Publications by authors named "Hongyan Sun"

195 Publications

Pivotal factors associated with the immunosuppressive tumor microenvironment and melanoma metastasis.

Cancer Med 2021 Jul 22;10(14):4710-4720. Epub 2021 Jun 22.

Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.

Background: Considering melanoma is the deadliest malignancy among dermatoma and presently lacks effective therapies, there is an urgent need to investigate the potential mechanisms underlying melanoma metastasis and determine prospective therapeutic targets for precise treatment of melanoma.

Method: Hub genes in melanoma metastasis were identified by analyzing RNA-seq data (mRNA, miRNA, and lncRNA) obtained from TCGA database. Then the identified hub genes were validated in human tissues with qRT-PCR, followed by survival analysis. Competing endogenous RNAs of the hub genes were defined to clarify potential molecular mechanism of melanoma progression. Then central gene-related signaling pathways were analyzed, followed by immune cell abundance analysis in tumor microenvironment with CYTERSORTx.

Result: A tetrad of IL2RA, IL2RG, IFNG, and IL7R genes were determined as hub genes and verified by qRT-PCR, which were significantly associated with unfavorable prognosis in melanoma. LINC02446, LINC01857, and LINC02384 may act as competing endogenous lncRNAs of IL2RA and IL7R through absorbing their shared miR.891a.5p and miR.203b.3p. JAK-STAT signaling pathway identified as the most relevant pathway in melanoma metastasis, as well as a wealthy of genes including TNFRSF 13B, TNFRSF17, TNFRSF9, TNFRSF8, TNFRSF13C, TNFRSF11B, LAG3, NRP1, ENTPD1, NT5E, CCL21, and CCR7, may induce tumor autoimmune suppression through enhancing regulatory T-cell abundance and performance in the tumor microenvironment. And regulatory T-cell proportion was indeed critically elevated in metastatic melanoma relative to primary melanoma, as well as in highly expressed IL2RA, IL2RG, IL7R, and IFNG group than their respective counterparts.

Conclusion: Elevated IL2RA, IL2RG, IL7R, and IFNG expression may play a central role in promoting melanoma metastasis through up regulation of intratumoral regulatory T-cell proportion mainly by activation of JAK-STAT signaling pathway. LINC02446, LINC01857, and LINC02384 may stimulate melanoma progression by reducing tumor-protecting miR.891a.5p and miR.203b.3p. A number of identified molecules including TNFRSF13B, LAG3, NRP1, ENTPD1, NT5E, CCL21, and CCR7 can serve as future therapeutic targets in melanoma treatment.
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http://dx.doi.org/10.1002/cam4.3963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290234PMC
July 2021

BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression.

Sci Rep 2021 Jun 9;11(1):12219. Epub 2021 Jun 9.

Department of Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR, China.

Antimicrobial peptides (AMPs) have emerged as a promising alternative to small molecule antibiotics. Although AMPs have previously been isolated in many organisms, efforts on the systematic identification of AMPs in fish have been lagging. Here, we collected peptides from the plasma of medaka (Oryzias latipes) fish. By using mass spectrometry, 6399 unique sequences were identified from the isolated peptides, among which 430 peptides were bioinformatically predicted to be potential AMPs. One of them, a thermostable 13-residue peptide named BING, shows a broad-spectrum toxicity against pathogenic bacteria including drug-resistant strains, at concentrations that presented relatively low toxicity to mammalian cell lines and medaka. Proteomic analysis indicated that BING treatment induced a deregulation of periplasmic peptidyl-prolyl isomerases in gram-negative bacteria. We observed that BING reduced the RNA level of cpxR, an upstream regulator of envelope stress responses. cpxR is known to play a crucial role in the development of antimicrobial resistance, including the regulation of genes involved in drug efflux. BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria. In addition, exposure to sublethal doses of BING delayed the development of antibiotic resistance. To our knowledge, BING is the first AMP shown to suppress cpxR expression in Gram-negative bacteria. This discovery highlights the cpxR pathway as a potential antimicrobial target.
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http://dx.doi.org/10.1038/s41598-021-91765-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190156PMC
June 2021

NBD-based synthetic probes for sensing small molecules and proteins: design, sensing mechanisms and biological applications.

Chem Soc Rev 2021 Jul;50(13):7436-7495

State Key Laboratory of Organic-Inorganic Composites and Beijing Key Lab of Bioprocess, Beijing University of Chemical Technology (BUCT), Beijing 100029, China.

Compounds with a nitrobenzoxadiazole (NBD) skeleton exhibit prominent useful properties including environmental sensitivity, high reactivity toward amines and biothiols (including H2S) accompanied by distinct colorimetric and fluorescent changes, fluorescence-quenching ability, and small size, all of which facilitate biomolecular sensing and self-assembly. Amines are important biological nucleophiles, and the unique activity of NBD ethers with amines has allowed for site-specific protein labelling and for the detection of enzyme activities. Both H2S and biothiols are involved in a wide range of physiological processes in mammals, and misregulation of these small molecules is associated with numerous diseases including cancers. In this review, we focus on NBD-based synthetic probes as advanced chemical tools for biomolecular sensing. Specifically, we discuss the sensing mechanisms and selectivity of the probes, the design strategies for multi-reactable multi-quenching probes, and the associated biological applications of these important constructs. We also highlight self-assembled NBD-based probes and outline future directions for NBD-based chemosensors. We hope that this comprehensive review will facilitate the development of future probes for investigating and understanding different biological processes and aid the development of potential theranostic agents.
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http://dx.doi.org/10.1039/d0cs01096kDOI Listing
July 2021

Characterization of Alternative Splicing (AS) Events during Chicken () Male Germ-Line Stem Cell Differentiation with Single-Cell RNA-seq.

