Publications by authors named "Yi Gong"

369 Publications

Discovery of 3-pyrazolyl-substituted pyrazolo[1,5-a]pyrimidine derivatives as potent TRK inhibitors to overcome clinically acquired resistance.

Eur J Med Chem 2022 Aug 5;241:114654. Epub 2022 Aug 5.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, 430079, PR China. Electronic address:

Several secondary tropomyosin receptor kinase (TRK) mutations located in the solvent front, xDFG, and gatekeeper regions, are a common cause of clinical resistance. Mutations in the xDFG motif in particular limit sensitivity to second-generation TRK inhibitors, which represent an unmet clinical need. We designed a series of 3-pyrazolyl-substituted pyrazolo[1,5-a]pyrimidine derivatives toward these secondary mutations using ring-opening and scaffold-hopping strategies. Compound 5n was the most potent, with IC values of 2.3 nM, 0.4 nM, and 0.5 nM against TRKA, TRKA, and TRKA, compared to selitrectinib with IC values of 12.6 nM, 5.8 nM, and 7.6 nM, respectively (approximately 5.4, 14.5, and 15.2-fold increases). Furthermore, 5n displayed favorable pharmacokinetic properties and satisfactory antitumor efficacy (tumor growth inhibition of 97% at 30 mg/kg and 73% at 100 mg/kg) in TRKA and TRKA xenograft mouse models. Collectively, 5n is a promising TRK inhibitor lead compound for overcoming clinically acquired resistance to second-generation inhibitors, particularly for resistant tumors harboring the TRKA mutation in the xDFG motif.
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http://dx.doi.org/10.1016/j.ejmech.2022.114654DOI Listing
August 2022

Distribution- and Metabolism-Based Drug Discovery: A Potassium-Competitive Acid Blocker as a Proof of Concept.

Research (Wash D C) 2022 22;2022:9852518. Epub 2022 Jul 22.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Conventional methods of drug design require compromise in the form of side effects to achieve sufficient efficacy because targeting drugs to specific organs remains challenging. Thus, new strategies to design organ-specific drugs that induce little toxicity are needed. Based on characteristic tissue niche-mediated drug distribution (TNMDD) and patterns of drug metabolism into specific intermediates, we propose a strategy of distribution- and metabolism-based drug design (DMBDD); through a physicochemical property-driven distribution optimization cooperated with a well-designed metabolism pathway, SH-337, a candidate potassium-competitive acid blocker (P-CAB), was designed. SH-337 showed specific distribution in the stomach in the long term and was rapidly cleared from the systemic compartment. Therefore, SH-337 exerted a comparable pharmacological effect but a 3.3-fold higher no observed adverse effect level (NOAEL) compared with FDA-approved vonoprazan. This study contributes a proof-of-concept demonstration of DMBDD and provides a new perspective for the development of highly efficient, organ-specific drugs with low toxicity.
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http://dx.doi.org/10.34133/2022/9852518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343080PMC
July 2022

Rab11a-Regulated Exosomes Inhibit Bacterial Infection through the Activation of Antilipopolysaccharide Factors in Crustaceans.

J Immunol 2022 Aug 27;209(4):710-722. Epub 2022 Jul 27.

Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China;

Exosomes, secreted by most cells, are critical antimicrobial immune factors in animals. Recent studies of certain key regulators of vesicular transport, the Rab GTPases, have linked Rab dysfunction to regulation of innate immune signaling. However, the relationship between exosomes and Rab GTPases, resulting in antimicrobial activity in vertebrates and invertebrates during pathogenic infection, has not been addressed. In this study, Rab11a was reported to have a protective effect on the survival rate of mud crabs after s challenge through the stimulation of exosome secretion and modulation of anti-LPS factor (ALF) expression. Furthermore, 14-3-3 was confirmed to be densely packaged in exosomes after s infection, which could recruit the MyD88 and TLR by binding the Toll/IL-1R domain to the plasma membrane, promoting the translocation of Dorsal from the cytoplasm into the nucleus, and thereby regulating ALFs expression in the hemocytes of mud crab in response to the bacterial infection. The findings therefore provide, to our knowledge, a novel mechanism that underlies the cross-talk between Rab11a-regulated exosome formation and ALFs expression in innate immune response in invertebrates, with a crustacean species, mud crab , as a model study.
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http://dx.doi.org/10.4049/jimmunol.2200094DOI Listing
August 2022

Fungicidal Activity of AP10W, a Short Peptide Derived from AP-2 Complex Subunit mu-A, In Vitro and In Vivo.

Biomolecules 2022 07 10;12(7). Epub 2022 Jul 10.

Department of Marine Biology, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.

With the increase in the incidence of fungal infections, and the restrictions of existing antifungal drugs, the development of novel antifungal agents is urgent. Here we prove that AP10W, a short peptide derived from AP-2 complex subunit mu-A, displays conspicuous antifungal activities against the main fungal pathogens of human infections and . We also show that AP10W suppresses the fungal biofilm formation, and reduces the pre-established fungal biofilms. AP10W appears to exert its fungicidal activity through a mode of combined actions, including interaction with the fungal cell walls via laminarin, mannan and chitin, enhancement of cell wall permeabilization, induction of membrane depolarization, and increase in intracellular ROS generation. Importantly, we demonstrate that AP10W exhibits little toxicity towards mammalian fibroblasts, and effectively promotes the healing of wounded skins infected by . These together indicate that AP10W is a new member of fungicidal agents. It also suggests that AP10W has a considerable potential for future development as a novel antifungal drug.
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http://dx.doi.org/10.3390/biom12070965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313395PMC
July 2022

Effect of body size, feeding ecology and maternal transfer on mercury accumulation of vulnerable silky shark Carcharhinus falciformis in the eastern tropical pacific.

Environ Pollut 2022 Sep 11;309:119751. Epub 2022 Jul 11.

