المؤلفون: Lu, Shaolei¹ (AUTHOR) slu@lifespan.org, Yakirevich, Evgeny¹ (AUTHOR), Wang, Li Juan¹ (AUTHOR), Resnick, Murray B.¹ (AUTHOR), Wang, Yihong¹ (AUTHOR) ywang6@lifespan.org

المصدر: BMC Cancer. 11/12/2019, Vol. 19 Issue 1, p1-10. 10p. 1 Diagram, 5 Charts, 1 Graph.

مصطلحات موضوعية: *GATA proteins, *CARRIER proteins, *BREAST cancer, *KERATIN, *TRIPLE-negative breast cancer, *ESTROGEN receptors, *PROTEIN metabolism, *PROTEINS, *IMMUNOHISTOCHEMISTRY, *PROGNOSIS, *TUMOR classification, *RESEARCH funding, *BREAST tumors, *PROPORTIONAL hazards models, *TUMOR grading

مستخلص: Background: Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited.Methods: This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient's age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival.Results: CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P = 0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2% of Grade 1 cases were GATA3 negative (P < 0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor.Conclusions: This is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis. [ABSTRACT FROM AUTHOR]

المؤلفون: Zhang, Yuling^1,2 (AUTHOR), Duan, Haiyang^1,2 (AUTHOR), Lu, Shaolei^1,2 (AUTHOR), Yang, Shaoxia³ (AUTHOR), Qiu, Yaqin⁴ (AUTHOR) 52351838@ncepu.edu.cn, Liu, Songtao^1,2 (AUTHOR), Wu, Yinwei^1,2 (AUTHOR)

المصدر: Particle & Particle Systems Characterization. Mar2024, p1. 12p. 13 Illustrations, 5 Charts.

مستخلص: The corrosion inhibition performance of air nanobubbles (A‐NBs) is expected to address the environmental problems arising from chemical corrosion. In order to regulate the corrosion inhibition performance of A‐NBs, the particle characteristics of A‐NBs in flowing composite salt solutions are investigated, and the corrosion inhibition effect of A‐NBs under different concentration ratios and rotational speed of simulated circulating cooling water is studied. High salt concentrations significantly reduced the particle size, concentration, and zeta‐potential value of A‐NBs, thus reducing the stability of A‐NBs. The flow velocity has a slight effect on A‐NBs. The results of the weight loss and electrochemical method showed that A‐NBs achieved the highest corrosion inhibition rate of 55% under a concentration ratio of 1.5 and a rotational speed of 100 r min−1. The surface characterization of brass specimens revealed that A‐NBs facilitated the formation of Cu2(OH)2CO3 passivation film, calcium carbonate scale film, and a layer of bubbles on the surface of brass, which subsequently mitigated the erosive impact of the fluid. A‐NBs can adsorb cations and thus reduce the concentration of corrosive ions. However, the increase in concentration ratio and rotational speed impeded the formation of the bubble layer and passivation film. [ABSTRACT FROM AUTHOR]

المؤلفون: Hui, Yiang¹, Lu, Shaolei¹, Wang, Hai¹, Resnick, Murray B.¹, Wang, Yihong¹

المصدر: Histopathology. Jan2019, Vol. 74 Issue 2, p358-362. 5p. 1 Color Photograph, 1 Chart.

مصطلحات موضوعية: *EPIDERMAL growth factor receptors, *IMMUNOHISTOCHEMISTRY, *GENE amplification, *DUCTAL carcinoma, *IN situ hybridization

مستخلص: The article focuses on the study related to the discordant human epidermal growth factor receptor 2 (HER2)immunohistochemical expression and gene amplification in ductal carcinoma. It mentions that HER2 expression is observed in ductal carcinoma in situ (DCIS) than in invasive breast carcinoma. It focuses on the comparison of HER2 immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH) in patients.

المؤلفون: Becker, Klaus A¹, Lu, Shaolei¹, Dickinson, Ellen S², Dunphy, Karen A¹, Mathews, Lesley³, Schneider, Sallie Smith³, Jerry, D Joseph¹ jjerry@vasci.umass.edu

المصدر: Oncogene. 9/22/2005, Vol. 24 Issue 42, p6345-6353. 9p.

