Publications by authors named "Jing Zhu"

1,487 Publications

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The Influence of Diabetes, Hypertension, and Hyperlipidemia on the Onset of Age-Related Macular Degeneration in North China: The Kailuan Eye Study.

Biomed Environ Sci 2022 Jul;35(7):613-621

Beijing Tongren Eye Center, Beijing key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology&Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD.

Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD.

Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD.

Conclusion: There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
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http://dx.doi.org/10.3967/bes2022.081DOI Listing
July 2022

Development and validation of a machine learning-derived radiomics model for diagnosis of osteoporosis and osteopenia using quantitative computed tomography.

BMC Med Imaging 2022 Aug 8;22(1):140. Epub 2022 Aug 8.

Department of Clinical Research Center, Dazhou Central Hospital, No.56 Nanyuemiao Street, Tongchuan District, Dazhou, 635000, Sichuan, China.

Background: To develop and validate a quantitative computed tomography (QCT) based radiomics model for discriminating osteoporosis and osteopenia.

Methods: A total of 635 patients underwent QCT were retrospectively included from November 2016 to November 2019. The patients with osteopenia or osteoporosis (N = 590) were divided into a training cohort (N = 414) and a test cohort (N = 176). Radiomics features were extracted from the QCT images of the third lumbar vertebra. Minimum redundancy and maximum relevance and least absolute shrinkage and selection operator were used for data dimensional reduction, features selection and radiomics model building. Multivariable logistic regression was applied to construct the combined clinical-radiomic model that incorporated radiomics signatures and clinical characteristics. The performance of the combined clinical-radiomic model was evaluated by the area under the curve of receiver operator characteristic curve (ROC-AUC), accuracy, specificity, sensitivity, positive predictive value, and negative predictive value.

Results: The patients with osteopenia or osteoporosis were randomly divided into training and test cohort with a ratio of 7:3. Six more predictive radiomics signatures, age, alkaline phosphatase and homocysteine were selected to construct the combined clinical-radiomic model for diagnosis of osteoporosis and osteopenia. The AUC of the combined clinical-radiomic model was 0.96 (95% confidence interval (CI), 0.95 to 0.98) in the training cohort and 0.96 (95% CI 0.92 to 1.00) in the test cohort, which were superior to the clinical model alone (training-AUC = 0.81, test-AUC = 0.79). The calibration curve demonstrated that the radiomics nomogram had good agreement between prediction and observation and decision curve analysis confirmed clinically useful.

Conclusions: The combined clinical-radiomic model that incorporates the radiomics score and clinical risk factors, can serve as a reliable and powerful tool for discriminating osteoporosis and osteopenia.
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http://dx.doi.org/10.1186/s12880-022-00868-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358842PMC
August 2022

Highly efficient incorporation of dATP in terminal transferase polymerization forming the ploy (A)-DITO-1 fluorescent probe sensing terminal transferase and T4 polynucleotide kinase activity.

Anal Chim Acta 2022 Aug 14;1221:340080. Epub 2022 Jun 14.

College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu Shandong, 273165, PR China.

Fluorescent dye DITO-1 has almost no fluorescence in the absence of nucleic acid. G bases in single strand DNA can induce maximum fluorescent enhancement followed by the A bases when it binds the DITO-1. However, the incorporation efficiency of the dATP was higher than dGTP in terminal transferase (TdT) polymerization. As a consequence, ploy (A), rather than ploy (G) via TdT polymerization had the superior photoluminance when it binded DITO-1 fluorescent dye. Here, we developed a high selective and sensitive sensing strategy for assaying TdT and T4 polynucleotide kinase activity (T4 PNK) based on the ploy (A)-DITO-1 fluorescent probe. An increasing amounts of TdT enzyme could promote the distinct incorporation of dATP on the DNA primer and form poly (A) ssDNA with a difference in length. A good linear relationship between the ΔF and the concentrations of TdT in a range of 0.2-50 U/mL was obtained and the detection limit was 0.05 U/mL. Based on the experimental results for TdT, we further expanded the application of this method for detection of a series of concentrations of T4 PNK. The ΔF and the logarithm concentrations of T4 PNK in the range of 0.1-10 U/mL showed a good linear response and the detection limit of 0.02 U/mL was obtained. In addition, the detection of T4 PNK in Hela cell lysate was achieved, demonstrating that the proposed method had the potential application in complex system. The ploy (A)-DITO-1 fluorescent probe had the excellent properties of one-step readout, robustness for target detection in complex system, and easiness operation, and showed the great potential in clinical diagnostics, inhibitor screening, and drug discovery.
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http://dx.doi.org/10.1016/j.aca.2022.340080DOI Listing
August 2022

Innate immune TLR7 signaling mediates platelet activation and platelet-leukocyte aggregate formation in murine bacterial sepsis.

Platelets 2022 Aug 3:1-9. Epub 2022 Aug 3.

Translational Research Program, Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD, USA.

Thrombocytopenia is a common complication in sepsis and is associated with higher mortality. Activated platelets express CD62P, which facilitates platelet-leukocyte aggregate (PLA) formation and contributes to thrombocytopenia in sepsis. We have reported that thrombocytopenia in murine sepsis is partly attributable to TLR7 signaling, but the underlying mechanism is unclear. In the current study, we tested the hypothesis that TLR7 mediates platelet activation and PLA formation during sepsis. In vitro, whole blood from WT mice treated with loxoribine, a TLR7 agonist, exhibited a dose-dependent increase in activated platelets compared to the control (PBS with 0.05% DMSO) or loxoribine-treated TLR7 whole blood. In a murine model of sepsis, there was a significant increase in platelet activation and PLA formation 24 hours after cecal ligation and puncture (CLP) as evidenced by double positive expression of CD41/CD62P and CD45/CD62P, respectively. The sepsis-induced PLA formation was significantly attenuated in TLR7 mice. Finally, in ex-vivo experiments, plasma isolated from septic mice induced WT platelet activation, but such effect was significantly attenuated in platelets deficient of TLR7. These findings demonstrate a pivotal role of TLR7 signaling in platelet activation and PLA formation during bacterial sepsis.
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http://dx.doi.org/10.1080/09537104.2022.2107627DOI Listing
August 2022

EEG based depression recognition using improved graph convolutional neural network.

Comput Biol Med 2022 Jul 8;148:105815. Epub 2022 Jul 8.

Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China; Joint Research Center for Cognitive Neurosensor Technology of Lanzhou University & Institute of Semiconductors, Chinese Academy of Sciences, China; Engineering Research Center of Open Source Software and Real-Time System (Lanzhou University), Ministry of Education, Lanzhou, China. Electronic address:

Depression is a global psychological disease that does serious harm to people. Traditional diagnostic method of the doctor-patient communication, is not objective and accurate enough. Thus, a more accurate and objective method for depression detection is urgently needed. Resting-state electroencephalography (EEG) can effectively reflect brain function, which have been used to study the difference of the brain between the depression patients and normal controls. In this work, the Resting-state EEG data of 27 depression patients and 28 normal controls was used in this study. We constructed the brain functional network using correlation, and extracted four linear features of EEG (activity, mobility complexity and power spectral density). We utilized a learnable weight matrix in the input layer of graph convolution neural network, creatively took the brain function network as the adjacency matrix input and the linear feature as the node feature input. We proposed our model Graph Input layer attention Convolutional Network (GICN), and it provided a good performance, showing the accuracy of 96.50% for recognition of depression and normal with 10-fold cross-validation, which indicated that our model could be used as an effective auxiliary tool for depression recognition. Besides, our method significantly outperformed other method. Additionally, the learnable weight matrix in the input layer was also used to find some edges and nodes that played an important role in depression recognition. Our findings showed that temporal lobe and parietal-occipital lobe had great effect in depression identification.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105815DOI Listing
July 2022

Studying the Interfacial Properties of Carbon/Glass Hybrid Composites via the Nanoindentation Method.

Polymers (Basel) 2022 Jul 16;14(14). Epub 2022 Jul 16.

School of Science, Inner Mongolia University of Technology, Hohhot 010051, China.

The mechanical properties of hybrid composite interfaces are critical in determining the overall properties of composite materials. To investigate the mechanical performance of hybrid composite interfaces, an accurate and efficient method must be developed. In this work, nanoindentation is used in this work to investigate the mechanical performance of the carbon/glass interface and the influence of the distance between carbon and the glass fibers on the modulus of the thermoset matrix. The results show that the interface sizes around the carbon and glass fibers are around 1.5 and 2.0 μm, respectively. The modulus around the carbon fibers is 5-11 GPa without the fiber effect, while that around the glass fibers is 4-10 GPa. The modulus of the matrix is not affected by the two types of fibers when the distance between them is greater than 4.5 μm.
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http://dx.doi.org/10.3390/polym14142897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318290PMC
July 2022

Establishment of CRISPR/Cas9 Genome-Editing System Based on Dual sgRNAs in .

J Fungi (Basel) 2022 Jun 30;8(7). Epub 2022 Jun 30.

Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, Department of Microbiology, College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.

, previously known as Asian , is one of the most commercially important edible fungi, with nutritional value and medicinal properties worldwide. However, precision genome editing using CRISPR/Cas9, which is a revolutionary technology and provides a powerful tool for molecular breeding, has not been established in . Here, plasmids harboring expression cassettes of Basidiomycete codon-optimized Cas9 and dual sgRNAs targeting under the control of the promoter and FfU6 promoter, respectively, were delivered into protoplasts of Dan3 strain through PEG-mediated transformation. The results showed that an efficient native U6 promoter of was identified, and ultimately several mutants exhibiting 5-fluorooric acid (5-FOA) resistance were obtained. Additionally, diagnostic PCR followed by Sanger sequencing revealed that fragment deletion between the two sgRNA target sites or small insertions and deletions (indels) were introduced in these mutants through the nonhomologous end joining (NHEJ) pathway, resulting in heritable changes in genomic information. Taken together, this is the first report in which a successful CRISPR/Cas9 genome-editing system based on dual sgRNAs was established in , which broadens the application of this advanced tool in Basidiomycetes.
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http://dx.doi.org/10.3390/jof8070693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318071PMC
June 2022

The Allele Increases Wheat Bread-Making Quality by Regulating SPA and SPR.

Int J Mol Sci 2022 Jul 8;23(14). Epub 2022 Jul 8.

Triticeae Research Institute, Sichuan Agricultural University, Chengdu 611130, China.

Common wheat ( L.) is an important food crop with a unique processing quality. The gene positively regulates the processing quality of wheat, but the underlying mechanism remains unclear. Here, a new allele () responsible for compact spikes and good bread performance was identified. Compared with the allele widely distributed in modern common wheat cultivars, had a missense mutation outside the miRNA172-binding site. This missense mutation led to a more compact messenger RNA (mRNA) secondary structure around the miRNA172-binding region, resulting in increased expression during the spike development stage and a consequent increase in spike density. Furthermore, this missense mutation weakened the physical interaction between Q and storage protein activator (SPA) in seeds and suppressed the expression of (). These changes increased the grain protein content and improved the bread-making quality of wheat. In conclusion, a missense mutation increases expression because of the resulting highly folded mRNA secondary structure around the miRNA172-binding site. Furthermore, this mutation improves the bread-making quality of wheat by repressing the expression of and influencing the physical interaction between Q and SPA. These findings provide new insights into the miRNA172-directed regulation of gene expression, with implications for wheat breeding.
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http://dx.doi.org/10.3390/ijms23147581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323144PMC
July 2022

Chitosan Increases Lysine Content through Amino Acid Transporters in .

Foods 2022 Jul 21;11(14). Epub 2022 Jul 21.

Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, Department of Microbiology, College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.

Lysine content is considered an important indicator of the quality of . In this study, chitosan was used to improve lysine content of . Optimal design conditions were obtained using central combination design (CCD): treatment concentration was 14.61 μg/mL, treatment time was 52.90 h, and the theoretical value of lysine content was 30.95 mg/g. We used Basic Local Alignment Search Tool Protein (BLASTP) to search the genome database using known AATs in the NCBI database. There were 11 members of AAT in . The expression levels of and genes increased significantly with chitosan treatment. Subsequently, and silencing strains were constructed using RNAi technology. The lysine content of the wild-type (WT) strain treated with chitosan increased by 26.41%. Compared with the chitosan-induced WT strain, chitosan-induced lysine content decreased by approximately 24.87% in the silencing strain, and chitosan-induced lysine content in the silencing strain increased by approximately 13.55%. The results indicate that AAT3 and AAT4 are involved in the regulation of the biosynthesis of lysine induced by chitosan in . AAT3 may participate in the absorption of lysine, and AAT4 may be involved in the excretion of lysine with chitosan treatment.
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http://dx.doi.org/10.3390/foods11142163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325215PMC
July 2022

Alteration of Trop-2 expression in breast cancer cells by clinically used therapeutic agents and acquired tamoxifen resistance.

