Publications by authors named "Siqi Wang"

276 Publications

Fabrication, evaluation and applications of dissolving microneedles.

Int J Pharm 2021 Jul 26;604:120749. Epub 2021 May 26.

Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address:

In recent years, transdermal preparations have emerged as one of the most promising modes of administration. In particular, dissolving microneedles have attracted extensive attention because of their painlessness, safety, high delivery efficiency and easily operation for patients. This article mainly reviews the preparation methods, the types of matrix polymer materials, the content of dissolving microneedles performance testing, and the applications of dissolving microneedles. It is expected to lay a solid knowledge foundation for the in-depth study of the dissolving microneedles.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120749DOI Listing
July 2021

Design, synthesis, and antibacterial evaluation of vancomycin-LPS binding peptide conjugates.

Bioorg Med Chem Lett 2021 Aug 17;45:128122. Epub 2021 May 17.

CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Center for Biotherapeutics Discovery Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, PR China; School of Pharmaceutical Science and Technology, Hangzhou, Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, PR China. Electronic address:

Developing novel antibiotics is urgently needed with emergency of drug resistance. Vancomycin, the last resort for intractable Gram-positive bacterial infections, is ineffective against Gram-negative bacteria and vancomycin resistant bacteria. Herein, we report a series of novel vancomycin derivatives carrying LPS binding peptides, vancomycin-LPS binding peptide conjugates (VPCs). The LPS binding peptides were conjugated onto 4 sites of vancomycin via CuAAC or maleimide- sulfydryl addition, and the formed VPCs were screened against VISA/VRE and Gram-negative strains. VPCs exhibited enhanced activity against vancomycin resistant bacteria and obtained the activity against Gram-negative bacteria in vitro, providing a novel strategy for vancomycin modification and glycopeptide antibiotics synthesis.
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http://dx.doi.org/10.1016/j.bmcl.2021.128122DOI Listing
August 2021

Rh-Catalyzed cascade C-H activation/C-C cleavage/cyclization of carboxylic acids with cyclopropanols.

Chem Commun (Camb) 2021 Jun;57(48):5929-5932

CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. and University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China and School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China.

Merging both C-H and C-C activation in a tandem process is a marked challenge. A novel Rh(iii)-catalyzed C-H activation/ring opening C-C cleavage/cyclization of carboxylic acids with cyclopropanols was developed for the synthesis of 3-substituted phthalides and α,β-butenolides. This reaction displays excellent functional group tolerance with respect to both carboxylic acids and cyclopropanols and features relatively mild conditions. Remarkably, the utility of this method was highlighted by the rapid construction of bioactive compounds bearing a 3-substituted phthalide framework via late-stage functionalization.
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http://dx.doi.org/10.1039/d1cc01778kDOI Listing
June 2021

Differential bone remodeling mechanism in hindlimb unloaded rats and hibernating Daurian ground squirrels: a comparison between artificial and natural disuse.

J Comp Physiol B 2021 Jul 18;191(4):793-814. Epub 2021 May 18.

Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an, 710069, People's Republic of China.

To determine that differential bone remodeling mechanism (especially Wnt signaling) in hindlimb unloaded rats and hibernating Daurian ground squirrels, the bone microstructure, mechanical properties, and expression levels of bone remodeling related proteins and key proteins of Wnt/β-catenin signaling were analyzed in this study. The thickness of cortical and trabecular bone was decreased in femur of hindlimb unloaded rats, while it was maintained in femur of hibernating ground squirrels. Interestingly, the ultimate bending energy and ultimate normalized displacement were reduced and the bending rigidity was increased in tibia of hibernating ground squirrels. Besides, the protein level of Runx2 was decreased in femur and tibia of unloaded rats, while it was maintained in tibia and even increased in femur of hibernating ground squirrels. The protein levels of RANKL and MMP-9 were increased in femur and tibia in unloaded rats, while they were maintained in both femur and tibia of hibernating ground squirrels. The protein level of GSK-3β was increased in femur and tibia of unloaded rats, while it was maintained in both femur and tibia of hibernating ground squirrels. The phospho-β-catenin expression was increased in both femur and tibia of unloaded rats, while it was only decreased in femur, but maintained in tibia of hibernating ground squirrels. In conclusion, the femur and tibia in hindlimb unloaded rats showed obvious bone loss, while they mitigated disuse-induced bone loss in hibernating ground squirrels, involving differential protein expression of key molecules in bone remodeling. In comparison with hindlimb unloaded rats, promoting osteoblast differentiation through activating canonical GSK-3β/β-catenin signaling involving Runx2 might be an adaptation to natural disuse in femur of hibernating Daurian ground squirrels. However, there was no statistical change in the protein levels of bone formation related proteins, GSK-3β and phospho-β-catenin in tibia of hibernating Daurian ground squirrels.
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http://dx.doi.org/10.1007/s00360-021-01375-9DOI Listing
July 2021

Towards Dosimetry for Prostate Radiotherapy with a Transperineal Ultrasound Array: A Simulation Study.

IEEE Trans Radiat Plasma Med Sci 2021 May 10;5(3):373-382. Epub 2020 Aug 10.

School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK, 73019, USA.

