108 exposure increased with dose. Overall, LPM4870108 exhibited a safety profile in treated monkeys, indicating that the Highest Non-Severely Toxic Dose (HNSTD) for LPM4870108 in monkeys was 20 mg/kg/day.
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http://dx.doi.org/10.1016/j.yrtph.2021.104886DOI Listing
June 2021

Analysis of volatile compounds and flavor fingerprint in Jingyuan lamb of different ages using gas chromatography-ion mobility spectrometry (GC-IMS).

Meat Sci 2021 May 23;175:108449. Epub 2021 Jan 23.

Lanzhou Institute of Animal Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; Quality Safety Risk Assessment of Animal Products (Lanzhou), Ministry of Agriculture, Lanzhou 730050, China.

In this study, gas chromatography coupled to an ion mobility spectrometry (GC-IMS) was used for analyzing some volatile components and flavor fingerprint in samples from Jingyuan lambs of different ages (2, 6, and 12 months). The data obtained from ion mobility were processed using laboratory analysis view processing software for fingerprint recognition, and the principal component analysis (PCA) was performed. GC-IMS provided information on the characteristics and strength of 66 volatile flavor compounds (monomers and dimers). The differences in flavoring substances between lambs of different ages were observed. The compounds with higher intensity peaks in the lamb meat samples were alcohols (1-octen-3-ol, ethanol, (E)-2-hexen-1-ol, 1-pentanol, and 2-propanol), ketones (2-pentanone, 2-heptanone, 3-hydroxy-2-butanone, 2-hexanone, 2-butanone, 2-propanone, and 4-methyl-2-pentanone), aldehydes (n-nonanal, octanal, heptanal, 3-methylbutanal, hexanal, pentanal, 2-methylbutanal, (E)-2-octenal, (E)-2-nonenal, methional, and phenylacetaldehyde), esters (methyl benzoate), furan (2-pentylfuran), and thiazole (trimethylthiazole). The results showed that the flavor fingerprint in samples from Jingyuan lambs of different ages (2, 6, and 12 months) can be established by GC-IMS and PCA based on the identified volatile compounds. This method might be used for the rapid and comprehensive analysis of volatile components in lamb meat.
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http://dx.doi.org/10.1016/j.meatsci.2021.108449DOI Listing
May 2021

[Diagnosis and treatment of 11 cases of subperiosteal orbital abscess caused by acute sinusitis].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Feb;35(2):125-130

Department of Otorhinolaryngology Head and Neck Surgery,Yantai Yuhuangding Hospital,Qingdao University,Yantai,264000,China.

The aim of this study is to explore the diagnosis, clinical manifestations and surgical treatment experience of acute sinusitis complicated with orbital subperiosteal abscess. The clinical data of 11 patients with acute sinusitis complicated by orbital subperiosteal abscess from 1 year and 8 months to 50 years were retrospectively analyzed, including clinical manifestations, imaging manifestations, bacteriological examinations, surgical methods and therapeutic effects. All patients were given antibacterial drugs, glucocorticoids, and surgery. All 11 patients had unilateral lesions. The imaging examinations all supported the appearance of orbital subperiosteal abscess. Nine patients underwent nasal endoscopic sinus opening+SPOA incision and drainage, 2 patients underwent nasal endoscopic sinus opening+ultrasound guided abscess puncture. Eyelid swelling and exophthalmia of all patients were alleviated when discharged. Ten of the 11 patients had no visual acuity change, and one patient had light perception only when she came to the hospital and recovered to 0.05 when discharged, there was no change in visual acuity after 3 months follow-up. The bacterial cultures of nasal secretion or pus were positive in 7 cases, the main pathogenic bacteria were Staphylococcus aureus(3 cases, includes one case of MRSA), Streptococcus anginosus(2 cases), and Streptococcus intermedius(2 cases). Rhinogenous orbital subperiosteal abscess has a rapid onset and progresses quickly. Once an abscess is formed, patients with poor conservative treatment should choose surgical treatment as soon as possible. The most common surgical method is nasal endoscopic sinus opening+SPOA incision and drainage. If the abscess is located above or above the eyeball, puncture or incision and drainage should be combined with ultrasound guidance.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.02.008DOI Listing
February 2021