4,411 results match your criteria: "G.X.; Clinical Pharmacology A.M. and Drug Metabolism Y.L.[Affiliation]"

3D Imaging Reveals Complex Microvascular Remodeling in the Right Ventricle in Pulmonary Hypertension.

Circ Res

June 2024

Department of Medicine, Division of Pulmonary, Allergy and Critical Care (K.I., M.B., A.M.A., K.S., Y.M., T.Z., X.T., R.V., W.T., M.R.N., E.S.).

Background: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure.

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Revealing novel and conservative T-cell epitopes with MHC B2 restriction on H9N2 avian influenza virus (AIV).

J Biol Chem

June 2024

National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, South China Agricultural University, Guangzhou, China. Electronic address:

B2 haplotype major histocompatibility complex (MHC) has been extensively reported to confer resistance to various avian diseases. But its peptide-binding motif is unknown, and the presenting peptide is rarely identified. Here, we identified its peptide-binding motif (X-A/V/I/L/P/S/G-X-X-X-X-X-X-V/I/L) in vitro using Random Peptide Library-based MHC I LC-MS/MS analysis.

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Ferroptosis is a cell death mechanism that has attracted significant attention as a potential basis for the development of new cancer therapies. Validation of ferroptosis biology in species commonly used in translation and pre-clinical development is a necessary foundation for enabling the advancement of such ferroptosis modulating drugs. Here, we demonstrate that canine cancer cells exhibit sensitivity to a wide range of ferroptosis-inducing perturbations in a manner indistinguishable from human cancer cells, and recapitulate characteristic patterns of ferroptotic response across tumor types seen in the human setting.

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Measuring Visual Fields in Children With Glaucoma Using a Portable Tablet.

Transl Vis Sci Technol

May 2024

Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.

Article Synopsis
  • The study aimed to compare visual field testing results between an iPad app (Melbourne Rapid Fields) and the standard Humphrey Field Analyser in children with glaucoma.
  • Sixteen children aged 7 to 15 participated, and findings showed that the app's results closely matched the standard device, demonstrating high correlation and faster test times.
  • The children favored the iPad app over the standard test, suggesting it's an effective and preferable option for assessing visual fields in pediatric glaucoma cases.
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Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2.

Circulation

July 2024

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China) College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.), First Affiliated Hospital, Harbin Medical University, China.

Article Synopsis
  • G protein-coupled receptors, especially galanin receptors (GALRs), are significant in understanding atrial fibrillation (AF), with spexin identified as a unique ligand affecting these receptors.
  • Research involving genetically modified mice showed that the absence of spexin increased the likelihood of AF and disrupted potassium currents and calcium handling in heart cells.
  • The study concluded that spexin lowers AF risk by inhibiting the phosphorylation of CREB, leading to decreased expression of specific channels and improved cardiac function.
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By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus.

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Article Synopsis
  • Preeclampsia is a serious pregnancy-related condition linked to improper remodeling of blood vessels in the uterus, but its early molecular causes are still not fully understood.
  • Research shows that preeclampsia is caused by underdeveloped trophoblasts and endothelial cells due to delayed epigenetic changes, leading to an excessive amount of immature trophoblast cells.
  • The study finds that high levels of a gene called PEG10, transferred from trophoblasts to maternal cells, disrupt normal blood vessel development by interfering with TGF-beta signaling, highlighting complex genetic interactions during pregnancy.
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The CRISPR-Cas12a system is more advantageous than the widely used CRISPR-Cas9 system in terms of specificity and multiplexibility. However, its on-target editing efficiency is typically much lower than that of the CRISPR-Cas9 system. Here we improved its on-target editing efficiency by simply incorporating 2-aminoadenine (base Z, which alters canonical Watson-Crick base pairing) into the crRNA to increase the binding affinity between crRNA and its complementary DNA target.

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Activating Inert Perovskite Oxides for CO Electroreduction via Slight Cu Doping in B-Sites.

Small

September 2024

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China.

Perovskite oxides are proven as a striking platform for developing high-performance electrocatalysts. Nonetheless, a significant portion of them show CO electroreduction (CORR) inertness. Here a simple but effective strategy is reported to activate inert perovskite oxides (e.

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Comprehensive proteogenomic characterization of rare kidney tumors.

Cell Rep Med

May 2024

Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes.

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X-linked Alport syndrome presenting in mother and son with the same unique histopathological features.

J Nephrol

April 2024

Service of Nephrology, L'Hôtel-Dieu de Québec Research Center, CHU de Québec-Université Laval, 10 McMahon Street (Room 3852), Québec, QC, G1R 2J6, Canada.

Article Synopsis
  • Alport syndrome is linked to three genes (COL4A3, COL4A4, COL4A5) and is marked by kidney issues like glomerulosclerosis and changes in the glomerular basement membrane.
  • A study reported a mother and son with COL4A5-related Alport syndrome, sharing unusual kidney biopsy results and a specific genetic variant (p.Gly1170Ser).
  • Findings indicate that changes in collagen expression in Bowman's capsule might be more affected by mutations in COL4A5, suggesting that certain genetic variants can play a significant role in how the disease presents.
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Article Synopsis
  • The LD oilfield shows improved recovery rates after weak gel flooding, but the distribution of remaining oil becomes complicated during high-water content stages.
  • Researchers conducted experiments using online NMR and microscopic techniques to better understand weak gel flooding effects and the remaining oil distribution.
  • Results indicated that weak gel flooding significantly enhances oil mobilization in porous media, leading to higher recovery efficiencies of 71.85% at 500 mD and 80.69% at 1500 mD compared to traditional methods.
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Rice (Oryza sativa L.) is an important member of the family Poaceae and more than half of world population depend for their dietary nutrition on rice. Rice cultivars with higher yield, resilience to stress and wider adaptability are essential to ensure production stability and food security.

