The lysosomes of cancer cells have lower pH and higher viscosity than those of normal cells. These features can be used as sensitive and selective markers for cancer diagnosis. In this work, a pH and ...viscosity dual responsive lysosome targeting fluorescent probe 1 was designed based on the transformation of amino- and imino- forms of pyronine and the twisted intramolecular charge shuttle (TICS) sensing mechanism. Live cancer cells and tumors were effectively distinguished from normal cells and organs through fluorescence imaging of probe 1, which indicated that probe 1 could serve as an effective tool for visualization of tumors at organ level with high selectivity.
Abstract
In recent publications, the construction of explicit symplectic integrators for Schwarzschild- and Kerr-type spacetimes is based on splitting and composition methods for numerical ...integrations of Hamiltonians or time-transformed Hamiltonians associated with these spacetimes. Such splittings are not unique but have various options. A Hamiltonian describing the motion of charged particles around the Schwarzschild black hole with an external magnetic field can be separated into three, four, and five explicitly integrable parts. It is shown through numerical tests of regular and chaotic orbits that the three-part splitting method is the best of the three Hamiltonian splitting methods in accuracy. In the three-part splitting, optimized fourth-order partitioned Runge–Kutta and Runge–Kutta–Nyström explicit symplectic integrators exhibit the best accuracies. In fact, they are several orders of magnitude better than the fourth-order Yoshida algorithms for appropriate time steps. The first two algorithms have a small additional computational cost compared with the latter ones. Optimized sixth-order partitioned Runge–Kutta and Runge–Kutta–Nyström explicit symplectic integrators have no dramatic advantages over the optimized fourth-order ones in accuracy during long-term integrations due to roundoff errors. The idea of finding the integrators with the best performance is also suitable for Hamiltonians or time-transformed Hamiltonians of other curved spacetimes including Kerr-type spacetimes. When the numbers of explicitly integrable splitting sub-Hamiltonians are as small as possible, such splitting Hamiltonian methods would bring better accuracies. In this case, the optimized fourth-order partitioned Runge–Kutta and Runge–Kutta–Nyström methods are worth recommending.
Airborne bacteria have gained increasing attention because they affect ecological balance and pose potential risks on human health. Recently, some studies have focused on the abundance and ...composition of airborne bacteria under heavy, hazy polluted weather in China, but they reached different conclusions about the comparisons with non-polluted days. In this study, we tested the hypothesis that meteorological factors could have a higher impact on shaping airborne bacterial communities than air pollutants by systematically monitoring the communities for 1year. Total suspended particles in Beijing were sampled for 20 consecutive days in each season of 2015. Bacterial abundance varied from 8.71×103 to 2.14×107 ribosomal operons per cubic meter according to the quantitative PCR analysis. There were relatively higher bacterial counts in spring and in autumn than in winter and summer. Airborne bacterial communities displayed a strong seasonality, according to the hierarchical cluster analysis. Only two exceptions overtook the seasonal trend, and both occurred in or after violent meteorological changes (sandstorm or rain). Aggregated boosted tree analysis performed on bacterial abundance showed that the dominant factors shaping bacterial communities were meteorological. They were air pressure in winter, air temperature and relative humidity in spring, RH in summer, and vapor pressure in autumn. Variation partition analysis on community structure showed that meteorological factors explained more variations than air pollutants. Therefore, both of the two models verified our hypothesis that the differences in airborne bacterial communities in polluted days or non-polluted days were mainly driven by the discrepancies of meteorological factors rather than by the presence of air pollutants.
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•The airborne bacteria concentrations and community structure showed strong seasonality.•However, violent weather events broke seasonal trends of bacteria community.•Within season, meteorological factors explained more variations in bacteria community structure than air pollution.
N6-methyladenosine (m6A) is the most abundant epigenetic modification in eukaryotic messenger RNAs and is essential for multiple RNA processing events in physiological and pathological processes. ...However, precisely how m6A methylation is involved in major depressive disorder (MDD) is not fully understood.
Circular RNA STAG1 (circSTAG1) was screened from the hippocampus of chronic unpredictable stress–treated mice using high-throughput RNA sequencing. Microinjection of circSTAG1 lentivirus into the mouse hippocampus was used to observe the role of circSTAG1 in depression. Sucrose preference, forced swim, and tail suspension tests were performed to evaluate the depressive-like behaviors of mice. Astrocyte dysfunction was examined by GFAP immunostaining and 3D reconstruction. Methylated RNA immunoprecipitation sequence analysis was used to identify downstream targets of circSTAG1/ALKBH5 (alkB homolog 5) axis. Cell Counting Kit-8 assay was performed to evaluate astrocyte viability in vitro.
circSTAG1 was significantly decreased in the chronic unpredictable stress–treated mouse hippocampus and in peripheral blood of patients with MDD. Overexpression of circSTAG1 notably attenuated astrocyte dysfunction and depressive-like behaviors induced by chronic unpredictable stress. Further examination indicated that overexpressed circSTAG1 captured ALKBH5 and decreased the translocation of ALKBH5 into the nucleus, leading to increased m6A methylation of fatty acid amide hydrolase (FAAH) messenger RNA and degradation of FAAH in astrocytes with subsequent attenuation of depressive-like behaviors and astrocyte loss induced by corticosterone in vitro.
Our findings dissect the functional link between circSTAG1 and m6A methylation in the context of MDD, providing evidence that circSTAG1 may be a novel therapeutic target for MDD.
