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In addition to presenting significant diagnostic and treatment challenges, lung adenocarcinoma (LUAD) is the most common form of lung cancer. Using scRNA-Seq and bulk RNA-Seq data, we identify three genes referred to as HMR, FAM83A, and KRT6A these genes are related to necroptotic anoikis-related gene expression. Initial validation, conducted on the GSE50081 dataset, demonstrated the model's ability to categorize LUAD patients into high-risk and low-risk groups with significant survival differences. This model was further applied to predict responses to PD-1/PD-L1 blockade therapies, utilizing the IMvigor210 and GSE78220 cohorts, and showed strong correlation with patient outcomes, highlighting its potential in personalized immunotherapy. Further, LUAD cell lines were analyzed using quantitative PCR (qPCR) and Western blot analysis to confirm their expression levels, further corroborating the model's relevance in LUAD pathophysiology. The mutation landscape of these genes was also explored, revealing their broad implication in various cancer types through a pan-cancer analysis. The study also delved into molecular subclustering, revealing distinct expression profiles and associations with different survival outcomes, emphasizing the model’s utility in precision oncology. Moreover, the diversity of immune cell infiltration, analyzed in relation to the necroptotic anoikis signature, suggested significant implications for immune evasion mechanisms in LUAD. While the findings present a promising stride towards personalized LUAD treatment, especially in immunotherapy, limitations such as the retrospective nature of the datasets and the need for larger sample sizes are acknowledged. Prospective clinical trials and further experimental research are essential to validate these findings and enhance the clinical applicability of our prognostic model.

Up-to-date laser-driven lightings confront a challenge of simultaneously achieving good photometric and chromatic performances. Herein, the coupling of “patterned package design” and “phosphor wheel” was proposed and demonstrated effectively to deal with this tough issue, based on a new architecture of CaAlSiN 3 :Eu 2+ (CASN:Eu) glass ceramic film (GCF) on Y 3 Al 5 O 12 :Ce 3+ (YAG:Ce) GC plate. The fabricated composite has no interface between the two functional layers and retains the admirable luminescent features from CASN:Eu and YAG:Ce for the microstructural integrity during co-sintering. The studies on laser-microcrystalline interactions reveal that the luminescence saturation is almost determined by thermal quenching for YAG:Ce, but is ascribed to thermal/intensity quenching which are equally crucial for CASN:Eu. Benefiting from the elaborate architecture design, good color chromaticity tunability was obtained, and severe photon reabsorption was reduced. Moreover, accompanied with the rotation induced increase of thermal convection to air and pulse-like excitation, the constructed lighting engine under blue laser driven shows bright white light with luminous flux (LF) higher than 1000 lm, adjustable chromaticity from cool to warm, and improved color rendering index (CRI) approaching to 70.

Neuroinflammation occurs early in Alzheimer’s disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aβ clearance and disruption of synaptic connection. CEBPβ, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPβ-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPβ facilitated the interaction of CEBPβ with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1β, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced β-amyloid (Aβ) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPβ with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aβ secretion by inhibiting the CEBPβ-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEβCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEβCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.

Kaempferol (Kae) is a natural flavonoid with potent antioxidant activity, but its therapeutic use is limited by its low aqueous solubility. Here, a series of Kae derivatives were synthesized to improve Kae dissolution property in water and antioxidant activity. These compounds included sulfonated Kae (Kae-SO3), gallium (Ga) complexes with Kae (Kae-Ga) and Kae-SO3 (Kae-SO3-Ga). The compound structures were characterized by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and thermal methods (TG/DSC). The results showed that a sulfonic group (-SO3) was successfully tethered on the C3’ of Kae to form Kae-SO3. And in the metal complexation, 4-CO and 3-OH of the ligand participated in the coordination with Ga(III). The metal-to-ligand ratio 1:2 was suggested for both complexes. Interestingly, Kae-SO3-Ga was obviously superior to other compounds in terms of overcoming the poor water-solubility of free Kae, and the solubility of Kae-SO3-Ga was about 300-fold higher than that of Kae-Ga. Furthermore, the evaluation of antioxidant activities in vitro was carried out for Kae derivatives by using α,α-diphenyl-β-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) free radical scavenging. The results showed that Kae-SO3-Ga was also optimal for scavenging free radicals in a dose-dependent manner. These data demonstrate that sulfonate kaempferol-gallium complex has a promising future as a potential antioxidant and as a potential therapeutic agent for further biomedical studies.

