Publications by authors named "Hui Sun"

1,559 Publications

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Nutrients recovery from fresh liquid manure through an airlift reactor to mitigate the greenhouse gas emissions of open anaerobic lagoons.

J Environ Manage 2021 Jun 12;294:112956. Epub 2021 Jun 12.

College of Engineering (Key Laboratory for Clean Renewable Energy Utilization Technology, Ministry of Agriculture), China Agricultural University, Beijing, 100083, PR China; Yantai Institute, China Agricultural University, Yantai, 264032, Shandong, PR China.

Open anaerobic lagoons are widely used for liquid manure storage and treatment, with excess greenhouse gas (GHG) and odor emissions. In this study, liquid manure was valorized through hybrid nitrogen and phosphorous recovery as value-added products using an airlift reactor. Also, the organic load of liquid manure was reduced before discharging into anaerobic lagoons, which simultaneously mitigated GHG emissions. The results showed that 14.5% of total nitrogen (TN) was recovered as ammonium sulfate, while 38.8% of TN and 79.3% of total phosphorus (TP) were recovered as phosphorus-rich sludge. After the pre-treatment in the reactor, the odor could be controlled effectively due to a 94.2% decrease in total VFAs. In addition, 59.0% of COD was removed, which decreased the theoretical modeled GHG emissions by 51.7% compared to the traditional direct discharging. The application is promising for upgrading anaerobic lagoons of liquid manure.
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http://dx.doi.org/10.1016/j.jenvman.2021.112956DOI Listing
June 2021

Soil Fungal Community Structure in Boreal Pine Forests: From Southern to Subarctic Areas of Finland.

Front Microbiol 2021 26;12:653896. Epub 2021 May 26.

Collaborative Innovation Center of Sustainable Forestry in Southern China, College of Forestry, Nanjing Forestry University, Nanjing, China.

The boreal forest environment plays an important role in the global C cycle due to its high carbon storage capacity. However, relatively little is known about the forest fungal community at a regional scale in boreal forests. In the present study, we have re-analyzed the data from our previous studies and highlighted the core fungal community composition and potential functional groups in three forests dominated by Scots pine ( L.) in Finland, and identified the fungal generalists that appear across geographic locations despite differences in local conditions. The three forests represent subarctic, northern and southern boreal forest, and are all in an un-managed state without human interference or management. The subarctic and northern areas are subject to reindeer grazing. The results showed that the three locations formed distinct fungal community structures ( < 0.05). Compared to the two northern locations, the southern boreal forest harbored a greater abundance of Zygomycota, , , and , in which aspect there were no differences between the two northern forests. , , and were the core fungal genera in the boreal Scots pine forest. Functionally, the southern boreal forest harbored a greater abundance of saprotroph, endophytes and fungal parasite-lichen, whereas a greater abundance of ectomycorrhizal fungi was observed in the northern boreal forests. Moreover, the pathotroph and wood saprotrophs were commonly present in these three regions. The three locations formed two distinct fungal community functional structures, by which the southern forest was clearly separated from the two northern forests, suggesting a distance-decay relationship via geographic location. This study provides useful information for better understanding the common fungal communities and functions in boreal forests in different geographical locations.
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http://dx.doi.org/10.3389/fmicb.2021.653896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188478PMC
May 2021

Hyperthyroidism Prevalence in China After Universal Salt Iodization.

Front Endocrinol (Lausanne) 2021 28;12:651534. Epub 2021 May 28.

Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China.

Background: Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination.

Methods: Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015-2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured.

Results: After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves' disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% . 0.64%, P<0.001; GD: 0.65% . 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30-39 years-of-age (OH:0.61% . 0.81%, P<0.001; GD: 0.38% . 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68-2.59; OR1.35, 95%CI 1.07-1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30-2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels.

Conclusion: OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.
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http://dx.doi.org/10.3389/fendo.2021.651534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194401PMC
May 2021

Upward Ingratiation Outside the Workplace and Supervisor's Human Resource Decisions: Moderating Effect of Zhongyong Thinking.

Front Psychol 2021 26;12:636756. Epub 2021 May 26.

School of Business, Jiangsu Ocean University, Lianyungang, China.

Ingratiation is a common strategy for subordinates to deal with their supervisors in eastern and western societies. Based on the theory of impression management, this study focuses on the impact of upward ingratiation outside the workplace on supervisor's human resource (HR) decisions in the Chinese context and the mechanism behind this impact. The data were collected from 252 supervisor-subordinate dyads in four manufacturing firms. The results demonstrate the following: first, supervisors hold a more favorable view of upward ingratiation outside the workplace; second, upward ingratiation outside the workplace has a positive effect on the supervisor's chance of promotion and bonus allocation decisions, and leader-member exchange (LMX) plays a mediation role in this influence; third, Zhongyong thinking (ZYT) moderates the relationship between LMX and supervisor's chance of promotion and bonus allocation decisions; and finally, ZYT moderates the indirect effect of ingratiation behavior outside the workplace on supervisor's chance of promotion and bonus allocation decisions through LMX, and the mediated relationship is weakened when a supervisor has a higher level of ZYT. This is one of the first empirical studies, which examines the validity of subordinate's upward ingratiation outside the workplace from the perspective of supervisor's ZYT. This study plays an important role in highlighting the effect of ZYT on the ingratiation behavior.
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http://dx.doi.org/10.3389/fpsyg.2021.636756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187586PMC
May 2021

Function and distribution of the conjugative plasmid pLM1686 in foodborne Listeria monocytogenes in China.

