Publications by authors named "Ning Sun"

556 Publications

The correlation between ERRα expression level and pathological grade, overall survival and cancer types: a study from a cohort of 150 patients with breast cancer.

Recent Pat Anticancer Drug Discov 2021 Jul 28. Epub 2021 Jul 28.

Department of Oncology, Zhongda Hospital, Medicine School of Southeast University, Nanjing 210009, China.

Background: Breast cancer is a common malignant tumor, threatening the general health of women worldwide. Estrogen-related receptor alpha (ERRα) is a member of nuclear receptor family and has been shown to involve in the pathophysiology of breast cancer. However, the specific relationship between ERRα and the triple negative breast cancer (TNBC), is not clear yet.

Objective: This study examined the relevance between ERRα expression and different clinical features of breast cancer patients.

Methods: The expression level of ERRα in 150 human breast cancer tissues (which contains 48 human triple negative breast cancer tissues) and 53 human benign breast tumor tissues using immunohistochemical staining.

Results: ERRα protein level was significantly higher in breast cancer tissues than that in benign tumors. High expression of ERRα was significantly associated with the high grade but not the clinical stage and human epidermal growth factor receptor 2 of the breast cancer tissues. Its high expression was also positively correlated with triple negative breast cancer in pathological grade 2 and 3, but not in grade 1. high expression of ERRα was positively correlated with triple negative breast cancer in each clinical stage. In addition, high expression of ERRα was associated with shorter overall survival of breast cancer patients.

Conclusion: In conclusion, highly expressed ERRα was associated with higher pathological grades triple-negative breast cancer and shorter overall survival. Future studies were required to recruit more patients to consolidate the current findings.
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http://dx.doi.org/10.2174/1574892816666210728120652DOI Listing
July 2021

Model-Based Meta-Analysis in Psoriasis: A Quantitative Comparison of Biologics and Small Targeted Molecules.

Front Pharmacol 2021 1;12:586827. Epub 2021 Jul 1.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed. Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90). A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71-92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12-92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91-77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8-75.7%). What's more, the risankizumab provided the highest response of PASI90 at week 16 and week 24. This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.
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http://dx.doi.org/10.3389/fphar.2021.586827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281289PMC
July 2021

Design and Validation of a Self-aligning Index Finger Exoskeleton for Post-Stroke Rehabilitation.

IEEE Trans Neural Syst Rehabil Eng 2021 Jul 16;PP. Epub 2021 Jul 16.

Rehabilitation of hand functions is necessary to improve post-stroke patients' quality of life. There is initial evidence that hand exoskeletons should exercise flexion/extension (f/e) and abduction/adduction (a/a) of the fingers to rebuild hand functions. However, designing a self-alignment mechanism of the metacarpophalangeal (MCP) joint to improve its wearing comfort is still a challenge. In this paper, a novel index finger exoskeleton with three motors is proposed to help post-stroke patients perform finger a/a and f/e training. A spatial mechanism with passive degrees of freedom for the MCP joint is designed to realize human-robot axes self-alignment. The proposed mechanism's kinematic compatibility is analyzed to show its self-aligning capability, and the kineto-statics analysis is performed to present the exoskeleton's static characteristics. Finally, kinematic and static experiments have been conducted, and the results indicate that the standardized reaction forces square sum of the exoskeleton to the MCP joint can be reduced by 65.8% compared with the state-of-the-art exoskeleton. According to the experimental results, the exoskeleton can achieve the a/a and f/e training and human-robot axes self-alignment, and improve its comfortability. In the future, clinical trials will be further studied to test the exoskeleton.
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http://dx.doi.org/10.1109/TNSRE.2021.3097888DOI Listing
July 2021

Linc00941 regulates esophageal squamous cell carcinoma via functioning as a competing endogenous RNA for miR-877-3p to modulate PMEPA1 expression.

Aging (Albany NY) 2021 07 13;13(13):17830-17846. Epub 2021 Jul 13.

Department of Medical Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China.

Esophageal squamous cell carcinoma (ESCC) represents one of the most common malignancies and is the fifth leading cause of cancer-related deaths. Long intergenic non-coding RNAs (lincRNAs) have been suggested to be dysregulated in various types of cancers, and a growing number of lincRNAs have been implicated to be functional in the ESCC progression. In this study, we examined the role of linc00941 in the ESCC progression and explored the underlying molecular mechanisms. The bioinformatics analysis identified the up-regulation of linc00941 in the ESCC tissues. Further studies showed that linc00941 was up-regulated in ESCC cell lines. The loss-of-function studies demonstrated that linc00941 knockdown suppressed ESCC cell proliferation, invasion and migration, and also suppressed the tumor growth. Furthermore, bioinformatics prediction along with luciferase reporter assay and RNA immunoprecipitation assay implied that linc00941 acted as a competing endogenous RNA for miR-877-3p, and linc00941 regulated ESCC cell progression via at least targeting miR-877-3p. Subsequently, miR-877-3p targeted prostate transmembrane protein, androgen induced 1 (PMEPA1) 3' untranslated region and repressed PMEPA1 expression in ESCC cells; overexpression of PMEPA1 attenuated the inhibitory effects of linc00941 knockdown on the ESCC cell progression. Linc00941 knockdown suppressed epithelial-mesenchymal transition (EMT) via targeting miR-877-3p/PMEPA1 axis in ESCC cells. In conclusion, our results indicated the oncogenic role of linc00941 in ESCC, and knockdown of linc00941 suppressed ESCC cell proliferation, invasion, migration and EMT via interacting with miR-877-3p/PMEPA1 axis.
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http://dx.doi.org/10.18632/aging.203286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312468PMC
July 2021

Cardiac Overexpression of XIN Prevents Dilated Cardiomyopathy Caused by ΔK210 Mutation.

