Publications by authors named "Jia Sun"

425 Publications

Transferrin receptor 1 ablation in satellite cells impedes skeletal muscle regeneration through activation of ferroptosis.

J Cachexia Sarcopenia Muscle 2021 May 6. Epub 2021 May 6.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

Background: Satellite cells (SCs) are critical to skeletal muscle regeneration. Inactivation of SCs is linked to skeletal muscle loss. Transferrin receptor 1 (Tfr1) is associated with muscular dysfunction as muscle-specific deletion of Tfr1 results in growth retardation, metabolic disorder, and lethality, shedding light on the importance of Tfr1 in muscle physiology. However, its physiological function regarding skeletal muscle ageing and regeneration remains unexplored.

Methods: RNA sequencing is applied to skeletal muscles of different ages to identify Tfr1 associated to skeletal muscle ageing. Mice with conditional SC ablation of Tfr1 were generated. Between Tfr1 and Tfr1 (n = 6-8 mice per group), cardiotoxin was intramuscularly injected, and transverse abdominal muscle was dissected, weighted, and cryosectioned, followed by immunostaining, haematoxylin and eosin staining, and Masson staining. These phenotypical analyses were followed with functional analysis such as flow cytometry, tread mill, Prussian blue staining, and transmission electron microscopy to identify pathological pathways that contribute to regeneration defects.

Results: By comparing gene expression between young (2 weeks old, n = 3) and aged (80 weeks old, n = 3) mice among four types of muscles, we identified that Tfr1 expression is declined in muscles of aged mice (~80% reduction, P < 0.005), so as to its protein level in SCs of aged mice. From in vivo and ex vivo experiments, Tfr1 deletion in SCs results in an irreversible depletion of SCs (~60% reduction, P < 0.005) and cell-autonomous defect in SC proliferation and differentiation, leading to skeletal muscle regeneration impairment, followed by labile iron accumulation, lipogenesis, and decreased Gpx4 and Nrf2 protein levels leading to reactive oxygen species scavenger defects. These abnormal phenomena including iron accumulation, activation of unsaturated fatty acid biosynthesis, and lipid peroxidation are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis further exacerbates SC proliferation and skeletal muscle regeneration. Ferrostatin-1, a ferroptosis inhibitor, could not rescue ferroptosis. However, intramuscular administration of lentivirus-expressing Tfr1 could partially reduce labile iron accumulation, decrease lipogenesis, and promote skeletal muscle regeneration. Most importantly, declined Tfr1 but increased Slc39a14 protein level on cellular membrane contributes to labile iron accumulation in skeletal muscle of aged rodents (~80 weeks old), leading to activation of ferroptosis in aged skeletal muscle. This is inhibited by ferrostatin-1 to improve running time (P = 0.0257) and distance (P = 0.0248).

Conclusions: Satellite cell-specific deletion of Tfr1 impairs skeletal muscle regeneration with activation of ferroptosis. This phenomenon is recapitulated in skeletal muscle of aged rodents and human sarcopenia. Our study provides mechanistic information for developing novel therapeutic strategies against muscular ageing and diseases.
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http://dx.doi.org/10.1002/jcsm.12700DOI Listing
May 2021

Elucidating direct kinase targets of compound Danshen dropping pills employing archived data and prediction models.

Sci Rep 2021 May 5;11(1):9541. Epub 2021 May 5.

GeneNet Pharmaceuticals Co. Ltd., No. 1, Tingjiang West Road, Beichen District, Tianjin, 300410, China.

Research on direct targets of traditional Chinese medicine (TCM) is the key to study the mechanism and material basis of it, but there is still no effective methods at present. We took Compound Danshen dropping pills (CDDP) as a study case to establish a strategy to identify significant direct targets of TCM. As a result, thirty potential active kinase targets of CDDP were identified. Nine of them had potential dose-dependent effects. In addition, the direct inhibitory effect of CDDP on three kinases, AURKB, MET and PIM1 were observed both on biochemical level and cellular level, which could not only shed light on the mechanisms of action involved in CDDP, but also suggesting the potency of drug repositioning of CDDP. Our results indicated that the research strategy including both in silico models and experimental validation that we built, were relatively efficient and reliable for direct targets identification for TCM prescription, which will help elucidating the mechanisms of TCM and promoting the modernization of TCM.
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http://dx.doi.org/10.1038/s41598-021-89035-4DOI Listing
May 2021

Extra-axillary nodal metastases in breast cancer: comparison of ultrasound, MRI, PET/CT, and CT.

Clin Imaging 2021 Apr 1;79:113-118. Epub 2021 Apr 1.

The University of Texas MD Anderson Cancer Center, Department of Breast Imaging, 1515 Holcombe Blvd, Unit 1350, Houston, TX 77030, United States of America. Electronic address:

Purpose: To evaluate how ultrasound (US), MRI, PET/CT, and CT predict extra-axillary nodal metastases.

Subjects And Methods: This IRB approved, retrospective study consisted of 124 suspicious supraclavicular and 88 internal mammary (IM) nodal cases with US and at least one additional cross-sectional examination (MRI, PET/CT or CT) from a total of 1472 invasive cancers with staging nodal US between January 2016-January 2019. Imaging findings were compared with the true node status, determined by fine needle aspirate (FNA) biopsy or evidence of response to chemotherapy on follow up imaging.

Results: In the supraclavicular region, US had accuracy 98.2%, consisting of 97 true positives (TP), 27 false positives (FP), and 1348 true negative (TN). 93.5% of suspicious supraclavicular nodes had FNA for a PPV 78.2%. PET/CT had accuracy 88.6% (26 TP, 5 TN and 4 false negatives (FN)). CT exams had accuracy 61.7% (42 TP, 16 TN, 7 FP, and 29 FN). In the IM region, US had accuracy 93.2% (82 TP, 1 FP, 5 FN, and 1384 TN) but only 43.2% of suspicious IM nodes had FNA for a PPV 98.8%. MRI had accuracy 100.0% (all 47 TP). PET/CT exams had accuracy 96.8% (30 TP and 1FN). CT exams had accuracy 62.7% (36 TP, 1 TN, and 22 FN).

