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Retinal oxygen extraction during systemic hypoxia assessed with laser-speckle flowgraphy and retinal oximetry

ACTA OPHTHALMOLOGICA 2025年第S284期103卷

作者： Pai, Viktoria Lindner, Theresa Janku, Patrick Schmetterer, Leopold Schmidl, Doreen Garhofer, Gerhard Department of Clinical Pharmacology Medical University of Vienna Vienna Austria Singapore National Eye Centre Singapore Eye Research Institute Singapore Singapore Duke-NUS Medical School Ophthalmology and Visual Sciences Academic Clinical Program Singapore Singapore SERI-NTU Advanced Ocular Engineering (STANCE) Nanyang Technological University Singapore Singapore Center for Medical Physics and Biomedical Engineering Medical University of Vienna Vienna Austria Institute of Molecular and Clinical Ophthalmology Basel Switzerland School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University Singapore Singapore

Aims/Purpose: Retinal oxygen extraction has been found to be altered in several ocular and systemic diseases, such as diabetic retinopathy, glaucoma or neurodegenerative diseases. However, measurement techniques for the assessment of retinal oxygen extraction are limited because most of them are based on time-consuming and custom-built devices. In the present pilot study, we assessed retinal oxygen extraction during systemic hypoxia with a combination of two commercially available devices: Laser-Speckle Flowgraphy (LSFG) and retinal oximetry. Methods: Retinal blood flow and retinal oxygen saturation were measured in each vessel around the optic nerve head at the same position. Arterial and venous oxygen content was estimated from the measured retinal oxygen saturation parameters and the difference between these two parameters was calculated (cO 2 , DIFF ). By using mean vessel flow rate (MV) for retinal blood flow and cO 2 , DIFF , retinal oxygen extraction was determined. For each healthy study participant, baseline measurement and measurement during inhalation of 88% nitrogen in 12% oxygen were performed. Results: Ten (10) healthy subjects (4 females, 6 males) with a mean age of 27 ± 3 years were included in this study. During systemic hypoxia, a significant decrease in arterial oxygen content occurred ( p = 0.046) while venous oxygen content did not change, leading to a decrease in cO 2 , DIFF . As expected, this was accompanied by a significant increase in MV ( p = 0.014). No change in retinal oxygen extraction was observed (46 ± 8 a.u. at baseline vs. 46 ± 5 a.u. during hypoxia, p = 0.997). Conclusions: Breathing of 88% nitrogen in 12% oxygen caused a significant decrease in retinal arterial oxygen content. This was compensated by an increase in retinal blood flow in order to keep retinal oxygen extraction constant. This was physiologically expected, and these findings are consistent with the literature. Therefore, the presented approach for measurement of reti

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molecular architecture of mammalian pyruvate dehydrogenase complex

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Protein & Cell 2025年第1期16卷 72-78页

作者： Maofei Chen Yutong Song Sensen Zhang Yitang Zhang Xudong Chen Minghui Zhang Meng Han Xin Gao Sai Li Maojun Yang Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological StructureSchool of Life SciencesTsinghua UniversityBeijing 100084China Ministry of Education Key Laboratory of Protein Science Tsinghua UniversityBeijing 100084China State Key Laboratory of Membrane Biology Tsinghua UniversityBeijing 100084China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesShenzhen University Health Science CenterShenzhen 518060China Protein Research Technology Center Protein Chemistry and Omics PlatformSchool of Life SciencesTsinghua UniversityBeijing 100084China Computer Science Program ComputerElectrical and Mathematical Sciences and Engineering DivisionKing Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Kingdom of Saudi Arabia Computational Bioscience Research Center King Abdullah University of Science and TechnologyThuwal 23955-6900Kingdom of Saudi Arabia Cryo-EM Facility Center Southern University of Science and TechnologyShenzhen 518055China Beijing Life Science Academy Beijing 102209China

Dear Editor,Pyruvate dehydrogenase complex(PDHc) is a large multienzyme assembly(Mr = 4–10 million Daltons) consisting of three essential components: pyruvate dehydrogenase(E1p), dihydrolipoyl transacetylase(E2p), and dihydrolipoyl dehydrogenase(E3). These three enzymes perform distinct functions sequentially to catalyze the oxidative decarboxylation of pyruvate with formation of nicotinamide adenine dinucleotide(NADH) and acetyl-coenzyme A(Patel and Roche, 1990).

