It is challenging to concurrently control the microstructure evolutions after undergoing casting, sheet forming and welding. This study successfully addressed this challenge via trace TiC–TiB2 ...nanoparticles in the amelioration of solidification-rolling-welding microstructural evolution. Nanoparticles refined the solidified microstructures and significantly increased the net driving force for recrystallization, promoting the precipitation of nanoscale Guinier–Preston zones and β'' phases. The coarsening of the fusion and heat-affected zones was also effectively suppressed. The yield strength (YS) and ultimate tensile strength (UTS) of the rolled plates were enhanced by 31.3% and 16.3%, respectively, without significantly sacrificing ductility. Additionally, the YS and UTS of the as-welded welding joints were enhanced by 30.2% and 7.8%, respectively. The amelioration mechanism of TiC–TiB2 throughout the microstructural evolution and strengthening process was systematically investigated. This study provides a typical model for the complete amelioration of microstructural evolution in aluminum alloys under multiple processing conditions.
•The nucleation of solidified phases is promoted, and their growth is hindered.•Recrystallization and formation of coherent nanoscale precipitates are promoted.•Coarsening of fusion zone and heat affected zone is suppressed.•Building better microstructure configuration for improved properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Alzheimer’s disease (AD) is an age-related neurological disorder. Currently, there is no effective cure for AD due to its complexity in pathogenesis. In light of the complex pathogenesis of AD, the ...traditional Chinese medicine (TCM) formula Kai-Xin-San (KXS), which was used for amnesia treatment, has been proved to improve cognitive function in AD animal models. However, the active ingredients and the mechanism of KXS have not yet been clearly elucidated. In this study, network pharmacology analysis predicts that KXS yields 168 candidate compounds acting on 863 potential targets, 30 of which are associated with AD. Enrichment analysis revealed that the therapeutic mechanisms of KXS for AD are associated with the inhibition of Tau protein hyperphosphorylation, inflammation, and apoptosis. Therefore, we chose 7-month-old senescence-accelerated mouse prone 8 (SAMP8) mice as AD mouse model, which harbors the behavioral and pathological hallmarks of AD. Subsequently, the potential underlying action mechanisms of KXS on AD predicted by the network pharmacology analyses were experimentally validated in SAMP8 mice after intragastric administration of KXS for 3 months. We observed that KXS upregulated AKT phosphorylation, suppressed GSK3β and CDK5 activation, and inhibited the TLR4/MyD88/NF-κB signaling pathway to attenuate Tau hyperphosphorylation and neuroinflammation, thus suppressing neuronal apoptosis and improving the cognitive impairment of aged SAMP8 mice. Taken together, our findings reveal a multi-component and multi-target therapeutic mechanism of KXS for attenuating the progression of AD, contributing to the future development of TCM modernization, including KXS, and broader clinical application.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The practical use of lithium–sulfur batteries faces the “shuttle effect” and lithium dendrite growth. Employing SiO instead of Li metal can fundamentally solve the above problems. Nevertheless, ...selecting a convenient prelithiation method is essential for normal operation of the battery system. Hence, this work proposed a novel SiO-sulfur battery with preloaded Li3N in a cathode as a prelithiation reagent, which can thoroughly solve the dendrite problem and the side reaction with polysulfides of lithium anode. The S@KB-Li3N vs SiO full cell can obtain a high specific capacity of 790 mAh g–1 after the activation process and be maintained at 478 mAh g–1 after 100 cycles. Our design will provide a new prelithiation strategy for a high-specific-energy SiO-sulfur battery system.
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IJS, KILJ, NUK, PNG, UL, UM
Experimental observations have shown that peptides are chemically modified under plasma treatment, which impacts the function and lifetime of a protein. This paper investigates the interactions of ...reactive oxygen species (ROS) produced in atmospheric plasmas and peptides. Results show that the reactions typically start with the H ion from the side chain of amino acids. As the reactions continue, the introduction of O atoms is the most common reaction, and the formation of double C = C bonds, detachment of carboxyl groups, and cleavage of the ring are also observed. Moreover, the degree of oxidative modification of the peptides increases with increasing doses of ROS. This study reveals the formation and breaking of chemical bonds and the generation of new reactive groups in the structure of peptides under plasma treatment, which enables us to understand the mechanisms of plasma medicine deeply.
In this manuscript, we present a modeling study on the interactions of CAP and peptides by a reactive molecular dynamic simulation. The formation and breaking of chemical bonds and the generation of new reactive groups on the structure of peptides are carefully investigated upon the impact of reactive oxygen species, and the final products are given, which agree well with the experimental observation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Helicobacter pylori
(
H. pylori
) is a gram-negative bacteria with a worldwide infection rate of 50%, known to induce gastritis, ulcers and gastric cancer. The interplay between
H. pylori
and immune ...cells within the gastric mucosa is pivotal in the pathogenesis of
H. pylori
-related disease. Following
H. pylori
infection, there is an observed increase in gastric mucosal macrophages, which are associated with the progression of gastritis.
H. pylori
elicits macrophage polarization, releases cytokines, reactive oxygen species (ROS) and nitric oxide (NO) to promote inflammatory response and eliminate
H. pylori
. Meanwhile,
H. pylori
has developed mechanisms to evade the host immune response in order to maintain the persistent infection, including interference with macrophage phagocytosis and antigen presentation, as well as induction of macrophage apoptosis. Consequently, the interaction between
H. pylori
and macrophages can significantly impact the progression, pathogenesis, and resolution of
H. pylori
infection. Moreover, macrophages are emerging as potential therapeutic targets for
H. pylori
-associated gastritis. Therefore, elucidating the involvement of macrophages in
H. pylori
infection may provide novel insights into the pathogenesis, progression, and management of
H. pylori
-related disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Study was focused on PD-L1 and TILs in HPSCC patients from 2014 to 2017.•High CD8 and FoxP3 TILs density in HPSCC contribute to longer patient survival.•PD-L1 positivity in combination with CD8high ...expression serve as a prognostic factor.
