Publications by authors named "Li Yan"

12,727 Publications

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Influence of hyperocclusion on the remodeling of gingival tissues.

Int Immunopharmacol 2021 Jun 18;98:107885. Epub 2021 Jun 18.

Department of Stomatology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, Shandong, China. Electronic address:

Objective: The purpose of this study was to observe the effect of hyperocclusion on the remodeling of gingival tissues and detect the related signaling pathways.

Design: Hyperocclusion models were established by tooth extraction in mice. The mice were sacrificed at 3, 7, 14, 28, or 56 days after the surgery, and the left mandibular first molars with gingival tissues were isolated and examinations were focused on the gingival tissues. Apoptotic cells were examined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technology. Proliferating cells, p65, inflammatory cytokines, and β-catenin were detected using immunohistochemical methods.

Results: A series of apoptosis and proliferation responses were triggered in stressed gingival tissues. It was observed that the levels of p65, proinflammatory factors including interleukin-1β and tumor necrosis factor-α in extraction group were higher compared with those from mice with intact dentition, and peaked on days 14, 14 and 7 respectively. The expression of β-catenin was increased under hyperocclusion situations, peaked on day 14, and declined to the initial levels over time.

Conclusions: The results of this study suggest that hyperocclusion causes remodeling of the gingival tissues by activating a series of adaptive responses. Both nuclear factor kappa B and Wnt/β-catenin signaling pathways may be responsible for those adaptive responses though the exact mechanism is not clear.
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http://dx.doi.org/10.1016/j.intimp.2021.107885DOI Listing
June 2021

The ERK/CREB/PTN/syndecan-3 pathway involves in heparin-mediated neuro-protection and neuro-regeneration against cerebral ischemia-reperfusion injury following cardiac arrest.

Int Immunopharmacol 2021 Jun 18;98:107689. Epub 2021 Jun 18.

Department of Anesthesiology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002, Ningxia, China; Ningxia Anesthesia Clinincal Medical Research Center, Yinchuan 750002, Ningxia, China. Electronic address:

Background: Heparin, a commonly used anticoagulant, has been found to improve cerebral ischemia-reperfusion injury (CIR-CA) following cardiopulmonary resuscitation (CPR). Here, we aimed to explore the role of pleiotrophin (PTN)/syndecan-3 pathway in heparin therapy for CIR-CA.

Materials And Methods: The CA-CPR model was constructed in Sprague-Dawley (SD) rats, which were treated with low molecular weight heparin, and the neurological changes and brain histopathological changes were evaluated. For in-vitro experiments, the ischemic injury model of primary neurons was established by oxygen and glucose deprivation (OGD), and the neuron regeneration was detected via the Cell counting Kit-8 (CCK8) method, flow cytometry and microscopy. CREB antagonist (KG-501), ERK antagonist (PD98059) and si-PTN were used respectively to inhibit the expression of CREB, ERK and PTN in cells, so as to explore the role of heparin in regulating neuronal regeneration.

Results: Compared with the sham rats, the neurological deficits and cerebral edema of CA-CPR rats were significantly improved after heparin treatment. Heparin also attenuated OGD-mediated neuronal apoptosis and promoted neurite outgrowth in vitro. Moreover, heparin attenuated CA-CPR-mediated neuronal apoptosis and microglial neuroinflammation. In terms of the mechanism, heparin upregulated the expression of ERK, CREB, NF200, BDNF, NGF, PTN and syndecan-3 in the rat brains. Inhibition of ERK, CREB and interference with PTN expression notably weakened the heparin-mediated neuroprotective effects and restrained the expression of ERK/CREB and PTN/syndecan-3 pathway.

Conclusion: Heparin attenuates the secondary brain injury induced by CA-CPR through regulating the ERK/CREB-mediated PTN/syndecan-3 pathway.
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http://dx.doi.org/10.1016/j.intimp.2021.107689DOI Listing
June 2021

Two-Dimensional Planar BGe Monolayer as an Anode Material for Sodium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jun 21. Epub 2021 Jun 21.

School of Materials, Zhengzhou University of Aeronautics, Zhengzhou 450015, China.

Using first-principles swarm intelligence structure prediction computations, we explore a fully planar BGe monolayer with unique mechanical and electrical properties. Theoretical calculations reveal that a free-standing BGe monolayer has excellent stability, which is confirmed by the cohesive energy (compared to experimentally synthetic borophene and germanene monolayers), phonon modes (no imaginary frequencies appeared in the phonon spectrum), ab initio molecular dynamics (AIMD) simulations (no broken bonds and geometric reconstructions), and mechanical stability criteria. The metallic feature of the BGe monolayer can be maintained after absorbing different numbers of Na atoms, ensuring good electronic conductivity during the charge/discharge process. The calculated migration energy barrier, open-circuit voltage, and theoretical specific capacity of the BGe monolayer are much better than those of some other two-dimensional (2D) materials. These findings render the BGe monolayer a potential candidate for reversible Na-ion battery anode materials with desirable performance.
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http://dx.doi.org/10.1021/acsami.1c08751DOI Listing
June 2021

Effects of cereal fibers on short-chain fatty acids in healthy subjects and patients: a meta-analysis of randomized clinical trials.