Int J Food Microbiol 2021 Aug 30;352:109261. Epub 2021 May 30.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China. Electronic address:

Listeria monocytogenes, a fatal foodborne pathogen has the extraordinary capacity to survive in harsh conditions and is a potential threat to public health. A novel 91 kb plasmid pLM1686 was found in the prevalent L. monocytogenes sequence type (ST) 87 strain in China. In this study, the function and distribution of pLM1686 were firstly investigated in L. monocytogenes. The results showed plasmid pLM1686 had self-transmissible ability and existed in various types of L. monocytogenes isolates belonging to two lineages (lineage I and II), four serotypes (1/2b, 3b, 1/2c and 1/2a) and four STs (ST87, ST59, ST9 and ST120). The wild strain LM1686 and transconjugant strain 10403S exhibited significantly higher growth rate and biofilm formation in Modification of Welshimer's medium (MWB), greater salinity tolerance, stronger cell invasion and higher cytotoxicity than plasmid-cured strain and reference strain 10403S. Moreover, plasmid curing caused the loss of cadmium resistance of strain, and the recipient strain acquired cadmium resistance after conjugation. Thus, pLM1686 would provide L. monocytogenes advantages of surviving in adverse environments.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109261DOI Listing
August 2021

Hyaluronan-mediated motility receptor expression functions as a prognostic biomarker in uterine carcinosarcoma based on bioinformatics analysis.

J Int Med Res 2021 Jun;49(6):3000605211021043

Department of Gynaecologic Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.

Objective: Uterine carcinosarcoma (UCS) is a rare, aggressive tumour with a high metastasis rate and poor prognosis. This study aimed to explore potential key genes associated with the prognosis of UCS.

Methods: Transcriptional expression data were downloaded from the Gene Expression Profiling Interactive Analysis database and differentially expressed genes (DEGs) were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses using Metascape. A protein-protein interaction network was constructed using the STRING website and Cytoscape software, and the top 30 genes obtained through the Maximal Clique Centrality algorithm were selected as hub genes. These hub genes were validated by clinicopathological and sequencing data for 56 patients with UCS from The Cancer Genome Atlas database.

Results: A total of 1894 DEGs were identified, and the top 30 genes were considered as hub genes. Hyaluronan-mediated motility receptor (HMMR) expression was significantly higher in UCS tissues compared with normal tissues, and elevated expression of HMMR was identified as an independent prognostic factor for shorter survival in patients with UCS.

Conclusions: These results suggest that HMMR may be a potential biomarker for predicting the prognosis of patients with UCS.
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http://dx.doi.org/10.1177/03000605211021043DOI Listing
June 2021

A novel multiplex of 12 multicopy Y-STRs for forensic application.

J Forensic Sci 2021 Jun 10. Epub 2021 Jun 10.

National Engineering Laboratory for Forensic Science, Beijing Engineering Research Center of Crime Scene Evidence Examination, Key Laboratory of Forensic Genetics, Institute of Forensic Science, Ministry of Public Security, Beijing, China.

Y chromosomal short tandem repeats (Y-STRs) have been applied overwhelmingly in forensic areas for solving paternity identification and sexual assault cases. Yet the widely used Y-STR kits contain mostly single-copy markers, which may restrict the discrimination power. Here, a novel Y-STR multiplex was developed and validated in order to complement the currently available Y-STR kits, especially on differentiating male relatives. The assay includes twelve multicopy Y-STR loci (DYF371, DYF383S1, DYS385, DYF387S1, DYS389I/II, DYF399S1, DYF404S1, DYF409S1, DYF411S1, DYS464, DYS526, DYS527; four of them are rapidly mutating ones), 1 single-copy Y-STR (DYS391), and Amelogenin, and was optimized to amplify at annealing temperature of 59°C and 28 cycles. Validation studies show that full profiles are obtained with 0.125 ng of male DNA. The system is capable of overcoming high concentrations of inhibitors such as hematin, EDTA, and humic acid. Besides, the results demonstrate good sizing precision and the ability to detect male-specific profiles in male/female DNA mixtures at a ratio of 1:800. Excellent species specificity was also observed in microorganisms and non-primates, while detectable peaks were found in some primates. Based on published genetic data, gene diversity values were above 0.7 for most of the loci in our multiplex, inferring a high capacity in discriminating unrelated and related male individuals. The kit is of great potential for forensic application.
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http://dx.doi.org/10.1111/1556-4029.14774DOI Listing
June 2021

O-GlcNAcylation Quantification of Certain Protein by the Proximity Ligation Assay and OGA(CpOGA).

ACS Chem Biol 2021 06 9;16(6):1040-1049. Epub 2021 Jun 9.

College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei Province, People's Republic of China.

O-GlcNAcylation is an O-linked β-N-acetyl-glucosamine (O-GlcNAc)-monosaccharide modification of serine or threonine in proteins that plays a vital role in many critical cellular processes. Owing to its low molecular weight, uncharged property, and difficulty in distinguishing from β-N-acetyl-galactosamine (GalNAc), the lack of high specificity and avidity tools and sophisticated quantification methods have always been the bottleneck in analyzing O-GlcNAc functions. Here, we compared glycan array data of the mutant of OGA (CpOGA), O-GlcNAc antibody CTD110.6, and several lectins. We found that CpOGA can effectively distinguish GlcNAc from GalNAc. Glycan array analysis and isothermal titration calorimetry (ITC) show that CpOGA has a GlcNAc specific binding characteristic. CpOGA could be used in far-western, flow cytometry analysis, and confocal imaging to demonstrate the existence of O-GlcNAc proteins. Using the CpOGA affinity column, we identified 84 highly confident O-GlcNAc modified peptides from 82 proteins in the MCF-7 cell line and 33 highly confident peptides in 33 proteins from mouse liver tissue; most of them are novel O-GlcNAc proteins and could not bind with wheat germ agglutinin (WGA). Besides being used as a facile enrichment tool, a combination of CpOGA with the proximity ligation assay (PLA) is successfully used to quantify O-GlcNAc modified histone H2B, which is as low as femtomoles in MCF-7 cell lysate. These results suggest that CpOGA is a specific tool for detection (far-western, flow cytometry analysis, and confocal imaging) and enrichment of O-GlcNAcylated proteins and peptides, and the CpOGA-PLA method is useful for quantifying certain O-GlcNAc protein.
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http://dx.doi.org/10.1021/acschembio.1c00185DOI Listing
June 2021

Single-parameter-tuned synthesis for shape-controlled gold nanocrystals stimulated by iron carbonyl.

