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Single-cell and spatial transcriptomics define 20E-driven developmental reprogramming in silkworm wing disc
Efficiency hierarchy and optimization of waste incineration in China to balance disposal and energy supply
The transcription factor EHF promotes the maturation and immunosuppression of conventional dendritic cells
Abstract The transcriptional program that regulates immunosuppression in CCR7 + conventional dendritic cells (cDCs) is currently unknown. Here, we identify ETS homologous factor (EHF) as a transcription factor that regulates cDC maturation and immunosuppression after TLR7/8/9 stimulation. Mice with conditional deletion of EHF in DCs exhibit increased resistance to autoimmune, infection or tumor challenge. EHF-deficient DCs promotes Th1- and Th17-biased CD4 + helper T cell response in vivo and in vitro. EHF-deficient cDC1s and cDC2s exhibit decreased expression of CCR7, CD200 and PD-L1, increased expression of DC-lineage transcriptional factor IRF4, and decreased expression of inhibitory NFκB family member Rel. EHF overexpression in DCs results in the opposite phenotype. CUT&TAG analysis suggests that EHF directly regulate Ccr7 , Cd200 , Cd274 , Irf4 and Rel expression. Additionally, single-cell RNA-sequencing demonstrates that Ehf expression is highly enriched in CCR7 hi DCs in mice and humans. Our study thus reveals a conserved transcriptional program that regulates cDC maturation and immunosuppression.
Development and validation of a prognostic model and scoring system for in-hospital mortality risk in neonates with heart failure within 28 days: a multicenter retrospective case-control study
A hardware-adaptive learning algorithm for superlinear-capacity associative memory on memristor crossbars
Insights from spatial Markov chain and dynamic QCA into the spatiotemporal evolution and configurational pathways of eco-efficiency in China’s coastal megaregions
Direct synthesis of bicyclo[1.1.1]pentane (BCP) boronates from carboxylic acids
Abstract Bicyclo[1.1.1]pentane (BCP) boronic esters are crucial intermediates for accessing BCP-containing drugs with improved pharmacokinetic profiles, yet their synthesis typically relies on pre-formed redox-active esters derived from carboxylic acids. Here we report a general, single-step method for the direct conversion of carboxylic acids into BCP boronic esters. Upon irradiation of carboxylic acids with [1.1.1]propellane and bis(pinacolato)diboron (B 2 pin 2 ) in dimethyl sulfoxide (DMSO), BCP boronates are obtained in good yields, which are further enhanced by the addition of an iron catalyst. Mechanistic studies suggest that photolytic cleavage of a B 2 pin 2 –DMSO complex initiates decarboxylation via hydrogen atom transfer (HAT), while iron catalysis enables a parallel ligand-to-metal charge transfer (LMCT) pathway. This synergistic HAT/LMCT process displays broad substrate scope and remarkable functional group tolerance. Additionally, BCP analogs of two approved drugs, butenafine and buclizine, have been readily synthesized, underscoring the potential of this dual HAT/LMCT paradigm to reshape strategies in synthetic chemistry and drug discovery.
How does agricultural product quality and safety regulation drive agricultural economic growth: a quasi-natural experiment from China’s agricultural product quality and safety county pilot policy
Structural and dynamic insights into agonist recognition and function of the thromboxane A2 receptor
Abstract The thromboxane A 2 receptor (TP), expressed in platelets and smooth muscle, plays an important role in blood clotting and muscle contraction. The endogenous ligand of this G protein-coupled receptor (GPCR), thromboxane A 2 (TXA 2 ), is a short-lived arachidonic acid metabolite with a half-life of ∼30 seconds, which makes investigating the TP structure and activation mechanism highly challenging. Here we determine the structures of the TP in complex with the synthetic agonists, U46619 and I-BOP, stable analogues of the natural ligand, in the presence of the signalling protein partner, G q . The structures reveal a unique activation switch for the receptor that differs from typical class A GPCR family members. Complemented by functional studies, mutational analysis, docking, and molecular dynamics (MD) simulations, our investigation highlights the differences between agonist and antagonist binding and explores the ligand entry mechanism to the binding pocket from within the membrane via a molecular gate composed of two transmembrane helices. In addition, our study provides crucial information to aid in the rational design of compounds targeting the TP, and offers mechanistic insights into inherited disorders associated with mutations in the TP.
Single cell multiomic landscape reveals gene programs driving lipid droplet heterogeneity in hepatic steatosis
Impact of maternal HIV infection on the gut microbiome and metabolome of mothers and infants: the PRACHITi cohort in Pune, India
Abstract Human immunodeficiency virus (HIV) affects millions of reproductive-age women globally, and during pregnancy is associated with adverse birth and infant health outcomes. Research on how maternal HIV shapes the gut microbiota, a potentially modifiable factor, during pregnancy, postpartum, and in infancy remains limited. The PRACHITi cohort study was conducted in India among 244 pregnant women with and without HIV, who were followed along with their children through 1 year postpartum. Our study focuses on secondary objectives of the PRACHITi study related to gut microbiota, with longitudinal samples being collected in the full cohort and more frequent sampling in a sub-study. Here, our findings reveal gut dysbiosis (based on 16S rRNA sequencing) and distinct plasma metabolomic profiles across pregnancy, postpartum, and their infants among women with HIV compared with seronegative women. We show that specific taxa and metabolites are differentially abundant by HIV status, some of which are linked to adverse outcomes, including preterm birth, low birth weight, and inflammation, conditions that are more common among populations with HIV. These results suggest potential biological pathways through which HIV affects maternal and infant health.
Response surface and TQM-ML analysis of a PCCI engine fueled with PO and microalgae biodiesel
S-nitrosoglutathione reductase GSNOR drives age-related obesity by promoting adipose tissue whitening through de-nitrosation of Beclin-1
An improved multi-objective animated oat optimization algorithm for resource-constrained construction project organization design
Perfectly harmonic spin cycloid and multi-Q textures in the Weyl semimetal GdAlSi
Synergistic effects of mulch type and deficit irrigation on physiological determinants and yield of spring maize (Zea mays L.)
Probing hidden symmetry via nonlinear transport in an altermagnet candidate Ca3Ru2O7
Rapid calibration of atrial electrophysiology models using Gaussian process emulators in the ensemble Kalman filter
Abstract Atrial fibrillation (AF) is a common cardiac arrhythmia characterised by disordered electrical activity in the atria. The standard treatment is catheter ablation, which is invasive and irreversible. Recent advances in computational electrophysiology offer the potential for patient-specific models that can be used to guide clinical decisions. To be of practical value, we must be able to rapidly calibrate physics-based models using routine clinical measurements. We pose this calibration task as a static inverse problem, where the goal is to infer spatially homogenous tissue-level electrophysiological parameters from the available observations. To make this tractable, we replace the expensive forward model with Gaussian process emulators (GPEs), and propose a novel adaptation of the ensemble Kalman filter (EnKF) for static non-linear inverse problems. The approach yields parameter samples that can be interpreted as coming from the best Gaussian approximation of the posterior distribution. We compare our results with those obtained using Markov chain Monte Carlo (MCMC) sampling and demonstrate the potential of the approach to enable near-real-time patient-specific calibration, a key step towards predicting outcomes of AF treatment within clinical timescales. The approach is readily applicable to a wide range of static inverse problems in science and engineering.