Search

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]

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]

A Janus layered metamaterial (JLM) operating in the terahertz (THz) region is proposed, which increases the direction dimension to manipulate the propagation of electromagnetic waves (EWs) through the introduction of nonlinear Kerr media. It achieves multi-scale multitasking with different logic gates and mode-switching biosensing, making a breakthrough on traditional single-function and single-scale THz devices. Due to the electro-optical effect, the liquid crystal (LC) is adjusted by the electric field, and the sharp transmission peak generated by the located defect mode resonance can be used to realize the forward scale logic product gate and the backward scale exclusive NOR gate. In addition, by locking the sharp transmission peak, the biosensing can have different detection ranges under the LC modulation. Therefore, when EWs propagate forward and backward, the mode switching of different biosensing categories with a glucose concentration of 300–550 g/l, creatinine concentration of 80.9–85.28 μmol/l, and the blood component in refractive index of 1.33–1.38 can be realized. The JLM proposed provides a possibility for the design of the chip-level compact optical integrated circuit and offers a new idea for multi-purpose biomedical detection, owning certain research value. [ABSTRACT FROM AUTHOR]

In this study, the form factors of B (s) to light D-wave tensor mesons with J PC = 2 - - ( ρ 2 , ω 2 , K 2 and ϕ 2 ) are calculated via the light cone sum rules (LCSR) in the framework of heavy quark effective eld theory (HQEFT). Firstly, the expressions of form factors in terms of the light cone distribution amplitudes (LCDAs) of tensor mesons are derived via the LCSR at the leading order of heavy quark expansion. Similar to the case of 2 + + tensor mesons, the penguin type form factors can be obtained directly from the corresponding semileptonic ones. Considering the light tensor meson LCDAs to twist-3 and quark mass corrections, we give the numerical results of form factors systematically. Based on the form factors given here, we investigate the branching ratios, longitudinal polarization fractions and forward-backward asymmetries of relevant charged current induced semileptonic decays. Our results may be tested by more precise experiments in the future. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage, is a cerebrovascular disease with high morbidity, mortality, and disability. Due to the lack of effective clinical treatments, the development of new drugs to treat intracerebral hemorrhage is necessary. In recent years, ferroptosis has been found to play an important role in the pathophysiological process of intracerebral hemorrhage, which can be treated by inhibiting ferroptosis and thus intracerebral hemorrhage. This article aims to explain the mechanism of ferroptosis and its relationship to intracerebral hemorrhage. In the meantime, it briefly discusses the molecules identified to alleviate intracerebral hemorrhage by inhibiting ferroptosis, along with other clinical agents that are expected to treat intracerebral hemorrhage through this mechanism. In addition, a brief overview of the morphological alterations of different forms of cell death and their role in ICH is provided. Finally, the challenges that may arise in translating ferroptosis inhibitors from basic research to clinical use are presented. This article serves as a reference and provides insights to aid in the treatment of intracerebral hemorrhage in the clinic., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Accurate tumor detection is crucial for the early discovery and subsequent treatment of small neoplastic foci. Molecular imaging, which combines non-invasiveness, high specificity, and strong sensitivity, excels in diagnosing early tumors and stands out among tumor diagnosis methods. Here, we introduced a dual-modal imaging probe capable of actively targeting tumor cells, suitable for both near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI). Dendritic mesoporous silica was used as a carrier for the probe, encapsulating Ag 2 S quantum dots (QDs) for NIR fluorescence imaging. Additionally, the probe conjugated the MRI contrast agent Gd-DOTA and cetuximab, which targeted EGFR on the tumor cell membrane surface, to achieve dual-modal imaging in the tumor area. This strategy provided a methodology for the accurate diagnosis of early-stage tumor lesions and guides precise lesion resection during surgery, offering significant potential for clinical application.