Positive feedback loop of c-myc/XTP6/NDH2/NF-κB to promote malignant progression in glioblastoma.

BACKGROUND: Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in sustaining the NF-κB signaling pathway's functionality. Despite these findings, the underlying molecular mechanisms through which lncRNAs influence the NF-κB pathway remain largely unexplored. METHODS: Bioinformatic analyses were utilized to investigate the differential expression and prognostic significance of XTP6. The functional roles of XTP6 were further elucidated through both in vitro and in vivo experimental approaches. To estimate the interaction between XTP6 and NDH2, RNA pulldown and RNA Immunoprecipitation (RIP) assays were conducted. The connection between XTP6 and the IκBα promoter was examined using Chromatin Isolation by RNA Purification (ChIRP) assays. Additionally, Chromatin Immunoprecipitation (ChIP) assays were implemented to analyze the binding affinity of c-myc to the XTP6 promoter, providing insights into the regulatory mechanisms at play. RESULTS: XTP6 was remarkedly upregulated in glioblastoma multiforme (GBM) tissues and was connected with adverse prognosis in GBM patients. Our investigations revealed that XTP6 can facilitate the malignant progression of GBM both in vitro and in vivo. Additionally, XTP6 downregulated IκBα expression by recruiting NDH2 to the IκBα promoter, which resulted in elevated levels of H3K27me3, thereby reducing the transcriptional activity of IκBα. Moreover, the progression of GBM was further driven by the c-myc-mediated upregulation of XTP6, establishing a positive feedback loop with IκBα that perpetuated the activation of the NF-κB signaling pathway. Notably, the application of an inhibitor targeting the NF-κB signaling pathway effectively inhibited the continuous activation induced by XTP6, leading to a significant reduction in tumor formation in vivo. CONCLUSION: The results reveal that XTP6 unveils an innovative epigenetic mechanism instrumental in the sustained activation of the NF-κB signaling pathway, suggesting a promising therapeutic target for the treatment of GBM.

Development and clinical evaluation of an online automated quality control system for improving laboratory quality management.

BACKGROUND: We developed an efficient online automated quality control (AUTO QC) system and tested its feasibility on automatic laboratory assembly lines. METHODS: AUTO QC is based on developed quality control software (Smart QC) and designed adaptable consumables before. We applied the system to two assembly lines in our laboratory. Using third-party quality control samples, we evaluated the impact of the online AUTO QC system on out-of-control rate, biosecurity risk, turnaround time (TAT) and cost. RESULTS: AUTO QC significantly decreased the occurrence rate of the Westgard quality control rules 13S/22S/R4s and 12S, representing out-of-control and warning, respectively. The out-of-control rates were reduced by 58%, and the potential biosecurity risk of the samples decreased by 90%. The AUTO QC implementation also reduced the median TAT (by 7 min), the number of full-time employees and the cost of the quality control samples (by 45%). CONCLUSIONS: The total laboratory AUTO QC system can improve the quality and stability of QC testing and reduce cost.

Gain-loss situation modulates neural responses to self-other decision making under risk.

Although self-other behavioral differences in decision making under risk have been observed in some contexts, little is known about the neural mechanisms underlying such differences. Using functional magnetic resonance imaging (fMRI) and the cups task, in which participants choose between risky and sure options for themselves and others in gain and loss situations, we found that people were more risk-taking when making decisions for themselves than for others in loss situations but were equally risk-averse in gain situations. Significantly stronger activations were observed in the dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI) when making decisions for the self than for others in loss situations but not in gain situations. Furthermore, the activation in the dmPFC was stronger when people made sure choices for others than for themselves in gain situations but not when they made risky choices, and was both stronger when people made sure and risky choices for themselves than for others in loss situations. These findings suggest that gain-loss situation modulates self-other differences in decision making under risk, and people are highly likely to differentiate the self from others when making decisions in loss situations.

Self-Other Differences in Decision-Making Under Risk.

Decisions made for others reflect not only decision-makers' cognitive and emotional states but also decision-makers' interpersonal concerns. People who make choices for others will potentially be blamed for unappealing outcomes by others. Therefore, we hypothesize that individuals will seek sure gains (which increase individuals' responsibility for desirable outcomes) and avoid sure losses (which decrease individuals' responsibility for undesirable outcomes) when making risky decisions for others more than when making such decisions for themselves. The results of two studies show that making decisions for others (vs. oneself) promotes risk-averse choices over gains. This effect may be driven by the perceived responsibility associated with different options. When both options exhibit variance in outcomes, such self-other difference disappears. However, no self-other difference over losses was observed. Taken together, our research highlights interpersonal concerns in making decisions for others, as well as the behavioral consequences of these concerns in decisions under risk.

Negative Differential Conductance in Polyporphyrin Oligomers with Nonlinear Backbones.

We study negative differential conductance (NDC) effects in polyporphyrin oligomers with nonlinear backbones. Using a low-temperature scanning tunneling microscope, we selectively controlled the charge transport path in single oligomer wires. We observed robust NDC when charge passed through a T-shape junction, bistable NDC when charge passed through a 90° kink and no NDC when charge passed through a 120° kink. Aided by density functional theory with nonequilibrium Green's functions simulations, we attributed this backbone-dependent NDC to bias-modulated hybridization of the electrode states with the resonant transport molecular orbital. We argue this mechanism is generic in molecular systems, which opens a new route of designing molecular NDC devices.