X-ray-induced acoustic computed tomography (XACT) is a promising imaging modality to monitor the position of the radiation beam and the deposited dose during external beam radiotherapy delivery. The purpose of this study was to investigate the feasibility of using a transperineal ultrasound transducer array for XACT imaging to guide the prostate radiotherapy. A customized two-dimensional (2D) matrix ultrasound transducer array with 10000 (100×100 elements) ultrasonic sensors with a central frequency of 1 MHz was designed on a 5 cm×5 cm plane to optimize three-dimensional (3D) volumetric imaging. The CT scan and dose treatment plan for a prostate patient undergoing intensity modulated radiation therapy (IMRT) were obtained. In-house simulation was developed to model the time varying X-ray induced acoustic (XA) signals detected by the transperineal ultrasound array. A 3D filtered back projection (FBP) algorithm has been used for 3D XACT image reconstruction. Results of this study will greatly enhance the potential of XACT imaging for real time dosimetry during radiotherapy.
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http://dx.doi.org/10.1109/trpms.2020.3015109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104130PMC
May 2021

Genome profiling of mismatch repair genes in eight types of tumors.

Cell Cycle 2021 Jun 9;20(11):1091-1106. Epub 2021 May 9.

Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.

Mismatch repair (MMR) plays an important role in the occurrence and development of tumors. At present, it is widely believed that MMR is a protective mechanism of tumors that plays a critical role in the progresses of cancer. In this study, 34 genes related to MMR selected from Gene Ontology (GO) database were scored by single sample Gene sets enrichment analysis (ssGSEA), and eight cancers were screened from 23 TCGA solid cancers to investigate the clinical significance of MMR score. MMR had different effects on the prognosis of the eight tumors, with a protective effect in three cancers and functioning as a risk factor in the remaining five cancers. We used unsupervised clustering to divide the patients into four clusters. We found that the immune and metabolic status of the four clusters were extremely different, among which cluster1 had the lowest tumor purity and the most complex microenvironment; this may explain its poor prognosis and immunotherapy effect. In summary, MMR scores can improve the predictive ability and provide effective guidance for immunotherapy in individual type of tumors.
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http://dx.doi.org/10.1080/15384101.2021.1922160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208120PMC
June 2021

Construction of evidence-based practice competencies for nurses in China: A modified Delphi study.

Nurse Educ Today 2021 Jul 24;102:104927. Epub 2021 Apr 24.

Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China. Electronic address:

Background: Evidence-based practice is considered as the core competency requirement for nursing practice internationally. However, there is limited information regarding the evidence-based practice competency indicators for clinical nurses in China.

Objective: To establish a set of evidence-based practice competencies specific to nurses in China.

Design: A modified Delphi study.

Setting: The study was mainly conducted in a university-affiliated hospital in China.

Participants: Twenty experts with evidence-based practice knowledge or practical experience from different regions and organizations in China.

Methods: A literature review was conducted to develop the initial list of competencies which consisted of 35 items in seven domains. A two-round Delphi survey used email to invite experts to rate the importance of each item and provide qualitative comments on their ratings. Consensus was predefined as a mean score is of 4.0 or above and at least 75% agreement among the participants.

Results: In round 1, 2 items were excluded, 5 items were added, and 12 items were required to be modified. In round 2, the consensus was achieved on 34 items in seven domains.

Conclusion: The study established a comprehensive set of evidence-based practice competencies for nurses in China, which provides benchmark standards for the assessment and training of nurses on evidence-based practice.
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http://dx.doi.org/10.1016/j.nedt.2021.104927DOI Listing
July 2021

Urinary benzophenones and synthetic progestin in Chinese adults and children: concentration, source and exposure.

Environ Sci Pollut Res Int 2021 May 6. Epub 2021 May 6.

School of Environmental and Chemical Engineering, Shanghai University, 99 Shangda Road, Shanghai, 200444, People's Republic of China.

The endocrine-disrupting activities of UV filters and synthetic progestin have raised concerns about their adverse risks. In this study, 208 urine samples were collected from Shanghai residents for the determination of seven benzophenones (BPs) and six synthetic progestins. The highest median concentration (6.21ng g Cr) was observed in young adults (21-50 years), followed by a concentration of 3.86 ng g Cr in elderly adults (over 50 years old), and the lowest median concentration (1.32 ng g Cr) was found in children (8-11 years old). The detection rates of BP-3 and EE2 in adults were 97% and 82%, and in children were 31% and 24%, respectively. Synthetic progestin levels in Shanghai, China, were relatively low compared to other countries. And the urinary BPs level showed an increasing trend in Chinese in the past 5 years. The principal component analysis suggested that adults' exposure to BP-1 and BP-3 was related, which occurs through food or dermal absorption of these chemicals present in cosmetic products and coatings. And diet was an important exposure pathway for children exposed to BPs. Despite relatively high levels of synthetic progestin for female and obese, the total estimated daily intake (EDI) was still lower than acceptable daily intake adopted by America. In the Monte-Carlo analysis, the 95th percentile of hazard quotients (HQs) was 0.83, which indicated that potential health risks were appreciated in the studied population.
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http://dx.doi.org/10.1007/s11356-021-13943-1DOI Listing
May 2021

Development of a High Internal Phase Emulsion of Antarctic Krill Oil Diluted by Soybean Oil Using Casein as a Co-Emulsifier.

Foods 2021 Apr 22;10(5). Epub 2021 Apr 22.

School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.

Antarctic krill oil (AKO) with 5-30% () dilution by soybean oil was co-emulsified by phospholipids (PLs) naturally present in AKO and 2% () casein in the aqueous phase to prepare high internal phase emulsions (HIPEs). The results showed that raising the AKO level resulted in concave-up changes in the mean size of oil droplets which became more densely packed. Confocal laser scanning microscopy (CLSM) and cryo-scanning electron microscopy (cryo-SEM) micrographs revealed that PLs at higher concentrations expelled more casein particles from the oil droplet surface, which facilitated the formation of a crosslinked network structure of HIPEs, leading to reduced mobility of water molecules, extended physical stability, and somewhat solid-like behavior. The rheological analysis showed at lower levels of AKO promoted fluidity of emulsions, while at higher levels it increased elasticity. Lastly, increasing the AKO level slowed down the oxidation of HIPEs. These findings provide useful insights for developing HIPEs of highly viscous AKO and its application in foods.
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http://dx.doi.org/10.3390/foods10050917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143571PMC
April 2021

Selenomethionine protects hematopoietic stem/progenitor cells against cobalt nanoparticles by stimulating antioxidant actions and DNA repair functions.

