Regulation of telomerase towards tumor therapy.

Cancer is an aging-related disease, while aging plays an important role in the development process of tumor, thus the two are inextricably associated. Telomere attrition is one of the recognized hallmark events of senescence. Hence, targeting telomerase which could extends telomere sequences to treat tumors is widely favored. Cancer cells rely on high activity of telomerase to maintain a strong proliferative potential. By inhibiting the expression or protein function of telomerase, the growth of cancer cells can be significantly suppressed. In addition, the human immune system itself has a defense system against malignant tumors. However, excessive cell division results in dramatic shortening on telomeres and decline in the function of immune organs that facilitates cancer cell evasion. It has been shown that increasing telomerase activity or telomere length of these immune cells can attenuate senescence, improve cellular viability, and enhance the immunosuppressive microenvironment of tumor. In this paper, we review the telomerase-targeting progress using different anti-tumor strategies from the perspectives of cancer cells and immune cells, respectively, as well as tracking the preclinical and clinical studies of some representative drugs for the prevention or treatment of tumors.

ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader.

Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway. Dysregulated R-loops can cause stalled replication forks and telomere instability. However, how R-loops are recognized and regulated, particularly at telomeres, is not well understood. We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination. Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses (DDR). In addition, ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway. Using the proximity-dependent biotin identification (BioID) technology, we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases, including DHX9. Importantly, ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9. Our findings suggest that ILF3 may function as a reader of telomeric R-loops, helping to prevent abnormal homologous recombination and maintain telomere homeostasis.

Synergistic Mechanism of Combined Inhibitors on the Selective Flotation of Arsenopyrite and Pyrite.

The selective action mechanism of sodium butyl xanthate (BX), ammonium salt (NH4 +), and sodium m-nitrobenzoate (m-NBO) on pyrite and arsenopyrite was examined by experiments and quantum chemistry. The experiments show that under alkaline conditions, ammonium salt (NH4 +) and m-NBO can have a strong inhibitory effect on arsenopyrite. At pH 11, the recovery rate of arsenopyrite reduces to 16%. The presence of ammonium salt (NH4 +) and m-NBO reduces the adsorption energy of BX on arsenopyrite to ΔE = -23.23 kJ/mol, which is far less than the adsorption energy on the surface of pyrite, ΔE = -110.13 kJ/mol. The results are helpful to understand the synergistic mechanism of the agent on the surface of arsenopyrite and pyrite, thus providing a reference for the selective separation of arsenopyrite.

Fish isotopic niches associated with environmental indicators and human disturbance along a disturbed large subtropical river in China.

Stable isotopes are increasingly used to detect and understand the impacts of environmental changes on riverine ecological properties. The δ13C and δ15N signatures of fish with different feeding habits were measured in a large subtropical river to evaluate how fish isotopic niches respond to environmental gradients and human disturbance. From basal resources to fish consumers, the high values of epilithic periphyton (biofilm) δ13C and suspended particulate organic matter δ15N concurrently determined the niche ranges and space (e.g., convex hull area) of fish communities. Along a longitudinal gradient (except in the industrial zone), the number of fish trophic guilds identified by Bayesian ellipses continuously increased; meanwhile, higher trophic diversity and less redundancy were observed near the lower reaches and estuary. Variance inflation factors were estimated to detect the multicollinearity of 40 environmental variables, 14 of which were selected as indicators. Relative importance (RI) analysis was used to evaluate the explanatory power of these indicators for the spatial variation in isotopic niche metrics; the results showed that riffle habitat area, water nitrate concentration, gravel-cobble substrate, and riparian buffer width were the 4 key environmental indicators (average RI > 12%) that determined the longitudinal pattern of fish isotopic niches. These findings suggested that community-level δ13C signatures are more responsive to changes in habitats (e.g., riffle) and substrates (e.g., gravel-cobble) supporting the productivity of autochthonous diatoms while δ15N signatures respond to water quality altered by nitrogen pollution from manure-fertilized farming and poultry livestock effluent. Furthermore, δ15N may be more robust and interpretable than δ13C as an isotopic indicator of ecosystem change in rivers exposed to multiple or complex anthropogenic stressors.

Effect of Dodecyl Trimethyl Ammonium Bromide on the Migration of Water Molecules in the Pores of Lignite: An Experimental and Molecular Simulation Study.

Molecular dynamics simulations and experiments were used to study the influence of dodecyl trimethyl ammonium bromide (DTAB) on the migration of water molecules in the pores of lignite. To simulate the accuracy, 13C NMR was used to confirm the structure of Shengli lignite. It was found through adsorption experiments that DTAB reduces the specific surface area and pore volume of lignite. Molecular simulations indicate that the lignite and water molecules are primarily connected by hydrogen bonding. DTAB impedes the movement of water molecules in the pores of lignite and the storage space of compressed water molecules. Water molecules are mainly present in the pores of lignite in a posture parallel to the XOY plane, which facilitates the formation of hydrogen-bonding networks. However, this also leads to a decrease in the mobility of water molecules. Experimental and simulation results show that DTAB can enter lignite pores, reducing the water absorption in lignite. This is highly significant for the processing and utilization of lignite.