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Immune checkpoint inhibitor (ICI) treatment has created the opportunity of improved outcome for patients with hepatocellular carcinoma (HCC). However, only a minority of HCC patients benefit from ICI treatment owing to poor treatment efficacy and safety concerns. There are few predictive factors that precisely stratify HCC responders to immunotherapy. In this study, we developed a tumour microenvironment risk (TMErisk) model to divide HCC patients into different immune subtypes and evaluated their prognosis. Our results indicated that virally mediated HCC patients who had more common tumour protein P53 (TP53) alterations with lower TMErisk scores were appropriate for ICI treatment. HCC patients with alcoholic hepatitis who more commonly harboured catenin beta 1 (CTNNB1) alterations with higher TMErisk scores could benefit from treatment with multi-tyrosine kinase inhibitors. The developed TMErisk model represents the first attempt to anticipate tumour tolerance of ICIs in the TME through the degree of immune infiltration in HCCs.

 

Understanding crystallization mechanisms in nano-sized metallic glasses (MGs) is important to the manufacturing and application of these new nanomaterials that possess a unique combination of structural and functional properties. Due to the two-dimensional projections and limited spatial and/or temporal resolutions in experiments, significant questions (e.g., whether nucleation takes place on the free surface or in a near-surface layer) regarding this subject remain under debate. Here, we address these outstanding questions using molecular dynamics simulations of crystallization in MG nanorods together with atomistic visualization and data analysis. We show that nucleation in the nano-sized MGs predominantly takes place on the surface by converting the high-energy liquid surface to a lower-energy crystal surface (the most close-packed atomic plane). This is true for all the nanorods with different diameters studied. On the other hand, the apparent growth mode (inward/radial, lateral or longitudinal) and the resulting grain structure are more dependent on the nanorod diameter. For a relatively big diameter of the nanorod, the overall growth rate does not differ much among the three directions and the resulting grains are approximately semispherical. For small diameters, grains appear to grow more in longitudinal direction and some grains may form relatively long single-crystal segments along the length of the nanorod. The reasons for the difference are discussed. The study provides direct atomistic insights into the crystallization mechanisms in nano-sized MGs, which can facilitate the manufacturing and application of these new advanced materials. 

Macrofossils with unambiguous biogenic origin and predating the one-billion-year-old multicellular fossilsBangiomorphaandProterocladusinterpreted as crown-group eukaryotes are quite rare.Horodyskiais one of these few macrofossils, and it extends from the early Mesoproterozoic Era to the terminal Ediacaran Period. The biological interpretation of this enigmatic fossil, however, has been a matter of controversy since its discovery in 1982, largely because there was no evidence for the preservation of organic walls. Here we report new carbonaceous compressions ofHorodyskiafrom the Tonian successions (~950–720 Ma) in North China. The macrofossils herein with bona fide organic walls reinforce the biogenicity ofHorodyskia. Aided by the new material, we reconstructHorodyskiaas a colonial organism composed of a chain of organic-walled vesicles that likely represent multinucleated (coenocytic) cells of early eukaryotes. Two species ofHorodyskiaare differentiated on the basis of vesicle sizes, and their co-existence in the Tonian assemblage provides a link between the Mesoproterozoic (H.moniliformis) and the Ediacaran (H.minor) species. Our study thus provides evidence that eukaryotes have acquired macroscopic size through the combination of coenocytism and colonial multicellularity at least ~1.48 Ga, and highlights an exceptionally long range and morphological stasis of this Proterozoic macrofossils.

 

Root‐knot nematodes (RKNs), includingMeloidogynespecies, are among the most destructive plant‐parasites worldwide. Recent evidence suggests that entomopathogenic fungi (EPF) can antagonize RKNs. Such antagonistic effects are likely mediated by toxic metabolites, including volatile organic compounds (VOCs), produced by the fungi. However, how widespread these effects are across EPF species, and which VOCs mediate negative interactions between EPF and RKNs needs to be further elucidated.

First, we evaluated the nematicidal effect of VOCs emitted by 46 EPF isolates againstMeloidogyne incognitaand found variable toxicity depending on the isolate. Second, we measured the nematicidal effect of highly toxic isolates, including species in the genusTalaromyces,Aspergillus,Clonostachys, andPurpureocilliumand, third, we analyzed the nematicidal effect of major VOCs, including 2‐methyl‐1‐propanol, 3‐methyl‐1‐butanol, isopropyl alcohol and 2‐methyl‐3‐pentanone. The mortality ofM. incognitajuveniles (J2s) was generally high (50%) either via airborne or in‐solution contact with VOCs. Moreover, the tested VOCs significantly inhibited egg hatching, and repelled J2s away from the VOCs.

This study not only provides insights into the ecological function of VOCs in the rhizosphere, but also provides new approaches for developing environmentally friendly control methods of RKNs in agroecosystems. © 2023 Society of Chemical Industry.