مصطلحات موضوعية: *ESTROGEN, *PROGESTERONE, *EPITHELIUM, *GROWTH factors, *ONCOGENES, *ONCOLOGY

مستخلص: DNA damage normally induces p53 activity, but responses to ionizing radiation in the mammary epithelium vary among developmental stages. The following studies examined the hormones and growth factors that regulate radiation-responsiveness of p53 in mouse mammary epithelium. Immunoreactive p21/WAF1 and TUNEL staining were used as indicators of p53 activity following exposure to ionizing radiation. In ovariectomized mice, radiation-induced accumulation of p21/WAF1 was minimal in the mammary epithelial cells (<1%). Systemic injections of estrogen and progesterone (E+P) for 72 h were necessary to recover maximal expression of p21/WAF1 following ionizing radiation (55%). The effects of E+P on radiation-induced p21/WAF1 were p53-dependent as responses were absent in Trp53−/− mice. Though hormonal treatments stimulated increases in the proportion of cycling cells (PCNA-positive), this was not directly correlated with p53 activity. Whole organ cultures were used to determine whether E+P act directly upon the mammary gland. Treatment with E+P was sufficient to render p53 responsive to radiation, but TGF-β-neutralizing antibodies blocked responsiveness. In the absence of E+P, TGF-β1 alone did not alter p53 activity. These results demonstrate that estrogen and progesterone together with TGF-β signaling are necessary for maintenance of p53 activity in the mammary epithelium.Oncogene (2005) 24, 6345–6353. doi:10.1038/sj.onc.1208787; published online 6 June 2005 [ABSTRACT FROM AUTHOR]

المؤلفون: Yan, Guanghua¹ (AUTHOR), Lu, Shaolei² (AUTHOR), Zhang, Minglei² (AUTHOR), Wang, Jiachang² (AUTHOR), Yang, Xudong³ (AUTHOR), Zhang, Ziyang³ (AUTHOR), Gu, Jianfeng³ (AUTHOR), Li, Chuanwei^1,3 (AUTHOR) li-chuanwei@sjtu.edu.cn

المصدر: Applied Surface Science. Nov2020, Vol. 530, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *GAS lasers, *NITRIDING, *SURFACE hardening, *WEAR resistance, *STEEL, *CORROSION resistance

مستخلص: • Enhanced hardness and deformation resistance are observed in surface modified layer. • Wear resistance is drastically improved by gas nitriding and laser surface hardening. • The gas nitriding processed P20 steel has superior corrosion resistance. Gas nitriding and laser surface engineering are popular technologies to improve the surface performance of steels. This study evaluates the effect of duplex treatment of gas nitriding and laser surface engineering on surface hardness, wear and corrosion resistance of P20 plastic mold steel. It is found that gas nitriding at 550 °C for 20 h with nitrogen potential of 0.18 generates a nitrided layer without nitrides, which drastically improves the wear resistance. Simultaneously, the corrosion resistance is also marginal improved by the gas nitriding. Laser surface hardening further elevates the surface hardness and wear resistance of the nitrided layer due to the formation of martensite. Besides, a small amount of austenite retains in surface layer after laser surface hardening, which may lead to the galvanic attack at the phase interface between martensite and retained austenite and deteriorate the surface corrosion resistance. Laser surface melting results in the denitrification of nitrided layer and the formation of holes at the bottom of melted layer, thus reducing the surface hardness and wear resistance. Meanwhile, the denitrified surface layer also exhibits a degraded corrosion resistance owe to the decreasing nitrogen content and the formation of mixed structure of martensite and retained austenite. [ABSTRACT FROM AUTHOR]

المؤلفون: Long, Shang‐Min^1,2,3 (AUTHOR) smlong@hhu.edu.cn, Zhao, Shichang^1,3 (AUTHOR), Gao, Zhen^3,4 (AUTHOR), Sun, Shantong⁴ (AUTHOR), Shi, Jia‐Rui⁵ (AUTHOR), Ying, Jun² (AUTHOR), Li, Guancheng⁶ (AUTHOR), Cheng, Lijing⁷ (AUTHOR), Chen, Jiajia^1,3 (AUTHOR), Cheng, Xuhua^1,3 (AUTHOR), Lu, Shaolei² (AUTHOR)

المصدر: Geophysical Research Letters. 4/16/2024, Vol. 51 Issue 7, p1-11. 11p.

