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  • Article
    Valipour J, Taghizadeh F, Esfahani R, Ramesh M, Rastegar T.
    Heliyon. 2024 May 15;10(9):e29752.
    Oxidative stress refers to a condition where there is an imbalance between the production of reactive oxygen species and their removal by antioxidants. While the function of reactive oxygen species as specific second messengers under physiological conditions is necessary, their overproduction can lead to numerous instances of cell and tissue damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of many cytoprotective genes that respond to redox stresses. Nrf2 is regularly degraded by kelch-like ECH-associated protein 1 through the ubiquitin-proteasome pathway. The kelch-like ECH-associated protein 1 and Nrf2 complex have attracted attention in both basic and clinical infertility research fields. Oxidative stress is implicated in the pathogenesis of female infertility, including primary ovarian insufficiency, polycystic ovarian syndrome, and endometriosis, as well as male infertility, namely varicocele, cryptorchidism, spermatic cord torsion, and orchitis. Most scientists believe that Nrf2 is a potential therapeutic method in female and male infertility disorders due to its antioxidant effect. Here, the potential roles of oxidative stress and Nrf2 in female and male infertility disorders are reviewed. Moreover, the key role of Nrf2 in the inhibition or induction of these diseases is discussed.
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  • Article
    Swartzman I, Gu JJ, Toner Z, Grover R, Suresh L, Ullman LE.
    Cureus. 2022 Sep;14(9):e29752.
    Coronavirus disease 2019 (COVID-19) infection has been linked to numerous autoimmune manifestations. Neither the mechanism nor the etiology of this association has been fully explored or elucidated. Prior studies have detected myositis in patients with proven COVID-19 infection, suggesting a relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of myositis. Studies have reported elevated levels of autoimmune antibodies, including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), in patients with COVID-19 infection, however the prevalence is not well documented. Our objective was to assess the prevalence of MSAs and MAAs in COVID-19 patients compared with unaffected subjects. Serum samples from 74 unvaccinated, polymerase chain reaction (PCR)-positive COVID-19 infected patients were compared with serum samples from 41 healthy, unaffected individuals. All serum samples were tested for MSA and MAA reactivity. Within the COVID-19-positive group, six (8.1%) patients exhibited MSA/MAA positivity, compared with only one (2.4%) individual from the control group. Although a higher prevalence of MSA/MAA positivity was observed within the COVID-19 infected group, the difference did not reach statistical significance (p=0.223). The autoantibodies detected in this study have a unique association with dermatomyositis and other inflammatory myopathies, and may play a role in COVID-19-associated myopathy. This article was previously presented as an abstract at Jacobs School of Medicine and Biomedical Sciences Research Day on June 3rd, 2022.
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  • Article
    Garvey CM, Spiller E, Lindsay D, Chiang CT, Choi NC, Agus DB, Mallick P, Foo J, Mumenthaler SM.
    Sci Rep. 2016 07 25;6:29752.
    Tumor progression results from a complex interplay between cellular heterogeneity, treatment response, microenvironment and heterocellular interactions. Existing approaches to characterize this interplay suffer from an inability to distinguish between multiple cell types, often lack environmental context, and are unable to perform multiplex phenotypic profiling of cell populations. Here we present a high-throughput platform for characterizing, with single-cell resolution, the dynamic phenotypic responses (i.e. morphology changes, proliferation, apoptosis) of heterogeneous cell populations both during standard growth and in response to multiple, co-occurring selective pressures. The speed of this platform enables a thorough investigation of the impacts of diverse selective pressures including genetic alterations, therapeutic interventions, heterocellular components and microenvironmental factors. The platform has been applied to both 2D and 3D culture systems and readily distinguishes between (1) cytotoxic versus cytostatic cellular responses; and (2) changes in morphological features over time and in response to perturbation. These important features can directly influence tumor evolution and clinical outcome. Our image-based approach provides a deeper insight into the cellular dynamics and heterogeneity of tumors (or other complex systems), with reduced reagents and time, offering advantages over traditional biological assays.
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  • Article
    Givechian KB, Garner C, Garban H, Rabizadeh S, Soon-Shiong P.
    Oncotarget. 2018 Jul 03;9(51):29743-29752.
