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关键词： 1/f noise   Graphene field-effect transistor   HOPS complex   membrane proteins   Rab GTPases  

摘要： Graphene field-effect transistors (GFETs) functionalized with lipid monolayers provide a sensitive platform for probing membrane protein dynamics. Here, we analyze the effect of peripheral membrane proteins on this assay. We focused on the prenylated Rab7 GTPase Ypt7 and its interacting HOPS tethering complex using liquid-gated GFETs combined with low-frequency noise spectroscopy. Current-voltage (I-V) transfer measurements reveal no or only very small changes upon binding of Ypt7 and after addition of HOPS. In contrast, noise analysis reveals pronounced flicker (1/f) noise level growth after Ypt7 binding, most likely due to conformational dynamics of Ypt7. Recruitment of the HOPS complex by Ypt7 to membranes inhibits these fluctuations, suggesting structural stabilization of Ypt7 via HOPS binding. Our findings demonstrate that noise spectroscopy allows for enhancing the sensitivity of GFET-based biosensing, offering insights into protein-membrane and protein-protein interactions beyond traditional electronic readouts.

关键词： Recombinant human parathyroid hormone (1-34)   PTCHD1   Cell contact inhibition   Keratinocytes   Psoriasis  

摘要： Psoriasis is a chronic, immune-mediated inflammatory skin disease induced by genetic and environmental factors, with dysfunctional contact inhibition of keratinocytes being a core pathological feature leading to hyperproliferation. Our previous gene chip screening identified a significant downregulation of PTCHD1 following treatment with recombinant human parathyroid hormone (1-34) (rhPTH(1-34)), which inhibited keratinocyte proliferation. PTCHD1 (Patched domain-containing protein 1) is a transmembrane protein that regulates intercellular communication and proliferative signaling. This study aimed to investigate whether rhPTH(1-34) restores contact inhibition and controls keratinocyte proliferation by downregulating PTCHD1 to modulate the Hippo signaling pathway. In vitro experiments showed that rhPTH(1-34) treatment significantly suppressed HaCaT cell viability, downregulated PTCHD1 mRNA and protein expression, and reduced the cell adhesion index. In a PTCHD1-overexpressing HaCaT model, enhanced cell adhesion, proliferation, and elevated IL-1β expression were observed, all of which were reversed by rhPTH(1-34). Inhibition of the Hippo pathway with Verteporfin recapitulated the contact inhibition phenotype. Mechanistically, rhPTH(1-34) downregulated PTCHD1, activated the key MST1/2-LATS1 kinase cascade, promoted phosphorylation of YAP at Ser127, and facilitated its cytoplasmic retention. In vivo, intraperitoneal injection of rhPTH(1-34) ameliorated psoriatic lesions in a mouse model, evidenced by reduced erythema, scaling, epidermal thickening, and lower inflammatory cytokine levels, without inducing fluctuations in serum calcium. In conclusion, rhPTH(1-34) restores contact inhibition and suppresses keratinocyte proliferation and inflammation by downregulating PTCHD1 to regulate the Hippo signaling pathway, demonstrating its potential as a treatment for psoriasis.

关键词： antimicrobial activity   cytotoxicity   fermentation modeling   phenazine-1-carboxylic acid (PCA)   Pseudomonas chlororaphis aureofaciens  

摘要： This study investigates phenazine-1-carboxylic acid (PCA) production by Pseudomonas chlororaphis subsp. aureofaciens under submerged batch fermentation. This nonpathogenic, flexible carbon-utilizing strain was selected as a safer and industrially adaptable PCA producer. Chemical and physical parameters were optimized, and phenazines were isolated by chloroform extraction followed by adsorption chromatography and characterized using UV-vis, FTIR, and H-1-NMR analyses. PCA production was identified as growth-associated, yielding 129.45 & micro;g/mL-comparable to wild-type Pseudomonas strains despite the use of low-cost glycerol medium-highlighting the process's industrial relevance. Key kinetic parameters were determined as Y-XS = 0.64 mg/mg, Y-PS = 0.12 mg/mg, Y-PX = 0.35 mg/mg, and mu = 0.39 h(-)(1). PCA exhibited antimicrobial activity against Klebsiella pneumoniae (10 mm) and Micrococcus luteus (22 mm) at 150 & micro;g/mL. Cytotoxicity was evaluated via MTT assay on A549 and SKOV3 cells, yielding IC50 values of 17.30 +/- 1.72, 13.04 +/- 0.76, and 5.69 +/- 0.35 & micro;g/mL at 24, 48, and 72 h, respectively, with notable effects also observed in SKOV3 cells. Overall, the findings demonstrate that PCA possesses significant antimicrobial and anticancer potential, supporting its further development as a natural bioactive compound.

