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Interferons (IFNs) activate JAK‐STAT pathways to induce downstream effector genes for host defense against invaded pathogens and tumors. Here both type I (β) and II (γ) IFNs are shown that can activate the transcription factor IRF3 in parallel with STAT1. IRF3‐deficiency impairs transcription of a subset of downstream effector genes induced by IFN‐β and IFN‐γ. Mechanistically, IFN‐induced activation of IRF3 is dependent on the cGAS‐STING‐TBK1 axis. Both IFN‐β and IFN‐γ cause mitochondrial DNA release into the cytosol. In addition, IFNs induce JAK1‐mediated tyrosine phosphorylation of cGAS at Y214/Y215, which is essential for its DNA binding activity and signaling. Furthermore, deficiency of cGAS, STING, or IRF3 impairs IFN‐β‐ or IFN‐γ‐mediated antiviral and antitumor activities. The findings reveal a novel IRF3 activation pathway parallel with the canonical STAT1/2 activation pathways triggered by IFNs and provide an explanation for the pleiotropic roles of the cGAS‐STING‐IRF3 axis in host defense. [ABSTRACT FROM AUTHOR]

Summary: Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems.Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM‐dominant effects on ecosystem functioning in forest biomes.Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal‐dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes.Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time. [ABSTRACT FROM AUTHOR]

Patient‐derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid‐guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression‐free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty‐six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%–91.9%) in predicting clinical responses. Thirty‐six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression‐free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33–0.85]; p =.01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44–18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor‐positive, human epidermal growth factor receptor 2‐negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO‐based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization. [ABSTRACT FROM AUTHOR]

Invasive plants usually experience population differentiation as they expand from their initial invasive range to the edge. Moreover, invasive plants usually encounter competitors which shared different co-evolutionary histories with them. These factors may lead to varying responses of invasive plant populations to elevated nitrogen deposition during expansion. However, this issue has received limited attention in prior research. To address these challenges, we conducted a greenhouse experiment to investigate how population differentiation of Galinsoga quadriradiata interacts with the presence of various competitors in response to increased nitrogen deposition. Competitor types (new or old that shared short or long co-evolutionary history with the invader, respectively) were set to compete with the invasive central and edge populations under different nitrogen addition treatments. Individuals from the central population of G. quadriradiata , originating from the initial invasion range, showed greater total mass, reproduction and interspecific competitiveness compared with the edge population. Nitrogen addition improved growth and reproductive performance in both populations, and the central population had a stronger response compared with the edge population. The performance of G. quadriradiata was inhibited more effectively by old competitors than new competitors. Our results indicate that population differentiation occurs in terms of growth and competitiveness during the range expansion of G. quadriradiata , with the central population exhibiting superior performance. Co-evolutionary history with competitors is considered unfavorable for invasive plants in this study. Our results highlight the combined effects of population differentiation in invasive species and their co-evolution history with competitors in the context of global change factors. [ABSTRACT FROM AUTHOR]

The immersion weakening effect of natural soil has always been a difficult problem encountered in geotechnical engineering practice. The bond dissolution is a common cause of soil strength deterioration, which is not yet fully understood. In this study, a thermodynamic-based constitutive model of structural soils based on the [alpha] model is first established, considering the bond strength by modifying the yield surface size and gradually reducing the bond strength with the development of plastic strain. Furthermore, by taking the meso-mechanisms of bond dissolution into account, the evolution rule of the free energy during the bond dissolution process is derived based on a homogenization approach, and a thermodynamic-based constitutive model of structural soil with bond dissolution is thereafter developed. By comparing with the results of one-dimensional compression tests and conventional triaxial tests, the model is verified to be capable of reflecting the gradual destructuration process of soil while loading. The comparison with triaxial test results of completely decomposed granite after different immersion durations and parametric studies show that based on the cross-scale energy equivalence, the model can well reflect the strength deterioration characteristics of completely decomposed granite with bond dissolution mechanisms at the mesoscale fully considered. Key words: immersion weakening, bond dissolution, structural soil, thermodynamics, constitutive model. L'effet d'affaiblissement par immersion du sol naturel a toujours ete un probleme difficile rencontre dans la pratique de l'ingenierie geotechnique. La dissolution des liaisons est une cause frequente de la deterioration de la resistance des sols, qui reste encore mal comprise. Dans cette etude, un modele constitutif thermodynamique des sols structurels base sur le modele a est d'abord etabli, en considerant la force de liaison en modifiant la taille de la surface d'elasticite et en reduisant progressivement la force de liaison avec le developpement de la deformation plastique. En outre, en tenant compte des meso-mecanismes de dissolution des liaisons, la regle d'evolution de l'energie libre pendant le processus de dissolution des liaisons est derivee sur la base d'une approche d'homogeneisation, et un modele constitutif du sol structurel avec dissolution des liaisons, base sur la thermodynamique, est ensuite developpe. En comparant avec les resultats des essais de compression unidimensionnelle et des essais triaxiaux conventionnels, on verifie que le modele est capable de refleter le processus de destructuration progressive des sols en charge. La comparaison avec les resultats d'essais triaxiaux du granit completement decompose apres differentes durees d'immersion et les etudes parametriques montrent que, sur la base de l'equivalence energetique a l'echelle croisee, le modele peut bien refleter les caracteristiques de deterioration de la resistance du granit completement decompose avec des mecanismes de dissolution des liaisons a la meso-echelle entierement pris en compte. [Traduit par la Redaction] Mots-cles: affaiblissement par immersion, dissolution des liaisons, sol structurel, thermodynamique, modele constitutif., 1. Introduction The physical and chemical changes of soil after immersion in water are important factors affecting the mechanical properties of soil. The immersion weakening effect of some particular kinds [...]