Food Funct 2021 Jun 21. Epub 2021 Jun 21.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Short-chain fatty acids (SCFAs) are involved in the regulation of a wide array of diseases. However, the effect of cereal dietary fibers on SCFA production remains unclear. We reviewed relevant clinical studies between 1950 and 2021 and aimed to evaluate the effect of cereal fiber consumption on SCFA production in healthy subjects and patients. PubMed, Web of Science, and the Cochrane Library databases were used for systematically searching published relevant trials with adults and a minimum intervention duration of 2 weeks. The effect size was estimated using standardized mean difference (SMD) and 95% confidence interval (CI). Of the 555 identified studies, 14 intervention groups involving 205 participants aged between 20 and 69 years are eligible. The results of meta-analysis revealed that cereal fiber supplementation significantly increased acetate [SMD: 0.86, 95% CI (0.46, 1.25), p < 0.0001], propionate [SMD: 0.48, 95% CI: (0.15, 0.81), p = 0.004], butyrate [SMD: 0.61, 95% CI: (0.20, 1.01), p = 0.003], and total SCFA [SMD, 0.96, 95% CI: (0.54, 1.39), p < 0.00001] concentrations. Subgroup analysis suggested that a long intervention duration (>4 weeks) significantly promoted acetate and propionate production, whereas a short intervention duration (≤4 weeks) significantly facilitated butyrate production. Cereal fiber supplementation had a more significant impact on overweight and obese subjects with body mass index (BMI) >29 kg m-2 than on individuals with BMI ≤29 kg m-2. Furthermore, we found that cereal fibers and wheat/rye arabinoxylan oligosaccharides, rather than wheat bran fibers, barley fibers, and barley β-glucan, could significantly elevate the SCFA concentration. Overall, our meta-analysis demonstrated that cereal fiber supplementation is helpful in increasing the SCFA concentration, which provided strong proof for the beneficial role of cereal fibers.
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http://dx.doi.org/10.1039/d1fo00858gDOI Listing
June 2021

Nickel (ii) effects on Anammox reaction: reactor performance, dehydrogenase, sludge morphology and microbial community changes.

Environ Technol 2021 Jun 21:1-27. Epub 2021 Jun 21.

School of Environmental Science and Spatial Informatics, CUMT, Xuzhou 221116, Jiangsu Province, China.

Nickel (ii) (Ni) is considered as one of the necessary trace elements in the process of Anammox culture, but it may have toxic effects at high concentration. This study explored the long-term influence of Ni on the denitrification efficiency of Anammox bioreactors. The results showed that when the concentration of Ni was 0.5 mg/L, the bioreactor had the highest denitrification efficiency, while the removal efficiency of ammonia nitrogen and nitrite nitrogen gradually decreased at concentrations higher than 2 mg/L, and the removal rates of ammonia nitrogen and nitrite nitrogen were 26% and 39.81% at the end of the experiment, respectively. The NRR was decreased from 7.47 kg N /m·d to 3.28 kg N /m·d during the whole process. The highest concentration of microbial dehydrogenase was attained in about 40 days; in the meantime, its ability to consume organic matter was also maximized. The sludge morphology was changed from granular cluster to loose flocculant with a small number of spherical and filamentous bacteria and bacilli distributed on the surface. At the end of the experiment, both species richness and community diversity were reduced, and the proportion of the dominant bacteria Kuenenia was also decreased from 59.89% to 36.72%.
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http://dx.doi.org/10.1080/09593330.2021.1946165DOI Listing
June 2021

Phagocytosis checkpoints on hematopoietic stem cells in patients with myelodysplastic syndromes.

Asia Pac J Clin Oncol 2021 Jun 21. Epub 2021 Jun 21.

Department of Hematology, General Hospital, Tianjin Medical University, Tianjin, China.

Background: The myelodysplastic syndrome (MDS) is a high-risk hemocytopenia easily converted to acute myeloid leukemia. CD47 plays an important role in regulating phagocytosis, and its role in the pathogenesis of MDS is unclear.

Methods: CD47 and PI3K/AKT/mTOR on CD34 CD38 cells were detected by flow cytometry. NF-κB, PI3K, AKT, PTEN, and mTOR mRNA overexpressed in CD34 CD38 CD47 cells were performed by real-time quantitative transcriptase-polymerase chain reaction. Phagocytic capacity of macrophages was measured with carboxyfluorescein succinimidyl ester and fluorescent microspheres. Sorted CD34 CD38 CD47 cells were injected into NOD-Prkdc Il2rg mice.

Results: The expression of CD47 on CD34 CD38 cells of the patients in high-risk MDS based on IPSS-R/WPSS score was higher than that in low-risk MDS and controls. The signaling pathway of PI3K/AKT/mTOR is active in CD34 CD38 CD47 cells of MDS patients. CD47 overexpressing CD34 CD38 cells has antiphagocytosis. CD47 overexpressing leukemia stem cell (LSC) -transplanted mice has a short survival time. The macrophages originated from MDS might elicit a pro-tumor response in MDS by inhibiting phagocytosis.

Conclusions: Phagocytosis checkpoints are impaired in MDS. High expression of CD47 on CD34+CD38 cells indicates poor clinical prognosis in MDS.
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http://dx.doi.org/10.1111/ajco.13566DOI Listing
June 2021

LncRNA BCAR4 expression and predicts the clinical response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Cancer Biomark 2021 Jun 19. Epub 2021 Jun 19.

Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Background: Neoadjuvant chemotherapy (NAC) is an important treatment for locally advanced breast cancer (LABC). However, there are no effective biomarkers to predict the efficacy. Therefore, there is an urgent need for new biomarkers to predict the response of LABC to NAC. LncRNA BCAR4 has been detected in a variety of malignant tumor tissues and used as a new biomarker for diagnosis and prognosis. However, LncRNA BCAR4 predicts the response of LABC to NAC is unclear.