College of Marine Sciences, Shanghai Ocean University, Shanghai, China; Key Laboratory of Sustainable Exploitation of Oceanic Fisheries Resources, Ministry of Education, Shanghai, China; National Engineering Research Centre for Oceanic Fisheries, Shanghai Ocean University, Shanghai, China; Key Laboratory of Oceanic Fisheries Exploration, Ministry of Agriculture and Rural Affairs, Shanghai, China. Electronic address:

The silky shark Carcharhinus falciformis is a large pelagic species distributed in the global oceans and was recently listed as "Vulnerable" by the IUCN because of its decline in population due to overfishing. As an apex predator, the silky shark can accumulate elevated quantities of mercury (Hg), posing a potential risk to its remaining population. In this study, total Hg (THg) concentrations were determined in silky shark muscle, liver, dermis, red blood cells (RBC) and plasma sampled from the eastern tropical Pacific, and δN values were measured to explore the influence of feeding ecology on Hg accumulation. The highest THg concentrations were in muscle (7.81 ± 6.70 μg g dry weight (dw) or 2.14 ± 1.83 μg g wet weight (ww)) and liver (7.88 ± 10.22 μg g dw or 4.66 ± 6.04 μg g ww) rather than dermis, RBC and plasma. The THg concentrations in all tissue types were significantly correlated with fork length and showed faster accumulation rates after maturity. Maternal THg transfer was observed in silky sharks with embryos having 33.16% and 1.98% in muscle and liver compared with their respective mothers. The potentially harmful THg concentrations in silky shark tissues and embryos may lead to health problems of sharks and consumers. THg concentrations were negatively correlated with δN values for all tissues, indicating likely baseline variations in δN values that reflect changes in the foraging habitats or regions of silky sharks with size or age. Lastly, strong correlations were observed among THg concentrations of all tissue types, indicating that nonlethal sampling of muscle and dermis tissue can be used effectively to quantify THg concentration of other internal tissues.
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http://dx.doi.org/10.1016/j.envpol.2022.119751DOI Listing
September 2022

Strategies and characterization methods for achieving high performance PEO-based solid-state lithium-ion batteries.

Chem Commun (Camb) 2022 Jul 21;58(59):8182-8193. Epub 2022 Jul 21.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

Polyethylene oxide (PEO) based polymer electrolytes have been widely used in solid-state lithium batteries (SSBs) owing to the high solubility of lithium salt, favourable ionic conductivity, flexibility for improved interfacial contact and scalable processing. In this work, we summarize the main limitations remaining to be solved before the large-scale commercialization of PEO-based SSBs, including (1) improving ionic conductivity toward high-rate performance and lower operating temperature, (2) enhancing mechanical strength for improved lithium dendrite resistance and large-scale processing, (3) strengthening electrochemical stability to match high energy density electrodes with high voltage, and (4) achieving high thermal stability toward safe operation. Meanwhile, the characterization methods to investigate the ion transportation mechanism, lithium dendrite growth and decomposition reaction are also discussed.
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http://dx.doi.org/10.1039/d2cc02306gDOI Listing
July 2022

Diagnostic classification of cancers using DNA methylation of paracancerous tissues.

Sci Rep 2022 Jun 23;12(1):10646. Epub 2022 Jun 23.

Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.

The potential role of DNA methylation from paracancerous tissues in cancer diagnosis has not been explored until now. In this study, we built classification models using well-known machine learning models based on DNA methylation profiles of paracancerous tissues. We evaluated our methods on nine cancer datasets collected from The Cancer Genome Atlas (TCGA) and utilized fivefold cross-validation to assess the performance of models. Additionally, we performed gene ontology (GO) enrichment analysis on the basis of the significant CpG sites selected by feature importance scores of XGBoost model, aiming to identify biological pathways involved in cancer progression. We also exploited the XGBoost algorithm to classify cancer types using DNA methylation profiles of paracancerous tissues in external validation datasets. Comparative experiments suggested that XGBoost achieved better predictive performance than the other four machine learning methods in predicting cancer stage. GO enrichment analysis revealed key pathways involved, highlighting the importance of paracancerous tissues in cancer progression. Furthermore, XGBoost model can accurately classify nine different cancers from TCGA, and the feature sets selected by XGBoost can also effectively predict seven cancer types on independent GEO datasets. This study provided new insights into cancer diagnosis from an epigenetic perspective and may facilitate the development of personalized diagnosis and treatment strategies.
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http://dx.doi.org/10.1038/s41598-022-14786-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226137PMC
June 2022

The Role of Thyroglobulin in Preoperative and Postoperative Evaluation of Patients With Differentiated Thyroid Cancer.

Front Endocrinol (Lausanne) 2022 2;13:872527. Epub 2022 Jun 2.

Department of Thyroid Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.

Thyroglobulin (Tg) is secreted by thyroid follicular cells and stored in the thyroid follicular lumen as a component of thyroid hormone. It is known that both benign and well-differentiated malignant thyroid tissue can secrete Tg. In recent years, growing lines of evidence have shown that Tg plays an important role in the diagnosis and metastasis of preoperative differentiated thyroid carcinoma (DTC). The levels of Tg, whether in the serum or in a fine-needle aspiration washout fluid, are usually viewed as an excellent indicator in the monitoring of postoperative DTC, including the guidance and evaluation of radioactive iodine ablation. Nevertheless, some factors limit the application of Tg, such as the method used to measure Tg and the presence of Tg antibodies. This review aimed to summarize the role of Tg in the preoperative and postoperative evaluation of patients with DTC, and the factors influencing Tg. This review could provide a reference for a more accurate application of Tg in patients with DTC.
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http://dx.doi.org/10.3389/fendo.2022.872527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200986PMC
June 2022

Double-drug loading upconversion nanoparticles for monitoring and therapy of a MYC/BCL6-positive double-hit diffuse large B-cell lymphoma.

Biomaterials 2022 May 31;287:121607. Epub 2022 May 31.