This document provides a summary of various methods for the synthesis of tetrasubstituted axially chiral alkenes. The methods discussed include urea group-directed organocatalytic dihalogenation, Rh(III)-catalyzed C-H activation and directing group migration, cationic rhodium(I)/H8-BINAP-catalyzed chelation-controlled cycloaddition, Cu/Pd dual catalysis for arylboration, nickel-catalyzed cross-electrophile trans-aryl-benzylation, palladium-catalyzed C-H functionalization, Pd(II)-catalyzed thioether-directed alkenyl C-H olefination, Suzuki-Miyaura cross-coupling, asymmetric N-alkylation, chiral phosphoric acid catalyzed kinetic resolution, and asymmetric allylic substitution-isomerization. The methods demonstrate broad substrate scope and high enantioselectivities, but further research is needed to explore stereodivergent synthesis and applications in pharmaceutical chemistry. [Extracted from the article]

Fast radio bursts (FRBs) have been found in great numbers, but the physical mechanism of these sources is still a mystery. The redshift evolutions of the FRB energy distribution function and the volumetric rate shed light on the origin of FRBs. However, such estimations rely on the dispersion measurement (DM)–redshift (z) relationship. A few FRBs that have been detected recently show large excess DMs beyond the expectation from the cosmological and Milky Way contributions, which indicates large spread of DMs from their host galaxies. In this work, we adopt two lognormal-distributed DM host models and estimate the energy function using the non-repeating FRBs selected from the Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB Catalog 1. By comparing the lognormal-distributed DM host models to a constant DM host model, the FRB energy function results are consistent within the measurement uncertainty. We also estimate the volumetric rate of the non-repeating FRBs in three different redshift bins. The volumetric rate shows that the trend is consistent with the stellar-mass density redshift evolution. Since the lognormal-distributed DM host model increases the measurement errors, the inference of FRBs tracking the stellar-mass density is nonetheless undermined. [ABSTRACT FROM AUTHOR]

In this paper,a novel three-phase rectifier based on triple line-voltage cascaded VIENNA converter(LVC-VC) has been proposed,which could be the high power factor rectifier under high power voltage.Compared to conventional three-phase cascaded H-bridge converters,in the proposed new multilevel converters,and fewer switches and dc capacitors are required under similar operating conditions.Based on the study to the operation principle of the new converter,the power factor correction of the proposed converter is realized by employing traditional one-cycle control strategy,the carrier phase-shifting modulation is designed to reduce the ac voltage harmonic.The dc side capacitor voltage steady state mathematical model is deduced,the scope of the dc side capacitor voltage is calculated,the controllers of dc-link voltages of the three Vienna rectifier modules are designed.Simulation and experimental results verified the availability of the new proposed multilevel converter and the validity of the corresponding control strategy applied.

Histone H3K27 demethylase JMJD3 plays a critical role in gene expression and T cell differentiation. However, the role and mechanisms of JMJD3 in T cell trafficking remain poorly understood. Here, we show that JMJD3 deficiency in [CD4.sup.+] T cells resulted in an accumulation of T cells in the thymus and reduction of T cell number in the secondary lymphoid organs. We identified PDLIM4 as a significantly downregulated target gene in JMJD3- deficient [CD4.sup.+] T cells by gene profiling and ChIP-Seq analyses. We further showed that PDLIM4 functioned as an adaptor protein to interact with sphingosine-1 phosphate receptor 1 (S1P1) and filamentous actin (F-actin), thus serving as a key regulator of T cell trafficking. Mechanistically, JMJD3 bound to the promoter and gene-body regions of the Pdlim4 gene and regulated its expression by interacting with zinc finger transcription factor KLF2. Our findings have identified Pdlim4 as a JMJD3 target gene that affects T cell trafficking by cooperating with S1P1 and have provided insights into the molecular mechanisms by which JMJD3 regulates genes involved in T cell trafficking., Introduction T cell development in the thymus is a multistep process. Early thymic progenitor cells (TPCs) differentiate into T cell receptor-expressing (TCR-expressing) [CD4.sup.+][CD8.sup.+] double-positive (DP) thymocytes in the cortex and [...]