مصطلحات موضوعية: *OCEANIC mixing, *ANTARCTIC oscillation, *OCEAN, *OCEAN circulation, *MERIDIONAL winds, *SUMMER

مستخلص: Temporal and spatial variations in the ocean surface mixed layer are important for the climate and ecological systems. During 1980–2019, the Southern Indian Ocean (SIO) mixed layer depth (MLD) displays a basin‐wide shoaling trend that is absent in the other basins within 40°S–40°N. The SIO MLD shoaling is mostly prominent in austral winter with deep climatology MLD, substantially weakening the MLD seasonality. Moreover, the SIO MLD changes are primarily caused by a southward shift of the subtropical anticyclonic winds and hence ocean gyre, associated with a strengthening of the Southern Annular Mode, in recent decades for both winter and summer. However, the poleward‐shifted subtropical ocean circulation preferentially shoals the SIO MLD in winter when the meridional MLD gradient is sharp but not in summer when the gradient is flat. This highlights the distinct subtropical MLD response to meridional mitigation in winds due to different background oceanic conditions across seasons. Plain Language Summary: The ocean surface mixed layer (ML) is a well‐mixed layer with uniform physical and chemical properties and is key for the ocean in exchanging materials and energy with the atmosphere. The present study shows that during 1980–2019, the Southern Indian Ocean (SIO) ML depth (MLD) displays a basin‐wide decreasing trend, which is absent in the other basins within 40°S–40°N. The SIO MLD shoaling primarily appears in austral winter when the climatology ML is deep but is insignificant in summer, substantially weakening the MLD seasonality. The SIO MLD changes are primarily explained by the ocean dynamical adjustment driven by the surface zonal wind changes. Specifically, the strengthened Southern Annular Mode in recent decades drives southward shifts of the subtropical anticyclonic winds and ocean gyre year‐round. However, the poleward‐shifted ocean gyre preferentially decreases the SIO winter MLD as the meridional MLD gradient is sharp and thus efficiently reduces the deep ML water converging from the Southern Ocean into the SIO. In contrast, the SIO MLD displays negligible change in summer when its meridional gradient is flat. The results highlight that despite under nearly identical southward‐shifted subtropical winds, the winter and summer MLD responses are distinct due to different background oceanic conditions. Key Points: The seasonality of the Southern Indian Ocean surface mixed layer (ML) depth prominently weakens during 1980–2019The weakened seasonality mainly results from a pronounced winter ML shoalingThe southward shift of the subtropical ocean gyre driven by the strengthened Southern Annular Mode dominates the ML shoaling [ABSTRACT FROM AUTHOR]

المؤلفون: Lu, Shaolei¹ slu@lifespan.org, Herzlinger, Michael², Cao, Weibiao¹, Noble, Lelia¹, Yang, Dongfang¹, Shapiro, Jason², Kurtis, Jonathan¹, LeLeiko, Neal², Resnick, Murray¹

المصدر: Scientific Reports. 9/28/2018, Vol. 8 Issue 1, p1-1. 1p.

مستخلص: The pathogenesis of eosinophilic esophagitis (EoE) involves Th2-mediated eosinophil recruitment and degranulation into the esophagus. However, measuring serum Th2 cytokines, eosinophils, and eosinophil-derived products does not reliably distinguish EoE from control populations. Non-invasive methods to diagnose EoE are lacking. We evaluated the diagnostic value of a novel candidate biomarker of EoE: 15(S)-hydroxyeicosatetraenoic acid (HETE). We used immunoassay to measure 15(S)-HETE and cytokine profiles in patients undergoing endoscopy with known or suspected EoE. 31 subjects were enrolled, 16 with EoE, and 15 with an alternate diagnosis. 15(S)-HETE was elevated in the EoE group compared to non-EoE group. The sensitivity and specificity of 15(S)-HETE to be used as a non-invasive marker is 50% and 80%, respectively. 15(S)-HETE may aid in the diagnosis of EoE. [ABSTRACT FROM AUTHOR]

المؤلفون: Luo, Shuchang¹ (AUTHOR) lsc840927@126.com, Tu, Ting¹ (AUTHOR), Chen, Zhuo¹ (AUTHOR), Zhong, Yong¹ (AUTHOR), Xu, Jun¹ (AUTHOR), Lu, Shaolei¹ (AUTHOR), Sun, Xiaoyuan¹ (AUTHOR) 253433534@qq.com

المصدر: International Journal of Quantum Chemistry. 9/5/2023, Vol. 123 Issue 17, p1-12. 12p.