Breast Cancer 2022 Jul 27. Epub 2022 Jul 27.

Department of Translational Oncology, St. Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.

Background: Sacituzumab govitecan is an antibody-drug conjugate that delivers SN-38, an active metabolite of irinotecan, to the target molecule, trophoblast cell-surface antigen 2 (Trop-2). It is a promising drug for triple-negative breast cancer and is anticipated to be effective for luminal breast cancer. The efficacy of the agent relies on the expression of Trop-2 rather than its intracellular function. However, conditions that alter the Trop-2 expression have not been well investigated.

Methods: We tested a range of clinically related treatments for their effect on Trop-2 expression in cultured breast cancer cell lines.

Results: The expression level of Trop-2 differed among cell lines, independent of their subtypes, and was highly variable on treatment with kinase inhibitors, tamoxifen, irradiation, and chemotherapeutic agents including irinotecan. While inhibitors of AKT, RSK, and p38 MAPK suppressed the Trop-2 expression, tamoxifen treatment significantly increased Trop-2 expression in luminal cancer cell lines. Notably, luminal cancer cells with acquired resistance to tamoxifen also exhibited higher levels of Trop-2. We identified transcription factor EB (TFEB) as a possible mechanism underlying tamoxifen-induced elevation of Trop-2 expression. Tamoxifen triggers dephosphorylation of TFEB, an active form of TFEB, and the effect of tamoxifen on Trop-2 was prevented by depletion of TFEB. A luciferase reporter assay showed that Trop-2 induction by TFEB was dependent on a tandem E-box motif within the Trop-2 promoter region.

Conclusions: Overall, these results suggest that the effectiveness of sacituzumab govitecan could be altered by concomitant treatment and that tamoxifen could be a favorable agent for combined therapy.
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http://dx.doi.org/10.1007/s12282-022-01389-3DOI Listing
July 2022

High Glucose Aggravates Retinal Endothelial Cell Dysfunction by Activating the RhoA/ROCK1/pMLC/Connexin43 Signaling Pathway.

Invest Ophthalmol Vis Sci 2022 Jul;63(8):22

Department of Ophthalmology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province, China.

Purpose: This research aims to explore the mechanism underlying the relationship between RhoA/ROCK signaling and Connexin43 (Cx43) in retinal endothelial cell dysfunction and to evaluate the protective effect of ROCK inhibitors against retinal endothelial cell dysfunction in diabetic retinopathy (DR) models.

Methods: TUNEL staining, hematoxylin and eosin staining, a retinal digestion assay, and Evans blue assay were conducted to explore the effect of fasudil in alleviating retinal dysfunction induced by DR. ELISA, the CCK-8 assay, and flow cytometry were conducted to study inflammation, viability, and apoptosis of mouse retinal microvascular endothelial cells treated with high glucose and ROCK inhibitors. The qRT-PCR and Western blotting were used to evaluate the expression of RhoA, ROCK1, ROCK2, MLC, pMLC, and Cx43. Co-immunoprecipitation was used to verify the interaction between pMLC and Cx43. Immunofluorescence and scrape-loading and dye transfer were used to evaluate the expression and function of Cx43.

Results: Marked endothelial cell dysfunction resulting from the activation of RhoA/ROCK1 signaling was found in in vivo and in vitro models of DR. Via interaction with pMLC, which is downstream of RhoA/ROCK1, a significant downregulation of Cx43 was observed in retinal endothelial cells. Treatment with ROCK inhibitors ameliorated retinal endothelial dysfunction in vitro. The ROCK inhibitor, fasudil, significantly alleviated retinal dysfunction as shown by a decrease of retinal acellular capillaries, an improvement of vascular permeability, and a reduction of cell apoptosis in vivo.

Conclusions: Our study highlights a novel mechanism that high glucose could activate RhoA/ROCK1/pMLC signaling, which targets the expression and localization of Cx43 and is responsible for cell viability, apoptosis, and inflammation, resulting in retinal endothelial cell injury. ROCK inhibitors markedly ameliorate endothelial cell dysfunction, suggesting their therapeutic potential for diabetic retinopathy.
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http://dx.doi.org/10.1167/iovs.63.8.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339693PMC
July 2022

Directed evolution of a cyclodipeptide synthase with new activities label-free mass spectrometric screening.

Chem Sci 2022 Jun 2;13(25):7581-7586. Epub 2022 Jun 2.

CAS Key Lib Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China.

Directed evolution is a powerful approach to engineer enzymes iterative creation and screening of variant libraries. However, assay development for high-throughput mutant screening remains challenging, particularly for new catalytic activities. Mass spectrometry (MS) analysis is label-free and well suited for untargeted discovery of new enzyme products but is traditionally limited by slow speed. Here we report an automated workflow for directed evolution of new enzymatic activities high-throughput library creation and label-free MS screening. For a proof of concept, we chose to engineer a cyclodipeptide synthase (CDPS) that synthesizes diketopiperazine (DKP) compounds with therapeutic potential. In recombinant , site-saturation mutagenesis (SSM) and error-prone PCR (epPCR) libraries expressing CDPS mutants were automatically created and cultivated on an integrated work cell. Culture supernatants were then robotically processed for matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) MS analysis at a rate of 5 s per sample. The resulting mass spectral data were processed custom computational algorithms, which performed a multivariant analysis of 108 theoretical mass-to-charge (/) values of 190 possible DKP molecules within a mass window of 115-373 Da. An F186L CDPS mutant was isolated to produce cyclo(l-Phe-l-Val), which is undetectable in the product profile of the wild-type enzyme. This robotic, label-free MS screening approach may be generally applicable to engineering other enzymes with new activities in high throughput.
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http://dx.doi.org/10.1039/d2sc01637kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241961PMC
June 2022

SMAD4 suppresses colitis-associated carcinoma through inhibition of CCL20/CCR6-mediated inflammation.

Gastroenterology 2022 Jul 18. Epub 2022 Jul 18.

Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN; Graduate Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee; Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, TN; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address:

Background & Aims: We previously reported that colon epithelial cell silencing of Smad4 increased epithelial expression of inflammatory genes, including the chemokine CCL20, and increased susceptibility to colitis-associated cancer. Here, we examine the role of the chemokine/receptor pair CCL20/CCR6 in mediating colitis-associated colon carcinogenesis induced by SMAD4 loss.

Methods: In silico analysis of SMAD4, CCL20, and CCR6 mRNA expression was performed on published transcriptomic data from human ulcerative colitis (UC), and colon and rectal cancer samples. Immunohistochemistry for CCL20 and CCR6 was performed on human tissue microarrays (TMAs) comprising human UC-associated cancer specimens, Mice with conditional, epithelial-specific Smad4 loss with and without germline deletion of the Ccr6 gene were subjected to colitis and followed for up to 3 months. Tumors were quantified histologically, and immune cell populations were analyzed by flow cytometry and immunostaining.

Results: In human UC-associated cancers, loss of epithelial SMAD4 was associated with increased CCL20 expression and CCR6+ cells. SMAD4 loss in mouse colon epithelium led to enlarged gut-associated lymphoid tissues and recruitment of immune cells to the mouse colon epithelium and stroma, particularly Treg, T17, and dendritic cells. Loss of CCR6 abrogated these immune responses and significantly reduced the incidence of colitis-associated tumors observed with loss of SMAD4 alone.

Conclusions: Regulation of mucosal inflammation is central to SMAD4 tumor suppressor function in the colon. A key downstream node in this regulation is suppression of epithelial CCL20 signaling to CCR6 in immune cells. Loss of SMAD4 in the colon epithelium increases CCL20 expression and chemoattraction of CCR6+ immune cells, contributing to greater susceptibility to colon cancer.
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http://dx.doi.org/10.1053/j.gastro.2022.07.016DOI Listing
July 2022

Financial Crisis in Management Stress: From the Perspective of Crisis Anxiety of Others.

Front Psychol 2022 4;13:854746. Epub 2022 Jul 4.

School of International Economics Trade, Jiangxi University of Finance and Economics, Nanchang, China.

The crisis anxiety of others is a phenomenon that goes hand in hand with the spread of the occupational health pandemic. It is becoming increasingly important to better understand its emergence process, especially in the era of greater uncertainty. This study aims to examine the impact of the external financial crisis on managerial stress among financial employees. The sample consists of 347 senior managers and financial employees from companies in China. The empirical analysis shows that external financial crises have significant effects on anxiety levels, especially external corporate crisis, debt crisis and growth crisis both have mediating effect on the relationship between anxiety level and pressure management and the relationship between external financial crisis and pressure management. This study explores the rules for the emergence of anxiety among corporate managers and expands the scope of environmental factors that need to be discussed in the study of corporate financial management. This study provides theoretical implications for the psychological study of Financial Management and practical implications for corporate financial management.
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http://dx.doi.org/10.3389/fpsyg.2022.854746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291433PMC
July 2022

Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway.

Stem Cell Res Ther 2022 07 18;13(1):326. Epub 2022 Jul 18.

Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China.

Background: Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting the application of BMSCs. Therefore, improving BMSCs viability in adverse microenvironments is an important means to improve the effectiveness of BMSCs therapy.

Objective: To illustrate the protective effect of andrographolide (AG) against glucose and serum deprivation under hypoxia (1% O) (GSDH)-induced cell injury in BMSCs and investigate the possible underlying mechanisms.

Methods: An in vitro primary rat BMSCs cell injury model was established by GSDH, and cellular viability, proliferation and apoptosis were observed after AG treatment under GSDH. Reactive oxygen species levels and oxidative stress-related genes and proteins were measured by flow cytometry, RT-qPCR and Western blotting. Mitochondrial morphology, function and number were further assessed by laser confocal microscopy and flow cytometry.

Results: AG protected BMSCs against GSDH-induced cell injury, as indicated by increases in cell viability and proliferation and mitochondrial number and decreases in apoptosis and oxidative stress. The metabolic status of BMSCs was changed from glycolysis to oxidative phosphorylation to increase the ATP supply. We further observed that the NRF2 pathway was activated by AG, and treatment of BMSCs with a specific NRF2 inhibitor (ML385) blocked the protective effect of AG.

Conclusion: Our results suggest that AG is a promising agent to improve the therapeutic effect of BMSCs.
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http://dx.doi.org/10.1186/s13287-022-03016-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290240PMC
July 2022

Risk factors of perioperative complications and management with enhanced recovery after primary surgery in women with epithelial ovarian carcinoma in a single center.

Oncol Lett 2022 May 16;23(5):155. Epub 2022 Mar 16.

Department of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I-IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4-5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3-5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3-5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3-5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3-5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.
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http://dx.doi.org/10.3892/ol.2022.13274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258594PMC
May 2022

Enzyme-nanozyme cascade colorimetric sensor platform: a sensitive method for detecting human serum creatinine.

Anal Bioanal Chem 2022 Aug 12;414(20):6271-6280. Epub 2022 Jul 12.

Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, China.

Creatinine, as a significant biomarker for kidney, thyroid, and muscle dysfunction-related diseases, detection is of great important meaning. In this paper, an enzyme-nanozyme cascade sensing platform was developed for visual creatinine detection. Perovskite oxide BiFeO synthesized by a sol-gel method was applied as a nanozyme, showing excellent peroxidase-like activity. During detection, creatinine was oxidized in turn by three natural enzymes (creatinase, creatininase, and sarcosine oxidase) to produce HO, and HO was then catalyzed by the BiFeO nanozyme, resulting in the change of achromatous 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB). Based on this principle, visual quantification of creatinine was realized. Due to the high stability and catalytic efficiency of nanozyme, the cascade sensing platform can be used to detect creatinine in a broad range of 0.5-150 μM with a detection limit of 0.09 μM. Meanwhile, thanks to the specificity of the natural enzymes, the platform exhibited admirable selectivity for creatinine determination despite the existence of a variety of interfering substances, which were successfully adopted to measure the level of creatinine in human serums. The cascade sensing platform is expected to serve the determination of a large number of biomarkers by simply alternating the natural enzymes.
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http://dx.doi.org/10.1007/s00216-022-04199-wDOI Listing
August 2022

Multi-omics analysis of the biomarkers and molecular mechanism of rheumatoid arthritis with bone destruction.

Joint Bone Spine 2022 Jul 9:105438. Epub 2022 Jul 9.

Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China. Electronic address:

Objectives: Our study aimed to elucidate the role of metabolites, bacteria, and fungi in rheumatoid arthritis (RA) patients with bone destruction (BD(+)) and identify some biomarkers to predicate bone progression of RA.

Methods: Plasma metabolites of the 127 RA patients and 69 healthy controls were conducted by using nontargeted liquid chromatography-mass spectrometry (LC-MS). The gut bacteria and fungi were assessed by 16S rRNA and internal transcribed spacer (ITS).

Results: Compared with RA patients without bone destruction (BD(-)), some metabolites, bacteria, and fungi were altered in BD(+). Seven metabolites were selected as key metabolites for classifying the BD(+) and BD(-) groups with moderate accuracy (AUC=0.71). Metabolites-groups, metabolites-metabolites, and metabolites-clinical factors had a certain correlation, and 7 metabolites were enriched in glycerophospholipid metabolism and L-arginine and proline metabolism pathways. The bacteria and fungi of the BD(+) group showed significant differences in composition and function compared with BD(-) group. The changed 4 bacteria and 12 fungi yielded accuracy (AUC=0.74 and AUC=0.87, respectively) for the two groups. Taking 7 metabolites, 4 bacteria, and 12 fungi as a panel for AUC analysis, an improved AUC of 0.99 significantly discriminated the two groups. The changed metabolites, gut bacteria, and fungi may affect the pathway related to L-arginine.

Conclusions: Our nontargeted LC-MS, 16S rRNA, and ITS highlighted a novel link among the metabolites, bacteria, fungi, and pathology of BD(+), which could contribute to our understanding of the role of metabolites, bacteria, and fungi in BD(+) etiology and offered some novel biomarkers to predict the bone progression of RA.
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http://dx.doi.org/10.1016/j.jbspin.2022.105438DOI Listing
July 2022

Platelet-rich Plasma Injection Can Be a Viable Alternative to Corticosteroid Injection for Conservative Treatment of Rotator Cuff Disease: A Meta-analysis of Randomized Controlled Trials.

Arthroscopy 2022 Jul 7. Epub 2022 Jul 7.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University; Chengdu, China. Electronic address:

Purpose: The purpose of this study was to explore whether PRP injection can be a viable alternative to CS injection for conservative treatment of rotator cuff disease.

Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, The Cochrane Library, and Web of Science were searched for English-written randomized controlled trials (RCTs) which compared PRP and CS injections for patients with rotator cuff disease from January 1, 1990, to March 20, 2022. Two evaluators independently screened the literature, extracted data, and assessed the level of evidence and methodological quality of the enrolled studies. The meta-analysis was conducted using RevMan 5.3.3 software.

Results: Thirteen non-surgical RCTs with 725 patients were included. Compared with CS, PRP provided statistically worse short-term (<2 months) changes (Δ) of the American Shoulder and Elbow Surgeons (ASES) assessment, Δ the Simple Shoulder Test (SST), Δ the Disability of Arm, Shoulder and Hand (DASH) questionnaires but better medium-term (2 to 6 months) Δ DASH, long-term (≥ 6 months) Δ Constant-Murley Score (CMS), Δ ASES and Δ SST. No statistical differences regarding pain reduction were found between the two groups. PRP injections led to worse short-term Δ forward flexion, Δ internal rotation but better medium-term Δ forward flexion and Δ external rotation. PRP had significantly lower rates of postinjection failure (requests for a subsequent injection or surgical intervention prior to 12 months) than CS. No outcome reached the minimal clinically important difference (MCID). After sensitivity analyses by excluding studies with substantial clinical and/or methodological heterogeneity, PRP showed better medium-term Δ ASES, Δ VAS, and long-term Δ VAS which reached the MCID.

Conclusions: Without the drawbacks of CS injection, PRP injection is not worse than CS injection in pain relief and function recovery at any time point of the follow-up. PRP injection may reduce rates of subsequent injection or surgery, and might provide better improvement in pain and function in the medium- to long-term. PRP injection can be a viable alternative to CS injection for conservative treatment of rotator cuff disease.

Level Of Evidence: Systematic review of Level I and II studies.
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http://dx.doi.org/10.1016/j.arthro.2022.06.022DOI Listing
July 2022

Preparation of three-dimensional matrices of human gingival tissue and comparison of induction of mesenchymal and blastema stem cell behaviors in prepared scaffolds.

Cell Mol Biol (Noisy-le-grand) 2022 May 22;68(1):102-108. Epub 2022 May 22.

Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

This study aimed to compare the behavior of rat bone marrow mesenchymal stem cells and rabbit auricle blastema cells implanted in non-cellular gingival tissue scaffold of human. In this regard, the tissues obtained from gingival surgeries in the dental clinic were de-cellulated using two detergents of sodium dodecyl sulfate and triton 100-X. After washing and sterilization, they were used as a scaffold for culture with bone marrow mesenchymal stem cells of rats. Using light and electron microscopy, these scaffolds were examined before and after 1, 2, and 4 weeks of cell culture. Also, the prepared three-dimensional scaffold was placed in the blastema ring obtained from the rabbit earlobe punch. The samples were evaluated 1, 2, and 4 weeks after culture based on histology techniques. The results showed that the study of scaffolds by electron microscopy showed preserving the epithelium matrix and the collagen fibers in the tissue. Structures similar to the epithelium were created in both samples. In addition, induction of cellular secretion was observed in scaffold cells migrating to the scaffold. In general, scaffolds made from human gums can be a good platform for studying cellular behaviors. Of course, further experiments to determine the nature of differentiated cells can help advance our knowledge of matrix cell interactions.
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http://dx.doi.org/10.14715/cmb/2022.68.1.13DOI Listing
May 2022

Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: Analysis of the open-label extension of the NEURO-TTR trial.

Muscle Nerve 2022 Jul 7. Epub 2022 Jul 7.

Analysis Group, Inc, Boston, Massachusetts.

Introduction/aims: Hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) progressively affects patients' functionality and compromises health-related quality of life (HRQL). The aim of this study was to quantify the projected long-term treatment effects of inotersen vs placebo on HRQL measures.