Decisions for Others Are Less Risk-Averse in the Gain Frame and Less Risk-Seeking in the Loss Frame Than Decisions for the Self.

Despite the fact that people make decisions for others as often as they make decisions for themselves, little is known about how decisions for others are different from those made for the self. In two experiments, we investigated the effect of social distance (i.e., making decisions for oneself, a friend, or a stranger) on risk preferences in both gain and loss situations. We found that people were more risk averse in gain situations when they made decisions for themselves than for a stranger (Studies 1 and 2), but were equally risk averse for themselves and their friends (Study 2). However, people were more risk seeking in loss situations when they made decisions for themselves than for their friends as well as for a stranger, and were more risk seeking for their friends than for a stranger (Study 2). Furthermore, the effect of social distance on risk preferences was stronger in loss than in gain situations. Mediation analysis indicated that outcome-induced loss aversion was responsible for effects of social distance on risk preferences. These findings demonstrate that social distance influences risk preferences via perceived loss aversion, which sheds new light on self-other differences in decision making.

Self-assembly of a binodal metal-organic framework exhibiting a demi-regular lattice.

Designing metal-organic frameworks with new topologies is a long-standing quest because new topologies often accompany new properties and functions. Here we report that 1,3,5-tris[4-(pyridin-4-yl)phenyl]benzene molecules coordinate with Cu atoms to form a two-dimensional framework in which Cu adatoms form a nanometer-scale demi-regular lattice. The lattice is articulated by perfectly arranged twofold and threefold pyridyl-Cu coordination motifs in a ratio of 1 : 6 and features local dodecagonal symmetry. This structure is thermodynamically robust and emerges solely when the molecular density is at a critical value. In comparison, we present three framework structures that consist of semi-regular and regular lattices of Cu atoms self-assembled out of 1,3,5-tris[4-(pyridin-4-yl)phenyl]benzene and trispyridylbenzene molecules. Thus a family of regular, semi-regular and demi-regular lattices can be achieved by Cu-pyridyl coordination.

Single-Molecule Investigations of Conformation Adaptation of Porphyrins on Surfaces.

The porphyrin macrocyclic core features dynamic conformational transformations in free space because of its structural flexibility. Once attached to a substrate, the molecule-substrate interaction often restricts this flexibility and stabilizes the porphyrin in a specific conformation. Here using molecular dynamic and density-functional theory simulations and scanning tunneling microscopy and spectroscopy, we investigated the conformation relaxation and stabilization processes of two porphyrin derivatives (5,15-dibromophenyl-10,20-diphenylporphyrin, Br2TPP, and 5,15-diphenylporphyrin, DPP) adsorbed on Au(111) and Pb(111) surfaces. We found that Br2TPP adopts either dome or saddle conformations on Au(111) but only the saddle conformation on Pb(111), whereas DPP deforms to a ruffled conformation on Au(111). We also resolved the structural transformation pathway of Br2TPP from the free-space conformations to the surface-anchored conformations. These findings provide unprecedented insights revealing the conformation adaptation process. We anticipate that our results may be useful for controlling the conformation of surface-anchored porphyrin molecules.

Resonant Charge Transport in Conjugated Molecular Wires beyond 10 nm Range.

Using a scanning tunneling microscope, we measured high-bias conductance of single polyporphyrin molecular wires with lengths from 1.3 to 13 nm. We observed several remarkable transport characteristics, including multiple sharp conductance peaks, conductances as high as 20 nS in wires with lengths of >10 nm, and nearly length-independent conductance (attenuation <0.001 Å(-1)). We carried out first-principles simulations on myriad metal-molecule-metal junctions. The simulations revealed that the measured conductance is coherent resonant transport via a delocalized molecular orbital.

Effects of municipal sewage sludge stabilized by fly ash on the growth of Manilagrass and transfer of heavy metals.

A greenhouse experiment was carried out to evaluate the feasibility of using an artificial soil for cultivation of Manilagrass. The transfer and transformation of heavy metals in the artificial soil-Manilagrass system were discussed at the same time. The results showed that fly ash-sludge indicated a positive effect on the growth of Manilagrass. The pots with 14% sludge and 6% fly ash mixture had the highest yield and nutrient concentrations of Manilagrass. With the increasing application of coal fly ash, the concentrations of Ni, Zn, Mn, Sb and Cu in Manilagrass decreased significantly, while Pb, V and Ti increased. Otherwise, the concentrations of Cd, As, Cr, Co, and Fe did not show a remarkable change. Except for Sb, the values of bio-concentration factor of heavy metals in Manilagrass were all below 1.0 after treated by the fly ash-sludge treatment, decreased as Sb>Ni>Zn>Cu>Pb>Mn>Co=Cr>Cd>Fe=V>Ti>As in an average for all treatments. Compared to the contrast check, the proportions of heavy metals in exchangeable, reducible and oxidizable fractions increased. Manilagrass could be used to reduce the eco-toxicity and bioavailability of Ti, V, Mn, Co, Cr and Cd in fly ash-sludge amended soil.