Publications by authors named "Guangtao Song"

Glioblastoma-associated macrophages & microglia (GAMs) are critical immune cells within the glioblastoma (GBM) microenvironment. Their phagocytosis of GBM cells is crucial for initiating both innate and adaptive immune responses. GBM cells evade this immune attack by upregulating the anti-phagocytic molecule CD47 on their surface.

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Cellular iron is inseparably related with the proper functionalities of mitochondria for its potential to readily donate and accept electrons. Though promising, the available endeavors of iron chelation antitumor therapies have tended to be adjuvant therapies. Herein, we conceptualized and fabricated an "iron-phagy" nanoparticle (Dp44mT@HTH) capable of inducing the absolute devastation of mitochondria via inhibiting the autophagy-removal of impaired ones for promoting cancer cell death.

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Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway is an essential DNA-sensing pathway to regulate the innate and adaptive immune response, which plays an important role in tumor immunotherapy. Although the STING agonists can be used, they are limited by their inability to target immune cells and systemic immunotoxicity, calling for novel strategies to accurately and effectively activate the cGAS-STING signaling pathway. Herein, mannose-modified stearic acid-grafted chitosan (M-CS-SA) micelles with the ability to activate the cGAS-STING signaling pathway and absorb tumor antigens were constructed.

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The abnormal tumor blood vessels with high leakage can promote tumor cells to infiltrate into the systemic circulation and increase the risk of tumor metastasis. In addition, chemotherapy may destroy tumor blood vessels and further aggravate metastasis. Normalizing tumor blood vessels can reduce vascular leakage and increase vascular integrity.

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The tumor microenvironment (TME) of breast cancer is hypoxic, which can promote tumor progression, including invasion and metastasis, and limit the efficacy of anti-tumor treatment. Nitric oxide (NO) can dilate blood vessels, effectively alleviate hypoxia, and regulate the TME, which has the potential to improve the anti-tumor therapeutic efficacy. Here, chitosan (CO) and octadecylamine (ODA) were linked by the disulfide bond, and the LinTT1 peptide was linked onto CO-SS-ODA for targeting tumor cells and endothelial cells in tumors.

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Tumor vessel normalization can alleviate hypoxia, reduce the intratumoral infiltration of immunosuppressive cells and increase the intratumoral infiltration of immune effector cells (CD8 T cells), further reversing the immunosuppressive microenvironment. Here, nanocomplexes (lipo/St@FA-COSA/BMS-202) which can accurately deliver drugs to tumor tissues and release different drugs at different sites with different rates were prepared to combine tumor vessel normalization with immune checkpoint blockade. The results of drug release showed that in a pH 6.

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Very little is known about how the material properties of protein condensates assembled via liquid-liquid phase separation (LLPS) are maintained and affect physiological functions. Here we show that liquid-like condensates of the transcription factor TFEB exhibit low fusion propensity in vitro and in living cells. We directly measured the attraction force between droplets, and we characterized the interfacial tension, viscosity, and elasticity of TFEB condensates.

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Translation elongation is a key step of protein synthesis, during which the nascent polypeptide chain extends by one amino acid residue during one elongation cycle. More and more data revealed that the elongation is a key regulatory node for translational control in health and disease. During elongation, elongation factor Tu (EF-Tu, eEF1A in eukaryotes) is used to deliver aminoacyl-tRNA (aa-tRNA) to the A-site of the ribosome, and elongation factor G (EF-G, EF2 in eukaryotes and archaea) is used to facilitate the translocation of the tRNA-mRNA complex on the ribosome.

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Background: Hepatocellular carcinoma (HCC) is among the most common forms of cancer and is associated with poor patient outcomes. The emergence of therapeutic resistance has hampered the efficacy of targeted treatments employed to treat HCC patients to date. In this study, we conducted a series of CRISPR/Cas9 screens to identify genes associated with synthetic lethality capable of improving HCC patient clinical responses.

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Ribosome recycling is the final step of the cyclic process of translation, where the post-termination complex (PoTC) is disassembled by the concerted action of ribosome recycling factor (RRF) and elongation factor G (EF-G) in the sub-second time range. Since, however, both the RRF and PoTC display highly dynamic action during this process, it is difficult to assess the molecular details of the interactions between the factors and the ribosome that are essential for rapid subunit separation. Here we characterized the molecular dynamics of RRF and PoTC by combined use of molecular dynamics simulations, single molecule fluorescence detection and single-particle cryo-EM analysis, with time resolutions in the sub-millisecond to minute range.

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Here, we develop an optical tweezers-based single-molecule manipulation assay to detect the formation of an R-loop complex in the Cas12a system and characterize its thermodynamic stability. We found that the formation of the R-loop complex induces a two-step unfolding of a DNA hairpin containing the target sequence, the non-target sequence binds loosely to Cas12a and can be easily released from the complex, and the Nuc domain of Cas12a plays key roles in target binding and R-loop formation.

