Publications by authors named "Jiaqi Li"

340 Publications

Self-Assembling Nanoparticle Vaccines Displaying the Receptor Binding Domain of SARS-CoV-2 Elicit Robust Protective Immune Responses in Rhesus Monkeys.

Bioconjug Chem 2021 May 5. Epub 2021 May 5.

Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.

SARS-CoV-2 caused the COVID-19 pandemic that lasted for more than a year. Globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against SARS-CoV-2 infection. Focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a SARS-CoV-2 spike protein receptor-binding domain (RBD) displayed on self-assembled ferritin nanoparticles. In a 293i cells eukaryotic expression system, this candidate vaccine was prepared and purified. After rhesus monkeys are immunized with 20 μg of RBD-ferritin nanoparticles three times, the vaccine can elicit specific humoral immunity and T cell immune response, and the neutralizing antibodies can cross-neutralize four SARS-CoV-2 strains from different sources. In the challenge protection test, after nasal infection with 2 × 10 CCID50 SARS-CoV-2 virus, compared with unimmunized control animals, virus replication in the vaccine-immunized rhesus monkeys was significantly inhibited, and respiratory pathology observations also showed only slight pathological damage. These analyses will benefit the immunization program of the RBD-ferritin nanoparticle vaccine in the clinical trial design and the platform construction to present a specific antigen domain in the self-assembling nanoparticle in a short time to harvest stable, safe, and effective vaccine candidates for new SARS-CoV-2 isolates.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00208DOI Listing
May 2021

Pristimerin synergistically sensitizes conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells to sorafenib through endoplasmic reticulum stress and ROS generation by modulating Akt/FoxO1/p27 signaling pathway.

Phytomedicine 2021 Apr 4;86:153563. Epub 2021 Apr 4.

Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, 510080 Guangzhou, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortality worldwide. Sorafenib (SORA), as a first-line therapeutic drug, has been used to treat HCC, but resistance poses a major limitation on the efficacy of SORA chemotherapy. Pristimerin (PRIS), a natural bioactive component isolated from various plant species in the Celastraceae and Hippocrateaceae families, has been reported to exhibit outstanding antitumor effects in several types of cells in vitro.

Purpose: The aim of this study was to investigate whether PRIS can exert synergistic anti-tumor effects with the combination of SORA, and if so, through what mechanism.

Methods: Conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells (CRHCs) were isolated from human liver cancer tissues and treated with SORA and PRIS. Cell proliferation, apoptosis, migration and tube formation ability were detected by DNA content quantification, flow cytometry, transwell assay and Matrigel-based angiogenesis assay. Gene and protein expression were assessed by qRT-PCR and Western blot respectively.

Results: Initially, we observed that the combination of the two drugs had a much stronger inhibitory effect on CRHCs growth than either drug alone. Moreover, the combination of 2 µM SORA and 1 µM PRIS exhibited a significant anti‑migrative and anti-invaded effect on CRHCs, and remarkably inhibited capillary structure formation of Human Umbilical Vein Endothelial Cells (HUVECs). Furthermore, the combined treatment with SORA and PRIS synergistically induced intrinsic apoptosis in CRHCs, involving a caspase-4-dependent mechanism paralleled by an increased Bax/Bcl-xL ratio. These activities were mediated through ROS generation and the induction of endoplasmic reticulum (ER) stress and mitochondrial dysfunction. GRP78 silencing or ER stress inhibitor 4-phenylbutyric acid administration was revealed to abolish the anticancer effects of PRIS, indicating the critical role of GRP78 in mediating the bioactivity of PRIS. The present study also provides mechanistic evidence that PRIS modulated the Akt/FoxO1/p27 signaling pathway, which is required for mitochondrial-mediated intrinsic apoptosis, activation of ER stress, and stimulation of caspase-4 induced by PRIS, and, consequently resulting in suppressed cell viability, migration and angiogenesis co-treated with SORA in CRHCs.

Conclusion: Our results suggest the use of PRIS as sensitizers of chemotherapy paving the way for innovative and promising targeted chemotherapy-based therapeutic strategies in human HCC.
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http://dx.doi.org/10.1016/j.phymed.2021.153563DOI Listing
April 2021

Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males.

Sci Rep 2021 May 4;11(1):9495. Epub 2021 May 4.

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu City, Sichuan Province, People's Republic of China.

Insulin aspart (IAsp) is one of the main therapies used to control blood glucose after a meal. This study aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 rapid-acting IAsp products: a new IAsp biosimilar (RD10046) and NovoRapid. In a single-center, randomized, single-dose, 2-period, crossover, euglycemic clamp study (registry number: CTR20180517, registration date: 2018-05-30), healthy Chinese males were randomized to receive 0.2 U/kg of the IAsp biosimilar RD10046 and NovoRapid under fasted conditions on two separate occasions. PK and PD were assessed for up to 10 h. Of the 30 randomized subjects, all 30 completed both treatment periods. The PK (area under the curve [AUC] of total IAsp; maximum observed IAsp concentration [C]) and PD (maximum glucose infusion rate [GIR]; total glucose infusion during the clamp [AUC]) were similar between the new IAsp biosimilar RD10046 and NovoRapid. In all cases, the 90% CIs for the ratios of the geometric means were completely contained in the prespecified acceptance limits of 0.80-1.25. No hypoglycemic events, allergic reactions, or local injection adverse reactions occurred in this trial. We concluded that the studied IAsp biosimilar (RD10046) was bioequivalent to NovoRapid.
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http://dx.doi.org/10.1038/s41598-021-88782-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096952PMC
May 2021

Effect of photoperiod on vitamin E and carotenoid biosynthesis in mung bean (Vigna radiata) sprouts.