مصطلحات موضوعية: *COPPER, *COUPLING constants, *BOND angles, *OVERLAP integral, *MAGNETIC structure, *SUPERCONDUCTING magnets

مستخلص: The theoretical understanding of the magneto‐structural correlations of an oximato‐bridged dinuclear copper(II) complex can help develop new applied molecular magnets. This study evaluated the magnetic coupling constant of a [Cu2(hfac)2(ppko)2] complex using the density functional theory combined with the broken symmetry approach (DFT‐BS). The magnetic structure correlation between the magnetic coupling constant (Jcalc) of the complex and the structural parameters, NOCu bond angle (α), ONCu bond angle (β), NO bond length (RN‐O), and Cu•••Cu distance (R0), was evaluated. The data showed that Jcalc initially decreased and then increased as bond angles α and β increased. These relationships were expressed by unary quadratic functions. However, Jcalc varied linearly with the bond length, RN‐O, and spacing, R0. Moreover, in the ground state, the magnetic coupling constant increased with a decrease in the spin density of Cu(1), but gradually decreased as the spin density of Cu(2) increased. An increase of parameters α, β, RN‐O, and R0, resulted in a gradual increase in the distance between Cu(II) ions, and the square of the overlap integral between the non‐orthogonal magnetic orbitals of Cu(II) ions to gradually decay. Finally, the contribution of the antiferromagnetic part decreased as the magnetic coupling constant gradually increased. [ABSTRACT FROM AUTHOR]

المؤلفون: Huntington, Kelsey E.^1,2,3,4,5 (AUTHOR), Louie, Anna D.^1,2,3,4,6,7 (AUTHOR), Srinivasan, Praveen R.^1,2,3,4,6 (AUTHOR), Schorl, Christoph^6,8,9 (AUTHOR), Lu, Shaolei^1,3,4,6 (AUTHOR), Silverberg, David¹⁰ (AUTHOR), Newhouse, Daniel¹¹ (AUTHOR), Wu, Zhijin¹² (AUTHOR), Zhou, Lanlan^1,2,3,4,6 (AUTHOR), Borden, Brittany A.⁶ (AUTHOR), Giles, Francis J.¹³ (AUTHOR), Dooner, Mark¹⁴ (AUTHOR), Carneiro, Benedito A.^3,4,6,14 (AUTHOR), El-Deiry, Wafik S.^{1,2,3,4,5,6,14} (AUTHOR) wafik@brown.edu

المصدر: International Journal of Molecular Sciences. Jul2023, Vol. 24 Issue 13, p10870. 33p.

مصطلحات موضوعية: *TUMOR-infiltrating immune cells, *GRANZYMES, *PROGRAMMED cell death 1 receptors, *GLYCOGEN synthase kinase-3, *COLORECTAL cancer, *IMMUNE checkpoint proteins, *REGULATORY T cells, *IMMUNE response

مستخلص: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that has been implicated in numerous oncogenic processes. GSK-3 inhibitor elraglusib (9-ING-41) has shown promising preclinical and clinical antitumor activity across multiple tumor types. Despite promising early-phase clinical trial results, there have been limited efforts to characterize the potential immunomodulatory properties of elraglusib. We report that elraglusib promotes immune cell-mediated tumor cell killing of microsatellite stable colorectal cancer (CRC) cells. Mechanistically, elraglusib sensitized CRC cells to immune-mediated cytotoxicity and enhanced immune cell effector function. Using western blots, we found that elraglusib decreased CRC cell expression of NF-κB p65 and several survival proteins. Using microarrays, we discovered that elraglusib upregulated the expression of proapoptotic and antiproliferative genes and downregulated the expression of cell proliferation, cell cycle progression, metastasis, TGFβ signaling, and anti-apoptotic genes in CRC cells. Elraglusib reduced CRC cell production of immunosuppressive molecules such as VEGF, GDF-15, and sPD-L1. Elraglusib increased immune cell IFN-γ secretion, which upregulated CRC cell gasdermin B expression to potentially enhance pyroptosis. Elraglusib enhanced immune effector function resulting in augmented granzyme B, IFN-γ, TNF-α, and TRAIL production. Using a syngeneic, immunocompetent murine model of microsatellite stable CRC, we evaluated elraglusib as a single agent or combined with immune checkpoint blockade (anti-PD-1/L1) and observed improved survival in the elraglusib and anti-PD-L1 group. Murine responders had increased tumor-infiltrating T cells, augmented granzyme B expression, and fewer regulatory T cells. Murine responders had reduced immunosuppressive (VEGF, VEGFR2) and elevated immunostimulatory (GM-CSF, IL-12p70) cytokine plasma concentrations. To determine the clinical significance, we then utilized elraglusib-treated patient plasma samples and found that reduced VEGF and BAFF and elevated IL-1 beta, CCL22, and CCL4 concentrations correlated with improved survival. Using paired tumor biopsies, we found that tumor-infiltrating immune cells had a reduced expression of inhibitory immune checkpoints (VISTA, PD-1, PD-L2) and an elevated expression of T-cell activation markers (CTLA-4, OX40L) after elraglusib treatment. These results address a significant gap in knowledge concerning the immunomodulatory mechanisms of GSK-3 inhibitor elraglusib, provide a rationale for the clinical evaluation of elraglusib in combination with immune checkpoint blockade, and are expected to have an impact on additional tumor types, besides CRC. [ABSTRACT FROM AUTHOR]

