Publications by authors named "Jie Yao"

490 Publications

Enhanced depletion of antibiotics and accelerated estabilization of dissolved organic matter by hydrothermal pretreatment during composting of oxytetracycline fermentation residue.

Bioresour Technol 2021 Jul 22;339:125618. Epub 2021 Jul 22.

College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China.

In this study, the feasibility of employing hydrothermal pretreatment (HTPT) to improve the composting of oxytetracycline fermentation residue (OFR) was evaluated by investigating the depletion of oxytetracycline (OTC) and evolution of dissolved organic matter (DOM). HTPT drastically declined the final content of OTC and its main transformation intermediates in OFR compost from 89.96 to 2.61 mg/kg. Although HTPT slightly increased the DOM content and significantly decreased the contents of biodegradable and humified compounds in OFR compost, it did not significantly change the germination index of OFR compost. Nevertheless, the time required for the overall pattern of DOM parameters to reach stabilization was shortened from 28 to 14 days by HTPT. Taken together, although HTPT did not change the maturity degree of OFR compost, it obviously shortened the OFR composting cycle and lowered the potential risk of OFR compost, confirming that HTPT could efficiently improve the OFR composting.
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http://dx.doi.org/10.1016/j.biortech.2021.125618DOI Listing
July 2021

CircTMC5 promotes gastric cancer progression and metastasis by targeting miR-361-3p/RABL6.

Gastric Cancer 2021 Jul 22. Epub 2021 Jul 22.

Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Xinzhan District, Hefei City, 230000, Anhui Province, China.

Background: Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC.

Methods: CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC).

Results: CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC.

Conclusions: CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.
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http://dx.doi.org/10.1007/s10120-021-01220-6DOI Listing
July 2021

Macrophage migration inhibitory factor in the pathogenesis of leukemia (Review).

Int J Oncol 2021 Aug 19;59(2). Epub 2021 Jul 19.

Department of Laboratory and Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, Guangdong 528308, P.R. China.

Leukemia is a group of malignant diseases of clonal hematopoietic stem‑progenitor cells and its pathological mechanisms remain to be elucidated. Genetic and epigenetic abnormalities, as well as microenvironmental factors, including cytokines, serve critical roles in leukaemogenesis. Macrophage migration inhibitory factor (MIF) has been presented as one of the key regulators in tumorigenesis, angiogenesis and tumor metastasis. This article focuses on the functional role of MIF and its pathway in cancer, particularly in leukemia. MIF/CD74 interaction serves prominent roles in tumor cell survival, such as upregulating BCL‑2 and CD84 expression, and activating receptor‑type tyrosine phosphatase ζ. Furthermore, MIF upregulation forms a pro‑tumor microenvironment in response to hypoxia‑induced factors and promotes pro‑inflammatory cytokine production. Additionally, polymorphisms of the MIF promoter sequence are associated with leukemia development. MIF signal‑targeted early clinical trials show positive results. Overall, these efforts provide a promising means for intervention in leukemia.
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http://dx.doi.org/10.3892/ijo.2021.5242DOI Listing
August 2021

The Influence of Walking Height and Width on the Gait.

J Healthc Eng 2021 23;2021:6675809. Epub 2021 Jun 23.

Department of Rehabilitation, Minhang Hospital, Fudan University, Shanghai, China.

Walking stability is an important factor that is related to working accidents at height. The understanding of the relationship between walking stability and walking conditions remains an unmet need. Therefore, this study aimed to investigate the effect of path height, width, and asymmetric conditions on the pressure and time information of the foot-ground interaction during walking. 12 subjects were required to walk at two height, three width, and asymmetric conditions. Plantar pressures during walking were measured with the F-scan insole sensors. The total pressures were normalized with body weight, and the temporal parameters were normalized with stance time. When the walking height increased, the plantar pressure at the "heel strike" phase did not change significantly, while that at "heel rise" and "toe off" phases significantly increased, and the "heel rise" occurred earlier, indicating a greater foot-ground interaction at the forefoot part of the sole. As the path width increased from 0.6 m to 1.2 m, the foot-ground interaction as well as the asymmetric effect approached to that of overground walking. The findings could help improve the risk assessment and footwear design.
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http://dx.doi.org/10.1155/2021/6675809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249159PMC
June 2021

hsa_circ_0060975 is highly expressed and predicts a poor prognosis in gastric cancer.

Oncol Lett 2021 Aug 24;22(2):619. Epub 2021 Jun 24.

Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China.