    Somatic mutations in DNA repair genes have been clinically associated with chemosensitivity, although few studies have interrogated the nucleotide synthesis pathways that supply DNA repair processes. Previous work suggests that bladder urothelial carcinoma is uniquely enriched for mutations in nucleotide excision repair genes, and that these mutations are associated with response to platinum-based therapy and favorable survival. Conversely, the de novo pyrimidine synthesis pathway has recently emerged as a putative clinical target. This anabolic process is thought to supply DNA repair processes such as nucleotide excision repair; that is, DNA repair enzymes may require a sufficient nucleotide supply available to reverse the intended genotoxic damage of systemic chemotherapy in rapidly proliferating cancer cells. Therefore, we explored the prognostic complementarity between de novo pyrimidine synthesis and nucleotide excision repair expression in a total of 570 bladder urothelial carcinoma patients. Ultimately, we show that the de novo pyrimidine synthesis gene CAD is associated with poor survival (P = 0.008) and is co-altered with the nucleotide excision repair gene POLD2. High expression of POLD2 was also associated with poor overall survival (P = 0.019) and was significantly correlated with CAD expression in pre-treatment patient tumor samples (P = 2.44e-4). Expression of each gene was associated with cisplatin-based therapy resistance, and accordingly, CADhighPOLD2high patients were associated with worse survival than CADhighPOLD2low and CADlowPOLD2high patients. Together, these biomarkers could help elucidate mechanisms of chemoresistance to further personalize therapeutic strategies in bladder urothelial carcinoma.
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  • Article
    Bai Y, Wang P, Qi Y, Li Y, Liu W, Gao L, Jiao H, An Y, Gong Y.
    Medicine (Baltimore). 2022 Aug 12;101(32):e29752.
    Hyaluronic acid (HA), type III procollagen III (PC-III), type IV collagen IV (IV-C), and laminin (LN) have certain diagnostic value for hepatobiliary diseases. No published studies have compared the diagnostic accuracy of these 4 indicators for the diagnosis of congenital biliary atresia (CBA) in infants. This study aimed to investigate the diagnostic value of HA, PC-III, IV-C, and LN in infants with CBA. From January 2017 to December 2020, 185 infants with nonphysiological jaundice in the Second Department of General Surgery at the Children's Hospital of Hebei were enrolled in this study. Forty-six infants with CBA (CBA group) and 139 infants without CBA (noncongenital biliary atresia group) were diagnosed using ultrasonography, magnetic resonance imaging, intraoperative exploration, and intraoperative cholangiography. The levels of HA, PC-III, IV-C, and LN in the 2 groups were statistically analyzed. The diagnostic accuracy was determined using receiver operating characteristic curves and by calculating the area under the curve. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors. Compared to the noncongenital biliary atresia group, the levels of HA, PC-III, IV-C, and LN were significantly increased in the CBA group (P <.05). The receiver operating characteristic analysis showed the optimal cutoff values for HA, PC-III, IV-C, and LN were 162.7, 42.5, 199.7, and 101.2 ng/mL, and the area under the curves were 0.892, 0.762, 0.804, and 0.768, respectively. The sensitivity values for the diagnosis of CBA were 76.82%, 71.61%, 70.32%, and 72.28%, and the specificity values for the diagnosis of biliary atresia were 70.22%, 70.44%, 66.34%, and 68.71%, respectively. In the multivariate model, HA ≥162.7 ng/mL (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 3.15-8.37), PC-III ≥42.5 ng/mL (OR = 4.61, 95% CI: 2.54-7.16), IV-C ≥199.7 ng/mL (OR = 5.02, 95% CI: 2.98-7.64), and LN ≥101.2 ng/mL (OR = 6.25, 95% CI: 2.41-10.07) remained associated with the occurrence of CBA. HA, PC-III, IV-C, and LN have high accuracy for the diagnosis of CBA in infants, and these factors are potential diagnostic biomarkers for CBA.
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  • Article
    Passarello L, Lau C, McCahon E, Popat H.
    Pediatr Blood Cancer. 2022 12;69(12):e29752.
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  • Article
    Yuzawa S, Ogura K, Horiuchi M, Suzuki NN, Fujioka Y, Kataoka M, Sumimoto H, Inagaki F.
    J Biol Chem. 2004 Jul 09;279(28):29752-60.