J Colloid Interface Sci 2021 May 29;601:773-781. Epub 2021 May 29.

Department of Chemistry, Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433, PR China. Electronic address:

Shape-controlled synthesis is essential for functional nanomaterials, allowing deeper insights intothe relationship between the structures and the catalytic properties. Synthesis of nanocrystals with particular morphologies are usually studied independently among various synthetic methods, those underline that different surface capping ligands or shape-directing agents bring about disparate shapes. However, a single quantitative parameter method is still lacking to realize precise control of well-defined morphology nanocrystals, especially anisotropic structures, which is essential to understanding the growth process of nanocrystals. Herein, we proposed a single-parameter-tuned synthesis strategy for preparation of shape-controlled gold nanocrystals by regulating the amount of iron carbonyl, by which we produced highly monodisperse Au nanocrystals with various shapes in organic phase including nanoplates (diameter of 16.02 ± 1.13 nm and thickness of 5.35 ± 0.58 nm), nanorods (length of 37.53 ± 3.73 nm and width of 5.26 ± 0.37 nm) and nanospheres (diameter of 8.26 ± 0.38 nm). The single-parameter-tuned method reveals the dual roles of iron carbonyl for controlling the shapes of gold nanocrystals including reductant and oxidative etchant and empowers versatility in synthetic methodology for other noble metals. Moreover, catalytic activity shifting in shapes of nanocrystals was revealed based on the reduction of 4-nitrophenol, showing that the as-synthesized Au nanoplates displayed the enhanced catalytic performance with the lowest activation energy. Our work provides a brand-new pathway for shape-controlled synthesis of noble-metal nanocrystals and has a strong practical value in application fields.
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http://dx.doi.org/10.1016/j.jcis.2021.05.114DOI Listing
May 2021

Dietary Inflammatory Index and Health Outcomes: An Umbrella Review of Systematic Review and Meta-Analyses of Observational Studies.

Front Nutr 2021 19;8:647122. Epub 2021 May 19.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

The dietary inflammatory index (DII) is associated with non-communicable disease. We conducted an umbrella review to systematically evaluate meta-analyses of observational studies on DII and diverse health outcomes. We comprehensively searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses of observational studies. Those investigating the association between DII and a wide range of health outcomes in humans were eligible for inclusion. For each meta-analysis, we estimated the summary effect size by using fixed and random effects models, the 95% confidence interval, and the 95% prediction interval. We assessed heterogeneity, evidence of small-study effects, and excess significance bias. The umbrella review identified 35 meta-analyses assessing associations between DII and various health outcomes: cancer ( = 24), mortality ( = 4), metabolic ( = 4), and other ( = 3). The methodological quality was high or moderate. Of the 35 meta-analyses, we observed highly suggestive evidence for harmful associations between digestive tract cancer, colorectal cancer, overall cancer, pharyngeal cancer, UADT cancer, and CVD mortality. Moreover, 11 harmful associations showed suggestive evidence: hormone-dependent cancer, rectal cancer, colon cancer, breast and prostate cancer, gynecological cancer, breast cancer, ovarian cancer, colorectal cancer, prostate cancer, all-cause mortality, and depression. DII is likely to be associated with harmful effects in multiple health outcomes. Robust randomized controlled trials are warranted to understand whether the observed results are causal. CRD42021218361.
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http://dx.doi.org/10.3389/fnut.2021.647122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169973PMC
May 2021

Adolescents experienced more treatment failure than children with chronic myeloid leukemia receiving imatinib as frontline therapy: a retrospective multicenter study.

Ann Hematol 2021 Jun 5. Epub 2021 Jun 5.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

To explore the differences in the clinical features, treatment responses, and outcomes among children, adolescents, and adults with chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib as first-line therapy. Data from children (0-8 years for girls and 0-10 years for boys), adolescents (9-19 years for girls and 11-19 years for boys), and adults (age ≥ 20 years) with newly diagnosed CML-CP receiving imatinib as first-line therapy between 2006 and 2019 were retrospectively reviewed. In total, 135 children (cohort 1), 189 adolescents (cohort 2), and 658 adults (cohort 3: age 20-39 years, n = 305; cohort 4: age 40-59 years, n = 270; and cohort 5: age 60-83 years, n = 83) were included in this study. When compared with children, adolescents showed a significantly higher white blood cell count (P = 0.033) and basophil percentage in peripheral blood (P = 0.002) and a significantly higher prevalence of splenomegaly (P = 0.004). Both children and adolescents presented with more aggressive clinical features than adults. During median follow-ups of 28 months (range, 3-161 months) in children, 33 months (range, 3-152 months) in adolescents, and 48 months (range, 3-157 months) in adults, multivariate analysis showed that children and adolescents had higher probabilities of achieving complete cytogenetic response, major molecular response, and molecular response. Notably, compared with not only adults (cohort 3 vs. cohort 1: HR = 2.03 [1.03, 3.98], P = 0.040; cohort 4 vs. cohort 1: HR = 2.15 [1.07, 4.33], P = 0.033; cohort 5 vs. cohort 1: HR = 4.22 [1.94, 9.15], P < 0.001) but also adolescents (cohort 2 vs. cohort 1: HR = 2.36 [1.18, 4.72], P = 0.015), children had significantly longer failure-free survival. Age was not associated with progression-free survival or overall survival. Although they exhibited more aggressive clinical features at diagnosis, both children and adolescents achieved superior treatment responses than adults. Adolescents showed even more adverse features and a poor FFS than children.
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http://dx.doi.org/10.1007/s00277-021-04544-6DOI Listing
June 2021

An Improved Recurrent Laryngeal Nerve-Monitoring Device: Technical Note for NIM Vital™.