Front Cell Dev Biol 2021 17;9:691749. Epub 2021 Jun 17.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

mutation is associated with a range of cardiac diseases, including dilated cardiomyopathy (DCM). However, the mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we found the expression of cardiac XIN protein was reduced in -ΔK210 hESCs-derived cardiomyocytes and mouse heart tissues. We further investigated whether XIN protects against mutation-induced DCM. Overexpression of the repeat-containing isoform XINB decreased the percentage of myofilaments disorganization and increased cell contractility of -ΔK210 cardiomyocytes. Moreover, overexpression of XINB by heart-specific delivery via AAV9 ameliorates DCM remodeling caused by -ΔK210 mutation in mice, revealed by partially reversed cardiac dilation, systolic dysfunction and heart fibrosis. These results suggest that deficiency of XIN may play a critical role in the development of DCM. Consequently, our findings may provide a new mechanistic insight and represent a therapeutic target for the treatment of idiopathic DCM.
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http://dx.doi.org/10.3389/fcell.2021.691749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247596PMC
June 2021

Toxic effects of benzovindiflupyr, a new SDHI-type fungicide on earthworms (Eisenia fetida).

Environ Sci Pollut Res Int 2021 Jul 2. Epub 2021 Jul 2.

School of Environmental Science and Engineering, America CRC for Environment & Health, Shandong University, 72# Jimo Binhai Road, Qingdao, Shandong, 266237, People's Republic of China.

Benzovindiflupyr has received increasing attention as a new novel succinate dehydrogenase inhibitor (SDHI)-type fungicide. Nonetheless, its traces remaining in soil potentially trigger an ecotoxicological threat to soil organisms including earthworms. This paper evaluates the eco-toxicity of different benzovindiflupyr doses (0.1, 1, 5, and 10 mg kg) on earthworms (Eisenia fetida) after long-term exposure. Consequently, benzovindiflupyr at higher doses significantly inhibited the activities of respiratory chain complex II and succinate dehydrogenase (SDH) in E. fetida. Besides, the reactive oxygen species (ROS) and lipid peroxidation (LPO) were significantly induced in earthworms when treated with this fungicide. After benzovindiflupyr exposure, activities of antioxidant enzymes including catalase, peroxidase, and superoxide dismutase were activated. However, glutathione S-transferase activity in E. fetida was initially induced then inhibited in earthworms after treatment. Furthermore, benzovindiflupyr exposure induced the protein carbonylation (PCO) level in cells indicating oxidative damage to the cellular protein. Due to the destruction of the normal function in the coelomocytes, the phagocytic activity was initially activated, then inhibited when earthworms were treated at 5 and 10 mg kg concentrations. Additionally, DNA damage was induced (larger olive tail moment (OTM) values) with the increase of benzovindiflupyr doses and exposure time. The weight was significantly decreased after benzovindiflupyr exposure on days 21 and 28. Benzovindiflupyr at higher doses significantly decreased the reproduction (number of cocoons and juveniles) of E. fetida. These findings reveal that benzovindiflupyr potentially induces a potential toxicological risk to earthworms when applied in the mentioned above dosages.
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http://dx.doi.org/10.1007/s11356-021-15207-4DOI Listing
July 2021

Vitamin A and retinoic acid accelerate the attenuation of intestinal adaptability upon feeding induced by high-fat diet in mice.

J Nutr Biochem 2021 Jun 18;97:108803. Epub 2021 Jun 18.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address:

With its unique cellular plasticity, the small intestinal mucosa exhibits efficient adaptability upon feeding. However, little is known about the effect of high-fat diet (HFD) feeding on this adaption and its underlying mechanism. Herein, we demonstrated that the cell proliferation ability, mitochondrial morphology, and global transcriptomic profile of the small intestine exhibited a prominent discrepancy between the fasted and refed state in mice, which were markedly attenuated by long-term HFD feeding. The retinol (Vitamin A, VA) metabolism pathway was dramatically affected by HFD feeding in the small intestine. Both VA and its active metabolite retinoic acid (RA), with the administration of lipid micelles, promoted the expression of genes involved in lipid absorption and suppressed the expression of genes involved in the cell proliferation of intestinal organoids. Via chip-qPCR and RT-qPCR, genes involved in lipid metabolism and cell proliferation were target genes of RARα/RXRα in small intestinal organoids treated with RA and lipid micelles. The role of VA in the in vivo attenuation of intestinal adaptability, in response to HFD, was evaluated. Mice were fed a normal chow diet, HFD, or HFD diet supplemented with additional 1.5-fold VA for 12 weeks. VA supplementation in HFD accelerated the attenuation of intestinal adaptability upon feeding induced by HFD, promoted lipid absorption gene expression, and increased body weight and serum cholesterol levels. In conclusion, the discrepancy of the small intestine between the fasted and refed state was dramatically attenuated by HFD feeding, in which VA and RA might play important roles.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108803DOI Listing
June 2021

Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile.

J Med Chem 2021 Jul 17;64(13):9152-9165. Epub 2021 Jun 17.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.

