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Should there be a national holiday in honour of chemists?

Phylogenomics reveals the slow-burning fuse of diatom evolution

Evolution is often uneven in its pace and outcomes, with long periods of stasis interrupted by abrupt increases in morphological and ecological disparity. With thousands of gene histories, phylogenomics can uncover the genomic signatures of these broad macroevolutionary trends. Diatoms are a species-rich lineage of microeukaryotes that contribute greatly to the global cycling of carbon, oxygen, and silica, which they use to build elaborately structured cell walls. We combined fossil information with newly sequenced transcriptomes from 181 diverse diatom species to reconstruct the pattern, timing, and genomic context of major evolutionary transitions. Diatoms originated 270 Mya, and after >100 My of relative stasis in morphology and ecology, a radiation near the Jurassic–Cretaceous boundary led to the diversity of habitats and cell wall architectures characteristic of modern diatoms. This transition was marked by a genome duplication and high levels of gene tree discordance. However, short generation times increase the probability of coalescence between speciation events, minimizing the impacts of incomplete lineage sorting and implicating sequence saturation and gene tree error as the main sources of discordance. Nevertheless, a rigorous tree-based approach to ortholog selection resulted in strongly supported relationships, including some that were uncertain previously. Three pulses of accelerated speciation were detected, two of which were associated with the evolution of novel traits and ecological transitions. The first 100 My of diatom evolution was a slow-burning fuse that led to a burst of innovations in ecology, morphology, and life history that are hallmarks of contemporary diatom assemblages.

Body mass index and mortality after elective open abdominal aortic aneurysm repair in a fifteen year multicenter cohort study

Targeted apoptotic immune modulator for the treatment of metastatic EGFR-positive solid tumors

Aberrant activation and overexpression of the epidermal growth factor receptor (EGFR) occurs in various solid cancers and often correlates with poor outcome. The clinical benefit from EGFR-targeted therapies is usually short-lived, with resistance being driven by tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). To address these limitations, we developed Targeted Apoptotic Immune Modulators (TAIM), a nonviral nanoparticle platform for the targeted delivery of polyinosine:polycytosine (polyIC), to simultaneously induce tumor cell death and activate antitumor immunity. The first TAIM compound, TAR001, was designed as a systemic treatment against metastatic EGFR-positive solid cancers. Here, we present TAR001’s multifaceted mode of action. We demonstrate that TAR001 is selective toward EGFR-overexpressing cancers, provoking a pattern recognition response, apoptosis, cytokine secretion, and antitumor immunity. TAR001 modulates the TME, recruiting and activating both innate and adaptive immune cells. Systemic delivery of TAR001 markedly extends survival and inhibits tumor growth in multiple murine tumor models. TAR001 represents an innovative, safe, multimodal treatment approach with the potential to benefit patients with metastatic head and neck, non–small cell lung cancer, colorectal, renal, and triple-negative breast cancers. This unique modality utilizes a broad range of mechanisms to overcome the tumor’s ability to escape apoptosis and immune cell activation.

Small extracellular vesicles from human bone marrow mesenchymal stromal cells enhance migration and regulate reparative gene expression in dermal fibroblasts

Abstract Studies have shown that mesenchymal stromal cells (MSCs) could secrete a variety of bioactive particles, including small extracellular vesicles (sEVs), that might be a key intermediate to the beneficial paracrine effects of MSC therapy. In this study, we harvested the conditioned medium (CM) from human bone marrow mesenchymal stromal cells (hBM-MSCs) and normal human dermal fibroblasts (NHDFs), fractionated into the sEV fraction and non-small extracellular vesicle (NsEV) fraction, and compared their functions on NHDF migration and proliferation—key processes in wound healing, coupled with transcriptomic analysis through mRNA sequencing to assess gene expression changes in the recipient NHDFs. Our findings show that sEV, NsEV and CM from hBM-MSCs had an overall promotive effect on migration behaviour of NHDFs, but MSC-sEV surpassed the effects of other MSC secretome fractions and their NHDF counterparts (HDF-sEV). Gene ontology analysis revealed enrichment of pathways related to migration, and significant changes in genes within the regulation of proliferation pathway. Our study provides referential significance for the choice of cellular secretome fractions to be used in wound healing studies and insights into the effects of MSC secretome in the migration and proliferation of healthy fibroblasts, besides their effects on gene expression changes.