    The phagocyte NADPH oxidase is a multisubunit enzyme responsible for the generation of superoxide anions (O(2).) that kill invading microorganisms. p47(phox) is a cytosolic subunit of the phagocyte NADPH oxidase, which plays a crucial role in the assembly of the activated NADPH oxidase complex. The molecular shapes of the p47(phox) tandem SH3 domains either with or without a polybasic/autoinhibitory region (PBR/AIR) at the C terminus were studied using small angle x-ray scattering. The tandem SH3 domains with PBR/AIR formed a compact globular structure, whereas the tandem SH3 domains lacking the PBR/AIR formed an elongated structure. Alignment anisotropy analysis by NMR based on the residual dipolar couplings revealed that the tandem SH3 domains with PBR/AIR were in good agreement with a globular module corresponding to the split half of the intertwisted dimer in crystalline state. The structure of the globular module was elucidated to represent a solution structure of the tandem SH3 domain in the autoinhibited form, where the PBR/AIR bundled the tandem SH3 domains and the linker forming a closed structure. Once PBR/AIR is released by phosphorylation, rearrangements of the SH3 domains may occur, forming an open structure that binds to the cytoplasmic proline-rich region of membrane-bound p22(phox).
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  • Article
    Yu CR, Mahdi RM, Ebong S, Vistica BP, Gery I, Egwuagu CE.
    J Biol Chem. 2003 Aug 08;278(32):29752-9.
    Suppressors of cytokine signaling (SOCS) have been implicated in regulation of T-cell activation and cytokine-mediated differentiation of T-helper cells. In this study we have characterized the pattern of SOCS expression in naïve and activated primary T-helper cells, examined whether expression of SOCS genes is regulated by cytokine or T-cell receptor signaling, and analyzed the function of SOCS in differentiated T-cells. We show that SOCS1, SOCS2, SOCS3, CIS (cytokine-induced SH2 protein) genes are constitutively expressed in naïve T-helper cells, with SOCS3 being the most abundant. Antigen stimulation of naïve T-helper cells down-regulates SOCS3 expression and concomitantly up-regulates SOCS1, SOCS2, and CIS gene transcription, suggesting that SOCS genes are regulated differentially by T-cell activation. Down-regulation of SOCS3 expression is subsequently followed by gradual increase in SOCS3 level and corresponding decline in interleukin 2 (IL-2) secretion. In fact, SOCS3 mRNA levels are inversely correlated with the amount of IL-2 secretion and proliferative responses of differentiating T-helper cells, suggesting mutually antagonistic effects of SOCS3 and IL-2 and feedback regulation of T-cell activation by SOCS3. Furthermore, the degree of SOCS3 inhibition is antigen concentration-dependent and is mediated in part by growth factor independence-1, a T-cell transcription factor that regulates S-phase entry in T-cells. Forced overexpression of SOCS3 inhibits proliferation of T-helper cells, whereas depletion of endogenous SOCS3 by antisense SOCS3 cDNA enhances T-cell receptor- and cytokine-induced proliferation. Taken together, these results suggest a role for SOCS3 in maintaining T-helper cells in a quiescent state. Transient inhibition of SOCS3 by antigen stimulation may therefore be essential in allowing activation of resting T-cells.
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  • Article
    Ng V, Sargeant JM.
    PLoS One. 2012;7(1):e29752.
    BACKGROUND: Zoonotic diseases account for over 60% of all communicable diseases causing illness in humans and 75% of recently emerging infectious diseases. As limited resources are available for the control and prevention of zoonotic diseases, it is necessary to prioritize diseases in order to direct resources into those with the greatest needs. The selection of criteria for prioritization has traditionally been on the basis of expert opinion; however, details of the methods used to identify criteria from expert opinion often are not published and a full range of criteria may not be captured by expert opinion.
    METHODOLOGY/PRINCIPAL FINDINGS: This study used six focus groups to identify criteria for the prioritization of zoonotic diseases in Canada. Focus groups included people from the public, animal health professionals and human health professionals. A total of 59 criteria were identified for prioritizing zoonotic diseases. Human-related criteria accounted for the highest proportion of criteria identified (55%), followed by animal-related criteria (26%) then pathogen/disease-related criteria (19%). Similarities and differences were observed in the identification and scoring of criteria for disease prioritization between groups; the public groups were strongly influenced by the individual-level of disease burden, the responsibility of the scientific community in disease prioritization and the experiences of recent events while the professional groups were influenced by the societal- and population-level of disease burden and political and public pressure.