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, China. Electronic address:

Diffuse large B-cell lymphoma (DLBCL) is a systemic hematological malignancy. Herein, through whole exome sequencing (WES), we found that DLBCL genome changes and expression characteristics are associated with various immune cells. Lenalidomide (Len) is a leading candidate for the immunomodulatory treatment of multiple myeloma in the clinic. Inspired by lenalidomide as an immunomodulatory drug for the treatment of multiple myeloma, we constructed a multifunctional nanoplatform with therapeutic and imaging properties for DLBCL by co-loading lenalidomide and dexamethasone (Dex) with upconversion nanoparticles using a GSH-sensitive linker (named as UCNPs-Len-Dex). In vitro cell experiments proved that the UCNPs-Len-Dex had good biocompatibility and obvious antitumor efficacy. UCNPs-Len-Dex also exhibited excellent anti-tumor efficacy and imaging properties in vivo. RNA sequencing showed that UCNPs-Len-Dex targeted and activated the E3 ligase of CRBN, resulting in IKZF1/3 degradation, which inhibited MYC/BCL6-positive DLBCL and maintained the stability of the immune microenvironment. Therefore, this study provided a new monitoring and therapeutic synergetic strategy for DLBCL.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121607DOI Listing
May 2022

Simvastatin inhibits prostatic hyperplasia in rats with metabolic syndrome.

Int Urol Nephrol 2022 Sep 13;54(9):2125-2131. Epub 2022 Jun 13.

Department of Urology, Anhui Provincial Hospital, First Affiliated Hospital of University of Science and Technology of China, 17#, Lujiang Rd, Hefei, 230001, China.

Objects: To evaluate the influence of metabolic syndrome (MetS) induced by high fat diet (HFD) on prostate tissue and local inflammatory factors in rats model, and the protective efficacy of statins against pathological changes of prostate.

Methods: 40 Sprague-Dawley rats were divided into 4 subgroups of normal diet (ND), HFD blank, HFD + saline and HFD + simvastatin. After the establishment of models, all subjects were killed to obtain body weight serum lipid, FBG level, FINS and HOMA-IR level. Hyperplasia level of prostate, as well as expression level of interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-α) were also measured.

Results: Models have been successfully established. Level of serum lipid, prostatic weight, hyperplasia as well as expressions of IL-6, TNF-α and IGF-1 in the blank and saline subgroups of HFD group were higher than that of ND group (P < 0.05). While simvastatin has significantly resisted the former effects of HFD on serum lipid and prostate (P < 0.05). No significant difference in serum FBG level was found between groups and subunits. FINS levels of ND group was lower than other groups (P < 0.05). In addition, There is no significant difference in FPG and HOMA-IR levels in blank control subunit, saline control subunit, simvastatin subunit (P > 0.05).

Conclusions: MetS induced by HFD is an important factor in the induction of BPH. Simvastatin can alleviate the hyperplasia of prostate through the relief of local inflammation in prostatic tissue.
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http://dx.doi.org/10.1007/s11255-022-03227-zDOI Listing
September 2022

Peroxisome Metabolism Contributes to PIEZO2-Mediated Mechanical Allodynia.

Cells 2022 06 4;11(11). Epub 2022 Jun 4.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Mutations in the peroxisomal half-transporter ABCD1 cause X-linked adrenoleukodystrophy, resulting in elevated very long-chain fatty acids (VLCFA), progressive neurodegeneration and an associated pain syndrome that is poorly understood. In the nervous system of mice, we found ABCD1 expression to be highest in dorsal root ganglia (DRG), with satellite glial cells (SGCs) displaying higher expression than neurons. We subsequently examined sensory behavior and DRG pathophysiology in mice deficient in ABCD1 compared to wild-type mice. Beginning at 8 months of age, mice developed persistent mechanical allodynia. DRG had a greater number of IB4-positive nociceptive neurons expressing PIEZO2, the mechanosensitive ion channel. Blocking PIEZO2 partially rescued the mechanical allodynia. Beyond affecting neurons, ABCD1 deficiency impacted SGCs, as demonstrated by high levels of VLCFA, increased glial fibrillary acidic protein (GFAP), as well as genes disrupting neuron-SGC connectivity. These findings suggest that lack of the peroxisomal half-transporter ABCD1 leads to PIEZO2-mediated mechanical allodynia as well as SGC dysfunction. Given the known supportive role of SGCs to neurons, this elucidates a novel mechanism underlying pain in X-linked adrenoleukodystrophy.
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http://dx.doi.org/10.3390/cells11111842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180358PMC
June 2022

Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China.

Arthritis Res Ther 2022 05 30;24(1):129. Epub 2022 May 30.

School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi, 710061, People's Republic of China.

Background: Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients.

Methods: Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed.

Results: The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing.

Conclusion: Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.
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http://dx.doi.org/10.1186/s13075-022-02819-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150333PMC
May 2022

Translation and validation of the Chinese version of Patient-completed Asthma Knowledge Questionnaire and its implementation in patient education.

J Thorac Dis 2022 Apr;14(4):905-918

Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Poor control of asthma results from many factors, partly due to inadequate knowledge towards asthma among patients. It is necessary to know patients' knowledge level before education. However, there is no accepted instrument to evaluate knowledge of asthma in Chinese patients with asthma. The study aims to develop a Chinese version of Patient-completed Asthma Knowledge Questionnaire (PAKQ) to assess its reliability, validity, and responsiveness for testing its clinical application in Chinese adult patients with asthma.

Methods: After translation, back-translation, and cross-cultural adaptation of the PAKQ into Chinese version, a survey of patients with asthma (n=464) in China was conducted. Demographics and clinical data were collected in addition to questionnaires concerning cognition of asthma, education, history, and asthma control test score. The PAKQ was then completed. 14±4 days after the initial assessment, the participants completed the retested questionnaire and again completed the questionnaire immediately after education. The reliability and the construct validity were evaluated. The optimal cut-off points for predicting disease knowledge among asthma patients were determined using the Youden index method.