关键词： Caputo Derivative   Porous Medium Equation   Qualitative Study   Finite Volume Element Method   Approximate Solution  

摘要： In order to provide a solid foundation for modeling heat and mass transfer in fractal porous media, this work investigates the (n + 1)-dimensional nonlinear Caputo fractional porous medium (CFPM) equation, which takes non-local interactions and memory effects into account. We are able to capture diffusion processes that classical models are unable to adequately describe by using fractional-order derivatives. We explore how changing the fractional order affects the diffusion dynamics numerically using the finite volume element method (FVEM), emphasizing the role of memory effects on the transport processes in porous media. Our results show that slower diffusion rates and more strong memory effects are introduced at lower fractional orders, which are important parameters in complex porous materials. Comprehensive 2D and 3D visuals illustrate the impact of fractional dynamics on the transport processes in these mediums.

关键词： Pristine (001) GaAs substrate   In situ Al2O3 atomic layer deposition   X-ray photoelectron spectroscopy analysis   And room-temperature photoluminescence measurements  

摘要： The study investigates the Al₂O₃/GaAs interface formed by in situ atomic layer deposition (ALD) of Al₂O₃ on pristine (0 0 1)-oriented GaAs substrate, using X-ray photoelectron spectroscopy (XPS) and room-temperature photoluminescence (PL). The Al₂O₃/GaAs interface is free of high-valence arsenic (As₂O₃ and As₂O₅) and gallium (Ga₂O₃) oxides when the Al₂O₃ layer thickness exceeds 3 nm. The Al₂O₃ deposition on an As-terminated GaAs substrate leads to the presence of low-valence arsenic oxides (As₂O and AsO) and As–As bonds related to As–As dimers at the interface. These dimers restrict the PL enhancement to approximately twice that of unpassivated GaAs. In contrast, Ga-terminated GaAs exhibits a reduction of roughly an order of magnitude in these interfacial species, as well as a PL intensity that is significantly (x20) higher than that of unpassivated GaAs. When the Al₂O₃ layer thickness is less than 3 nm, both the low- and high-valence oxides, as well as elemental As, are detected in the near-interface region of Ga- and As-terminated GaAs samples. The PL intensity of GaAs capped with an Al₂O₃ layer thinner than 3 nm is still considerably (x8) higher than that of unpassivated GaAs and is mainly limited by elemental arsenic. According to XPS data, oxide deposition reduces band bending in GaAs at the Al₂O₃/GaAs interface by 0.2–0.4 eV, indicating a decrease in interface state density, i.e. the unpinned state of the Fermi level at the interface. The study delivers criteria for the high-quality passivation of (0 0 1) GaAs surface.

关键词： 1-Hydroxyethyl radical   Chemical composition   EPR   Huangjiu   Multivariate regression  

摘要： The Fenton reaction represents the key chemical oxidation in fermented alcoholic beverage (FABs), with the generated free radicals potentially contributing to the unique flavor of aged Huangjiu. This study identified 1-hydroxyethyl radical (1-HDR) as the key free radical in aged Huangjiu via electron paramagnetic resonance spectroscopy, and 1-HDR content showed a fluctuating increase during aging (1957–9526 nmol/L). To clarify the relationship between chemical composition and 1-HDR, 39 compounds (phenols, organic acids, metals, and sulfur-containing compounds) in Huangjiu were quantitated by high-performance liquid chromatography-tandem mass spectrometry, inductively coupled plasma mass spectrometry, and ion chromatography. Pearson correlation analysis and partial least squares regression showed that the variables were classified as either pro-oxidant (Fe, Mn, oxalic acid, tartaric acid, succinic acid, glutaric acid, caffeic acid, and acetic acid) or antioxidants (glutathione, L-cysteine, and 4-coumaric acid). This study provides a novel theoretical foundation for the regulation of free radicals and flavor for FABs.

关键词： DN   DNA methylation   DNMT1   NF2   YAP  

摘要： Aberrant DNA methylation patterns have been linked to diverse pathological conditions, including chronic kidney diseases. However, it remains unclear whether DNA methyltransferase 1 (DNMT1) affects renal tubular function in diabetic nephropathy (DN) DNMT1 and neurofibromatosis type 2 (NF2) expression levels were assessed using quantitative real-time PCR, Western blotting, immunohistochemical, and immunofluorescence analyses. The methylation status of the NF2 promoter was assessed through methylation-specific PCR and bisulfite genomic sequencing PCR. Cell viability was evaluated using the MTT assay, and cell apoptosis was quantified through flow cytometry analysis. Additionally, inflammatory responses were evaluated by quantifying IL-1 beta and IL-6 concentrations with enzyme-linked immunosorbent assays. DNMT1 expression was markedly elevated in the renal samples of DN patients and db/db mice. The DNA methylation inhibitor 5-aza-2 '-deoxycytidine alleviated kidney tubular injury in db/db mice, and it also reduced inflammatory responses and cell apoptosis in HK-2 cells exposed to high glucose (HG). Hypermethylation of the NF2 promoter was observed in HK-2 cells exposed to HG. Furthermore, DNMT1 knockdown was found to protect against cell apoptosis and inflammatory injury by modulating NF2 expression. These results demonstrated that DNMT1 can inhibit renal tubular cell apoptosis and inflammation in DN by regulating NF2 expression, which may have therapeutic applications in the development and treatment of DN.

