A Study on the Properties of Composite Modified Mortar with Styrene-Butadiene Rubber Latex and Silica Fume.

To solve the problem of the poor abrasion resistance of concrete pavement surface mortar, this study substituted cement with equal amounts of styrene-butadiene rubber (SBR) latex and silica fume (SF) to investigate the effects of organic/inorganic material composite modification on the fluidity, drying shrinkage, mechanical properties, and abrasion resistance of cement mortar. Also in this study, the microstructure, product, and pore structure characteristics of the composite modified cement mortar were investigated using scanning electron microscope (SEM), X-Ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and the Brunauer-Emmett-Teller (BET) method. This research found that the sole substitution of SF negatively impacted the mortar's fluidity and drying shrinkage yet enhanced its mechanical strength and abrasion resistance; the incorporation of SBR latex improved fluidity, reduced shrinkage, and increased flexural strength but adversely affected the compressive strength of the mortar. Additionally, the enhancement of the mortar's abrasion resistance with SBR latex was significantly greater than that with SF. When SBR latex and SF were used together as substitutes, the latex struggled to offset the negative impact of SF on mortar fluidity but effectively reduced shrinkage; SF compensated for the detrimental effect of the latex on compressive strength. Moreover, the primary role in enhancing the mortar's abrasion resistance was played by the latex. Microscopic tests showed that SBR latex and SF could increase the content of calcium silicate hydrate (C-S-H) gel, inhibit the formation of ettringite (AFt) and reduce carbonation, refine the pore size of cement mortar, and effectively improve the microstructure of mortar.

DNA methylation analysis explores the molecular basis of plasma cell-free DNA fragmentation.

Plasma cell-free DNA (cfDNA) are small molecules generated through a non-random fragmentation procedure. Despite commendable translational values in cancer liquid biopsy, however, the biology of cfDNA, especially the principles of cfDNA fragmentation, remains largely elusive. Through orientation-aware analyses of cfDNA fragmentation patterns against the nucleosome structure and integration with multidimensional functional genomics data, here we report a DNA methylation - nuclease preference - cutting end - size distribution axis, demonstrating the role of DNA methylation as a functional molecular regulator of cfDNA fragmentation. Hence, low-level DNA methylation could increase nucleosome accessibility and alter the cutting activities of nucleases during DNA fragmentation, which further leads to variation in cutting sites and size distribution of cfDNA. We further develop a cfDNA ending preference-based metric for cancer diagnosis, whose performance has been validated by multiple pan-cancer datasets. Our work sheds light on the molecular basis of cfDNA fragmentation towards broader applications in cancer liquid biopsy.

Tim-3 mediates T cell trogocytosis to limit antitumor immunity.

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1-positive (PD-1+) Tim-3+CD8+ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on Tim-3+ APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen-specific CD8+ T cells and PD-1+Tim-3+ CD8+ TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of CD8+ TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in CD8+ T cells impeded the trogocytosis of CD8+ TILs in vivo. Trogocytosed CD8+ T cells presented tumor peptide-major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity.

Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.

Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.