Surg Technol Int 2021 Jun 3;38. Epub 2021 Jun 3.

Division for Endocrine and Minimally Invasive Surgery, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University Hospital G. Martino, University of Messina, Messina, Italy.

A new device for monitoring the laryngeal nerves during thyroid surgery has been developed. NIM Vital™ (Medtronic Xomed, Inc., Jacksonville, FL, USA) incorporates (a) a new wireless design, (b) NIM NerveTrendTM (Medtronic Xomed) EMG reporting, (c) intelligent noise-reduction technology that suppresses artifacts, (d) smart troubleshooting pop-up alerts, and (e) NIM Nervassure ™ (Medtronic Xomed) for continuous monitoring. This device offers enhanced stability and flexibility for both intermittent and continuous laryngeal nerve monitoring. The new NIM NerveTrend ™ EMG reporting makes it possible to track the recurrent laryngeal nerve condition throughout a procedure, even when using intermittent nerve monitoring. During both continuous and intermittent monitoring, green, yellow and red status bars provide visual information and associated tones provide audible cues, making it easy to monitor nerve function and interpret EMG trends. This new tool for laryngeal nerve monitoring has the potential to augment nerve dissection during surgery. Measurements of long-term outcome are needed to establish their efficacy.
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June 2021

Comparative Proteomics Analysis for Elucidating the Interaction Between Host Cells and .

Front Cell Infect Microbiol 2021 13;11:643001. Epub 2021 May 13.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), National Health Commission of People's Republic of China Key Laboratory of Parasite and Vector Biology, World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China.

, a representative model organism belonging to the phylum Apicomplexa, can infect almost all warm-blooded organisms, including humans. The invasion of host cells host-parasite interaction is the key step for to complete its life cycle. Herein we performed tandem mass tag analysis to investigate global proteomic changes in host cells (human foreskin fibroblasts, HFFs) [HFFs infected with (HT) . HFFs (H)] and [HT . (T)] during intracellular infection. Overall, 3477 and 1434 proteins were quantified, of which 375 and 1099 proteins were differentially expressed (adjusted p-value < 0.05 and >1.5 or <0.67-fold change) in host cells and , respectively. invasion relies on the secretion of numerous secretory proteins, which originate from three secretory organelles: micronemes, rhoptries, and dense granules. In the HT . T group, few secretory proteins were upregulated, such as microneme proteins (MICs: MIC6, MIC10), rhoptry bulb proteins (ROPs: ROP5, ROP17), and dense granule proteins (GRAs: GRA4, GRA5, GRA12). In contrast, dozens of known secretory proteins were significantly downregulated in -infected HFFs. In HFFs, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed a large number of differentially expressed proteins (DEPs) enriched in metabolic processes and immune-associated signaling pathways, such as NF-κB, cAMP, and Rap1 signaling pathways. Further, in case of , DEPs were involved in ribosome biogenesis, citrate cycle, and galactose metabolism, indicating that cell biosynthesis and metabolism of were altered after host cell invasion. These findings reveal novel modifications in the proteome of host cells as well as , helping us better understand the mechanisms underlying host-parasite interaction.
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http://dx.doi.org/10.3389/fcimb.2021.643001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158437PMC
May 2021

[Design and application of a new type of oral humidifier].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Apr;33(4):494-496

Department of Emergency, the First Hospital of Jiaxing, Jiaxing 314001, Zhejiang, China. Corresponding author: Yang Dongmei, Email:

Oral feeding of water cannot be accomplished in some critical patients due to coma, mouth-breathing or long-term indwelling of gastric tube, causing dry mouth which results in oral pain, ulcer, or infection, aggravating patients' discomfort and even affecting the prognosis. To solve this problem, the medical staff of the First Hospital of Jiaxing developed a novel oral humidifier and obtained the National Utility Model Patent of China (ZL 2019 2 0066979.0). The oral humidifier consists of a spraying device and a fixation device. The spraying device is a spraying housing with a water tank, and a spraying port where nanometer water mist can be emitted. The spraying housing is also equipped with a flashlight with a switch, and a schematic diagram of pupil size, which can be used to assess the pupil size conveniently. The fixing device is composed of a fixing frame, an adjustable rod and a clamp. The two ends of the adjustable rod are connected to the fixing frame and the clamp respectively, and can be adjusted to proper shape. The spraying housing can be placed on the fixing frame and installed on the bed and adjusted to the proper position quickly. This novel oral humidifier is a simple device which combines a spraying system with a pupil evaluation tool, implying significant clinical application in improving the convenience of nursing and alleviating dry mouth of critical patients.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201231-00785DOI Listing
April 2021

C2 Xplore® for Intermittent and Continuous Laryngeal Nerve Monitoring: Technical Note.

Surg Technol Int 2021 05 27;38. Epub 2021 May 27.

Division for Endocrine and Minimally Invasive Surgery, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University Hospital G. Martino, University of Messina, Messina, Italy.

