Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands.

Severe fever with thrombocytopenia syndrome virus was found in Northern Jiangxi Province, China.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. SFTS monitoring has been carried out since 2010 in mainland China. In recent years, human infection with SFTS virus (SFTSV) has frequently been detected in Jiujiang of Jiangxi Province, Central China.

Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy.

Ionizable lipids are a key component of lipid nanoparticles, the leading nonviral messenger RNA delivery technology. Here, to advance the identification of ionizable lipids beyond current methods, which rely on experimental screening and/or rational design, we introduce lipid optimization using neural networks, a deep-learning strategy for ionizable lipid design. We created a dataset of >9,000 lipid nanoparticle activity measurements and used it to train a directed message-passing neural network for prediction of nucleic acid delivery with diverse lipid structures.

Producing multiple chemicals through biological upcycling of waste poly(ethylene terephthalate).

Poly(ethylene terephthalate) (PET) waste is of low degradability in nature, and its mismanagement threatens numerous ecosystems. To combat the accumulation of waste PET in the biosphere, PET bio-upcycling, which integrates chemical pretreatment to produce PET-derived monomers with their microbial conversion into value-added products, has shown promise. The recently discovered Rhodococcus jostii RPET strain can metabolically degrade terephthalic acid (TPA) and ethylene glycol (EG) as sole carbon sources, and it has been developed into a microbial chassis for PET upcycling.

Structural variation in the pangenome of wild and domesticated barley.

Pangenomes are collections of annotated genome sequences of multiple individuals of a species. The structural variants uncovered by these datasets are a major asset to genetic analysis in crop plants. Here we report a pangenome of barley comprising long-read sequence assemblies of 76 wild and domesticated genomes and short-read sequence data of 1,315 genotypes.

RSNA 2023 Abdominal Trauma AI Challenge: Review and Outcomes.

Purpose To evaluate the performance of the winning machine learning models from the 2023 RSNA Abdominal Trauma Detection AI Challenge. Materials and Methods The competition was hosted on Kaggle and took place between July 26 and October 15, 2023. The multicenter competition dataset consisted of 4274 abdominal trauma CT scans, in which solid organs (liver, spleen, and kidneys) were annotated as healthy, low-grade, or high-grade injury.

Enhancement and mechanism of mechanical properties and functionalities of polyacrylamide/polyacrylic acid hydrogels by 1D and 2D nanocarbon.

Highly flexible hydrogels are widely used in fields such as agriculture, drug delivery, and tissue engineering. However, the simultaneous integration of excellent mechanical properties, swelling properties, and high electrical conductivity into a hydrogel is still a great challenge. This work introduces 1D tubular multi-walled carbon nanotubes (MWCNTs) and 2D layered graphene oxide (GO) into polyacrylamide/poly-acrylic acid (PAM/PAA) hydrogels.

Wood Cell Wall Nanoengineering toward Anisotropic, Strong, and Flexible Cellulosic Hydrogel Sensors.

Achieving highly ionic conductive hydrogels from natural wood remains challenging owing to their insufficient surface area and low number of active sites on the cell wall. This study proposes a viable strategy to design a strong and anisotropic wood-based hydrogel through cell wall nanoengineering. By manipulating the microstructure of the wood cell wall, a flexible cellulosic hydrogel is achieved through Schiff base bonding via the polyacrylamide and cellulose molecular chains.

Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia.

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected.

Enhancement of hybrid organohydrogels by interpenetrating crosslinking strategies for multi-source signal recognition over a wide temperature range.

With substantial temperature differentials between summer and winter in polar regions, there exists a pressing necessity for flexible sensors capable of functioning across a broad temperature spectrum to facilitate the construction of a more intelligent human-machine interface. Nevertheless, developing flexible sensors resilient to extremely low temperatures remains a significant challenge. In this study, we present an organohydrogel capable of functioning ranging from ambient to -78 °C, enabling real-time monitoring of multi-source signals, including motion, physiology, speech, and pressure.

Assessing the Performance of Models from the 2022 RSNA Cervical Spine Fracture Detection Competition at a Level I Trauma Center.

Purpose To evaluate the performance of the top models from the RSNA 2022 Cervical Spine Fracture Detection challenge on a clinical test dataset of both noncontrast and contrast-enhanced CT scans acquired at a level I trauma center. Materials and Methods Seven top-performing models in the RSNA 2022 Cervical Spine Fracture Detection challenge were retrospectively evaluated on a clinical test set of 1828 CT scans (from 1829 series: 130 positive for fracture, 1699 negative for fracture; 1308 noncontrast, 521 contrast enhanced) from 1779 patients (mean age, 55.8 years ± 22.

Disease prediction with multi-omics and biomarkers empowers case-control genetic discoveries in the UK Biobank.

The emergence of biobank-level datasets offers new opportunities to discover novel biomarkers and develop predictive algorithms for human disease. Here, we present an ensemble machine-learning framework (machine learning with phenotype associations, MILTON) utilizing a range of biomarkers to predict 3,213 diseases in the UK Biobank. Leveraging the UK Biobank's longitudinal health record data, MILTON predicts incident disease cases undiagnosed at time of recruitment, largely outperforming available polygenic risk scores.

Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity.

Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD.

Measurement of Energy Correlators inside Jets and Determination of the Strong Coupling α_{S}(m_{Z}).

Energy correlators that describe energy-weighted distances between two or three particles in a hadronic jet are measured using an event sample of sqrt[s]=13  TeV proton-proton collisions collected by the CMS experiment and corresponding to an integrated luminosity of 36.3  fb^{-1}. The measured distributions are consistent with the trends in the simulation that reveal two key features of the strong interaction: confinement and asymptotic freedom.

Cell cycle-regulated transcription factor AP2XII-9 is a key activator for asexual division and apicoplast inheritance in tachyzoite.

Unlabelled: is an intracellular parasitic protozoan that poses a significant risk to the fetus carried by a pregnant woman or to immunocompromised individuals. tachyzoites duplicate rapidly in host cells during acute infection through endodyogeny. This highly regulated division process is accompanied by complex gene regulation networks.