Publications by authors named "Li Sun"

2,417 Publications

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Oxygen-Deficient α-MnO Nanotube/Graphene/N, P Codoped Porous Carbon Composite Cathode To Achieve High-Performing Zinc-Ion Batteries.

ACS Appl Mater Interfaces 2022 Aug 8. Epub 2022 Aug 8.

Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 100083, China.

A major drawback of α-MnO-based zinc-ion batteries (ZIBs) is the poor rate performance and short cycle life. Herein, an oxygen-deficient α-MnO nanotube (V-α-MnO)-integrated graphene (G) and N, P codoped cross-linked porous carbon nanosheet (CNPK) composite (V-α-MnO/CNPK/G) has been prepared for advanced ZIBs. The introduction of V in MnO can decrease the value of the Gibbs free energy of Zn adsorption near V (ca. -0.73 eV) to the thermal neutral value. The thermal neutral value demonstrates that the Zn adsorption/desorption process on V-α-MnO is more reversible than that on α-MnO. The as-made Zn/V-α-MnO battery is able to deliver a large capacity of 305.0 mAh g and high energy density up to 408.5 Wh kg. The good energy storage properties can be attributed to V. Additionally, the V-α-MnO/CNPK/G composite possesses the structure of nanotube arrays, which results from the vertical growth of α-MnO nanotubes on CNPK. This unique array structure helps to realize fast ion/electron transfer and stable microstructure. The electrochemical performance of V-α-MnO has been comprehensively improved by compositing with G and CNPK. The V-α-MnO/CNPK/G can achieve capacity up to 405.2 mAh g, energy density of 542.2 Wh kg, and long cycle life (80% capacity retention after 2000 cycles).
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http://dx.doi.org/10.1021/acsami.2c09152DOI Listing
August 2022

New insights into the evolutionary dynamic and lineage divergence of gasdermin E in metazoa.

Front Cell Dev Biol 2022 22;10:952015. Epub 2022 Jul 22.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.

Gasdermin (GSDM) is a family of pore-forming proteins that induce pyroptosis. To date, the origin and evolution of GSDM in Metazoa remain elusive. Here, we found that GSDM emerged early in Placozoa but is absent in a large number of invertebrates. In the lower vertebrate, fish, three types of GSDME, i.e., GSDMEa, GSDMEb, and a previously unreported type (designated GSDMEc), were idenitied. Evolutionarily, the three GSDMEs are distinctly separated: GSDMEa is closely related to tetrapod GSDME; GSDMEb exists exclusively in fish; GSDMEc forms the lineage root of tetrapod GSDMA/B/C/D. GSDMEc shares conserved genomic features with and is probably the prototype of GSDMA, which we found existing in all tetrapod classes. GSDMEc displays fast evolutionary dynamics, likely as a result of genomic transposition. A cross-metazoan analysis of GSDME revealed that GSDMEa shares a conserved caspase recognition motif with the GSDME of tetrapods and cnidarians, whereas GSDMEb has a unique caspase recognition motif similar to that of mammalian GSDMD, and GSDMEc exhibits no apparent caspase recognition motif. Through functional test, four highly conserved residues in vertebrate GSDME proved to be essential to auto-inhibition. Together our results provide new insights into the origin, evolution, and function of metazoan GSDMs.
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http://dx.doi.org/10.3389/fcell.2022.952015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355259PMC
July 2022

The diagnostic utility of IL-10, IL-17, and PCT in patients with sepsis infection.

Front Public Health 2022 22;10:923457. Epub 2022 Jul 22.

Department of Laboratory Medicine, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

Objective: The purpose of this study is to determine the diagnostic value and net clinical benefit of interleukin-10 (IL-10), interleukin-17 (IL-17), procalcitonin (PCT), and combination tests in patients with sepsis, which will serve as a standard for sepsis early detection.

Patients And Methods: An investigation of 84 sepsis patients and 81 patients with local inflammatory diseases admitted to the ICU of Tongji University Hospital in 2021. In addition to comparing inter-group variability, indicators relevant to sepsis diagnosis and therapy were screened.

Results: LASSO regression was used to examine PCT, WBC, CRP, IL-10, IFN-, IL-12, and IL-17. Multivariate logistic regression linked IL-10, IL-17, and PCT to sepsis risk. The AUC values of IL-10, IL-17, PCT, and the combination of the three tests were much higher than those of standard laboratory infection indicators. The combined AUC was greater than the sum of IL-10, IL-17, and PCT ( < 0.05). A clinical decision curve analysis of IL-10, IL-17, PCT, and the three combined tests found that the three combined tests outperformed the individual tests in terms of total clinical benefit rate. To predict the risk of sepsis using IL-10, IL-17, and PCT had an AUC of 0.951, and the model's predicted probability was well matched. An examination of the nomogram model's clinical value demonstrated a considerable net therapeutic benefit between 3 and 87%.

Conclusion: The IL-10, IL-17, and PCT tests all have a high diagnostic value for patients with sepsis, and the combination of the three tests outperforms the individual tests in terms of diagnostic performance, while the combined tests have a higher overall clinical benefit rate.
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http://dx.doi.org/10.3389/fpubh.2022.923457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355284PMC
August 2022

Time-Modulated Transmissive Programmable Metasurface for Low Sidelobe Beam Scanning.

Research (Wash D C) 2022 9;2022:9825903. Epub 2022 Jul 9.

Department of Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Programmable metasurfaces have great potential for the implementation of low-complexity and low-cost phased arrays. Due to the difficulty of multiple-bit phase control, conventional programmable metasurfaces suffer a relatively high sidelobe level (SLL). In this manuscript, a time modulation strategy is introduced in the 1-bit transmissive programmable metasurface for reducing the SLLs of the generated patterns. After the periodic time modulation, harmonics are generated in each reconfigurable unit and the phase of the first-order harmonic can be dynamically controlled by applying different modulation sequences onto the corresponding unit. Through the high-speed modulation of the real-time periodic coding sequences on the metasurface by the programmable bias circuit, the equivalent phase shift accuracy to each metasurface unit can be improved to 6-bit and thus the SLLs of the metasurface could be reduced remarkably. The proposed time-modulated strategy is verified both numerically and experimentally with a transmissive programmable metasurface, which obtains an aperture efficiency over 34% and reduced SLLs of about -20 dB. The proposed design could offer a novel approach of a programmable metasurface framework for radar detection and secure communication applications.
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http://dx.doi.org/10.34133/2022/9825903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297726PMC
July 2022

Roll to roll in situ preparation of recyclable, washable, antibacterial Ag loaded nonwoven fabric.