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Although serum iron status and sarcopenia are closely linked, the presence of comprehensive evidence to establish a causal relationship between them remains insufficient. The objective of this study is to employ Mendelian randomization techniques to clarify the association between serum iron status and sarcopenia. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationship between iron status and sarcopenia.

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An pair of an atypical NLR encoding genes confer Asian soybean rust resistance in soybean.

Nat Commun

April 2024

Soybean Genetics and breeding team, Institute of Oil Crops Research, Chinese Academy of Agriculture Sciences, Wuhan, 430062, China.

Article Synopsis
  • Asian soybean rust (ASR), caused by the fungus Phakopsora pachyrhizi, severely impacts soybean crops, with a lack of resistant varieties hindering effective management.
  • Researchers isolated two genes, Rpp6907-7 and Rpp6907-4, from a resistant Chinese soybean landrace, which together provide broad-spectrum resistance to ASR.
  • The study reveals that Rpp6907-7 is the primary gene conferring resistance, while Rpp6907-4 regulates its activity, indicating their potential in breeding improved soybean varieties.
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Reciprocal antagonism of PIN1-APC/C governs mitotic protein stability and cell cycle entry.

Nat Commun

April 2024

Departments of Biochemistry and Oncology, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A 3K7, Canada.

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/C) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/C activity to treat cancer.

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Structural basis for dimerization of a paramyxovirus polymerase complex.

Nat Commun

April 2024

Roche Pharma Research and Early Development, Lead Discovery, Roche Innovation Center Shanghai, 201203, Shanghai, China.

The transcription and replication processes of non-segmented, negative-strand RNA viruses (nsNSVs) are catalyzed by a multi-functional polymerase complex composed of the large protein (L) and a cofactor protein, such as phosphoprotein (P). Previous studies have shown that the nsNSV polymerase can adopt a dimeric form, however, the structure of the dimer and its function are poorly understood. Here we determine a 2.

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A lung disease diagnosis algorithm based on 2D spectral features of ultrasound RF signals.

Ultrasonics

May 2024

Key Laboratory of Modern Acoustics (MOE), Department of Physics, Collaborative Innovation Center of Advanced Microstructure, Nanjing University, Nanjing 210093, China. Electronic address:

Lung diseases are commonly diagnosed based on clinical pathological indications criteria and radiological imaging tools (e.g., X-rays and CT).

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Article Synopsis
  • The study focused on identifying high dry matter yielding soybean genotypes suitable for various environments in southwestern Ethiopia, with evaluations conducted over two cropping seasons (2019-2020).
  • The analysis revealed that environmental conditions and genotype-environment interactions significantly influenced soybean yield, accounting for a larger variation in yield than genotype alone.
  • Genotype G4 (TGX1990114FN) emerged as the top performer in terms of dry matter yield and stability, making it a recommended option for forage soybean in Ethiopia, with further studies suggested to assess its impact on animal performance.
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The main objective of this project was to compare in the field conditions two strategies of re-nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three-arm, open-label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo-oligosaccharides (6 g/day if age ≥12 months and 4 g if age <12 months) = arm 3.

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Low field controllable continuous spin switching in the thulium-ytterbium single crystal.

Phys Chem Chem Phys

April 2024

Department of Physics, Materials Genome Institute, Institute for Quantum Science and Technology, Shanghai University, Shanghai, 200444, China.

We report the spin reorientation transition (SRT) and the low field controllable continuous spin switching (SSW) of the TmYbFeO (TYFO) single crystal in this study. The SRT, characterized by the transition from (, , )-(, , ), occurs within the temperature range of 20-27 K. Under an external magnetic field of 50 Oe, the SSW occurs along the -axis at approximately 98 K due to the reversal of Tm magnetic moment induced by the magnetic coupling change between Tm and Fe, transitioning from a parallel to an antiparallel alignment.

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Objective: To identify whether conventional methods of estimating fetal growth (Hadlock's formula), which relies heavily on abdominal circumference measurements, are accurate in fetuses with gastroschisis.

Methods: A retrospective cohort study was performed between the period January 1, 2011 and December 31, 2021 in a tertiary referral maternity hospital identifying all pregnancies with a diagnosis of gastroschisis. Projected fetal weight was obtained using the formula (EFW [Hadlock's formula] + 185 g × [X/7]) where X was the number of days to delivery.

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Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer's disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls.

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Low Dose Radiation and Solid Tumors Mortality Risk.

J Occup Environ Med

June 2024

From the Division of Occupational and Environmental Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland (T.G.X.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (F.C.C.), and the Russell H. Morgan Department of Radiology and Radiological Science and Division of Cardiology Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (M.M.).

Background: US nuclear capable shipyard workers have increased potential for occupational radiation exposure.

Objective: The aim of the study is to examine solid tumor mortality risks at low doses.

Method: 437,937 workers working from 1957 to 2004 at eight US shipyards were studied.

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Late-stage guanine C8-H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction.

Nat Commun

March 2024

Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis.

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