Objective: Explore the predictive effect of LncRNA BCAR4 on the efficacy of NAC for LABC in three different evaluation systems.

Methods: First, the TCGA database was used to analyze the expression of LncRNA BCAR4 in 33 kinds of malignant tumors, and further explore its expression in breast cancer and its impact on the survival and prognosis of breast cancer. Furthermore, quantitative methods were used to measure the expression level of LncRNA BCAR4 in cancer tissues of 48 LABC patients, and the correlation between LncRNA BCAR4 and clinicopathological status and response to NAC under the evaluation system of 3, RECIST1.1, Miller-Payne (MP) score and whether it reaches pCR,was analyzed.

Results: TCGA data analysis found that LncRNA is highly expressed in a variety of malignant tumor tissues, including breast cancer. And relatively low expression, the shorter the overall survival time of high expression patients. The high expression of LncRNA BCAR4 is related to the size of the tumor, and there are differences in expression between stage I and other stages, but there is no obvious correlation with the positive lymph node and hormone receptor status. Among the three evaluation systems, only in the RECIST 1.1 evaluation system LncRNA BCAR4 has a predictive effect on NAC for LABC. The expression of LncRNA BCAR4 has no significant correlation with clinical stage, Ki-67% and hormone receptor status, and has no significant correlation with whether patients with locally advanced breast cancer obtain pCR during neoadjuvant chemotherapy.

Conclusion: LncRNA BCAR4 is highly expressed in LABC tissues and may be an effective marker for predicting the efficacy of NAC for LABC.
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http://dx.doi.org/10.3233/CBM-210048DOI Listing
June 2021

Decreased Levels of Insulin-Like Growth Factor-1 Are Associated with Alzheimer's Disease: A Meta-Analysis.

J Alzheimers Dis 2021 Jun 17. Epub 2021 Jun 17.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing P.R. China.

Background: Alterations in levels of peripheral insulin-like growth factor-1 (IGF-1) in Alzheimer's disease (AD) have been reported in several studies, and results are inconsistent.

Objective: We conducted a meta-analysis to investigate the relationship between peripheral and cerebrospinal fluid IGF-1 levels and AD or mild cognitive impairment (MCI).

Methods: A systematic search in PubMed, Medline, Web of Science, Embase, and Cochrane Library was conducted and 18 studies were included.

Results: Results of random-effects meta-analysis showed that there was no significant difference between AD patients and healthy control (17 studies; standard mean difference [SMD], -0.01; 95%CI, -0.35 to 0.32) and between MCI patients and healthy control (6 studies; SMD, -0.20; 95%CI, -0.52 to 0.13) in peripheral IGF-1 levels. Meta-regression analyses identified age difference might explain the heterogeneity (p = 0.017). However, peripheral IGF-1 levels were significantly decreased in AD subjects (9 studies; SMD, -0.44; 95%CI, -0.81 to -0.07) and MCI subjects exhibited a decreasing trend (4 studies; SMD, -0.31; 95%CI, -0.72 to 0.11) in studies with sample size≥80. Cerebrospinal fluid IGF-1 levels also significantly decreased in AD subjects (3 studies; SMD, -2.40; 95%CI, -4.36 to -0.43).

Conclusion: These findings suggest that decreased peripheral and cerebrospinal fluid IGF-1 levels might be a potential marker for the cognitive decline and progression of AD.
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http://dx.doi.org/10.3233/JAD-210516DOI Listing
June 2021

Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming.

J Alzheimers Dis 2021 Jun 17. Epub 2021 Jun 17.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.

Background: Dysfunction of microglia has been increasingly recognized as a causative factor in Alzheimer's disease (AD); thus, developing medicines capable of restoring microglial functions is critically important and constitutes a promising therapeutic strategy. Honokiol is a natural neuroprotective compound extracted from Magnolia officinalis, which may play roles in AD therapy.

Objective: This study aimed to evaluate the role and the underlying mechanisms of honokiol in microglial phagocytosis.

Methods: MTT and flow cytometry were used to assess the cell viability and apoptosis, respectively. Phagocytic capacity, mitochondrial reactive oxygen species production, and membrane potential were evaluated using fluorescence microscopy. Seahorse XF24 extracellular flux analyzer was for cell glycolysis and oxidative phosphorylation (OXPHOS) detection. Mass spectrometry was applied for metabolites measurement. Quantitative real-time polymerase chain reaction and western blotting were performed to detect the mRNA and protein level of PPARγ and PGC1α, respectively.

Results: Honokiol alleviated Aβ 42-induced BV2 neurotoxicity. Honokiol promoted phagocytic efficiency of BV2 cells through reversing a metabolic switch from OXPHOS to anaerobic glycolysis and enhancing ATP production. Meanwhile, honokiol reduced mitochondrial reactive oxygen species (ROS) production and elevated mitochondrial membrane potential. Moreover, honokiol increased the expression of PPARγ and PGC1α, which might play positive roles in energy metabolism and microglial phagocytosis.

Conclusion: In this study, honokiol was identified as an effect natural product capable of enhancing mitochondrial function thus promoting microglial phagocytic function.
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http://dx.doi.org/10.3233/JAD-210177DOI Listing
June 2021

Randomised, Double-Blind, Placebo-Controlled Study of Iguratimod in the Treatment of Active Spondyloarthritis.