Animals (Basel) 2021 May 20;11(5). Epub 2021 May 20.

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

Alternative splicing (AS) is a ubiquitous, co-transcriptional, and post-transcriptional regulation mechanism during certain developmental processes, such as germ cell differentiation. A thorough understanding of germ cell differentiation will help us to open new avenues for avian reproduction, stem cell biology, and advances in medicines for human consumption. Here, based on single-cell RNA-seq, we characterized genome-wide AS events in manifold chicken male germ cells: embryonic stem cells (ESCs), gonad primordial germ cells (gPGCs), and spermatogonia stem cells (SSCs). A total of 38,494 AS events from 15,338 genes were detected in ESCs, with a total of 48,955 events from 14,783 genes and 49,900 events from 15,089 genes observed in gPGCs and SSCs, respectively. Moreover, this distribution of AS events suggests the diverse splicing feature of ESCs, gPGCs, and SSCs. Finally, several crucial stage-specific genes, such as NANOG, POU5F3, LIN28B, BMP4, STRA8, and LHX9, were identified in AS events that were transmitted in ESCs, gPGCs, and SSCs. The gene expression results of the RNA-seq data were validated by qRT-PCR. In summary, we provided a comprehensive atlas of the genome-wide scale of the AS event landscape in male chicken germ-line cells and presented its distribution for the first time. This research may someday improve treatment options for men suffering from male infertility.
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http://dx.doi.org/10.3390/ani11051469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160964PMC
May 2021

Development and application of novel electrophilic warheads in target identification and drug discovery.

Biochem Pharmacol 2021 Aug 29;190:114636. Epub 2021 May 29.

School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China; MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, China. Electronic address:

Nucleophilic amino acids play important roles in maintenance of protein structure and function, covalent modification of such amino acid residues by therapeutic agents is an efficient way to treat human diseases. Most of current clinical drugs are structurally limited to α,β-unsaturated amide as an electrophilic warhead. To alleviate this issue, many novel electrophiles have been developed in recent years that can covalently bind to different amino acid residues and provides a unique way to interrogate proteins, including "undruggable" targets. With an activity-based protein profiling (ABPP) approach, the activity and functionality of a protein and its binding sites can be assessed. This facilitates an understanding of protein function, and contributes to the discovery of new druggable targets and lead compounds. Meanwhile, many novel inhibitors bearing new reactive warhead were developed and displayed remarkable pharmaceutical properties. In this perspective, we have reviewed the recent remarkable progress of novel electrophiles and their applications in target identification and drug discovery.
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http://dx.doi.org/10.1016/j.bcp.2021.114636DOI Listing
August 2021

Prognostic Value of ctDNA Mutation in Melanoma: A Meta-Analysis.

J Oncol 2021 4;2021:6660571. Epub 2021 May 4.

Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, China.

Purpose: Melanoma is the most aggressive form of skin cancer. Circulating tumor DNA (ctDNA) is a diagnostic and prognostic marker of melanoma. However, whether ctDNA mutations can independently predict survival remains controversial. This meta-analysis assessed the prognostic value of the presence or change in ctDNA mutations in melanoma patients.

Methods: We identified studies from the PubMed, EMBASE, Web of Science, and Cochrane databases. We estimated the combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) using either fixed-effect or random-effect models based on heterogeneity.

Results: Sixteen studies including 1,781 patients were included. Both baseline and posttreatment detectable ctDNA were associated with poor OS (baseline detectable vs. undetectable, pooled HR = 1.97, 95% CI = 1.64-2.36, < 0.00001; baseline undetectable vs. detectable, pooled HR = 0.19, 95% CI = 0.11-0.36, < 0.00001; posttreatment detectable vs. undetectable, pooled HR = 2.36, 95% CI = 1.30-4.28, =0.005). For PFS, baseline detectable ctDNA may be associated with adverse PFS (baseline detectable vs. undetectable, pooled HR = 1.41, 95% CI = 0.84-2.37, =0.19; baseline undetectable vs. detectable, pooled HR = 0.43, 95% CI = 0.19-0.95, =0.04) and baseline high ctDNA and increased ctDNA were significantly associated with adverse PFS (baseline high vs. low/undetectable, pooled HR = 3.29, 95% CI = 1.73-6.25, =0.0003; increase vs. decrease, pooled HR = 4.48, 95% CI = 2.45-8.17, < 0.00001). The baseline BRAF ctDNA mutation-positive group was significantly associated with adverse OS compared with the baseline ctDNA-negative group (pooled HR = 1.90, 95% CI = 1.58-2.29, < 0.00001). There were no significant differences in PFS between the baseline BRAF ctDNA mutation-detectable group and the undetectable group (pooled HR = 1.02, 95% CI = 0.72-1.44, =0.92).

Conclusion: The presence or elevation of ctDNA mutation or BRAF ctDNA mutation was significantly associated with worse prognosis in melanoma patients.
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http://dx.doi.org/10.1155/2021/6660571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116156PMC
May 2021

Production of viable chicken by allogeneic transplantation of primordial germ cells induced from somatic cells.

Nat Commun 2021 05 20;12(1):2989. Epub 2021 May 20.

