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Enhanced FeIV═O Generation via Peroxymonosulfate Activation by an Edge-Site Engineered Single-Atom Iron Catalyst
No full textAs an oxidant, the ferryl-oxo complex (FeIV & boxH;O) offers excellent reactivity and selectivity for degrading recalcitrant organic contaminants. However, enhancing FeIV & boxH;O generation on heterogeneous surfaces remains challenging because the underlying formation mechanism is poorly understood. This study introduces edge defects onto a single-atom Fe catalyst (FeNC-edge) to promote FeIV & boxH;O generation via peroxymonosulfate (PMS) activation. In the presence of PMS, the FeNC-edge catalyst at a low dose (20 mg L-1, equivalent to 0.14 mg L-1 Fe) exhibits unprecedented activity for organic contaminant degradation. Electrochemical analysis, in situ Raman spectroscopy, and FeIV & boxH;O probe experiments confirm that FeIV & boxH;O generation is enhanced on the surface of FeNC-edge. Density functional theory calculations reveal that the introduced edge sites concentrate electron density on active Fe atoms, facilitating charge transfer from Fe to PMS. Notably, FeNC-edge immobilized on a polymeric membrane functioned as a continuous-flow oxidation system with efficient catalyst recycling and minimal Fe leaching.N
AI Applications for Thoracic Imaging: Considerations for Best Practice
No full textArtificial intelligence (AI) technology is rapidly being introduced into thoracic radiology practice. Current representative use cases for AI in thoracic imaging show cumulative evidence of effectiveness. These include AI assistance for reading chest radiographs and low-dose (1.5-mSv) chest CT scans for lung cancer screening and triaging pulmonary embolism on chest CT scans. Other potential use cases are also under investigation, including filtering out normal chest radiographs, monitoring reading errors, and automated opportunistic screening of nontarget diseases. However, implementing AI tools in daily practice requires establishing practical strategies. Practical AI implementation will require objective on-site performance evaluation, institutional information technology infrastructure integration, and postdeployment monitoring. Meanwhile, the remaining challenges of adopting AI technology need to be addressed. These challenges include educating radiologists and radiology trainees, alleviating liability risk, and addressing potential disparities due to the uneven distribution of data and AI technology. Finally, next-generation AI technology represented by large language models (LLMs), including multimodal models, which can interpret both text and images, is expected to innovate the current landscape of AI in thoracic radiology practice. These LLMs offer opportunities ranging from generating text reports from images to explaining examination results to patients. However, these models require more research into their feasibility and efficacy.N
Dual C2 Synthon Strategy for the Synthesis of Pyrimidines: Copper-Catalyzed Aerobic α,β-C(sp3)−H Bond Difunctionalization of Tertiary Alkylamines
No full textHerein, we describe a two-component methodology developed for the synthesis of pyrimidine derivatives using tertiary alkylamines and amidines. Tertiary alkylamines serve as dual C2 synthons through copper-catalyzed aerobic difunctionalization of the alpha,beta-C(sp3)-H bonds. The process operates under mild conditions and uses atmospheric oxygen as the oxidant. Notably, by this methodology yields up to 85% yields are obtained and a broad substrate scope is shown. Mechanistic studies indicate that the annulation proceeds via a radical-mediated oxidation and C-N bond coupling process. This approach provides a pathway for synthesizing various heterocycles by employing tertiary alkylamines as dual C2 synthons.N
Adenylate kinase 5 deficiency impairs epididymal white adipose tissue homeostasis and decreases fat mass
No full textImportance: The brain and adipose tissue interact metabolically, and if there is a problem with the energy metabolism of the brain, it cannot maintain the energy balance with the adipose tissue. Therefore, when adenylate kinase 5 ( AK5), which regulates energy metabolism in the brain, is knocked out, problems with lipid metabolism may occur. Objective: We aimed to elucidate the metabolic function and phenotype of AK5, a gene with an unknown function in metabolism. Methods: We generated AK5 knockout (KO) mice and administered high-fat and fasting diets to the mice to confirm their physiological phenotype and metabolic differences. Results: In the high-fat diet (HFD) test, no differences in body weight, epididymal white adipose tissue (eWAT), or fat mass of AK5 KO mice were observed. In indirect calorimetry, the respiratory exchange ratio