Front Med (Lausanne) 2021 2;8:678864. Epub 2021 Jun 2.

Department of Rheumatology and Immunology, First Medical Center, General Hospital of Chinese People's Liberation Army, Beijing, China.

The effect of Iguratimod in the treatment of rheumatoid arthritis was confirmed in past studies. In terms of the mechanism of the effect and clinical application experience, Iguratimod has a potential value in the treatment of spondyloarthritis (SpA). This study evaluated the efficacy and safety of Iguratimod on active SpA. Subjects with active SpA were enrolled and randomly divided into two groups at a ratio of 1:2 (placebo vs. Iguratimod). On the basis of non-steroidal anti-inflammatory drugs, combined treatment with Iguratimod or placebo, followed by follow-up every 4 weeks for 24 weeks. The primary efficacy endpoint was to evaluate the alleviation rate of ASAS20; the important improvement of ASDAS and the efficacy of spinal mobility, physical function and quality of life at the 24th week. A total of 48 cases in the Iguratimod group and 25 cases in the placebo group were included in the final analysis. On the 24th week, the percentage of responders to ASAS20 (80 vs. 44%) and ASAS40 (56 vs. 20%) treated with Iguratimod were significantly higher than that in the placebo group ( < 0.05). Twelve cases had gastrointestinal discomfort, of which eight were in the Iguratimod group (16.7%, one case withdrew from the study due to diarrhoea) and four were in the placebo group (16.0%). No significant difference was found between the two groups ( < 0.05). Three cases of elevated transaminase were observed in the Iguratimod group and none in the placebo group, with no significant difference ( < 0.05). Iguratimod could significantly reduce the symptoms and signs of patients with active SpA. It could improve the physical function and quality of life of these patients and the overall safety and tolerance are good.
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http://dx.doi.org/10.3389/fmed.2021.678864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208078PMC
June 2021

Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia.

Front Oncol 2021 2;11:677034. Epub 2021 Jun 2.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.

Although pediatric-like treatment regimen has remarkably improved the survival rates of adults with acute lymphoblastic leukemia (ALL), the outcome of some adult patients is still poor owing to adverse genetic features. These molecular abnormalities, especially gene deletions, may be considered for the prognosis assessment for adult patients with ALL. In this study, using multiplex ligation-dependent probe amplification (MLPA) method, gene deletions were analyzed in from 211 adult B-ALL patients treated in our center. The data showed that 68.2% (144/211) adult B-ALL patients carried gene deletions, and the frequency is much higher in PhB-ALL patients. gene deletion is the most common gene deletion in adult B-ALL, followed by deletion. In PhB-ALL patients, the overall survival of patients with gene deletions is inferior to that of patients without any gene deletions. More obviously, patients with or deletion had a worse prognosis, whereas, allogeneic hematopoietic stem cell transplantation could improve OS in patients with deletion, but not in patients with CDKN2A/B deletion. Moreover, the outcome of PhB-ALL patients with double deletion of and may be much worse than that of patients with or alone. Minimal residual disease (MRD) was also analyzed together with gene deletions and demonstrated that gene deletions have a negative impact on survival only in MRD positive PhB-ALL patients. In conclusion, gene deletions are closely related with the prognosis of adult PhB-ALL patients.
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http://dx.doi.org/10.3389/fonc.2021.677034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206559PMC
June 2021

Molecular Traits and Functional Analysis of the CLAVATA3/Endosperm Surrounding Region-Related Small Signaling Peptides in Three Species of Genus.

Front Plant Sci 2021 4;12:671626. Epub 2021 Jun 4.

Research Base, Zhengzhou University, State Key Laboratory of Cotton Biology, Institute of Cotton Research of Chinese Academy of Agricultural Sciences, Anyang, China.

The CLAVATA3/endosperm surrounding region-related (CLE) small peptides are a group of C-terminally encoded and post-translationally modified signal molecules involved in regulating the growth and development of various plants. However, the function and evolution of these peptides have so far remained elusive in cotton. In this study, 55, 56, and 86 genes were identified in the , and genomes, respectively, and all members were divided into seven groups. These groups were distinctly different in their protein characteristics, gene structures, conserved motifs, and multiple sequence alignment. Whole genome or segmental duplications played a significant role in the expansion of the family in cotton, and experienced purifying selection during the long evolutionary process in cotton. is-acting regulatory elements and transcript profiling revealed that the genes of cotton exist in different tissues, developmental stages, and respond to abiotic stresses. Protein properties, structure prediction, protein interaction network prediction of GhCLE2, GhCLE33.2, and GhCLE28.1 peptides were, respectively, analyzed. In addition, the overexpression of , or in , respectively, resulted in a distinctive shrub-like dwarf plant, slightly purple leaves, large rosettes with large malformed leaves, and lack of reproductive growth. This study provides important insights into the evolution of cotton and delineates the functional conservatism and divergence of genes in the growth and development of cotton.
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http://dx.doi.org/10.3389/fpls.2021.671626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213210PMC
June 2021

RIPK3-Dependent Necroptosis Limits PRV Replication in PK-15 Cells.

Front Microbiol 2021 4;12:664353. Epub 2021 Jun 4.

Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, China.