关键词： sequentially oxidative Dalton

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Polarization-driven dynamic laser speckle analysis for characterizing breast cancer cells 36

Polarization-driven dynamic laser speckle analysis for chara...

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Optical Interactions with Tissue and Cells XXXVI 2025

作者： Abbasian, Vahid Rad, Vahideh Farzam Ahmadvand, Davoud Darafsheh, Arash Department of Radiation Oncology Washington University School of Medicine in St. Louis St. LouisMO63110 United States Imaging Science Program McKelvey School of Engineering Washington University in St. Louis St. LouisMO63130 United States Department of Molecular Imaging Faculty of Advanced Technologies in Medicine Iran University of Medical Sciences Tehran Iran

ISBN: (纸本)9781510683822

The study of breast cancer cells is essential to advance our knowledge of tumor biology and therapeutic strategies. Optical techniques, particularly polarimetric imaging, have significantly enhanced our understanding of cancer cells, but conventional methods face challenges in capturing and interpreting polarization characteristics. Coherent light sources offer high-contrast imaging but introduce speckle noise, while incoherent sources reduce noise but lack contrast and polarization distinction. To address these issues, we integrated polarimetric imaging with dynamic laser speckle analysis (DLSA), a method that extracts information from intensity variations in the speckle pattern. The polarization-driven DLSA maintains laser advantages while transforming challenges into opportunities. This approach involves capturing a series of intensity images under different polarization modulations and then analyzing sequence-based variations in the resultant speckle pattern across the polarimetric images. In this study, we extend the approach to the microscopy domain and apply it to MCF7 breast cancer cell samples, showing the potential of this novel technique as a robust and label-free diagnostic tool. © 2025 SPIE.

关键词： Laser beams

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Glycolysis model shows that allostery maintains high ATP and limits accumulation of intermediates

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Biophysical Journal 2025年第10期124卷 1562-1586页

作者： Choe, Mangyu Einav, Tal Phillips, Rob Titov, Denis V. Department of Nutritional Sciences and Toxicology University of California Berkeley Berkeley California United States Department of Molecular and Cell Biology University of California Berkeley Berkeley California United States Center for Computational Biology University of California Berkeley Berkeley California United States Division of Biology and Biological Engineering California Institute of Technology Pasadena California United States Department of Physics California Institute of Technology Pasadena California United States Basic Sciences Division and Computational Biology Program Fred Hutchinson Cancer Research Center Seattle WA United States Center for Vaccine Innovation La Jolla Institute for Immunology La Jolla California United States

Glycolysis is a conserved metabolic pathway that produces ATP and biosynthetic precursors. It is not well understood how the control of mammalian glycolytic enzymes through allosteric feedback and mass action accomplishes various tasks of ATP homeostasis, such as controlling the rate of ATP production, maintaining high and stable ATP levels, ensuring that ATP hydrolysis generates a net excess of energy, and maintaining glycolytic intermediate concentrations within physiological levels. To investigate these questions, we developed a biophysical model of glycolysis based on enzyme rate equations derived from in vitro kinetic data. This is the first biophysical model of human glycolysis that successfully recapitulates the above tasks of ATP homeostasis and predicts absolute concentrations of glycolytic intermediates and isotope tracing kinetics that align with experimental measurements in human cells. We use the model to show that mass action alone is sufficient to control the ATP production rate and maintain the high energy of ATP hydrolysis. Meanwhile, allosteric regulation of hexokinase and phosphofructokinase by ATP, ADP, inorganic phosphate, and glucose-6-phosphate is required to maintain high ATP levels and to prevent uncontrolled accumulation of phosphorylated intermediates of glycolysis. Allosteric feedback achieves the latter by maintaining hexokinase and phosphofructokinase enzyme activity at one-half of ATP demand and, thus, inhibiting the reaction of Harden and Young, which otherwise converts glucose to supraphysiological levels of phosphorylated glycolytic intermediates at the expense of ATP. Our methodology provides a roadmap for a quantitative understanding of how metabolic homeostasis emerges from the activities of individual enzymes. © 2025 Biophysical Society

关键词： allosteric feedback glycolysis metabolism modeling

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Integrating computational and experimental insights into osmolyte-driven activation of Geobacillus kaustophilus L-asparaginase for acrylamide mitigation