المؤلفون: Ollila, Thomas A.^1,2 (AUTHOR) thomas_ollila@brown.edu, Masel, Rebecca H.¹ (AUTHOR), Reagan, John L.^1,2 (AUTHOR), Lu, Shaolei^1,3 (AUTHOR), Rogers, Ralph D.^1,4 (AUTHOR), Paiva, Kimberly J.³ (AUTHOR), Taher, Rashida² (AUTHOR), Burguera‐Couce, Ella⁵ (AUTHOR), Zayac, Adam S.^1,2 (AUTHOR), Yakirevich, Inna² (AUTHOR), Niroula, Rabin^1,2 (AUTHOR), Barth, Peter^1,2 (AUTHOR), Olszewski, Adam J.^1,2 (AUTHOR), Burguera-Couce, Ella⁶ (AUTHOR)

المصدر: Cancer (0008543X). Sep2022, Vol. 128 Issue 18, p3319-3329. 11p.

مستخلص: Background: Patients with hematologic malignancies have impaired humoral immunity secondary to their malignancy and its treatment, placing them at risk of severe coronavirus disease-19 (COVID-19) infection and reduced response to vaccination.Methods: The authors retrospectively analyzed serologic responses to initial and booster COVID-19 vaccination in 378 patients with hematologic malignancy and subsequently tracked COVID-19-related outcomes.Results: Seroconversion occurred in 181 patients (48%) after initial vaccination; patients who had active malignancy or those who were recently treated with a B-cell-depleting monoclonal antibody had the lowest rates of seroconversion. For initial nonresponders to vaccination, seroconversion after a booster dose occurred in 48 of 85 patients (56%). The seroconversion rate after the booster was similar for patients on (53%) and off (58%) active therapy (p = .82). Thirty-three patients (8.8%) developed a COVID-19 infection, and there were three COVID-19-related deaths (0.8%). Although no significant association was observed between postvaccination seroconversion and the incidence of COVID-19 infection, no patient with seroconversion died from COVID-19, and no patient who received tixagevimab/cilgavimab (N = 25) was diagnosed with a COVID-19 infection.Conclusions: Booster vaccinations can promote seroconversion in a significant proportion of patients who are seronegative after the initial vaccination course regardless of the specific vaccine or on/off treatment status at the time of revaccination. Although postvaccination seroconversion may not be associated with a decrease in any (including asymptomatic) COVID-19 infection, the authors' experience suggested that effective vaccination (including a booster), supplemented by passive immunization using tixagevimab/cilgavimab in case of lack of seroconversion, effectively eliminated the risk of COVID-19 death in the otherwise high-risk population.Lay Summary: Patients with hematologic malignancy, especially lymphoma, have an impaired response to coronavirus disease 2019 (COVID-19) vaccination. In this single-institution review, less than one half of the patients studied made detectable antibodies. For those who did not make detectable antibodies after initial vaccination, over one half (65%) were able to produce antibodies after booster vaccination. By the end of February 2022, 33 of the original 378 patients had a documented COVID-19 infection. The only deaths from COVID-19 were in those who had undetectable antibodies, and no patient who received prophylactic antibody therapy developed a COVID-19 infection. [ABSTRACT FROM AUTHOR]