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Miyaoka-type inequalities for terminal threefolds with nef anti-canonical divisors

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Science China Mathematics 2025年第1期68卷 1-18页

作者： Masataka Iwai Chen Jiang Haidong Liu Department of Mathematics Graduate School of ScienceOsaka University Shanghai Center for Mathematical sciences & School of Mathematical sciences Fudan University Department of mathematics Sun Yat-sen University

In this paper,we study Miyaoka-type inequalities on Chern classes of terminal projective 3-folds with nef anti-canonical *** X be a terminal projective 3-fold such that-KXis *** show that if c1（X） · c2（X）≠0,then c1（X） · c2（X） ≥ 1/252;if further X is not rationally connected,then c1（X） · c2（X） ≥ 4/5 and this inequality is *** order to prove this,we give a partial classification of such varieties along with many *** also study the nonvanishing of c1（X）dim X-2· c2（X） for terminal weak Fano varieties and prove a Miyaoka-Kawamata-type inequality.

关键词： terminal threefolds Miyaoka-type inequality boundedness

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher J.O’Connell Matthew J.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience graduate program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin Lim Department of Biochemistry&Molecular Biology Ajou University School of MedicineSuwonSouth Korea Department of Biomedical sciences Graduate School of Ajou UniversitySuwonSouth Korea Department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

Long-read sequencing reveals novel genetic polymorphisms in the major histocompatibility complex region and their impacts on the Han Chinese population

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Science China Life sciences 2025年

作者： Cong Zhou Tingting Gong Shuhang Li Li Jin Shaohua Fan State Key Laboratory of Genetic Engineering Lab for Evolutionary Synthesis School of Life Sciences Human Phenome Institute Fudan University Research Unit of Dissecting the Population Genetics and Developing New technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences

Human leukocyte antigen(HLA) genes in the major histocompatibility complex(MHC) region are crucial for immunity and are associated with numerous diseases and phenotypes. The MHC region's complexity and high genetic diversity make it challenging to analyze using short-read sequencing(SRS) technology. We sequence the MHC region of 100 Han Chinese individuals using both long-read sequencing(LRS) and SRS platforms at approximately 30X coverage to study genetic alterations and their potential functional impacts. LRS provides significantly greater coverage of the MHC region and eight classical HLA genes, particularly at the HLA-DRB1 locus, compared with SRS. We detect 78,249 single nucleotide polymorphisms(SNPs) using LRS, with 26.0% undetectable by SRS. Based on SNP and inferred HLA allele types, we construct an LRS-based MHC reference panel for the Han Chinese, containing approximately 2.6 times more genetic variants than the SRS-based Han-MHC reference panel. A phenome-wide association study assessing 26,024 phenotypes across 15 categories identifies significant associations for 7,879 independent variants(including 809 LRS-specific SNPs) with 409 phenotypes in nine categories. This analysis reveals 24 unreported HLA allele associations in the bioelectric and cellular categories. The conditional analysis identifies 530independent signals across the 409 phenotypes, including 28 previously unreported signals of eight classical HLA genes associated with 33phenotypes. Of the top-associated SNPs, 191 are detected by LRS only. Fine-mapping identifies 126 independent candidate causal SNPs for three immune-related cellular phenotypes, with 17 detected exclusively by LRS. Our study reveals previously unreported variants and their functional impacts in the MHC region, enhancing our understanding of genetic diversity and its potential biological implications in the Han Chinese population.

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Exit options sustain altruistic punishment and decrease the second-order free-riders, but it is not a panacea

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Science China(Information sciences) 2025年第1期68卷 278-291页

作者： Chen SHEN Zhao SONG Lei SHI Jun TANIMOTO Zhen WANG Faculty of Engineering sciences Kyushu University School of Statistics and Mathematics Yunnan University of Finance and Economics School of Computing Engineering and Digital Technologies Teesside University School of Artificial Intelligence OPtics and Electro Nics (iOPEN) Northwestern Polytechnical University