    CONCLUSIONS/SIGNIFICANCE: This was the first study to describe a mixed semi-quantitative and qualitative approach to deriving criteria for disease prioritization. This was also the first study to involve the opinion of the general public regarding disease prioritization. The number of criteria identified highlights the difficulty in prioritizing zoonotic diseases. The method presented in this paper has formulated a comprehensive list of criteria that can be used to inform future disease prioritization studies.
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  • Article
    Qin X, Luo C, Li Y, Cui H.
    ACS Omega. 2021 Nov 09;6(44):29752-29758.
    In this letter, we perform a first-principles study on the adsorption performance of the InP3 monolayer upon three SF6 decomposed species, including SO2, SOF2, and SO2F2, to investigate its potential as a resistance-type, optical or field-effect transistor gas sensor. Results indicate that the InP3 monolayer exhibits strong chemisorption upon SO2 but weak physisorption upon SO2F2. The most admirable adsorption behavior is upon SOF2, which provides a favorable sensing response (-19.4%) and recovery property (10.4 s) at room temperature as a resistance-type gas sensor. A high response of 180.7% upon SO2 and a poor one of -1.9% upon SO2F2 are also identified, which reveals the feasibility of the InP3 monolayer as a resistance-type sensor for SO2 detection with recycle use via a heating technique to clean the surface. Moreover, the InP3 monolayer is a promising optical sensor for SO2 detection due to the obvious changes in adsorption peaks within the range of ultraviolet and is a desirable field-effect transistor sensor for selective and sensitive detection of SO2 and SOF2 given the evident changes of Q T and E g under the applied electric field.
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  • Article
    Nielsen LB, McCormick SP, Pierotti V, Tam C, Gunn MD, Shizuya H, Young SG.
    J Biol Chem. 1997 Nov 21;272(47):29752-8.
    We reported previously that approximately 80-kilobase pair (kb) P1 bacteriophage clones spanning either the human or mouse apoB gene (clones p158 and p649, respectively) confer apoB expression in the liver of transgenic mice, but not in the intestine. We hypothesized that the absence of intestinal expression was due to the fact that these clones lacked a distant DNA element controlling intestinal expression. To test this possibility, transgenic mice were generated with 145- and 207-kb bacterial artificial chromosomes (BACs) that contained the human apoB gene and more extensive 5'- and 3'-flanking sequences. RNase protection, in situ hybridization, immunohistochemical, and genetic complementation studies revealed that the BAC transgenic mice manifested appropriate apoB gene expression in both the intestine and the liver, indicating that both BACs contained the distant intestinal element. To determine whether the regulatory element was located 5' or 3' to the apoB gene, transgenic mice were generated by co-microinjecting embryos with p158 and either the 5'- or 3'-sequences from the 145-kb BAC. Analysis of these mice indicated that the apoB gene's intestinal element is located 5' to the structural gene. Cumulatively, the transgenic mouse studies suggest that the intestinal element is located between -33 and -70 kb 5' to the apoB gene.
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  • Article
    Chen H, Wu F, Xu Y, Liu Y, Song L, Chen X, He Q, Liu W, Han Q, Zhang Z, Zou Y, Liu W.
    RSC Adv. 2021 Sep 01;11(47):29752-29761.