Conclusion: US/FNA has accuracy 98.2% and 93.2% in the supraclavicular and IM regions, however only 43.2% of suspicious IM nodes are directly sampled. In these cases, MRI or PET/CT can be used to problem solve and guide treatment decisions.
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http://dx.doi.org/10.1016/j.clinimag.2021.03.028DOI Listing
April 2021

Accuracy of Prostate Magnetic Resonance Imaging: Reader Experience Matters.

Eur Urol Open Sci 2021 May 23;27:53-60. Epub 2021 Mar 23.

Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Prostate magnetic resonance imaging (MRI) is increasingly used in the detection, image-guided biopsy, and active surveillance of prostate cancer. The accuracy of prostate MRI may differ based on factors including imaging technique, patient population, and reader experience.

Objective: To determine whether the accuracy of prostate MRI varies with reader experience.

Design Setting And Participants: We rescored regions of interest from 194 consecutive patients who had undergone MRI/ultrasonography fusion biopsy. Original prostate MRI scans had been interpreted by one of 33 abdominal radiologists (AR group). More than 14 mo later, rescoring was performed by two blinded, prostate MRI radiologists (PR group). Likert scoring was used for both original MRI reports and rescoring.

Outcome Measurements And Statistical Analysis: Test performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of prostate MRI was defined for the AR and PR groups. A Likert score of 4-5 was considered test positive and clinically significant prostate carcinoma (csPCa; Gleason grade group [GGG] ≥2) was considered outcome positive.

Results And Limitations: MRI-positive lesions (Likert 4-5) scored by the PR group resulted in csPCa more frequently than those scored by the AR group (64.9% vs 39.3%). MRI-negative lesions (Likert 2-3) were more likely to result in a clinically insignificant biopsy (benign pathology or GGG 1) when scored by the PR versus the AR group (91.8% vs 76.6%). Sensitivity and specificity of MRI to detect csPCa were higher for the PR group than for the AR group (sensitivity 85.9% vs 70.7%; specificity 77.3% vs 46.8%). Overall diagnostic accuracy was higher for the PR group than for the AR group (80.1% vs 54.6%).

Conclusions: Sensitivity, specificity, PPV, and NPV of prostate MRI were higher for the PR group than for the AR group.

Patient Summary: We examined the accuracy of prostate magnetic resonance imaging (MRI) in two groups of radiologists. Experienced radiologists were more likely to detect clinically significant prostate cancer on MRI.
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http://dx.doi.org/10.1016/j.euros.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061889PMC
May 2021

Correspondence between DOM molecules and microbial community in a subtropical coastal estuary on a spatiotemporal scale.

Environ Int 2021 Apr 23;154:106558. Epub 2021 Apr 23.

State Key Laboratory for Marine Environmental Science, Institute of Marine Microbes and Ecospheres, College of Ocean and Earth Sciences, Xiamen University, Xiang'an Campus, Xiang'an South Road, Xiamen 361102, China; Fujian Key Laboratory of Marine Carbon Sequestration, Xiamen University, Xiang'an Campus, Xiang'an South Road, Xiamen 361102, China. Electronic address:

Dissolved organic matter (DOM) changes in quantity and quality over time and space, especially in highly dynamic coastal estuaries. Bacterioplankton usually display seasonal and spatial variations in abundance and composition in the coastal regions, and influence the DOM pool via assimilation, transformation and release of organic molecules. The change in DOM can also affect the composition of bacterial community. However, little is known on the correspondence between DOM molecules and bacterial composition, particularly through a systematic field survey. In this study, the spatiotemporal signatures of microbial communities and DOM composition in the subtropical coastal estuary of Xiamen are investigated over one and half years. The co-occurrence analysis between bacteria and DOM suggested microorganisms likely transformed the DOM from a relatively high (>400 Da) to a low (<400 Da) molecular weight, corresponding to an apparent increase in overall aromaticity. This might be the reason why microbial transformation renders "dark" organic matter visible in mass spectrometry due to more efficient ionization of microbial metabolites, as well as photodegradation processes. K- and r-strategists exhibited different correlations with two-size categories of DOM molecules owing to their different lifestyles and responses to environmental nutrient conditions. A comparison of the environmental variables and DOM composition with the microbial communities showed that the environmental/DOM variations played a more important role in shaping the microbial communities than vice versa. This study sheds light on the interactions between microbial populations and DOM molecules at the spatiotemporal scale, improving our understanding of microbial roles in marine biogeochemical cycles.
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http://dx.doi.org/10.1016/j.envint.2021.106558DOI Listing
April 2021

Transport of charge carriers and optoelectronic applications of highly ordered metal phthalocyanine heterojunction thin films.

Phys Chem Chem Phys 2021 Apr;23(16):9631-9642

Synergetic Innovation Center for Quantum Effects and Application, Key Laboratory of Low-dimensional Quantum Structures and Quantum Control of Ministry of Education, Department of Physics, Hunan Normal University, Changsha, 410081, P. R. China.

Organic semiconductor thin films based on polycrystalline small molecules exhibit many attractive properties that have already led to their applications in optoelectronic devices, which can be produced by less expensive and stringent processes. Conduction of electric charges typically occurs in polycrystalline organic thin films. Unavoidably, the crystalline domain size, orientation, domain boundaries and energy level of the interface affect the transport of the charge carriers in organic thin films. In this comprehensive perspective, we focus on highly ordered organic heterojunction thin films fabricated by the weak epitaxy growth method. Transport of charge carriers in these highly ordered organic heterojunction thin films was systematically studied with various characterization techniques. Recent advances are presented in high-performance optoelectronic applications based on highly ordered organic heterojunction thin films, including organic photodetectors, photovoltaic cells, photomemory devices and artificial optoelectronic synapses.
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http://dx.doi.org/10.1039/d1cp00889gDOI Listing
April 2021

Correcting a major error in assessing organic carbon pollution in natural waters.

