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CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells

world journal of Gastroenterology 2013年第17期19卷 2621-2628页

作者： jános P Kósa Péter Horváth jános wlfling Dóra Kovács Bernadett Balla Péter Mátyus Evelin Horváth Gábor Speer István Takács Zsolt Nagy Henrik Horváth Péter Lakatos 1 st Department of Internal Medicine Semmelweis University Department of Organic Chemistry University of Szeged Department of Organic Chemistry Semmelweis University

AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:we examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.

关键词： Colorectal cancer CYP24A1 inhibition Vitamin D3 Tetralone derivatives Caco-2 cell culture

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Two examples of surfaces with normal crossing singularities

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Science China Mathematics 2011年第8期54卷 1707-1712页

作者： KOLLR jános Department of Mathematics Princeton University

This note gives two examples of surfaces with normal crossing *** the first example the canonical ring is not finitely *** the second,the canonical line bundle is not ample but its pull back to the normalization is *** latter answers in the negative a problem left unresolved in Ⅲ.2.6.2 of lments de gometrie algbrique,1961,and raised again by Viehweg.

关键词： singular surface canonical ring ampleness criteria

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Moduli of Polarized Calabi–Yau Pairs

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Acta Mathematica Sinica,English Series 2020年第6期36卷 631-637页

作者： jános KOLLáR Chen Yang XU Princeton University Princeton NJ 08544-1000USA MIT CambridgeMA 02139-4307USA

we prove that the irreducible components of the moduli space of polarized Calabi–Yau pairs are projective.

关键词： Polarized Calabi–Yau stable pairs Moduli spaces

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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

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A Tutorial Review of the Solar Power Curve: Regressions, Model Chains, and Their Hybridization and Probabilistic Extensions

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Advances in Atmospheric Sciences 2024年第6期41卷 1023-1067页

作者： Dazhi YANG Xiang’ao XIA Martin jános MAYER School of Electrical Engineering and Automation Harbin Institute of TechnologyHarbin 150001HeilongjiangChina Key Laboratory for Middle Atmosphere and Global Environment Observation(LAGEO) Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Department of Energy Engineering Faculty of Mechanical EngineeringBudapest University of Technology and EconomicsMűegyetem rkp.3Budapest H-1111Hungary

Owing to the persisting hype in pushing toward global carbon neutrality,the study scope of atmospheric science is rapidly *** numerous trending topics,energy meteorology has been attracting the most attention *** essential skill of solar energy meteorologists is solar power curve modeling,which seeks to map irradiance and auxiliary weather variables to solar power,by statistical and/or physical *** this regard,this tutorial review aims to deliver a complete overview of those fundamental scientific and engineering principles pertaining to the solar power *** power curves can be modeled in two primary ways,one of regression and the other of model *** classes of modeling approaches,alongside their hybridization and probabilistic extensions,which allow accuracy improvement and uncertainty quantification,are scrutinized and contrasted thoroughly in this review.

关键词： review energy meteorology solar power curve model chain solar power prediction

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Drying of suspensions and solutions on inert particle surface in mechanically spouted bed dryer

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China Particuology 2007年第5期5卷 337-344页

作者： Elisabeth Pallai-Varsányi judit Tóth jános Gyenis University of Pannonia Faculty of Information TechnologyResearch Institute of Chemical and Process Engineering Egyetem u. 2H-8200 VeszprémHungary Hungarian Academy of Sciences Chemical Research CentreInstitute of Materials and Environmental ChemistryPusztaszeri u. 59-67H-1025 BudapestHungary

To eliminate some disadvantages of the conventional spouted bed dryers the mechanically spouted bed （MSB） system was developed. This dryer type is convenient to use inert particles providing an increased surface area for drying of materials of high-moisture content and heat sensitive materials. On three different drying tasks are demonstrated the experimental optimization of process parameters to obtain products of demanded quality. The main object was at drying of AIO（OH） suspension to preserve the particle size under 2.5μm and to obtain product with a moisture content of about 0.05 kg/kg （d.b.）. For this reason a very thin particle coating and intensive abrasion had to be assured. At drying of tomato concentrates the thermoplasticity makes the process very difficult. To jump over the deliquescent and sticky state developed at the critical temperature-moisture content values a very short drying time （8-10 s） must be provided. The third task was to form powder-like product from bovine serum albumin （BSA） solution having very low solid content （2-4%）. The selected process parameters given in this paper resulted in a mean particle size of less than 20 μm while the soluble oreserved orotein content was higher than 90%.