Sci Rep 2022 Aug 1;12(1):13206. Epub 2022 Aug 1.

Engineering Research Center for Nanomaterials, Henan University, Kaifeng, 475004, China.

Functional fabrics with antibacterial performance are more welcome nowadays. However, the fabrication of functional fabrics with durable, steady performance via a cost-effective way remains a challenge. Polypropylene (denoted as PP) nonwoven fabric was modified by polyvinyl alcohol (denoted as PVA), followed by the in-situ deposition of silver nanoparticles (denoted as Ag NPs) to afford PVA-modified and Ag NPs-loaded PP (denoted as Ag/PVA/PP) fabric. The encapsulation of PP fiber by PVA coating contributes to greatly enhancing the adhesion of the loaded Ag NPs to the PP fiber, and the Ag/PVA/PP nonwoven fabrics exhibit significantly improved mechanical properties as well as excellent antibacterial activity against Escherichia coli (coded as E. coli). Typically, the Ag/PVA/PP nonwoven fabric obtained at a silver ammonia concentration of 30 mM has the best mechanical properties and the antibacterial rate reaches 99.99% against E. coli. The fabric retains excellent antibacterial activity even after washing for 40 cycles, showing prospects in reuse. Moreover, the Ag/PVA/PP nonwoven fabric could find promising application in industry, thanks to its desired air-permeability and moisture-permeability. In addition, we developed a roll-to-roll production process and conducted preliminary exploration to verify the feasibility of this method.
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http://dx.doi.org/10.1038/s41598-022-17484-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342839PMC
August 2022

Micro ribonucleic acid-448 regulates zinc finger e-box binding homeobox 1 to inhibit the growth of breast cancer cells and increase their sensitivity to chemotherapy.

Clinics (Sao Paulo) 2022 Jul 26;77:100089. Epub 2022 Jul 26.

Department of Oncology, the First Affiliated Hospital of Soochow University, Soochow, Jiangsu, China. Electronic address:

Objective: This study aimed to investigate the effect of Zinc Finger E-box Binding Homeobox 1 (ZEB1) regulation by Micro Ribonucleic acid (miR)-448 on Breast Cancer (BC) cells and their sensitivity to chemotherapy.

Methods: miR-448 and ZEB1 mRNA levels in BC and normal tissues were detected by qPCR, and ZEB1 protein was detected by Western Blotting (WB). The correlation between miR-448 and tumor metastasis, clinical staging, and ZEB1 expression was analyzed. MCF-7 cells were transfected or co-transfected with the miR-448 mimic, oe-ZEB1, or their negative controls. Changes in miR-448 and ZEB1 expression were detected by qPCR and WB. Cell proliferation was determined by CCK-8 assays, invasion changes were analyzed by Transwell assays, and apoptosis was detected by flow cytometry.

Results: miR-448 expression in BC tissues was lower than that in normal tissues, while ZEB1 expression was increased in the former. ZEB1 expression was lower in BC patients with lymph node metastasis than in those without. In patients with clinical stage I-III BC, miR-448 expression decreased with an increase in tumor stage, which was negatively correlated with ZEB1 expression. Upregulation of miR-448 expression can suppress MCF-7 cell proliferation and invasion and promote apoptosis. Upregulation of ZEB1 expression in cells overexpressing miR-448 can partially reverse the inhibition of BC cell growth induced by miR-448. miR-448 can enhance the sensitivity of cells toward paclitaxel and 5-fluorouracil.

Conclusions: miR-448 suppresses cell proliferation and invasion and promotes apoptosis by targeting ZEB1. Moreover, it can increase the sensitivity of cells toward paclitaxel and 5-fluorouracil.
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http://dx.doi.org/10.1016/j.clinsp.2022.100089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335378PMC
July 2022

Genetic variations in UCA1, a lncRNA functioning as a miRNA sponge, determine endometriosis development and the potential associated infertility via regulating lipogenesis.

PLoS One 2022 28;17(7):e0271616. Epub 2022 Jul 28.

Institute of Biomedical Sciences, National Sun Yatsen University, Kaohsiung, Taiwan.

Endometriosis is a hormone-associated disease which has been considered as the precursor for certain types of ovarian cancer. In recent years, emerging evidence demonstrated potent roles of lncRNA in regulating cancer development. Since endometriosis shares several features with cancer, we investigated the possible involvement of cancer-related lncRNAs in endometriosis, including UCA1, GAS5 and PTENP1. By using massARRAY system, we investigated certain genetic variations in cancer-related lncRNAs that can change the thermo-stability, leading to up-regulation or down-regulation of those lncRNAs. Our data indicated three risk genetic haplotypes in UCA1 which can stabilize the RNA structure and increase the susceptibility of endometriosis. Of note, such alterations were found to be associated with long-term pain and infertility in patients. It has been known that UCA1 can function as a ceRNA to sponge and inhibit miRNAs, resulting in loss-of-control on downstream target genes. Gene network analyses revealed fatty acid metabolism and mitochondria beta-oxidation as the major pathways associated with altered UCA1 expression in endometriosis patients. Our study thus provides evidence to highlight functional/epigenetic roles of UCA1 in endometriosis development via regulating fatty acid metabolism in women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271616PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333278PMC
August 2022

Pleiotropic Effect of the Gene and Its Combined Effects with Other Loci for Spike and Grain-Related Traits in Wheat.