Food Chem 2021 Apr 21;358:129915. Epub 2021 Apr 21.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Light affects the accumulation of vitamin E and carotenoids in many crops. This study investigated the impact of photoperiods on the metabolic regulation of vitamin E and carotenoids in mung bean sprouts considering their dietary health benefits. Mung beans were germinated under three different photoperiods: constant light, semilight and constant dark. Results revealed that the semilight photoperiod was optimum for vitamin E and carotenoid accumulation in mung bean sprouts. DXS was activated in the constant dark and was inhibited by constant light. GGPPS and HPT were sensitive to semilight photoperiod in the vitamin E biosynthetic pathway, playing dominant roles in vitamin E accumulation. The PSY, LCYE, LUT5, LUT1 and ZE genes, which are associated with carotenoid biosynthesis, were activated under semilight treatment and significantly regulated the accumulation of carotenoids. This knowledge improves knowledge on light-mediated regulation of vitamin E and carotenoids in mung bean sprouts.
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http://dx.doi.org/10.1016/j.foodchem.2021.129915DOI Listing
April 2021

A novel small-molecule fatty acid synthase inhibitor with antitumor activity by cell cycle arrest and cell division inhibition.

Eur J Med Chem 2021 Apr 20;219:113407. Epub 2021 Apr 20.

Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, 214012, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, 214012, China. Electronic address:

Fatty acid synthase (FASN), the key enzyme in de novo lipogenesis, is an attractive therapeutic target for diseases characterized by excessive lipid accumulation. Many FASN inhibitors have failed in the clinical trial phase, largely because of poor solubility and safety. In this study, we generated a novel small-molecule FASN inhibitor by structure-based virtual screening. PFI09, the lead compound, is easy to synthesize, and inhibits the lipid synthesis in OP9 mammalian cell line and Caenorhabditis elegans as well as the proliferation of several cancer cell lines via the blockade of FASN. Mechanistic investigations show that PFI09 induces S-phase arrest, cell division reduction and apoptosis. We also develop a chemically stable analog of PFI09, MFI03, which reduces the proliferation of PC3 tumor cells both in vitro and in vivo, without toxicity to mice. In summary, our data suggest that MFI03 is an effective FASN inhibitor and a promising antineoplastic drug candidate.
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http://dx.doi.org/10.1016/j.ejmech.2021.113407DOI Listing
April 2021

β-elemonic acid inhibits growth and triggers apoptosis in human castration-resistant prostate cancer cells through the suppression of JAK2/STAT3/MCL-1 and NF-ĸB signal pathways.

Chem Biol Interact 2021 Apr 18;342:109477. Epub 2021 Apr 18.

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, People's Republic of China. Electronic address:

Castration-resistant prostate cancer (CRPC) has become a significant problem in the current treatment of prostate cancer (PCa) with the characteristics of high metastatic potential, resistance and easy recurrence. The abnormal activation of JAK2/STAT3/MCL-1 and NF-κB has been confirmed as the main reason for the development of CRPC. We previously found that β-elemonic acid (β-EA) as a natural triterpene has potential anti-inflammatory and anti-osteosarcoma effects with lower toxicity. But it remains unknown whether it had effects on CRPC. The present research in vitro and in vivo systematically investigates anti-cancer effects and mechanisms of β-EA on human CRPC. β-EA treatment resulted in apoptotic cell death in human PCa cells by mitochondrial apoptotic pathways (including up-regulation of cleaved caspase-3, cleaved PARP, and Bax or down-regulation of Bcl-2). Besides, β-EA at relatively lower levels inhibited colony-forming, the migration and invasion potential of PCa cells, indicating its anti-proliferation and anti-metastasis activities. After exploring the potential mechanism, our results suggested that it subsequently inhibited the activation of JAK2/STAT3/MCL-1 and NF-κB signaling pathway by the administration of β-EA. The silencing of NF-κB/p65, JAK2 and STAT3, respectively, increased the sensitivity of the PCa cells to β-EA induced apoptosis. Moreover, β-EA exhibited a strong affinity with its essential proteins JAK2, RELA/p65, NF-κBIα/IκBα by molecular docking analysis. Importantly, β-EA retards tumor growth in a murine xenograft model, consistent with our study in vitro. Taken together, findings from this study reveal for the first time the potential role and mechanisms of β-EA on CRPC.
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http://dx.doi.org/10.1016/j.cbi.2021.109477DOI Listing
April 2021

The effects of Fushen Granule on the composition and function of the gut microbiota during Peritoneal Dialysis-Related Peritonitis.

Phytomedicine 2021 Mar 28;86:153561. Epub 2021 Mar 28.

Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, PR China. Electronic address:

Background: Peritoneal dialysis (PD) is an acknowledged treatment for patients with irreversible kidney failure. The treatment usually causes peritoneal dialysis-related peritonitis (PDRP), a common complication of PD that can lead to inadequate dialysis, gastrointestinal dysfunction, and even death. Recent studies indicated that Fushen Granule (FSG), a Chinese herbal formula, improves the treatment of PD. However, the mechanism of how FSG plays its role in the improvement is still unclear. Gut microbiota has been closely related to the development of various diseases. We carried out a randomized controlled trial to assess whether FSG can modulate the gut microbiota during PDRP treatment.