Due to the direct anatomical relationship between the recurrent laryngeal nerve (RLN) and the thyroid gland, the function and anatomical integrity of the RLN is fundamentally at risk in every thyroid operation. While a RLN morbidity rate of less than 5% is achieved in specialized clinics, the morbidity rates are significantly higher in non-specialized centers. Thus, the aim is to reduce the complication rate by establishing standardized interventions. Exact knowledge of the anatomical course of the RLN, the nerve-sparing dissection technique and the supportive use of intraoperative neuro-monitoring (IONM) to identify anatomical variations are the basis for nerve-sparing surgery. We tested the new C2 Xplore® system (inomed Medizintechnik GmbH, Emmendingen, Germany) as a tool for performing intermittent and continuous laryngeal nerve monitoring during thyroid surgery. The C2 Xplore® helps to enhance surgeon-IONM interaction, and provides comprehensive digital EMG documentation with EMG quantification. EMG artifacts are removed. Image quality and EMG feedback are highly acceptable for intraoperative monitoring. The C2 Xplore® system does not have a deleterious impact on the proper function of other surgical instruments. C2 Xplore® is effective for intraoperative monitoring, optimizing RLN dissection, and supporting surgical deliberations, and for forensic use and research. A step-by-step C2 Xplore® procedure is described.
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May 2021

Use of Vivostat® Autologous Fibrin Sealant in Thyroid Surgery.

Surg Technol Int 2021 05 27;38. Epub 2021 May 27.

Division for Endocrine and Minimally Invasive Surgery, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University Hospital G. Martino, University of Messina, Messina, Italy.

Introduction: Post-thyroidectomy hemorrhage is a rare but potentially life-threatening and unpredictable complication of thyroid surgery. Therefore, intraoperative bleeding control and hemostasis are crucial. However, the most efficient, cost-effective, and standardized way to achieve this is not clear. This study aimed to evaluate the outcome of total thyroidectomy (TT) and partial thyroidectomy (PT) performed using the Vivostat® hemostatic system (Vivostat A/S, Lillerød, Denmark).

Methods: Patients underwent TT and PT for benign and malignant diseases (multinodular goiter, Graves' disease, differentiated thyroid carcinoma). The primary endpoint was 1st-day postoperative drain output and bleeding that required reintervention. Secondary endpoints included surgery duration and postsurgical complications (vocal fold palsy, hypocalcemia, seroma, wound infection).

Results: Between October 2020 and December 2020, 56 patients were enrolled; 69.6% female; mean age 49.5 years. The mean 24-h drain output was 40 ml. No redo surgery was needed. Seroma was present in 5.3% of cases; no permanent vocal palsy or hypocalcemia was observed.

Conclusion: This study shows that the Vivostat® system is both safe and effective for hemostasis during thyroid surgery.
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May 2021

Microbes in lung cancer initiation, treatment, and outcome: Boon or bane?

Semin Cancer Biol 2021 May 21. Epub 2021 May 21.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; School of Materials Science and Engineering, Tongji University, Shanghai, 201804, People's Republic of China. Electronic address:

Lung cancer is the top reason for cancer-related deaths worldwide. The 5-year overall survival rate of lung cancer is approximately 20 % due to the delayed diagnosis and low response rate to regular treatments. Microbiota, both host-microbiota and alien pathogenic microbiota, have been investigated to be involved in a complicated and contradictory relationship with lung cancer initiation, treatments, and prognosis. Disorders of certain host-microbiota and pathogen infection are associated with the risk of lung cancers based on epidemiological evidence, and antibiotics (ATBs) could dramatically impair anti-cancer treatment efficacy, including chemotherapy and immunotherapy. Moreover, probiotics and microbe-mediated drugs are potential approaches to enhance regular anti-tumor treatments. Therefore, the knowledge of the complex dual effect of microbes on lung cancer is beneficial to take their essence and remove their dross. This review offers insight into the current trends and advancements in microbiota or microbial components related to lung cancer.
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http://dx.doi.org/10.1016/j.semcancer.2021.05.025DOI Listing
May 2021

Chaperonin-Containing TCP1 Subunit 6A Is a Prognostic Potential Biomarker That Correlates With the Presence of Immune Infiltrates in Colorectal Cancer.

Front Genet 2021 4;12:629856. Epub 2021 May 4.

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Aims: Chaperonin-containing TCP1 subunit (CCT) 6A is an oncogenic 6th subunit of the CCT family. Nevertheless, not much is documented regarding its function in colorectal cancer (COAD). This investigation seeks to explore the role of in the prognosis of COAD.

Main Methods: Sequencing data from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas database (TCGA) were employed to analyze the expression of and its involvement in various regulatory networks behind COAD. Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) analyzed Levels of expression and survival rates, while GEPIA was used to uncover further the functional networks that involved . Database for Annotation, Visualization, and Integrated Discovery (DAVID) tools were used to interpret Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Evaluation of the expression levels of in COAD samples was also verified via immunohistochemistry.

Key Findings: We found that the expression of is up-regulated in COAD. correlated with poor prognosis and decreased immune infiltrates such as CD4 T cells, B cells, and dendritic cells. is increased in COAD patients. is associated with several gene networks related to the DDX family and mismatch repair pathways.

Significance: Our data showed that data mining was able to uncover data regarding levels of and its involvement in genetic regulating pathways in COAD.
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http://dx.doi.org/10.3389/fgene.2021.629856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129517PMC
May 2021

FOXP3-based immune risk model for recurrence prediction in small-cell lung cancer at stages I-III.

J Immunother Cancer 2021 May;9(5)

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No 507 Zhengmin Road, Shanghai 200433, China

Background: Immunotherapies may prolong the survival of patients with small-cell lung cancer (SCLC) to some extent. The role of forkhead box protein P3 (FOXP3) in tumor microenvironment (TME) remains controversial. We aimed to examine FOXP3-related expression characteristics and prognostic values and to develop a clinically relevant predictive system for SCLC.