Aging (Albany NY) 2021 04 19;13(8):11705-11726. Epub 2021 Apr 19.

Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) can differentiate into all blood lineages to maintain hematopoiesis, wound healing, and immune functions. Recently, cobalt-chromium alloy casting implants have been used extensively in total hip replacements; however, cobalt nanoparticles (CoNPs) released from the alloy were toxic to HSCs and HPCs. We aimed to investigate the mechanism underlying the toxic effect of CoNPs on HSCs/HPCs and to determine the protective effect of selenomethionine (SeMet) against CoNPs and . Human and rat CD34+ HSCs/HPCs were isolated from cord blood and bone marrow, respectively. CoNPs decreased the viability of CD34+ HSCs/HPCs and increased apoptosis. SeMet attenuated the toxicity of CoNPs by enhancing the antioxidant ability of cells. The protective effect of SeMet was not completely abolished after adding H2O2 to abrogate the improvement of the antioxidant capacity by SeMet. SeMet and CoNPs stimulated ATM/ATR DNA damage response signals and inhibited cell proliferation. Unlike CoNPs, SeMet did not damage the DNA, and cell proliferation recovered after removing SeMet. SeMet inhibited the CoNP-induced upregulation of hypoxia inducible factor (HIF)-1α, thereby disrupting the inhibitory effect of HIF-1α on breast cancer type 1 susceptibility protein (BRCA1). Moreover, SeMet promoted BRCA1-mediated ubiquitination of cyclin B by upregulating UBE2K. Thus, SeMet enhanced cell cycle arrest and DNA repair post-CoNP exposure. Overall, SeMet protected CD34+ HSCs/HPCs against CoNPs by stimulating antioxidant activity and DNA repair.
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http://dx.doi.org/10.18632/aging.202865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109066PMC
April 2021

Observation of strong excitonic magneto-chiral anisotropy in twisted bilayer van der Waals crystals.

Nat Commun 2021 Apr 7;12(1):2088. Epub 2021 Apr 7.

Nanoscale Science and Engineering Center, University of California, Berkeley, CA, USA.

The interplay between chirality and magnetism generates a distinct physical process, the magneto-chiral effect, which enables one to develop functionalities that cannot be achieved solely by any of the two. Such a process is universal with the breaking of parity-inversion and time-reversal symmetry simultaneously. However, the magneto-chiral effect observed so far is weak when the matter responds to photons, electrons, or phonons. Here we report the first observation of strong magneto-chiral response to excitons in a twisted bilayer tungsten disulfide with the amplitude of excitonic magneto-chiral (ExMCh) anisotropy reaches a value of ~4%. We further found the ExMCh anisotropy features with a spectral splitting of ~7 nm, precisely the full-width at half maximum of the excitonic chirality spectrum. Without an externally applied strong magnetic field, the observed ExMCh effect with a spontaneous magnetic moment from the ferromagnetic substrate of thulium iron garnet at room temperature is favorable for device applications. The unique ExMCh processes provide a new pathway to actively control magneto-chiral applications in photochemical reactions, asymmetric synthesis, and drug delivery.
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http://dx.doi.org/10.1038/s41467-021-22412-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027870PMC
April 2021

Current practice and perspectives of healthcare providers regarding preconception care for women with type 1 diabetes in China.

Diabetes Metab Res Rev 2021 May 13;37(4):e3454. Epub 2021 Apr 13.

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Aims: We aimed to investigate the current practice and perspectives of healthcare providers (HCPs) regarding preconception care (PCC) for women with type 1 diabetes (T1D) in China.

Materials And Methods: A questionnaire based on in-depth interviews with HCPs involved in PCC was released online and advertised via doctor unions in China. The data were categorical variables and were analysed by multivariable logistic regression, Chi-square test, or Wilcoxon rank-sum test.

Results: From November 2016 to January 2017, 992 responses from 31 provinces of China were received (77.3% doctors and 22.7% nurses). Regarding the current status of PCC for T1D, 62.5% of HCPs treated ≤1 woman with T1D monthly on average. Only 16.5% thought they provided proper PCC, and 29.6% reported having sufficient knowledge. Regarding attitudes towards pregnancy with T1D, 92.2% were in favour of women with T1D getting pregnant after proper glycaemic control, and 94.7% perceived their worries regarding pregnancy. Regarding doctor-patient communication, 56.6% spent <10 min per visit, while 58.3% thought ≥20 min was required for adequate communication. HCPs emphasised the importance of multidisciplinary PCC, professional training, and social support. PCC practice was associated with hospital level (OR = 2.450, 95%CI: 1.580-3.799, p < 0.001), HCPs' experience of treating women with T1D (OR = 2.196, 95%CI: 1.516-3.180, p < 0.001), and their communication sufficiency (OR = 3.706, 95%CI: 2.550-5.387, p < 0.001).

Conclusions: The current PCC practice for T1D in China was suboptimal and it was associated with hospital level, HCPs' experience and communication. It is necessary to reinforce professional training and appeal for social resources to improve PCC.
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http://dx.doi.org/10.1002/dmrr.3454DOI Listing
May 2021

Comparative Transcriptomic Analysis of (Hemiptera: Alydidae) to Characterize Wing Formation across All Developmental Stages.

Insects 2021 Mar 5;12(3). Epub 2021 Mar 5.