    As a kind of new psychoactive substance (NPS), synthetic cathinones have drawn great worldwide attention. In this study, molecularly imprinted polymers (MIPs), as adsorbents for the extraction and determination of 4-methyldimethcathinone (4-MDMC), were first synthesized by coprecipitation polymerization. The physicochemical analyses of MIPs were successfully performed by XRD, FTIR, FESEM and TGA techniques. Furthermore, rebinding properties of temperature and pH dependence, and selectivity and reusability tests for MIPs and non-imprinted polymers (NIPs) were performed using an ultraviolet-visible spectrometer (UV-vis). The obtained results indicate that the imprinting efficiency has strong dependence on temperature and pH, and the optimal adsorption for targets is achieved under the condition of 318 K and pH = 6.0. This means that the combination between the polymers and 4-MDMC is a strong spontaneous and endothermic process. Compared with NIPs, MIPs exhibit prominent adsorption capacity (Q e = 9.77 mg g-1, 318 K). The selectivity coefficients (k) of MIPs for 4-MDMC, methylenedioxypentedrone (βk-MBDP), 4-ethylmethcathinone (4-EMC), methoxetamine (MXE) and tetrahydrofuranylfentanyl (THF-F) were found to be 1.70, 3.49, 7.14 and 5.82, respectively. Moreover, it was found that the adsorption equilibrium was achieved within 30 min. The aim of this work is the simple synthesis of MIPs and the optimal performance of the molecular recognition of 4-MDMC. Moreover, the synthesized MIPs can be easily regenerated and repeatedly used with negligible loss of efficiency (only 9.94% loss after six times adsorption-desorption tests). Satisfying recoveries in the range of 69.3-78.9% indicate that MIPs have good applicability for analyte removal from urine samples. Ultimately, this material shows great promise for the rapid extraction and separation of synthetic cathinones, which are dissolved in the liquid for the field of criminal sciences.
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  • Article
    Wen PH, Blumenthal KM.
    J Biol Chem. 1996 Nov 22;271(47):29752-8.
    Chemical modification implicates arginine residues of the Cerebratulus lacteus neurotoxin B-IV in biological activity. In the present study, we used site-directed mutagenesis to assess the functional contributions of each of these residues. Panels of mutants at each site have been constructed by polymerase chain reaction and recombinant proteins expressed and purified to homogeneity using an Escherichia coli expression system developed in this laboratory. All substitutions for Arg-17 (Gln, Ala, or Lys) yield proteins having undetectable levels of activity, while charge neutralizing replacement of Arg-25 (R25Q) causes a 400-fold reduction in specific toxicity. However, the R25K mutein is almost as active as natural toxin. Circular dichroism spectroscopy indicates that there are no major conformational changes in any of these muteins. These results therefore demonstrate the requirement for a guanidinium group at position 17, and a positive charge at position 25. NMR analyses (Hansen, P. E., Kem, W. R., Bieber, A. L., and Norton, R. S. (1992) Eur. J. Biochem. 210, 231-240) reveal neurotoxin B-IV to contain two antiparallel alpha-helices, which together include 57% of the sequence. Both Arg-17 and Arg-25 lie on the same face of the N-terminal helix (residues 13-26), as do the carboxyl groups of Glu-13 and Asp-21. However, charge neutralizing mutations of the latter two sites have no effects on biological activity. Arg-34, situated near the N terminus of helix 2 (residues 33-49) is also important for activity, as its replacement by Gln or Ala diminishes activity by 20- and 80-fold, respectively. However, unlike Arg-17 and Arg-25, thermal denaturation experiments suggest that R34Q may be structurally destabilized relative to wild-type B-IV.
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  • Article
    Wu XR, Medina JJ, Sun TT.
    J Biol Chem. 1995 Dec 15;270(50):29752-9.
    The transmembrane 4 (TM4) superfamily contains many important leukocyte differentiation-related surface proteins including CD9, CD37, CD53, and CD81; tumor-associated antigens including CD63/ME491, CO-029, and SAS; and a newly identified metastasis suppressor gene R2. Relatively little is known, however, about the structure and aggregation state of these four transmembrane-domained proteins. The asymmetrical unit membrane (AUM), believed to play a major role in stabilizing the apical surface of mammalian urothelium thus preventing it from rupturing during bladder distention, contains two TM4 members, the uroplakins (UPs) Ia and Ib. In association with two other (single transmembrane-domained) membrane proteins, UPII and UPIII, UPIa and UPIb form 16-nm particles that naturally form two-dimensional crystalline arrays, thus providing unique opportunities for studying membrane structure and function. To better understand how these proteins interact to form the 16-nm particles, we analyzed their nearest neighbor relationship by chemical cross-linking. We show here that UPIa and UPIb, which share 39% of their amino acid sequence, are cross-linked to UPII and UPIII, respectively. We also show that UPIa has a propensity to oligomerize, forming complexes that are stable in SDS, and that UPII can be readily cross-linked to form homodimers. The formation of UPII homodimers is sensitive, however, to octyl glucoside that can solubilize the AUMs. These data suggest that there exist two types of 16-nm AUM particles that contain UPIa/UPII or UPIb/UPIII, and support a model in which the UPIa and UPII occupy the inner and outer domains, respectively, of the UPIa/UPII particle. This model can account for the apparent "redundancy" of the uroplakins, as the structurally related UPIa and UPIb, by interacting with different partners, may play different roles in AUM formation. The model also suggests that AUM plaques with different uroplakin compositions may differ in their assembly, and in their abilities to interact with an underlying cytoskeleton. Our data indicate that two closely related TM4 proteins, UPIa and UPIb, can be present in the same cell, interacting with distinct partners. AUM thus provides an excellent model system for studying the targeting, processing, and assembly of TM4 proteins.