Proteolysis-targeting chimera (PROTAC) is an attractive technology in drug discovery. Canonically, targets act as a basic starting point in the most previous PROTAC design. Here, we designed degraders considering from the view of clinical benefits. With this novel design, Brigatinib was turned into a degrader SIAIS164018 and endowed with unique features. First, SIAIS164018 could degrade not only ALK fusion proteins in activating or G1202R-mutated form but also mutant EGFR with L858R + T790M, which are two most important targets in non-small-cell lung cancer. Second, SIAIS164018 strongly inhibited cell migration and invasion of Calu-1 and MDA-MB-231. Third and surprisingly, SIAIS164018 degrades several important oncoproteins involved in metastasis such as FAK, PYK2, and PTK6. Interestingly, SIAIS164018 reshuffled the kinome ranking profile when compared to Brigatinib. Finally, SIAIS164018 is orally bioavailable and well tolerated in vivo. SIAIS164018 is an enlightening degrader for us to excavate the charm of protein degradation.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00373DOI Listing
July 2021

The cerebral mechanism underlying the acupoints with specific effect for gallbladder stone disease: protocol for a randomized controlled task-fMRI trial.

Trials 2021 Jun 14;22(1):399. Epub 2021 Jun 14.

Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Clinical Research Center for Acupuncture and Moxibustion in Sichuan province, 37 Shierqiao Road, Chengdu, 610075, Sichuan, China.

Background: As it has been recorded in ancient Chinese classics, Yanglingquan (GB34) and Dannangxue (EX-LE6) are two important acupoints that can regulate the function of the gallbladder. Acupuncture at these two acupoints is considered particularly effective for gallbladder disease treatment, especially for alleviating gallbladder stone disease (GSD) symptoms that can be aggravated after intaking high-fat food. However, the superior effect between the two acupoints still needs to be further explored, as well as the underlying central mechanism has never been investigated to date.

Methods And Design: Ninety participants diagnosed with GSD will be randomly divided into group A (acupuncture at GB34), group B (acupuncture at EX-LE6), and group C (acupuncture at non-acupoint) in a ratio of 1:1:1. All of them will receive a 30-min acupuncture treatment with fatty-food cues being presented before and after acupuncture. During the task, participants will be scanned by MRI and required to rate their desire for high-/low-fat food with an 11-point Likert scale. Additionally, the participants' pain/discomfort sensation will be evaluated using the Numeric Rating Scale (NRS) at four timepoints, including before the 1st task fMRI scan, before and after acupuncture, and after the 2nd task fMRI scan. For both behavior and fMRI data, the ANOVA analysis will be conducted among three groups to testify the immediate effect of GB34 and EX-LE6. The post hoc t-test will be employed to further explore the superiority between acupuncture with GB34 and EX-LE6. Furthermore, correlation analyses will be conducted to investigate a possible correlation between neural changes and clinical data.

Discussion: In comparison to the non-acupoint, the results will firstly explore the superior effect between acupuncture with GB34 and EX-LE6 on GSD patients by observing their behavioral and neural response change to fatty-food cue, and then to investigate the underlying central mechanism.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2000034368 . Registered on 3 July 2020.
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http://dx.doi.org/10.1186/s13063-021-05356-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204415PMC
June 2021

Psychoactive Effects of Against Restraint Stress-Induced Memory Dysfunction in Mice Through Modulating Intestinal Inflammation and permeability-a Study Based on the Gut-Brain Axis Hypothesis.

Front Pharmacol 2021 26;12:662148. Epub 2021 May 26.

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Though the underlying mechanism remains elusive, a close relationship between psychological stress and intestinal inflammation has been widely accepted. Such a link is very important to set the basis for our understanding of the critical role of gut-brain axis (GBA) in homeostatic processes in health and disease. Probiotics that could confer benefits to mental health through GBA are referred to as "psychobiotics". This study aimed to further determine whether a potential psychobiotic strain, BS15 could prevent memory dysfunction in mice induced by psychological stress through modulating the gut environment, including intestinal inflammation and permeability. Memory dysfunction in mice was induced by restraint stress (RS), one of the most commonly utilized models to mimic psychological stress. The mice were randomly categorized into three groups including no stress (NS), restraint stress (RS), and probiotic (RS-P) and administered with either phosphate buffered saline (NS and RS groups) or BS15 (RS-P group) every day from day 1-28. From days 22-28, the mice in RS and RS-P groups were subjected to RS each day. Results revealed that BS15-pretreatment enhanced the performance of RS-induced mice during three different behavioral tests for memory ability and positively modulated the hypothalamic-pituitary-adrenal axis by attenuating the serum corticosterone level. In the hippocampus, BS15 positively modulated the memory-related functional proteins related to synaptic plasticity, increased neurotransmitter levels, and prevented RS-induced oxidative stress and mitochondria-mediated apoptosis. In the intestines, BS15 protected the RS-induced mice from damaged gut barrier by enhancing the mRNA levels of tight junction proteins and exerted beneficial effects on the anti-inflammatory cytokine levels reduced by RS. These findings provided more evidence to reveal the psychoactive effect of BS15 against memory dysfunction in RS-induced mice by modulating intestinal inflammation and permeability.
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http://dx.doi.org/10.3389/fphar.2021.662148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189558PMC
May 2021

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Jun 11;111:110386. Epub 2021 Jun 11.

Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Objective: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure.

Method: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms.

Results: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe.

Conclusion: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110386DOI Listing
June 2021

uc.77- Downregulation Promotes Colorectal Cancer Cell Proliferation by Inhibiting FBXW8-Mediated CDK4 Protein Degradation.

Front Oncol 2021 19;11:673223. Epub 2021 May 19.

Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Transcribed ultraconserved regions (T-UCRs) are a new type of long non-coding RNA, and the UCR has 481 segments longer than 200 base pairs that are 100% conserved between humans, rats, and mice. T-UCRs involved in colorectal cancer (CRC) have not been studied in detail. We performed T-UCR microarray analysis and found that uc.77- was significantly downregulated in CRC tissues and cell lines. Ectopic expression of uc.77- significantly inhibited the proliferation of CRC cells and the growth of xenograft tumors in nude mice . Mechanistic studies showed that uc.77- competed with FBXW8 mRNA for binding to microRNA (miR)-4676-5p through a competing endogenous RNA mechanism and inhibited the proliferation of CRC cells by negatively regulating CDK4. The present findings highlight the role of the uc.77-/miR-4676-5p/FBXW8 axis in CRC and identify uc.77- as a potential novel target for the treatment of CRC.
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http://dx.doi.org/10.3389/fonc.2021.673223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172171PMC
May 2021

Integrated Pharmacological Analysis on the Mechanism of Fuyou Formula in Treating Precocious Puberty.

Front Pharmacol 2021 7;12:649732. Epub 2021 May 7.

Department of Pharmacy, National Center for Children Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Fu-you formula (FY), a Traditional Chinese Medicine (TCM) formula composed of 12 herbs, as an in-hospital preparation, has been used treat to precocious puberty (PP) for decades. However, the lack of phytochemical characterization and mechanism of FY remains the main limitation for its spreading. In this study, we analyze the components and mechanisms of FY in PP, based on the integrated pharmacology. Investigated main constituents, targets, pathways of FY by using an integrative pharmacology, and recognized main constituents by HPLC-MS/MS. Then, observed the levels of Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E) in danazol-induced PP in Sprague-Dawley (SD) rats. Lastly, retrospective study analyzed the clinical data of 575 patients who were diagnosed PP, treated by the FY, and followed-up in our hospital from 2014-2020. The result that total of 116 important candidate targets were selected based on pharmacological analysis. Selected the top 10 values key targets such as the estrogen receptor alpha (ESR1) and insulin-like growth factor 1 (IGF1), were localized and the related gene functions were determined. Gene functions were associated with biological regulation, a cellular process, or signaling pathway, such as the Estrogen signaling pathway, MAPK signaling pathway and PI3K-Akt signaling pathway. By recognizing the five compounds related to the ESR1 and IGF1, which are Quercetin, kaempferol, Luteolin, Apigenin, and Emodin. The results of the molecular docking study further showed that the flavonoids had a strong binding affinity for ESR1 and IGF1 after docking into the crystal structure. The results showed that the FY could effectively reduce E, LH, and FSH levels in SD rats. Furthermore, the results of the retrospective analysis of medical records showed that the FY could remarkably reduce E levels in girls with PP.
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http://dx.doi.org/10.3389/fphar.2021.649732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138182PMC
May 2021

Corrigendum to 'Engineering human ventricular heart tissue based on macroporous iron oxide scaffolds' [Acta Biomaterialia 88 (2019) 540-553].

Acta Biomater 2021 Jun 2;127:353. Epub 2021 May 2.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address:

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http://dx.doi.org/10.1016/j.actbio.2021.04.031DOI Listing
June 2021

Study of the microscopic mechanism of lauryl glucoside wetting coal dust: Environmental pollution prevention and control.

J Hazard Mater 2021 06 27;412:125223. Epub 2021 Jan 27.

State Key Laboratory of Mining Disaster Prevention and Control Co-found by Shandong Province and the Ministry of Science and Technology, Shandong University of Science and Technology, Qingdao 266590, China; College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, Shandong Province, China.

Molecular dynamics simulation combined with experimental methods were used to investigate the adsorption and wetting process of 25 lauryl glucoside (APG-12) molecules on coal molecules and in turn study the dust suppression mechanism by APG-12 at the molecular level. Through wetting experiments, our preliminary findings showed that APG-12 does have a certain wetting effect on coal dust. According to density functional theory in molecular dynamics simulations, the electrostatic potential and surface charge of the APG-12 and coal molecular models were analyzed to identify their nucleophilic and electrophilic regions, and illustrate the hydrogen bond adsorption mechanism. The dynamics simulation results showed that APG-12 molecules can be easily adsorbed on the surface of coal molecules and then adsorb water molecules around them under the action of hydrogen bonds. This was consistent with the results of an analysis of the system's radial distribution function and the relative concentration distribution of each component in the Z-axis direction. The results are in good agreement with the experimental results from scanning electron microscopy and energy dispersive spectrometer analysis. These data provide further evidence that APG-12 can clearly improve the wettability and suppression of coal dust, which is of great importance for controlling coal dust pollution.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125223DOI Listing
June 2021

Correlation of Neutralizing Antibodies (NAbs) between Sows and Piglets and Evaluation of Protectability Associated with Maternally Derived NAbs in Pigs against Circulating Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) under Field Conditions.

Vaccines (Basel) 2021 Apr 21;9(5). Epub 2021 Apr 21.

Animal Disease Diagnostic Center, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.