Methods: Forty-two PDRP patients were recruited into the clinical trial, and they were randomly divided into control(CON), probiotics(PRO) or Fushen granule group(FSG). To check whether FSG improve the PD treatment, we assessed the clinical parameters, including albumin(ALB), hemoglobin(HGB), blood urea nitrogen(BUN) and creatinine(CR). Fecal samples were collected before hospitalization and discharge, and stored at -80°C within 1 hour. And we assessed the microbial population and function by applying the 16S rRNA gene sequencing and functional enrichment analysis.

Results: Compared to control group, ALB is improved in both probiotics and FSG groups, while HGB is increased but BUN and CR is reduced in FSG group. Sequencing of 16S rRNA genes revealed that FSG and PRO affected the composition of the microbial community. FSG significantly increased a abundant represented by Bacteroides, Megamonas and Rothia, which was significantly correlated with the improvements in carbohydrate and amino acid metabolism.

Conclusions: This study demonstrates that FSG ameliorates the nutritional status and improves the quality of life by enriching beneficial bacteria associated with metabolism. These results indicate that FSG as alternative medicine is a promising treatment for patients with PDRP.
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http://dx.doi.org/10.1016/j.phymed.2021.153561DOI Listing
March 2021

An atypical KLRG1 in Nile tilapia involves in adaptive immunity as a potential marker for activated T lymphocytes.

Fish Shellfish Immunol 2021 Mar 31;113:51-60. Epub 2021 Mar 31.

State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China. Electronic address:

Killer cell lectin-like receptor G subfamily 1 (KLRG1) is a receptor generally expressed on effector CD8 T cells or NK cells at terminal differentiation stage, and it will be highly induced for lymphocyte cytotoxicity upon pathogen infection or lymphocyte activation. However, little is known about the character or function of KLRG1 in lower vertebrates. In present study, we reappraised a molecule that previously defined as KLRG1 in the genomic sequence of Nile tilapia Oreochromis niloticus, and identified it as an atypical KLRG1-like molecule (defined as On-KLRG1-L), and illustrated its potential function serving as a marker representing effector T lymphocytes of fish species. On-KLRG1-L consists of two C-type lectin-like domains (CTLDs) without transmembrane region, and the tertiary structure of the CTLD is highly alike to that in mouse KLRG1. As a CTLD-containing protein, the recombinant On-KLRG1-L could bind PGN and several microbes in vitro. On-KLRG1-L was widely expressed in immune-associated tissues, with the highest expression level in the gill. Once Nile tilapia is infected by Aeromonas hydrophila, mRNA level of On-KLRG1-L in spleen lymphocytes were significantly up-regulated on 5 days after infection. Meanwhile, On-KLRG1-L protein was also induced on 5 or 8 days after A. hydrophila infection. Furthermore, we found both mRNA and protein levels of On-KLRG1-L were dramatically enhanced within several hours after spleen lymphocytes were activated by T cell-specific mitogen PHA in vitro. More importantly, the ratio of On-KLRG1-L T cells was also augmented after PHA stimulation. The observations suggested that the KLRG1-like molecule from Nile tilapia participated in lymphocyte activation and anti-bacterial adaptive immune response, and could serve as an activation marker of T lymphocytes. Our study thus provided new evidences to understand lymphocyte-mediated adaptive immunity of teleost.
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http://dx.doi.org/10.1016/j.fsi.2021.03.016DOI Listing
March 2021

Asymmetric Bubble Formation at Rectangular Orifices.

Langmuir 2021 Apr 2;37(14):4302-4307. Epub 2021 Apr 2.

Mechanical Science and Engineering, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, United States.

Bubble formation in liquids is frequently observed in nature and applied in various industrial processes. These include pool and flow boiling for thermal management systems, where bubbles may form asymmetrically at narrow slits and in convective flows. While previous studies have focused on symmetric bubble formation at circular orifices, the dynamics of asymmetric bubble formation remains poorly understood. Here, we experimentally investigate bubble formation at rectangular orifices and examine the effects of the orifice size and aspect ratio and the gas flow rate on the bubble size. The asymmetric bubble shape evolution at the rectangular orifice is analyzed, and we find that the size of the bubble neck is controlled either by the orifice size or by the capillary length. Based on these findings, we develop a static force balance model to predict the bubble size in the quasi-static regime, where the roles of Bond number and aspect ratio are identified. The bubble size evolution in the dynamic regime is further understood by introducing a Weber number that evaluates the effect of the virtual mass force induced by gas flow. Our study provides physical understanding of the dynamics of asymmetric bubble formation and guidance to predict the bubble size at asymmetric orifices.
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http://dx.doi.org/10.1021/acs.langmuir.1c00287DOI Listing
April 2021

The usefulness of the combined high-dose dexamethasone suppression test and desmopressin stimulation test in establishing the source of ACTH secretion in ACTH-dependent Cushing's syndrome.

Endocr J 2021 Mar 31. Epub 2021 Mar 31.

Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Bilateral inferior petrosal sinus sampling (BIPSS) is the current gold standard test for differentially diagnosing ACTH-dependent Cushing's syndrome (CS). However, BIPSS is an invasive procedure, and its availability is limited. We retrospectively analysed the 24-hour urinary free cortisol (UFC) level during the high-dose dexamethasone suppression test (HDDST) and plasma ACTH/cortisol levels after the desmopressin stimulation test (DDAVP test) in subjects with confirmed Cushing's disease (CD) (n = 92) and ectopic ACTH-dependent CS (EAS) (n = 16), and evaluated the positive predictive value (PPV) of the two combined-tests in the aetiological diagnosis of ACTH-dependent CS. The percent changes in UFC levels after the HDDST and in ACTH/cortisol levels after DDAVP administration relative to the corresponding basal levels and the area under the receiver operating characteristic (ROC) curve (AUC) were analysed. UFC suppression below 62.7% suggested a pituitary origin with a sensitivity (SE) of 80% (95% CI: 70-88) and a specificity (SP) of 80% (95% CI: 52-96). A threshold increase in the ACTH level after DDAVP stimulation of 44.6% identified CD with an SE of 91% (95% CI: 83-97) and an SP of 75% (95% CI: 48-93). The combination of both tests yielded an SE of 95.5% and PPV of 98.4% for CD, and significantly improved the efficiency of the differential diagnosis between CD and EAS. These dual non-invasive endocrine tests may substantially reduce the need for BIPSS in the etiological investigation of ACTH-dependent CS.
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http://dx.doi.org/10.1507/endocrj.EJ20-0837DOI Listing
March 2021

Interaction mechanism of flavonoids with whey protein isolate: A spectrofluorometric and theoretical investigation.

Food Chem 2021 Sep 19;355:129617. Epub 2021 Mar 19.

Key Laboratory of Dairy Science, Ministry of Education, College of Food Science and Technology, Northeast Agricultural University, Harbin 150030, China. Electronic address:

The interaction mechanism between whey protein isolate (WPI) and flavonoids was investigated based on the spectrofluorometric and theoretical methods in this study. The binding capacities of 15 flavonoids with WPI were compared. Then, the 3D-QSAR model describing their binding behavior was established to illustrate the effect of flavonoid structure on binding. It was found that the flavonoids with electronegative group at C-3 or large substituent at C-3 and C-7 possessed high binding performance. The thermodynamic analysis further indicated the hydrophobic force was the main driving force for binding of WPI and flavonoids. Both synchronous and 3D fluorescence analysis suggested that the microenvironment around tryptophan residues had changed, which coincided with the result of molecular docking that tryptophan residue of α-lactalbumin contributed significantly to hydrogen bonding. Our results suggested that the combination of 3D-QSAR and molecular docking may prompt the interaction research between food-derived proteins and polyphenols.
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http://dx.doi.org/10.1016/j.foodchem.2021.129617DOI Listing
September 2021

Protein phase separation and its role in chromatin organization and diseases.

Biomed Pharmacother 2021 Jun 23;138:111520. Epub 2021 Mar 23.

Dr. Neher's Laboratory for innovative Drug Discovery, Macau University of Science and Technology, Macao, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, China. Electronic address:

In the physical sciences, solid, liquid, and gas are the most familiar phase states, whose essence is their existence reflecting the different spatial distribution of molecular components. The biological molecules in the living cell also have differences in spatial distribution. The molecules organized in the form of membrane-bound organelles are well recognized. However, the biomolecules organized in membraneless compartments called biomolecular condensates remain elusive. The liquid-liquid phase separation (LLPS), as a new emerging scientific breakthrough, describes the biomolecules assembled in special distribution and appeared as membraneless condensates in the form of a new "phase" compared with the surrounding liquid milieu. LLPS provides an important theoretical basis for explaining the composition of biological molecules and related biological reactions. Mounting evidence has emerged recently that phase-separated condensates participate in various biological activities. This article reviews the occurrence of LLPS and underlying regulatory mechanisms for understanding how multivalent molecules drive phase transitions to form the biomolecular condensates. And, it also summarizes recent major progress in elucidating the roles of LLPS in chromatin organization and provides clues for the development of new innovative therapeutic strategies for related diseases.
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http://dx.doi.org/10.1016/j.biopha.2021.111520DOI Listing
June 2021

Droplet evaporation residue indicating SARS-COV-2 survivability on surfaces.

Phys Fluids (1994) 2021 Jan 15;33(1):013309. Epub 2021 Jan 15.

We conducted a systematic investigation of droplet evaporation on different surfaces. We found that droplets formed even with distilled water do not disappear with evaporation but instead shrink to a residue of a few micrometers lasting over 24 h. The residue formation process differs across surfaces and humidity levels. Specifically, under 40% relative humidity, 80% of droplets form residues on plastic and uncoated and coated glass, while less than 20% form on stainless steel and none on copper. The formation of residues and their variability are explained by modeling the evaporation process considering the presence of nonvolatile solutes on substrates and substrate thermal conductivity. Such variability is consistent with the survivability of SARS-CoV-2 measured on these surfaces. We hypothesize that these long-lasting microscale residues can potentially insulate the virus against environmental changes, allowing them to survive and remain infectious for extended durations.
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http://dx.doi.org/10.1063/5.0038562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976051PMC
January 2021

Leukocyte Count and Risks of Stroke and Coronary Heart Disease: The Circulatory Risk in Communities Study (CIRCS).

J Atheroscler Thromb 2021 Mar 21. Epub 2021 Mar 21.

Public Health, Department of Social Medicine, Graduate School of Medicine, Osaka University.

Aim: This study aimed to investigate the associations of leukocyte count with the risks of stroke and coronary heart disease among the general Japanese population.

Methods: A total of 5,242 residents aged 40-69 years living in two Japanese communities underwent leukocyte count measurements between 1991 and 2000, and the data were updated using 5- or 10-year follow-ups or both. Participants who had histories of stroke, coronary heart disease, or high values of leukocyte count (>130×10 cells/mm) were excluded. Hazard ratios with 95% confidence intervals (CIs) were calculated according to quartiles of cumulative average leukocyte count.