Gastric cancer (GC) is the fifth most common cancer and GC has a high mortality rate worldwide. Circular (circ) RNAs serve an important role in cancer. The present study aimed to investigate the expression level of hsa_circ_0060975 in gastric cancer (GC) and to determine the clinical pathological significance of hsa_circ_0060975 in patients with GC. Reverse transcription-quantitative PCR was used to detect expression level of hsa_circ_0060975 in 192 GC and adjacent non-cancerous gastric tissues, in GC cell lines (MKN-45, HGC27 and AGS) and a human gastric epithelium cell line (GES-1), as well as in plasma samples from 126 patients with GC and 92 healthy volunteers. All plasma and tissue samples of were obtained from The First Affiliated Hospital of Anhui Medical University (Hefei, China). The relationship between hsa_circ_0060975 expression and clinical pathological factors was analyzed using the χ test. The diagnostic value of hsa_circ_0060975 was analyzed using the receiver operating characteristic curve (ROC curve), while the Kaplan-Meier method was used to analyze the relationship of hsa_circ_0060975 expression with the survival of patients with GC as determined by log-rank tests. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors, including hsa_circ_0060975 expression and clinical pathological factors. In addition, the potential function of hsa_circ_0060975 was evaluated via bioinformatics analysis. The expression level of hsa_circ_0060975 was higher in GC tissues compared with adjacent non-cancerous gastric tissues, GC cell lines compared with GES-1 and plasma samples from patients with GC compared with plasma samples from healthy volunteers. In addition, higher hsa_circ_0060975 expression was associated with histological grade, pathological stage and tumor (T) classification in GC tissues and plasma samples (P<0.05). The area under the ROC curves of hsa_circ_0060975, the combination with hsa_circ_0060975 and carcinoembryonic antigen (CEA) or CEA alone were 0.804 (sensitivity, 0.746; specificity, 0.783; P<0.001); 0.931 (sensitivity, 0.937; specificity, 0.870; P<0.001) and 0.924 (sensitivity, 0.937; sspecificity, 0.804; P<0.001) respectively. The Kaplan-Meier survival analysis revealed that the overall survival (OS) and disease-free survival (DFS) time of patients with higher hsa_circ_0060975 expression were shorter compared with those in patients with lower hsa_circ_0060975 expression. Univariate and multivariate Cox regression analyses in OS and DFS time determined that the expression level of hsa_circ_0060975, histological grade and pathological stage were independent prognostic factors for patients with GC. In addition, the bioinformatics analysis results suggested that the abnormal expression of hsa_circ_0060975 may serve an important role in tumorigenesis. Hence, hsa_circ_0060975 expression may be an independent prognostic factor for patients with GC and may be a potential marker for biological malignancy.
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http://dx.doi.org/10.3892/ol.2021.12880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243078PMC
August 2021

Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation.

J Cancer Res Clin Oncol 2021 Jul 13. Epub 2021 Jul 13.

Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Purpose: Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells.

Methods: The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI's efficacy in vitro.

Results: Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI.

Conclusion: OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy.
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http://dx.doi.org/10.1007/s00432-021-03731-2DOI Listing
July 2021

Multiethnic Genome-wide Association Study of Subclinical Atherosclerosis in Individuals with Type 2 Diabetes.

Circ Genom Precis Med 2021 Jul 9. Epub 2021 Jul 9.

Department of Epidemiology, University of North Carolina, Chapel Hill, NC.

- Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease (CVD). Type 2 diabetes (T2D) is an independent CVD risk factor that accelerates atherosclerosis. - We performed meta-analyses of genome-wide association studies (GWAS) in up to 2,500 T2D individuals of European ancestry (EA) and 1,590 T2D individuals of African ancestry (AA) with or without exclusion of prevalent CVD, for CAC measured by cardiac computed tomography, and 3,608 EA and 838 AA with T2D for cIMT measured by ultrasonography within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. - We replicated two loci (rs9369640 and rs9349379 near and rs10757278 near ) for CAC and one locus for cIMT (rs7412 and rs445925 near ) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near at 13q13.3) at =2.0×10 in EA. No additional loci were identified with the meta-analyses of EA and AA. The expression QTL analysis with nearby expressed genes derived from arterial wall and metabolic tissues from GTEx pinpoints , encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (<3.1×10) for three previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near and rs11170820 near for CAC, and rs7412 near for cIMT). - Our results provide potential biological mechanisms that could link CAC and cIMT to increased CVD risk in individuals with T2D.
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http://dx.doi.org/10.1161/CIRCGEN.120.003258DOI Listing
July 2021

Homocysteine Causes Endothelial Dysfunction via Inflammatory Factor-Mediated Activation of Epithelial Sodium Channel (ENaC).

Front Cell Dev Biol 2021 17;9:672335. Epub 2021 Jun 17.

Departments of Pharmacy and Cardiology, Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Heilongjiang Key Laboratory for Metabolic Disorder and Cancer Related Cardiovascular Diseases, NHC Key Laboratory of Cell Transplantation, Harbin Medical University and Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China.

Background: Hyperhomocysteinemia (HHcy) causes cardiovascular diseases via regulating inflammatory responses. We investigated whether and how the epithelial sodium channel (ENaC), a recently identified ion channel in endothelial cells, plays a role in HHcy-induced endothelial dysfunction.

Methods: Cell-attached patch-clamp recording in acute split-open aortic endothelial cells, western blot, confocal imaging, and wire myograph combined with pharmacological approaches were used to determine whether HHcy-mediated inflammatory signaling leads to endothelial dysfunction via stimulating ENaC.

Results: The data showed that 4 weeks after L-methionine diet the levels of plasma Hcy were significantly increased and the ENaC was dramatically activated in mouse aortic endothelial cells. Administration of benzamil, a specific ENaC blocker, ameliorated L-methionine diet-induced impairment of endothelium-dependent relaxation (EDR) and reversed Hcy-induced increase in ENaC activity. Pharmacological inhibition of NADPH oxidase, reactive oxygen species (ROS), cyclooxygenase-2 (COX-2)/thromboxane B2 (TXB2), or serum/glucocorticoid regulated kinase 1 (SGK1) effectively attenuated both the Hcy-induced activation of endothelial ENaC and impairment of EDR. Our data showed that both NADPH oxidase inhibitor and an ROS scavenger reversed Hcy-induced increase in COX-2 expression in human umbilical vein endothelial cells (HUVECs). Moreover, Hcy-induced increase in expression levels of SGK-1, phosphorylated-SGK-1, and phosphorylated neural precursor cell-expressed developmentally downregulated protein 4-2 (p-Nedd4-2) in HUVECs were significantly blunted by a COX-2 inhibitor.