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

The allogeneic transplantation of primordial germ cells (PGCs) derived from somatic cells overcomes the limitation of avian cloning. Here, we transdifferentiate chicken embryo fibroblasts (CEFs) from black feathered Langshan chickens to PGCs and transplant them into White Plymouth Rock chicken embryos to produce viable offspring with characteristics inherited from the donor. We express Oct4/Sox2/Nanog/Lin28A (OSNL) to reprogram CEFs to induced pluripotent stem cells (iPSCs), which are further induced to differentiate into PGCs by BMP4/BMP8b/EGF. DNA demethylation, histone acetylation and glycolytic activation elevate the iPSC induction efficiency, while histone acetylation and glycolytic inhibition facilitate PGCs formation. The induced PGCs (iPGCs) are transplanted into the recipients, which are self-crossed to produce 189/509 somatic cells derived chicken with the donor's characteristics. Microsatellite analysis and genome sequencing confirm the inheritance of genetic information from the donor. Thus, we demonstrate the feasibility of avian cloning from somatic cells.
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http://dx.doi.org/10.1038/s41467-021-23242-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138025PMC
May 2021

Microalgae separation by inertia-enhanced pinched flow fractionation.

Electrophoresis 2021 May 2. Epub 2021 May 2.

College of Marine Engineering, Dalian Maritime University, Dalian, P. R. China.

To improve the accuracy and efficiency of ships' ballast water detection, the separation of microalgae according to size is significant. In this article, a method to separate microalgae based on inertia-enhanced pinched flow fractionation (iPFF) was reported. The method utilized the inertial lift force induced by flow to separate microalgae according to size continuously. The experimental results show that, as the Reynolds number increases, the separation effect becomes better at first, but then stays unchanged. The best separation effect can be obtained when the Reynolds number is 12.3. In addition, with the increase of the flow rate ratio between sheath fluid and microalgae mixture, the separation effect becomes better and the best separation effect can be obtained when the flow rate ratio reaches 10. In this case, the recovery rate of Tetraselmis sp. is about 90%, and the purity is about 86%; the recovery rate of Chlorella sp. is as high as 99%, and the purity is about 99%. After that, the separation effect keeps getting better but very slowly. In general, this study provides a simple method for the separation of microalgae with different sizes, and lays a foundation for the accurate detection of microalgae in the ballast water.
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http://dx.doi.org/10.1002/elps.202000325DOI Listing
May 2021

Asymptomatic Hyperuricemia and Metabolically Unhealthy Obesity: A Cross-Sectional Analysis in the Tianning Cohort.

Diabetes Metab Syndr Obes 2021 25;14:1367-1374. Epub 2021 Mar 25.

Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People's Republic of China.

Objective: The relationship between obesity and hyperuricemia has been demonstrated by many studies. However, whether or to what extent metabolic condition influents the association between obesity and hyperuricemia was not clear. Here, we aimed to examine the association between obese-metabolic phenotype and hyperuricemia in a large sample of Chinese adults.

Methods: According to BMI and metabolic syndrome, obese-metabolic phenotype was defined as metabolically unhealthy obesity (MUO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically healthy non-obesity (MHNO)in the Tianning cohort (N=5072). We conducted a cross-sectional analysis between obese-metabolic phenotype and hyperuricemia, followed by a Mendelian Randomization analysis using GWAS summary data to confirm the causality between uric acid and BMI.

Results: The average level of serum UA showed 41.87-higher μmol/L in participants with MHO (β=41.87, <0.001) and 63.18-higher μmol/L in participants with MUO (β=63.18, <0.001), compared to those with MHNO. Compared to participants with MHNO, those with MUO had the highest likelihood to have hyperuricemia (OR=4.56, <0.001), followed by those with MHO (OR=3.32, <0.001). Mendelian randomization analysis indicated that uric acid was more likely to be a consequence of BMI (β=0.059, =6.54×10).

Conclusion: MUO, in comparison with MHO, was significantly associated with hyperuricemia in Chinese adults.
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http://dx.doi.org/10.2147/DMSO.S301363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006809PMC
March 2021

Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549.

Oncol Lett 2021 May 19;21(5):403. Epub 2021 Mar 19.

National Health Commission Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, Jilin 130000, P.R. China.

Radiotherapy is widely used in the management of lung cancer, and physicians are aware that the effect of radiotherapy is dependent on radiosensitivity. Although a series of blockers and activators targeting molecules related to radioresistance have been developed as radiation sensitizers, compensatory mechanisms or drug resistance limits their clinical efficacy. The identification of a key molecule related to lung cancer cell radioresistance or an effective molecular target is a challenging but important problem in radiation oncology. A previous study found that neuropilin 1 (NRP1) is related to radioresistance in A549 cells and is associated with VEGF, PI3K-Akt, MAPK-ERK, P38, NF-κβ and TGF-β. Inhibition of NRP1 can increase the radiosensitivity of A549 cells. Therefore, NRP1 may be a molecular target for radiotherapy-sensitizing drugs in lung cancer. The present study investigated the key downstream genes of NRP1, verified their regulation and clarified their roles in regulating lung cancer radioresistance. NRP1 positively regulated the downstream homeobox genes (HOXs) HOXA6, HOXA9 and mixed lineage leukaemia 5 (MLL5) in addition to MLL5-regulated HOXA6 and HOXA9, but these genes did not regulate NRP1. MLL5, HOXA6 and HOXA9 levels were decreased in tumour tissues and positively correlated with NRP1. All of these genes were induced by ionizing radiation and . NRP1 expression was significantly lower in squamous cell carcinoma compared with that in adenocarcinoma, and lymph node metastasis occurred more often in patients with lung cancer with high MLL5 and NRP1 expression compared with patients with low MLL5 and NRP1 expression. Collectively, these data confirmed that NRP1 is associated with MLL5 and regulates radioresistance through HOXA6 and HOXA9.
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http://dx.doi.org/10.3892/ol.2021.12664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988706PMC
May 2021

Influence of particle size on the aggregation behavior of nanoparticles: Role of structural hydration layer.