Sci Adv 2021 Apr 14;7(16). Epub 2021 Apr 14.

State Key Laboratory of Heavy Oil Processing, China University of Petroleum-Beijing, Beijing 102249, China.

Microbial degradation of dissolved organic carbon (DOC) in aquatic environments can cause oxygen depletion, water acidification, and CO emissions. These problems are caused by labile DOC (LDOC) and not refractory DOC (RDOC) that resists degradation and is thus a carbon sink. For nearly a century, chemical oxygen demand (COD) has been widely used for assessment of organic pollution in aquatic systems. Here, we show through a multicountry survey and experimental studies that COD is not an appropriate proxy of microbial degradability of organic matter because it oxidizes both LDOC and RDOC, and the latter contributes up to 90% of DOC in high-latitude forested areas. Hence, COD measurements do not provide appropriate scientific information on organic pollution in natural waters and can mislead environmental policies. We propose the replacement of the COD method with an optode-based biological oxygen demand method to accurately and efficiently assess organic pollution in natural aquatic environments.
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http://dx.doi.org/10.1126/sciadv.abc7318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046372PMC
April 2021

Nox2 contributes to reactive oxygen species-induced redox imbalance in cancer-induced bone pain.

Am J Transl Res 2021 15;13(3):1269-1279. Epub 2021 Mar 15.

Cancer Center, Shanxi Bethune Hospital, Shanxi Medical University, Shanxi Academy of Medical Sciences Taiyuan 030032, China.

We have recently demonstrated that reactive oxygen species (ROS) scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain (CIBP). In the present study, we investigated anti-nociceptive effect of Nox inhibitor apocynin in CIBP in rats. Mechanical allodynia was assessed by Von Frey tests in sham and CIBP group of rats. Western blotting and immunofluorescence technique were conducted to assess the expression levels and cellular localization of Nox2. Results illustrated that after intra-tibial implantation with tumor cells, Nox2 and ROS were both up-regulated in the spinal cord of rats. Injection of apocynin could dose-dependently decrease the abundance of Nox2 and inhibit the development of CIBP. Furthermore, pretreatment with the apocynin could delay the development of CIBP. This study for the first time proved that Nox2 inhibitors could downregulate the production of ROS in CIBP rats, which highlights the fact that Nox inhibitor is an important therapeutic option for CIBP and that, precise targeting inhibitor of different subtypes of Nox enzymes is needed to developed in future.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014423PMC
March 2021

GPR109A deficiency promotes IL-33 overproduction and type 2 immune response in food allergy in mice.

Allergy 2021 Apr 8. Epub 2021 Apr 8.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

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http://dx.doi.org/10.1111/all.14849DOI Listing
April 2021

Laboratory and Field Evaluation of the Phytotoxic Activity of Gaertn Pulp Extract and Identification of a Phytotoxic Substance.

Molecules 2021 Mar 2;26(5). Epub 2021 Mar 2.

SFA Key Laboratory of Bamboo and Rattan Science and Technology, International Centre for Bamboo and Rattan, No. 8 Futong Dongdajie, Wangjing, Chaoyang District, Beijing 100102, China.

Interest in finding plant-based herbicides to supplement synthesized herbicides is increasing. Although the extract of Gaertn has been reported to have herbicidal activity, little is known about phytotoxic substances and their efficacy of weed control in the field. To identify phytotoxic substances, the bioassay-guided fractionation by column chromatography and high-speed counter-current chromatography (HSCCC) was carried out. The phytotoxic activity assay, performed by the agar medium method, showed that the 70% ethanol fraction exhibited strong root growth inhibition against with an 50% inhibitory concentration (IC) value of 35.13 mg/L. An active compound was isolated from the 70% ethanol fraction and identified as hederagenin 3---D-xylopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (Compound A). Compound A had an IC value of 16.64 mg/L. Finally, a new formulation was prepared based on the 70% ethanol fraction, which exhibited good efficacy against broadleaf weeds in a carrot field. The fresh weight control efficacy was 78.7% by 45 days after treatment at the dose of 1500 g a. i./ha. Hence, the extract of pulp could be a promising supplement to the synthesized herbicides. Furthermore, compound A from may be responsible for its phytotoxic activity.
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http://dx.doi.org/10.3390/molecules26051318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957876PMC
March 2021

Assessing the ecological balance between supply and demand of blue-green infrastructure.

J Environ Manage 2021 Jun 27;288:112454. Epub 2021 Mar 27.

Key Laboratory of Regional Ecology and Environmental Change, School of Geography and Information Engineering, China University of Geosciences, Wuhan, 430074, China.

Given that improving urban ecological environment requires a clear recognition of the urban ecological elements, investigating the ecosystem service capabilities of urban green-blue infrastructures (UGBIs) becomes ever important. This study aims to reveal and compare the synergistic ecosystem service ability of UGBIs with different characteristics and the relationship with human demand in Wuhan city. It was found that the climate regulation service and water regulation service value of lake-type parks both reached the highest over the other UGBIs. Nature-type parks revealed the most capable cultural service, and green-type parks demonstrated the greatest exercise cultural service value. The analysis showed that the ecosystem services delivered by the UGBIs were influenced by the park area, the total value of the normalized difference vegetation index and normalized water body index, and the distance from the city centre. Furthermore, a significant spatial phenomenon was found that the ecological capacity of lake-type parks in the city centre was higher than that of the other UGBIs at the same location. Regarding the relationship with the human activity intensity, the high-demand and high-supply regions were mainly concentrated in highly developed areas in terms of regulating services. Nevertheless, a severe environmental inequality occurred in small urban centres, which requires urgent attention from the government. This work answered the question of where and how to optimize the green-blue infrastructures in Wuhan, and it contributes to the construction of the existing blue-green space.
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http://dx.doi.org/10.1016/j.jenvman.2021.112454DOI Listing
June 2021

Resilience, coping style, and COVID-19 stress: effects on the quality of life in frontline health care workers.