Plants (Basel) 2022 Jul 13;11(14). Epub 2022 Jul 13.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Cytogenetics Institute, Nanjing Agricultural University/JCIC-MCP, Nanjing 210095, China.

Club wheat ( ssp. ) with a distinctly compact spike morphology was conditioned by the dominant () locus on chromosome 2D and resulted in a redistribution of spike yield components. The disclosure of the genetic basis of club wheat was a prerequisite for the development of widely adapted, agronomically competitive club wheat cultivars. In this study, we used a recombinant inbred line population derived from a cross between club wheat Hiller and modern cultivar Yangmai 158 to construct a genetic linkage map and identify quantitative trait loci associated with 15 morphological traits. The club allele acted in a semi-dominant manner and the gene was mapped to 370.12-406.29 Mb physical region on the long arm of 2D. Apart from compact spikes, exhibited a pleiotropic effect on ten other agronomic traits, including plant height, three spike-related traits and six grain-related traits. The compact spike phenotype was correlated with decreased grain size and weight, but with an increase in floret fertility and grain number. These pleiotropic effects make club wheat have compatible spike weight with a normal spike from common wheat. The genetic effects of various gene combinations of with four yield-related genes, including , , and , were evaluated. had no epistatic interaction with any of these genes, indicating that their combinations would have an additive effect on other agronomically important traits. Our research provided a theoretical foundation for the potentially effective deployment of gene into modern breeding varieties in combination with other favorable alleles.
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http://dx.doi.org/10.3390/plants11141837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316965PMC
July 2022

Derivation of Soil Criteria of Cadmium for Safe Rice Production Applying Soil-Plant Transfer Model and Species Sensitivity Distribution.

Int J Environ Res Public Health 2022 Jul 21;19(14). Epub 2022 Jul 21.

College of Environment Science and Engineering, Yangzhou University, Yangzhou 225127, China.

Widespread soil contamination is hazardous to agricultural products, posing harmful effects on human health through the food chain. In China, Cadmium (Cd) is the primary contaminant in soils and easily accumulates in rice, the main food for the Chinese population. Therefore, it is essential to derive soil criteria to safeguard rice products by assessing Cd intake risk through the soil-grain-human pathway. Based on a 2-year field investigation, a total of 328 soil-rice grain paired samples were collected in China, covering a wide variation in soil Cd concentrations and physicochemical properties. Two probabilistic methods used to derive soil criteria are soil-plant transfer models (SPT), with predictive intervals, and species sensitivity distribution (SSD), composed of soil type-specific bioconcentration factor (BCF, Cd concentration ratio in rice grain to soil). The soil criteria were back-calculated from the Chinese food quality standard. The results suggested that field data with a proper Cd concentration gradient could increase the model accuracy in the soil-plant transfer system. The derived soil criteria based on soil pH were 0.06-0.11, 0.33-0.59, and 1.51-2.82 mg kg for protecting 95%, 50% and 5% of the rice safety, respectively. The soil criteria with soil pH further validated the soil as being safe for rice grains.
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http://dx.doi.org/10.3390/ijerph19148854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315542PMC
July 2022

protoscoleces enhance glycolysis to promote M2 Macrophages through PI3K/Akt/mTOR Signaling Pathway.

Pathog Glob Health 2022 Jul 25:1-8. Epub 2022 Jul 25.

Central Laboratory of Qinghai University Affiliated Hospital, Qinghai University Affiliated Hospital, Xining, Qinghai province, China.

Alveolar Echinococcosis (AE) is a zoonotic parasitic disease caused by , but its pathogenesis remains unclear. The primary objective of this study is to explore whether protoscoleces (PSCs) regulate macrophage polarization and glucose metabolism by PI3K/Akt/mTOR signaling pathway. We found that large numbers of CD68 macrophages gathered in close liver issue from the lesion in AE patients. PSCs preferentially differentiated into M2 macrophages and the expressions of HK1, PFKL, PKM2, PI3K, Akt, p-Akt, mTOR and p-mTOR increased. The above results show that protoscoleces enhance glycolysis to promote M2 macrophages through PI3K/Akt/mTOR signaling pathway.
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http://dx.doi.org/10.1080/20477724.2022.2104055DOI Listing
July 2022

MULT1-Encoding DNA Alleviates Schistosomiasis-Associated Hepatic Fibrosis via Modulating Cellular Immune Response.

J Inflamm Res 2022 16;15:4027-4045. Epub 2022 Jul 16.

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Purpose: In schistosomiasis-associated hepatic fibrosis, the role of murine UL16-binding protein-like transcript 1 (MULT1), the strongest ligand of natural killer group 2-member D receptor (NKG2D), remains unclear. Here, -infected mice administered with MULT1-encoding DNA were used to test MULT1 as a potential therapy for schistosomiasis-associated hepatic fibrosis and explore relevant mechanisms.

Materials And Methods: A recombinant plasmid encoding MULT1 (p-rMULT1) was constructed and administered to -infected BALB/c mice via hydrodynamic tail vein injection. Egg granulomas in liver, hepatic fibrosis biomarkers and levels of cytokines were investigated. Comparisons of CD4+ T, CD8+ T, NK and NKT proportions as well as their phenotype were performed not only between infected, p-rMULT1 treated group and infected, backbone plasmid pEGFP-N1 treated group but also between infected, nontreated group and health control group.

Results: Reduced area of granuloma formation and fibrosis around single eggs, downregulated expression of collagen I, α-smooth muscle actin, TGF-β and IL-10, and upregulated expression of IFN-γ, were observed in the livers of p-rMULT1 treated mice. p-rMULT1 treatment improved infection impacted immune microenvironment by modulating proportion of CD4 T CD8 T, natural killer (NK) and NKT cells, enhancing expression of NKG2D, in lymphocytes, and augmenting IFN-γ secretion by CD4 T, CD8 T, NK and NKT cells, as well as partially reversing some other phenotype changes of lymphocytes.