Methods: The inotersen phase 2/3 randomized, double-blind, placebo-controlled trial NEURO-TTR (NCT01737398, 65 weeks) and its subsequent open-label extension (OLE; NCT02175004, 104 weeks) included 172 (112 inotersen and 60 placebo) patients. Placebo double-blind period and overall inotersen-inotersen (double-blind/OLE) treatment period (170 weeks) data were used to extrapolate the long-term placebo-placebo effect using mixed-effects models with repeated measures. Changes from baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) and 36-Item Short Form Health Survey version 2 (SF-36v2) in hATTR-PN were estimated. Differences in changes were compared between the inotersen-inotersen and extrapolated placebo-placebo arms.

Results: Inotersen-inotersen patients maintained their HRQL with an observed change ranging from 10.3% improvement (Norfolk QoL-DN item "Pain kept you awake at night") to 11.6% deterioration (SF-36v2 Activities of Daily Living subdomain). The extrapolated placebo-placebo results suggest greater deterioration over time compared with inotersen-inotersen treatment on Norfolk QoL-DN total score (23.6; 95% confidence interval [CI], 8.9-38.3; P < .01), Activities of Daily Living (4.6; 95% CI, 2.0-7.3; P < .001), and "Pain kept you awake at night" (1.2; 95% CI, 0.4-1.9; P < .01). Similarly, greater deterioration was expected for the SF-36v2 Physical Component Summary (8.0; 95% CI, 3.2-12.8, P < .01), Bodily Pain (7.8; 95% CI, 2.0-13.5; P < .01), and Physical Functioning (10.6; 95% CI, 5.5-15.6; P < .0001).

Discussion: Long-term (>3 years) inotersen treatment was associated with slowing and, in some domains, halting of deterioration in key HRQL outcome measures, particularly physical functioning and pain.
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http://dx.doi.org/10.1002/mus.27675DOI Listing
July 2022

Notoginsenoside R1-loaded mesoporous silica nanoparticles targeting the site of injury through inflammatory cells improves heart repair after myocardial infarction.

Redox Biol 2022 08 24;54:102384. Epub 2022 Jun 24.

Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Notoginsenoside R1 (NGR1) is the main monomeric component extracted from the dried roots and rhizomes of Panax notoginseng, and exerts pharmacological action against myocardial infarction (MI). Owing to the differences in compound distribution, absorption, and metabolism in vivo, exploring a more effective drug delivery system with a high therapeutic targeting effect is crucial. In the early stages of MI, CD11b-expressing monocytes and neutrophils accumulate at infarct sites. Thus, we designed a mesoporous silica nanoparticle-conjugated CD11b antibody with loaded NGR1 (MSN-NGR1-CD11b antibody), which allowed NGR1 precise targeted delivery to the heart in a noninvasively manner. By increasing targeting to the injured myocardium, intravenous injection of MSN-NGR1-CD11b antibody nanoparticle in MI mice improved cardiac function and angiogenesis, reduced cell apoptosis, and regulate macrophage phenotype and inflammatory factors and chemokines. In order to further explore the mechanism of NGR1 protecting myocardium, cell oxidative stress model and oxygen-glucose deprivation (OGD) model were established. NGR1 protected H9C2 cells and primary cardiomyocytes against oxidative injury induced by HO and OGD treatment. Further network pharmacology and molecular docking analyses suggested that the AKT, MAPK and Hippo signaling pathways were involved in the regulation of NGR1 in myocardial protection. Indeed, NGR1 could elevate the levels of p-Akt and p-ERK, and promote the nuclear translocation of YAP. Furthermore, LY294002 (AKT inhibitor), U0126 (ERK1/2 inhibitor) and Verteporfin (YAP inhibitor) administration in H9C2 cells indicated the involvement of AKT, MAPK and Hippo signaling pathways in NGR1 effects. Meanwhile, MSN-NGR1-CD11b antibody nanoparticles enhanced the activation of AKT and MAPK signaling pathways and the nuclear translocation of YAP at the infarcted site. Our research demonstrated that MSN-NGR1-CD11b antibody nanoparticle injection after MI enhanced the targeting of NGR1 to the infarcted myocardium and improved cardiac function. More importantly, our pioneering research provides a new strategy for targeting drug delivery systems to the ischemic niche.
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http://dx.doi.org/10.1016/j.redox.2022.102384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287735PMC
August 2022

Upregulation of cadherin-11 contributes to cholestatic liver fibrosis.

Pediatr Investig 2022 Jun 22;6(2):100-110. Epub 2022 Mar 22.

Department of Pediatric Surgery, Xin Hua Hospital School of Medicine, Shanghai Jiao Tong University Shanghai China.

Importance: Cadherin-11 (CDH11), a cell-to-cell adhesion molecule, is implicated in the fibrotic process of several organs. Biliary atresia (BA) is a common cholestatic liver disease featuring cholestasis and progressive liver fibrosis in children. Cholestatic liver fibrosis may progress to liver cirrhosis and lacks effective therapeutic strategies. Currently, the role of CDH11 in cholestatic liver fibrosis remains unclear.

Objective: This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis.

Methods: The expression of in BA livers was evaluated by database analysis and immunostaining. Seven BA liver samples were used for immunostaining. The wild type (Wt) and knockout ( ) mice were subjected to bile duct ligation (BDL) to induce cholestatic liver fibrosis. The serum biochemical analysis, liver histology, and western blotting were used to assess the extent of liver injury and fibrosis as well as activation of transforming growth factor-β (TGF-β)/Smad pathway. The effect of CDH11 on the activation of hepatic stellate cell line LX-2 cells was investigated.

Results: Analysis of public RNA-seq datasets showed that expression levels were significantly increased in livers of BA, and CDH11 was correlated with liver fibrosis in BA. BDL-induced liver injury and liver fibrosis were attenuated in mice compared to Wt mice. The protein expression levels of phosphorylated Smad2/3 were decreased in livers of BDL mice compared to Wt BDL mice. knockdown inhibited the activation of LX-2 cells.

Interpretation: CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease, such as BA.
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http://dx.doi.org/10.1002/ped4.12317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218970PMC
June 2022

Sex Differences in Epicardial Adipose Tissue: Association With Atrial Fibrillation Ablation Outcomes.

Front Cardiovasc Med 2022 13;9:905351. Epub 2022 Jun 13.

Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

Background: There are significant differences in the prevalence and prognosis of atrial fibrillation (AF) between sexes. Epicardial adipose tissue (EAT) has been found as a risk factor for AF. This study aimed to evaluate whether sex-based EAT differences were correlated with AF recurrence and major adverse cardiovascular events (MACE).