Psychol Health Med 2021 Mar 29:1-13. Epub 2021 Mar 29.

Shandong Public Health Clinical Center, Cheeloo College of Medicine, Shandong University, Jinan, China.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P<0.001), whereas, working in confirmed case wards, COVID-19 stress, and passive coping were negatively correlated with the QOL (P<0.001). Resilience and the active coping were negatively correlated with COVID-19 stress (P<0.001). Resilience, coping style,and COVID-19 stressaccounted for 32%, 13%, and 8% of the variance in predicting the Global QOL, respectively. In conclusion, working in confirmed COVID-19 case wards and COVID-19 stress impaired the QOL in HCWs. Psychological intervention to improve the resilience and coping style, and reduce COVID-19 stress are important in improving the QOL and mental health of HCWs.
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http://dx.doi.org/10.1080/13548506.2021.1905860DOI Listing
March 2021

Metabolic Regulation of Hypoxia-Inducible Factors in Hypothalamus.

Front Endocrinol (Lausanne) 2021 8;12:650284. Epub 2021 Mar 8.

Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

The earliest hypoxia-inducible factor (HIF) function was to respond to hypoxia or hypoxic conditions as a transcription factor. Recent studies have expanded our understanding of HIF, and a large amount of evidence indicates that HIF has an essential effect on central regulation of metabolism. The central nervous system's response to glucose, inflammation, and hormones' main influence on systemic metabolism are all regulated by HIF to varying degrees. In the hypothalamus, HIF mostly plays a role in inhibiting energy uptake and promoting energy expenditure, which depends not only on the single effect of HIF or a single part of the hypothalamus. In this paper, we summarize the recent progress in the central regulation of metabolism, describe in detail the role of HIF in various functions of the hypothalamus and related molecular mechanisms, and reveal that HIF is deeply involved in hypothalamic-mediated metabolic regulation.
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http://dx.doi.org/10.3389/fendo.2021.650284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984363PMC
March 2021

Histone deacetylase 3 inhibition alleviates type 2 diabetes mellitus-induced endothelial dysfunction via Nrf2.

Cell Commun Signal 2021 Mar 18;19(1):35. Epub 2021 Mar 18.

School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.

Background: The mechanism underlying endothelial dysfunction leading to cardiovascular disease in type 2 diabetes mellitus (T2DM) remains unclear. Here, we show that inhibition of histone deacetylase 3 (HDAC3) reduced inflammation and oxidative stress by regulating nuclear factor-E2-related factor 2 (Nrf2), which mediates the expression of anti-inflammatory- and pro-survival-related genes in the vascular endothelium, thereby improving endothelial function.

Methods: Nrf2 knockout (Nrf2 KO) C57BL/6 background mice, diabetic db/db mice, and control db/m mice were used to investigate the relationship between HDAC3 and Nrf2 in the endothelium in vivo. Human umbilical vein endothelial cells (HUVECs) cultured under high glucose-palmitic acid (HG-PA) conditions were used to explore the role of Kelch-like ECH-associated protein 1 (Keap1) -Nrf2-NAPDH oxidase 4 (Nox4) redox signaling in the vascular endothelium in vitro. Activity assays, immunofluorescence, western blotting, qRT-PCR, and immunoprecipitation assays were used to examine the effect of HDAC3 inhibition on inflammation, reactive oxygen species (ROS) production, and endothelial impairment, as well as the activity of Nrf2-related molecules.

Results: HDAC3 activity, but not its expression, was increased in db/db mice. This resulted in de-endothelialization and increased oxidative stress and pro-inflammatory marker expression in cells treated with the HDAC3 inhibitor RGFP966, which activated Nrf2 signaling. HDAC3 silencing decreased ROS production, inflammation, and damage-associated tube formation in HG-PA-treated HUVECs. The underlying mechanism involved the Keap1-Nrf2-Nox4 signaling pathway.

Conclusion: The results of this study suggest the potential of HDAC3 as a therapeutic target for the treatment of endothelial dysfunction in T2DM. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00681-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977318PMC
March 2021

Liver proteomics analysis reveals abnormal metabolism of bile acid and arachidonic acid in Chinese hamsters with type 2 diabetes mellitus.

J Proteomics 2021 May 17;239:104186. Epub 2021 Mar 17.

Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan 030001, China. Electronic address:

Non-obese, spontaneous, and genetically predisposed type 2 diabetic Chinese hamsters exhibit metabolic abnormalities similar to those observed in human T2DM. Here, tandem mass tag (TMT)-based quantitative proteomics technology was used to screen and identify differentially abundant proteins in the liver that are associated with diabetes in Chinese hamsters. GO and KEGG pathway enrichment analysis were conducted to validate the findings, as well as qRT-PCR and western blotting. In total, 103 proteins were identified in the livers of diabetic hamsters, of which 48 were up-regulated and 55 were down-regulated. KEGG pathway enrichment analysis further demonstrated that linoleic acid metabolism, arachidonic acid metabolism, bile secretion, and other pathways were affected. Moreover, AQP9 and EPHX1 were significantly down-regulated in the bile secretion pathway, whereas PTGES2, Cyp2c27, and Cyp2c70 were associated with the arachidonic acid metabolic pathway. Serum levels of bile acid (BA) and arachidonic acid (AA) in diabetic Chinese hamsters were significantly higher than those in control hamsters. Cumulatively, our findings indicate that the five candidate proteins may be associated with abnormal BA and AA metabolism, suggesting their involvement in pathological changes in the livers of Chinese hamsters with T2DM. SIGNIFICANCE: The liver proteomics of Chinese hamsters describes differentially abundant proteins associated with T2DM, while promoting this animal model as an appropriate and ideal platform for investigating underlying molecular mechanisms of T2DM. This study reveals abnormal bile acid and arachidonic acid metabolism in T2DM hamsters, which may provide insights for studying the relationship between candidate proteins and KEGG pathways to elucidate the underlying molecular mechanism associated with T2DM.
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http://dx.doi.org/10.1016/j.jprot.2021.104186DOI Listing
May 2021

[Intestinal absorption characteristics of Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats via everted intestinal sac models].