Purpose Drawing on conservation of resources theory, this study aims to investigate the impact of online customer engagement on brand love via dual mediating mechanisms, empowerment (bright side) and stress (dark side). The roles of perceived brand quality and extroversion as weakener and facilitator respectively on the dark side effect are also examined. Design/methodology/approach An online survey is conducted, targeting people who have experience in participating in online engagement activities. The dual mediation and moderation analysis are examined. Findings The results confirm the proposed dual mediating mechanisms. Perceived brand quality and extroversion also significantly moderate the engagement–stress link. Research limitations/implications This study explains the mediating mechanisms between online customer engagement and brand love, with a focus on the fast-moving consumer goods industry. This calls for further research on other industries. Practical implications This study provides marketers with insights that online customer engagement strategies are not always good and that they should be more careful in formulating such strategies. Originality/value This study advances the understanding of the relationship between customer engagement and brand love in the virtual community especially in the social media context.

Summary Kaempferol has been identified as a potential cancer therapeutic agent by an increasing amount of evidences. However, the changes in the topography of cell membrane induced by kaempferol at subcellular‐ or nanometer‐level were still unclear. In this work, the topographical changes of cytomembrane in human cervical cancer cell (SiHa) induced by kaempferol, as well as the role of kaempferol in apoptosis induction and its possible mechanisms, were investigated. At the macro level, MTT assays showed that kaempferol inhibited the proliferation of SiHa cells in a time‐ and dose‐dependent manner. Flow cytometry analysis demonstrated that kaempferol could induce SiHa cell apoptosis, mitochondrial membrane potential disruption, and intracellular free calcium elevation. At the micro level, fluorescence imaging by laser scanning confocal microscopy (LSCM) indicated that kaempferol could also destroy the networks of microtubules. Using high resolution atomic force microscopy (AFM), we determined the precise changes of cellular membrane induced by kaempferol at subcellular or nanometer level. The spindle‐shaped SiHa cells shrank after kaempferol treatment, with significantly increased cell surface roughness. These data showed structural characterizations of cellular topography in kaempferol‐induced SiHa cell apoptosis and might provide novel integrated information from macro to nano level to assess the impact of kaempferol on cancer cells, which might be important for the understanding of the anti‐cancer mechanisms of drugs. SCANNING 38:644–653, 2016. © 2016 Wiley Periodicals, Inc.

To increase the thermostability of Rhizomucor miehei lipase, the software Disulfide by Design was used to engineer a novel disulfide bond between residues 96 and 106, and the corresponding double cysteine mutants were constructed. The R. miehei lipase mutant could be expressed by Pichia pastoris in a free secreted form or could be displayed on the cell surface. The new disulfide bond spontaneously formed in the mutant R. miehei lipase. Thermostability was examined by measuring of hydrolysis activity using 4-nitrophenyl caprylate as a substrate. The engineered disulfide bond contributed to thermostability in the free form of the R. miehei lipase variant. The variant displayed on the yeast cell surface had significantly increased residual hydrolytic activity in aqueous solution after incubation at 60°C for 5 h and increased synthetic activity in organic solvent at 60°C. These results indicated that yeast surface display might improve the stability of R. miehei lipase, as well as amplifying the thermostability through the engineered disulfide bond.