Conclusion: We show that Hcy activates endothelial ENaC and subsequently impairs EDR of mouse aorta, via ROS/COX-2-dependent activation of SGK-1/Nedd4-2 signaling. Our study provides a rational that blockade of the endothelial ENaC could be potential method to prevent and/or to treat Hcy-induced cardiovascular disease.
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http://dx.doi.org/10.3389/fcell.2021.672335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247579PMC
June 2021

Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma.

Cancer Cell Int 2021 Jul 3;21(1):340. Epub 2021 Jul 3.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism. A systematic understanding of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in lung adenocarcinoma (LUAD) is essential for new diagnostic and therapeutic strategies.

Methods: FIRLs were obtained through Pearson correlation analysis between ferroptosis and iron-metabolism related genes and all lncRNAs. Univariate and multivariate Cox regression analysis were used to identify optimal prognostic lncRNAs. Next, a novel signature was constructed and risk score of each patient was calculated. Survival analysis and ROC analysis were performed to evaluate the predictive performance using The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus (GEO) datasets, respectively. Furthermore, multivariate Cox and stratification analysis were used to assess prognostic value of this signature in whole cohort and various subgroups. The correlation of risk signature with immune infiltration and gene mutation was also discussed. The expression of lncRNAs was verified by quantitative real-time PCR (qRT-PCR).

Results: A 7-FIRLs signature including ARHGEF26-AS1, LINC01137, C20orf197, MGC32805, TMPO-AS1, LINC00324, and LINC01116 was established in the present study to assess the overall survival (OS) of LUAD. The survival analysis and ROC curve indicated good predictive performance of the signature in both the TCGA training set and the GEO validation set. Multivariate Cox and stratification analysis indicated that the 7-FIRLs signature was an independent prognostic factor for OS. Nomogram exhibited robust validity in prognostic prediction. Differences in immune cells, immune functions and gene mutation were also found between high-risk and low-risk groups.

Conclusions: This risk signature based on the FIRLs may be promising for the clinical prediction of prognosis and immunotherapeutic responses in LUAD patients.
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http://dx.doi.org/10.1186/s12935-021-02027-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254945PMC
July 2021

Bismuth Nanoparticles Confined in Carbonaceous Nanospheres as Anodes for High-Performance Potassium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jul 1;13(27):31766-31774. Epub 2021 Jul 1.

Institut für Physik & IMN MacroNano (ZIK), Technische Universität Ilmenau, Ilmenau 98693, Germany.

Bismuth (Bi) has been considered as a promising alloying-type anode for potassium-ion batteries (PIBs), owing to its high theoretical capacity and suitable working voltage plateaus. However, Bi suffers from dramatic volume fluctuation and significant pulverization during the discharge/charge processes, resulting in fast capacity decay. Herein, we synthesize Bi nanoparticles confined in carbonaceous nanospheres (denoted as [email protected]) for PIBs by first utilizing BiOCl nanoflakes as a hard template and a Bi precursor. The construction of the loose structure buffers the mechanical stresses resulting from the volume expansion of Bi during the alloying reaction and avoids the fracture of the electrode structure, thus improving the cycling performance. Moreover, the carbonaceous layers increase the electronic conductivity and disperse the Bi nanoparticles, enhancing the charge transportation and ionic diffusion, which further promotes the rate capability of [email protected] It exhibits a superior capacity (389 mAh g at 100 mA g after 100 cycles), excellent cycling stability (206 mAh g at 500 mA g over 1000 cycles), and an improved rate capability (182 mAh g at 2.0 A g). This work provides a new structuring strategy in alloying materials for boosting reversible and stable potassium-ion storage.
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http://dx.doi.org/10.1021/acsami.1c09286DOI Listing
July 2021

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Genome Biol 2021 Jun 29;22(1):194. Epub 2021 Jun 29.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.

Results: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.

Conclusion: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
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http://dx.doi.org/10.1186/s13059-021-02398-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243879PMC
June 2021

Tunable room-temperature ferromagnetism in Co-doped two-dimensional van der Waals ZnO.

Nat Commun 2021 Jun 25;12(1):3952. Epub 2021 Jun 25.

Department of Materials Science and Engineering, University of California, Berkeley, CA, USA.

The recent discovery of ferromagnetism in two-dimensional van der Waals crystals has provoked a surge of interest in the exploration of fundamental spin interaction in reduced dimensions. However, existing material candidates have several limitations, notably lacking intrinsic room-temperature ferromagnetic order and air stability. Here, motivated by the anomalously high Curie temperature observed in bulk diluted magnetic oxides, we demonstrate room-temperature ferromagnetism in Co-doped graphene-like Zinc Oxide, a chemically stable layered material in air, down to single atom thickness. Through the magneto-optic Kerr effect, superconducting quantum interference device and X-ray magnetic circular dichroism measurements, we observe clear evidences of spontaneous magnetization in such exotic material systems at room temperature and above. Transmission electron microscopy and atomic force microscopy results explicitly exclude the existence of metallic Co or cobalt oxides clusters. X-ray characterizations reveal that the substitutional Co atoms form Co states in the graphitic lattice of ZnO. By varying the Co doping level, we observe transitions between paramagnetic, ferromagnetic and less ordered phases due to the interplay between impurity-band-exchange and super-exchange interactions. Our discovery opens another path to 2D ferromagnetism at room temperature with the advantage of exceptional tunability and robustness.
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http://dx.doi.org/10.1038/s41467-021-24247-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233323PMC
June 2021

The immune regulatory effects of tetrahedral framework nucleic acid on human T cells via the mitogen-activated protein kinase pathway.