Porcine reproductive and respiratory syndrome (PRRS), which is caused by a highly transmissible pathogen called porcine reproductive and respiratory syndrome virus (PRRSV), has caused severe problems, including reproductive disorders in sows and respiratory symptoms in nursery pigs worldwide, since the early 1990s. However, currently available PRRSV vaccines do not supply complete immunity to confront the viral infection. Elicitation of PRRSV-specific neutralizing antibodies (NAbs) during the preinfectious period has been deemed to be a feasible strategy to modulate this virus, especially in farms where nursery pigs are seized with PRRSVs. A total of 180 piglets in a farrow-to-finish farm that had a natural outbreak of PRRS were distributed into three groups based on the different PRRSV NAbs levels in their dams. In the present study, piglets that received superior maternal-transferred NAbs showed delayed and relatively slight viral loads in serum and, on the whole, higher survival rates against wild PRRSV infections. A positive correlation of maternal NAbs between sows and their piglets was identified; moreover, high NAbs titers in piglets can last for at least 4 weeks. These results provide updated information to develop an appropriate immune strategy for breeding and for future PRRSV control under field conditions.
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http://dx.doi.org/10.3390/vaccines9050414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143086PMC
April 2021

Genome of the butterfly hillstream loach provides insights into adaptations to torrential mountain stream life.

Mol Ecol Resour 2021 Aug 12;21(6):1922-1935. Epub 2021 May 12.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Butterfly hillstream loach (Beaufortia kweichowensis), a benthic fish in the torrential mountain streams, possesses a totally flat ventrum, flattened craniofacial and body skeletons, and enlarged paired fins covered by substantially small keratinous structures. However, little is known about the genetic basis of these specialized morphological adaptations. Here we present a 448.52-Mb genome assembly with contig N50 length of 5.53 Mb by integrating Illumina short-read sequencing, Nanopore long-read sequencing and HiC-based chromatin map. Demographic history reconstruction of the butterfly hillstream loach reveals that the population dynamics is correlated with the different stages of uplifting of the Tibetan Plateau. Comparative genomic analysis finds evidence of six keratin genes in butterfly hillstream loach evolving under positive selection. Within these genes, two keratin genes exhibit species-specific and divergent amino acid changes, suggesting a role in the formation of the unculi. Additionally, a series of positively selected genes, rapid evolving genes, specific variant genes and expanded gene families are found, including genes related to Hedgehog, Notch and BMP pathways, which may be involved in craniofacial development. These findings may have important implications for understanding the genetic basis of phenotypic adaptation to torrential mountain stream life.
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http://dx.doi.org/10.1111/1755-0998.13400DOI Listing
August 2021

Isogenic human pluripotent stem cell disease models reveal ABRA deficiency underlies cTnT mutation-induced familial dilated cardiomyopathy.

Protein Cell 2021 Apr 22. Epub 2021 Apr 22.

Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

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http://dx.doi.org/10.1007/s13238-021-00843-wDOI Listing
April 2021

Behavior of the particulate matter (PM) emitted by trackless rubber-tyred vehicle (TRTV) at an idle speed under different movement conditions and ventilation optimization.

Sci Total Environ 2021 Aug 10;783:147008. Epub 2021 Apr 10.

College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, Shandong Province, China; State Key Laboratory of Mining Disaster Prevention and Control Co-found by Shandong Province and the Ministry of Science and Technology, Shandong University of Science and Technology, Qingdao 266590, China.

The particulate matter (PM) emitted by a trackless rubber-tyred vehicle (TRTV) in coal mines can seriously threaten the health and safety of the exposed workers underground. In this paper, in order to effectively reduce the PM concentration and improve the underground working environment, a combination of numerical simulations and field measurements was adopted to study the migration distribution of the PM emitted by a TRTV at an idle speed for 60 s under different movement conditions, and the dilution effects of the ventilation rate on the PM. The results showed that under different movement conditions, the PM mainly moved along the floor of the roadway, but upward diffusion trends were shown overall, which meant that the chambers are in high-risk areas. Field measurements were then performed under the two conditions to verify the effectiveness of the simulations. Furthermore, the dilution effects of the increased ventilation rate on the PM were analyzed. It was concluded that the optimal dilution ventilation rate under condition 1 was 4600m/min, and that under condition 2 was 2800m/min. Accordingly, the driver of the TRTV should try to move forward when entering the chamber.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147008DOI Listing
August 2021

Electroacupuncture Inhibits Autophagy of Neuron Cells in Postherpetic Neuralgia by Increasing the Expression of miR-223-3p.

Biomed Res Int 2021 8;2021:6637693. Epub 2021 Mar 8.

Department of Neurobiology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, China.

Postherpetic neuralgia (PHN) is a complication of herpes zoster viral infection. Its main manifestations are continuous or intermittent burning-like and electroshock-like pain in the affected nerves. Electroacupuncture (EA) is widely used in clinical treatment and exerts effects in alleviating neuropathic pain. In this study, we investigated the effect and underlying mechanism of EA on PHN. Sprague-Dawley rats were treated with resiniferatoxin (RTX) to establish a PHN model and subjected to EA and/or miR-223-3p overexpression (OV) or interference. Mechanical withdrawal latency was measured as an indication of pain sensitivity. Hematoxylin-eosin staining and transmission electron microscopy were performed to observe neuron cell morphology and autophagic vacuoles, respectively. ELISA was performed to detect reactive oxygen species (ROS) production and the levels of tumor necrosis factor- (TNF-) , inducible nitric oxide synthase (iNOS), interleukin- (IL-) 6, and IL-10. Changes in autophagy and apoptosis-related miRNAs were detected by immunofluorescence and qRT-PCR, respectively. In RTX-treated rats, OV and EA reduced pain sensitivity, decreased the number of eosinophils, and increased that of nerve cells. ROS generation and the levels of TNF- and iNOS were significantly reduced, while those of IL-6 and IL-10 were increased. OV and EA induced fewer autophagic vacuoles than those in the model group. The expression of autophagy-related protein microtubule-associated protein 1 light chain 3-II, ATG9, and Rab1 was decreased by OV and EA, whereas that of P62 was increased. qRT-PCR revealed that miR-223-3p expression in the model group decreased but was increased by EA. EA inhibits neuron cell autophagy in PHN by increasing miR-223-3p expression.
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http://dx.doi.org/10.1155/2021/6637693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026292PMC
May 2021

Probiotic alleviate fluoride-induced memory impairment by reconstructing gut microbiota in mice.