Illustrators call out journals and news sites for using AI art

Maximum spreading of impacting shear-thinning and shear-thickening drops

The maximum spreading of an impacting liquid drop is a key metric for characterizing the fundamental fluid process of drop impact. While extensively studied for Newtonian liquids, how far a non-Newtonian drop can spread upon impacting a solid substrate remains an open question. Here, by combining simulations, experiments, and scaling analyses, we establish a general framework for predicting the maximum spreading of drops of generalized Newtonian liquids, encompassing both shear-thinning and shear-thickening behaviors. Through an analysis of the energy budget at maximum spreading, we identify a characteristic shear rate that governs the viscous dissipation during drop impact. The finding allows us to map the spreading of non-Newtonian drops onto that of Newtonian drops, revealing the quantitative dependence of the maximum spreading diameter on various impact parameters and rheological properties of liquids. Our study addresses the long-standing challenge of understanding the impact dynamics of non-Newtonian drops, and provides valuable guidance for designing non-Newtonian liquids to achieve desired impact outcomes.

TPS genes expression pattern and terpenoids content in the leaves and flowers of Chimonanthus praecox and C. salicifolius

Nucleoporins cooperate with Polycomb silencers to promote transcriptional repression and repair at DNA double-strand breaks

DNA double-strand breaks (DSBs) are harmful lesions and major sources of genomic instability. Studies have suggested that DSBs induce local transcriptional silencing that consequently promotes genomic stability. Several factors have been proposed to actively participate in this process, including Ataxia-telangiectasia mutated (ATM) and Polycomb repressive complex 1 (PRC1). Here, we found that disrupting PRC1 clustering disrupts DSB-induced gene silencing. Interactome analysis of PHC2, a PRC1 subunit that promotes the PRC1 clustering, found several nucleoporins found in the nuclear pore complex (NPC). Similar to PHC2, depleting the nucleoporins also disrupted the DSB-induced gene silencing. We found that some of these nucleoporins, such as NUP107 and NUP43, which are members of the Y-complex of NPC, localize to DSB sites. The presence of nucleoporins and PHC2 at DSB regions was interdependent, suggesting that they act cooperatively in the DSB-induced gene silencing. We further found two structural components within NUP107 to be necessary for the transcriptional repression at DSBs: ATM/ Ataxia telangiectasia and Rad3-related-mediated phosphorylation at the Serine37 residue within the N-terminal disordered tail and the NUP133-binding surface at the C-terminus. These results provide a functional interplay among nucleoporins, ATM, and the Polycomb proteins in the DSB metabolism and underscore their emerging roles in genome stability maintenance.

Resistance and propulsion performance of a twin skeg ship with different rudder angle

Abstract Rudder angle will change the flow field, resulting in different loads and interactions on the hull-propeller-rudder, which will affect the resistance and self-propulsion performance of the ship, and this effect will be amplified on the twin skeg ship. Resistance of the ship-rudder at the rudder angle of 0 ° -8 °, lift, moment, axial wake, the rudder profile velocity vector at the propeller shaft height, and the dynamic pressure distribution on the inner and outer surfaces of the rudder were simulated by CFD(Computational Fluid Dynamics) method, and verified by the EFD(Experimental Fluid Dynamics) method. Self-propulsion factors of the hull-propeller-rudder with rudder angle of 0 ° -6 ° were calculated by CFD method, and compared with the EFD results. Axial wake, dynamic pressure on the surface of the propeller and rudder and the velocity vector near the rudder, and the flow field and vorticity field of the hull-propeller-rudder were analyzed. The results showed that : 1 ) The CFD results had the same trend as the EFD results. When the rudder angle was 6 °, the total resistance of the ship-rudder was the smallest, and the resistance decreased by about 1%. 2 ) The change of rudder angle had little effect on the wake field in front, but it had a great influence on the flow field around the rudder, which in turn affected the resistance, lift and moment. 3 ) Self-propulsion performance was the best when the rudder angle was 4 °, and the self-propulsion power can decrease by about 4%, mainly due to the beneficial interaction between the propeller and the rudder. 4 ) Rudder angle had little effect on the surface pressure of the propeller, but it will slightly change the axial wake behind the propeller, and the dynamic pressure of the rudder was quite different. 5 ) When the rudder angle exceeded the optimal rudder angle of 4 °, the interaction between the hull-propeller-rudder became unfavorable, resulting in the chaos of the vorticity field and the overall performance degradation. For twin skeg ships, proper arrangement of rudder angle can effectively improve ship performance and achieve energy saving purpose.