Results: The Chinese version of PAKQ showed high internal consistency (Cronbach's alpha =0.888) at baseline and an acceptable 2-week test-retest reliability (ICC =0.932, r=0.874). On the basis of large modification indices (>10), this four-factor questionnaire was found to fit the data satisfactorily (χ/df =1.695, RMSEA =0.039, GFI =0.856, CFI =0.885, and SRMR =0.058). Paired -tests showed significant changes on pre-educational and post-educational tests (t=22.83, df=463, P<0.0001). The optimal cut-off value of the PAKQ total score for assessing patients' knowledge level was 35 points (AUC =0.757).

Conclusions: The Chinese version of the PAKQ questionnaire was developed and validated in terms of reliability and validity as an effective instrument for the insight into asthma knowledge of adult patients with asthma in China. Future research will evaluate the utility of the instrument in clinical practice.
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http://dx.doi.org/10.21037/jtd-21-1604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096276PMC
April 2022

Investigation of selenium nutritional status and dietary pattern among children in Kashin-Beck disease endemic areas in Shaanxi Province, China using duplicate portion sampling method.

Environ Int 2022 06 22;164:107255. Epub 2022 Apr 22.

School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, 710061, PR China; Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address:

Background And Objectives: Selenium deficiency is a primary risk factor of Kashin-Beck disease (KBD). This study aimed to investigate whether children in endemic areas could maintain sufficient selenium intake after termination of selenium supplement administration, and evaluate their comprehensive nutritional status and dietary structure.

Methods: Duplicate portion sampling combined with a questionnaire was adopted to collect data on categories and quantity of all food ingested in three consecutive days. Occipital hair was also collected to detect selenium content by hydride generation atomic fluorescence spectrometry (HGAFS). CDGSS3.0 software and factor analysis were integrated to assess the children's comprehensive nutritional status and dietary structure.

Results: This study included 240 sex-matched (1:1) children aged 7-12 years from KBD endemic (n = 120) and non-endemic (n = 120) areas. Overall, 720 solid food, 720 liquid, and 240 hair samples were collected for selenium determination. The mean selenium level in hair of children in endemic areas (0.38 ± 0.16 mg/kg) was significantly lower than that in children in non-endemic areas (0.56 ± 0.28 mg/kg, Z = -5.249, p < 0.001). The dietary selenium intake of children in endemic areas was 40.0% lower than that in children in non-endemic areas (Z = -9.374, p < 0.001). Children in endemic areas consumed significantly less diverse dietary items leading to significantly less intake of multiple nutrients compared to children in non-endemic areas.

Conclusions: The dietary selenium intake of most children in endemic areas was less than the recommended amount. The dietary structure of children was undiversified, which limited the intake of multiple nutrients. Therefore, comprehensive nutrition rather than sole selenium intake should be the primary concern in the future.
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http://dx.doi.org/10.1016/j.envint.2022.107255DOI Listing
June 2022

The biofunctionalization of titanium nanotube with chitosan/genipin heparin hydrogel and the controlled release of IL-4 for anti-coagulation and anti-thrombus through accelerating endothelialization.

RSC Adv 2021 Apr 5;11(27):16510-16521. Epub 2021 May 5.

Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University No. 1 Minde Road Nanchang 330006 Jiangxi China +86 137 6711 7511.

The valve replacement is the main treatment of heart valve disease. However, thrombus formation following valve replacement has always been a major clinical drawback. Accelerating the endothelialization of cardiac valve prosthesis is the main approach to reduce thrombus. In the current study, a titanium nanotube was biofunctionalized with a chitosan/genipin heparin hydrogel and the controlled release of interleukin-4 (IL-4), and its regulation of macrophages was investigated to see if it could influence endothelial cells to eventually accelerate endothelialization. TNT60 (titanium dioxide nanotubes, 60 V) with nanoarray was obtained by anodic oxidation of 60 V, and IL-4 was loaded into the nanotube by vacuum drying. The hydrogel (chitosan : genipin = 4 : 1) was applied to the surface of the nanotubes following drying, and the heparin drops were placed on the hydrogel surface with chitosan as the polycation and heparin as the polyanion. A TNT/IL-4/G (G = gel, chitosan/genipin heparin) delivery system was prepared. Our results demonstrated that the biofunctionalization of titanium nanotube with chitosan/genipin heparin hydrogel and the controlled release of IL-4 had a significant regulatory effect on macrophage M2 polarization, reducing the inflammatory factor release and higher secretion of VEGF (vascular endothelial growth factor), which can accelerate the endothelialization of the implant.
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http://dx.doi.org/10.1039/d0ra09295aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031326PMC
April 2021

The Status of Selenium and Zinc in the Urine of Children From Endemic Areas of Kashin-Beck Disease Over Three Consecutive Years.

Front Nutr 2022 8;9:862639. Epub 2022 Apr 8.

Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Selenium deficiency is one of the main risk factors for Kashin-Beck disease (KBD). This study aimed to detect the status of selenium and zinc in the urine of children from endemic areas of KBD over three consecutive years and to evaluate whether selenium and zinc levels in children in Shaanxi Province remain normal after stopping selenium supplementation. The samples of urine were collected in consecutive years (2017-2019) to detect selenium content by hydride generation atomic fluorescence spectrometry (HGAFS) and to detect zinc content by atomic absorption spectrophotometry (AAS). Generalized estimation equation (GEE) analysis was integrated to assess the comprehensive nutritional status and dietary structure of children. Data were processed in duplicate and analyzed by SPSS 18.0. This study included 30 X-ray-positive KBD cases and 123 healthy children aged 7-12 years. A total of 424 urine and 137 hair samples were collected over three consecutive years for selenium determination. The mean value of urinary selenium in all subjects was 6.86 μg/l (2017), 8.26 μg/l (2018), and 4.04 μg/l (2019), and the mean value of urinary zinc in all subjects was 0.36 mg/l (2017), 0.39 mg/l (2018), and 0.31 mg/l (2019) for the three consecutive years of 2017-2019. The mean values of urinary selenium were 6.56 and 6.94 μg/l (2017), 8.69 and 8.14 μg/l (2018), and 4.57 and 3.90 μg/l (2019) in the KBD-X and normal groups, respectively; and the mean value of urinary zinc were 0.38 and 0.35 mg/l (2017), 0.41 and 0.39 mg/l (2018), and 0.43 and 0.28 mg/l (2019) in the KBD-X and normal groups, respectively. The mean value of hair selenium in 137 subjects was 275.08 μg/kg and the mean values of hair selenium were 267.48 and 276.61 μg/kg in the KBD-X group and normal group, respectively. The level of selenium/zinc showed a trend of increasing first and then decreasing during the three consecutive years. The level of selenium in all subjects from the endemic areas was lower than normal, which reminds us to monitor the state of KBD constantly and adjust selenium salt supplementation in accordance with the changes in the KBD state.
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http://dx.doi.org/10.3389/fnut.2022.862639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033266PMC
April 2022

A Survey on Artificial Intelligence Aided Internet-of-Things Technologies in Emerging Smart Libraries.

Sensors (Basel) 2022 Apr 13;22(8). Epub 2022 Apr 13.

Commonwealth Scientific and Industrial Research Organisation, Sydney, NSW 2122, Australia.

With the boom in artificial intelligence (AI) and Internet-of-Things (IoT), thousands of smart devices are interconnected with each other and deeply applied into human society. This prosperity has significantly improved public service and management, which were traditionally based on manual work. As a notable scenario, librarianship has embraced an era of "Smart Libraries" enabled by AI and IoT. Unlike existing surveys, our work comprehensively overviews the AI- and IoT-based technologies in three fundamental aspects: smart service, smart sustainability, and smart security. We then further highlight the trend towards future smart libraries.
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http://dx.doi.org/10.3390/s22082991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029361PMC
April 2022

Value of Contrast-Enhanced Ultrasound in Mummified Thyroid Nodules.

Front Endocrinol (Lausanne) 2022 18;13:850698. Epub 2022 Mar 18.

Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, China.

Mummified thyroid nodules (MTNs) are rarely reported and are usually misdiagnosed as malignant nodules. This article first reviewed the contrast-enhanced ultrasound (CEUS) enhancement features of 218 MTNs and classified them into three (A, B, C) patterns. The A pattern MTNs show linear hypo-enhancement, the B pattern MTNs show heterogeneous hypo-enhancement, and the C pattern MTNs show no enhancement in thyroid nodules. The A and C pattern enhancements of MTNs demonstrated a high specificity compared with the enhancement of previously reported typical papillary thyroid carcinomas (PTCs). To further study the B pattern MTNs, 24 B pattern MTNs and 42 PTCs were enrolled in this study, and CEUS parameters for each nodule were evaluated. Univariate analysis indicated that compared with PTCs, the B pattern MTNs more frequently exhibited heterogeneous hypo-enhancement and clear margins after clearance (p <0.05). A multivariate analysis revealed that heterogeneous hypo-enhancement and clear margins after clearance were independent characteristics related to the B pattern MTNs for differentiating them from PTCs (p <0.05). Thus, preoperative CEUS may provide more important information for distinguishing MTNs from malignant thyroid nodules to avoid surgical excisions or unnecessary fine-needle aspiration (FNA).
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http://dx.doi.org/10.3389/fendo.2022.850698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971290PMC
April 2022

LncRNA NEAT1 knockdown ameliorates LPS-induced human kidney injury by mediating the miR-330-5p/FOXO3 axis.

Int Urol Nephrol 2022 Apr 1. Epub 2022 Apr 1.

Department of Cardiology and Macrovascular Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi, China.

Background: Sepsis is a systemic process with multiple inflammatory responses and organ injuries, particularly in the damage of the kidney. Recently, numerous studies suggest that long non-coding RNAs (lncRNAs) are involved in sepsis-related kidney injury. This study aimed to investigate the functional role and mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in sepsis-related kidney injury.

Methods: Cell model of kidney injury was constructed in human kidney 2 (HK-2) cells with the treatment of lipopolysaccharide (LPS). The expression of NEAT1 was measured by quantitative real-time PCR (qRT-PCR). Cell viability was examined using CCK-8 assay. Flow cytometry was performed to detect cell apoptosis, and apoptosis-related proteins were quantified by western blot. The release of proinflammatory cytokines was assessed by ELISA. Oxidative stress was assessed by the levels of SOD and MDA using kits. The putative relationship between miR-330-5p and NEAT1 or FOXO3 was confirmed using dual-luciferase reporter assay, RIP assay and pull-down assay.

Result: The expression of NEAT1 was increased in LPS-treated HK-2 cells. LPS exposure promoted apoptotic rate, inflammatory responses and oxidative stress in HK-2 cells, which were largely ameliorated by NEAT1 knockdown. MiR-330-5p was verified as a target of NEAT1, and miR-330-5p inhibition reversed the effects of NEAT1 knockdown in LPS-treated HK-2 cells. Moreover, FOXO3 was a target of miR-330-5p, and miR-330-5p restoration-blocked cell apoptosis, inflammation and oxidative stress in LPS-treated HK-2 cells were recovered by FOXO3 overexpression.

Conclusion: NEAT1 downregulation meliorated LPS-induced HK-2 cell injuries partly by regulating the miR-330-5p/FOXO3 pathway.
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http://dx.doi.org/10.1007/s11255-022-03179-4DOI Listing
April 2022

[Microplastics in the stomach and intestine of pelagic squid: A case study of in open sea of Peru].

Ying Yong Sheng Tai Xue Bao 2022 Jan;33(1):255-260

College of Marine Sciences, Shanghai Ocean University, Shanghai 201306, China.