Cell Prolif 2021 Jun 25:e13084. Epub 2021 Jun 25.

Sichuan Cancer Hospital & Institute, Centre for Translational Research in Cancer, Sichuan Cancer Center, Chengdu, China.

Objectives: Autoimmune diseases are a heterogeneous group of diseases which lose the immunological tolerance to self-antigens. It is well recognized that irregularly provoked T cells participate in the pathological immune responses. As a novel nanomaterial with promising applications, tetrahedral framework nucleic acid (TFNA) nanostructure was found to have immune regulatory effects on T cells in this study.

Materials And Methods: To verify the successful fabrication of TFNA, the morphology of TFNA was observed by atomic force microscopy (AFM) and dynamic light scattering. The regulatory effect of TFNA was evaluated by flow cytometry after cocultured with CD3+ T cells isolated from healthy donors. Moreover, the associated signaling pathways were investigated. Finally, we verified our results on the T cells from patients with neuromyelitis optica spectrum disorder (NMOSD), which is a typical autoimmune disease induced by T cells.

Results: We revealed the alternative regulatory functions of TFNA in human primary T cells with steady status via the JNK signaling pathway. Moreover, by inhibiting both JNK and ERK phosphorylation, TFNA exhibited significant suppressive effects on IFNγ secretion from provoking T cells without affecting TNF secretion. Similar immune regulatory effects of TFNA were also observed in autoreactive T cells from patients with NMOSD.

Conclusions: Overall, our results revealed a potential application of TFNA in regulating the adaptive immune system, as well as shed a light on the treatment of T cell-mediated autoimmune diseases.
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http://dx.doi.org/10.1111/cpr.13084DOI Listing
June 2021

Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL.

Hum Mol Genet 2021 Jun 24. Epub 2021 Jun 24.

Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, 91101, USA.

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC), and hip circumference (HIP) adjusted for body mass index (adjBMI), using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL; and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban, and Dominican) background residing in the US. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for WHRadjBMI, 22 for WCadjBMI, and 28 for HIPadjBMI that reached suggestive significance (P < 1x10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed 4 novel loci (P < 0.05 and consistent direction of effect, and P < 5x10-8 after meta-analysis), including 2 for WHRadjBMI (rs13301996, rs79478137); 1 for WCadjBMI (rs3168072); and 1 for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI; 10 for WCadjBMI; 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity-susceptibility that may be ancestry-specific.
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http://dx.doi.org/10.1093/hmg/ddab166DOI Listing
June 2021

Flat Bands in Magic-Angle Bilayer Photonic Crystals at Small Twists.

Phys Rev Lett 2021 Jun;126(22):223601

Department of Materials Science and Engineering, University of California, Berkeley, California 94720, USA.

The new physics of magic-angle twisted bilayer graphene (TBG) motivated extensive studies of flat bands hosted by moiré superlattices in van der Waals structures, inspiring the investigations into their photonic counterparts with potential applications including Bose-Einstein condensation. However, correlation between photonic flat bands and bilayer photonic moiré systems remains unexplored, impeding further development of moiré photonics. In this work, we formulate a coupled-mode theory for low-angle twisted bilayer honeycomb photonic crystals as a close analogy of TBG, discovering magic-angle photonic flat bands with a non-Anderson-type localization. Moreover, the interlayer separation constitutes a convenient degree of freedom in tuning photonic moiré bands without high pressure. A phase diagram is constructed to correlate the twist angle and separation dependencies to the photonic magic angles. Our findings reveal a salient correspondence between fermionic and bosonic moiré systems and pave the avenue toward novel applications through advanced photonic band or state engineering.
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http://dx.doi.org/10.1103/PhysRevLett.126.223601DOI Listing
June 2021

ZNF655 is involved in development and progression of non-small-cell lung cancer.

Life Sci 2021 Sep 16;280:119727. Epub 2021 Jun 16.

Department of Thoracic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, # 88 Jiefang Road, Hangzhou, 310009 China. Electronic address:

Aims: Non-small cell lung cancer (NSCLC) is a malignant tumor with high mortality, which seriously endangers human health. The clinical significance, biological function and potential mechanism of Zinc finger protein 655 (ZNF655) in NSCLC are discussed in this study.

Materials And Methods: The expression level of ZNF655 in NSCLC was clarified by immunohistochemical (IHC) staining. Subsequently, lentivirus-mediated shRNA was used to construct ZNF655 knock down NSCLC cells NCI-H1299 and A549. In vitro and in vivo loss of function assays were used to evaluate the malignant behaviors of the cells.

Key Findings: The expression level of ZNF655 was abnormally abundant in NSCLC. The decrease of ZNF655 expression led to the inhibition of the malignant behaviors of NSCLC, which was manifested by weakened proliferation, increased sensitivity to apoptosis, cycle repression at G2 and weakened migration. Consistently, downregulation of ZNF655 reduced tumorigenesis in mouse xenograft model. Moreover, decreased expression of ZNF655 resulted in upregulated expression of Bad, Bax, Fas, p21, p27, Caspase 3 and Caspase 8 in NSCLC cells. NCI-H1299 cells with ZNF655 knockdown resulted in decreased phosphorylation of Akt, downregulation of CDK6 and PIK3CA, and upregulation of MAPK9. Collectively, ZNF655 may regulate apoptosis of NSCLC cells through PI3K/Akt and p53 signaling pathways.