and activity counts increased in normal chow diet mice, but there was no difference between the HFD groups. At the mRNA level, there were no significant differences in the expression of lipid metabolism markers between wild-type and AK5 KO mice. Still, the glucose signal of adipocytes increased in AK5 KO mice. In the fasting test, the eWAT of AK5 KO mice was significantly reduced, as was the expression of lipid metabolism and inflammation-related immune markers. Thus, the apoptosis of adipocytes increased, and an imbalance in energy metabolism occurred. Conclusions and Relevance: When AK5 KO mice are energy deficient, it becomes difficult to use eWAT for energy storage, imbalance occurs, and apoptosis of adipocytes in eWAT increases.N
Optimizing HDAC inhibitors to enhance HDR-associated CRISPR-Cas9 gene editing efficiency in vivo and in vitro
No full textGene editing by CRISPR-Cas9 via homology-directed repair (HDR) offers precise and desirable modifications, but its low efficiency remains a challenge due to the dominance of the non-homologous end joining (NHEJ) pathway in DNA repair. To identify compounds that improve HDR-associated gene editing efficiency, we established a high-throughput screening system capable of detecting HDR events and assessing cell viability simultaneously, excluding drugs with severe cytotoxicity. We screened 2485 compounds from a clinical collection library and identified several histone deacetylase inhibitors that significantly enhance HDR efficiency. Tacedinaline and entinostat exhibited the high efficiency in promoting HDR-associated gene editing among them. Notably, entinostat treatment led to a significant increase in HDR-associated gene editing in vivo. Our study provides optimized HDAC inhibitor conditions for high-efficiency HDR-associated gene editing both in vivo and in vitro.Y
A 42Gb/s Single-Ended Hybrid-DFE PAM-3 Receiver for GDDR7 Memory Interfaces
No full textDemand for high-bandwidth graphics memory is rapidly increasing for various applications such as AI, deep learning, autonomous cars, etc. To meet this demand, GDDR6X uses multi-level signaling (PAM4) for the first time in DRAM [1], while GDDR7 targets data-rates 28Gb/s or higher using PAM3 signaling. However, the increased data rate incurs higher inter-symbol interference (ISI), while PAM3 is more vulnerable to ISI than PAM2 signaling. Decision feedback equalizers (DFEs) are widely used in receivers (RX) to remove post-cursor ISI without amplifying noise. A PAM3 RX, with an analog DFE, typically employs a direct feedback (DF) implementation, which must meet stringent feedback timing requirements. As the target speed increases it is challenging to reduce the feedback time to within 1 unit interval (UI) for a PAM3 RX due to the increased line parasitics and gate loading. While the loop-unrolled (LU) DFE technique mitigates feedback timing constraints, implementing a PAM3 LU DFE results in additional area and power overhead. In view of these drawbacks, this paper proposes a new type of PAM3 DFE, which combines the qualities of DF and LU DFEs to minimize area and power overhead, while also reducing the feedback time.N
Central Nervous System Depression After Topical Administration of Brimonidine Eye Drops to Induce Vomiting in a Cat
No full textBrimonidine stimulates the chemoreceptor trigger zone via alpha-2 adrenergic receptors in the postrema of the medulla, which triggers vomiting in cats. This case report details the occurrence of central nervous system (CNS) depression following brimonidine administration to induce vomiting in a cat that had ingested a toxic substance. A 12-year-old neutered male American Shorthair cat was presented to the hospital after ingesting two leaves of Anthurium polyschistum, which is toxic to cats. 0.15% of brimonidine eye drops intended for ocular administration were accidentally administered onto the upper eyelids, resulting in the administration of four drops in total. Three incidents of projectile vomiting were then observed 30 min after the brimonidine administration. The cat began to show signs of CNS depression, including deep sedation and respiratory depression after vomiting. Brimonidine use was the suspected aetiology of the CNS depression. Atipamezole (200 mu g/kg) was administered intramuscularly; after 5 min, the clinical signs of the CNS depression resolved. This case suggests that while brimonidine may serve as an effective emetic agent in feline patients, its systemic effects, particularly CNS depression, warrant careful monitoring. The potential impact of higher concentrations and increased dosing volume remains uncertain, highlighting the need for further research to establish safe and standardized dosing guidelines.Y
Autophagy induction enhances homologous recombination-associated CRISPR-Cas9 gene editing
