Synthetic mammalian signaling circuits for robust cell population control

In multicellular organisms, cells actively sense, respond to, and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and improve cell therapies. However, a key challenge is avoiding their inherent sensitivity to “cheater” mutations that evade control. Here, we repurposed the plant hormone auxin to enable orthogonal mammalian cell-cell communication and quorum sensing. Further, we show that a “paradoxical” circuit design, in which auxin stimulates and inhibits net cell growth at different concentrations, achieves population control that is robust to cheater mutations, controlling growth for 43 days of continuous culture. By contrast, a non-paradoxical control circuit limited growth but was susceptible to mutations. These results establish a foundation for future cell therapies that can respond to and control their own population sizes

Comorbid depressive symptoms can aggravate the functional changes of the pain matrix in patients with chronic back pain: A resting-state fMRI study

ObjectiveThe purposes of this study are to explore (1) whether comorbid depressive symptoms in patients with chronic back pain (CBP) affect the pain matrix. And (2) whether the interaction of depression and CBP exacerbates impaired brain function.MethodsThirty-two patients with CBP without comorbid depressive symptoms and thirty patients with CBP with comorbid depressive symptoms were recruited. All subjects underwent functional magnetic resonance imaging (fMRI) scans. The graph theory analysis, mediation analysis, and functional connectivity (FC) analysis were included in this study. All subjects received the detection of clinical depressive symptoms and pain-related manifestations.ResultCompared with the CBP group, subjects in the CBP with comorbid depressive symptoms (CBP-D) group had significantly increased FC in the left medial prefrontal cortex and several parietal cortical regions. The results of the graph theory analyses showed that the area under the curve of small-world property (t = −2.175, p = 0.034), gamma (t = −2.332, p = 0.023), and local efficiency (t = −2.461, p = 0.017) in the CBP-D group were significantly lower. The nodal efficiency in the ventral posterior insula (VPI) (t = −3.581, p = 0.0007), and the network efficiency values (t = −2.758, p = 0.008) in the pain matrix were significantly lower in the CBP-D group. Both the topological properties and the FC values of these brain regions were significantly correlated with self-rating depression scale (SDS) scores (all FDR corrected) but not with pain intensity. Further mediation analyses demonstrated that pain intensity had a mediating effect on the relationship between SDS scores and Pain Disability Index scores. Likewise, the SDS scores mediated the relationship between pain intensity and PDI scores.ConclusionOur study found that comorbid depressive symptoms can aggravate the impairment of pain matrix function of CBP, but this impairment cannot directly lead to the increase of pain intensity, which may be because some brain regions of the pain matrix are the common neural basis of depression and CBP

Atomistic Insights into the Effects of Residual Stress during Nanoindentation

The influence of in-plane residual stress on Hertzian nanoindentation for single-crystal copper thin film is investigated using molecular dynamics simulations (MD). It is found that: (i) the yield strength of incipient plasticity increases with compressive residual stress, but decreases with tensile residual stress; (ii) the hardness decreases with tensile residual stress, and increases with compressive residual stress, but abruptly drops down at a higher compressive residual stress level, because of the deterioration of the surface; (iii) the indentation modulus reduces linearly with decreasing compressive residual stress (and with increasing tensile residual stress). It can be concluded from the MD simulations that the residual stress not only strongly influences the dislocation evolution of the plastic deformation process, but also significantly affects the size of the plastic zone

Promoter CpG content regulates DNMT-dependent silencing dynamics

Raw data for paper "Promoter CpG content regulates DNMT-dependent silencing dynamics

Source Analysis of Heavy Metal Pollution Using UNMIX and PMF Models in Soils along the Shuimo River in Urumqi, China