Methods: We enrolled 102 patients with histologically confirmed SCLC at stages I-III. Through immunohistochemistry, we determined the expression pattern of FOXP3 and its association with other immune biomarkers. By machine learning and statistical analysis, we constructed effective immune risk score models. Furthermore, we examined FOXP3-related enrichment pathways and TME traits in distinct cohorts.

Results: In SCLC, FOXP3 level was significantly associated with status of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), CD4, CD8, and CD3 (p=0.002, p=0.001, p=0.002, p=0.030, and p<0.001). High FOXP3 expression showed longer relapse-free survival (RFS) than the low-level group (41.200 months, 95% CI 26.937 to 55.463, vs 14.000 months, 95% CI 8.133 to 19.867; p=0.008). For tumor-infiltrating lymphocytes (TILs), subgroup analysis demonstrated FOXP3 and PD-1, PD-L1, lymphocyte activation gene-3, CD3, CD4, or CD8 double positive were significantly correlated with longer RFS. We further performed importance evaluation for immune biomarkers, constructed an immune risk score incorporating the top three important biomarkers, FOXP3, TIL PD-L1, and CD8, and found their independently prognostic role to predict SCLC relapse. Better predictive performance was achieved in this immune risk model compared with single-indicator-based or two-indicator-based prediction systems (area under the curve 0.715 vs 0.312-0.711). Then, relapse prediction system integrating clinical staging and immune risk score was established, which performed well in different cohorts. High FOXP3-related genes were enriched in several immune-related pathways, and the close relationships of interleukin-2, , basic excision repair genes , , , and oxidative phosphorylation related gene cytochrome c oxidase subunit 8A with FOXP3 expression were revealed. Moreover, we found low-immune risk score group had statistically higher activated CD4 memory T cells (p=0.014) and plasma cells (p=0.049) than the high-risk group. The heterogeneity of tumor-infiltrating immune cells might represent a promising feature for risk prediction in SCLC.

Conclusion: FOXP3 interacts closely with immune biomarkers on tumor-infiltrating cells in TME. This study highlighted the crucial prognostic value and promising clinical applications of FOXP3 in SCLC.
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http://dx.doi.org/10.1136/jitc-2021-002339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137193PMC
May 2021

Dietary Carbohydrate and Diverse Health Outcomes: Umbrella Review of 30 Systematic Reviews and Meta-Analyses of 281 Observational Studies.

Front Nutr 2021 29;8:670411. Epub 2021 Apr 29.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

The associations between dietary carbohydrate and diverse health outcomes remain controversial and confusing. To summarize the existing evidence of the association between dietary carbohydrate intake and diverse health outcomes and to evaluate the credibility of these sources of evidence. We performed this umbrella review of evidence from meta-analyses of observational studies. PubMed, Embase, Web of Science databases, and manual screening of references up to July 2020 were searched. Systematic reviews with meta-analyses of observational studies in humans investigating the association between dietary carbohydrate intake and multiple health outcomes were identified. We assessed the evidence levels by using summary effect sizes, 95% prediction intervals, between-study heterogeneity, evidence of small-study effects, and evidence of excess significance bias for each meta-analysis. We included 43 meta-analyses of observational research studies with 23 health outcomes, including cancer ( = 26), mortality ( = 4), metabolic diseases ( = 4), digestive system outcomes ( = 3), and other outcomes [coronary heart disease ( = 2), stroke ( = 1), Parkinson's disease ( = 1), and bone fracture ( = 2)]. This umbrella review summarized 281 individual studies with 13,164,365 participants. Highly suggestive evidence of an association between dietary carbohydrate intake and metabolic syndrome was observed with adjusted summary odds ratio of 1.25 [95% confidence interval (CI) 1.15-1.37]. The suggestive evidences were observed in associations of carbohydrate consumption with esophageal adenocarcinoma (0.57, 95% CI = 0.42-0.78) and all-cause mortality (adjusted summary hazard ratio 1.19, 95% CI = 1.09-1.30). Despite the fact that numerous systematic reviews and meta-analyses have explored the relationship between carbohydrate intake and diverse health outcomes, there is no convincing evidence of a clear role of carbohydrate intake. However, there is highly suggestive evidence suggested carbohydrate intake is associated with high risk of metabolic syndrome, suggestive evidence found its association with increased risk of all-cause mortality and decreased risk of esophageal adenocarcinoma. CRD42020197424.
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http://dx.doi.org/10.3389/fnut.2021.670411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116488PMC
April 2021

The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)--poly(d,l-lactic acid) in rat.

Acta Pharm Sin B 2021 Apr 4;11(4):1003-1009. Epub 2021 Mar 4.

Research Center for Drug Metabolism, School of Life Sciences, Jilin University, Changchun 130012, China.

Monomethoxy poly(ethylene glycol)--poly(d,l-lactic acid) (PEG-PLA) is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier (nanocarrier) in drug delivery. Understanding the fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems. However, acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA. In this study, the pharmacokinetics, biodistribution, metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration. The results show that unchanged PEG-PLA is mainly distributed to spleen, liver, and kidney before being eliminated in urine over 48 h mainly (>80%) in the form of its PEG metabolite. Our study provides a clear and comprehensive picture of the fate of PEG-PLA which we anticipate will facilitate the scientific design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development.
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http://dx.doi.org/10.1016/j.apsb.2021.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105770PMC
April 2021

Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer.

Nat Commun 2021 05 14;12(1):2812. Epub 2021 May 14.

Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.

Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Released SHCBP1 responds to HER2 cascade by translocating into the nucleus following Ser273 phosphorylation, and then contributing to cell mitosis regulation through binding with PLK1 to promote the phosphorylation of the mitotic interactor MISP. Meanwhile, Shc1 is recruited to HER2 for MAPK or PI3K pathways activation. Also, clinical evidence shows that increased SHCBP1 prognosticates a poor response of patients to trastuzumab therapy. Theaflavine-3, 3'-digallate (TFBG) is identified as an inhibitor of the SHCBP1-PLK1 interaction, which is a potential trastuzumab sensitizing agent and, in combination with trastuzumab, is highly efficacious in suppressing HER2-positive gastric cancer growth. These findings suggest an aberrant mitotic HER2-SHCBP1-PLK1 axis underlies trastuzumab sensitivity and offer a new strategy to combat gastric cancer.
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http://dx.doi.org/10.1038/s41467-021-23053-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121856PMC
May 2021

Efficacy of berberine in treatment of rheumatoid arthritis: From multiple targets to therapeutic potential.

Pharmacol Res 2021 Jul 11;169:105667. Epub 2021 May 11.

National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, China; National Engineering Laboratory for the Development of Southwestern Endangered Medicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, Guangxi, China. Electronic address:

Rheumatoid arthritis is a systemic autoimmune disorder involved in persistent synovial inflammation. Berberine is a nature-derived alkaloid compound with multiple pharmacological activities in different pathologies, including RA. Recent experimental studies have clarified several determinant cellular and molecular targets of BBR in RA, and provided novel evidence supporting the promising therapeutic potential of BBR to combat RA. In this review, we recapitulate the therapeutic potential of BBR and its mechanism of action in ameliorating RA, and discuss the modulation of gut microbiota by BBR during RA. Collectively, BBR might be a promising lead drug with multi-functional activities for the therapeutic strategy of RA.
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http://dx.doi.org/10.1016/j.phrs.2021.105667DOI Listing
July 2021

Proprieties of adhesive surface arrays to thyroid cartilage for recurrent laryngeal nerve monitoring.

Ann Transl Med 2021 Apr;9(8):690

Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China.

Background: To investigate the optimal placement and size of adhesive thyroid cartilage electrodes (ATCEs) placed on the thyroid cartilage in porcine models for evaluating recurrent laryngeal nerve function compared with the other 3 recording electrode types.

Methods: Four Meishan piglets were used for this study. The electromyogram (EMG) signal stability was detected by intraoperative nerve monitoring (IONM). Best location and size of ATCEs were detected, and the EMG signals from each were compared. Latency data were tested by stimulating the different nerve points, and 6 manipulations of the trachea and endotracheal tube (ET) were applied to test the stability of EMG signals. ET electrodes, needle electrodes, and transcutaneous recording electrodes were simultaneously tested with comparison to ATCEs.

Results: The optimal placement locations and sizes of ATCEs were determined. The amplitudes and latencies recorded from the ATCEs were consistent with those of the ET electrodes. More anti-interference was observed with the ATCEs than with the ET electrodes in surgical manipulations. ATCEs could be used during intermittent and continuous monitoring in similar fashion to ET electrodes and needle electrodes.

Conclusions: ATCEs had consistent monitoring function with ET electrodes and needle electrodes. Feasibility, EMG stability, and optimal location and size of ATCEs for IONM were resolved. The EMG profiles from the ATCEs were more stable during surgical manipulations.
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http://dx.doi.org/10.21037/atm-21-1229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106000PMC
April 2021

High-powered optical superlattice with robust phase stability for quantum gas microscopy.

Opt Express 2021 Apr;29(9):13876-13886

Optical superlattice has a wide range of applications in the study of ultracold atom physics. Especially, it can be used to trap and manipulate thousands of atom pairs in parallel which constitutes a promising system for quantum simulation and quantum computation. In the present work, we report on a high-power optical superlattice formed by a 532-nm and 1064-nm dual-wavelength interferometer with a short lattice spacing of 630 nm. The short-term fluctuation (in 10 seconds) of the relative phase between the short lattice and the long lattice is measured to be 0.003π, which satisfies the needs for performing two-qubit gates among neighboring lattice sites. We further implement this superlattice in a Rb experiment with a quantum gas microscope of single-site resolution, where the high-power 532-nm laser is necessary for pinning atoms in the short lattice during imaging, providing a unique platform for engineering quantum states.
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http://dx.doi.org/10.1364/OE.423776DOI Listing
April 2021

Adjustment for body mass index changes inverse associations of HDL-cholesterol with blood pressure and hypertension to positive associations.

J Hum Hypertens 2021 May 11. Epub 2021 May 11.

School of Science, Psychology and Sport, Federation University Australia, Ballarat, VIC, Australia.

The associations between high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP) or hypertension are inconsistent in previous studies. This study aimed to assess these associations in a large cohort of Chinese adults and across different age groups. This cross-sectional association study included 22,081 Chinese adults. Associations of HDL-C with BP and hypertension were analyzed using linear or logistic regression, with or without adjustment for confounding factors. HDL-C was inversely associated with BP and hypertension. These associations were still apparent after adjustment for age, sex, fasting plasma glucose, and low-density lipoprotein cholesterol. Sub-analyses revealed: (1) in the whole cohort and females alone, HDL-C was inversely associated with BP and hypertension in young and middle-aged but not older participants; (2) in males alone, HDL-C was not associated with systolic BP or hypertension. However, HDL-C was either inversely, or not, or positively associated with BP in young, middle-aged, and older males, respectively. After further adjustment for body mass index (BMI), the negative associations of HDL-C with BP and hypertension in the whole cohort became positive ones, and the positive associations only presented in males. These findings suggest that further adjustment for BMI changes inverse associations of HDL-cholesterol with BP and hypertension to positive associations in a cohort of Chinese adults.
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http://dx.doi.org/10.1038/s41371-021-00548-xDOI Listing
May 2021

Effects of Bacillus subtilis iturin A on HepG2 cells in vitro and vivo.