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Journal of molecular Liquids 2025年 423卷

作者： Özdemir, F.İnci Servili, Burak Demirtaş, Özge Şükür, Gözde Tülek, Ahmet Yildirim, Deniz Gebze Technical University Department of Molecular Biology and Genetics Kocaeli Gebze41400 Turkey Kadir Has University of Science and Engineering Bioinformatics and Genetics Program İstanbul Fatih35430 Turkey Iğdır University Postgraduate Education Institute Department of Bioengineering and Sciences Iğdır Merkez76000 Turkey Cukurova University Faculty of Ceyhan Engineering Department of Chemical Engineering Adana Ceyhan01950 Turkey

Osmolytes play a critical role in enhancing the stability and activity of enzymes for industrial applications. This study systematically investigated the effects of various osmolytes on the activity, optimal pH, temperature, stability, metal ion effects, storage, and acrylamide mitigation performance of L-asparaginase from the thermophilic Geobacillus kaustophilus (GkASNase). The experimental findings were further supported by computationally integrated tools such as homology modeling, docking, and molecular dynamics (MD) simulations. Among the selected osmolytes (maltose, sorbitol, trehalose, glycine, and sucrose), GkASNase showed the highest stability during 30 days of storage in the presence of maltose and arginine. Maltose increased GkASNase activity approximately 2-fold at 37 °C and 55 °C. In the presence of osmolytes, the Km values of GkASNase decreased and the Vmax values increased compared to controls at 37 °C and 55 °C. In the presence of osmolytes, the acrylamide mitigation performance of GkASNase increased by 1.7-fold in a 15 min reaction. The computational analysis indicates that L-asparagine as substrate enhances protein compactness and stability, while arginine as osmolyte increases flexibility and optimizes water distribution around the enzyme. These findings provide novel insights into enzyme stabilization that have implications for therapeutic and biotechnological applications. © 2025 Elsevier B.V.

关键词： Maltose

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Causes of and risk factors for postpartum haemorrhage: a systematic review and meta-analysis

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The Lancet 2025年第10488期405卷 1468-1480页

作者： Yunas, Idnan Islam, Md Asiful Sindhu, Kulandaipalayam N Devall, Adam J Podesek, Marcelina Alam, Sayeda Sadia Kundu, Shoumik Mammoliti, Kristie-Marie Aswat, Ashraf Price, Malcolm J Zamora, Javier Oladapo, Olufemi T Gallos, Ioannis Coomarasamy, Arri Department of Metabolism and Systems Science College of Medicine and Health University of Birmingham Birmingham United Kingdom Department of Applied Health Sciences College of Medicine and Health University of Birmingham Birmingham United Kingdom Department of Biomedical Science and Physiology School of Pharmacy and Life Sciences Faculty of Science and Engineering University of Wolverhampton Wolverhampton United Kingdom Department of Biochemistry and Molecular Biology Faculty of Biological Sciences Jahangirnagar University Savar Bangladesh Department of Chemistry and Biochemistry Texas Tech University Lubbock TX United States Department of Public Health Faculty of Communication Arts and Sciences Canadian University Dubai Dubai United Arab Emirates Clinical Biostatistics Unit Hospital Universitario Ramón y Cajal – IRYCIS Madrid Spain Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) Madrid Spain United Nations (UN) Development Program UN Population Fund UN Children's Fund World Health Organization (WHO) World Bank Special Program of Research Development and Research Training in Human Reproduction Department of Sexual and Reproductive Health and Research WHO Geneva Switzerland