Eight kinds of heavy metals in soil within 0–2 km from the banks of Shuimo River in Urumqi were analyzed by using an X-ray fluorescence spectrometer and national standard detection methods. Unmix and PMF models are comprehensively used to analyze potential pollutant sources and contribution rates. Soil samples are sampled in three layers of 0–20, 20–40, and 40–60 cm, and each group of sample points in each layer is 5 m, 1 km, and 2 km away from the riverbank, respectively. Only the average concentration of Mn in each layer of soil is lower than the background value, according to the analytical results, while the average concentration of other heavy metals surpasses the background value. The highest proportion of exceeding the background value is Ni in the 40–60 cm soil layer, up to 1.92 times. Unmix and PMF models are used to analyze pollutants’ source quantity and contribution rate, respectively. The results show that the two models can identify two pollution sources at the three soil layers, and their contribution rates are similar, and each index of the analysis results of the two models is within the required range of model reliability. By comparing with the Pearson correlation coefficient and distribution map of heavy metal concentration in surface soil, it is concluded that Zn, Pb, Cr, and Cu are mainly from industrial sewage and air pollution from coal combustion, while As, Mn, Ni, and V are mainly from agricultural pollution and light industrial pollution. In future research, it is necessary to investigate the change of heavy metal concentration in detail from the time dimension to further quantitatively calculate the potential pollutant source and contribution rate

Promoter CpG content regulates DNMT-dependent silencing dynamics

Raw data for paper "Promoter CpG content regulates DNMT-dependent silencing dynamics

Synthetic mammalian signaling circuits for robust cell population control

Synthetic signaling circuits could allow engineered cells to sense and control their own population density. The ideal circuit would operate independently of endogenous pathways and be robust to selection pressure for mutations that allow cells to evade population size limits. Here, we show that the plant hormone auxin can be repurposed as an orthogonal communication channel and linked to pathways that control cell survival and death to create synthetic mammalian population control circuits. We identified enzymes, transporters, and other components that allow sending and receiving of two auxin variants. Using these components, we constructed a synthetic quorum sensing system and coupled it to regulation of antibiotic resistance to limit cell population size. Because this population control circuit was susceptible to mutations in signal sensing, we then designed a paradoxical population control circuit, in which auxin both stimulates and inhibits net cell growth at different concentrations. This design provides evolutionarily robust control in a 43 day continuous culture experiment. These results demonstrate robust synthetic population control in mammalian cells and establish a foundation for future cell therapies that can respond to and control their own population sizes within multicellular organisms

Enhanced glioma cell death with ZnO nanorod flowers and temozolomide combination therapy through autophagy and mitophagy pathways

In recent years, the application of engineered NMts has significantly contributed to various biomedical fields. ZnO NMts (ZnO NMts) are widely utilized due to their biocompatibility, unique physical and chemical properties, stability, and cost-effectiveness for large-scale production. They have emerged as potential materials for anti-cancer applications. This study aims to study the impact of ZnO Nanorod flowers (ZnO NRfs) and their combination with temozolomide (TMZ) on glioma cells. Normal mouse microglia (BV2) will be used as a control to assess the effects on mouse glioma cells (G422) and human glioma cells (LN229). The effects of these substances were evaluated on G422 and LN229 cells through various parameters such as IC50 value, Zn2+ accumulation, ROS production, apoptosis, mitochondrial membrane potential (MMP) depolarization, and examination of organelles like mitochondria and lysosomes. Additionally, hypoxia-inducible factor-1α (HIF-1α), endothelial cell PAS domain protein 1 (EPAS1), autophagy markers (LC3), mitophagy and phagocytosis marker (BNIP3) were assessed. The results demonstrated that the combination of ZnO NRfs and TMZ could influence the expression of HIF-1α, EPAS1, LC3, and BNIP3 proteins, leading to mitophagy in glioma cells. This combination treatment has the potential to effectively eliminate glioma cells by activating the mitophagy pathway, which provides a good prospect for the clinical treatment of glioma

Synthetic mammalian signaling circuits for robust cell population control

In multicellular organisms, cells actively sense, respond to, and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and improve cell therapies. However, a key challenge is avoiding their inherent sensitivity to “cheater” mutations that evade control. Here, we repurposed the plant hormone auxin to enable orthogonal mammalian cell-cell communication and quorum sensing. Further, we show that a “paradoxical” circuit design, in which auxin stimulates and inhibits net cell growth at different concentrations, achieves population control that is robust to cheater mutations, controlling growth for 43 days of continuous culture. By contrast, a non-paradoxical control circuit limited growth but was susceptible to mutations. These results establish a foundation for future cell therapies that can respond to and control their own population sizes