Microplastic (MP) ingestion by marine animals has been well documented, but less being known about pelagic squid. Jumbo squid supports the world's largest cephalopod fishery and plays an important ecological role in the Eastern Pacific Ocean. In this study, taken from the open sea of the Peruvian Exclusive Economic Zone were selected as research objects. We estimated the abundance and characteristics of MPs in the stomach and intestine of and investigated the differences between tissues and sexes. Similar abundance and characteristics of MPs were observed in the same tissue of females and males. However, the stomach had a higher abundance of MPs with larger size than the intestine, while the MP abundance by stomach wet weight was lower than that of the intestine. The MPs were predominantly fiber-shaped, with blue or black color. The most frequent polymers were high-density cellophane and polyacrylic acid. These polymers could sink into deeper sea layers and were available for living there during the daytime. Our findings revealed the distribution pattern of MPs in the waters of the Peruvian fishing ground. This study could improve our understanding of the MP contamination level in pelagic squid, and have implications for evaluating the ecological effects of MP on cephalopods.
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http://dx.doi.org/10.13287/j.1001-9332.202201.038DOI Listing
January 2022

Value of Contrast-Enhanced Ultrasound for Evaluation of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Front Endocrinol (Lausanne) 2022 3;13:812475. Epub 2022 Feb 3.

Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, China.

The aim of the study was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in distinguishing between benign and malignant cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). Two hundred and one cervical LNs (157 metastatic from PTC and 44 benign) were evaluated using conventional ultrasonography (US) and CEUS before biopsy or surgery. Histopathology was used as the gold standard. We evaluated the size, long axis/short axis ratio (L/S), fatty hilum, hyper-echogenicity, calcification, cystic change, peripheral vascularity and CEUS parameters for each lymph nodule. The CEUS parameters included enhancement type, homogeneity, perfusion type, ring enhancement, peak intensity (PI) index and area under the curve (AUC) index. Univariate analysis demonstrated that compared with benign LNs, malignant LNs more frequently had L/S < 2, absence of a fatty hilum, presence of hyper-echogenicity, presence of calcification, peripheral vascularity, hyper-enhancement, heterogeneous enhancement, centripetal perfusion, ring enhancement, PI index > 1 and AUC index > 1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that hyper-enhancement, centripetal perfusion, and ring enhancement are independent CEUS characteristics related to malignant LNs for their differentiation from benign LNs (all p < 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to identify malignant cervical LNs from benign cervical LNs.
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http://dx.doi.org/10.3389/fendo.2022.812475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850786PMC
March 2022

In vitro and in vivo wound healing-promoting activities of phosvitin-derived peptide Pt5-1c.

Eur J Pharmacol 2022 Apr 17;920:174833. Epub 2022 Feb 17.

Department of Marine Biology, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, 266003, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266003, China. Electronic address:

The closure of skin wounds is indispensable for resistance against pathogens, and fibroblast plays a critical role in skin wound healing. Our previous study demonstrates that the phosvitin-derived small peptide Pt5-1c not only possesses broad-spectrum antimicrobial activity but also exhibits synergistic effect and antibiofilm activity with traditional antibiotics against bacteria, including multi-drug resistant (MDR) strains. Here we provided the first evidence that Pt5-1c promoted the wound closure of surrogate scratch "wounds" of fibroblasts in vitro, and speeded up the healing and re-epithelialization of murine dermal wounds in vivo. We also showed that Pt5-1c activated migration of fibroblasts via a combined action of inducing migratory phenotype and trans-activating epidermal growth factor receptor (EGFR). Moreover, Pt5-1c accelerated attachment and proliferation of fibroblasts in vitro. Interestingly, Pt5-1c was able to promote collagen contraction through activation/differentiation of fibroblasts into myofibroblasts. These data together suggest that Pt5-1c is a promising candidate with therapeutic potential to promote wound healing.
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http://dx.doi.org/10.1016/j.ejphar.2022.174833DOI Listing
April 2022

Comparison of globular albumin methacryloyl and random-coil gelatin methacryloyl: Preparation, hydrogel properties, cell behaviors, and mineralization.

Int J Biol Macromol 2022 Apr 10;204:692-708. Epub 2022 Feb 10.

Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325011, China; Oujiang Laboratory (Zhejiang Lab for Rengerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China. Electronic address:

Bovine serum albumin methacryloyl (BSAMA) is a newly emerging photocurable globular protein-based material whereas gelatin methacryloyl (GelMA) is one of the most popular photocurable fibrous protein-based materials. So far, the influence of their different structural conformations as building blocks on hydrogel properties and mineral deposition has not been investigated. Here, we compared their differences in structures, gelation kinetics, hydrogel properties, mineralization, and cell behaviors. BSAMA maintained a stable globular structure while GelMA exhibited temperature-sensitive conformations (4 - 37 °C). BSAMA displayed slower gelation kinetics and much more retarded enzymatic degradation compared to GelMA. Photocurable BSAMA (6.41 - 390.95 kPa) and GelMA hydrogels (36.09 - 199.70 kPa) exhibited tunable mechanical properties depending on their concentrations (10 - 20%). Interestingly, BSAMA hydrogels mineralized needle-like apatite (Ca/P: 1.409) with higher crystallinity compared to GelMA hydrogels (Ca/P: 1.344). BSAMA and GelMA supported satisfactory cell (MC3T3-L1) viability of 99.43 ± 0.57% and 97.14 ± 0.69%, respectively. However, BSAMA gels were less favorable to cell proliferation and migration than GelMA gels. In serum-free environments, cells on GelMA displayed a higher amount of attachment, a more elongated shape, and a longer protrusion compared to those on BSAMA (p < 0.01) during the early adhesion.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.02.028DOI Listing
April 2022

Retrospective stable isotopes of vertebrae reveal sexual ontogenetic patterns and trophic ecology in oceanic whitetip shark, .