Results: During follow-up of 21 years, 327 stroke and 130 coronary heart disease cases were determined. After adjustments for age, sex, community, and updated cardiovascular risk factors, the multivariable hazard ratio (95% CI) for the highest versus lowest quartile of leukocyte count was 1.50 (1.08-2.08) for ischemic stroke, 1.59 (1.00-2.51) for lacunar infarction, 1.42 (0.90-2.26) for non-lacunar infarction, 2.17 (1.33-3.55) for coronary heart disease, and 1.40 (1.11-1.76) for total cardiovascular disease. In smoking status-stratified analyses, the corresponding multivariable hazard ratio (95% CI) was 2.45 (1.11-5.38) for ischemic stroke, 2.73 (1.37-5.44) for coronary heart disease in current smokers, 2.42 (1.07-5.46), 1.55 (0.58-4.15) in former smokers, and 1.17 (0.75-1.82), 1.78 (0.83-3.82) in never smokers.

Conclusion: Leukocyte count was positively associated with the risks of ischemic stroke and coronary heart disease among the general Japanese population, especially in current smokers.
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http://dx.doi.org/10.5551/jat.60889DOI Listing
March 2021

Research Progress on the Mechanism of Lumbarmultifidus Injury and Degeneration.

Oxid Med Cell Longev 2021 26;2021:6629037. Epub 2021 Feb 26.

Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei Province, China.

This review summarizes recent research progress in the clinical features, image manifestations, and pathological mechanism of multifidus injury. After a brief introduction to the fiber classification, innervation, blood supply, and multifidus function, some factors of multifidus injury, consisting of denervation, intraoperative incision selection and traction, and lumbar degenerative disease are overviewed. In addition, the clinical index of multifidus injury including myoglobin, creatine kinase, IL-6, C-reactive protein, the cross-sectional area of multifidus, the degree of fat infiltration, and intraoperative biopsy are summarized. Furthermore, we recommend that patients with chronic low back pain should take the long-term exercise of lumbodorsal muscles. Finally, some remaining issues, including external fixation and the imaging quantitative evaluation criteria of multifidus, need to be further explored in the future.
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http://dx.doi.org/10.1155/2021/6629037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936897PMC
February 2021

A new species of the Asian leaf litter toad genus Smith, 1925 (Anura, Megophryidae) from northwest Guizhou Province, China.

Zookeys 2021 2;1021:81-107. Epub 2021 Mar 2.

Department of Resources and Environment, Moutai Institute, Renhuai 564500, China Moutai Institute Renhuai China.

A new species of the Asian leaf litter toad genus is described from Guizhou Province, China. Molecular phylogenetic analyses support the new species as an independent lineage deeply nested in the clade. The new species is distinguished from its congeners by a combination of the following morphological characters: body size medium (SVL 29.7-31.2 mm in five adult males); dorsal skin shagreened, some of the granules forming longitudinal short skin ridges; tympanum distinctly discernible, slightly concave; supra-axillary, femoral, pectoral and ventrolateral glands distinctly visible; absence of webbing and lateral fringes on fingers; toes with narrow lateral fringes but without webbing; heels overlapping when thighs are positioned at right angles to the body; tibia-tarsal articulation reaching the middle of eye when leg stretched forward. The discovery highlighted the underestimated species diversity in the toads in southwestern China.
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http://dx.doi.org/10.3897/zookeys.1021.60729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943530PMC
March 2021

Fish NF-κB couples TCR and IL-17 signals to regulate ancestral T-cell immune response against bacterial infection.

FASEB J 2021 Apr;35(4):e21457

State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, China.

As fish constitute the first evolutionary group with primordial T cells, they are of importance for understanding the origin and evolution of adaptive immunity. Yet, the knowledge about how ancestral T cells function remains limited. Therefore, the teleost model Nile tilapia (Oreochromis niloticus) was used in this study to investigate the regulatory mechanisms of T-cell immunity in fish. We identified an evolutionarily conserved canonical NF-κB signaling pathway in Nile tilapia, which participates in primary adaptive immune response during Streptococcus agalactiae infection. Blockade of NF-κB activity severely impairs T-cell activation and expansion, rendering the animals more vulnerable to pathogen attack. Meanwhile, NF-κB signaling is indispensable for fish T cells to produce IL-17A during the antibacterial immune response. Moreover, IL-17A binds its receptor IL-17RA, initiates the ACT1-TRAF6-TAK1 axis, and triggers NF-κB-dependent T-cell activation, thus forming a positive feedback loop of T-cell immunity in Nile tilapia. Furthermore, IL-17A seems to promote innate immunity by regulating pro-inflammatory cytokines via TRAF6-NF-κB axis, indicating the presence of an NF-κB-dependent IL-17A signaling pathway for coordinating adaptive and innate immunity in fish. Our results suggest that fish NF-κB couples TCR and IL-17 signals to modulate ancestral T-cell immunity against bacterial infection, and the regulation of T-cell immunity by NF-κB and IL-17 is a strategy that existed prior to the divergence of the tetrapod lineage from teleost fish. This study, therefore, provides a new perspective on the evolution of adaptive immunity.
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http://dx.doi.org/10.1096/fj.202002393RRDOI Listing
April 2021

Characterization of rat and mouse acidic milk oligosaccharides based on hydrophilic interaction chromatography coupled with electrospray tandem mass spectrometry.

Carbohydr Polym 2021 May 2;259:117734. Epub 2021 Feb 2.