Significance: ZNF655 possessed a promoting effect in the progression of NSCLC, which may serve as a promising molecular target for clinical treatment.
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http://dx.doi.org/10.1016/j.lfs.2021.119727DOI Listing
September 2021

Correction to: M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway.

J Transl Med 2021 Jun 16;19(1):263. Epub 2021 Jun 16.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuhan, 430071, Hubei, China.

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http://dx.doi.org/10.1186/s12967-021-02920-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207724PMC
June 2021

NaHS or Lovastatin Attenuates Cyclosporine A-Induced Hypertension in Rats by Inhibiting Epithelial Sodium Channels.

Front Pharmacol 2021 26;12:665111. Epub 2021 May 26.

Department of Physiology, Emory University School of Medicine, Atlanta, GA, United States.

The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) activation of NADPH oxidase p47, serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell-expressed developmentally downregulated protein 4-2 (-Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, -, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of HS which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress.
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http://dx.doi.org/10.3389/fphar.2021.665111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187945PMC
May 2021

Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Endoplasmic Reticulum Stress-Related Gene Analysis.

Front Oncol 2021 21;11:641487. Epub 2021 May 21.

Medical College of Yangzhou University, Yangzhou, China.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and its incidence continues to increase year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding within the secretory pathway in cells and has an extensive and deep impact on cancer cell progression and survival. Growing evidence suggests that the genes related to ERS are closely associated with the occurrence and progression of HCC. This study aimed to identify an ERS-related signature for the prospective evaluation of prognosis in HCC patients. RNA sequencing data and clinical data of patients from HCC patients were obtained from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC). Using data from TCGA as a training cohort (n=424) and data from ICGC as an independent external testing cohort (n=243), ERS-related genes were extracted to identify three common pathways IRE1, PEKR, and ATF6 using the GSEA database. Through univariate and multivariate Cox regression analysis, 5 gene signals in the training cohort were found to be related to ERS and closely correlated with the prognosis in patients of HCC. A novel 5-gene signature (including HDGF, EIF2S1, SRPRB, PPP2R5B and DDX11) was created and had power as a prognostic biomarker. The prognosis of patients with high-risk HCC was worse than that of patients with low-risk HCC. Multivariate Cox regression analysis confirmed that the signature was an independent prognostic biomarker for HCC. The results were further validated in an independent external testing cohort (ICGC). Also, GSEA indicated a series of significantly enriched oncological signatures and different metabolic processes that may enable a better understanding of the potential molecular mechanism mediating the progression of HCC. The 5-gene biomarker has a high potential for clinical applications in the risk stratification and overall survival prediction of HCC patients. In addition, the abnormal expression of these genes may be affected by copy number variation, methylation variation, and post-transcriptional regulation. Together, this study indicated that the genes may have potential as prognostic biomarkers in HCC and may provide new evidence supporting targeted therapies in HCC.
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http://dx.doi.org/10.3389/fonc.2021.641487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175984PMC
May 2021

Synthesis, SAR study, and bioactivity evaluation of a series of Quinoline-Indole-Schiff base derivatives: Compound 10E as a new Nur77 exporter and autophagic death inducer.

Bioorg Chem 2021 Aug 23;113:105008. Epub 2021 May 23.

School of Pharmaceutical Sciences and School of Public Health, Xiamen University, Xiamen 361102, China. Electronic address:

We previously reported 5-((8-methoxy-2-methylquinolin-4-yl)amino)-1H-indole- 2-carbohydrazide derivatives as new Nur77 modulators. In this study, we explored whether the 8-methoxy-2-methylquinoline moiety and bicyclic aromatic rings at the N'-methylene position were critical for their antitumor activity against hepatocellular carcinoma (HCC). For this purpose, a small library of 5-substituted 1H-indole-2-carbohydrazide derivatives was designed and synthesized. We found that the 8-methoxy-2-methylquinoline moiety was a fundamental structure for its biological function, while the introduction of the bicyclic aromatic ring into the N'-methylene greatly improved its anti-tumor effect. We found that the representative compound 10E had a high affinity to Nur77. The K values were in the low micromolar (2.25-4.10 μM), which were coincident with its IC values against the tumor cell lines (IC < 3.78 μM). Compound 10E could induce autophagic cell death of liver cancer cells by targeting Nur77 to mitochondria while knocking down Nur77 greatly impaired anti-tumor effect. These findings provide an insight into the structure-activity relation of Quinoline-Indole-Schiff base derivatives and further demonstrate that antitumor agents targeting Nur77 may be considered as a promising strategy for HCC therapy.
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http://dx.doi.org/10.1016/j.bioorg.2021.105008DOI Listing
August 2021

A general prodrug nanohydrogel platform for reduction-triggered drug activation and treatment of taxane-resistant malignancies.

Acta Biomater 2021 08 1;130:409-422. Epub 2021 Jun 1.