The proofreading mechanism of the human leading-strand DNA polymerase ε holoenzyme

The eukaryotic leading-strand DNA polymerase ε (Polε) is a dual-function enzyme with a proofreading 3′-5′ exonuclease ( exo ) site located 40 Å from the DNA synthesizing pol site. Errors in Polε proofreading can cause various mutations, including C-to-G transversions, the most prevalent mutation in cancers and genetic diseases. Polε interacts with all three subunits of the PCNA ring to assemble a functional holoenzyme. Despite previous studies on proofreading of several Pol’s, how Polε—or any Pol complexed with its sliding clamp—proofreads a mismatch generated in situ has been unknown. We show here by cryo-EM that a template/primer DNA substrate with a preexisting mismatch cannot enter the exo site of Polε–PCNA holoenzyme, but a mismatch generated in situ in the pol site yields three bona fide proofreading intermediates of Polε–PCNA holoenzyme. These intermediates reveal how the mismatch is dislodged from the pol site, how the DNA unwinds six base pairs, and how the unpaired primer 3′-end is inserted into the exo site for cleavage. These results unexpectedly demonstrate that PCNA imposes strong steric constraints that extend unwinding and direct the trajectory of mismatched DNA and that this trajectory is dramatically different than for Polε in the absence of PCNA. These findings suggest a physiologically relevant proofreading mechanism for the human Polε holoenzyme.

Versatile tethering system to control cell-specific targeting of bioengineered extracellular vesicles

Robustness revisited: On the neutral evolution of centrality and localization

This study investigates the intricate interplay among neutral landscape structure, mutation rate, recombination rate, and population dynamics in shaping evolutionary robustness. We provide a comprehensive framework that elucidates how different evolutionary forces interact to influence genotypic robustness and localization within haploid and diploid populations. We demonstrate that in haploid populations, high mutation rates relative to recombination typically drive the population toward regions of increased eigencentrality, a graph-theoretic measure of centrality which is correlated while not identical to mutational robustness. On the other hand, recombination increases the localization of the population to a smaller region of genotypic space, while high values of recombination relative to mutation can introduce shifts in distribution away from regions of high eigencentrality and toward attractors of the recombination dynamics. Diploid dynamics further complicate these interactions, showing reduced alignment with eigencentrality under both high mutation and recombination rates, with the exception of structured diploid landscapes where dynamics are still aligned with increasing eigencentrality. Our findings underscore the nuanced dependencies of evolutionary outcomes on both local and global landscape structures as well as evolutionary parameters.

Enhanced nuclear information fusion and visual transformer for pathological breast cancer image classification

Abstract Breast cancer poses a significant threat to women’s health. Early diagnosis using pathological images is crucial for effective treatment planning. However, the low resolution of pathological images poses significant challenges for the extraction of valid information, while their high complexity greatly increases the difficulty of image analysis. To address these challenges, this paper introduces an innovative classification method for breast cancer histopathological images, combining enhanced nuclear information with an Enhanced Vision Transformer (EVT) model using wavelet position embedding. The quintessence of the proposed method resides in its capacity to efficiently extract both biological and foundational image features from pathological images. This is accomplished by initially enhancing nuclear information through the application of segmentation models and sophisticated image processing techniques. Subsequently, wavelet positional embedding within the EVT model is leveraged to precisely capture key information embedded within the images. Experimental outcomes have demonstrated that our method attains an accuracy rate of 94.61% and an AUC value of 99.07% on the BreaKHis dataset, significantly outperforming other baseline network models in terms of classification efficacy. Furthermore, through visual representation, this study underscores the significance of nuclear information enhancement and wavelet position transformation in the EVT model, thereby further confirming the effectiveness and effectiveness of the method we proposed.

Freeze-induced crystallization: An overlooked pathway for mineral genesis in natural waters

Natural ice plays salient roles in making the Earth habitable and sustainable. Previously overlooked, its role in chemical processes is now of emerging interest, particularly due to the freeze concentration effect, which can substantially promote chemical reactions during ice formation. We demonstrate here that ice formation can serve as a dynamic and unique pathway for mineral genesis. Freezing solutions containing dissolved manganese and carbonates produced rhodochrosite (Mn II CO 3 ) even under slightly undersaturated conditions. At room temperature, by contrast, this occurred when the solution saturation level was increased by ca. 30,000 times. The cryogenic rhodochrosite formed spherical aggregates of nano-polycrystallites, distinctly different from the cubic monocrystalline particles observed at room temperature. The distinct feature likely resulted from the combined effects of the intensified supersaturation induced by the freeze concentration effect and the low temperatures within liquid-like layers, conditions that make liquid-like layers an exceptional environment for mineral genesis, unlike typical natural water systems. The cryogenic rhodochrosite formation was successfully demonstrated using in situ, real-time X-ray absorption spectroscopy (XAS), enabling direct observation of freeze-induced solid formation. Our findings reveal that freeze-induced crystallization may be an active mineralization pathway, potentially influencing elemental cycles within the cryosphere and contributing to minerals with distinguishing properties and reactivities in the environment.