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Key Laboratory of Separation Science for Analytical Chemistry, Dalian, 116023, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Oligosaccharides are one of the most important components in mammalian milk. Milk oligosaccharides can promote colonization of gut microbiota and protect newborns from infections. The diversity and structures of MOs differ among mammalian species. MOs in human and farm animals have been well-documented. However, the knowledge on MOs in rat and mouse have been very limited even though they are the most-widely used models for studies of human physiology and disease. Herein, we use a high-sensitivity online solid-phase extraction and HILIC coupled with electrospray tandem mass spectrometry to analyze the acidic MOs in rat and mouse. Among the fifteen MOs identified, twelve were reported for the first time in rat and mouse together with two novel sulphated oligosaccharides. The complete list of acidic oligosaccharides present in rat and mouse milk is the baseline information of these animals and should contribute to biological/biomedical studies using rats and mice as models.
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http://dx.doi.org/10.1016/j.carbpol.2021.117734DOI Listing
May 2021

Study on Acoustic Emission Characteristics of Low-Temperature Asphalt Concrete Cracking Damage.

Materials (Basel) 2021 Feb 12;14(4). Epub 2021 Feb 12.

School of Civil Engineering, Chongqing Jiaotong University, Chongqing 400074, China.

In this study, asphalt concrete specimens were subjected to a semicircle bending test at -10 °C to simulate the process of the development of cracks in asphalt concrete at low temperature. The acoustic emission parameters were collected during the test, the variation characteristics of acoustic emission parameters were analyzed, and the peakedness value was introduced to evaluate the damage of asphalt concrete. The dynamic evolution of fracture development was analyzed by periods with acoustic emission source location. The results indicate that the damage of asphalt mixtures shows an obvious brittle characteristic at low temperature, acoustic emission signals mainly originate from the crack damage caused by tensile stress, and the strength and number of signals can reflect the degree of crack development. Based on acoustic emission parameters and load curves, the cracking damage of asphalt concrete at low temperature in this study can be divided into three periods: a calm period, a stable development period, and a rapid fracture period. The crack point occurred and propagated upward rapidly in the rapid fracture period. During this period, acoustic emission parameters such as ringing count, acoustic emission energy, and amplitude increased suddenly; furthermore, the peakedness value reached its peak in this period and corresponded well with the low-temperature damage of asphalt concrete. Acoustic emission source location technology can track position of crack points and the propagation path of cracks, reflecting the dynamic evolution process of asphalt concrete crack damage at low temperature.
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http://dx.doi.org/10.3390/ma14040881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918095PMC
February 2021

The Association of an SNP in the Gene and Reproductive Traits Suggests Its Use as a Breeding Marker in Pigs.

Animals (Basel) 2021 Feb 17;11(2). Epub 2021 Feb 17.

Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

In mammals, the exocyst complex component 4 () gene has often been reported to be involved in vesicle transport. The SNP rs81471943 (C/T) is located in the intron of porcine , while six quantitative trait loci (QTL) within 5-10 Mb around are associated with ovary weight, teat number, total offspring born alive, and corpus luteum number. However, the molecular mechanisms between and the reproductive performance of pigs remains to be elucidated. In this study, rs81471943 was genotyped from a total of 994 Duroc sows, and the genotype and allele frequency of SNP rs81471943 (C/T) were statistically analyzed. Then, the associations between SNP rs81471943 and four reproductive traits, including number of piglets born alive (NBA), litter weight at birth (LWB), number of piglets weaned (NW), and litter weight at weaning (LWW), were determined. Sanger sequencing and PCR restriction fragment length polymorphism (PCR-RFLP) were utilized to identify the rs81471943 genotype. We found that the genotype frequency of CC was significantly higher than that of CT and TT, and CC was the most frequent genotype for NBA, LWB, NW, and LWW. Moreover, 5'-deletion and luciferase assays identified a positive transcription regulatory element in the promoter. After exploring the promoter, SNP -1781G/A linked with SNP rs81471943 (C/T) were identified by analysis of the transcription activity of the haplotypes, and SNP -1781 G/A may influence the potential binding of , E26 transformation specific sequence -like 1 transcription factor (), and myeloid zinc finger 1 (). These findings provide useful information for identifying a molecular marker of -assisted selection in pig breeding.
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http://dx.doi.org/10.3390/ani11020521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921996PMC
February 2021

Rapid Identification of Plasmid Replicon Type and Coexisting Plasmid-Borne Antimicrobial Resistance Genes by S1-Pulsed-Field Gel Electrophoresis-Droplet Digital Polymerase Chain Reaction.

Foodborne Pathog Dis 2021 Mar 4. Epub 2021 Mar 4.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Bacterial drug resistance is a significant food safety problem and public health threat. Plasmids carrying drug resistance genes may result in the rapid spread of resistance among different bacteria, hosts, and environments; therefore, antibiotic resistance monitoring and continuing research into the mechanisms of drug resistance are urgently needed. Southern blotting with probes for antibiotic resistance genes and even next-generation sequencing have been used previously to detect plasmid-borne resistance genes, but these approaches are complex and time-consuming. The next-generation sequencing requires strict laboratory conditions and bioinformatics analysis ability. In this study, we developed a simplified and sensitive method to detect plasmid-borne antimicrobial resistance genes and plasmid replicon types. strains carrying plasmids of three different replicon types that contained and two ESBL-producing genes were used to verify the new method. The plasmids harbored by the strains were separated by S1 nuclease treatment and pulsed-field gel electrophoresis (PFGE), then recovered and used as the templates for droplet digital polymerase chain reaction (ddPCR) to identify target genes. The target genes were present in significantly higher copy numbers on the plasmids than the background noise. These results were consistent with the plasmid sequencing results. This S1-PFGE-ddPCR method was less time-consuming to perform than Southern blot and complete plasmid sequencing. Therefore, this method represents a time-saving alternative for detecting plasmid-borne genes, and is likely to be a valuable tool for detecting coexisting plasmid-borne drug resistance genes.
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http://dx.doi.org/10.1089/fpd.2020.2865DOI Listing
March 2021

An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens.