Haze in China has been increasing in frequency of occurrence as well as the area of the affected region. Here, we report on a new mechanism of haze formation, in which coexistence with NOx can reduce ...the environmental capacity for SO2, leading to rapid conversion of SO2 to sulfate because NO2 and SO2 have a synergistic effect when they react on the surface of mineral dust. Monitoring data from five severe haze episodes in January of 2013 in the Beijing-Tianjin-Hebei regions agreed very well with the laboratory simulation. The combined air pollution of motor vehicle exhaust and coal-fired flue gases greatly reduced the atmospheric environmental capacity for SO2, and the formation of sulfate was found to be a main reason for the growth of fine particles, which led to the occurrence of haze. These results indicate that the impact of motor vehicle exhaust on the atmospheric environment might be underestimated.
In the past, most research focused on the children living near a typical contaminated area but ignored the health risks of children living in the fourth or fifth tier cities without typical ...contaminated sources. These cities are now facing a series of problems, such as serious environmental pollution, undeveloped health system and so on. Furthermore, the development of modern logistics for food delivery has altered lifestyles that directly impact diets and eating patterns. In this study, multiple exposure pathways and health risks of children to heavy metal(loid)s were studied based on questionnaire-based surveys and field sampling of soil, dust, fine particulates, drinking water and food. We found that Pb, Cd and Mn levels in environmental samples were very high indicating a serious pollution problem. Inhalation exposure via aerosol particles was the most important pathway and was greater than exposure by food ingestion. The hazard index for Mn via aerosol particles was >1 even at the 5th percentile and Mn levels in urine was 10 times higher than those of people living in typical contaminated areas. The total incremental lifetime cancer risk (ILCR) for all metal(loid)s was also higher than the threshold at the 95th percentile. This study highlights health risks to children living in fourth tier cities and the importance of air pollution control to protect heavy metal exposure for children.
•Multiple exposure pathways and health risks of children are analyzed.•Inhalation exposure via aerosol particles has become the main exposure pathway.•Metals in food were low, which were only one-tenth of previously reported values.•The local Mn pollution most likely contributes to high environmental exposure.•High health risks happen to the local children living in fourth-tier cities.
Functional dyspepsia is a clinically common functional gastrointestinal disorder with a high prevalence, high impact and high consumption of medical resources. The microbiota in the gastrointestinal ...tract is a large number of families and is one of the most complex microbial reservoirs in the human body. An increasing number of studies have confirmed the close association between dysbiosis of the gastrointestinal microbiota and the occurrence and progression of functional dyspepsia. Therefore, we reviewed the role of dysbiosis of the gastrointestinal microbiota,
H. pylori
infection and gastrointestinal microbiota metabolites in functional dyspepsia, focusing on the possible mechanisms by which dysbiosis of the gastrointestinal microbiota contributes to the pathogenesis of functional dyspepsia. Several studies have confirmed that dysbiosis of the gastrointestinal microbiota may cause the occurrence and progression of functional dyspepsia by disrupting the biological barrier of the intestinal mucosa, by disturbing the immune function of the intestinal mucosa, or by causing dysregulation of the microbial-gut-brain axis. Probiotics and antibiotics have also been chosen to treat functional dyspepsia in clinical studies and have shown some improvement in the clinical symptoms. However, more studies are needed to explore and confirm the relationship between dysbiosis of the gastrointestinal microbiota and the occurrence and progression of functional dyspepsia, and more clinical studies are needed to confirm the therapeutic efficacy of microbiota modulation for functional dyspepsia.
Major depressive disorder is associated with abnormalities in the brain and the immune system. Chronic stress in animals showed that epigenetic and inflammatory mechanisms play important roles in ...mediating resilience and susceptibility to depression. Here, through a high-throughput screening, we identify two phytochemicals, dihydrocaffeic acid (DHCA) and malvidin-3'-O-glucoside (Mal-gluc) that are effective in promoting resilience against stress by modulating brain synaptic plasticity and peripheral inflammation. DHCA/Mal-gluc also significantly reduces depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of hematopoietic progenitor cells from stress-susceptible mice. DHCA reduces pro-inflammatory interleukin 6 (IL-6) generations by inhibiting DNA methylation at the CpG-rich IL-6 sequences introns 1 and 3, while Mal-gluc modulates synaptic plasticity by increasing histone acetylation of the regulatory sequences of the Rac1 gene. Peripheral inflammation and synaptic maladaptation are in line with newly hypothesized clinical intervention targets for depression that are not addressed by currently available antidepressants.
Four aggregation‐induced emission (AIE)‐active chiral binaphthyl‐based molecules, (R/S)‐1 and (R/S)‐2, were designed and synthesized. Interestingly, all of them can exhibit reversal circularly ...polarized luminescence (CPL) signals from solution to aggregation, which could be attributed to the different dihedral angle of binaphthyl units from cis‐conformation in pure THF solution to trans‐conformation in THF/water mixtures.
The closing scene: Four aggregation‐ induced emission (AIE)‐active chiral binaphthyl‐based molecules, (R/S)‐1 and (R/S)‐2, were designed and synthesized. Interestingly, all of them can exhibit reversal circularly polarized luminescence (CPL) signals from solution to aggregation, which could be attributed to the different dihedral angle of binaphthyl units from cis‐conformation in pure THF solution to trans‐conformation in THF/water mixtures.