No full textCRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9)-based gene editing via homologous recombination (HR) enables precise gene correction and insertion. However, its low efficiency poses a challenge due to the predominance of nonhomologous end-joining during DNA repair processes. Although numerous efforts have been made to boost HR efficiency, there remains a critical need to devise a novel method that can be universally applied across cell types and in vivo animals, which could ultimately facilitate therapeutic treatments. This study demonstrated that autophagy induction using different protocols, including nutrient deprivation or chemical treatment, significantly improved HR-associated gene editing at diverse genomic loci in mammalian cells. Notably, interacting cofactor proteins that bind to Cas9 under the autophagic condition have been identified, and autophagy induction could also enhance in vivo HR-associated gene editing in mice. These findings pave the way for effective gene correction or insertion for in vivo therapeutic treatments.N
Identification of conserved gene expression changes across common glomerular diseases by spatial transcriptomics
No full textBackgroundGlomerular diseases encompass a group of kidney diseases that may share common gene expression pathways. Here, we analyzed glomerular-specific gene expression profiles across various glomerular diseases.MethodsWe performed spatial transcriptomic profiling using formalin-fixed paraffin-embedded kidney biopsy specimens of controls and patients with five types of glomerular diseases using the GeoMx Digital Spatial Profiler. Disease-representative glomerular regions of interest (ROIs) were configured, probed with oligonucleotide barcodes linked with target complimentary sequence. The UV-cleaved barcodes were amplified to generate libraries and subsequently sequenced. Common differentially expressed genes across glomerular diseases were identified and Gene Ontology annotation was performed using the ToppGene suite.ResultsThe mean age of patients with glomerular diseases and kidney donors was 49.5 +/- 12.2 and 49.5 +/- 9.8 years, respectively. A total of 35 differentially expressed genes were consistently downregulated in glomeruli across the disease compared to the control, while none of the differentially expressed genes were consistently upregulated. Twelve of 35 downregulated differentially expressed genes, including the two hub genes JUN and FOS, were annotated with molecular function Gene Ontology terms related to DNA-binding transcription factor activity. The annotated biological process Gene Ontology terms included response to lipid-related (17/35 differentially expressed genes), response to steroid hormone (12/35 differentially expressed genes), or cell cycle regulation (10/35 differentially expressed genes). Xenium and immunofluorescence staining confirmed the reduced expression of JUN, ZFP36, and KLF9 in intraglomerular cells of glomerular diseases.ConclusionsIdentifying common differentially expressed genes by spatial transcriptomic analysis provides insights into the underlying molecular mechanisms of glomerular diseases and may lead to novel assessment or therapeutic strategies.Y
Osteoprotective Activity of Sambucus javanica Reinw Ex Blume subsp. javanica Leaf Extracts by Suppressing ROS Production
No full textSambucus javanica subsp. javanica (SJ) has been used in traditional medicine in the northern region of Thailand for healing bone fractures; however, studies on how this plant stimulates bone formation are still scarce. The present study aimed to investigate the potential of crude extracts and fractions obtained from SJ leaves for osteoporotic protection. All samples were investigated in murine preosteoblast MC3T3-E1 cells for bone formation and resorption biomarkers, namely alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), and the OPG/RANKL ratio. Additionally, calcium deposits were determined using the alizarin red S staining technique. The results indicated that the crude water and the crude ethanol extracts contained gallic acid, rutin, and chlorogenic acid as major compounds. The extracts stimulated osteoblastic cell differentiation and enhanced osteoprotective activity, as measured by a significant increase in ALP activity, OC, OPG, the OPG/RANKL ratio, and the degree of calcification. Additionally, they exhibited a negative impact on bone resorption by significantly reducing RANKL and reactive oxygen species (ROS) production. Therefore, our findings add novel evidence indicating that the SJ crude extracts from water and ethanol extraction could be further utilized as a natural active pharmaceutical ingredient (NAPI) for the development of bone health products.Y