Front Immunol 2021 15;12:645426. Epub 2021 Feb 15.

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. The most efficacious vaccine, CVI988/Rispens (CVI988), against MD has been used for several decades. However, the mechanisms leading to protective immunity following vaccination are not fully understood. In this study, employing multi-parameter flow cytometry, we performed a comprehensive analysis of T cell responses in CVI988-vaccinated chickens. CVI988 vaccination induced significant expansion of γδ T cells and CD8α T cells but not CD4 T cells in spleen, lung and blood at early time-points. The expansion of these cells was CVI988-specific as infection with very virulent MDV RB1B did not elicit expansion of either γδ or CD8α T cells. Phenotypic analysis showed that CVI988 vaccination elicited preferential proliferation of CD8α γδ T cells and CD8αα co-receptor expression was upregulated on γδ T cells and CD8α T cells after immunization. Additionally, cell sorting and quantitative RT-PCR showed that CVI988 vaccination activated γδ T cells and CD8α T cells which exhibited differential expression of cytotoxic and T cell-related cytokines. Lastly, secondary immunization with CVI988 induced the expansion of CD8 T cells but not γδ T cells at higher magnitude, compared to primary immunization, suggesting CVI988 did induce memory CD8 T cells but not γδ T cells in chickens. Our results, for the first time, reveal a potential role of γδ T cells in CVI988-induced immune protection and provide new insights into the mechanism of immune protection against oncogenic MDV.
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http://dx.doi.org/10.3389/fimmu.2021.645426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917234PMC
February 2021

Tracing cell-type evolution by cross-species comparison of cell atlases.

Cell Rep 2021 Mar;34(9):108803

Center for Stem Cell and Regenerative Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Stem Cell Institute, Zhejiang University, Hangzhou 310058, China. Electronic address:

Cell types are the basic building units of multicellular life, with extensive diversities. The evolution of cell types is a crucial layer of comparative cell biology but is thus far not comprehensively studied. We define a compendium of cell atlases using single-cell RNA-seq (scRNA-seq) data from seven animal species and construct a cross-species cell-type evolutionary hierarchy. We present a roadmap for the origin and diversity of major cell categories and find that muscle and neuron cells are conserved cell types. Furthermore, we identify a cross-species transcription factor (TF) repertoire that specifies major cell categories. Overall, our study reveals conservation and divergence of cell types during animal evolution, which will further expand the landscape of comparative genomics.
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http://dx.doi.org/10.1016/j.celrep.2021.108803DOI Listing
March 2021

Grayscale image for broadband linear polarization measurement by an ultracompact metasurface.

Opt Lett 2021 Mar;46(5):1117-1120

The polarization of light, the vector nature of electromagnetic waves, is one of the fundamental parameters. Finding a direct and efficient method to measure the state of polarized light is extremely urgent for nano-optical applications. Based on Malus's law, we design an ultracompact metasurface composed of silver nanorods, which is demonstrated to directly measure the state of linear polarization by a grayscale image. Using an ultrathin metasurface, we generate grayscale images with gradient grayscale levels which are linked directly to the polarization state of the incident light. The direction of the linear polarization of incident light can be conveniently and efficiently obtained through extracting the angle of the brightest area of the grayscale image. The ultrathin metasurface operates in the broadband 750-1100 nm spectral range. It is a novel and significant method to analyze the linear polarization state of light, which provides opportunities for various applications, such as polarimetric multispectral imaging and miniaturized polarimeter.
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http://dx.doi.org/10.1364/OL.415844DOI Listing
March 2021

Structure-Activity Relationship Studies of Coumarin-like Diacid Derivatives as Human G Protein-Coupled Receptor-35 (hGPR35) Agonists and a Consequent New Design Principle.

J Med Chem 2021 Mar 25;64(5):2634-2647. Epub 2021 Feb 25.

Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116034, China.

A series of coumarin-like diacid derivatives were designed and synthesized as novel agonists of human G-protein-coupled receptor 35 (hGPR35). Active compounds were characterized to possess one acidic group on both sides of a fused tricyclic aromatic scaffold. Most of them functioned as full agonists selective to hGPR35 and exhibited excellent potency at low nanomolar concentrations. Substitution on the middle ring of the scaffold could effectively regulate compound potency. Structure-activity relationship studies and docking simulation indicated that compounds that carried two acidic groups with a proper special distance and attached to a rigid aromatic scaffold would most likely show a potent agonistic activity on hGPR35. Following this principle, we screened a list of known compounds and some were found to be potent GPR35 agonists, and compound even had an EC of 8 nM. Particularly, a dietary supplement pyrroloquinoline quinone (PQQ) was identified as a potent agonist (EC = 71.4 nM). To some extent, this principle provides a general strategy to design and recognize GPR35 agonists.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01624DOI Listing
March 2021

Temporally coherent perturbation of neural dynamics during retention alters human multi-item working memory.

Prog Neurobiol 2021 Jun 19;201:102023. Epub 2021 Feb 19.