The First Affiliated Hospital, School of Medicine, Zhejiang University; NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou 310003, PR China. Electronic address:

Chemotherapy has been widely used for treating the vast majority of cancer patients. Unfortunately, only a fraction of patients can respond to chemotherapies, but these patients still experience severe side effects. In this context, a wide range of nanotherapeutic platforms have been developed with the aim of improving treatment outcomes while reducing drug toxicities. Nanohydrogels are highly appealing "smart" biocompatible and biodegradable vehicles for either local or systemic delivery of bioactive compounds. Here, we developed prodrug hydrogelators that can undergo one-step distillation-precipitation polymerization to form systemically injectable nanohydrogels. The optimized nanohydrogels were capable of rapidly releasing active agents (e.g., the cytotoxic agent cabazitaxel or the PI3K molecular inhibitor PI103) in response to the reducing tumor microenvironment, while drug release was very slow in the absence of the reductive reagent glutathione. Cabazitaxel-loaded nanogels showed preferential tumor accumulation, and administration of nanogels produced durable tumor regression in a docetaxel-resistant cervical tumor xenograft-bearing mouse model. More significantly, nanogel-based therapy was proven to demonstrate a higher safety profile than solution-based free cabazitaxel. Collectively, this study provides an alternative formulation that meets the essential requirements of high stability in the blood, spontaneous drug release at diseased sites, favorable safety in vivo, and translational capacity for further investigations. STATEMENT OF SIGNIFICANCE: Chemotherapy remains a considerable challenge and only a fraction of patients can respond to chemotherapies. Here we report an intratumoral reducing agent-activatable, tumor-targeting prodrug nanogel platform for therapeutic delivery. To this end, two anticancer agents (e.g., cytotoxic cabazitaxel or PI3K molecular inhibitor PI103) are tested. Prodrug nanogels are stable in the blood but performed reduction-triggered release of chemically unmodified drug molecules in cancerous tissues. Cabazitaxel-loaded nanogels exhibit satisfactory anticancer performance in a preclinical docetaxel-resistant tumor model. This is a practical and expedient approach that combines the prodrug strategy and nanogel scaffold to re-engineer a hydrophobic and toxic anticancer drug. The approach also is broadly applicable for the formulation of other agents to improve the therapeutic index.
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http://dx.doi.org/10.1016/j.actbio.2021.05.047DOI Listing
August 2021

miR-29c-3p regulates TET2 expression and inhibits autophagy process in Parkinson's disease models.

Genes Cells 2021 Jun 4. Epub 2021 Jun 4.

Department of Geriatric Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Autophagy in dopamine (DA) neurons is concerned to be associated with Parkinson's disease (PD), but the detailed mechanism remains unknown. Herein, we aimed to investigate the function of microRNA (miR)-29c-3p in autophagy in PD models. Intraperitoneal injection of MPTP (20 mg/kg) was given to C57BL/6 mice to establish PD mouse model. SH-SY5Y cells were treated with MPP (1 mmol/L) to establish in vitro PD model. The results indicated that in the substantia nigra pars compacta (SNpc) DA neurons of PD mice, autophagy was activated accompanied by down-regulated miR-29c-3p and up-regulated ten-eleven translocation 2 (TET2) expression. Up-regulation of miR-29c-3p inhibited TET2 expression and SNpc (including DA neurons) autophagy in PD mice. In vitro PD model confirmed that MPP treatment markedly down-regulated miR-29c-3p expression and up-regulated TET2 expression in SH-SY5Y cells in a dose/time-dependent manner. Moreover, miR-29c-3p up-regulation also inhibited autophagy and TET2 expression in vitro. Additionally, TET2 was proved to be targeted and down-regulated by miR-29c-3p. TET2 knockdown inhibited MPP -induced autophagy, whereas TET2 over-expression reversed the effects of miR-29c-3p over-expression on SH-SY5Y cell autophagy. Overall, miR-29c-3p over-expression inhibits autophagy in PD models, which may be mediated by TET2. Our finding may provide new insights for regulating autophagy to improve PD progression.
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http://dx.doi.org/10.1111/gtc.12877DOI Listing
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Effect of High-Flow Nasal Cannula for Hypoxemia Following Sun's Procedure in Acute Aortic Dissection Type a Patients.

Front Surg 2021 7;8:630624. Epub 2021 May 7.

Cardiac Surgery Department, Southwest Hospital, Army Medical University, Chongqing, China.

Patients with acute aortic dissection type A (AADA) often have hypoxemia (partial pressure of oxygen [PaO]/fraction of inspired oxygen [FiO] <300 mmHg) before weaning in the intensive care unit (ICU). This study compared the efficacy of high-flow nasal cannula (HFNC) with that of conventional oxygen therapy (COT) in patients with AADA following Sun's procedure. The medical records of 87 adult patients with AADA who underwent Sun's procedure and met the inclusion criteria (PaO/FiO <300 mmHg before weaning) were retrospectively analyzed. After surgery, 41 patients were treated with HFNC and 46 were treated with COT. The oxygenation level, FiO, partial pressure of carbon dioxide, heart rate, respiratory rate, subjective discomfort, and reintubation rate were recorded. The difference in lung volume loss between the HFNC and COT groups was assessed using the radiological atelectasis score (chest radiograph) or calculated from three-dimensional (3D) reconstructed computed tomography (CT) images. From day 1 to day 5 after weaning, there was no significant difference in PaO/FiO between the HFNC and COT groups, although the FiO was significantly lower in the HFNC group than in the COT group ( < 0.05). Further studies indicated that the percentage of lung volume loss (pleural effusion and/or pulmonary atelectasis) by 3D reconstruction of CT images at 4-8 days post-operation was significantly lower in the HFNC group ( < 0.05). The subjective experience of breathing discomfort, reintubation rate, and length of stay in the ICU were significantly reduced in the HFNC group ( < 0.05). There was no significant difference in readmission to the ICU and in-hospital mortality between the two groups. HFNC can be used as an effective oxygen therapy for AADA patients with hypoxemia after Sun's procedure.
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http://dx.doi.org/10.3389/fsurg.2021.630624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138463PMC
May 2021

Topotactic Growth of Free-Standing Two-Dimensional Perovskite Niobates with Low Symmetry Phase.