Zhongguo Zhong Yao Za Zhi 2021 Jan;46(1):196-205

Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University Guiyang 550004, China.

The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201010.201DOI Listing
January 2021

Central Neural Circuits Orchestrating Thermogenesis, Sleep-Wakefulness States and General Anesthesia States.

Curr Neuropharmacol 2021 Feb 25. Epub 2021 Feb 25.

Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Ave 1095, Wuhan 430030. China.

Great progress has been made in specifically identifying the central neural circuits (CNCs) of the core body temperature (Tcore), sleep-wakefulness states (SWs), and general anesthesia states (GAs), mainly utilizing optogenetic or chemogenetic manipulations. We summarize the neuronal populations and neural pathways of these three CNCs, which gives evidence for the orchestration within these three CNCs, and the integrative regulation of these three CNCs by different environmental light signals. We also outline some transient receptor potential (TRP) channels that function in the CNCs-Tcore and are modulated by some general anesthetics, which makes TRP channels possible targets for addressing the general-anesthetics-induced-hypothermia (GAIH). We suggest this review will provide new orientations for further consummating these CNCs and elucidating the central mechanisms of GAIH.
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http://dx.doi.org/10.2174/1570159X19666210225152728DOI Listing
February 2021

Functional Tumor Volume by Fast Dynamic Contrast-Enhanced MRI for Predicting Neoadjuvant Systemic Therapy Response in Triple-Negative Breast Cancer.

J Magn Reson Imaging 2021 Feb 15. Epub 2021 Feb 15.

Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: Dynamic contrast-enhanced (DCE) MRI is useful for diagnosis and assessment of treatment response in breast cancer. Fast DCE MRI offers a higher sampling rate of contrast enhancement curves in comparison to conventional DCE MRI, potentially characterizing tumor perfusion kinetics more accurately for measurement of functional tumor volume (FTV) as a predictor of treatment response.

Purpose: To investigate FTV by fast DCE MRI as a predictor of neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Study Type: Prospective.

Population/subjects: Sixty patients with biopsy-confirmed TNBC between December 2016 and September 2020.

Field Strength/sequence: A 3.0 T/3D fast spoiled gradient echo-based DCE MRI ASSESSMENT: Patients underwent MRI at baseline and after four cycles (C4) of NAST, followed by definitive surgery. DCE subtraction images were analyzed in consensus by two breast radiologists with 5 (A.H.A.) and 2 (H.S.M.) years of experience. Tumor volumes (TV) were measured on early and late subtractions. Tumors were segmented on 1 and 2.5-minute early phases subtractions and FTV was determined using optimized signal enhancement thresholds. Interpolated enhancement curves from segmented voxels were used to determine optimal early phase timing.

Statistical Tests: Tumor volumes were compared between patients who had a pathologic complete response (pCR) and those who did not using the area under the receiver operating curve (AUC) and Mann-Whitney U test.

Results: About 26 of 60 patients (43%) had pCR. FTV at 1 minute after injection at C4 provided the best discrimination between pCR and non-pCR, with AUC (95% confidence interval [CI]) = 0.85 (0.74,0.95) (P < 0.05). The 1-minute timing was optimal for FTV measurements at C4 and for the change between C4 and baseline. TV from the early phase at C4 also yielded a good AUC (95%CI) of 0.82 (0.71,0.93) (P < 0.05).

Data Conclusion: FTV and TV measured at 1 minute after injection can predict response to NAST in TNBC.

Level Of Evidence: 1 TECHNICAL EFFICACY: 4.
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http://dx.doi.org/10.1002/jmri.27557DOI Listing
February 2021

Novel deep learning-based noise reduction technique for prostate magnetic resonance imaging.

Abdom Radiol (NY) 2021 Feb 12. Epub 2021 Feb 12.

Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 1515 Holcombe Blvd., Houston, TX, USA.

Introduction: Magnetic resonance imaging (MRI) has played an increasingly major role in the evaluation of patients with prostate cancer, although prostate MRI presents several technical challenges. Newer techniques, such as deep learning (DL), have been applied to medical imaging, leading to improvements in image quality. Our goal is to evaluate the performance of a new deep learning-based reconstruction method, "DLR" in improving image quality and mitigating artifacts, which is now commercially available as AIR Recon DL (GE Healthcare, Waukesha, WI). We hypothesize that applying DLR to the T2WI images of the prostate provides improved image quality and reduced artifacts.

Methods: This study included 31 patients with a history of prostate cancer that had a multiparametric MRI of the prostate with an endorectal coil (ERC) at 1.5 T or 3.0 T. Four series of T2-weighted images were generated in total: one set with the ERC signal turned on (ERC) and another set with the ERC signal turned off (Non-ERC). Each of these sets then reconstructed using two different reconstruction methods: conventional reconstruction (Conv) and DL Recon (DLR): ERC, ERC, Non-ERC, and Non-ERC. Three radiologists independently reviewed and scored the four sets of images for (i) image quality, (ii) artifacts, and (iii) visualization of anatomical landmarks and tumor.

Results: The Non-ERC scored as the best series for (i) overall image quality (p < 0.001), (ii) reduced artifacts (p < 0.001), and (iii) visualization of anatomical landmarks and tumor.