Pigs infected by pseudorabies virus (PRV) display necrotic pathology in multiple organs. The mechanism by which PRV induces cell death is still unclear. Recently, necroptosis was identified as a programmed process dependent on the receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase-like protein (MLKL). In this study, we demonstrated that PRV induced RIPK3-dependent necroptosis in PK-15 cells. The data showed that PRV infection caused cell death with Propidium Iodide (PI)-positive staining. Transmission electron microscopy analysis indicated plasma membrane disruption in PRV-infected cells. A pan-caspase inhibitor did not prevent PRV-induced necrotic cell death. Western blot analysis indicated that caspase-3 and caspase-8 were not cleaved during PRV infection. Although the transcription of tumor necrosis factor-alpha (TNF-α) was increased by PRV infection, RIPK1 was shown to be not involved in PRV-induced necrotic cell death by use of its specific inhibitor. Further experiments indicated that the phosphorylation of RIPK3 and MLKL was upregulated in PRV-infected cells. Stable shRNA knockdown of RIPK3 or MLKL had a recovery effect on PRV-induced necrotic cell death. Meanwhile, viral titers were enhanced in RIPK3 and MLKL knockdown cells. Hence, we concluded that initiation of necroptosis in host cells plays a limiting role in PRV infection. Considering that necroptosis is an inflammatory form of programmed cell death, our data may be beneficial for understanding the necrotic pathology of pigs infected by PRV.
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http://dx.doi.org/10.3389/fmicb.2021.664353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211757PMC
June 2021

Ultrasound-guided thermal ablation for papillary thyroid microcarcinoma: a multicenter retrospective study.

Int J Hyperthermia 2021 ;38(1):916-922

Department of Ultrasound, the First Affiliated Hospital of Dalian Medical University, Dalian, China.

Purpose: Ultrasound-guided thermal ablation (including microwave ablation [MWA] and radiofrequency ablation [RFA]) has emerged as a remarkable technology for the treatment of benign and malignant diseases. The objective of this multicenter study was to assess the efficacy and safety of thermal ablation in a large cohort of patients with papillary thyroid microcarcinoma (PTMC).

Materials And Methods: Retrospective study of 725 patients who underwent MWA/RFA at 11 centers between March 2015 and March 2020. The mean age of patients was 46 ± 11 years (range, 22-81); the mean follow-up time was 21 ± 13 months (range, 6-60). Changes in size of tumor, the rates of tumor disappearance, disease progression, and complications were assessed.

Results: From 6 months post-ablation, the size of tumors was significantly reduced compared with those recorded pre-ablation ( < 0.001 for all). Five hundred and fifteen (71.0%) PTMCs had completely disappeared as assessed by ultrasound examination. Six (0.8%) patients developed disease progression post-ablation; of these, 5 (0.7%) patients developed new PTMCs, while one (0.1%) patient developed cervical lymph node metastasis. Nineteen (2.6%) patients developed complications post-ablation; of these 14 (1.9%) patients developed voice hoarseness, 4 (0.6%) developed hematoma, and one (0.1%) patient developed cough.

Conclusions: Ultrasound-guided thermal ablation represents an effective and safe treatment for patients with PTMC besides active surveillance and surgery.
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http://dx.doi.org/10.1080/02656736.2021.1936218DOI Listing
January 2021

Fucoidan-Based Theranostic Nanogel for Enhancing Imaging and Photodynamic Therapy of Cancer.

Nanomicro Lett 2020 Feb 4;12(1):47. Epub 2020 Feb 4.

Division of Translational Science, Research Institute, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi, 10408, Republic of Korea.

In this study, a fucoidan-based theranostic nanogel (CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve activatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy (PDT) to induce the complete death of cancer cells. A CFN-gel has nanomolar affinity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention effect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar affinity for the vascular endothelial growth factor, it also provides a significant anti-tumor effect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high efficacy and specificity.
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http://dx.doi.org/10.1007/s40820-020-0384-8DOI Listing
February 2020

Applications of MSe (M = Fe, Co, Ni) and Their Composites in Electrochemical Energy Storage and Conversion.

Nanomicro Lett 2019 May 15;11(1):40. Epub 2019 May 15.

School of Chemistry and Chemical Engineering, Guangling College, Yangzhou University, Yangzhou, 225009, Jiangsu, People's Republic of China.

Transition-metal selenides (MSe, M = Fe, Co, Ni) and their composites exhibit good storage capacities for sodium and lithium ions and occupy a unique position in research on sodium-ion and lithium-ion batteries. MSe and their composites are used as active materials to improve catalytic activity. However, low electrical conductivity, poor cycle stability, and low rate performance severely limit their applications. This review provides a comprehensive introduction to and understanding of the current research progress of MSe and their composites. Moreover, this review proposes a broader research platform for these materials, including various bioelectrocatalytic performance tests, lithium-sulfur batteries, and fuel cells. The synthesis method and related mechanisms of MSe and their composites are reviewed, and the effects of material morphologies on their electrochemical performance are discussed. The advantages and disadvantages of MSe and their composites as well as possible strategies for improving the storage and conversion of electrochemical energy are also summarized.
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http://dx.doi.org/10.1007/s40820-019-0272-2DOI Listing
May 2019

Identification of 3, 4-disubstituted pyridine derivatives as novel CDK8 inhibitors.

Eur J Med Chem 2021 Jun 11;223:113634. Epub 2021 Jun 11.

Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address:

Selective inhibition of cyclin-dependent kinase 8 (CDK8) has been recently regarded as a potential approach for cancer therapy. A series of novel CDK8 inhibitors with the pyridine core was identified via scaffold hopping from the known CDK8 inhibitor A-7. The new inhibitors were designed to improve the ligand efficiency so as to enhance drug-likeness. Most of the compounds showed significant inhibition against CDK8/cyclin C, and the most active compounds (5d, 5e and 7') displayed IC values of 2.4 nM, 5.0 nM and 7.7 nM, respectively. Preliminary kinase profiling of selected compounds against a panel of kinases from different families indicated that this compound class might selectively inhibit CDK8 as well as its paralog CDK19. Some compounds exhibited cellular activity in both MTT and SRB assays against a variety of tumor cells, including HCT-116, A549, MDA-MB-231, KB, KB-VIN and MCF-7. Further flow cytometry analysis revealed a dose-dependent G2/M phase arrest in MDA-MB-231 cells treated with compounds 6'a, 6'b, 6'j and 6'k. In addition, compound 6'k demonstrated moderate antitumor efficacy in HCT-116 mouse models, although unfavorable pharmacokinetic profiles were suggested by preliminary study in mice. The results provided a new structural prototype for the search of selective CDK8 inhibitors as antitumor agents.
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http://dx.doi.org/10.1016/j.ejmech.2021.113634DOI Listing
June 2021

Levels of polycyclic aromatic hydrocarbons in edible and fried vegetable oil: a health risk assessment study.

Environ Sci Pollut Res Int 2021 Jun 19. Epub 2021 Jun 19.

School of Food & Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, 526061, China.

Polycyclic aromatic hydrocarbons (PAHs) are environmental chemicals that are formed due to incomplete combustion of the organic matters, or during heat treatment of the food. The objectives of the present study were first to estimate levels of the 15-priority PAHs in the edible vegetable oil (corn oil, sunflower oil, olive oil, and canola oil) collected from Egypt. Furthermore, the effect of heat treatment on the formation of PAHs in the canola oil was further examined. In addition, dietary intakes and cancer risk among Egyptian consumers were additionally calculated. The achieved results indicated presence of 15-priority PAHs in all examined oil samples. Canola oil had the highest residual concentrations of PAHs compared with the other tested oil species. Heat treatment of canola oil led to a drastic increase in the formed B[a]P (316.55%), total 2-PAHs (322.47%), total 4-PAHs (297.42%), total 8-PAHs (285.26%), and total 15-PAHs (443.32%), respectively. The incremental lifetime cancer risk among the Egyptian population is considered safe when was calculated for all examined oil samples.
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http://dx.doi.org/10.1007/s11356-021-14755-zDOI Listing
June 2021

Wittichenite semiconductor of CuBiS films for efficient hydrogen evolution from solar driven photoelectrochemical water splitting.

Nat Commun 2021 Jun 18;12(1):3795. Epub 2021 Jun 18.

Institute of Semiconductor Science and Technology, South China Normal University, Guangzhou, P. R. China.

A highly efficient, low-cost and environmentally friendly photocathode with long-term stability is the goal of practical solar hydrogen evolution applications. Here, we found that the CuBiS film-based photocathode meets the abovementioned requirements. The CuBiS-based photocathode presents a remarkable onset potential over 0.9 V with excellent photoelectrochemical current densities (~7 mA/cm under 0 V) and appreciable 10-hour long-term stability in neutral water solutions. This high onset potential of the CuBiS-based photocathode directly results in a good unbiased operating photocurrent of ~1.6 mA/cm assisted by the BiVO photoanode. A tandem device of CuBiS-BiVO with an unbiased solar-to-hydrogen conversion efficiency of 2.04% is presented. This tandem device also presents high stability over 20 hours. Ultimately, a 5 × 5 cm large CuBiS-BiVO tandem device module is fabricated for standalone overall solar water splitting with a long-term stability of 60 hours.
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http://dx.doi.org/10.1038/s41467-021-24060-5DOI Listing
June 2021

Reappraisal of anticancer nanomedicine design criteria in three types of preclinical cancer models for better clinical translation.

Biomaterials 2021 Jun 3;275:120910. Epub 2021 Jun 3.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 1600 Huron Parkway, North Campus Research Complex, Building 520, Ann Arbor, MI, 48109, USA. Electronic address:

Anticancer nanomedicines are designed to improve anticancer efficacy by increasing drug accumulation in tumors through enhanced permeability retention (EPR) effect, and to reduce toxicity by decreasing drug accumulation in normal organs through long systemic circulation. However, the inconsistent efficacy/safety of nanomedicines in cancer patients versus preclinical cancer models have provoked debate for nanomedicine design criteria. In this study, we investigate nanomedicine design criteria in three types of preclinical cancer models using five clinically used nanomedicines, which identifies the factors for better clinical translations of their observed clinical efficacy/safety compared to free drug or clinical micelle formulation. When those nanomedicines were compared with drug solution or clinical micelle formulation in breast tumors, long and short-circulating nanomedicines did not enhance tumor accumulation by EPR effect in transgenic spontaneous breast cancer model regardless of their size or composition, although they improved tumor accumulations in subcutaneous and orthotopic breast cancer models. However, when tumors were compared to normal breast tissue, nanomedicines, drug solution and clinical micelle formulation showed enhanced tumor accumulation regardless of the breast cancer models. In addition, long-circulating nanomedicines did not further increase tumor accumulation in transgenic mouse spontaneous breast cancer nor universally decrease drug accumulations in normal organs; they decreased or increased accumulation in different organs, potentially changing the clinical efficacy/safety. In contrast, short-circulating nanomedicines decreased blood concentration and altered drug distribution in normal organs, which are correlated with their clinical efficacy/safety. A reappraisal of current nanomedicine design criteria is needed to ensure consistent clinical translation for improvement of their clinical efficacy/safety in cancer patients.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120910DOI Listing
June 2021

Top-k Self-Adaptive Contrast Sequential Pattern Mining.