Why do humans punish free riders at their own expense? This behavior represents an evolutionary puzzle in human societies. This study explores the role of exit strategies in fostering altruistic punishment within evolutionary game theory. We extend the traditional prisoner's dilemma model by incorporating exiters, players who opt out for a small payoff while nullifying their opponent's payoff, and altruistic punishers who cooperate and punish non-cooperators. Our findings indicate that in well-mixed populations, exiters destabilize defection but do not promote altruistic punishment. In social networks, however,exiters enable altruistic punishment via cyclic dominance among altruistic punishers, defectors, and exiters. Notably, this cyclic dominance is sensitive to exit payoffs; adjustments can lead to cyclic dominance of non-punishing cooperators, defectors, and exiters, or to a bi-stable state between these two types of cyclic dominance. These results highlight the nuanced impact of exiters on altruistic punishment, emphasizing the need for careful incentivization of exit behavior. While exiters can support altruistic punishment in networked populations, their effectiveness is not a panacea and is highly sensitive to exit payoffs, indicating limits to the voluntary participation mechanism.

关键词： evolutionary game theory altruistic punishment coexistence cyclic dominance bi-stable

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

In vitro inhibitory effects of plumbagin,the promising antimalarial candidate,on human cytochrome P450 enzymes

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Asian Pacific Journal of Tropical Medicine 2015年第11期8卷 894-898页

作者： Wiriyaporn Sumsakul Wanna Chaijaroenkul Kesara Na-Bangchang graduate program in Biomedical sciences.Faculty of Allied health sciences Thammasat University Center of Excellence in Pharmacology and Molecular Biology Graduate Program in Bioclinical SciencesChulabhorn International College of MedicineThammasat University

Objective:To investigate the propensity of plumbagin to inhibit the three isoforms of human cytochrome P450(CYP),ie.,CYP1A2,CYP2C19,and CYP3A4 using human liver microsomes in ***:Inhibitory effects of plumbagin on the three human CYP isoformswere investigated using pooled human liver *** O-deethylation,omeprazole hydroxylation and nifedipine oxidation were used as selective substrates for CYP1A2,CYP2C19 and CYP3A4 activities,*** of paracetamol,5-hydroxyomeprazole,and oxidized nifedipine were determined in microsomal incubation mixture using high performance liquid ***:Plumbagin showed significantinhibitory effects on all CYP *** with the most potent activity on CYP2C19-mediated omeprazole *** IC50(concentration that inhibits enzyme activity by 50%) values of plumbagin and nootkatone(selective inhibitor) for CYP2C19 were(0.78±0.01) and(27.31±0.66) μM,*** inhibitory activities on CYP1 A2-mediated phenacetin O-deethylation and CYP3A4-mediated nifedipine oxidation were *** IC_(50) values of plumbagin and-naphthoflavone(selective inhibitor) for CYP1A2 were(1.39±0.01) and(0.02±.0.36) μM,*** corresponding IC_(50) values of plumbagin and ketoconazole(selective inhibitor) for CYP3A4 were(2.37+0.10) and(0.18±0.06) μM,***:Clinical relevance of the interference of human drug metabolizing enzymes should be aware of for further development scheme of plumbagin as antimalarial drug when used in combination with other antimalarial drugs which are metabolized by these CYP isoforms.

关键词： Metabolism Human liver microsomes Plumbagin Cytoch

Physical Implementation of the Eight-Core Godson-3B Microprocessor

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Journal of Computer Science & Technology 2011年第3期26卷 520-527页

作者：王茹范宝峡杨梁高燕萍刘动肖斌王江嵋张译夫王宏胡伟武 Institute of Computing Technology Chinese Academy of Sciences graduate School of Chinese Academy of sciences Loongson technologies Corporation Limited

The Godson-3B processor is a powerful processor designed for high performance servers including Dawning Servers. It offers significantly improved performance over previous Godson-3 series CPUs by incorporating eight CPU cores and vector computing units. It contains 582.6 M transistors within 300 mm2 area in 65 nm technology and is implemented in parallel with full hierarchical design flows. In Godson-3B, advanced clock distribution mechanisms including GALS （Globally Asynchronous Locally Synchronous） and clock mesh are adopted to obtain an OCV tolerable clock network. Custom-designed de-skew modules are also implemented to afford further latency balance after fabrication. The power reduction of Godson- 3B is maintained by MLMM （Multi Level Multi Mode） clock gating and multi-threshold-voltage cells substitution schemes. The highest frequency of Godson-3B is 1.05 GHz and the peak performance is 128 GFlops （double-precision） or 256 GFlops （single-precision） with 40 W power consumption.

关键词： physical implementation hierarchical design flow GALS clock mesh low power