摘要： Whether a T-cell response to dead cells arises depends on whether they harbor recognizable antigens, but also how dead cell debris impacts conventional dendritic cells (cDCs). In all tissues, cell debris is continuously phagocytosed by cDCs that can migrate to lymph nodes (LNs) and initiate T-cell responses, depending on their maturation state. The cDC1 lineage excels at antigen cross-presentation, which is required for induction of the CD8+ cytotoxic T-lymphocyte (CTL) response. At steady state, cDC1s undergo homeostatic maturation, which leads to T-cell non-responsiveness. This cDC1 state has recently been defined by ex vivo transcriptomics as resulting from phagocytosis of apoptotic cell debris. Necroptotic (tumor) cell death has been described as more immunogenic than apoptotic cell death, but its impact on cDC maturation has not been defined. In this study, we use an in vitro model to compare side-by-side the impact of well-defined apoptotic versus necroptotic tumor cell debris on the CTL response induced by cDCs, as well as on phenotype and function of both cDC1s and cDC2s. We confirm that cDC2s are less efficient than cDC1s in dead cell phagocytosis and find that they minimally respond to it in terms of gene expression. Apoptotic cell debris is more efficiently phagocytosed by cDC1s than necroptotic cell debris and induces a cDC1 cell state in vitro that has an evident transcriptomic relationship to the homeostatic maturation state defined ex vivo, thus validating our approach. We identify necroptosis as more potent than apoptosis in inducing a CTL response and attribute this to the ability of necroptotic cell debris to induce a specific, transcriptomically defined maturation state in cDC1s, characterized by cytokine and phosphoinositide signaling, cytoskeletal and metabolic activity and functional differentiation. We suggest that this cDC1 signature may be used to diagnose immunogenicity of necroptosis ex vivo.

关键词： Al(3+)   Dual detection   Fe(3+)   Fluorescence turn-on   Food samples   Multifunctional probe  

摘要： To achieve the development of fluorescence turn-on probe and dual detection of Al³⁺ and Fe³⁺, three organic molecules (named KN, KP and KS) were synthesized based on quinolinone, Schiff base, 1,3,4-thiadiazole or benzothiazole units. Their fluorescence characteristics and response mechanism were investigated thoroughly. The recognition process created obvious color change under sunlight and nearly 30 to 66 folds fluorescence enhancement under ultraviolet light. The formation of stable complexes leads to inhibition of intramolecular charge transfer, restriction of imine isomerization and consequent optical behaviors. For KN, Al³⁺ and Fe³⁺ could be distinguished via different UV–vis response or by using masking agent with detection limits of 0.18 μM and 0.20 μM, respectively. Another satisfactory result for distinguishing two ions was achieved with KS under pH = 2 or 10 condition. More importantly, KN and KS were successfully used to detect Al³⁺ or Fe³⁺ in foods, water samples and pharmaceutical products.

关键词： Dimers  

摘要： Inclusion of a fused pyridine ring onto the core motif of an azaphosphinine heterocycle, as well as functionalization with anN-acetamide group, furnishes a chiral, quadruple hydrogen bonding face that is capable of strong homodimerization. Eleven different azaphosphinine derivatives were prepared with variable electron donor and acceptor functionalization. Contrary to simple DA azaphosphinine dimers, trends from substituent effects showed that the hydrogen bond acceptors (A) were more sensitive to the substituents than the hydrogen bond donors (D). With electron donating groups appended onto the azaphosphinine scaffold, dimerization constants rose to as high as 209 M–1in 10% DMSO-d6in water-saturated CDCl3. X-ray crystallographic data unexpectedly showed that the quadruply hydrogen bonding system preferred the theoretically less stable donor–acceptor–donor–acceptor (DADA) H-bond orientation despite having the capability to tautomerize to the potentially more stable DDAA structure. Computational analysis revealed that maintaining pyridine aromaticity was more stabilizing than the secondary interactions that would be created from a DDAA dimer. Additionally, these molecules associate as the first examples ofR,R-andS,S-azaphosphinine homodimers, compared to theR,S-heterodimers typically found for simple azaphosphinines. This observation was explained by computational analysis, which found a geometric difference between the nitrogen atoms adjacent to the phosphorus chiral center of theHomoandHeterodimer, leading to a stronger hydrogen bonding interaction in theHomodimer. Further understanding of this quadruply hydrogen bonding core will allow us to explore further applications that integrate this strongly hydrogen bonding system into larger and more complex supramolecular frameworks such as supramolecular polymers or capsules.