Background: An understanding of the causes of postpartum haemorrhage is needed to provide appropriate treatment and services. Knowledge of the risk factors for postpartum haemorrhage can help address modifiable risk factors. We did a systematic review and meta-analysis to identify and quantify the various causes and risk factors for postpartum haemorrhage. Methods: In this systematic review and meta-analysis, we did a systematic literature search in MEDLINE, Embase, Web of Science, Cochrane Library, and Google Scholar for cohort studies of postpartum haemorrhage from Jan 1, 1960, to Nov 30, 2024 without language restrictions. At least two authors independently undertook study selection, data extraction, and quality assessment. Population-based cohort studies available in English were eligible. Rates of postpartum haemorrhage causes as well as crude and adjusted odds ratios (ORs) for risk factors were pooled using a random-effects model. Risk factors were classified as having weak, moderate, or strong association based on the pooled ORs: weak (OR >1 to 1·5), moderate (OR >1·5 to 2), and strong (OR >2). This study is registered with PROSPERO, CRD42023479686. Findings: We synthesised data from 327 studies, including 847 413 451 women with no restriction on age, race, or ethnicity. Most studies were of high methodological quality. The pooled rates of the five commonly reported causes of postpartum haemorrhage were uterine atony (70·6% [95% CI 63·9–77·3];n=834 707 women, 14 studies), genital tract trauma (16·9% [9·3–24·6];n=18 449 women, six studies), retained placenta (16·4% [12·3–20·5];n=235 021 women, nine studies), abnormal placentation (3·9% [0·1–7·6];n=29 638 women, two studies), and coagulopathy (2·7% [0·8–4·5];n=236 261, nine studies). The pooled rate of women with multiple postpartum haemorrhage causes was 7·8% (95% CI 4·7–10·8;n=666, two studies). Risk factors with a strong association with postpartum haemorrhage included anaemia, previous postpartum haemorrhag

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NMD-mediated posttranscriptional regulation fine-tunes the NLR-WRKY regulatory module to modulate bacterial defense response

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Plant Science 2025年 356卷 112528页

作者： Nasim, Zeeshan Karim, Nouroz Blilou, Ikram Ahn, Ji Hoon Department of Molecular Life Sciences Korea University Seoul 02841 South Korea Plant Science Program Biological and Environmental Science and Engineering Division (BESE) King Abdullah University of Science and Technology (KAUST) Thuwal 23955-6900 Saudi Arabia

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance system that maintains transcriptome integrity by degrading aberrant RNA transcripts. NMD ensures proper growth and development by preventing autoimmunity through the direct regulation of nucleotide-binding, leucine-rich repeat (NLR) genes. Whether NMD directly regulates WRKY genes remains unclear, despite their upregulation in NMD-deficient plants, and potential feedback between NLRs and WRKYs is also poorly understood. In this study, we showed that NMD also directly regulates a subset of WRKY (WRKY15, 18, 25, 33, 46, 60, and 70) genes, particularly at lower temperatures (16°C). NMD signature-containing transcripts of WRKY46 and WRKY70, selected as representative NMD-regulated WRKY genes, showed increased half-lives in NMD-deficient mutants. Transcriptome analyses showed that these seven NMD-regulated WRKY genes are induced in response to bacterial infection. Potential homologues of these seven NMD-regulated WRKY genes in maize and rice showed similar induction in response to bacterial pathogen infection. Furthermore, these NMD-regulated WRKY genes are induced in plants overexpressing RESISTANT TO P. SYRINGAE 4 (RPS4) in a temperature-dependent manner. By using ChIP-seq and DAP-seq data of WRKY transcription factors, we showed that WRKYs potentially regulate a significant number of NLR genes by directly binding to the W-box in their promoter regions. Taken together, our findings revealed that in addition to the NLRs, the NMD machinery also regulates WRKY genes to keep the basal defense levels in check and the WRKY transcription factors directly regulate NLR genes to constitutes a positive feedback regulatory loop to optimize the plant response to invading pathogens. © 2025 Elsevier B.V.

关键词： Arabidopsis Defense NLR NMD UPF WRKY

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Human induced pluripotent stem cell derived nanovesicles for cardiomyocyte protection and proliferation

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Bioactive Materials 2025年 50卷 585-602页

作者： Wei, Yuhua Geng, Xiaoxiao You, Qing Zhang, Yu Cao, Fangfang Narayanan, Gunaseelan Nguyen, Thanh Chen, Xiaoyuan Zhang, Jianyi Ye, Lei Department of Diagnostic Radiology Yong Loo Lin School of Medicine National University of Singapore 1190742 United States Department of Chemical and Biomolecular Engineering College of Design and Engineering National University of Singapore 1175753 Singapore Department of Biomedical Engineering College of Design and Engineering National University of Singapore 1175754 Singapore Department of Pharmacy and Pharmaceutical Sciences Faculty of Science National University of Singapore 1175445 Singapore Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore 1175996 Singapore Nanomedicine Translational Research Program Yong Loo Lin School of Medicine National University of Singapore 1175977 Singapore Theranostics Center of Excellence (TCE) Yong Loo Lin School of Medicine National University of Singapore 1386678 Singapore Institute of Molecular and Cell Biology Agency for Science Technology and Research (A∗STAR) 138673 United States