Institute of Entomology, College of Life Sciences, Nankai University, Tianjin 300071, China.

(Hemiptera: Alydidae) is a major agricultural pest in East Asia that causes considerable economic losses to the soybean crop each year. However, the molecular mechanisms governing the growth and development of have not been fully elucidated. In this study, the Illumina HiSeq6000 platform was employed to perform de novo transcriptome assembly and determine the gene expression profiles of this species across all developmental stages, including eggs, first-, second-, third-, fourth-, and fifth-instar nymphs, and adults. In this study, a total of 60,058 unigenes were assembled from numerous raw reads, exhibiting an N50 length of 2126 bp and an average length of 1199 bp, and the unigenes were annotated and classified with various databases, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Gene Ontology (GO). Furthermore, various numbers of differentially expressed genes (DEGs) were calculated through pairwise comparisons of all life stages, and some of these DEGs were associated with immunity, metabolism, and development by GO and KEGG enrichment. In addition, 35,158 simple sequence repeats (SSRs) and 715,604 potential single nucleotide polymorphisms (SNPs) were identified from the seven transcriptome libraries of . Finally, we identified and summarized ten wing formation-related signaling pathways, and the molecular properties and expression levels of five wing development-related genes were analyzed using quantitative real-time PCR for all developmental stages of . Taken together, the results of this study may establish a foundation for future research investigating developmental processes and wing formation in hemimetabolous insects and may provide valuable data for pest control efforts attempting to reduce the economic damage caused by this pest.
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http://dx.doi.org/10.3390/insects12030226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999114PMC
March 2021

IAP-1 promoted cisplatin resistance in nasopharyngeal carcinoma via inhibition of caspase-3-mediated apoptosis.

Am J Cancer Res 2021 1;11(3):640-667. Epub 2021 Mar 1.

Department of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University Guangzhou 510282, China.

Recurrent/metastatic nasopharyngeal carcinoma (NPC) is known for having a poor prognosis due to its unfavorable response to chemoradiotherapy. However, the specific processes involved remain poorly understood. This study focused on the cisplatin-resistance mechanism in NPC to help understand the occurrence of advanced NPC and aims to explore the potential therapeutic target for cisplatin-resistant NPC. Two cisplatin-resistant NPC cell lines, HNE-1/DDP and CNE-2/DDP, were established and the differentially expressed genes (DEGs) between parental and cisplatin-resistance cell lines, filtering from high-throughput sequencing results, were analyzed. Next, the effects of IAP-1 on cisplatin-resistant nasopharyngeal cancer cell proliferation, apoptosis, drug resistance and associated cell signaling were evaluated in vitro and in vitro. From our bioinformatic results, more than 15,000 differentially expressed genes (DEGs) were found between parental and resistant cell lines. Nine related DEGs were found in the classic platinum resistance pathway, three of which (ATM, IAP-1, and IAP-2) also appeared in the top five differentially expressed pathways, with elevated IAP-1 showing the highest fold change. Further studies revealed that high IAP-1 expression can lead to an increased cisplatin inhibitory concentration and apoptosis inhibition. IAP-1 silencing can induce upregulation of the caspase-3 and enhance the antiproliferation and proapoptotic effects of cisplatin. Clinical data also showed that IAP-1 overexpression was associated with a worse survival status. In summary, in vitro and in vivo experiments demonstrated that IAP-1 plays a vital role in cisplatin resistance by regulating caspase induced apoptosis and serve as a potential novel therapeutic target and a prognostic indicator for advanced NPC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994165PMC
March 2021

Functional Network of the Long Non-coding RNA Growth Arrest-Specific Transcript 5 and Its Interacting Proteins in Senescence.

Front Genet 2021 10;12:615340. Epub 2021 Mar 10.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, Division of Life Sciences and Medicine, School of Life Sciences, University of Science and Technology of China, Hefei, China.

Increasing studies show that long non-coding RNAs (lncRNAs) play essential roles in various fundamental biological processes. Long non-coding RNA growth arrest-specific transcript 5 (GAS5) showed differential expressions between young and old mouse brains in our previous RNA-Seq data, suggesting its potential role in senescence and brain aging. Examination using quantitative reverse transcription-polymerase chain reaction revealed that GAS5 had a significantly higher expression level in the old mouse brain hippocampus region than the young one. Cellular fractionation using hippocampus-derived HT22 cell line confirmed its nucleoplasm and cytoplasm subcellular localization. Overexpression or knockdown of GAS5 in HT22 cell line revealed that GAS5 inhibits cell cycle progression and promotes cell apoptosis. RNA-Seq analysis of GAS5-knockdown HT22 cells identified differentially expressed genes related to cell proliferation (e.g., DNA replication and nucleosome assembly biological processes). RNA pull-down assay using mouse brain hippocampus tissues showed that potential GAS5 interacting proteins could be enriched into several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and some of them are involved in senescence-associated diseases such as Parkinson's and Alzheimer's diseases. These results contribute to understand better the underlying functional network of GAS5 and its interacting proteins in senescence at brain tissue and brain-derived cell line levels. Our study may also provide a reference for developing diagnostic and clinic biomarkers of GAS5 in senescence and brain aging.
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http://dx.doi.org/10.3389/fgene.2021.615340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987947PMC
March 2021

A wideband picosecond pulsed electric fields (psPEF) exposure system for the nanoporation of biological cells.

Bioelectrochemistry 2021 Aug 26;140:107790. Epub 2021 Feb 26.

Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.