J Environ Sci (China) 2021 May 24;103:33-42. Epub 2020 Oct 24.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

More and more attention has been paid to the aggregation behavior of nanoparticles, but little research has been done on the effect of particle size. Therefore, this study systematically evaluated the aggregation behavior of nano-silica particles with diameter 130-480 nm at different initial particle concentration, pH, ionic strength, and ionic valence of electrolytes. The modified Smoluchowski theory failed to describe the aggregation kinetics for nano-silica particles with diameters less than 190 nm. Besides, ionic strength, cation species and pH all affected fast aggregation rate coefficients of 130 nm nanoparticles. Through incorporating structural hydration force into the modified Smoluchowski theory, it is found that the reason for all the anomalous aggregation behavior was the different structural hydration layer thickness of nanoparticles with various sizes. The thickness decreased with increasing of particle size, and remained basically unchanged for particles larger than 190 nm. Only when the distance at primary minimum was twice the thickness of structural hydration layer, the structural hydration force dominated, leading to the higher stability of nanoparticles. This study clearly clarified the unique aggregation mechanism of nanoparticles with smaller size, which provided reference for predicting transport and fate of nanoparticles and could help facilitate the evaluation of their environment risks.
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http://dx.doi.org/10.1016/j.jes.2020.10.007DOI Listing
May 2021

An early global role for Axin is required for correct patterning of the anterior-posterior axis in the sea urchin embryo.

Development 2021 Mar 31;148(7). Epub 2021 Mar 31.

Department of Biology, University of Miami, Coral Gables, FL 33146, USA

Activation of Wnt/β-catenin (cWnt) signaling at the future posterior end of early bilaterian embryos is a highly conserved mechanism for establishing the anterior-posterior (AP) axis. Moreover, inhibition of cWnt at the anterior end is required for development of anterior structures in many deuterostome taxa. This phenomenon, which occurs around the time of gastrulation, has been fairly well characterized, but the significance of intracellular inhibition of cWnt signaling in cleavage-stage deuterostome embryos for normal AP patterning is less well understood. To investigate this process in an invertebrate deuterostome, we defined Axin function in early sea urchin embryos. is ubiquitously expressed at relatively high levels in early embryos and functional analysis revealed that Axin suppresses posterior cell fates in anterior blastomeres by blocking ectopic cWnt activation in these cells. Structure-function analysis of sea urchin Axin demonstrated that only its GSK-3β-binding domain is required for cWnt inhibition. These observations and results in other deuterostomes suggest that Axin plays a crucial conserved role in embryonic AP patterning by preventing cWnt activation in multipotent early blastomeres, thus protecting them from assuming ectopic cell fates.
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http://dx.doi.org/10.1242/dev.191197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034878PMC
March 2021

Identification of Potential BRAF Inhibitor Joint Therapy Targets in PTC based on WGCAN and DCGA.

J Cancer 2021 21;12(6):1779-1791. Epub 2021 Jan 21.

Shanghai Center for Thyroid Disease, Shanghai Tenth People's Hospital, Shanghai, China.

As the most common mutation in papillary thyroid cancer (PTC), B-type Raf kinase V600E mutation ( ) has become an important target for the clinical treatment of PTC. However, the clinical application still faces the problem of resistance to BRAF inhibitors (BRAFi). Therefore, exploring BRAF-associated prognostic factors to providing potential joint targets is important for combined targeted therapy with BRAFi. In this study, we combined transcript data and clinical information from 199 wild-type ( ) patients and 283 mutant patients collected from The Cancer Genome Atlas (TCGA), and screened 455 BRAF- associated genes through differential analysis and weighted gene co-expression network analysis. Based on these -associated genes, we performed functional enrichment analysis and co-expression differential analysis and constructed a core co-expression network. Next, genes in the differential co-expression network were used to predict drugs for therapy in the crowd extracted expression of differential signatures (CREEDS) database, and the key genes were selected based on the hub co-expression network through survival analyses and receiver operating characteristic (ROC) curve analyses. Finally, we obtained eight BRAF -associated biomarkers with both prognostic and diagnostic values as potential BRAFi joint targets, including , , , , , , , and . Among these genes, FN1, MET, PROS1, and were validated through GEO database. Two novel biomarkers, PROS1 and , were further validated by qRT-PCR experiment. Besides, we obtained four potential targeted drugs that could be used in combination with BRAFi to treat PTC, including MET inhibitor, ERBB3 inhibitor, anti-NaPi2b antibody-drug conjugate, and carboplatin through literature review. The study provided potential drug targets for combination therapy with BRAFi for PTC to overcome the drug resistance for BRAFi.
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http://dx.doi.org/10.7150/jca.51551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890315PMC
January 2021

Glycolysis Combined with Core Pluripotency Factors to Promote the Formation of Chicken Induced Pluripotent Stem Cells.

Animals (Basel) 2021 Feb 6;11(2). Epub 2021 Feb 6.