IEEE Trans Cybern 2021 Jun 18;PP. Epub 2021 Jun 18.

For sequence classification, an important issue is to find discriminative features, where sequential pattern mining (SPM) is often used to find frequent patterns from sequences as features. To improve classification accuracy and pattern interpretability, contrast pattern mining emerges to discover patterns with high-contrast rates between different categories. To date, existing contrast SPM methods face many challenges, including excessive parameter selection and inefficient occurrences counting. To tackle these issues, this article proposes a top-k self-adaptive contrast SPM, which adaptively adjusts the gap constraints to find top-k self-adaptive contrast patterns (SCPs) from positive and negative sequences. One of the key tasks of the mining problem is to calculate the support (the number of occurrences) of a pattern in each sequence. To support efficient counting, we store all occurrences of a pattern in a special array in a Nettree, an extended tree structure with multiple roots and multiple parents. We employ the array to calculate the occurrences of all its superpatterns with one-way scanning to avoid redundant calculation. Meanwhile, because the contrast SPM problem does not satisfy the Apriori property, we propose Zero and Less strategies to prune candidate patterns and a Contrast-first mining strategy to select patterns with the highest contrast rate as the prefix subpattern and calculate the contrast rate of all its superpatterns. Experiments validate the efficiency of the proposed algorithm and show that contrast patterns significantly outperform frequent patterns for sequence classification. The algorithms and datasets can be downloaded from https://github.com/wuc567/Pattern-Mining/tree/master/SCP-Miner.
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http://dx.doi.org/10.1109/TCYB.2021.3082114DOI Listing
June 2021

Arhgef2 regulates neural differentiation in the cerebral cortex through mRNA mA-methylation of Npdc1 and Cend1.

iScience 2021 Jun 24;24(6):102645. Epub 2021 May 24.

Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China.

-methyladenosine (mA) is emerging as a vital factor regulating neural differentiation. Here, we report that deficiency of , a novel cause of a neurodevelopmental disorder we identified recently, impairs neurogenesis, neurite outgrowth, and synaptic formation by regulating mA methylation. knockout decreases expression of and total mA level significantly in the cerebral cortex. mA sequencing reveals that loss of reduces mA methylation of 1,622 mRNAs, including and which are both strongly associated with cell cycle exit and terminal neural differentiation. deficiency decreases mA methylations of the and mRNAs via down-regulation of Mettl14, and thereby inhibits the translation of and nuclear export of mRNAs. Overexpression of Mettl14, Npdc1, and Cend1 rescue the abnormal phenotypes in knockout mice, respectively. Our study provides a critical insight into a mechanism by which defective mediates mA-tagged target mRNAs to impair neural differentiation.
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http://dx.doi.org/10.1016/j.isci.2021.102645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185223PMC
June 2021

Tension hydropneumothorax in a Boerhaave syndrome patient: A case report.

World J Emerg Med 2021 ;12(3):235-237

Emergency Department, Peking Union Medical College Hospital, Beijing 100730, China.

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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188275PMC
January 2021

Performance of D-dimer for predicting sepsis mortality in the intensive care unit.

Biochem Med (Zagreb) 2021 Jun;31(2):020709

Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.

Introduction: The prognostic value of D-dimer (DD) in sepsis remains controversial. This study aimed to investigate the performance of DD for predicting sepsis mortality in the hospital and for identifying its potential correlates.

Materials And Methods: The clinical and laboratory data of adult sepsis patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III, v1.4) database using the structured query language (SQL). The database contains critical illness admitted to the intensive care unit at Beth Israel Deaconess Medical Center between June 2001 and October 2012. The association between DD and mortality was investigated with receiver operating characteristic (ROC) curve, restricted cubic spline and logistic regression analysis. Subgroup analysis was also used for identifying DD correlates.

Results: The study population consisted of 358 sepsis patients. Those who died during hospital stay (N = 160) had significantly higher DD values than those who survived (N = 198). The area under the ROC curve (AUC) of DD was 0.59 (P < 0.010). In subgroup analysis, white blood cell (WBC) count > 18 x10/L and vasopressor therapy significantly decreased DD diagnostic performance. Categorical DD value was independently associated with hospital mortality after sequential organ failure score (SOFA) and blood lactate adjustment. Restricted cubic spline analysis revealed a U-shape relationship between DD and in-hospital mortality.

Discussion: We conclude that the accuracy of DD for predicting in-hospital sepsis mortality depends on WBC count and vasopressor therapy. Both low and extremely elevated DD values are associated with higher risk of death.
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http://dx.doi.org/10.11613/BM.2021.020709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183117PMC
June 2021

A pig BodyMap transcriptome reveals diverse tissue physiologies and evolutionary dynamics of transcription.

Nat Commun 2021 06 17;12(1):3715. Epub 2021 Jun 17.

Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China.

A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter-enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits.
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http://dx.doi.org/10.1038/s41467-021-23560-8DOI Listing
June 2021

Knocking out c-Jun promotes cardiomyocyte differentiation from embryonic stem cells.