Conclusion: To the best of our knowledge, we provided the first in vivo evidence that MULT1 is a favorable anti-fibrosis factor in the context of schistosomiasis. The inhibitory effect of MULT1 overexpression on schistosomiasis associated with hepatic fibrosis may result from augmenting the proportion and function of NKG2D-expressing immune cells, and from enhancing NK- and T-cell activation, as well as regulating the helper T (Th)1/Th2 balance.
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http://dx.doi.org/10.2147/JIR.S354224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301018PMC
July 2022

Modifiable risk factors for incident dementia and cognitive impairment: An umbrella review of evidence.

J Affect Disord 2022 Oct 19;314:160-167. Epub 2022 Jul 19.

Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Background: Dementia and cognitive impairment can be attributed to genetic and modifiable factors. Considerable evidence emerged in modifiable factors and urgently requires standardized evaluation. We conducted an umbrella review to evaluate the strength and validity of the existing evidence.

Methods: We searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors. For each association, we analyzed the summary effect size, 95 % confidence interval, 95 % prediction interval, heterogeneity, small study effect and excess significance bias. Mendelian randomization studies were descriptively reviewed further exploring the causality of the associations.

Results: In total, 12,015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, BMI, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for that of midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified causal relationships of education and plasma glucose with Alzheimer's disease.

Limitations: Low quality of the studies included.

Conclusions: Modifiable risk factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Our results support a valuable rationale for future experimental designs to establish further evidence for the associations in larger populations.
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http://dx.doi.org/10.1016/j.jad.2022.07.008DOI Listing
October 2022

Screening of different chemical components of sedative and hypnotic effects of Ziziphi Spinosae Semen before and after frying and determination of the Q-Marker.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Jul 1;1207:123349. Epub 2022 Jul 1.

Grade Three-level Laboratory of TCM Preparation, State Administration of Traditional Chinese Medicine, The First Affiliated Hospital/College of integrated Chinese and Western Medicine of Anhui University of Chinese Medicine, Hefei 230031, China. Electronic address:

Ziziphi Spinosae Semen (ZSS) is a traditional Chinese medicine used for sedation and hypnosis. Preliminary studies have shown that frying it could increase its sedative and hypnotic effects due to an increase in its chemical contents. However, the correlation between increased ZSS contents and therapeutic effects remains unclear. This study aimed to identify chemical components that change between ZSS and Fried Ziziphi Spinosae Semen (FZSS) and Q-markers related to these changed components' sedative and hypnotic effects. Differences between ZSS and FZSS were investigated using the UPLC fingerprint analysis. Components significantly different between ZSS and FZSS were screened using the UPLC-Q-TOF-MS analysis combined with a multivariate statistical method. In addition, ZSS and FZSS extracts were treated with diazepam in vitro to observe their differences in saturation competition between ZSS extract and diazepam, before and after processing, and diazepam on the GABA receptor in SD rats' brain tissue. Then, the chemical components of ZSS and FZSS that competed with diazepam to bind to the GABA receptor were identified by LC-MS/MS analysis. Finally, the binding efficiency of the different medicinal components was assessed using molecular docking technology. The results indicated significant differences in the content of various chemical components between ZSS and FZSS. Among them, the contents of adenosine, spinosin, 6'″-feruloylspinosin, jujuboside A and betulinic acid were found to be significantly increased after frying. LC-MS/MS and molecular docking analysis screened spinosin, 6'″-feruloylspinosin and betulinic acid as Q markers for the sedative and hypnotic effects of ZSS and FZSS. In summary, this study identified the changed sedative-hypnotic chemical components and Q-markers of ZSS before and after frying.
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http://dx.doi.org/10.1016/j.jchromb.2022.123349DOI Listing
July 2022

Successful secondary radical operation on unretractable metastatic platinum-sensitive recurrent ovarian cancer by immunotherapy: a case report.

Ann Transl Med 2022 Jun;10(12):718

National Cancer Center/National Clinical Research Center for Cancer/Department of Gynecology, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.

Background: Although rechallenge with platinum-based chemotherapy is effective for most platinum-sensitive recurrent ovarian cancer (ROC) patients, there is still a subset of patients who have no responses to the standard care. Overcoming multidrug resistance (MDR) is a top priority in oncology clinics, but it remains intricate. It is difficult for clinicians to manage unretractable ROC when conventional therapy yields no results. The rational and effective use of immunotherapy will contribute to the clinical benefit of these patients, especially in patients without approved immunotherapy biomarkers. Here we present a case of successful secondary radical surgery for unretractable metastatic MDR ROC by immunotherapy based on her immune-infiltrating tumor microenvironment signatures.

Case Description: A 57-year-old woman, diagnosed with IC2 stage high-grade serous ovarian cancer in 2015, underwent immediate ultra-radical cytoreductive surgery followed by 6 cycles of platinum-containing adjuvant chemotherapy. After nearly 37 months of disease-free status, the woman complained of spontaneous pain from the right subcostal margin for 1 month and was diagnosed with ROC accompanied by multiple unretractable colorectal and hepatic metastases. Standard chemotherapies were ineffective and quickly resulted in disease progression and grade IV myelosuppression followed impaired gastrointestinal function. Notably, after standard chemotherapy, the patient was tested negative for all immune biomarkers, but multiple fluorescence immunohistochemistry indicated that her tumor tissue was significantly infiltrated with the cluster of differentiation 8 (CD8) T cells and natural killer (NK) cells, implying potential benefits of immunotherapy. Then changed to 3 cycles of intravenous pembrolizumab, the main pelvic tumor and hepatic metastases showed significant shrinkage and achieved partial response, but the disease progressed after 8.7 months. Subsequently, arterial perfusion with pembrolizumab was performed combined with the chemotherapy. A comfortingly partial response was achieved again that enabled the patient to successfully undergo a secondary radical surgery for colorectal and liver metastases. Since that time the patient's postoperative course has been favorable, and she remains disease-free at present for at least 17 months.