Limited information is available regarding programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in hypopharyngeal squamous cell carcinoma (HPSCC). Therefore, we investigated the expression of PD-L1 and the volume of TILs in HPSCC to determine whether these biomarkers were associated with patient clinicopathologic characteristics and prognosis. Furthermore, we explored p16 status and analyzed its possible correlations with clinical outcomes.
Tissues of 111 HPSCC patients were immunohistochemically analyzed for PD-L1, CD8, CD4, and Foxp3 expression to assess the microenvironment. We also assessed the p16 status. The expression of PD-L1 and TILs were analyzed with respect to patient clinicopathologic variables and prognosis.
Twenty-four (21.6%) patients had PD-L1 expression in ≥1% of tumor cells. PD-L1 expression was significantly correlated with a high level of TILs (P < 0.05). Kaplan–Meier analysis showed that higher CD8+ and FoxP3+ TIL infiltration was strongly associated with superior overall survival (OS, P = 0.005 and P = 0.008) and disease-free survival (DFS, P = 0.015 and P = 0.048). Univariate and multivariate analyses confirmed that CD8+ TIL exhibited strong prognostic significance. The combination of PD-L1+ with CD8high expression was a prognostic factor and was associated with better OS (P = 0.025). Moreover, p16 positivity was detected in five patients (4.5%) and was only occasionally involved in HPSCC.
Our findings indicate that high CD8 and FoxP3 expression in HPSCC contributes to longer patient survival. Although PD-L1 expression was not associated with outcome, PD-L1 positivity in combination with CD8high expression may have greater predictive potential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A (4 + 2)-cyclization of benzofuran derived oxa-dienes with malononitrile was established, and benzofuranopyrans with potential antitumor activity were synthesized in generally good yields (up to ...85 %). This reaction not only has confronted the challenges in developing (4 + 2)- cyclization involving benzofuran derived oxa-dienes, but also provides an atom-economic method for the construction of biologically important benzofuranopyran frameworks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A novel metal-free nitrative bicyclization of 1,7-diynes with
BuONO in the presence of H
O is reported, producing three types of skeletally diverse tricyclic pyrroles, namely pyrrolo3,4-
quinolines, ...chromeno3,4-
pyrroles and benzo
isoindoles, with moderate to good yields by simply tuning the linkers of the 1,7-diynes. This domino protocol demonstrates remarkable compatibility regarding 1,7-diynes with different linkers, such as nitrogen and oxygen atoms and a hydroxymethyl group, and
BuONO plays dual roles as a nitro precursor as well as a nitrogen atom source.
The time-dependent quantum wave packet approach has been improved and formulated to treat the multiple surface problems and thus provided a new simple, yet a clear quantum picture for interpreting ...the reaction mechanism underlying the nonadiabatic dynamical processes. The method keeps the salient feature of the original quantum wave packet theory developed for single surface problems, i.e. the introduction of the absorbing potential and the grid basis including the discrete variable representation and the fast Fourier transformation, which makes the present methodology a very efficient implement for the nonadiabatic quantum scattering calculations. Here, we review the theoretical basis of this approach and its applications to the fundamental triatomic chemical reactions, the latter include the nonadiabatic dynamics calculations on the F + H
2
, F + HD, F + D
2
, O(
1
D) + N
2
, O(
3
P,
1
D) + H
2
, D
+
+ H
2
, and H
+
+ D
2
reactions. We also present a thorough historical overview of the theoretically nonadiabatic dynamical investigations particularly on the triatomic systems, and show how the time-dependent wave packet approach complements the time-independent quantum scattering theory.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Kinetochore-associated proteins are critical components of mitotic checkpoints, which are essential for faithful chromosomal segregation and spindle assembly during cell division. Recent advances ...have demonstrated that kinetochore-associated proteins are upregulated and serve significant roles in the carcinogenesis of numerous types of cancer. However, the effects of kinetochore-associated protein 1 (KNLC1) on human cancer, particularly on esophageal squamous cell carcinoma (ESCC), remain unclear. Lhe present study revealed that KNLC1 was highly expressed in ESCC cell lines. Subsequently, lentivirus-mediated short hairpin RNAs were used to knockdown KNLC1 expression in human ESCC cell lines. Cell growth and viability were measured using multiparametric high-content screening and the MLL assay, respectively. Cell apoptosis was assessed by staining cells with Annexin V-allophycocyanin and was detected using FACScan flow cytometry. Lhe results demonstrated that knockdown of KNLC1 effectively inhibited cell viability and increased apoptosis. In addition, a gene set enrichment analysis of online ESCC datasets indicated that KNLC1 overexpression was associated with increases in the mitotic spindle and hypoxia pathways, and decreases in the DNA repair and mismatch repair pathways. Lhe findings of the present study suggested that KNLC1 may have an essential role in mediating cell viability and apoptosis in human ESCC cells and may serve as a novel therapeutic target for ESCC. Key words: apoptosis, esophageal squamous cell carcinoma, kinetochore-associated proteins, mitosis, viability
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