Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair

Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.

Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.

Mechanism of the December 2015 Catastrophic Landslide at the Shenzhen Landfill and Controlling Geotechnical Risks of Urbanization

This paper presents findings from an investigation of the large-scale construction solid waste （CSW） landslide that occurred at a landfill at Shenzhen, Guangdong, China, on December 20, 2015, and which killed 77 people and destroyed 33 houses. The landslide involved 2.73 - 106 m3 of CSW and affected an area about 1100 m in length and 630 m in maximum width, making it the largest landfill landslide in the world. The investigation of this disaster used a combination of unmanned aerial vehicle surveillance and multistage remote-sensing images to reveal the increasing volume of waste in the landfill and the shifting shape of the landfill slope for nearly two years before the landslide took place, beginning with the creation of the CSW landfill in March, 2014, that resulted in the uncertain conditions of the landfill＇s boundaries and the unstable state of the hydrologic performance. As a result, applying conventional stability analysis methods used for natural landslides to this case would be difficult. In order to analyze this disaster, we took a multistage modeling technique to analyze the varied characteristics of the land- fill slope＇s structure at various stages of CSW dumping and used the non-steady flow theory to explain the groundwater seepage problem. The investigation showed that the landfill could be divided into two units based on the moisture in the land： （1） a front uint, consisted of the landfill slope, which had low water content; and （2） a rear unit, consisted of fresh waste, which had a high water content. This struc- ture caused two effects-surface-water infiltration and consolidation seepage that triggered the landslide in the landfill. Surface-water infiltration induced a gradual increase in pore water pressure head, or piezometric head, in the front slope because the infiltrating position rose as the volume of waste placement increased. Consolidation seepage led to higher excess pore water pressures as the loading of waste increased. We also investigated the post-failure soil dynamics parameters of the landslide deposit using cone penetration, triaxial, and ring-shear tests in order to simulate the characteristics of a flowing slide with a long run-out due to the liquefaction effect. Finally, we conclude the paper with lessons from the tens of catastrophic landslides of municipal solid waste around the world and discuss how to better manage the geotechnical risks of urbanization.

过表达tRNA基因tL(CAA)K提高酿酒酵母乙酸耐受性

乙酸是木质纤维素类生物质水解液中的常见毒性抑制物,选育乙酸耐受性好的酿酒酵母菌株,有利于高效利用木质纤维素类生物质,发酵生产生物燃料和生物基化学品。目前对酿酒酵母抗逆性的研究多集中在转录水平,但对转运RNA(Transfer RNA,tRNA)在耐受性中的作用研究较少。在对酿酒酵母抗逆性研究过程中发现,一些转运RNA基因在耐受性好的酿酒酵母菌株中转录明显上调。本文深入分析了精氨酸tRNA基因tR(ACG)D和亮氨酸tRNA基因tL(CAA)K过表达对酿酒酵母耐受木质纤维素水解液的影响。结果表明,在4.2 g/L乙酸胁迫条件下进行乙醇发酵时,过表达tL(CAA)K的菌株生长和发酵性能均优于对照酵母菌株,乙醇生产强度比对照菌株提高了29.41%,但过表达tR(ACG)D基因的菌株生长和代谢能力较对照菌株明显降低,体现了不同tRNA的不同调控作用。进一步分析发现,过表达tL(CAA)K的重组酵母菌株乙酸耐受性调控相关基因HAA1、MSN2和MSN4等胁迫耐受性相关转录因子编码基因的转录水平上调。本文的研究为选育高效利用木质纤维素资源进行生物炼制的酵母菌株提供了新的改造策略,也为进一步揭示酿酒酵母tRNA基因表达调控对抗逆性的影响提供了基础。

A Strigolactone Biosynthesis Gene Contributed to the Green Revolution in Rice

Plant architecture is a complex agronomic trait and a major factor of crop yield,which is affected by several important hormones.Strigolactones(SLs)are identified as a new class hormoneinhibiting branching in many plant species and have been shown to be involved in various developmental processes.Genetical and chemical modulation of the SL pathway is recognized as a promising approach to modify plant architecture.However,whether and how the genes involved in the SL pathway could be utilized in breeding still remain elusive.Here,we demonstrate that a partial loss-of-function allele of the SL biosynthesis gene,HIGH TILLERING AND DWARF 1/DWARF17(HTD1/D17),which encodes CAROTENOID CLEAVAGE DIOXYGENASE 7(CCD7),increases tiller number and improves grain yield in rice.We found that the HTD1 gene had been widely utilized and co-selected with Semidwarf 1(SD1),both contributing to the improvement of plant architecture in modern rice varieties since the Green Revolution in the 1960s.Understanding how phytohormone pathway genes regulate plant architecture and how they have been utilized and selected in breeding will lay the foundation for developing the rational approaches toward improving crop yield.

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics

Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

CXCR6-based immunotherapy in autoimmune,cancer and inflammatory infliction

T cells, including both CD4^(+) and CD8^(+)T cells, play a pivotal role in mediating various inflammation and immune disorders. A long-standing challenge in T cell-based immunotherapy is to precisely inactivate or delete the pathogenic T cells in inflammation and autoimmune diseases, or to selectively expand the immunocompetent T cell in tumor or other immune compromised situations, without inducing global immunosuppression or zealous immune activation respectively. To achieve this, a specific marker is needed to differentiate the pathogenic or immunocompetent T cell among the rests. Indeed,recent progress of immunology strongly suggests that CXC chemokine receptor 6(CXCR6, CD186) is such a kind of marker. Here, we review the emerging role of CXCR6 as a novel target for immunotherapy and discuss the underlying mechanism. We propose that CXCR6-based immunotherapy will play a significant role in autoimmune, nonalcoholic steatohepatitis(NASH), tumor, coronavirus disease 2019(COVID-19) and even ageing-related inflammatory infliction.