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  • Article
    Vilalta A, Kickhoefer VA, Rome LH, Johnson DL.
    J Biol Chem. 1994 Nov 25;269(47):29752-9.
    A novel gene transcribed by RNA polymerase (pol) III has been recently identified that produces an RNA component of a large cytoplasmic ribonucleoprotein complex (Kickhoefer, V. A., Searles, R. P., Kedersha, N. L., Garber, M. E., Johnson, D. L., and Rome, L. H. (1993) J. Biol. Chem. 268, 7868-7873). Since sequence analysis revealed that this gene contains promoter elements from two different classes of RNA pol III gene promoters, we examined the function of the 5'-flanking type-3 and internal type-2 sequences on transcription activity and the production of stable transcription complexes. We find that the vRNA gene contains a novel RNA pol III promoter, where both the external and internal sequences are essential for template activity and for the productive interaction of TFIIIC with the internal elements. Thus, the vRNA gene represents the first example of a template that requires both type-2 and type-3 promoter elements that appear to function synergistically in the formation of productive transcription complexes. We have further examined the function of the unique arrangement of an internal A box and two B box elements. We find that at least one B element is required for template activity. In the absence of the 5'-flanking sequence the presence of both B elements inhibits transcription and the binding of TFIIIC. The formation of active complexes is restored when either the B2 element is inactivated or the distance separating the two B elements is increased. Therefore, the B2 element appears to negatively regulate template activity in the absence of the upstream sequences. This unique RNA pol III promoter arrangement may provide a novel mechanism for the regulation of vRNA gene activity.
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  • Article
    Liang CJ, Cheng KL, Liang JJ.
    Environ Sci Pollut Res Int. 2018 Oct;25(29):29752-29765.
    This study integrated the results of photochemical grid modeling and assessment monitoring to quantify the impact of the offshore petrochemical industrial park (OPIP), with area of 26.03 km2, on ambient ozone in a coastal region of Taiwan. A highly repetitive ozone-spreading phenomenon in the adjacent OPIP area was observed, which shows that ozone spreading follows a clear cycle between offshore and inland areas during the prevailing periods of ozone events (≥ 120 ppb). The incremental ratio of ambient ozone for the OPIP on ozone event days during the southwest and northeast monsoons in 2011-2016 ranged from 1.05 to 1.25 (average = 1.15) and 1.04-1.27 (average = 1.17), respectively. Data from ten photochemical assessment monitoring stations surrounding the OPIP in 2016 showed that the ratio of monthly average concentrations of volatile organic compounds (VOCs) during the northeast monsoon to the southwest monsoon was approximately 1.5. The ratio of the monthly latent incremental amount of ozone to the total volatile organic amount in the same month during the northeast and southwest monsoons was in the ranges of approximately 0.84-0.97 and 1.01-1.12, respectively. Moreover, the latent incremental amount of ozone during the daytime was greater than that at night. The results indicate that the observed ozone concentration increases as the latent incremental amount of ozone or ambient VOCs decreases.
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  • Article
    Xu X, Wang W, Zou J, Kratz K, Deng Z, Lendlein A, Ma N.
    ACS Appl Mater Interfaces. 2023 Jun 28;15(25):29752-29766.