Int J Cardiol 2021 Jun 14. Epub 2021 Jun 14.

Department of Cardiovascular Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address:

Background: Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation.

Methods: The c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses.

Results: Compared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group.

Conclusions: Knocking out c-Jun directs ESCs towards a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development.
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http://dx.doi.org/10.1016/j.ijcard.2021.06.017DOI Listing
June 2021

Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile.

J Med Chem 2021 Jun 17. Epub 2021 Jun 17.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.

Proteolysis-targeting chimera (PROTAC) is an attractive technology in drug discovery. Canonically, targets act as a basic starting point in the most previous PROTAC design. Here, we designed degraders considering from the view of clinical benefits. With this novel design, Brigatinib was turned into a degrader SIAIS164018 and endowed with unique features. First, SIAIS164018 could degrade not only ALK fusion proteins in activating or G1202R-mutated form but also mutant EGFR with L858R + T790M, which are two most important targets in non-small-cell lung cancer. Second, SIAIS164018 strongly inhibited cell migration and invasion of Calu-1 and MDA-MB-231. Third and surprisingly, SIAIS164018 degrades several important oncoproteins involved in metastasis such as FAK, PYK2, and PTK6. Interestingly, SIAIS164018 reshuffled the kinome ranking profile when compared to Brigatinib. Finally, SIAIS164018 is orally bioavailable and well tolerated in vivo. SIAIS164018 is an enlightening degrader for us to excavate the charm of protein degradation.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00373DOI Listing
June 2021

Excellent Response to Atezolizumab After Clinically Defined Hyperprogression Upon Previous Treatment With Pembrolizumab in Metastatic Triple-Negative Breast Cancer: A Case Report and Review of the Literature.

Front Immunol 2021 31;12:608292. Epub 2021 May 31.

Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.

Immunotherapy with immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors, has revolutionized the systematic treatment of advanced and metastatic solid tumors. However, the response rate to ICIs is unsatisfactory, and unexpected hyperprogressive disease (HPD) is even observed in a small subgroup of patients. Patients with HPD usually have worsening clinical symptoms and poorer survival, and therapeutic strategies are extremely limited. Here, we presented a patient with HPD who had used a PD-L1 inhibitor and was highly responsive to the sequential use of a PD-1 inhibitor. A 67-year-old woman with metastatic triple-negative breast cancer was treated with pembrolizumab plus chemotherapy after progression on previous multiple-line chemotherapy treatments. After 2 cycles of treatments, she rapidly developed HPD, as confirmed by radiological evaluation and worsening symptoms. At that time, pembrolizumab was discontinued, and she switched to the PD-L1 inhibitor atezolizumab plus chemotherapy. This patient partially responded to atezolizumab plus chemotherapy without experiencing severe drug-related adverse effects. This is the first reported case of metastatic breast cancer in a patient with radiologically confirmed HPD after pembrolizumab therapy in which successful rechallenge with atezolizumab relieved clinical symptoms. Further studies with larger sample sizes involving a deeper translational investigation of HPD are needed to confirm the efficacy and mechanism of sequential application of different ICIs for the clinical management of HPD.
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http://dx.doi.org/10.3389/fimmu.2021.608292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201609PMC
May 2021

The Risk Threshold for Hemoglobin A1c Associated With Albuminuria: A Population-Based Study in China.

Front Endocrinol (Lausanne) 2021 31;12:673976. Epub 2021 May 31.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Diabetic kidney disease (DKD) is a kind of common microvascular complication of diabetes. This study aims to explore the possible links between blood sugar level and albuminuria, providing the exact cut point of the "risk threshold" for blood glucose with DKD.

Methods: The relationship between blood glucose and albuminuria was modeled using linear and logistic regression in the REACTION study cohorts (N= 8932). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. Two-slope linear regression was used to simulate associations between blood glucose and ACR.

Results: We found that the increase in ACR was accompanied by increased HbA1c, with a turning point at 5.5%. The positive correlation remained highly significant (P<0.001) when adjusted for age, sex, marital status, education, smoking status, drinking status, BMI, waistline, SBP and DBP. In subgroup analyses including gender, obesity, hypertension, and smoking habits, the relationship was significant and stable.

Conclusions: We determined a risk threshold for HbA1c associated with albuminuria in a Chinese population over the age of 40. HbA1c ≥ 5.5% was positively and independently associated with ACR. These results suggest the necessity of early blood glucose control and renal function screening for DKD in at-risk populations.
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http://dx.doi.org/10.3389/fendo.2021.673976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202121PMC
May 2021

SARS-CoV-2 NSP12 protein is not an IFN-β antagonist.

J Virol 2021 Jun 16:JVI0074721. Epub 2021 Jun 16.

State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 non-structural protein 12 (NSP12) was able to suppress interferon-β (IFN-β) activation in IFN-β promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-β promoter mediated luciferase activity was reduced during co-expression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-β production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-β promoter luciferase assays. In conclusion, unlike previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-β antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling, and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-β activation. However, most of these results were generated from IFN-β promoter luciferase reporter assay, and have not been validated functionally. In our study, we found that although NSP12 could suppress IFN-β promoter luciferase activity, it showed no inhibitory effect on IFN-β production or it downstream signaling. Further study revealed that contradictory results could generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-β signaling. On the other hand, our study suggests that cautions need to be taken with the interpretation of SARS-CoV-2 related luciferase assays.
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http://dx.doi.org/10.1128/JVI.00747-21DOI Listing
June 2021