Nano Lett 2021 Jun 21;21(11):4700-4707. Epub 2021 May 21.

Department of Materials Science and Engineering, University of California, Berkeley, California 94720, United States.

Here, we report a novel topotactic method to grow 2D free-standing perovskite using KNbO (KN) as a model system. Perovskite KN with monoclinic phase, distorted by as large as ∼6 degrees compared with orthorhombic KN, is obtained from 2D KNbO after oxygen-assisted annealing at relatively low temperature (530 °C). Piezoresponse force microscopy (PFM) measurements confirm that the 2D KN sheets show strong spontaneous polarization () along [101̅] direction and a weak in-plane polarization, which is consistent with theoretical predictions. Thickness-dependent stripe domains, with increased surface displacement and PFM phase changes, are observed along the monoclinic tilt direction, indicating the preserved strain in KN induces the variation of nanoscale ferroelectric properties. 2D perovskite KN with low symmetry phase stable at room temperature will provide new opportunities in the exploration of nanoscale information storage devices and better understanding of ferroelectric/ferroelastic phenomena in 2D perovskite oxides.
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http://dx.doi.org/10.1021/acs.nanolett.1c00918DOI Listing
June 2021

[Research and Application of Stem Cell-Based Therapy in Idiopathic Pulmonary Fibrosis: A Review].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 May;52(3):373-379

Centre for Basic and Translational Research in Cancer, Sichuan Cancer Hospital & Institute, University of Electronic Science and Technology of China, Chengdu 610041, China.

Idiopathic pulmonary fibrosis (IPF) is a type of pulmonary disease that progresses acutely or slowly into irreversible pulmonary diseases, resulting in the end severe damages to patients' lung functions, as well as deaths. At present, the pathogenesis of pulmonary fibrosis is still not clear and there is no effective therapeutic measure available to control the progression of the disease. Research findings indicate that stem cells, being the origin of all cells of organisms, participate in the development of individuals at various stages and play an important role in repairing pulmonary tissue damage. Stem cells are attracting growing attention in the field of regenerative medicine, providing new ideas for treating IPF with transplanted stem cells. Herein, in order to better explore the potential applications of stem cell transplantation in treating IPF, we attempt to summarize preliminary studies of stem cell-mediated pulmonary remodeling after IPF, as well as cutting-edge clinical trials in stem cell-based IPF therapy.
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http://dx.doi.org/10.12182/20210560304DOI Listing
May 2021

UHRF1 regulates the transcriptional repressor HBP1 through MIF in T acute lymphoblastic leukemia.

Oncol Rep 2021 Jul 20;46(1). Epub 2021 May 20.

Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China.

Macrophage migration inhibitory factor (MIF) has been confirmed as an oncogene in solid tumor development, and its overexpression causes cell proliferation in T acute lymphoblastic leukemia (T‑ALL); however, the underlying mechanisms remain unclear. The overexpression of MIF promotes cellular transformation and proliferation, in part, through interaction with UHRF1. Nevertheless, overexpression of UHRF1 cannot upregulate  expression in T‑ALL. New insights into MIF regulation in T‑ALL are imperative to offer the opportunity for therapeutic intervention. In the present study, using RT‑qPCR, western blot analysis, confocal microscopy and RNA sequence, we report the identification and validation of UHRF1 as a negative regulator of , which functions to downregulate MIF expression by binding to the CATT repeat sequence of the  promoter. By contrast, HMG‑box protein 1 () functions as a positive regulator of MIF. Moreover, we demonstrated that HBP1 suppressive signaling is reduced by UHRF1 through promotion of the interaction between MIF and HBP1.  deficiency caused by  knockdown resulted in enhanced apoptosis in T‑ALL as compared with that caused by decreased MIF or increased HBP1 expression alone. These results identify UHRF1 as a key regulator of  transcription in T‑ALL, although these transcription factors possess opposite regulatory functions. Thus, this mechanism may provide insight into how to effectively prevent MIF‑dependent oncogenic activity. Finally, T‑ALL mice possessing high HBP1 or low UHRF1 expression levels are associated with longer survival as compared with control mice, with ‑knockdown mice living the longest. Taken together, these findings indicate that MIF and its regulators are potential treatment targets and biomarkers for the prediction of prognosis in T‑ALL.
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http://dx.doi.org/10.3892/or.2021.8082DOI Listing
July 2021

Risk perceptions and DUI decisions of drivers in different legal environments: New evidence on differential deterrence from a Chinese sample.

Accid Anal Prev 2021 Jul 14;157:106188. Epub 2021 May 14.

School of Humanities and Social Sciences, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055, China. Electronic address:

Objectives: Research on the deterrent effects of driving-under-the-influence (DUI) laws has been limited in China, which has criminalized drunk driving since May 2011 yet the effectiveness of this legislation remains unclear. Primary studies are needed to confirm whether government reports of reductions in DUI rates since then can indeed match changes in driver perceptions of DUI risk, and if so, be attributed to what specific components of the DUI legal environments. Based on the classical theory of deterrence and recent advances in differential deterrence, this study adopted a conjoint experiment from a previous US study that simulated the decision-making process of potential drinking drivers, and evaluated how DUI sanctions and enforcement practices contributed differentially to the three components of deterrence (i.e., certainty, swiftness, and severity of punishment). Key individual characteristics and nonlegal factors, as suggested by differential deterrence research to moderate the impact of DUI laws, were also considered.