The effects and mechanisms of ultrashort and intense pulsed electric fields on biological cells remain some unknown. Especially for picosecond pulsed electric fields (psPEF) with a high pulse repetition rate, electroporation or nanoporation effects could be induced on cell membranes and intracellular organelle membranes. In this work, the design, implementation, and experimental validation of a wideband psPEF exposure system (WPES) is reported, comprising picosecond pulser and wideband biochip, for the in vitro exposure of suspended cells to high-intensity psPEF. Excited by repetitive picosecond pulses (the duration of 200 ps and the amplitude of a few kilovolts), the proposed biochip adopts grounded coplanar waveguide (GCPW) for a wide working bandwidth, which was fabricated with 160 μm thick electrodes for uniform distribution of psPEF in the cross-section. To ensure that only psPEF is generated in the biological medium containing cells except for ionic current, this work proposes to install capillary tubes in the electrode gaps for electrical insulation and cells delivery. By electrical measurements in the time domain and frequency domain, the exposure system is adapted for local generation of extremely high-intensity psPEF with the 3 dB bandwidth up to 4.2 GHz. Furthermore, biological experiments conducted on the developed exposure system verified its capability to permeabilize biological cells under the exposure of high-intensity psPEF.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107790DOI Listing
August 2021

Transcriptomic Data Analyses Reveal That Sow Fertility-Related lincRNA Is Essential for the Normal States and Functions of Granulosa Cells.

Front Cell Dev Biol 2021 23;9:610553. Epub 2021 Feb 23.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

, the first lincRNA associated with sow fertility, has been shown to control granulosa cell (GC) functions and follicular atresia. However, the underlying mechanism is not fully understood. In this study, RNA-seq was performed and we noticed that inhibition of led to dramatic transcriptomic alterations in porcine GCs. A total of 1,272 differentially expressed transcripts were identified, including 1167 DEmRNAs and 105 DEmiRNAs. Furthermore, protein-protein interaction, gene-pathway function, and TF-miRNA-mRNA regulatory networks were established and yielded four regulatory modules with multiple hub genes, such as , , , , , , , , and . Functional assessment showed that these hub DEGs were mainly enriched in TGF-β, PI3K-Akt, FoxO, Wnt, MAPK, and ubiquitin pathways that are essential for GC states (apoptosis and proliferation) and functions (hormone secretion). , we also found that knockdown of in porcine GCs significantly induced cell apoptosis, impaired cell viability, and suppressed 17β-estradiol (E2) synthesis. Notably, four candidate genes for sow reproductive traits (, , β, and ) were also identified as potential targets of . These findings present a panoramic view of the transcriptome in -reduced GCs, highlighting that , a candidate lincRNA for sow fertility, is crucial for the normal states and functions of GCs.
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http://dx.doi.org/10.3389/fcell.2021.610553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940361PMC
February 2021

Susceptibility of Isolates from the China-Myanmar Border Area to Piperaquine and Association with Candidate Markers.

Antimicrob Agents Chemother 2021 Mar 8. Epub 2021 Mar 8.

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, FL, USA

from the Greater Mekong subregion has evolved resistance to the artemisinin-based combination therapy dihydroartemisinin and the partner drug piperaquine. To monitor the potential westward spread or independent evolution of piperaquine resistance, we evaluated the susceptibility of 120 isolates collected at the China-Myanmar border during 2007-2016. The parasite isolates displayed a relatively wide range of piperaquine susceptibility estimates. While 56.7% of the parasites showed bimodal drug response curves, all but five generated area-under-the-curve (AUC) estimates consistent with a susceptible phenotype. Using the piperaquine survival assay (PSA), 5.6% parasites showed reduced susceptibility. Of note, parasites from 2014-2016 showed the highest AUC value and the highest proportion with a bimodal curve, suggesting falling effectiveness in these later years. Unsupervised K-mean analysis of the combined data assigned parasites into three clusters and identified significant correlations between IC, IC and AUC values. No parasites carried the E415G mutation in a putative exo-nuclease, new mutations in PfCRT, or amplification of the genes, suggesting mechanisms of reduced piperaquine susceptibility that differ from those described in other countries of the region. The association of increased AUC, IC, and IC values with major PfK13 mutations (F446I and G533S) suggests that piperaquine resistance may evolve in these PfK13 genetic backgrounds. Additionally, the Pfmdr1 F1226Y mutation was associated with significantly higher PSA values. Further elucidation of piperaquine resistance mechanisms and continuous surveillance are warranted.
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http://dx.doi.org/10.1128/AAC.02305-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092910PMC
March 2021

Glycemic control in children and teenagers with type 1 diabetes around lockdown for COVID-19: A continuous glucose monitoring-based observational study.

J Diabetes Investig 2021 Sep 2;12(9):1708-1717. Epub 2021 Mar 2.

Department of Endocrinology and Metabolic Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Aims/introduction: The coronavirus disease 2019 (COVID-19) pandemic urged authorities to impose rigorous quarantines and brought considerable changes to people's lifestyles. The impact of these changes on glycemic control has remained unclear, especially the long-term effect. We aimed to investigate the impact of COVID-19 lockdown on glycemic control in children and adolescents with type 1 diabetes.

Materials And Methods: This observational study enrolled children with type 1 diabetes using continuous glucose monitoring. Continuous glucose monitoring data were extracted from the cloud-based platform before, during and after lockdown. Demographics and lifestyle change-related information were collected from the database or questionnaires. We compared these data before, during and after lockdown.