Conclusion: Prostate imaging without the use of an endorectal coil could benefit from deep learning reconstruction as demonstrated with T2-weighted imaging MRI evaluations of the prostate.
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http://dx.doi.org/10.1007/s00261-021-02964-6DOI Listing
February 2021

Unsupervised Cross Domain Person Re-Identification by Multi-Loss Optimization Learning.

IEEE Trans Image Process 2021 12;30:2935-2946. Epub 2021 Feb 12.

Unsupervised cross domain (UCD) person re-identification (re-ID) aims to apply a model trained on a labeled source domain to an unlabeled target domain. It faces huge challenges as the identities have no overlap between these two domains. At present, most UCD person re-ID methods perform "supervised learning" by assigning pseudo labels to the target domain, which leads to poor re-ID performance due to the pseudo label noise. To address this problem, a multi-loss optimization learning (MLOL) model is proposed for UCD person re-ID. In addition to using the information of clustering pseudo labels from the perspective of supervised learning, two losses are designed from the view of similarity exploration and adversarial learning to optimize the model. Specifically, in order to alleviate the erroneous guidance brought by the clustering error to the model, a ranking-average-based triplet loss learning and a neighbor-consistency-based loss learning are developed. Combining these losses to optimize the model results in a deep exploration of the intra-domain relation within the target domain. The proposed model is evaluated on three popular person re-ID datasets, Market-1501, DukeMTMC-reID, and MSMT17. Experimental results show that our model outperforms the state-of-the-art UCD re-ID methods with a clear advantage.
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http://dx.doi.org/10.1109/TIP.2021.3056889DOI Listing
February 2021

Microbial transformation of distinct exogenous substrates into analogous composition of recalcitrant dissolved organic matter.

Environ Microbiol 2021 Feb 8. Epub 2021 Feb 8.

State Key Laboratory of Marine Environmental Science and College of Ocean and Earth Sciences, Xiamen University, Xiamen, 361005, China.

Oceanic dissolved organic matter (DOM) comprises a complex molecular mixture which is typically refractory and homogenous in the deep layers of the ocean. Though the refractory nature of deep-sea DOM is increasingly attributed to microbial metabolism, it remains unexplored whether ubiquitous microbial metabolism of distinct carbon substrates could lead to similar molecular composition of refractory DOM. Here, we conducted microbial incubation experiments using four typically bioavailable substrates (L-alanine, trehalose, sediment DOM extract, and diatom lysate) to investigate how exogenous substrates are transformed by a natural microbial assemblage. The results showed that although each-substrate-amendment induced different changes in the initial microbial assemblage and the amended substrates were almost depleted after 90 days of dark incubation, the bacterial community compositions became similar in all incubations on day 90. Correspondingly, revealed by ultra-high resolution mass spectrometry, molecular composition of DOM in all incubations became compositionally consistent with recalcitrant DOM and similar toward that of DOM from the deep-sea. These results indicate that while the composition of natural microbial communities can shift with substrate exposures, long-term microbial transformation of distinct substrates can ultimately lead to a similar refractory DOM composition. These findings provide an explanation for the homogeneous and refractory features of deep-sea DOM.
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http://dx.doi.org/10.1111/1462-2920.15426DOI Listing
February 2021

Efficacy of water fraction from Dioscorea cirrhosa on oxidative stress and apoptosis in H9c2 cardiomyocytes induced by H2O2.

J Tradit Chin Med 2021 02;41(1):51-58

Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China.

Objective: To investigate the efficacy of water fraction from Dioscorea cirrhosa (WF) on oxidative damage and apoptosis of cardiomyocytes induced by H2O2, and to study its mechanism.

Methods: Cell viability was measured by the MST assay kit. The content of malondialdehyde (MDA), release of lactate dehydrogenase (LDH) and activity of catalase (CAT) and superoxide dismutase (SOD) were detected by biochemical kit. The content of reactive oxygen species (ROS) was assessed by nonfluorescent probe 2' ,7'-dichlorofluorescin diacetate (DCFH-DA). JC-1 was used to analyze the mitochondrial membrane potential (mtΔΨ) and Annexin-V-FITC/PI staining was applied to assess apoptosis of H9c2 by flow cytometry. Moreover, the expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), caspase-3, caspase-9, cleaved-caspase-3 and cleaved-caspase -9 proteins was determined by western blot analysis.

Results: WF increased cell viability and decreased LDH leakage in H9c2 cells exposed to H2O2. WF treatment decreased ROS and MDA level, enhanced SOD and CAT activities, improved mtΔΨ and inhibited apoptosis. Western blot analysis demonstrated that the ratio of Bcl-2/Bax was increased and the expression cleaved-caspase-3, caspase-3, cleaved-caspase-9 and caspase-9 were decreased in group treated with WF.

Conclusion: WF protects H9c2 myocardial cells on H2O2-induced oxidative stress and apoptosis by scavenging ROS, improving antioxidant capacity, protecting mitochondrial and regulating the proteins expression related to apoptosis.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2021.01.007DOI Listing
February 2021

Non-surgical periodontal treatment improves rheumatoid arthritis disease activity: a meta-analysis.

Clin Oral Investig 2021 Jan 29. Epub 2021 Jan 29.

Tianjin Stomatological Hospital, School of Medicine, Nankai University, 75th Dagubei Road, Tianjin, 300041, China.

Objectives: The aim of the meta-analysis was to clarify the efficacy of non-surgical periodontal treatment (NSPT) in improving rheumatoid arthritis (RA) disease activity.

Methods: A systematic literature search was conducted using the PubMed, Embase, and Cochrane databases up to October 2020. A total of nine studies were included for the comparison of RA-related indicator changes between the NSPT group and no treatment (NT) group. Mean differences (MD) and 95% confidence intervals (CI) were calculated for disease activity score (DAS28), erythrocyte sedimentation rate (ESR), tender joint counts (TJC), swollen joint counts (SJC), visual analogical scale (VAS), morning stiffness (MS), rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6).