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) in vitro. Previously, a lentivirus induction strategy of introducing Oct4, Sox2, Nanog and Lin28 (OSNL) into the iPSC process has been shown as a possible way to produce chicken iPSCs from chicken embryonic fibroblasts, but the induction efficiency of this method was found to be significantly limiting. In order to help resolve this efficiency obstacle, this study seeks to clarify the associated regulation mechanisms and optimizes the reprogramming strategy of chicken iPSCs. This study showed that glycolysis and the expression of glycolysis-related genes correlate with a more efficient reprogramming process. At the same time, the transcription factors Oct4, Sox2 and Nanog were found to activate the expression of glycolysis-related genes. In addition, we introduced two small-molecule inhibitors (2i-SP) as a "glycolysis activator" together with the OSNL cocktail, and found that this significantly improved the induction efficiency of the iPSC process. As such, the study identifies direct molecular connections between core pluripotency factors and glycolysis during the chicken iPSC induction process and, with its results, provides a theoretical basis and technical support for chicken somatic reprogramming.
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http://dx.doi.org/10.3390/ani11020425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915628PMC
February 2021

Molecular characterization, expression and function analysis of Epinephelus coioides MKK4 response to SGIV and Vibrio alginolyticus infection.

Dev Comp Immunol 2021 Jun 19;119:104020. Epub 2021 Jan 19.

Joint Laboratory of Guangdong Province and Hong Kong Regions on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, Guangdong Province, PR China. Electronic address:

Mitogen-activated protein kinase 4 (MKK4), a member of the MAP kinase family, play important roles in response to many environmental and cellular stresses in mammals. In this study, three MKK4 subtypes, EcMKK4-1, EcMKK4-2 and EcMKK4-3, were obtained from grouper Epinephelus coioides. The open reading frame (ORF) of EcMKK4s are obtained and the EcMKK4s proteins contain highly conserved domains: a S_TKc domain, a canonical diphosphorylation group and two conserved MKKK ATP binding motifs, Asp-Phe-Gly (DFG) and Ala-Pro-Glu (APE). EcMKK4s could be found both in the cytoplasmic and nuclear. The EcMKK4s mRNA were detected in all E. coioides tissues examined with the different expression levels, and the expression were up-regulated during SGIV (Singapore grouper iridescent virus) or Vibrio alginolyticus infection. EcMKK4 could significantly reduce the activation of AP-1 reporter gene. The results suggested that EcMKK4s might play important roles in pathogen-caused inflammation.
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http://dx.doi.org/10.1016/j.dci.2021.104020DOI Listing
June 2021

Single-step fluorescent probes to detect decrotonylation activity of HDACs through intramolecular reactions.

Eur J Med Chem 2021 Feb 30;212:113120. Epub 2020 Dec 30.

Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China; Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China. Electronic address:

Lysine crotonylation plays vital roles in gene transcription and cellular metabolism. Nevertheless, methods for dissecting the molecular mechanisms of decrotonyaltion remains limited. So far, there is no single-step fluorescent method developed for enzymatic decrotonylation activity detection. The major difficulty is that the aliphatic crotonylated lysine doesn't allow π-conjugation to a fluorophore and decrotonylation can not modulate the electronic state directly. Herein, we have designed and synthesized two activity-based single-step fluorogenic probes KTcr-I and KTcr-II for detecting enzymatic decrotonylation activity. These two probes can be recognized by histone deacetylases and undergo intramolecular nucleophilic exchange reaction to generate fluorescence signal. Notably, peptide sequence-dependent effect was observed. KTcr-I can be recognized by Sirt2 more effectively, while KTcr-II with LGKcr peptide sequence preferentially reacted with HDAC3. Compared to other methods of studying enzymatic decrotonylation activity, our single-step fluorescent method has a number of advantages, such as facileness, high sensitivity, cheap facility and little material consumed. We envision that the probes developed in this study will provide useful tools to screen inhibitors which suppress the decrotonylation activity of HDACs. Such probes will be useful for further delineating the roles of decrotonylation enzyme and aid in biomarker identification and drug discovery.
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http://dx.doi.org/10.1016/j.ejmech.2020.113120DOI Listing
February 2021

Study on the Synthesized Rosin Glyceride over LaZSM-5 Zeolite Catalyst Synthesized by the in Situ Method.

ACS Omega 2020 Dec 7;5(49):31543-31550. Epub 2020 Dec 7.

Taiyuan University of Science and Technology, College of Environment and Safety, Taiyuan 030024, PR China.

LaZSM-5 zeolite was synthesized by the in situ method and used as catalysts to catalyze the synthesis of rosin glyceride. As a comparison, ZSM-5 was also synthesized and used as catalysts to catalyze the synthesis of rosin glyceride. The synthesized ZSM-5 and LaZSM-5 zeolite catalysts were characterized and analyzed. The experimental results showed that the in situ synthesis of LaZSM-5 made La into the skeleton of ZSM-5 zeolite and increased the amount of Lewis acid on the LaZSM-5 zeolite. Also, Lewis acid was the key to liquid-phase esterification reaction. Compared with ZSM-5 zeolite, LaZSM-5 zeolite contributed to a higher yield and better stability as a catalyst for the synthesis of rosin glycerides.
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http://dx.doi.org/10.1021/acsomega.0c03427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745225PMC
December 2020

Experimental and Theoretical Investigations of the Radical-Radical Reaction: NH + NO.

J Phys Chem A 2020 Dec 2;124(50):10434-10446. Epub 2020 Dec 2.

In-Space Propulsion Branch, Air Force Research Laboratory, AFRL/RQRS, Edwards Air Force Base, California 93524, United States.