Methods: A Web-based conjoint experiment was conducted on a sample of 109 college students from two major universities in Shenzhen, China. Participants were randomly assigned to blocks of hypothetical scenarios composed of different levels of DUI enforcement and penalties, and asked to choose from a pair of scenarios each time, in which they were more likely to drink and drive. They also answered questions adapted from previous studies that measured key individual factors in relation to differential deterrence, such as informal sanction threat, moral inhibition, and personal and vicarious experiences with punishment. Such individual differences were accounted for in both a conventional two-level mixed logit aggregate model and a Hierarchical Bayes model.

Results: Consistent with prior findings in Western countries, DUI enforcement intensity, was found to be the strongest deterrent to potential drinking drivers in China. License suspension, as an administrative punishment that can be swiftly implemented, was also effective in deterring the Chinese drivers, who however were much more likely to fear the revocation of their licenses rather than a 6-month suspension only. Meanwhile, they were notably deterred by the possibility of being in jail for 1-3 days, let alone for 1-2 months. Altogether, enforcement, license suspension and jail penalties accounted for more than 75 percent of attribute impact on drivers' decision to drink and drive, whereas fine penalty and license points had almost no effect. On the other hand, nonlegal factors such as informal sanction threat and vicarious experiences were found to have significantly moderated the deterrent effects of DUI laws.

Conclusions: Overall, this study quantified the unique effects of perceived certainty, swiftness, and severity of DUI punishment in the Chinese context, and supported the usefulness of conjoint experiments for examining risk perceptions and DUI decisions in different legal environments. It also provided new empirical evidence on differential deterrence and pointed out the need of determining for which subsets of individuals and under what conditions can legal sanctions successfully deter potential offenders. Such research will help researchers and policy makers better understand the role of deterrence, for more effective policy development related to DUI as well as other important traffic safety issues.
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http://dx.doi.org/10.1016/j.aap.2021.106188DOI Listing
July 2021

Discovery and Validation of Circulating EVL mRNA as a Prognostic Biomarker in Pancreatic Cancer.

J Oncol 2021 20;2021:6656337. Epub 2021 Apr 20.

Clinic Medical College, Yangzhou University, Yangzhou 225000, China.

Background: Circulating plasma mRNAs can be analyzed to identify putative cancer biomarkers. This study was conducted in an effort to detect plasma mRNA biomarkers capable of predicting pancreatic cancer (PACA) patient prognosis. . First, prognostic mRNAs that were differentially expressed in PACA in The Cancer Genome Atlas (TCGA) were established, after which microarray expression profiles from PACA patient plasma samples were utilized to specifically identify potential prognostic plasma mRNA biomarkers associated with this cancer type. In total, plasma samples were then collected from 79 PACA patients and 19 healthy controls to confirm differential mRNA expression via qPCR, while Kaplan-Meier analyses were used to examine the link between mRNA expression and patient overall survival.

Results: In total, three prognostic differentially expressed genes were identified in PACA patient plasma samples, including SMAP2, PTPN6, and EVL (Ena/VASP-like). Plasma EVL levels were confirmed via qPCR to be correlated with tumor pathology ( < 0.01), while the overall survival of patients with low plasma EVL levels was poor ( < 0.01). Multivariate Cox regression analyses further confirmed that plasma EVL levels were independent predictors of PACA patient prognosis.

Conclusion: We found that PACA is associated with the downregulation of plasma EVL mRNA levels, indicating that this mRNA may be a viable biomarker associated with patient prognosis.
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http://dx.doi.org/10.1155/2021/6656337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079208PMC
April 2021

Surface roughness of titanium orthopedic implants alters the biological phenotype of human MSCs.

Tissue Eng Part A 2021 May 11. Epub 2021 May 11.

Mayo Clinic, Orthopedic Surgery, 200 First Street SW, Rochester, Minnesota, United States, 55902;

Metal orthopedic implants are largely biocompatible and generally achieve long-term structural fixation. However, some orthopedic implants may loosen over time even in the absence of infection. In vivo fixation failure is multifactorial, but the fundamental biological defect is cellular dysfunction at the host-implant interface. Strategies to reduce the risk of short- and long-term loosening include surface modifications, implant metal alloy type, and adjuvant substances such as polymethylmethacrylate cement. Surface modifications (e.g., increased surface rugosity) can increase osseointegration and biological ingrowth of orthopedic implants. However, the localized responses of cells to implant surface modifications need to be better characterized. As an in vitro model for investigating cellular responses to metallic orthopedic implants, we cultured mesenchymal stromal/stem cells (MSCs) on clinical-grade titanium disks (Ti6Al4V) that differed in surface roughness as high (porous-structured), medium (grit-blasted), and low (bead-blasted). Topological characterization of clinically relevant Ti materials combined with differential mRNA expression analyses (RNA-seq and RT-qPCR) revealed alterations to the biological phenotype of cells cultured on titanium structures that favor early ECM production and observable responses to oxidative stress and heavy metal stress. These results provide a descriptive model for the interpretation of cellular responses at the interface between native host tissues and 3-D printed modular orthopedic implants, and will guide future studies aimed at increasing the long-term retention of such materials after TJA.
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http://dx.doi.org/10.1089/ten.TEA.2020.0369DOI Listing
May 2021
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