Ecotoxicol Environ Saf 2021 Jun 30;215:112108. Epub 2021 Mar 30.

Animal Microecology Institute, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China. Electronic address:

Fluoride which is widespread in our environment and food due to its geological origin and industrial pollution has been identified as a developmental neurotoxicant. Gut-brain axis provides new insight into brain-derived injury. We previously found the psychoactive effects of a probiotic strain, Lactobacillus johnsonii BS15 against fluoride-induced memory dysfunction in mice by modulating the gut-brain axis. In this study, we aimed to detect the link between the reconstruction of gut microbiota and gut-brain axis through which probiotic alleviate fluoride-induced memory impairment. We also added an hour of water avoidance stress (WAS) before behavioral tests and sampling, aiming to demonstrate the preventive effects of the probiotic on fluoride-induced memory impairment after psychological stress. Mice were given fluoridated drinking water (sodium fluoride 100 ppm, corresponding to 37.8 ± 2.4 ppm F¯) for 70 days and administered with PBS or a probiotic strain, Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70 day exposure to sodium fluoride. Results showed that fluoride increases the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and reduces the exploration ratio in novel object recognition (NOR) test and the spontaneous exploration during the T-maze test in mice following WAS, which were significantly improved by the probiotic. 16S rRNA sequencing showed a significant separation in ileal microbiota between the fluoride-treated mice and control mice. Lactobacillus was the main targeting bacteria and significantly reduced in fluoride-treated mice. BS15 reconstructed the fluoride-post microbiota and increased the relative abundance of Lactobacillus. D-lactate content and diamine oxidase (DAO) activity, two biomarkers of gut permeability were reduced in the serum of probiotic-inoculated mice. ZO-1, an intestinal tight junction protein was reduced by fluoride in mRNA, and its protein levels were increased by the probiotic treatment. Moreover, the hippocampus which is essential to learning and memory, down-regulated mRNA level of both the myelin-associated glycoprotein (MAG), and protein levels of brain-derived neurotrophic factor (BDNF), including the improvement of cAMP response element-binding protein (CREB) by BS15 in fluoride-exposed mice after WAS. Via spearman correlation analysis, Lactobacillus displayed significantly positive associations with the behavioral tests, levels of nerve development related factors, and intestinal tight junction proteins ZO-1, and negative association with TNF-α of the hippocampus, highlighting regulatory effects of gut bacteria on memory potential and gut barrier. These results suggested the psychoactive effects of BS15 on fluoride-induced memory dysfunction after psychological stress. In addition, there may be some correlations between fluoride-induced memory dysfunction and reconstruction of gut microbiota. AVAILABILITY OF DATA AND MATERIALS: 16S rRNA sequencing reads have uploaded to NCBI. The accession code of 16S rRNA sequencing reads in the National Center for Biotechnology Information (NCBI) BioProject database: PRJNA660154.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112108DOI Listing
June 2021

Harmine is an effective therapeutic small molecule for the treatment of cardiac hypertrophy.

Acta Pharmacol Sin 2021 Mar 30. Epub 2021 Mar 30.

Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Harmine is a β-carboline alkaloid isolated from Banisteria caapi and Peganum harmala L with various pharmacological activities, including antioxidant, anti-inflammatory, antitumor, anti-depressant, and anti-leishmanial capabilities. Nevertheless, the pharmacological effect of harmine on cardiomyocytes and heart muscle has not been reported. Here we found a protective effect of harmine on cardiac hypertrophy in spontaneously hypertensive rats in vivo. Further, harmine could inhibit the phenotypes of norepinephrine-induced hypertrophy in human embryonic stem cell-derived cardiomyocytes in vitro. It reduced the enlarged cell surface area, reversed the increased calcium handling and contractility, and downregulated expression of hypertrophy-related genes in norepinephrine-induced hypertrophy of human cardiomyocytes derived from embryonic stem cells. We further showed that one of the potential underlying mechanism by which harmine alleviates cardiac hypertrophy relied on inhibition of NF-κB phosphorylation and the stimulated inflammatory cytokines in pathological ventricular remodeling. Our data suggest that harmine is a promising therapeutic agent for cardiac hypertrophy independent of blood pressure modulation and could be a promising addition of current medications for cardiac hypertrophy.
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http://dx.doi.org/10.1038/s41401-021-00639-yDOI Listing
March 2021

Facile synthesis of [email protected] hollow structure for excellent microwave absorption and anticorrosion performance.

J Colloid Interface Sci 2021 Jul 15;594:604-620. Epub 2021 Mar 15.