School of Psychological and Cognitive Sciences, Peking University, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, China; Beijing Key Laboratory of Behavior and Mental Health, Peking University, China. Electronic address:

Temporarily storing a list of items in working memory (WM), a fundamental ability in cognition, has been posited to rely on the temporal dynamics of multi-item neural representations during retention. However, the causal evidence, particularly in human subjects, is still lacking, let alone WM manipulation. Here, we develop a novel "dynamic perturbation" approach to manipulate the relative memory strength of WM items held in human brain, by presenting temporally correlated luminance sequences during retention to interfere with the multi-item neural dynamics. Six experiments on more than 150 subjects confirm the effectiveness of this WM manipulation approach. A computational model combining continuous attractor neural network (CANN) and short-term synaptic plasticity (STP) principles further reproduces all the empirical findings. The model reveals that the "dynamic perturbation" modifies the synaptic efficacies of WM items through STP principles, eventually leading to changes in their relative memory strengths. Our results support the causal role of temporal dynamics of neural network in mediating multi-item WM, and offer a promising, purely bottom-up approach to manipulate WM.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102023DOI Listing
June 2021

Lateral Gradient Ambidextrous Optical Reflection in Self-Organized Left-Handed Chiral Nematic Cellulose Nanocrystals Films.

Front Bioeng Biotechnol 2021 5;9:608965. Epub 2021 Feb 5.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Changchun, China.

Artificial photonic materials displaying ordered reflected color patterns are desirable in the field of photonic technologies, however, it is challenging to realize. Here we present that self-assembly of cellulose nanocrystals (CNC) in a tilted cuvette leads to the formation of rainbow color CNC films. We show that the self-organized CNC films enable simultaneous reflection of left-handed circularly polarized (LCP) and right-handed circularly polarized (RCP) light with lateral gradient transmittance ratio (LCP/RCP: 8.7-0.9) and the maximum reflectance value up to 72%. This unique ambidextrous optical reflection arises from left-handed chiral photonic architectures with lateral gradient photonic bandgaps and nematic-like defects at the film-substrate interface and between left-handed photonic bandgap layers acting as a half-wavelength retarder. We demonstrate that the tilted angle self-assembly method provides a feasible step toward color patterning of CNC-based photonic films capable of ambidextrous optical reflection.
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http://dx.doi.org/10.3389/fbioe.2021.608965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892906PMC
February 2021

Genome-wide cell-free DNA methylation analyses improve accuracy of non-invasive diagnostic imaging for early-stage breast cancer.

Mol Cancer 2021 02 19;20(1):36. Epub 2021 Feb 19.

Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, 325027, China.

Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.
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http://dx.doi.org/10.1186/s12943-021-01330-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893735PMC
February 2021

Akt1/mTORC1 signaling modulates adaptive immune response of Nile tilapia by promoting lymphocyte activation and proliferation.

Dev Comp Immunol 2021 Jun 12;119:104042. Epub 2021 Feb 12.

State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China. Electronic address:

Serving as a significant signaling molecule, RAC-alpha serine/threonine-protein kinase (Akt1) plays indispensable roles in cell cycle, growth, survival, metabolism, as well as immune response. However, how Akt1 regulates adaptive immune response in early vertebrate, especially the teleost, is largely unknown. Here, using a Nile tilapia Oreochromis niloticus model, we investigated the regulatory role of Akt1 in adaptive immunity of teleost. Both sequence and structure of the O. niloticus Akt1 (OnAkt1), were evolutionarily conserved comparing with the counterparts from other vertebrates. mRNA of OnAkt1 was widely expressed in lymphoid organs/tissues of Nile tilapia, with relative higher level in PBL. After Nile tilapia was infected by Aeromonas hydrophila, both transcription and phosphorylation levels of OnAkt1 were obviously elevated in spleen lymphocytes at the adaptive immune stage, suggesting Akt1 participated in primary adaptive immune response of Nile tilapia. Furthermore, OnAkt1 transcript or phosphorylation was dramatically augmented after spleen lymphocytes were activated by T cell specific mitogen PHA or lymphocyte agonist PMA. More critically, inhibition of Akt1 by specific inhibitor crippled the activation of downstream mTORC1 signaling, and impaired the up-regulation of T cell activation markers CD44, IFN-γ and CD122 in spleen lymphocytes upon PHA-induced T cell activation. Meanwhile, blockade of Akt1-activated mTORC1 signaling also decreased the frequency of BrdU lymphocytes during A. hydrophila infection, indicating the critical role of Akt1 in regulating lymphocyte proliferation of Nile tilapia. Together, our results demonstrated that Akt1 modulated adaptive immune response of Nile tilapia by promoting lymphocyte activation and proliferation via mTORC1 signaling. Our study enriched the regulatory mechanism of lymphocyte-mediated adaptive immunity in teleost, and thus provided novel insights into the evolution of adaptive immune system.
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http://dx.doi.org/10.1016/j.dci.2021.104042DOI Listing
June 2021

[Research progress on exosome-mediated immune regulation of acute lung injury].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jan;33(1):118-121

Department of Burn, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Corresponding author: Guo Guanghua, Email:

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a respiratory disorder with high morbidity and mortality caused by various causes. Exosomes can mediate cell communication through paracrine pathways, transfer proteins, lipids, nucleic acids, etc., and interfere with the biological functions of recipient cells. Various cell-derived exosomes have been reported to play an immunomodulatory role in the ALI/ARDS inflammatory model. This article reviews the mechanism of exosomes involved in immune regulation of ALI/ARDS and possible therapeutic approaches.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200408-00262DOI Listing
January 2021