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Let |$X$| be a Calabi–Yau variety of Picard number two with infinite birational automorphism group. We show that the numerical dimension |$\kappa ^{\mathbb{R}}_{\sigma }$| of the extremal rays of the closed movable cone of |$X$| is |$\dim X/2$|⁠. More generally, we investigate the relation between the two numerical dimensions |$\kappa ^{\mathbb{R}}_{\sigma }$| and |$\kappa ^{\mathbb{R}}_{\textrm{vol}}$| for Calabi–Yau varieties. We also compute |$\kappa ^{\mathbb{R}}_{\sigma }$| for non-big divisors in the closed movable cone of a projective hyperkähler manifold. [ABSTRACT FROM AUTHOR]

We show that the anti-canonical volume of a canonical weak |${\mathbb {Q}}$| -Fano three-fold is at most |$324$|⁠. [ABSTRACT FROM AUTHOR]

Antibodies are essential to life, and knowing their structures can facilitate the understanding of antibody–antigen recognition mechanisms. Precise antibody structure prediction has been a core challenge for a prolonged period, especially the accuracy of H3 loop prediction. Despite recent progress, existing methods cannot achieve atomic accuracy, especially when the homologous structures required for these methods are not available. Recently, RoseTTAFold, a deep learning-based algorithm, has shown remarkable breakthroughs in predicting the 3D structures of proteins. To assess the antibody modeling ability of RoseTTAFold, we first retrieved the sequences of 30 antibodies as the test set and used RoseTTAFold to model their 3D structures. We then compared the models constructed by RoseTTAFold with those of SWISS-MODEL in a different way, in which we stratified Global Model Quality Estimate (GMQE) into three different ranges. The results indicated that RoseTTAFold could achieve results similar to SWISS-MODEL in modeling most CDR loops, especially the templates with a GMQE score under 0.8. In addition, we also compared the structures modeled by RoseTTAFold, SWISS-MODEL and ABodyBuilder. In brief, RoseTTAFold could accurately predict 3D structures of antibodies, but its accuracy was not as good as the other two methods. However, RoseTTAFold exhibited better accuracy for modeling H3 loop than ABodyBuilder and was comparable to SWISS-MODEL. Finally, we discussed the limitations and potential improvements of the current RoseTTAFold, which may help to further the accuracy of RoseTTAFold's antibody modeling. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524–9.048), 1.261 (IQR, 0.817–2.000), and 1.00 (IQR, 0.726–1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U  = 234.0; P < .001) and lymph node metastasis (U  = 240.0; P < .001). The receiver operating characteristic (ROC) curve showed that the sensitivity of the combined determination of hsa_circ_0002874 and the serum markers CEA and CA19-9 was 95.8% in patients with GC compared with that of the healthy group and 93.0% compared with that of patients with benign gastric tumor lesions. The specificity of hsa_circ_0002874 in differentiating GC from benign lesions was 98.3%. The results showed that plasma hsa_circ_0002874 may prove to be a useful biomarker for auxiliary diagnosis, the grading of malignant neoplasms, and the prognostic prediction of GC. [ABSTRACT FROM AUTHOR]

Theory suggests that the orbits of a large fraction of binary systems, including planet–star binary systems, shrink by a few orders of magnitude after formation. But so far, only one hot Jupiter with tidally driven orbital decay has been found by transit timing variations. We propose to search for orbital decay companions in heartbeat star systems because the orbital angular momentum is effectively transferred to the host star, causing tidal dissipation. KIC 3766353 is one of the heartbeat stars with tidally excited oscillations. We acquired the primary and the secondary eclipse time variations from the Kepler photometric light curves. Timing analysis shows that KIC 3766353 is a hierarchical triple system with a hidden third body and a red dwarf (mass 0.35 M⊙, radius 0.34  R ⊙) in its inner orbit. The minimum mass of the third body is ∼0.26 M⊙, and the distance from the inner orbital is ∼111.4  R ⊙. The period decay rate of the red dwarf is approximately 358 ms yr−1. The combined effects of the light-traveltime and the orbital decay lead to the observed timing variations. Future monitoring with long-time baseline observations is required to delve into the contributions of these two effects. [ABSTRACT FROM AUTHOR]

Activation of inflammasomes—immune system receptor sensor complexes that selectively activate inflammatory responses—has been associated with diverse human diseases, and many nanomedicine studies have reported that structurally and chemically diverse inorganic nanomaterials cause excessive inflammasome activation. Here, in stark contrast to reports of other inorganic nanomaterials, we find that nickel-cobalt alloy magnetic nanocrystals (NiCo NCs) actually inhibit activation of NLRP3, NLRC4 and AIM2 inflammasomes. We show that NiCo NCs disrupt the canonical inflammasome ASC speck formation process by downregulating the lncRNA Neat1 , and experimentally confirm that the entry of NiCo NCs into cells is required for the observed inhibition of inflammasome activation. Furthermore, we find that NiCo NCs inhibit neutrophil recruitment in an acute peritonitis mouse model and relieve symptoms in a colitis mouse model, again by inhibiting inflammasome activation. Beyond demonstrating a highly surprising and apparently therapeutic impact for an inorganic nanomaterial on inflammatory responses, our work suggests that nickel- and cobalt-containing nanomaterials may offer an opportunity to design anti-inflammatory nanomedicines for the therapeutics of macrophage-mediated diseases. [ABSTRACT FROM AUTHOR]

Apurinic/apyrimidinic (AP) sites are one of the most abundant DNA lesions and are mainly repaired by AP endonucleases (APEs). While most eukaryotic genomes encode two APEs, plants usually possess three APE s, namely APE1L , APE2 , and ARP. To date, the biological relevance and functional divergence of plant APEs are unclear. Here, we show that the three plant APEs have ancient origins, with the APE1L clade being plant-specific. In Arabidopsis thaliana , simultaneously mutating APE1L and APE2 , but not ARP alone or in combination with either APE1L or APE2 , results in clear developmental defects linked to genotoxic stress. Genetic analyses indicated that the three plant APEs have different substrate preferences in vivo. ARP is mainly responsible for AP site repair, while APE1L and APE2 prefer to repair 3′-blocked single-stranded DNA breaks. We further determined that APEs play an important role in DNA repair and the maintenance of genomic integrity in meiotic cells. The ape1l ape2 double mutant exhibited a greatly enhanced frequency of sporulation 1 (SPO11-1)-dependent and SPO11-1-independent double-stranded DNA breaks. The DNA damage response (DDR) was activated in ape1l ape2 to trigger pollen abortion. Our findings suggest functional divergence of plant APEs and reveal important roles of plant APEs during vegetative and reproductive development. [ABSTRACT FROM AUTHOR]