School of Materials Science and Engineering, Ocean University of China, Qingdao 266100, China. Electronic address:

A three-dimensional hollow NiCoO structure was successfully prepared with a precipitation-hydrothermal method. A balance between magnetic and dielectric losses was achieved by using a hollow NiCoO structure loaded with benzotriazole (BTA), and thus the performance of electromagnetic waves was attenuated. The minimum reflection loss value of [email protected] at 16.01 GHz was -35.39 dB when the absorber thickness was 2 mm, at which the absorption bandwidth for an RL of less than -10 dB is as high as 4.64 GHz. The absorption mechanism was characterized by the synergy among interfacial polarization, multiple reflection, and dipole polarization enhancement between NiCoO and BTA. Interestingly, the epoxy/[email protected] coating not only exhibited an outstanding microwave absorption (MA) performance but also has excellent anticorrosion and self-healing properties, as shown by the results of electrochemical impedance spectroscopy and confocal laser scanning microscopy. This work would be very helpful to the development of novel coatings with excellent MA performance and anticorrosion and self-healing properties.
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http://dx.doi.org/10.1016/j.jcis.2021.03.048DOI Listing
July 2021

Effective degradation of EGFR mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems.

Eur J Med Chem 2021 Jun 7;218:113328. Epub 2021 Mar 7.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, 201210, China; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. Electronic address:

Targeted therapy of treating patients with specific tyrosine kinase inhibitors (TKIs) is currently the standard care for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer. However, the inevitably developed drug resistance in patients to EGFR TKIs is the biggest obstacle for cancer targeted therapy. About 60% of drug resistance to the 1st generation of EGFR TKIs was resulted from an acquired T790M mutation in the kinase domain of EGFR protein. Proteolysis targeting chimera (PROTAC) is a lately-developed technology to target point of interest proteins for degradation. Because EGFR-mutant lung cancers are highly dependent on EGFR proteins, designing specific PROTAC molecules to degrade EGFR proteins from cancer cells provides a very promising strategy to treat such patients and eradicate drug resistance. Currently, there is no cereblon (CRBN)-based PROTAC reported able to degrade T790M-containing EGFR resistant proteins. In this study, we synthesized two novel CRBN-based EGFR PROTACs, SIAIS125 and SIAIS126, based on EGFR inhibitor canertinib and cereblon ligand pomalidomide. These two degraders displayed potent and selective antitumor activities in EGFR TKI resistant lung cancer cells. Firstly, they could selectively degrade EGFR resistant proteins in H1975 cells at the concentration of 30-50 nM, and EGFR proteins in PC9 cells. But they did not degrade EGFR mutant proteins in PC9Brca1 cells or wild type EGFR in A549 lung cancer cells. They could also selectively inhibit the growth of EGFR mutant lung cancer cells but not that of normal cells or A549 cells. Secondly, the degradation of EGFR proteins was long lasting up to 72 h. Thirdly, these degraders displayed better inhibition of EGFR phosphorylation in H1975 cells and PC9Brca1 cells comparing to canertinib. Finally, these degraders could also induce significant apoptosis and cell cycles arrest in H1975 cells. Pre-incubation with canertinib, pomalidomide or ubiquitination inhibitor MLN4924 totally blocked EGFR degradation by PROTACs. Mechanistic studies showed that PROTAC could induce autophagy in lung cancer cells. PROTAC-induced EGFR degradation acted through both ubiquitin/proteosome system and ubiquitin/autophagy/lysosome system. Elevating autophagy activities enhanced EGFR degradation and cell apoptosis induced by PROTACs. Our research not only offered a novel PROTAC tool to target EGFR TKI drug resistance in lung cancer, but also firstly demonstrated that the involvement of autophagy/lysosome system in PROTAC- mediated target protein degradation.
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http://dx.doi.org/10.1016/j.ejmech.2021.113328DOI Listing
June 2021

Structure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib.

Eur J Med Chem 2021 May 11;217:113335. Epub 2021 Mar 11.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, 201210, China; CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. Electronic address:

Fusion proteins of the anaplastic lymphoma kinase (ALK) are promising therapeutic targets for cancer and other human diseases, especially for non-small cell lung cancer (NSCLC) and anaplastic large-cell lymphomas (ALCLs). We described herein a structure-based design, synthesis, and evaluation of ALK PROTACs (proteolysis-targeting chimeras) based on Alectinib as the warhead. We firstly screened CRBN ligands as the E3 ligase moiety, then obtained a series of potent ALK degraders based on different CRBN ligands, exemplified by SIAIS091 and SIAIS001 with lenalidomide/thalidomide-based linkers. Both of them induced effective ALK degradation at low nanomolar concentrations in cells, and showed much better growth inhibition effects than Alectinib. SIAIS091 or SIAIS001 also promoted cell cycle arrest in G1/S phase. Finally, SIAIS001 exhibited good oral bioavailability in Pharmacokinetics study.
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http://dx.doi.org/10.1016/j.ejmech.2021.113335DOI Listing
May 2021

Synergistic influence of education and marriage on the risk for cognition loss among the older people in China.

Nurs Open 2021 Mar 16. Epub 2021 Mar 16.

NingBo College of Health Sciences, Yinzhou, China.

Aim: The study aimed to prove that both rationality and emotion are indispensable for older people to maintain their ability to live independently during the twilight of their lives. The resilience of older people to dementia were investigated by considering the interactions between educational levels and marriage status.

Design: A quantitative study was conducted using questionnaires.

Methods: Four sociodemographic variables (age, sex, educational level and marital status) were collected from 1,177 older Chinese participants, whose mini-mental state examination scores (MMSE scores) were measured.

Results: A lower educational level coupled with being widowed caused a greater risk for severe cognitive impairment (relative risk [RR] 1.48; 95% confidence interval [CI] 1.20-1.82; p < .001) for high-aged older participants (age range: ≥80) than for their low-aged counterparts (age range: ≥60 and <80). In contrast, a higher educational level coupled with being married levelled this age-related risk for cognitive loss (RR 0.91; 95% CI 0.65-1.27; p = .62).
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http://dx.doi.org/10.1002/nop2.801DOI Listing
March 2021

Synergistic influence of education and marriage on the risk for cognition loss among the older people in China.