It remains a significant challenge to reactivate the cell cycle activity of adult mammalian cardiomyocytes (CMs). This study created a hypo-immunogenic human induced pluripotent stem cell (hiPSC) line using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 gene editing to knockout β2-microglobulin in hiPSCs (^B2MKOhiPSCs) for manufacturing nanovesicles (^B2MKOhiPSC-NVs). Approximately 9500 ^B2MKOhiPSC-NVs were produced from a single ^B2MKOhiPSC. Proteomic analyses indicated that, compared to ^B2MKOhiPSCs, the cargos of ^B2MKOhiPSC-NVs were enriched in spindle and chromosomal proteins, as well as proteins that regulate the cell cycle and scavenge reactive oxygen species (ROS). When administrated to hiPSCs derived CMs (hiPSC-CMs), ^B2MKOhiPSC-NVs reduced lactate dehydrogenase leakage and apoptosis in hypoxia-cultured hiPSC-CMs through activating the AKT pathway, protected hiPSC-CMs from H₂O₂-induced damage by ROS scavengers in the NV cargo, increased hiPSC-CM proliferation via the YAP pathway, and were hypoimmunogenic when co-cultured with human CD8⁺ T cells or delivered to mice. Furthermore, when ^B2MKOhiPSC-NVs or 0.9 % NaCl were intramyocardially injected into mice after cardiac ischemia/reperfusion injury, cardiac function and infarct size, assessed 4 weeks later, were significantly improved in the ^B2MKOhiPSC-NV group, with increased mouse CM survival and cell cycle activity. Thus, the proteins in the ^B2MKOhiPSC-NV cargos convergently activated the AKT pathway, scavenged ROS to protect CMs, and upregulated YAP signaling to induce CM cell cycle activity. Thus, ^B2MKOhiPSC-NVs hold great potential for cardiac protection and regeneration. © 2025 The Authors

关键词： Cell cycle Myocardial protection Nanovesicles Pluripotent stem cells Regeneration

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Biomedical data and AI

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Science China Life sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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Cell-Instructive Biomaterials with Native-Like Biochemical Complexity

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Annual review of biomedical engineering 2025年第1期27卷 185-209页

作者： Marjan, Tuba Lafuente-Gómez, Nuria Rampal, Akaansha Mooney, David J. Peyton, Shelly R. Qazi, Taimoor H. Weldon School of Biomedical Engineering Purdue University West Lafayette Indiana USA email: tqazi@purdue.edu John A. Paulson School of Engineering and Applied Sciences Harvard University Cambridge Massachusetts USA email: mooneyd@seas.harvard.edu Wyss Institute for Biologically Inspired Engineering at Harvard University Boston MA United States Molecular and Cellular Biology Graduate Program University of Massachusetts Amherst MA United States John A. Paulson School of Engineering and Applied Sciences Harvard University Cambridge Massachusetts USA email: Department of Chemical Engineering University of Massachusetts Amherst MA United States Department of Biomedical Engineering Tufts University Medford Massachusetts USA email: Weldon School of Biomedical Engineering Purdue University West Lafayette Indiana USA email:

Biochemical signals in native tissue microenvironments instruct cell behavior during many biological processes ranging from developmental morphogenesis and tissue regeneration to tumor metastasis and disease progression. The detection and characterization of these signals using spatial and highly resolved quantitative methods have revealed their existence as matricellular proteins in the matrisome, some of which are bound to the extracellular matrix while others are freely diffusing. Including these biochemical signals in engineered biomaterials can impart enhanced functionality and native-like complexity, ultimately benefiting efforts to understand, model, and treat various diseases. In this review, we discuss advances in characterizing, mimicking, and harnessing biochemical signals in developing advanced engineered biomaterials. An overview of the diverse forms in which these biochemical signals exist and their effects on intracellular signal transduction is also provided. Finally, we highlight the application of biochemically complex biomaterials in the three broadly defined areas of tissue regeneration, immunoengineering, and organoid morphogenesis.

关键词： biomimetic scaffolds cell-adhesive ligands ECM extracellular matrix matricellular matrisome

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