Results: A total of 43 children with type 1 diabetes were recruited (20 girls; mean age 7.45 years; median diabetes duration 1.05 years). We collected 41,784 h of continuous glucose monitoring data. Although time in range (3.9-10.0 mmol/L) was similar before, during and after lockdown, the median time below range <3.9 mmol/L decreased from 3.70% (interquartile range [IQR] 2.25-9.53%) before lockdown to 2.91% (IQR 1.43-5.95%) during lockdown, but reversed to 4.95% (IQR 2.11-9.42%) after lockdown (P = 0.004). Time below range <3.0 mmol/L was 0.59% (IQR 0.14-2.21%), 0.38% (IQR 0.05-1.35%) and 0.82% (IQR 0.22-1.69%), respectively (P = 0.008). The amelioration of hypoglycemia during lockdown was more prominent among those who had less time spent <3.9 mmol/L at baseline. During lockdown, individuals reduced their physical activity, received longer sleep duration and spent more time on diabetes management. In addition, they attended outpatient clinics less and turned to telemedicine more frequently.

Conclusion: Glycemic control did not deteriorate in children and teenagers with type 1 diabetes around the COVID-19 pandemic. Hypoglycemia declined during lockdown, but reversed after lockdown, and the changes related to lifestyle might not provide a long-term effect.
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http://dx.doi.org/10.1111/jdi.13519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014845PMC
September 2021

Circulating serum exosomal as a novel biomarker for early diagnosis of gastric cancer.

Future Oncol 2021 Mar 3;17(8):907-919. Epub 2021 Feb 3.

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, China.

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curve for serum exosomal was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal , CEA and CA19-9 was more sensitive than any of the three alone or any pair. These results showed that serum exosomal could be used as a novel new tumor biomarker to improve diagnostic efficiency in GC.
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http://dx.doi.org/10.2217/fon-2020-0792DOI Listing
March 2021

Effect of pre-frying on distribution of protons and physicochemical qualities of mackerel.

J Sci Food Agric 2021 Aug 17;101(11):4838-4846. Epub 2021 Feb 17.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.

Background: In this work, low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging were used to investigate the changes in protons (from water and oil) distribution of mackerel during the frying process. The relationship between proton migration and some physicochemical indexes was established by partial least squares regression (PLSR). The changing mechanism of the quality characteristics and physicochemical properties of fish meat under different frying conditions was analysed by LF-NMR combined with PLSR, which provided theoretical support for the development of canned mackerel food.

Results: LF-NMR results showed that three kinds of T protons assigned to protein-water interaction (T ), multilayer bound water (T ), oil and free water (T ), respectively. As the frying temperature increased, protons from the T peak significantly decreased, while protons from the T peak remarkably increased. The microstructure of fried mackerel was destroyed; cooking loss, oil content, a* value, b* value, hardness and chewiness increased; and the protein content and L* value decreased. Furthermore, PLSR analysis revealed that significant correlation was observed between the cooking loss, TPA parameter (chewiness), colour parameter (L*) and LF-NMR parameters.

Conclusion: Different frying temperatures and times had a strong effect on the physicochemical properties of mackerel. Good prediction models could be established by proton migration using the LF-NMR technique and PLSR for fried mackerel. Quality control of fried fish could be realized by monitoring the change in LF-NMR data. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11130DOI Listing
August 2021

Influence of Refrigerated Storage on Water Status, Protein Oxidation, Microstructure, and Physicochemical Qualities of Atlantic Mackerel ().

Foods 2021 Jan 21;10(2). Epub 2021 Jan 21.

National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.

Moisture migration, protein oxidation, microstructure, and the physicochemical qualities of Atlantic mackerel during storage at 4 °C and 0 °C were explored in this study. Three proton components were observed in mackerel muscle using low-field nuclear magnetic resonance relaxation, which were characterized as bound water, immobilized water, and lipid. The relaxation peak of immobilized water shifted to a shorter relaxation time and its intensity decreased with the proceeding of the storage process. and weighted images obtained by magnetic resonance imaging showed a slightly continuous decrease in the intensity of water. The significant decrease in sulfhydryl (SH) content and the increase in carbonyl group (CP) content, disulfide bond content, and hydrophobicity revealed the oxidation of protein during storage. The contents of α-helixes in proteins decreased while that of random coils increased during storage, which suggested changes in the secondary structure of mackerel protein. The storage process also caused the contraction and fracture of myofibrils, and the granulation of endolysin protein. In addition, the drip loss, total volatile basic nitrogen (TVB-N), thiobarbituric acid-reactive substances (TBARS) value, and * value increased significantly with the storage time.
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http://dx.doi.org/10.3390/foods10020214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909831PMC
January 2021

Skillfully collaborating chemosynthesis with GOx-enabled tumor survival microenvironment deteriorating strategy for amplified chemotherapy and enhanced tumor ablation.

Biomater Sci 2021 Mar;9(5):1855-1871

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China.

The satisfactory efficient tumor treatment and complete tumor ablation using a mono-therapeutic approach are limited owing to the tumor complexity, diversity, heterogeneity and the multiple pathways involved in tumor pathogenesis. Herein, novel, intelligent and tumor microenvironment (TME)-responsive biotin/R8 peptide co-modified nanocarriers (BRNC) loading paclitaxel (PTX)/glucose oxidase (GOx) were constructed. GOx could catalyze the oxidation of intracellular glucose to gluconic acid and poisonous H2O2 to cause the deterioration of the tumor survival microenvironment, simultaneously achieving starvation and oxidation therapy. The acidic amplification during the GOx-mediated oxidation progress could in turn accelerate the cleavage of the acid-degradable hydrazone bond, promoting the deep penetration of nanocarriers into tumors. Even better, the aforementioned two aspects further increased the tumors' sensitivity to chemotherapeutic agents. Both in vitro and in vivo investigations indicated that the co-administration of GOx-BRNC and PTX-BRNC can remarkably improve the therapeutic efficacy and reduce side effects through the high-specific tumor targeting multimodal synergistic starvation/oxidation/chemotherapy, which would be a promising strategy for the next generation cancer therapy.
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http://dx.doi.org/10.1039/d0bm01950jDOI Listing
March 2021

Pharmacokinetic study of three different formulations of l-tetrahydropalmatine in brain tissues of rats.