Nurs Open 2021 Mar 16. Epub 2021 Mar 16.

NingBo College of Health Sciences, Yinzhou, China.

Aim: The study aimed to prove that both rationality and emotion are indispensable for older people to maintain their ability to live independently during the twilight of their lives. The resilience of older people to dementia were investigated by considering the interactions between educational levels and marriage status.

Design: A quantitative study was conducted using questionnaires.

Methods: Four sociodemographic variables (age, sex, educational level and marital status) were collected from 1,177 older Chinese participants, whose mini-mental state examination scores (MMSE scores) were measured.

Results: A lower educational level coupled with being widowed caused a greater risk for severe cognitive impairment (relative risk [RR] 1.48; 95% confidence interval [CI] 1.20-1.82; p < .001) for high-aged older participants (age range: ≥80) than for their low-aged counterparts (age range: ≥60 and <80). In contrast, a higher educational level coupled with being married levelled this age-related risk for cognitive loss (RR 0.91; 95% CI 0.65-1.27; p = .62).
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http://dx.doi.org/10.1002/nop2.801DOI Listing
March 2021

Identification of Novel Tricyclic Benzo[1,3]oxazinyloxazolidinones as Potent Antibacterial Agents with Excellent Pharmacokinetic Profiles against Drug-Resistant Pathogens.

J Med Chem 2021 03 11;64(6):3234-3248. Epub 2021 Mar 11.

Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, P. R. China.

A series of conformationally constrained novel benzo[1,3]oxazinyloxazolidinones were designed, synthesized, and evaluated on their activities against , Gram-positive bacteria, and Gram-negative bacteria. The studies identified a new compound that displayed good to excellent antibacterial and antitubercular profiles against drug-resistant TB strains (MIC = 0.48-0.82 μg/mL), MRSA (MIC = 0.25-0.5 μg/mL), MRSE (MIC = 1 μg/mL), VISA (MIC = 0.25 μg/mL), and VRE (MIC = 0.25 μg/mL) and some linezolid-resistant strains (MIC 1-2 μg/mL). Compound was demonstrated as a promising candidate through ADME/T evaluation including microsomal stability, cytotoxicity, and inhibition of hERG and monoamine oxidase. Notably, showed excellent mouse PK profile with high plasma exposure (AUC = 78 669 h·ng/mL), high peak plasma concentration ( = 10 253 ng/mL), appropriate half-life of 3.76 h, and superior oral bioavailability (128%). The present study not only successfully provides a novel benzo[1,3]oxazinyloxazolidinone scaffold with superior druggability but also lays a good foundation for new antibacterial drug development.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02153DOI Listing
March 2021

Population Pharmacokinetics of Phosphocreatine and Its Metabolite Creatine in Children With Myocarditis.

Front Pharmacol 2020 16;11:574141. Epub 2020 Nov 16.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

This study aimed to develop a parent-metabolite joint population pharmacokinetic model to characterize the pharmacokinetic (PK) profile for phosphocreatine (PCr) and its metabolite creatine (Cr) in children with myocarditis and to use this model to study the PK profile of different dosing schemes. One hundred pediatric patients with myocarditis were enrolled. Blood samples were collected at baseline and approximately 30, 40 or 50, 75, and 180 min after a single dose of phosphocreatine sodium. Plasma PCr and Cr concentrations were determined using an HPLC-MS/MS method. A nonlinear mixed effect model approach was used to build the population pharmacokinetic model. After validation, the model was used for simulations to evaluate the PK profile of different dosing schemes. A total of 997 plasma concentrations (498 for PCr and 499 for Cr) were included in the analysis. A four-compartment chain model (central and peripheral compartments for both PCr and Cr) with the first-order elimination adequately characterized the process of PCr and Cr. Allometric scaling based on bodyweight was applied to the PK parameters. The covariate analysis identified that the glomerular filtration rate (GFR) was strongly associated with Cr clearance. Bootstrapping and visual predictive checks suggested that a robust and reliable pharmacokinetic model was developed. The simulation results showed that PCr had no accumulation . With the infusion of PCr, the concentration of Cr increased rapidly. A joint population pharmacokinetic model for PCr and Cr in pediatric patients with myocarditis was successfully developed for the first time.
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http://dx.doi.org/10.3389/fphar.2020.574141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919190PMC
November 2020

Treatment of pediatric intracranial dissecting aneurysm with clipping and angioplasty, and next-generation sequencing analysis: A case report and literature review.

World J Clin Cases 2021 Feb;9(5):1103-1110

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Background: Large intracranial dissecting aneurysm (IDA) in the anterior cerebral circulation is rare in children. There has been no consensus on the diagnosis and treatment for IDA in children.

Case Summary: We report a 3-year-old boy with a large ruptured IDA in the right middle cerebral artery (16 mm × 14 mm). The IDA was successfully managed with clipping and angioplasty. Next-generation sequencing of the blood sample followed by bioinformatics analysis suggested that the rs78977446 variant of the gene is a risk for pediatric IDA. Three years after surgery, the boy was develop-mentally normal.

Conclusion: Clipping and angioplasty are effective treatments for ruptured IDA in the anterior cerebral circulation. rs78977446 is a risk factor for pediatric IDA.
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http://dx.doi.org/10.12998/wjcc.v9.i5.1103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896649PMC
February 2021
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