Ecol Evol 2022 Jan 23;12(1):e8452. Epub 2021 Dec 23.

College of Marine Sciences Shanghai Ocean University Shanghai China.

There is a common phenomenon in nature whereby some animals have differences in their ontogenetic changes in dietary preferences between sexes, especially apex predators. These reflect changes in the needs of development during their lifetimes. Apex predators potentially have diverse dietary niches and a large impact on the trophic dynamics within ecosystems. However, the difference in life history between males and females often leads to increased difficulty in management and conservation. In this study, 25 oceanic whitetip sharks, , were collected from the central and eastern tropical Pacific. Retrospective stable isotope analysis of vertebrae was used to evaluate the potential ontogenetic differences in feeding habits and niche width between sexes. Results showed that had a wide range of δC values (-18.1 to -12.3‰) and δN values (8.9-14.8‰). However, males and females had similar trophic positions with large niche overlap at similar growth stages. Both sexes had increasing δC values but relatively constant δN values along the vertebrae. These results indicated that male and female may share similar feeding strategies and movement patterns. The results presented in this study enhance our understanding of sexual ontogenetic patterns and ecological role of and highlighted the applicability of vertebrae for characterizing shark life-history traits.
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http://dx.doi.org/10.1002/ece3.8452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796903PMC
January 2022

Higher Damping Capacities in Gradient Nanograined Metals.

Nano Lett 2022 Feb 3;22(4):1491-1496. Epub 2022 Feb 3.

Department of Aeronautics and Astronautics, Fudan University, Shanghai 200433, China.

The capability of damping mechanical energy in polycrystalline metals depends on the activities of defects such as dislocation and grain boundary (GB). However, operating defects has the opposite effect on strength and damping capacity. In the quest for high damping metals, maintaining the level of strength is desirable in practice. In this work, gradient nanograined structure is considered as a candidate for high-damping metals. The atomistic simulations show that the gradient nanograined models exhibit enhanced damping capacities compared with the homogeneous counterparts. The property can be attributed to the long-range order of GB orientations in gradient grains, where shear stresses facilitate GB sliding. Combined with the extraordinary mechanical properties, the gradient structure achieves a strength-ductility-damping synergy. The results provide promising solutions to the conflicts between mechanical properties and damping capacity in polycrystalline metals.
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http://dx.doi.org/10.1021/acs.nanolett.1c03600DOI Listing
February 2022

p53 Ubiquitination Comediated by HUWE1 and TRAF6 Contributes to White Spot Syndrome Virus Infection in Crustacean.

J Virol 2022 03 2;96(6):e0202921. Epub 2022 Feb 2.

Guangdong Provincial Key Laboratory of Marine Biology, Shantou Universitygrid.263451.7, Shantou, China.

p53, the guardian of the genome, is a short-lived protein that is tightly controlled at low levels by constant ubiquitination and proteasomal degradation in higher organisms. p53 stabilization and activation are early crucial events to cope with external stimuli in cells. However, the role of p53 ubiquitination and its relevant molecular mechanisms have not been addressed in invertebrates. In this study, our findings revealed that both HUWE1 (HECT, UBA, and WWE domain-containing E3 ubiquitin-protein ligase 1) and TRAF6 (tumor necrosis factor receptor-associated factor 6) could serve as E3 ubiquitin ligases for p53 in mud crabs (Scylla paramamosain). Moreover, the expression of HUWE1 and TRAF6 was significantly downregulated during white spot syndrome virus (WSSV) infection, and therefore the ubiquitination of p53 was interrupted, leading to the activation of apoptosis and reactive oxygen species (ROS) signals through p53 accumulation, which eventually suppressed viral invasion in the mud crabs. To the best of our knowledge, this is the first study to reveal the p53 ubiquitination simultaneously induced by two E3 ligases in arthropods, which provides a novel molecular mechanism of invertebrates for resistance to viral infection. p53, which is a well-known tumor suppressor that has been widely studied in higher animals, has been reported to be tightly controlled at low levels by ubiquitin-dependent proteasomal degradation. However, recent p53 ubiquitination-relevant research mainly involved an individual E3 ubiquitin ligase, but not whether there exist other mechanisms that need to be explored. The results of this study show that HUWE1 and TRAF6 could serve as p53 E3 ubiquitin ligases and synchronously mediate p53 ubiquitination in mud crabs (Scylla paramamosain), which confirmed the diversity of the p53 ubiquitination regulatory pathway. In addition, the effects of p53 ubiquitination are mainly focused on tumorigenesis, but a few are focused on the host immune defense in invertebrates. Our findings reveal that p53 ubiquitination could affect ROS and apoptosis signals to cope with WSSV infection in mud crabs, which is the first clarification of the immunologic functions and mechanisms of p53 ubiquitination in invertebrates.
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http://dx.doi.org/10.1128/jvi.02029-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941888PMC
March 2022

Circ_0011385 knockdown inhibits cell proliferation, migration and invasion, whereas promotes cell apoptosis by regulating miR-330-3p/MYO6 axis in colorectal cancer.

Biomed J 2022 Jan 25. Epub 2022 Jan 25.

Department of Clinical Oncology, Renmin Hospital of Wuhan University, The First Clinical College of Wuhan University, Wuhan, 430060, China. Electronic address:

Background: Colorectal cancer (CRC) is a malignant tumor. Recent studies have showed circular RNA (circRNA) participates in the development of CRC. The study was designed to reveal the role of circ_0011385 in CRC progression and underneath mechanism.

Methods: The expression circ_0011385, microRNA-330-3p (miR-330-3p) and myosin VI (MYO6) mRNA were determined by quantitative real-time polymerase chain reaction. Protein expression was detected by western blot assay. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), cell colony formation and flow cytometry assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by wound-healing assay and transwell invasion assay, respectively. The binding sites between miR-330-3p and circ_0011385 or MYO6 were predicted by CircInteractome or starBase online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation assays.