Results: NSPT induced significant reductions of DAS28 (MD: 0.61, 95% CI: 0.37, 0.85, P < 0.001), TJC (MD: 0.65, 95% CI: 0.37, 0.93, P < 0.001), SJC (MD: 0.67, 95% CI: 0.18, 1.17, P = 0.008), VAS (MD: 0.48, 95% CI: 0.08, 0.88, P = 0.02), and CRP (MD: 0.34, 95% CI: 0.07, 0.64, P = 0.01) in RA patients with periodontitis. Other parameters showed a trend toward reduction, but results were not statistically significant.

Conclusions: This meta-analysis indicates that NSPT could improve RA activity as assessed by DAS28, TJC, SJC, VAS, and CRP.

Clinical Relevance: The results emphasize the effectiveness and need for periodontal diagnosis and periodontal therapy in rheumatoid arthritis patients to reduce disease activity.
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http://dx.doi.org/10.1007/s00784-021-03807-wDOI Listing
January 2021

Early-life fingolimod treatment improves intestinal homeostasis and pancreatic immune tolerance in non-obese diabetic mice.

Acta Pharmacol Sin 2021 Jan 20. Epub 2021 Jan 20.

Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.

Fingolimod has beneficial effects on multiple diseases, including type 1 diabetes (T1D) and numerous preclinical models of colitis. Intestinal dysbiosis and intestinal immune dysfunction contribute to disease pathogenesis of T1D. Thus, the beneficial effect of fingolimod on T1D may occur via the maintenance of intestinal homeostasis to some extent. Herein, we investigated the role of fingolimod in intestinal dysfunction in non-obese diabetic (NOD) mice and possible mechanisms. NOD mice were treated with fingolimod (1 mg · kg per day, i.g.) from weaning (3-week-old) to 31 weeks of age. We found that fingolimod administration significantly enhanced the gut barrier (evidenced by enhanced expression of tight junction proteins and reduced intestinal permeability), attenuated intestinal microbial dysbiosis (evidenced by the reduction of enteric pathogenic Proteobacteria clusters), as well as intestinal immune dysfunction (evidenced by inhibition of CD4 cells activation, reduction of T helper type 1 cells and macrophages, and the expansion of regulatory T cells). We further revealed that fingolimod administration suppressed the activation of CD4 cells and the differentiation of T helper type 1 cells, promoted the expansion of regulatory T cells in the pancreas, which might contribute to the maintenance of pancreatic immune tolerance and the reduction of T1D incidence. The protection might be due to fingolimod inhibiting the toll-like receptor 2/4/nuclear factor-κB/NOD-like receptor protein 3 inflammasome pathway in the colon. Collectively, early-life fingolimod treatment attenuates intestinal microbial dysbiosis and intestinal immune dysfunction in the T1D setting, which might contribute to its anti-diabetic effect.
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http://dx.doi.org/10.1038/s41401-020-00590-4DOI Listing
January 2021

CT features predictive of nodal positivity at surgery in pancreatic cancer patients following neoadjuvant therapy in the setting of dual energy CT.

Abdom Radiol (NY) 2021 Jan 20. Epub 2021 Jan 20.

Department of Abdominal Radiology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.

Purpose: Evaluate utility of dual energy CT iodine material density images to identify preoperatively nodal positivity in pancreatic cancer patients who underwent neoadjuvant therapy.

Methods: This IRB approved retrospective study evaluated 62 patients between 2012 and 2016 with proven pancreatic ductal adenocarcinoma, who underwent neoadjuvant therapy, tumor resection and both baseline and preoperative assessment with pancreatic multiphasic rapid switching dual energy CT. Three radiologists in consensus identified on imaging nodes > 0.5 cm in short axis, evaluated nodal morphology, size and on each phase density in HU, and concentrations on iodine material density images normalized to the aorta.

Results: Of 62 patients, 33 were N0, 20 N1, and 9 N2. Total of 145 lymph nodes were evaluated, with average number of nodes per anatomic site ranging from 1.3 (body tumors) to 5 (uncinate) versus average of 24 and 30 nodes recovered respectively at surgery. Most (N = 44) were pancreatic head tumors. For all patients, regardless of site of primary tumor, the minimum measured iodine value of all of a patient's measured nodes taken as a group on preoperative studies, as normalized to the aorta, was significant at P = 0.041 value in differentiating N0 from N1/2 and ROC analysis showed an AUC of 0.67. With a cutoff of 0.2857, sensitivity was 0.78 and specificity was 0.58, with values < 0.2857 indicative of N1/2. Node morphology and changes in nodal size weren't statistically significant.

Conclusion: The dual energy based minimum normalized iodine value of all nodes in the surgical field on preoperative studies has modest utility in differentiating N0 from N1/2, and generally outperformed conventional features for identifying nodal metastases.
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http://dx.doi.org/10.1007/s00261-020-02917-5DOI Listing
January 2021

Bioactive sesquiterpenoids from the flower buds of Tussilago farfara.

Bioorg Chem 2021 Feb 7;107:104632. Epub 2021 Jan 7.