AMB Express 2021 May 10;11(1):67. Epub 2021 May 10.

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, 710072, Shaanxi, China.

Iturin A with cyclic peptide and fatty acid chain isolated from Bacillus subtilis fermentation shows a variety of biological activities. Among them, the anticancer activity attracted much attention. However, the molecular mechanism of its inhibitory effect on hepatocellular carcinoma was still unclear. Thus its effect on hepatocellular carcinoma was tested in this research. It was found that iturin A could enter HepG2 cells immediately and cause reactive oxygen species burst, disrupt cell cycle and induce apoptosis, paraptosis and autophagy in vitro. The iturin A without fatty acid chain showed no antitumor activity. Amphiphilic is critical to the activity of iturin A. The anticancer activity of iturin A to hepatocellular carcinoma was also verified in mice models carrying xenograft tumors constructed by HepG2 cells. At a dosage of 3 mg/kg/day, iturin A significantly inhibited the further increase of the tumor weight by 58.55%, and reduced the expression of Ki67 in tumor. In the tumor treated with iturin A, lymphocyte infiltration was found, and the expressions of TGF-β1and PD-L1 were decreased, which indicated that the tumor immune microenvironment was improved. Besides, iturin A showed no significant harm on the health of mice except slight disturbance of liver function. These results suggested that iturin A had significant antitumor effect in vitro and vivo, and provide a basis for the application of iturin A as anticancer agent.
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http://dx.doi.org/10.1186/s13568-021-01226-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110684PMC
May 2021

Effects of Bacillus subtilis iturin A on HepG2 cells in vitro and vivo.

AMB Express 2021 May 10;11(1):67. Epub 2021 May 10.

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, 710072, Shaanxi, China.

Iturin A with cyclic peptide and fatty acid chain isolated from Bacillus subtilis fermentation shows a variety of biological activities. Among them, the anticancer activity attracted much attention. However, the molecular mechanism of its inhibitory effect on hepatocellular carcinoma was still unclear. Thus its effect on hepatocellular carcinoma was tested in this research. It was found that iturin A could enter HepG2 cells immediately and cause reactive oxygen species burst, disrupt cell cycle and induce apoptosis, paraptosis and autophagy in vitro. The iturin A without fatty acid chain showed no antitumor activity. Amphiphilic is critical to the activity of iturin A. The anticancer activity of iturin A to hepatocellular carcinoma was also verified in mice models carrying xenograft tumors constructed by HepG2 cells. At a dosage of 3 mg/kg/day, iturin A significantly inhibited the further increase of the tumor weight by 58.55%, and reduced the expression of Ki67 in tumor. In the tumor treated with iturin A, lymphocyte infiltration was found, and the expressions of TGF-β1and PD-L1 were decreased, which indicated that the tumor immune microenvironment was improved. Besides, iturin A showed no significant harm on the health of mice except slight disturbance of liver function. These results suggested that iturin A had significant antitumor effect in vitro and vivo, and provide a basis for the application of iturin A as anticancer agent.
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http://dx.doi.org/10.1186/s13568-021-01226-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110684PMC
May 2021

MiR-34a suppression targets Nampt to ameliorate bone marrow mesenchymal stem cell senescence by regulating NAD-Sirt1 pathway.

Stem Cell Res Ther 2021 May 6;12(1):271. Epub 2021 May 6.

The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xin Min Street, Changchun, Jilin Province, People's Republic of China.

Background: Expansion-mediated replicative senescence and age-related natural senescence have adverse effects on mesenchymal stem cell (MSC) regenerative capability and functionality, thus severely impairing the extensive applications of MSC-based therapies. Emerging evidences suggest that microRNA-34a (miR-34a) has been implicated in the process of MSC senescence; however, the molecular mechanisms with regard to how miR-34a influencing MSC senescence remain largely undetermined.

Methods: MiR-34a expression in MSCs was evaluated utilizing RT-qPCR. The functional effects of miR-34a exerting on MSC senescence were investigated via gene manipulation. Relevant gene and protein expression levels were analyzed by RT-qPCR and western blot. Luciferase reporter assays were applied to confirm that Nampt is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting Nampt in MSC senescence was further explored by measuring intracellular NAD content, NAD/NADH ratio and Sirt1 activity.

Results: In contrast to Nampt expression, miR-34a expression incremented in senescent MSCs. MiR-34a overexpression in young MSCs resulted in senescence-associated characteristics as displayed by senescence-like morphology, prolonged cell proliferation, declined osteogenic differentiation potency, heightened senescence-associated-β-galactosidase activity, and upregulated expression levels of the senescence-associated factors. Conversely, miR-34a suppression in replicative senescent and natural senescent MSCs contributed to diminished senescence-related phenotypic features. We identified Nampt as a direct target gene of miR-34a. In addition, miR-34a repletion resulted in prominent reductions in Nampt expression levels, NAD content, NAD/NADH ratio, and Sirt1 activity, whereas anti-miR-34a treatment exerted the opposite effects. Furthermore, miR-34a-mediated MSC senescence was evidently rescued following the co-treatment with Nampt overexpression.

Conclusion: This study identifies a significant role of miR-34a playing in MSC replicative senescence and natural senescence via targeting Nampt and further mediating by NAD-Sirt1 pathway, carrying great implications for optimal strategies for MSC therapeutic applications.
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http://dx.doi.org/10.1186/s13287-021-02339-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101138PMC
May 2021