    The clinical success of orthopedic implants is closely related to their integration in the bone tissue promoted by rough device surfaces. The biological response of precursor cells to their artificial microenvironments plays a critical role in this process. In this study, we elucidated the relation between cell instructivity and surface microstructure of polycarbonate (PC)-based model substrates. The rough surface structure (hPC) with an average peak spacing (Sm) similar to the trabecular spacing of trabecular bone improved osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), as compared to the smooth surface (sPC) and the surface with a moderate Sm value (mPC). The hPC substrate promoted the cell adhesion and assembling of F-actin and enhanced cell contractile force by upregulating phosphorylated myosin light chain (pMLC) expression. The increased cell contractile force led to YAP nuclear translocation and the elongation of cell nuclei, presenting higher levels of active form of Lamin A/C. The nuclear deformation alternated the histone modification profile, particularly the decrease of H3K27me3 and increase of H3K9ac on the promoter region of osteogenesis related genes (ALPL, RUNX2, and OCN). Mechanism study using inhibitors and siRNAs elucidated the role of YAP, integrin, F-actin, myosin, and nuclear membrane proteins in such a regulatory process of surface topography on stem cell fate. These mechanistical insights on the epigenetic level give a new perspective in understanding of the interaction of substrate and stem cells as well as provide valuable criteria for designing bioinstructive orthopedic implants.
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  • Article
    Li X, Tan Y, Lai H, Li S, Chen Y, Li S, Xu P, Yang J.
    ACS Appl Mater Interfaces. 2019 Aug 21;11(33):29746-29752.
    Nowadays, inorganic CsPbBr3 perovskite is emerging as a promising candidate as a light-absorbing layer in photovoltaic devices due to its excellent photoelectric property and superior stability under humidity and thermal attacks in comparison with organic cation-based hybrid perovskites. However, the impure perovskite phase and severe interfacial charge recombination have limited the further improvement of device performance. In this work, a vapor-assisted solution technique was introduced to prepare a high-purity CsPbBr3 film in a perovskite solar cell (PSC). To further reduce the electron-hole recombination and enhance charge extraction, we introduced the novel intermediate energy level of manganese sulfide (MnS) as a hole transport layer in CsPbBr3 PSC. The as-optimized CsPbBr3 PSC based on all-inorganic transport layers delivers a power conversion efficiency (PCE) of 10.45% in comparison with 8.16% for the device free of an intermediate layer, which is one of the highest PCEs achieved among the CsPbBr3-based PSCs to date. Moreover, the optimized device retained 80% PCE of its initial efficiency over 90 days under 80% relative humidity at 85 °C, indicating an excellent environmental tolerance to boost the commercial application of low-cost, efficient, and stable all-inorganic PSCs.
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  • Article
    Lv Q, Si W, Yang Z, Wang N, Tu Z, Yi Y, Huang C, Jiang L, Zhang M, He J, Long Y.
    ACS Appl Mater Interfaces. 2017 Sep 06;9(35):29744-29752.
    Metal-free catalysts for oxygen reduction reaction (ORR) are the desired materials for low-cost proton exchange membrane fuel cells. Graphdiyne (GDY), a novel type of two-dimensional carbon allotrope, is featured by its sp- and sp2-hybridized carbon atoms, different from the other existing carbon materials. Thus, nitrogen (N) can be doped in new styles by substituting sp-hybridized carbon atoms, effective for ORR, which has been displayed in this study using both experimental and theoretical technologies. The N-doped GDY was synthesized with pyridine and NH3 as N sources successively, expressing an electrocatalytic activity at a potential above 0.8 V similar to that of commercial Pt/C for ORR in alkaline solution and higher stability and better methanol tolerance than those of Pt/C.
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  • Article
    Döppler H, Bastea L, Borges S, Geiger X, Storz P.
    Oncotarget. 2015 Oct 06;6(30):29740-52.
    Vasodilator-stimulated phosphoprotein (VASP) signaling is critical for dynamic actin reorganization processes that define the motile phenotype of cells. Here we show that VASP is generally highly expressed in normal breast tissue and breast cancer. We also show that the phosphorylation status of VASP at S322 can be predictive for breast cancer progression to an aggressive phenotype. Our data indicate that phosphorylation at S322 is gradually decreased from normal breast to DCIS, luminal/ER+, HER2+ and basal-like/TN phenotypes. Similarly, the expression levels of PKD2, the kinase that phosphorylates VASP at this site, are decreased in invasive ductal carcinoma samples of all three groups. Overall, the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors.
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