The NH + NO reaction plays a key role during the early stages of hypergolic ignition between NH and NO. Here for the first time, the reaction kinetics of NH in excess NO was studied in 2.0 Torr of N and in the narrow temperature range 298-348 K in a pulsed photolysis flow-tube reactor coupled to a mass spectrometer. The temporal profile of the product, HONO, was determined by direct detection of the / +47 amu ion signal. For each chosen [NO], the observed [HONO] trace was fitted to a biexponential kinetics expression, which yielded a value for the pseudo-first-order rate coefficient, ', for the reaction of NH with NO. The slope of the plot of ' versus [NO] yielded a value for the observed bimolecular rate coefficient, , which could be fitted to an Arrhenius expression of (2.36 ± 0.47) × 10 exp((520 ± 350)/) cm molecule s. The errors are 1σ and include estimated uncertainties in the NO concentration. The potential energy surface of NH + NO was investigated by advanced ab initio quantum chemistry theories. It was found that the reaction occurs via a complex reaction mechanism, and all of the reaction channels have transition state energies below that of the entrance asymptote. The radical-radical addition forms the NHNO adducts, while roaming-mediated isomerization reactions yield the NHONO isomers, which undergo rapid dissociation reactions to several sets of distinct products. The RRKM multiwell master equation simulations revealed that the major product channel involves the formation of -HONO and -NH below 500 K and the formation of NO + NHNHO above 500 K, which is nearly pressure independent. The pressure-dependent rate coefficients of the product channels were computed over a wide pressure-temperature range, which encompassed the experimental data.
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http://dx.doi.org/10.1021/acs.jpca.0c07985DOI Listing
December 2020

Removal of phenolic contaminants from water by in situ coated surfactant on Keggin-aluminum nanocluster and biodegradation.

Chemosphere 2021 Apr 4;269:128692. Epub 2020 Nov 4.

Key Laboratory of drinking Water Science and Technology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Science, Beijing, 100049, China. Electronic address:

Recent water treatment plants require multi-process techniques to remove contaminants from aqua media. In this study, we investigate the novel, in situ coated sodium dodecylsulphate (SDS), on kegging Al nanocluster as a single water treatment alternative for the removal of phenolic contaminants and suspension. FTIR, TEM-EDX and Zeta potential analysis characterized the nanocluster decoration. The resulting property was examined by emission (λ-max) of the molecular probe, the online aggregate image of fluorescence microscopy, and mixing isochrone, fat-soluble dye solubilization. The coated media was examined as nearly resembling the hydrophobicity of 1-octanol. The elemental line scanning and mapping showed different morphologies of floc depending on the SDS concentration. The material was found to follow Brownian motion to enmesh suspended particles like a ladder, and served as entrapper for small organic contaminants by the sorbed SDS aggregate, based on their log K. About 85% and ≥95% removal archived for contaminants with the least and highest K value, respectively. The residual solutes in the supernatant were well decomposed by using a bacterial agent. One-step removal (less footprint) and ease of operation make this approach an environmentally compatible and cost-effective alternative for the large-scale treatment process.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128692DOI Listing
April 2021

The difference of aggregation mechanism between microplastics and nanoplastics: Role of Brownian motion and structural layer force.

Environ Pollut 2021 Jan 28;268(Pt B):115942. Epub 2020 Oct 28.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

In recent years, microplastics (MPs) and nanoplastics (NPs) have attracted worldwide attention because of the potential risks they pose to aquatic environments, but there are few studies on the difference of aggregation mechanism between MPs and NPs. In this study, 100 nm and 1 μm polystyrene plastics were selected as models to explore the aggregation mechanism of MPs/NPs under different aquatic environments. The influence of ion species and concentrations on the aggregation behaviors and kinetics were systematically investigated to predict the effects of water quality on the occurrence form of MPs and NPs based on DLVO theory and revised modified Smoluchowski theory. Results showed concentration, valence and hydrated ability of cations jointly affected the aggregation behavior of NPs. The critical coagulation concentration ratio of cations were consistent with Schulze-Hardy rules. But the different aggregation rate coefficients of same valent cations were ascribed to the structural layer force. Anion species played a role in the reaction-controlled regime by producing hydrogen ions to neutralize negative charges on NPs surfaces. Due to the strong Brownian motion and structural layer force, NPs would be stable in freshwater but preferentially aggregated when transport through brackish water, estuaries, eutrophication and high hardness areas and sea water, forming the accumulation hot spots of NPs in the sediment. While for MPs, physical process controlled the aggregation mechanism of them, leading to high stability in natural water and eventually transporting into marine environments. This study provided a theoretical foundation for assessing the transport, distribution, fate and ecological risks of MPs and NPs in realistic aquatic environments.
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http://dx.doi.org/10.1016/j.envpol.2020.115942DOI Listing
January 2021

Effects of Exogenous Hormones and Reproductive Factors on Female Melanoma: A Meta-Analysis.

Clin Epidemiol 2020 29;12:1183-1203. Epub 2020 Oct 29.

Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People's Republic of China.

Epidemiological findings on the effects of hormones on melanoma risk have been inconsistent. We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women. We performed a search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) database through April 2020 for relevant studies. Based on heterogeneity, we performed the meta-analysis of the risk estimates using either fixed effect or random effect models. We identified 38 studies that met the analytical criteria, involving 3,571,910 participants. The results showed that long-term use of oral contraceptives (OC) may increase the risk of melanoma in women (≥5 years [pooled RR=1.18; 95% CI: 1.07-1.31; I=0%] and ≥10 years [pooled RR=1.25; 95% CI: 1.06-1.48; I=0%]). Women who first used OC 15-19 years previously were more likely to develop melanoma (pooled RR=1.52; 95% CI: 1.03-2.24; I=0%), while the years since the last use and the age at first use were not associated with the development of melanoma in women. Hormone replacement therapy (HRT) increased the incidence of melanoma in women (pooled RR=1.12, 95% CI: 1.02-1.24; I=50%) and was especially associated with an increased risk of superficial spreading melanoma (SSM) (pooled RR=1.26; 95% CI: 1.17-1.37; I=0%), and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma, but these results may be due to a combination of sun exposure factors. With regard to reproductive factors, decreased parity and being aged ≥20 years at first birth may be associated with an increased risk of melanoma in females, while menopausal status and age at menarche are not associated with the incidence of melanoma in females. Further large-scale prospective studies are necessary to reveal new pathophysiological mechanisms and new therapeutic targets for cutaneous melanoma.
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http://dx.doi.org/10.2147/CLEP.S273566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605627PMC
October 2020

A pyrene-based ratiometric fluorescent probe with a large Stokes shift for selective detection of hydrogen peroxide in living cells.