Biomed Chromatogr 2021 May 15;35(5):e5066. Epub 2021 Jan 15.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China.

l-Tetrahydropalmatine (l-THP), an active alkaloid compound isolated from Rhizoma Corydalis-yanhusuo, has been reported to possess biological activity for treating cocaine use. To enhance both oral bioavailability and brain penetration, three formulations of l-THP suspension, mixture of l-THP-puerarin and self-microemulsifying drug delivery systems (SMEDDS) were prepared. A sensitive and reliable ultra-high-performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of l-THP and its active metabolite l-isocorypalmine (l-ICP) in rat brain. Diazepam was used as the internal standard. The chromatographic separation was achieved on a Bonshell ASB C column at 30°C using acetonitrile-aqueous formic acid as mobile phase in gradient mode. The linearity was validated over the concentration ranges of 4.00-2,500 ng/ml for l-THP and 0.400-500 ng/ml for l-ICP. Full method validation was within the acceptance limits. The method was successfully used to determine the pharmacokinetics of two analytes following oral administration of these three formulations to rats. A significant difference was observed in the main pharmacokinetic parameters between SMEDDS and the suspension, and a 3.25- and 2.97-fold increase in the relative bioavailability of l-THP and l-ICP, respectively, was observed with the SMEDDS compared with the suspension formulation. It was concluded that SMEDDS enhanced the absorption of l-THP and l-ICP and delayed their release in brain.
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http://dx.doi.org/10.1002/bmc.5066DOI Listing
May 2021

Nomogram Predicting the Risk of Locoregional Recurrence After Mastectomy for Invasive Micropapillary Carcinoma of the Breast.

Clin Breast Cancer 2021 08 16;21(4):e368-e376. Epub 2020 Dec 16.

Department of Breast Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. Electronic address:

Background: The risk of locoregional recurrence (LRR) after mastectomy for breast invasive micropapillary carcinoma (IMPC) remains poorly defined. We aimed to construct an effective prognostic nomogram to estimate the individualized risk of LRR for providing accurate information for long-term follow-up.

Patients And Methods: A total of 388 patients with breast IMPC were included in the current study. Based on the Cox regression and clinical significance, a nomogram with an online prediction version was created. This model was evaluated and internally validated by concordance index and calibration plot. Receiver operating characteristic curve and decision curve analysis were used to assess the discrimination and clinical utility, and Kaplan-Meier curves estimated the probability of LRR.

Results: The variables (age, lymph node metastasis, hormone receptor status, lymphovascular invasion, histologic grade, and adjuvant radiotherapy) were included in the nomogram. This model was well-calibrated to predict the possibility of LRR and displayed favorable clinical utility; the concordance index was 0.86 (95% confidence interval, 0.81-0.91), which was higher than any single predictor. The area under the curve of the nomogram was 0.89, whereas that of the conventional staging system was 0.72. An online prognostic nomogram was built for convenient use. Kaplan-Meier curves showed that the nomogram had a better risk stratification than the conventional staging system.

Conclusions: The nomogram could accurately predict the individualized risk of LRR after mastectomy for breast IMPC. By identifying the risk stratification, this model is expected to assist clinicians and patients in improving long-term follow-up strategies.
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http://dx.doi.org/10.1016/j.clbc.2020.12.003DOI Listing
August 2021

Integrative analysis of long extracellular RNAs reveals a detection panel of noncoding RNAs for liver cancer.

Theranostics 2021 1;11(1):181-193. Epub 2021 Jan 1.

MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Long extracellular RNAs (exRNAs) in plasma can be profiled by new sequencing technologies, even with low abundance. However, cancer-related exRNAs and their variations remain understudied. We investigated different variations (i.e. differential expression, alternative splicing, alternative polyadenylation, and differential editing) in diverse long exRNA species (e.g. long noncoding RNAs and circular RNAs) using 79 plasma exosomal RNA-seq (exoRNA-seq) datasets of multiple cancer types. We then integrated 53 exoRNA-seq datasets and 65 self-profiled cell-free RNA-seq (cfRNA-seq) datasets to identify recurrent variations in liver cancer patients. We further combined TCGA tissue RNA-seq datasets and validated biomarker candidates by RT-qPCR in an individual cohort of more than 100 plasma samples. Finally, we used machine learning models to identify a signature of 3 noncoding RNAs for the detection of liver cancer. We found that different types of RNA variations identified from exoRNA-seq data were enriched in pathways related to tumorigenesis and metastasis, immune, and metabolism, suggesting that cancer signals can be detected from long exRNAs. Subsequently, we identified more than 100 recurrent variations in plasma from liver cancer patients by integrating exoRNA-seq and cfRNA-seq datasets. From these datasets, 5 significantly up-regulated long exRNAs were confirmed by TCGA data and validated by RT-qPCR in an independent cohort. When using machine learning models to combine two of these validated circular and structured RNAs () with a miRNA () as a panel to classify liver cancer patients from healthy donors, the average AUROC of the cross-validation was 89.4%. The selected 3-RNA panel successfully detected 79.2% AFP-negative samples and 77.1% early-stage liver cancer samples in the testing and validation sets. Our study revealed that different types of RNA variations related to cancer can be detected in plasma and identified a 3-RNA detection panel for liver cancer, especially for AFP-negative and early-stage patients.
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http://dx.doi.org/10.7150/thno.48206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681086PMC
August 2021

Direct observation of Klein tunneling in phononic crystals.

Science 2020 12;370(6523):1447-1450

Nano-scale Science and Engineering Center, University of California, Berkeley, CA 94720, USA.