Methods: In this study, postmenopausal women and age, BMI, and type of AF matched men who had received first catheter ablation were included. EAT volume was quantified based on the pre-ablation cardiac computed tomography (CT) images. Clinical, CT, and echocardiographic variables were compared by sex groups. The predictors of AF recurrence and MACE were determined through Cox proportional hazards regression.

Results: Women were found with significantly lower total EAT volumes ( < 0.001) but higher periatrial/total (P/T) EAT ratios ( = 0.009). The median follow-up duration was 444.5 days. As revealed by the result of the Kaplan-Meier survival analysis, the women were found to have a significantly higher prevalence of AF recurrence (log rank, = 0.011) but comparable MACE (log rank, = 0.507) than men. Multivariate analysis demonstrated that female gender (HR: 1.88 [95% CI: 1.03, 4.15], = 0.032), persistent AF (HR: 2.46 [95% CI: 1.19, 5.05], = 0.015), left atrial (LA) dimension (HR: 1.47 [95% CI: 1.02, 2.13], = 0.041), and P/T EAT ratio (HR: 1.73 [95% CI: 1.12, 2.67], = 0.013) were found as the independent predictors of AF recurrence. Sex-based subgroup multivariable analysis showed that the P/T EAT ratio was an independent predictor of AF recurrence in both men (HR: 1.13 [95% CI: 1.01, 1.46], = 0.047) and women (HR: 1.37 [95% CI: 1.11, 1.67], = 0.028). While age (HR: 1.81 [95% CI: 1.18, 2.77], = 0.007), BMI (HR: 1.44 [95% CI: 1.02, 2.03], = 0.038), and periatrial EAT volume (HR: 1.31 [95% CI: 1.01, 1.91], = 0.046) were found to be independent of MACE.

Conclusion: Women had a higher P/T EAT ratio and AF post-ablation recurrence but similar MACE as compared with men. Female gender and P/T EAT ratio were found to be independent predictors of AF recurrence, whereas age and periatrial EAT volume were found to be independent predictors of MACE.
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http://dx.doi.org/10.3389/fcvm.2022.905351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234200PMC
June 2022

Relationship Between TNF-α and the Risk of Cerebral Palsy: A Systematic Review and Meta-Analysis.

Front Neurol 2022 13;13:929280. Epub 2022 Jun 13.

Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, China.

Objective: We performed a meta-analysis to investigate the relationship between blood tumor necrosis factor-alpha (TNF-α) levels and the risk of cerebral palsy (CP) in children.

Methods: PubMed, Web of Science, Cochrane Library and Ovid databases were searched from the date of database inception to 26 April 2022. Data were extracted and pooled from observational studies related to TNF-α and the risk of CP in children. Quality was assessed using the Newcastle-Ottawa Scale. We used the inverse variance method with a random-effects model to estimate the odds ratios with 95% confidence intervals (CIs), and stratified analyses and sensitivity analysis were utilized to analyse heterogeneity.

Results: Nine studies with 1,117 cases and 3,563 controls were included in our meta-analysis. The quality of the literature was good, and no publication bias was noted. According to the random-effects model, blood TNF-α levels were associated with the risk of CP (OR 1.82; 95% CI, 1.25-2.66) in a heterogeneous set of studies ( = 81.2%, = 0.000).

Conclusion: Our findings indicate that elevated TNF-α levels in the blood are associated with an increased risk of CP. The association of TNF-α with CP requires further investigation.
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http://dx.doi.org/10.3389/fneur.2022.929280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234274PMC
June 2022

Circulating lymphocyte subsets are prognostic factors in patients with nasopharyngeal carcinoma.

BMC Cancer 2022 Jun 29;22(1):716. Epub 2022 Jun 29.

Department of Clinical Laboratory, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, No 1, East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China.

Background: Nasopharyngeal carcinoma (NPC) is a geographically and racially variable disease that has a high incidence in Southeast China. According to previous studies on tumor immunity, we compared multiple clinical parameters and blood indexes with outcomes regarding to Epstein-Barr virus (EBV) status in NPC patients.

Methods: According to the EBV load at diagnosis, 220 NPC patients who received concurrent chemoradiotherapy (CRT) were divided into two groups: EBV DNA ≥ 1500 copies/mL and EBV DNA < 1500 copies/mL, respectively. We compared clinical parameters with peripheral blood mononuclear cells, lymphocyte subsets and biochemical indexes. We also analyzed distant metastases and the overall survival rate regarding to these characteristics.

Results: In most cases, the two groups showed the same trends. Most blood indexes were decreased during CRT and the decrease of the absolute count was more significant than the percentage. Patients with younger age showed the higher CD3+ and CD3 + CD8+ percentages. Patients whose EBV DNA ≥ 1500 copies/mL showed a higher N classification than those with EBV DNA < 1500 copies/mL at first diagnosis. Within patients with EBV DNA ≥ 1500 copies/mL, a higher CD3 + CD8+ percentage or lower CD3-CD56+ percentage had better OS rates, and the CD3 + CD8+ percentage was an independent prognostic factor by multivariate survival analyses.

Conclusions: CRT caused an overall decrease of blood cells in NPC patients. Among all the blood indexes, the CD3 + CD8+ percentage showed a correlation with age and was an independent prognostic factor in patients with EBV DNA ≥ 1500 copies/mL at first diagnosis, which is worthy for further large cohort study.
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http://dx.doi.org/10.1186/s12885-022-09438-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241295PMC
June 2022

A Novel YTHDF3-Based Model to Predict Prognosis and Therapeutic Response in Breast Cancer.

Front Mol Biosci 2022 9;9:874532. Epub 2022 Jun 9.

Department of Breast Cancer, Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan, China.