J Pharm Anal 2020 Oct 4;10(5):490-497. Epub 2020 Aug 4.

Department of Chemistry and Center of Super-Diamond and Advanced Films, City University of Hong Kong, Hong Kong, China.

Hydrogen peroxide (HO) plays a significant role in regulating a variety of biological processes. Dysregulation of HO can lead to various diseases. Although numerous fluorescent imaging probes for HO have been reported, the development of HO ratiometric fluorescent probe with large Stokes shift remains rather limited. Such probes have shown distinct advantages, such as minimized interference from environment and improved signal-to noise ratio. In this work, we reported a new pyrene-based compound as HO fluorescent probe in vitro. The probe demonstrated ratiometric detection behavior, large Stokes shift and large emission shift. In addition, the probe showed high sensitivity and selectivity towards HO in vitro. Based on these excellent properties, we successfully applied to the visualization of exogenous and endogenous HO in living cells. Cell imaging study also showed that our probe was localized in the mitochondria. We envision that the probe can provide a useful tool for unmasking the biological roles of mitochondrial HO in living systems.
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http://dx.doi.org/10.1016/j.jpha.2020.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591780PMC
October 2020

An activity-based fluorescent probe and its application for differentiating alkaline phosphatase activity in different cell lines.

Chem Commun (Camb) 2020 Nov;56(87):13323-13326

Department of Chemistry and Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China. and Chengdu Research Institute, City University of Hong Kong, Chengdu, 610200, China.

Herein, a new fluorescent probe, AE-Phos, is reported for detecting the ALP activity with the combined advantages of aggregation-induced emission (AIE) and excited state intramolecular proton transfer (ESIPT). Further detailed fluorescence experiments demonstrated that AE-Phos exhibited excellent selectivity and sensitivity, a large Stokes shift, and a fast response towards ALP. Furthermore, AE-Phos was applied to imaging the ALP activity in different cell lines quantitatively.
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http://dx.doi.org/10.1039/d0cc06129hDOI Listing
November 2020

Desuccinylation-Triggered Peptide Self-Assembly: Live Cell Imaging of SIRT5 Activity and Mitochondrial Activity Modulation.

J Am Chem Soc 2020 10 11;142(42):18150-18159. Epub 2020 Oct 11.

Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China.

Mimicking nature's ability to orchestrate molecular self-assembly in living cells is important yet challenging. Molecular self-assembly has found wide applications in cellular activity control, drug delivery, biomarker imaging, etc. Nonetheless, examples of suborganelle-confined supramolecular self-assembly are quite rare and research in this area remains challenging. Herein, we have presented a new strategy to program supramolecular self-assembly specifically in mitochondria by leveraging on a unique enzyme SIRT5. SIRT5 is a mitochondria-localized enzyme belonging to a family of NAD-dependent histone deacetylases. Accumulating studies suggest that SIRT5 is involved in regulating diverse biological processes, such as reactive oxygen defense, fatty acid metabolism, and apoptosis. In this study, we designed a novel class of succinylated peptide precursors that can be transformed into self-assembling building blocks through SIRT5 catalysis, leading to the formation of supramolecular nanofibers in vitro and in living cells. The increased hydrophobicity arising from self-assembly remarkably enhanced the fluorescence of nitrobenzoxadiazole (NBD) in the nanofibers. With this approach, we have enabled activity-based imaging of SIRT5 in living cells for the first time. Moreover, SIRT5-mediated peptide self-assembly was found to depolarize mitochondria membrane potential and promote ROS formation. Coincubation of the peptide with three different chemotherapeutic agents significantly boosted the anticancer activities of these drugs. Our work has thus illustrated a new way of mitochondria-confined peptide self-assembly for SIRT5 imaging and potential anticancer treatment.
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http://dx.doi.org/10.1021/jacs.0c08463DOI Listing
October 2020

Crystal Phase Control of Gold Nanomaterials by Wet-Chemical Synthesis.

Acc Chem Res 2020 10 24;53(10):2106-2118. Epub 2020 Sep 24.

Department of Chemistry, City University of Hong Kong, Hong Kong, China.