Conclusions: Immune infiltration signatures of the tumor microenvironment could serve as an indication for immunotherapy in patients with unretractable platinum-sensitive ROC with MDR. In addition, the introduction of immunotherapy might bring some degree of chemotherapy resensitization.
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http://dx.doi.org/10.21037/atm-22-2128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279770PMC
June 2022

Gonadotropin receptor polymorphisms (FSHR N680S and LHCGR N312S) are not predictive of clinical outcome and live birth in assisted reproductive technology.

Fertil Steril 2022 Jul 13. Epub 2022 Jul 13.

Instituto Valenciano de Infertilidad Reproductive Medicine Associates, New Jersey; Thomas Jefferson University.

Objective: To study the consequences of specific genotype profiles of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone choriogonadotropin receptor (LHCGR) on assisted reproductive technology outcomes when preimplantation genetic testing for aneuploidy is used for controlling the embryo ploidy status. The most common reported single-nucleotide polymorphisms in the amino acid position for the FSHR (N680S; N: asparagine, S: serine; [rs6166]) and the LHCGR (N312S variant; N: asparagine, S: serine [rs2293275]) were chosen for this study.

Design: Retrospective cohort study.

Setting: Private Fertility Clinic.

Patient(s): All women aged 18-40 years undergoing their first assisted reproductive technology cycle with aneuploidy screening between 2006 and 2017 with body mass index of >18 and <40 kg/m were included.

Intervention(s): All patients received both recombinant follicle-stimulating hormone and human menopausal gonadotropin or low dose human chorionic gonadotropin. Genomic DNA was isolated from patients' blood. Genotyping of the FSHR and LHCGR polymorphisms was performed using TaqMan genotyping assays. Associations between both receptor genotypes and clinical outcomes were assessed using generalized regression and ANOVA.

Main Outcomes Measure(s): Live birth rate was the primary outcome. Secondary outcomes included oocyte yield, mature oocytes, blastulation rate, usable blastocyst rate, and implantation rate.

Result(s): A total of 1,183 patients met the inclusion criteria and generated reliable genotype results. The overall genotype frequencies in the study population for the FSHR gene were as follows: 21.7% homozygous for S in codon 680, 29.2% homozygous for N680, and 48.1% heterozygous (N680S). As for the LHCGR, 15.6% were homozygous for N312, 38.5% homozygous for S312 and 45.9% heterozygous (N312S). Our study population consisted of 53.8% non-Hispanic white; 6.1% Hispanic white; 4.1% Afro-American; 15.4% Asian; and 20.6% other or unknown. No significant association was found with any of the studied variables (oocyte yield, usable blastocyst rate, implantation rate, live birth) when genotypes were analyzed per receptor or in combination with one another. There was a statistically significant but clinically irrelevant difference in the rate of mature oocytes across different variant combinations.

Conclusion(s): Our findings suggest that the presence of gonadotropin receptor polymorphisms in both FSHR N680S and LHCGR N312S are not associated with assisted reproductive technology outcomes; therefore, these variants should not be considered reproductive predictors.
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http://dx.doi.org/10.1016/j.fertnstert.2022.06.011DOI Listing
July 2022

Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial.

Curr Med Res Opin 2022 Jul 22:1-10. Epub 2022 Jul 22.

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Qiao Estuary Hankou, Wuhan, China.

Objective: This phase 3 confirmatory diabetes mellitus treatment study compared the safety and efficacy of Rapilin and NovoRapid insulin asparts in combination with metformin.

Methods: This 24-week, open-label, randomized, active-controlled, noninferiority phase 3 confirmatory study conducted across centers in China aimed to enroll patients with type 2 diabetes mellitus and blood sugar glucose inadequately controlled by oral antidiabetic drugs. Randomized patients received subcutaneous mealtime Rapilin or NovoRapid (3:1) injections, with metformin. The primary objectives were to demonstrate noninferiority (margin of 0.4%) in HbA1c change from baseline and compare safety profiles of Rapilin versus NovoRapid after 24 weeks. Secondary outcomes included 2-h postprandial plasma glucose (PPG), fasting plasma glucose (FPG), and patients achieving HbA1c <7.0% and ≤6.5%.

Results: 590 patients with type 2 diabetes mellitus were randomized to Rapilin ( = 441) and NovoRapid ( = 149) groups. After 24 weeks, the mean HbA1c change from baseline was -2.20% (Rapilin) and -2.32% (NovoRapid); the estimated treatment difference based on least-square means was 0.04% (95% CI: -0.17, 0.26), meeting the noninferiority criteria for Rapilin versus NovoRapid. Comparable improvements were reported for mean 2-hour PPG (6.14 and 6.29 mmol/L), FPG (2.02 and 1.70 mmol/L), and patients with HbA1c <7.0% (52.6% and 51.0%) and ≤6.5% (34.2% and 30.9%), in the Rapilin and NovoRapid groups, respectively, with no significant safety or immunogenicity outcome differences.

Conclusions: Rapilin demonstrated non-inferior glycemic control, and matching safety and immunogenicity to NovoRapid in patients with type 2 diabetes mellitus also receiving metformin over 24 weeks.

Trial Registration: ChiCTR20003129041.
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http://dx.doi.org/10.1080/03007995.2022.2100652DOI Listing
July 2022

Fluorescent aptamer-modified mesoporous silica nanoparticles for quantitative acetamiprid detection.

Environ Sci Pollut Res Int 2022 Jul 13. Epub 2022 Jul 13.

School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, 225009, China.