Results: Circ_0011385 and MYO6 expression were dramatically upregulated, while miR-330-3p expression was downregulated in CRC tissues or cells compared with control groups. Circ_0011385 expression was associated with tumor size, tumor-node-metastasis stage (TNM) stage and lymph node metastasis of CRC patients. Circ_0011385 silencing or MYO6 absence repressed cell proliferation, migration and invasion, whereas induced cell apoptosis in CRC. Additionally, miR-330-3p inhibitor or MYO6 overexpression attenuated the repressive impacts of circ_0011385 silencing on CRC process. Circ_0011385 was associated with miR-330-3p, and miR-330-3p targeted MYO6. Circ_0011385 knockdown inactivated MEK1/2/ERK1/2 signaling pathway by miR-330-3p/MYO6 axis. Furthermore, circ_0011385 knockdown suppressed tumor growth in vivo.

Conclusion: Circ_0011385 regulated CRC process by miR-330-3p/MYO6 axis through MEK1/2/ERK1/2 signaling pathway, providing a novel therapeutic target for CRC.
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http://dx.doi.org/10.1016/j.bj.2022.01.007DOI Listing
January 2022

Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy.

Front Genet 2021 11;12:773534. Epub 2022 Jan 11.

Key Laboratory of Trace Elements and Endemic Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, National Health Commission of the People's Republic of China, Xi'an, China.

The mechanism of environmental factors in Kashin-Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin-responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin-responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, = 0.012; dominant model: OR = 0.45, = 0.049; recessive model: OR = 0.18, = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, = 0.019; dominant model: OR = 0.52, = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls ( < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.
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http://dx.doi.org/10.3389/fgene.2021.773534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787141PMC
January 2022

The Apolipoprotein B/A1 Ratio is Associated With Metabolic Syndrome Components, Insulin Resistance, Androgen Hormones, and Liver Enzymes in Women With Polycystic Ovary Syndrome.

Front Endocrinol (Lausanne) 2021 5;12:773781. Epub 2022 Jan 5.

Department of Obstetrics and Gynecology, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.

Aim: To evaluate the association between the apolipoprotein B/A1 ratio (ApoB/ApoA1) and metabolic and endocrine parameters in women with polycystic ovary syndrome (PCOS).

Methods: This study was a secondary analysis of the Acupuncture and Clomiphene for Chinese Women with Polycystic Ovary Syndrome trial (PCOSAct), and 957 subjects with available ApoB and ApoA1 measurements were included. Tests for linear trends and linear regression were used to assess the relation between the ApoB/ApoA1 ratio and metabolic and endocrine parameters. Logistic regression was used to estimate the association between the ratio and risk of metabolic syndrome (MetS) and insulin resistance (IR). The receiver operating characteristics (ROC) curve was used to determine the predictive value of the ApoB/ApoA1 ratio for MetS and IR.

Results: The results showed that the ApoB/ApoA1 ratio was positively associated with waist circumference, systolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein, fasting plasma glucose, fasting insulin, homeostatic model assessment-insulin resistance, high free testosterone, high free androgen index, alanine transferase, aspartate transferase, and higher prevalence of MetS and IR, but was negatively correlated with high-density lipoprotein and sex hormone-binding globulin after adjusting for age and body mass index. Logistic regression showed that compared with the ApoB/ApoA1 ratio in first quartile, those in the fourth quartile demonstrated a higher risk of MetS (OR: 24.48, 95%CI: 8.54-70.15, P trend <0.001) and IR (OR: 1.78, 95%CI: 1.10-2.87, P trend <0.05) after adjusting for confounding factors. ROC curve results showed that the AUC was 0.84 (95%CI: 0.81-0.86) and had 86.8% sensitivity and 70.3% specificity with a threshold value of 0.64, and the AUC was 0.68 (95%CI: 0.64-0.71) and had 74.3% sensitivity and 58.2% specificity with a threshold value of 0.56.

Conclusions: Increased ApoB/ApoA1 ratio was associated with worse MetS components, IR, and elevated androgen hormones and liver enzymes. The ratio might be a useful tool to screen for MetS and IR in PCOS patients.
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http://dx.doi.org/10.3389/fendo.2021.773781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766308PMC
March 2022

SpBAG3 assisted WSSV infection in mud crab (Scylla paramamosain) by inhibiting apoptosis.

Dev Comp Immunol 2022 04 8;129:104349. Epub 2022 Jan 8.

Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, 515063, China; Marine Biology Institute, Shantou University, Shantou, 515063, China; STU-UMT Joint Shellfish Research Laboratory, Shantou University, Shantou, 515063, China. Electronic address:

The function of B-cell lymphoma-2 (Bcl-2) family proteins can be divided into two categories: anti-apoptotic and pro-apoptotic. As an anti-apoptotic protein, Bcl2-associated athanogene 3 (BAG3) plays a key role in regulating apoptosis, development, cell movement, and autophagy, and mediating the adaptability of cells to stimulation. However, SpBAG3 has not been reported in mud crab (Scylla paramamosain), and the regulatory effect of SpBAG3 on apoptosis in mud crab and its function in antiviral immunity is still unknown. In this study, SpBAG3 was found, and characterized, which encoded a total of 175 amino acid (molecular mass 19.3 kDa), including a specific conserved domain of the BAG family. SpBAG3 was significantly down-regulated at 0-48 h post-infection with WSSV in vivo. The antiviral effect of SpBAG3 was investigated using RNA interference. The results indicated that SpBAG3 might be involved in assisting the replication of WSSV in the host. SpBAG3 could change the mitochondrial membrane potential (△ψm), and affect cell apoptosis through mitochondrial apoptotic pathways. Therefore, the results of this study suggested that SpBAG3 could assist WSSV infection by inhibiting the apoptosis of the hemocytes in mud crab.
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http://dx.doi.org/10.1016/j.dci.2022.104349DOI Listing
April 2022
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