A clinical study on the preservation of pulp sensitivity in affected teeth with jaw cysts using concentrated growth factor: a retrospective Cross-sectional study

ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D

Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. High-throughput studies showed interconnection between ATP8B1 and phosphoinositide (PIPs), but the mechanism linking ATP8B1, lipid metabolism, and inflammation remains unclear. Atp8b1 G308V/G308V mouse model, unbiased RNAseq, high-resolution-stimulation emission depltion (STED)-microscopy, and Crispr-Cas9 generated ATP8B1 −/− knockouts in hepatocytes/monocytes/macrophages were used to determine role of ATP8B1 in phosphatidylinositol,4-5-bisphosphate (PIP2) trafficking and inflammation. Human ATP8B1, purified from Sf9 insect cells and reconstituted in proteoliposomes, was used to test cell-free PIP2 flip. Various in-vitro techniques were used for testing direct interaction between PIP2 and ATP8B1. ATP8B1 maintains PIP2 at the inner leaflet of plasma membrane (PM). ATP8B1 flips PIP2 in cells, without altering flip of PE or bulk-endocytosis. ATP8b1 flips PIP2 in a cell-free system. ATP8B1 deletion promotes bile-salt-mediated cholesterol extraction from hepatocytes in a PIP2-dependent manner. PIP2 directly binds to the P-loop of ATP8B1. Unbiased RNAseq showed upregulation of inflammatory cytokines in ATP8b1 −/− immune cells. ATP8B1 −/− monocytes/macrophages showed aberrant lipopolysaccharide (LPS)-induced cleavage of GSDMD, formation of GSDMD pores, and interleukin-1beta (IL1β) release. Inflammation-resolving efferocytosis was impaired in ATP8B1 −/− macrophages. Biophysical properties of PM were altered in ATP8b1 −/− cells, with the mechanism being disrupted localization of PIP2. Atp8b1 G308V/G308V mice exposed to LPS showed higher plasma IL1β and lower survival rates vs. WT mice. ATP8B1 maintains PIP2 at the inner leaflet of PM. ATP8b1 directly flips and binds PIP2. ATP8B1 regulates LPS-induced GsdmD cleavage, formation of GsdmD pores, IL1β release, and mortality in mice.

Immuno-transcriptomic analysis based on machine learning identifies immunity signature genes of chronic rhinosinusitis with nasal polyps

Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1

FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 and vitamin K. These quinone antioxidants function as radical scavenging agents that prevent the propagation of lipid peroxidation and the induction of ferroptosis. Although several small-molecule inhibitors of FSP1 have been developed and found to sensitize cancer cells to ferroptosis, our understanding of their molecular mechanisms remains limited and no structures of FSP1 in complex with its inhibitors have been solved. Here, we solve the cocrystal structure of FSP1 in complex with the FSP1 inhibitor FSEN1, revealing that FSEN1 binds within the FSP1 substrate-binding pocket. FSEN1 makes key interactions with a critical phenylalanine, which is absent in mouse FSP1, providing an explanation for the selectivity of FSEN1 for human FSP1. These conclusions are supported by mutagenesis of FSP1 and biochemical and cellular assays of FSP1 function. Our findings provide the first cocrystal structure of FSP1 in complex with an inhibitor, enhancing our understanding of the mechanism of FSP1 inhibition and enabling future rational medicinal chemistry efforts to advance FSP1 inhibitors as therapeutics.

Oxytocin activity is not linked to out-group prosociality in wild bonobos

Abstract In many group-living species, cooperative group defense is crucial to the reproduction and survival of group members. In humans and chimpanzees, this adaptive behavior is regulated by oxytocin, a highly conserved neurohormone. In humans, oxytocin can also enhance prosocial attitudes towards out-group individuals and reduces xenophobia. While the role of oxytocin in supporting cooperative group defense is likely evolutionarily ancient, it is unclear to what extent oxytocin’s role in promoting out-group prosociality is conserved. Bonobos, our closest living relatives together with chimpanzees, can provide valuable insights into this question, because they are not known to engage in collective group defense but instead exhibit tolerance and prosocial behaviors across groups. Through examining variation in bonobo cooperative behavior, specifically coalition formation, we reinforce the idea that bonobo coalitions do not serve as a form of group defense. Despite increased competition, bonobos formed fewer coalitions in the presence of out-groups. Further, bonobo coalitions included both in- and out-group partners, reflecting reduced xenophobia and between-group cooperation. Physiologically, neither females nor males showed increased oxytocin activity with out-group presence. This suggests that, unlike in humans, oxytocin is not involved in regulating out-group prosociality in bonobos.