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Argonaute (AGO) proteins play central roles in nucleic acid-guided interference that regulates gene expression and defend against foreign genetic elements in all life. Although much progress has been made with respect to the function of argonaute proteins in target recognition and cleavage, the detailed mechanism of their biological functions is not fully understood. Here, using atomic force microscopy-based single-molecule force spectroscopy, we studied target-guide dissociation in the absence or presence of Thermus thermophilus AGO (TtAGO).

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CRISPR-Cas9 system has been widely used for efficient genome editing. Although the structures of Cas9 protein in complex with single-guided RNA (sgRNA) and target DNA have been resolved, the molecular details about the formation of Cas9 endonuclease R-loop structure remain elusive. Here we examine the DNA cleavage activities of Streptococcus pyogenes Cas9 (SpyCas9) and its mutants using various target sequences and study the conformational dynamics of R-loop structure during target binding using single-molecule fluorescence energy transfer (smFRET) technique.

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By applying a controlled mechanical load using optical tweezers, we measured the diffusive barrier crossing in a 49 nt long P5ab RNA hairpin. We find that in the free-energy landscape the barrier height (G) and transition distance (x) are dependent on the loading rate (r) along the pulling direction, x, as predicted by Bell. The barrier shifted toward the initial state, whereas ΔG reduced significantly from 50 to 5 kT, as r increased from 0 to 32 pN/s.

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In the translating ribosomal complex, transfer RNA (tRNA) is stabilized in the ribosome by its anticodon stem-loop (ASL) and 3'-CCA end through base-pairing interactions with mRNA codon on the small subunit and rRNA in the peptidyl transferase center (PTC) of large subunit, respectively.Elongation factor 4 (EF4), a highly conserved translational GTPase, has been identified to trigger back-translocation. Early this year, we reported high resolution cryo-EM structures of EF4 in complex with Escherichia coli 70S ribosome in pre- and post-translocational states with direct observations that EF4 disrupts the base pairs between the 3'-end of peptidyl-tRNA and the P-loop of rRNA in PTC.

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EF4 catalyzes tRNA back-translocation through an unknown mechanism. We report cryo-EM structures of Escherichia coli EF4 in post- and pretranslocational ribosomes (Post- and Pre-EF4) at 3.7- and 3.

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During translation, elongation factor G (EF-G) plays a catalytic role in tRNA translocation and a facilitative role in ribosome recycling. By stabilizing the rotated ribosome and interacting with ribosome recycling factor (RRF), EF-G was hypothesized to induce the domain rotations of RRF, which subsequently performs the function of splitting the major intersubunit bridges and thus separates the ribosome into subunits for recycling. Here, with systematic mutagenesis, FRET analysis and cryo-EM single particle approach, we analyzed the interplay between EF-G/RRF and post termination complex (PoTC).

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During translation, elongation factor G (EF-G) catalyzes the translocation of tRNA2-mRNA inside the ribosome. Translocation is coupled to a cycle of conformational rearrangements of the ribosomal machinery, and how EF-G initiates translocation remains unresolved. Here we performed systematic mutagenesis of Escherichia coli EF-G and analyzed inhibitory single-site mutants of EF-G that preserved pretranslocation (Pre)-state ribosomes with tRNAs in A/P and P/E sites (Pre-EF-G).

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By using space series to replace time series, this paper studied the relationships between the vegetation characteristics and soil properties at different restoration stages on the slope land with purple soils in Hengyang of Hunnan Province South-central China. There existed obvious differences in the soil physical and chemical properties at different restoration stages. From grassplot, grass-shrub, shrub to shrub-arbor, the soil organic matter, total and available N, and moisture contents increased markedly, soil bulk density had an obvious decrease, soil total and available P contents changed little, and soil pH decreased gradually, but no significant differences were observed among different restoration stages.

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A strategy to speed up DNA walking devices through the use of DNA catalysts has been developed. The DNA walker is designed to move on a three-foothold molecular track with the assistance of fuel strands. The movement can be accelerated in the presence of catalysts.

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DNA and RNA are both polymorphic. Depending on the sequences and environmental conditions, they could exist in a variety of secondary structures that play key roles in many biological processes. Recognition of these structures by small ligands is very important for the development of new drugs and new tools.

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A label-free colorimetric assay, using non-crosslinking AuNP aggregation, has been developed for the screening of specific triplex DNA binders. The relative binding affinities can be simultaneously determined. Our novel assay is simple in design and fast in operation, avoiding either AuNPs modification or oligonucleotide labeling, and easy to implement for visual detection.

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A novel multi-functional, proton-fueled DNA tweezers has been constructed. Starting from simple conformation change of i-motif DNA, the nanodevice can accomplish movements such as repeatedly capture or release target DNA and protein. The DNA tweezers, driven by the solution pH without the need of injecting external energy, are robust and highly reversible with the responses of 1-2 orders of magnitude faster than the DNA-fueled machine, and does not accumulate duplex waste products to poison the system.

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