Due to high tumor heterogeneity, breast cancer (BC) patients still suffer poor survival outcomes. YTHDF3 plays a critical role in the prognosis of BC patients. Hence, we aimed to construct a YTHDF3-based model for the prediction of the overall survival (OS) and the sensitivity of therapeutic agents in BC patients. Based on The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) database, we obtained BC patients' data ( = 999) with YTHDF3 expression profiles. The association between YTHDF3 expression and 5-year OS was determined Cox proportional hazards regression (CPHR) analysis. By integrating the variables, we established a prognostic nomogram. The model was estimated discrimination, calibration ability, and decision curve analysis (DCA). The performance of the model was compared with the TNM stage system through receiver operating characteristic (ROC) curves and DCA. By means of the Genomics of Drug Sensitivity in Cancer (GDSC) database (https://www.cancerrxgene.org/), the therapeutic agents' response was estimated. Gene set enrichment analysis (GSEA) demonstrated possible biological mechanisms related to YTHDF3. TIMER and CIBERSORTx were employed to analyze the association between YTHDF3 and tumor-infiltrating immune cells. The high YTHDF3 expression was significantly correlated with poor 5-year OS in BC patients. Through multivariate CPHR, four independent prognostic variables (age, TNM stage, YTHDF3 expression, and molecular subtype) were determined. On the basis of the four factors, a YTHDF3-based nomogram was built. The area under the curve (AUC) of the ROC curve for the model surpassed that of the TNM stage system (0.72 vs. 0.63, = 0.00028). The model predictions showed close consistency with the actual observations via the calibration plot. Therapeutic response prediction was conducted in high- and low-risk groups and compared with each other. The BC patients with higher risk scores showed more therapeutic resistance than those with a lower risk score. YTHDF3 was verified as a prognostic biomarker of BC, and a novel YTHDF3-based model was constructed to predict the 5-year OS of BC patients. Our model could be applied to effectively predict the therapeutic response of commonly used agents for BC patients.
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http://dx.doi.org/10.3389/fmolb.2022.874532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218665PMC
June 2022

P4HB UFMylation regulates mitochondrial function and oxidative stress.

Free Radic Biol Med 2022 Aug 23;188:277-286. Epub 2022 Jun 23.

Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

UFMylation is a ubiquitin-like modification which attaches the ubiquitin-fold modifier 1 to target proteins. To date, only a few UFMylation targets have been identified. In the current study, we demonstrated that P4HB is a new target protein for UFMylation and it can be UFMylated at three lysine residues in the form of mono-UFMylation. P4HB has oxidoreductase, chaperone and isomerase effects. It presents in the endoplasmic reticulum, mitochondria and cytosol. Next, we generated a stable HepG2 cell line, the hepatocellular cells, with defective P4HB UFMylation. Our data show that P4HB UFMylation defect promotes P4HB protein degradation via the ubiquitin-proteasome pathway. Defective P4HB UFMylation causes mitochondrial function damage, oxidative stress, and endoplasmic reticulum stress in HepG2 cells. These effects are more obvious when treating HepG2 cells with palmitic acid, which is frequently used as one of the cell models of non-alcoholic fatty liver disease (NAFLD). Our results identify UFMylation as a key post-translational modification for the maintenance of P4HB stability and biological functions in HepG2 cells, and point to P4HB UFMylation as a potential direction in the study of NAFLD.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.06.237DOI Listing
August 2022

Apparent Diffusion Coefficient Map-Based Radiomics Features for Differential Diagnosis of Pleomorphic Adenomas and Warthin Tumors From Malignant Tumors.

Front Oncol 2022 7;12:830496. Epub 2022 Jun 7.

Department of MRI, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Purpose: The magnetic resonance imaging (MRI) findings may overlap due to the complex content of parotid gland tumors and the differentiation level of malignant tumor (MT); consequently, patients may undergo diagnostic lobectomy. This study assessed whether radiomics features could noninvasively stratify parotid gland tumors accurately based on apparent diffusion coefficient (ADC) maps.

Methods: This study examined diffusion-weighted imaging (DWI) obtained with echo planar imaging sequences. Eighty-eight benign tumors (BTs) [54 pleomorphic adenomas (PAs) and 34 Warthin tumors (WTs)] and 42 MTs of the parotid gland were enrolled. Each case was randomly divided into training and testing cohorts at a ratio of 7:3 and then was compared with each other, respectively. ADC maps were digitally transferred to ITK SNAP (www.itksnap.org). The region of interest (ROI) was manually drawn around the whole tumor margin on each slice of ADC maps. After feature extraction, the Synthetic Minority Oversampling TEchnique (SMOTE) was used to remove the unbalance of the training dataset. Then, we applied the normalization process to the feature matrix. To reduce the similarity of each feature pair, we calculated the Pearson correlation coefficient (PCC) value of each feature pair and eliminated one of them if the PCC value was larger than 0.95. Then, recursive feature elimination (RFE) was used to process feature selection. After that, we used linear discriminant analysis (LDA) as the classifier. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the ADC.

Results: The LDA model based on 13, 8, 3, and 1 features can get the highest area under the ROC curve (AUC) in differentiating BT from MT, PA from WT, PA from MT, and WT from MT on the validation dataset, respectively. Accordingly, the AUC and the accuracy of the model on the testing set achieve 0.7637 and 73.17%, 0.925 and 92.31%, 0.8077 and 75.86%, and 0.5923 and 65.22%, respectively.

Conclusion: The ADC-based radiomics features may be used to assist clinicians for differential diagnosis of PA and WT from MTs.
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http://dx.doi.org/10.3389/fonc.2022.830496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210443PMC
June 2022

High Temperature Tribological Performance of Steel/Copper Friction Pairs Lubricated with a Modified C-WS-(FeO + TiN) Nanoadditives in Non-Copper Coated Solid Wires.

Nanomaterials (Basel) 2022 Jun 17;12(12). Epub 2022 Jun 17.

Shandong Juli Welding Co., Ltd., Dezhou 253011, China.

In this study, four kinds of nanoparticles, graphite, WS, FeO, and TiN, were used as lubricating additives for steel/copper friction pairs to solve the problem of welding contact tube wear with non-copper-coated solid wire at high temperature. The single and composite nanoparticles have excellent dispersion stability in absolute ethanol under the action of the compound surfactant NaSTA + OA + PVP (i.e., sodium stearate, oleic acid, and polyvinylpyrrolidone). The tribological test results showed that the maximum decrement, with reference to the average coefficient of friction and wear volumes, were measured with nanoparticle concentration in 1:1:1 ratio at 300 °C. Compared with dry friction, the average friction coefficient and wear volume are reduced by 74.3% and 84.8%, respectively, which may be attributed to the formation of a stable tribo-film mainly composed of C-O, FeO, WO, TiO, TiNO composite on the worn surface. Therefore, it is considered that the combined lubrication effects of the ball-bearing effect, repairing of worn surfaces, and the tribo-film resulted in the lowest friction and wear.
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http://dx.doi.org/10.3390/nano12122091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229732PMC
June 2022
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