Tunneling plays an essential role in many branches of physics and has found important applications. It is theoretically proposed that Klein tunneling occurs when, under normal incidence, quasiparticles exhibit unimpeded penetration through potential barriers independent of their height and width. We created a phononic heterojunction by sandwiching two types of artificial phononic crystals with different Dirac point energies. The direct observation of Klein tunneling as shown by the key feature of unity transmission is demonstrated. Our experiment reveals that Klein tunneling occurs over a broad band of acoustic frequency. The direct observation of Klein tunneling in phononic crystals could find applications in signal processing, supercollimated beams, and communications.
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http://dx.doi.org/10.1126/science.abe2011DOI Listing
December 2020

Cobalt-Catalyzed Direct C-H Carbonylative Synthesis of Free ()-Indolo[1,2-]quinoxalin-6(5)-ones.

Org Lett 2021 01 15;23(1):178-182. Epub 2020 Dec 15.

Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People's Republic of China.

A cobalt-catalyzed direct C-H carbonylative reaction of -(2-(1-indol-1-yl)phenyl)picolinamides for the synthesis of ()-indolo[1,2-]quinoxalin-6(5)-one skeletons has been developed. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source and picolinamide as the traceless directing group, various free ()-indolo[1,2-]quinoxalin-6(5)-ones were obtained in good yields (up to 88%). Additionally, a series of product derivatizations were demonstrated, and the core fragment of PARP-1 inhibitor can be readily constructed by this protocol.
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http://dx.doi.org/10.1021/acs.orglett.0c03900DOI Listing
January 2021

Identification of H7N9 hemagglutinin novel protein epitopes that elicit strong antibody-dependent, cell-mediated cytotoxic activities with protection from influenza infection in mouse model.

Cell Immunol 2021 01 6;359:104255. Epub 2020 Dec 6.

Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China. Electronic address:

Background: Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the mechanisms connecting humoral immunity and cellular immunity and has been well-demonstrated in recent studies. Neutralizing antibodies and antibodies can mediate ADCC effects and both build a strong defense against H7N9 influenza virus infection. In our previous study, we found that H7N9 patients' plasma displayed low neutralizing activities that were not sufficient for host protection; however, the plasma of some patients can mediate strong ADCC effects.

Methods: Based on the plasma samples of H7N9 infected patients collected, we measured the ADCC activities of these samples and selected the best to locate the dominant epitopes on H7N9 hemagglutinin (HA) protein that can elicit antibodies and strong ADCC activities. We constructed a yeast surface-display H7N9 HA protein epitope library and screened this library against plasma samples with different potencies in mediating ADCC effects.

Results: Two dominant epitopes were selected from the screening. Plasma samples with depleted antibodies that were specific to the epitopes showed reduced ADCC activities. The serum of mice immunized with the epitopes elicited strong ADCC activities. Three monoclonal antibodies were isolated which showed high ADCC effects in vitro. Vaccination with isolated ADCC activating epitopes can provide partial protection from influenza infection in mouse model. And mice with vaccinated with combination of epitopes and extracellular domain can provide full protection from influenza infection in the same mouse model.

Conclusions: In this study, the epitopes isolated on H7N9 HA were immunogenic and elicited antibodies and strong ADCC activities in mice. Although the protective effect of the epitopes is partial, the combination of epitopes and extracellular domain can provide 100% protection from influenza virus infection in the same mouse model. Our study provides information on the potential use of epitope vaccine design against H7N9 viral infection.
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http://dx.doi.org/10.1016/j.cellimm.2020.104255DOI Listing
January 2021

Pericarpium protects against isoproterenol-induced chronic heart failure via activation of PPARγ.

Ann Transl Med 2020 Nov;8(21):1396

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Accumulated clinical trials and animal studies showed that Qiliqiangxin (QLQX), a traditional Chinese medicine formula containing extracts of 11 herbs, exerts beneficial effects on chronic heart failure (HF). Pericarpium (CRP), one herbal medicine in QLQX, has been widely used in treatment against digestive, respiratory and cardiovascular diseases (CVDs) in China. However, the cardiac protective effects and mechanisms of CRP are still unclear.

Methods: The effects of CRP were investigated in isoproterenol (ISO)-induced chronic HF mice model and neonatal rat ventricular cardiomyocytes (NRVMs) treated with ISO. Echocardiography was used to determine cardiac function. Hematoxylin-eosin (HE) staining and α-actinin immunofluorescent staining were used to measure cardiomyocyte size. Cardiac fibrosis was evaluated by Masson's trichrome staining. The expression of atrial natriuretic polypeptide (ANP) and brain natriuretic polypeptide (BNP) were determined by quantitative real time PCR (qRT-PCR). Western blot was applied to examine the expression of peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1α (PGC-1α), fibrosis-related and apoptosis-related proteins.

Results: We found that CRP could significantly attenuate ISO-induced cardiac dysfunction, inhibit cardiac pathological hypertrophy and alleviate myocardial fibrosis and apoptosis. Mechanistically, the downregulation of PPARγ and PGC-1α in ISO-injected mice hearts and ISO-treated NRVMs could be reversed by CRP treatment. The beneficial effects of CRP against ISO-induced HF were abolished by PPARγ inhibitor (T0070907), suggesting that CRP-mediated PPARγ upregulation was essential for the preventive effect of CRP on ISO-induced cardiac dysfunction.

Conclusions: In conclusion, our study demonstrated that CRP attenuates ISO-induced cardiac remodeling via PPARγ activation, which represents a new application for CRP in the prevention of chronic HF.
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http://dx.doi.org/10.21037/atm-20-2200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723657PMC
November 2020
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