Acetamiprid (ACE) is widely used to control aphids, brown planthoppers, and other pests in agricultural production. However, ACE is difficult to degrade in the environment, resulting in excessive residue, which causes acute and chronic toxicity to human beings and non-target organisms. Therefore, the development of a rapid, convenient, and highly sensitive method to quantify ACE is essential. In this study, aminated mesoporous silica nanoparticles (MSNs-NH) were synthesized by one-pot method, and 6-carboxyl fluorescein modified aptamers (FAM-Apt) of ACE were adsorbed on the surface of MSNs-NH by electrostatic interaction. Finally, a simple and sensitive fluorescence analysis method for the rapid detection of ACE was established. In the absence of ACE, the negatively charged FAM-Apt was electrostatically bound to the positively charged MSNs-NH, followed by centrifugation to precipitate [email protected], and no fluorescent signal was detected in the supernatant. In the presence of ACE, the specific combination of FAM-Apt with ACE was greater than its electrostatic interaction with MSNs-NH, so that FAM-Apt was separated from MSNs-NH, and the supernatant had strong fluorescence signal after centrifugation. For ACE detection, the linear concentration range was 50-1100 ng/mL, and the detection limit (LOD) was 30.26 ng/mL. The method exhibited high sensitivity, selectivity and reproducibility, which is suitable for practical sample analysis and provides guidance for rapid detection of pesticide residues.
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http://dx.doi.org/10.1007/s11356-022-21970-9DOI Listing
July 2022

A Teleost CXCL10 Is Both an Immunoregulator and an Antimicrobial.

Front Immunol 2022 20;13:917697. Epub 2022 Jun 20.

Chinese Academy of Sciences (CAS) and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology; CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.

Chemokines are a group of cytokines that play important roles in cell migration, inflammation, and immune defense. In this study, we identified a CXC chemokine, CXCL10, from Japanese flounder (named PoCXCL10) and investigated its immune function. Structurally, PoCXCL10 possesses an N-terminal coil, three β-strands, and a C-terminal α-helix with cationic and amphipathic properties. PoCXCL10 expression occurred in multiple tissues and was upregulated by bacterial pathogens. Recombinant PoCXCL10 (rPoCXCL10) promoted the migration, cytokine expression, and phagocytosis of flounder peripheral blood leukocytes (PBLs). rPoCXCL10 bound to and inhibited the growth of a variety of common Gram-negative and Gram-positive fish pathogens. rPoCXCL10 killed the pathogens by causing bacterial membrane permeabilization and structure destruction. When introduced , rPoCXCL10 significantly inhibited bacterial dissemination in fish tissues. A peptide derived from the C-terminal α-helix exhibited bactericidal activity and competed with rPoCXCL10 for bacterial binding. Deletion of the α-helix affected the bactericidal activity but not the chemotaxis or antimicrobial activity of PoCXCL10. Together, these results indicate that PoCXCL10 exerts the role of both an immunoregulator and a bactericide/bacteriostatic different structural domains. These findings provide new insights into the immune function and working mechanism of fish CXC chemokines.
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http://dx.doi.org/10.3389/fimmu.2022.917697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251016PMC
June 2022

Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis.

Authors:
Yan Zhao Li Sun

Cell Death Discov 2022 Jul 4;8(1):305. Epub 2022 Jul 4.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.

Bacillus cereus is well known as a causative agent of foodborne gastrointestinal diseases and systemic non-gastrointestinal diseases. We have recently identified a pathogenic B. cereus (named H2) from a deep-sea cold-seep. H2 possesses the pyroptosis-inducing capacity and contains a number of enterotoxins including cytotoxin K (CytK). In the present work, we examined the cytotoxicity of the CytK of H2 to human macrophages. CytK bound macrophages by interaction with the plasma membrane and caused cellular structure damage. CytK-cell interaction triggered rapid pyroptosis mediated by caspase 1-activated gasdermin D (GSDMD). CytK-induced pyroptosis required NLRP3 inflammasome activation, K efflux, and intracellular Ca accumulation. CytK exhibited apparent binding to several cytomembrane lipids, in particular phosphatidic acid, which proved to be essential to CytK-elicited cell death. Together, these results add new insights into the cytotoxic mechanism of CytK.
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http://dx.doi.org/10.1038/s41420-022-01091-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253000PMC
July 2022

Efficacy of Osimertinib in EGFR-Mutated Advanced Non-small-Cell Lung Cancer With Different T790M Status Following Resistance to Prior EGFR-TKIs: A Systematic Review and Meta-analysis.

Front Oncol 2022 7;12:863666. Epub 2022 Jun 7.

Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.

Purpose: Epidermal growth factor receptor (EGFR) T790M-negative/unknown advanced non-small cell lung cancer (NSCLC) patients lack subsequent approved targeted therapies. This meta-analysis aimed to assess the efficacy of osimertinib in advanced NSCLC patients with different T790M status after resistance to prior first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and to predict the subgroups that may benefit beside T790M-positive disease.

Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant trials. Meeting abstracts were also reviewed to identify appropriate studies. Studies evaluating the efficacy and/or survival outcomes of osimertinib in patients with different T790M status (positive, negative, or unknown) after resistance to prior first- or second-generation EGFR-TKIs were enrolled, and data were pooled to assess hazard ratios (HRs) or relative risk ratios (RRs) in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

Results: A total of 1,313 EGFR-mutated NSCLC patients from 10 retrospective and one prospective studies treated with osimertinib after resistance to first- or second-generation EGFR-TKIs were included. In overall groups, T790M-positive patients showed an improved OS (HR=0.574, p=0.015), PFS (HR = 0.476, p = 0.017), and ORR (RR = 2.025, p = 0.000) compared with T790M-negative patients. In the brain metastases subgroup, no significant difference in OS was observed between T790M-positive and T790M-negative patients (HR = 0.75, p = 0.449) or between T790M-positive and T790M-unknown patients (HR = 0.90, p = 0.673). In the plasma genotyping subgroup, PFS was similar between T790M-positive and T790M-negative patients (HR = 1.033, p = 0.959).

Conclusion: Patients with progressive brain metastases on first- or second-generation EGFR-TKIs can benefit from subsequent osimertinib therapy regardless of T790M status. Patients with plasma T790M-negative status and lack of tissue genotyping should be allowed to receive osimertinib treatment.
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http://dx.doi.org/10.3389/fonc.2022.863666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242653PMC
June 2022

Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state.

PLoS Biol 2022 06 30;20(6):e3001682. Epub 2022 Jun 30.