关键词： Mechanically spouted bed Film-like drying Inert particles Heat sensitive material

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NEw wAYS TO OBTAIN NEw ANTIBIOTICS

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中国抗生素杂志 1984年第4期9卷 348-360页

作者： jános Bérdy Budapest Hungary Institute for Drug Research

The antibiotic research is one ofthe most productive and successfulareas of the natural product *** early forties up to now more than9000 natural products were discoveredwhich have some antimicrobial, antiviral,antitumor or similar activities. Table1. illustrates the approximate numberof presently known antibiotic compoundsaccording to their main sources. The numbers in Table 1. include

关键词： than NEw wAYS TO OBTAIN NEw ANTIBIOTICS OI

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A remark on density theorems for Riemann's zeta-function

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Science China Mathematics 2023年第12期66卷 2795-2802页

作者： janos Pintz ELKH Alfréd Rényi Mathematical Institute Budapest H-1053Hungary

The goal of this paper is to give a relatively simple proof of some known zero density estimates for Riemann's zeta-function which are sufficiently strong to break the density hypothesis for Re s>7/*** from a simple but ingenious idea of Halász the proof uses only classical knowledge about the zeta-function,results known for at least hundred years.

关键词： Riemann's zeta-function density hypothesis density theorems

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A novel method for clustering cellular data to improve classification

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Neural Regeneration Research 2025年第9期20卷 2697-2705页

作者： Diek w.wheeler Giorgio A.Ascoli Center for Neural Informatics Structures&PlasticityKrasnow Institute for Advanced Study Bioengineering Department Volgenau School of Engineering George Mason University FairfaxVAUSA

Many fields,such as neuroscience,are experiencing the vast prolife ration of cellular data,underscoring the need fo r organizing and interpreting large datasets.A popular approach partitions data into manageable subsets via hierarchical clustering,but objective methods to determine the appropriate classification granularity are *** recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within *** we present the corresponding protocol to classify cellular datasets by combining datadriven unsupervised hierarchical clustering with statistical *** general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values,including molecula r,physiological,and anatomical *** demonstrate the protocol using cellular data from the janelia MouseLight project to chara cterize morphological aspects of neurons.

关键词： cellular data clustering dendrogram data classification Levene's one-tailed statistical test unsupervised hierarchical clustering

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Start the Earth System Governance that Integrates “Climate-Altering Technologies”

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Chinese journal of Urban and Environmental Studies 2020年第2期8卷 136-140页

作者： jános PáSZTOR Carnegie Climate Governance Initiative (C2G)

Addressing climate emergencies requires a radical social change, and an “earth system” governance approach that combines different factors(including technologies that affect climate). As the Paris Agreement has been reached for four years and came into force for three years, there is a growing recognition that the global average temperature rise cannot be limited to 1.5–2°C only by emissions reduction or existing carbon removal measures. The reason is that the world has not taken enough actions to deal with the crisis. As reported by IPCC(2018), hundreds of millions of people worldwide are already experiencing the harsh consequences of climate change, from storms to floods, to heatwaves and droughts [IPCC. 2018. “International Panel on Climate Change Special Report on Global warming of 1.5 Degrees.” https://***/sr15(accessed November 5, 2019)]. According to Spratt and Dunlop(2019), as the climate change intensifies,all sectors of society have realized the need to avoid the risks brought by climate change and to deal with the severe disasters that already exist [Spratt, David, and Ian Dunlop. 2019.“Existential Climate-related Security Risk: A Scenario Approach.” https://***/ugd/***(accessed November 5, 2019)]. This raises some profound questions. For instances, should people consider a new responsive measure that is compatible with the natural system which sustains life on the earth, and within the limits of the earth’s tolerance? what forms of decision-making might we need, to help us make the smart collective choices needed for a world where no risk-free options remain? Are familiar governance and decision-making processes still suitable for the goals? who will make the decisions to promote this transformation? If people really want to change the way they make decisions, they may need to create new forms of governance and decide how this transformation begins and which authority is subject to.

关键词： climate-altering technology Earth system governance shared learning platform

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