Silver nanoparticles (AgNPs) have been widely used in antibacterial fields due to their excellent antibacterial effects. Here, by using a dietary flavonoid found in edible plants, kaempferol (Kae), as reducing and capping agent, a facile and eco-friendly method was developed to synthesize the uniform and long-term stable silver nanoparticle/kaempferol composites (Kae-AgNPs). Kae-AgNPs were characterized by ultraviolet visible (UV–Vis) spectroscopy, Fourier transform infrared spectrum (FT-IR) spectroscopy, dynamic light scattering (DLS), high resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Kae-AgNPs with a size about 10 nm were synthesized by 0.1 mmol/L Kae. Lower concentration of Kae was shown with smaller Kae-AgNPs due to a few of Kae molecules expected to reduce a small number of Ag + ions to metallic silver. Aqueous Kae-AgNPs were very stable and could be stably dispersed in water for about two months as evidenced by DLS detection, and the stability was further confirmed by XPS. Antibacterial analysis against Escherichia coli (ATCC 8099) and Staphylococcus aureus (ATCC 6538) strains showed that Kae-AgNPs displayed superior antibacterial effects than AgNPs or Kae alone, and interestingly, much better than that of the analogous nano-silver composites in the previous studies. Moreover, Kae-AgNPs with a low concentration of 2 μg/mL demonstrated highly effective antibacterial activity against E. coli (1 × 10 6  CFU/mL). The antibacterial mechanisms of Kae-AgNPs included the destruction of the membrane structure of bacteria, leakage of the cell contents, inducing the production of reactive oxygen species (ROS), and eventually resulting in bacteria death. The results suggest that Kae-AgNPs have high efficiency against bacteria, and have the potential to be further developed as promising antibacterial nanocomposites.

To effectively treat the pollutant in sewage, a new-type three-dimensional aerogel based on graphene oxide and waste paper was fabricated via simple mixing and freeze-drying processes. Therein, waste paper was activated in advance, and polyvinyl alcohol served as physical crosslinking agent. The results showed that the obtained aerogel with porous three-dimensional network structure exhibited good thermal stability. When it acted as adsorbent for treating organic dye (methylene blue) and antibiotic (ciprofloxacin), the adsorption process was explored. In single system, the pseudo-first-order and pseudo-second-order kinetic models were used to discuss the detail about the aerogel adsorbing pollutant. Moreover, the Langmuir and Freundlich adsorption models were applied to describe the equilibrium isotherms and calculate the isotherm constants. Thermodynamic results stated that the adsorption of pollutant onto aerogel was feasible and spontaneous. In binary system, the adsorption capacity of methylene blue by aerogel increased, while the adsorption capacity of ciprofloxacin by aerogel declined. The pseudo-second-order kinetics was consistent with the adsorption of pollutant by aerogel in such binary system. This study would provide a new boulevard to develop environmental, low-cost and high-efficiency adsorbent for removing pollutant from wastewater. Graphical abstract

Background Dengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally. Results Phylogenetic analysis revealed at least four distinct DENV3/III lineages. Two of the lineages (DENV3/III-B and DENV3/III-C) are current actively circulating whereas the DENV3/III-A and DENV3/III-D were no longer recovered since the 1980s. Selection pressure analysis revealed strong evidence of positive selection on a number of amino acid sites in PrM, E, NS1, NS2a, NS2b, NS3, NS4a, and NS5. The Malaysian DENV3/III isolates recovered in the 1980s (MY.59538/1987) clustered into DENV3/III-B, which was the lineage with cosmopolitan distribution consisting of strains actively circulating in the Americas, Africa, and Asia. The Malaysian isolates recovered after the 2000s clustered within DENV3/III-C. This DENV3/III-C lineage displayed a more restricted geographical distribution and consisted of isolates recovered from Asia, denoted as the Asian lineage. Amino acid variation sites in NS5 (NS5–553I/M, NS5–629 T, and NS5–820E) differentiated the DENV3/III-C from other DENV3 viruses. The codon 629 of NS5 was identified as a positively selected site. While the NS5-698R was identified as unique to the genome of DENV3/III-C3. Phylogeographic results suggested that the recent Malaysian DENV3/III-C was likely to have been introduced from Singapore in 2008 and became endemic. From Malaysia, the virus subsequently spread into Taiwan and Thailand in the early part of the 2010s and later reintroduced into Singapore in 2013. Conclusions Distinct clustering of the Malaysian old and new DENV3/III isolates suggests that the currently circulating DENV3/III in Malaysia did not descend directly from the strains recovered during the 1980s. Phylogenetic analyses and common genetic traits in the genome of the strains and those from the neighboring countries suggest that the Malaysian DENV3/III is likely to have been introduced from the neighboring regions. Malaysia, however, serves as one of the sources of the recent regional spread of DENV3/III-C3 within the Asia region.