Center for Reproductive Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a senescent-like state, marked by cell cycle arrest, the down-regulation of ribosomes and histones and down-regulation of MYC and p53 activity. The arrested embryos can be divided into 3 types. Type I embryos fail to complete the maternal-zygotic transition, and Type II/III embryos have low levels of glycolysis and either high (Type II) or low (Type III) levels of oxidative phosphorylation. Treatment with the SIRT agonist resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype, which is accompanied by changes in metabolic activity. Overall, our data suggests metabolic and epigenetic dysfunctions underlie the arrest of human embryos.
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http://dx.doi.org/10.1371/journal.pbio.3001682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246109PMC
June 2022

Downregulation of GPR160 inhibits the progression of glioma through suppressing epithelial to mesenchymal transition (EMT) biomarkers.

Basic Clin Pharmacol Toxicol 2022 Jun 30. Epub 2022 Jun 30.

Jiangsu key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, China.

Background: Glioma is one of the most fatal types of malignant tumours, the cause of which is mostly unknown. Orphan GPCRs (GPRs) have been previously implicated in tumour growth and metastasis. Therefore, these GPRs could prove to be alternative and promising therapeutic targets for cancer treatment.

Objective: The role of GPR160 in glioma has not yet been assessed. This study aims to explore the association of GPR160 with glioma progression and investigate its role in epithelial-to-mesenchymal transition (EMT) and metastasis.

Methods: Changes in protein expression were assessed using western blot analysis and immunofluorescent staining assays, while mRNA expression changes were evaluated using qRT-PCR. To detect the changes in progression and metastasis, MTT, EdU proliferation, wound healing, transwell migration, and flow cytometry assays were carried out in vitro. An epithelial to mesenchymal phenotypic analysis was performed to detect EMT.

Results: We demonstrated that knockdown of GPR160 inhibited proliferation, colony formation, and cell viability and promoted apoptosis. Pro-apoptotic biomarkers were upregulated, while anti-apoptotic biomarkers were downregulated. Cell lines with GPR160 knockdown (GPR160 KD) showed a slowed migration rate and decreased invasion ability. EMT mesenchymal biomarkers were downregulated in GPR160 KD cell lines, while epithelial biomarkers were upregulated.

Conclusion: This study provides evidence that GPR160 is a potential therapeutic target in glioma for the first time. These findings can be used to discover in detail the molecular mechanism and pathways through which GPR160 promotes glioma progression.
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http://dx.doi.org/10.1111/bcpt.13769DOI Listing
June 2022

Do Local Religious Beliefs Affect Firms' Earnings Management Practice? Evidence From the United States.

Front Psychol 2022 13;13:883596. Epub 2022 Jun 13.

Center for Quantitative Economics, Jilin University, Changchun, China.

This paper investigates whether local religious beliefs have a significant impact on the practice of earnings management. We extend the existing literature on the role of firm characteristics in mitigating earnings management by showing that local religious beliefs significantly impact the practice of earnings management. Specifically, exploring firms located in the U.S. counties that vary from 2000 through 2010, we document the negative relationship between religiosity and earnings management using multivariate regression analysis. Our results show that firms in counties with strong religious social norms are less likely to engage in earnings management. Furthermore, we attempt to mitigate endogeneity concerns by employing a modified Difference-Differences model and Propensity score matching methods. We find that the negative effects of religion on earnings management still hold. Overall, these findings emphasize the empirical relevance of the association between the local social norms and earnings manipulations.
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http://dx.doi.org/10.3389/fpsyg.2022.883596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234393PMC
June 2022

Edwardsiella tarda TraT is an anti-complement factor and a cellular infection promoter.

Commun Biol 2022 Jun 29;5(1):637. Epub 2022 Jun 29.

CAS & Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China.

Edwardsiella tarda is a well-known bacterial pathogen with a broad range of host, including fish, amphibians, and mammals. One eminent virulence feature of E. tarda is its strong ability to resist the killing of host serum complement, but the involving mechanism is unclear. In this report, we identified E. tarda TraT as a key player in both complement resistance and cellular invasion. TraT, a surface-localized protein, bound and recruited complement factor H onto E. tarda, whereby inhibiting complement activation via the alternative pathway. TraT also interacted with host CD46 in a specific complement control protein domain-dependent manner, whereby facilitating the cellular infection and tissue dissemination of E. tarda. Thus, by acting as an anti-complement factor and a cellular infection promoter, TraT makes an important contribution to the complement evasion and systemic infection of E. tarda. These results add insights into the pathogen-host interaction mechanism during E. tarda infection.
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http://dx.doi.org/10.1038/s42003-022-03587-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243006PMC
June 2022

Preparation and characterization of emamectin benzoate nanocapsules based on the dual role of polydopamine.

Pest Manag Sci 2022 Jun 29. Epub 2022 Jun 29.

School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, China.

Background: Developing pesticide-controlled release formulations with foliage adhesion has become the focus of current research in the field of crop protection. In this study, an excellent adhesive nanocapsule loaded with emamectin benzoate ([email protected]) was prepared via emulsion interfacial polymerization based on the self-polymerization ability and adhesion properties of polydopamine (PDA).

Results: The physicochemical properties of the [email protected] were characterized by scanning electron microscopy, transmission electron microscopy, particle size statistics, Fourier transform infrared spectroscopy and X-ray diffraction. The [email protected] presented a regular spherical shape, with an average particle size of 163.8 nm. Compared with conventional formulations, it had higher pesticide-loading content (34%) and excellent adhesion onto corn leaf. In addition, [email protected] showed sustained-release characteristics, facilitating the release of Eb at low pH and high temperature. [email protected] could effectively protect Eb against photodegradation and had a longer effective period for controlling Spodoptera frugiperda and Spodoptera exigua. Furthermore, acute toxicity tests showed that the 50% lethal concentration (LC ) was 80.91 and 57.91 mg kg at 7 and 14 days, respectively, indicating a lower toxicity of the [email protected] to earthworms. The cells (L02) treated with [email protected] showed a higher cell viability but a lower apoptosis rate (only 5.75%), demonstrating the lower cytotoxicity of the [email protected]

Conclusion: The self-prepared [email protected] could be used as a formulation with the advantages of slow release, UV shielding, strong leaf adhesion, superior insecticidal properties, sustained effectiveness and biosafety. It will also facilitate the development of an efficient and safe pesticide delivery system. © 2022 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.7061DOI Listing
June 2022

The diversity of elaborate petals in Isopyreae (Ranunculaceae): a special focus on nectary structure.