School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address:

Eleven new compounds including five bisabolane (1-5) and three oplopane (6-8) sesquiterpenoids, a pair of benzopyran enantiomers (9 & 10) and a benzofuran derivative (11), along with six known sesquiterpenoid co-metabolites (12-17), have been obtained from the flower buds of Tussilago farfara. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. The absolute configurations of all the compounds except 11 were unequivocally assigned by various techniques, including Mosher's method and time-dependent density functional theory (TD-DFT) based calculations of C NMR and electronic circular dichroism (ECD) data. The C-8 absolute configuration on the sidechain of this group of bisabolane sesquiterpenoids was assigned for the first time. Our bioassays have established that compounds 3, 4, 13 and 14 showed significant α-glucosidase inhibitory activities, while 6, 8 and 14 displayed moderate antiproliferative effects against two human tumor cell lines A549 and MDA-MB-231. Further flow cytometric analysis revealed that 14 effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in A549 cells, in a dose-dependent manner.
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http://dx.doi.org/10.1016/j.bioorg.2021.104632DOI Listing
February 2021

Acetylation-dependent glutamate receptor GluR signalosome formation for STAT3 activation in both transcriptional and metabolism regulation.

Cell Death Discov 2021 Jan 14;7(1):11. Epub 2021 Jan 14.

Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.

Besides their original regulating roles in the brain, spinal cord, retina, and peripheral nervous system for mediating fast excitatory synaptic transmission, glutamate receptors consisting of metabotropic glutamate receptors (GluRs) and ionotropic glutamate receptors (iGluRs) have emerged to have a critical role in the biology of cancer initiation, progression, and metastasis. However, the precise mechanism underpinning the signal transduction mediated by ligand-bound GluRs is not clearly elucidated. Here, we show that iGluRs, GluR1 and GluR2, are acetylated by acetyltransferase CREB-binding protein upon glutamate stimulation of cells, and are targeted by lysyl oxidase-like 2 for deacetylation. Acetylated GluR1/2 recruit β-arrestin1/2 and signal transducer and activator of transcription 3 (STAT3) to form a protein complex. Both β-arrestin1/2 and STAT3 are subsequently acetylated and activated. Simultaneously, activated STAT3 acetylated at lysine 685 translocates to mitochondria to upregulate energy metabolism-related gene transcription. Our results reveal that acetylation-dependent formation of GluR1/2-β-arrestin1/2-STAT3 signalosome is critical for glutamate-induced cell proliferation.
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http://dx.doi.org/10.1038/s41420-020-00389-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809112PMC
January 2021

Multifunctional Coaxial Energy Fiber toward Energy Harvesting, Storage, and Utilization.

ACS Nano 2021 Jan 11;15(1):1597-1607. Epub 2021 Jan 11.

Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, P. R. China.

Fibrous energy-autonomy electronics are highly desired for wearable soft electronics, human-machine interfaces, and the Internet of Things. How to effectively integrate various functional energy fibers into them and realize versatile applications is an urgent need to be fulfilled. Here, a multifunctional coaxial energy fiber has been developed toward energy harvesting, energy storage, and energy utilization. The energy fiber is composed of an all fiber-shaped triboelectric nanogenerator (TENG), supercapacitor (SC), and pressure sensor in a coaxial geometry. The inner core is a fibrous SC by a green activation strategy for energy storage; the outer sheath is a fibrous TENG in single-electrode mode for energy harvesting, and the outer friction layer and inner layer (covered with Ag) constitute a self-powered pressure sensor. The electrical performances of each energy component are systematically investigated. The fibrous SC shows a length specific capacitance density of 13.42 mF·cm, good charging/discharging rate capability, and excellent cycling stability (∼96.6% retention). The fibrous TENG shows a maximum power of 2.5 μW to power an electronic watch and temperature sensor. The pressure sensor has a good enough sensitivity of 1.003 V·kPa to readily monitor the real-time finger motions and work as a tactile interface. The demonstrated energy fibers have exhibited stable electrochemical and mechanical performances under mechanical deformation, which make them attractive for wearable electronics. The demonstrated soft and multifunctional coaxial energy fiber is also of great significance in a sustainable human-machine interactive system, intelligent robotic skin, security tactile switches,
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http://dx.doi.org/10.1021/acsnano.0c09146DOI Listing
January 2021

microRNA-27b shuttled by mesenchymal stem cell-derived exosomes prevents sepsis by targeting JMJD3 and downregulating NF-κB signaling pathway.

Stem Cell Res Ther 2021 Jan 7;12(1):14. Epub 2021 Jan 7.

Respiratory and Critical Care Medicine Department, Shenzhen People's Hospital, No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, Guangdong Province, People's Republic of China.

Background: Exosomal microRNAs (miRs) derived from mesenchymal stem cells (MSCs) have been shown to play roles in the pathophysiological processes of sepsis. Moreover, miR-27b is highly enriched in MSC-derived exosomes. Herein, we aimed to investigate the potential role and downstream molecular mechanism of exosomal miR-27b in sepsis.

Methods: Inflammation was induced in bone marrow-derived macrophages (BMDMs) by lipopolysaccharide (LPS), and mice were made septic by cecal ligation and puncture (CLP). The expression pattern of miR-27b in MSC-derived exosomes was characterized using RT-qPCR, and its downstream gene was predicted by in silico analysis. The binding affinity between miR-27b, Jumonji D3 (JMJD3), or nuclear factor κB (NF-κB) was characterized to identify the underlying mechanism. We induced miR-27b overexpression or downregulation, along with silencing of JMJD3 or NF-κB to examine their effects on sepsis. The production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 was detected by ELISA.

Results: miR-27b was highly expressed in MSC-derived exosomes. Mechanistic investigations showed that miR-27b targeted JMJD3. miR-27b decreased expression of pro-inflammatory genes by inhibiting the recruitment of JMJD3 and NF-κB at gene promoter region. Through this, MSC-derived exosomal miR-27b diminished production of pro-inflammatory cytokines in LPS-treated BMDMs and septic mice, which could be rescued by upregulation of JMJD3 and NF-κB. Besides, in vitro findings were reproduced by in vivo findings.

Conclusion: These data demonstrated that exosomal miR-27b derived from MSCs inhibited the development of sepsis by downregulating JMJD3 and inactivating the NF-κB signaling pathway.
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http://dx.doi.org/10.1186/s13287-020-02068-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791667PMC
January 2021