Gold (Au), a transition metal with an atomic number of 79 in the periodic table of elements, was discovered in approximately 3000 B.C. Due to the ultrahigh chemical stability and brilliant golden color, Au had long been thought to be a most inert material and was widely utilized in art, jewelry, and finance. However, it has been found that Au becomes exceptionally active as a catalyst when its size shrinks to the nanometer scale. With continuous efforts toward the exploration of catalytic applications over the past decades, Au nanomaterials show critical importance in many catalytic processes. Besides catalysis, Au nanomaterials also possess other promising applications in plasmonics, sensing, biology and medicine, due to their unique localized surface plasmon resonance, intriguing biocompatibility, and superior stability. Unfortunately, the practical applications of Au nanomaterials could be limited because of the scarce reserves and high price of Au. Therefore, it is quite essential to further explore novel physicochemical properties and functions of Au nanomaterials so as to enhance their performance in different types of applications.Recently, phase engineering of nanomaterials (PEN), which involves the rearrangement of atoms in the unit cell, has emerged as a fantastic and effective strategy to adjust the intrinsic physicochemical properties of nanomaterials. In this Account, we give an overview of the recent progress on crystal phase control of Au nanomaterials using wet-chemical synthesis. Starting from a brief introduction of the research background, we first describe the development history of wet-chemical synthesis of Au nanomaterials and especially emphasize the key research findings. Subsequently, we introduce the typical Au nanomaterials with untraditional crystal phases and heterophases that have been observed, such as 2H, 4H, body-centered phases, and crystal-phase heterostructures. Importantly, crystal phase control of Au nanomaterials by wet-chemical synthesis is systematically described. After that, we highlight the importance of crystal phase control in Au nanomaterials by demonstrating the remarkable effect of crystal phases on their physicochemical properties (e.g., electronic and optical properties) and potential applications (e.g., catalysis). Finally, after a concise summary of recent advances in this emerging research field, some personal perspectives are provided on the challenges, opportunities, and research directions in the future.
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http://dx.doi.org/10.1021/acs.accounts.0c00487DOI Listing
October 2020

For Wnt Signaling, Fucosylation of LRP6 Is a Bitter Pill.

Cell Chem Biol 2020 09;27(9):1114-1116

Department of Chemistry and Chemical Biology and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address:

In this issue of Cell Chemical Biology, Hong et al. (2020) use in situ chemoenzymatic labeling to discover that fucosylation of the Wnt co-receptor LRP6 induces its endocytosis and downregulates Wnt/β-catenin signaling. Their findings reveal a glycosylation-based mechanism for regulating Wnt signaling that could be targeted in cancer.
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http://dx.doi.org/10.1016/j.chembiol.2020.08.003DOI Listing
September 2020

A Peptide Stapling Strategy with Built-In Fluorescence by Direct Late-Stage C(sp )-H Olefination of Tryptophan.

Chemistry 2020 Dec 27;26(68):16122-16128. Epub 2020 Oct 27.

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, P.R. China.

Fluorescent stapled peptides are important chemical tools for detecting intracellular distribution, protein-protein interactions, and localization of target proteins. These peptides are usually labeled with bulky sized fluorophores through reactive functional groups, which may alter the physical properties and biological activities of peptides. Herein, a unique strategy is developed for synthesizing new stapled peptides with built-in fluorescence. The stapled peptides were prepared through Rh-catalyzed C(sp )-H olefination in tryptophan (Trp) residues by using pyridine/pyrimidine as the directing groups under mild conditions. This method displays good regioselectivity and high efficiency. Furthermore, as a proof of concept for its biological applications, stapled peptides without additional fluorophore 9 a and 9 b were constructed for a cell imaging study. These peptides displayed strong binding affinity toward integrin αvβ3 in A549 cells by cell imaging experiments. Notably they demonstrated even better anticancer activity than commercial antagonist cyclic (RGDfK). The method will provide robust tools for the peptide macrocyclization field.
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http://dx.doi.org/10.1002/chem.202003548DOI Listing
December 2020

Intracellular delivery of therapeutic proteins through N-terminal site-specific modification.

Chem Commun (Camb) 2020 Sep;56(77):11473-11476

Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore.

A versatile strategy for the intracellular delivery of functional proteins/antibodies was developed using N-terminal site-specific modification. Adopting orthogonal dual-labeling strategies, a cell-permeable RNase A prodrug was designed complementing N-terminal site-specific modification with lysine labeling. Upon successful cytosolic uptake, the prodrug showed reactive oxygen species (ROS)-dependent targeted cancer therapy.
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http://dx.doi.org/10.1039/d0cc04728gDOI Listing
September 2020

A meta-analysis of fractional CO laser combined with PRP in the treatment of acne scar.

Lasers Med Sci 2021 Feb 10;36(1):1-12. Epub 2020 Aug 10.

Department of Dermatology, China-Japan Union Hospital of Jilin University, Xiantai Road 126, Changchun, 130033, Jilin, People's Republic of China.

This study aimed to analyze the effectiveness and safety of ablative fractional carbon dioxide laser systems (CO AFL) combined with autologous platelet-rich plasma (PRP) in the treatment of acne scars through the retrieval and collection of related literature to further guide the treatment of acne scars. We searched Web of Science, PubMed, Embase, Wanfang Data, Chinese National Knowledge Infrastructure, and VIP Database. All randomized and nonrandomized controlled trials on CO AFL combined with PRP in the treatment of acne scars were included, and Revman5.3 systematic review software was used in the meta-analysis. Nine studies were included in this meta-analysis. The data analysis results showed that the CO AFL combined with PRP treatment group showed significantly better results than the pure CO AFL control group in terms of clinical improvement score, clinical improvement rate, patient satisfaction, and crusting period. The results of this meta-analysis showed that CO AFL combined with PRP in the treatment of acne scars is more effective and safer than CO AFL alone.
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http://dx.doi.org/10.1007/s10103-020-03105-zDOI Listing
February 2021

Narrow H3K4me2 is required for chicken PGC formation.

J Cell Physiol 2021 Feb 4;236(2):1391-1400. Epub 2020 Aug 4.

Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

The development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC-related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor-β). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds.
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http://dx.doi.org/10.1002/jcp.29945DOI Listing
February 2021
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