Protoplasma 2022 Jun 27. Epub 2022 Jun 27.

Key Laboratory of Medicinal Plant Resource and Natural Pharmaceutical Chemistry of Ministry of Education, Shaanxi Normal University, Xi'an, 710062, China.

Elaborate petals are highly diverse in morphology, structure, and epidermal differentiation and play a key role in attracting pollinators. There have been few studies on the elaborate structure of petals in the tribe Isopyreae (Ranunculaceae). Seven genera in Isopyreae (Aquilegia, Semiaquilegia, Urophysa, Isopyrum, Paraquilegia, Dichocarpum, and Leptopyrum) have petals that vary in morphology, and two genera (Enemion and Thalictrum) have no petals. The petals of nine species belonged to 7 genera in the tribe were studied to reveal their nectary structure, epidermal micromorphology and ancestral traits. The petal nectaries of Isopyreae examined in this study were located at the tip of spurs (Aquilegia yabeana and A. rockii), or the bottom of shallow sacs (Semiaquilegia adoxoides, Urophysa henryi, Isopyrum manshuricum, and Paraquilegia microphylla), a cup-shaped structure (Dichocarpum fargesii) and a bilabiate structure (Leptopyrum fumarioides). The petal nectary of eight species in Isopyreae (except A. ecalcarata) was composed of secretory epidermis, nectary parenchyma, and vascular tissues, and some sieve tubes reached the secretory parenchyma cells. Among the eight species with nectaries examined in the present study, A. yabeana had the most developed nectaries, with 10-15 layers of secretory parenchyma cells. The epidermal cells of mature petals of the nine species were divided into 11 types. Among these 11 types, there were two types of secretory cells and two types of trichomes. Aquilegia yabeana and A. rockii had the highest number of cell types (eight types), and I. manshuricum and L. fumarioides had the lowest number of cell types (three types). Aquilegia ecalcarata had no secretory cells, and the papillose conical polygonal secretory cells of D. fargesii were different from those of the other seven species with nectaries. Trichomes were found only in Aquilegia, Semiaquilegia, Urophysa, and Paraquilegia. The ancestral mode of nectar presentation in Isopyreae was petals with hidden nectar (70.58%). The different modes of nectar presentation in petals may reflect adaptations to different pollinators in Isopyreae.
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http://dx.doi.org/10.1007/s00709-022-01787-6DOI Listing
June 2022

TNFR2 is a regulatory target of pol-miR-194a and promotes the antibacterial immunity of Japanese flounder Paralichthys olivaceus.

Dev Comp Immunol 2022 Jun 22;135:104477. Epub 2022 Jun 22.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, CAS Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

MicroRNAs (miRNAs) are regulatory RNAs that modulate target gene expression after transcription. Pol-miR-194a had been reported to be a miRNA of Japanese flounder (Paralichthys olivaceus) involved in Edwardsiella tarda infection. Here, we identified tumor necrosis factor receptor 2 (TNFR2) as a target gene of pol-miR-194a. Pol-miR-194a markedly repressed the protein expression of flounder TNFR2 (PoTNFR2) via specific interaction with the 3'UTR of PoTNFR2. PoTNFR2 responded to E. tarda infection in a manner that was opposite to that of pol-miR-194a and inhibited E. tarda invasion by activating the NF-κB pathway. Consistently, dysregulation of PoTNFR2 had a significant impact on E. tarda dissemination in flounder tissues. Together, these results add new insights into the regulation mechanism and immune function of fish TNFR2 and pol-miR-194a.
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http://dx.doi.org/10.1016/j.dci.2022.104477DOI Listing
June 2022

Combined Transcriptomic and Proteomic Profiling to Unravel Osimertinib, CARP-1 Functional Mimetic (CFM 4.17) Formulation and Telmisartan Combo Treatment in NSCLC Tumor Xenografts.

Pharmaceutics 2022 May 28;14(6). Epub 2022 May 28.

College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.

The epidermal growth factor receptor (EGFR) is highly expressed in many non-small cell lung cancers (NSCLC), necessitating the use of EGFR-tyrosine kinase inhibitors (TKIs) as first-line treatments. Osimertinib (OSM), a third-generation TKI, is routinely used in clinics, but T790M mutations in exon 20 of the EGFR receptor lead to resistance against OSM, necessitating the development of more effective therapeutics. Telmisartan (TLM), OSM, and cell cycle and apoptosis regulatory protein 1 (CARP-1) functional mimetic treatments (CFM4.17) were evaluated in this study against experimental H1975 tumor xenografts to ascertain their anti-cancer effects. Briefly, tumor growth was studied in H1975 xenografts in athymic nude mice, gene and protein expressions were analyzed using next-generation RNA sequencing, proteomics, RT-PCR, and Western blotting. TLM pre-treatment significantly reduced the tumor burden when combined with CFM-4.17 nanoformulation and OSM combination (TLM_CFM-F_OSM) than their respective single treatments or combination of OSM and TLM with CFM 4.17. Data from RNA sequencing and proteomics revealed that TLM_CFM-F_OSM decreased the expression of Lamin B2, STAT3, SOD, NFKB, MMP-1, TGF beta, Sox-2, and PD-L1 proteins while increasing the expression of AMPK proteins, which was also confirmed by RT-PCR, proteomics, and Western blotting. According to our findings, the TLM_CFM-F_OSM combination has a superior anti-cancer effect in the treatment of NSCLC by affecting multiple resistant markers that regulate mitochondrial homeostasis, inflammation, oxidative stress, and apoptosis.
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http://dx.doi.org/10.3390/pharmaceutics14061156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230742PMC
May 2022
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