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A novel acquired resistance mechanism to 5-aminolevulinic acid-mediated photodynamic therapy with ABCG2 inhibition. ABCG2抑制5-氨基乙酰丙酸介导的光动力治疗的新获得性耐药机制。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-02-03 DOI: 10.1111/php.14077
Sharayu Chandratre, Jordyn Olsen, Bin Chen

We report the occurrence of acquired tumor cell resistance to 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) in combination with ABCG2 inhibition. ALA-PDT in combination with either an ABCG2 tool inhibitor Ko143 or a repurposed clinically-relevant ABCG2 inhibitor lapatinib was highly effective in eradicating the H4 human glioma cells, resulting in minimal cell survival after treatment. However, after seven rounds of repeated treatments with light dose escalation, the resultant tumor cells became resistant to the combination therapy. The resistant sublines and the parental cell line showed similar ABCG2 activities and protein levels, indicating that it was not ABCG2 that caused the resistance. They also exhibited similar responses to PpIX-PDT and mTOR inhibitor AZD2014, suggesting that alterations in PDT sensitivity and mTOR pathway had little contribution to the development of resistance phenotype. By determining the intracellular and extracellular PpIX levels, the activities and protein levels of heme biosynthesis enzymes, we found that porphobilinogen deaminase (PBGD) activity and protein level were significantly reduced in the resistant sublines, causing resistance to PDT by substantially reducing PpIX biosynthesis. A novel acquired resistance mechanism to ALA-PDT with ABCG2 inhibition has been uncovered.

我们报道了获得性肿瘤细胞对5-氨基乙酰丙酸(ALA)介导的光动力治疗(PDT)联合ABCG2抑制的耐药性。ALA-PDT联合ABCG2工具抑制剂Ko143或重新定位的临床相关ABCG2抑制剂拉帕替尼在根除H4人胶质瘤细胞方面非常有效,治疗后细胞存活率最低。然而,经过7轮轻剂量递增的重复治疗后,所产生的肿瘤细胞对联合治疗产生了耐药性。抗性亚系与亲本细胞系表现出相似的ABCG2活性和蛋白水平,表明ABCG2不是引起抗性的原因。它们对PpIX-PDT和mTOR抑制剂AZD2014也表现出类似的反应,这表明PDT敏感性和mTOR途径的改变对耐药表型的发展贡献不大。通过测定细胞内和细胞外PpIX水平、血红素生物合成酶活性和蛋白水平,我们发现耐药亚系中卟啉胆色素原脱氨酶(porphobilinogen deaminase, PBGD)活性和蛋白水平显著降低,通过大幅减少PpIX的生物合成而对PDT产生抗性。ABCG2抑制ALA-PDT的一种新的获得性耐药机制已经被发现。
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引用次数: 0
Photodynamic treatment in glioma: Metabolic and structural evaluation after therapy. 胶质瘤的光动力治疗:治疗后的代谢和结构评价。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-07 DOI: 10.1111/php.70032
Marina Gabriela Teixeira, Luciana Maria Cortez Marcolino, Juliana Guerra Pinto, Rainara Moreno Sanches de Almeida, Isabelle Ferreira, Juliana Ferreira-Strixino

Gliomas are malignant tumors of the central nervous system, and one severe variant is called gliosarcoma. Photodynamic therapy (PDT) is a technique that stands out in the oncology area for minimizing side effects for the patient, triggering cell death at the site of irradiation, and can be used concomitantly with conventional treatments. This study aimed to evaluate the interaction of chlorine e6 with the cytoskeleton and mitochondria, as well as morphological changes and the death mechanism triggered after PDT. Chlorin e6 was used at concentrations of 200, 12.5, and 6.25 μg/mL, and cytoskeletal changes were analyzed by alpha-tubulin staining and mitochondrial membrane potential (MMP) analysis by JC-1 and Rhodamine 123 in flow cytometry. Surface features were examined using scanning electron microscopy, and the type of cell death mechanism was determined by flow cytometry with annexin and propidium iodide. Changes in the cytoskeleton were observed after PDT. Cytometry showed that cell death occurred predominantly via the apoptosis pathway, followed by the necrosis pathway. Chlorin e6 associated with PDT causes damage to gliosarcoma cells, regardless of concentration, showing cytoskeletal disruption, a decrease in MMP, and the percentage of cell death varies according to the concentration of PS.

胶质瘤是中枢神经系统的恶性肿瘤,其中一种严重的变体被称为胶质瘤肉瘤。光动力疗法(PDT)是一项在肿瘤领域脱颖而出的技术,因为它可以最大限度地减少患者的副作用,在照射部位触发细胞死亡,并且可以与常规治疗同时使用。本研究旨在探讨氯e6与细胞骨架和线粒体的相互作用,以及PDT后引起的形态学变化和死亡机制。氯胺e6浓度分别为200、12.5和6.25 μg/mL,流式细胞术中采用α -微管蛋白染色和JC-1、罗丹明123线粒体膜电位(MMP)分析分析细胞骨架的变化。用扫描电镜观察其表面特征,用膜联蛋白和碘化丙啶流式细胞术测定细胞死亡机制。PDT后观察到细胞骨架的变化。细胞计数显示细胞死亡主要通过凋亡途径发生,其次是坏死途径。与PDT相关的氯e6对胶质肉瘤细胞造成损伤,无论浓度如何,均表现为细胞骨架破坏,MMP降低,细胞死亡百分比随PS浓度而变化。
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引用次数: 0
Grape constituents for protection against photodamage to skin. 保护皮肤免受光损伤的葡萄成分。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-05-21 DOI: 10.1111/php.14110
Yuri Kwon, Rubina Shafi, Allen Oak, Mohammad Athar, Andrzej Slominski, Craig A Elmets

Cutaneous overexposure to ultraviolet radiation has a variety of deleterious effects. The extent to which dietary factors are effective at moderating UV damage is a significant issue. Grapes contain phytochemicals that protect against excessive UV damage. Components of grapes, in particular resveratrol, proanthocyanidins, and cyanidin-3-glucoside, are receiving considerable attention for their photoprotective actions because of their lack of toxicity, abundance, and low cost. Resveratrol and proanthocyanidins are potent antioxidants that interfere with signal transduction and immunosuppressive pathways activated by UV radiation, which are responsible for its harmful effects. Studies in humans provide a rationale for their further development as a novel method of photoprotection.

皮肤过度暴露于紫外线辐射有多种有害影响。饮食因素在多大程度上有效地减缓紫外线伤害是一个重要的问题。葡萄含有植物化学物质,可以防止过度的紫外线伤害。葡萄成分,特别是白藜芦醇、原花青素和花青素-3-葡萄糖苷,由于其毒性低、含量丰富和价格低廉,其光保护作用受到了广泛的关注。白藜芦醇和原花青素是有效的抗氧化剂,干扰紫外线辐射激活的信号转导和免疫抑制途径,这是其有害影响的原因。对人体的研究为其作为一种新型光防护方法的进一步发展提供了理论依据。
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引用次数: 0
Long-term sub-erythemal UVB exposure does not impact circadian rhythms in mice under standard and rotating shift light conditions. 在标准和旋转移位光条件下,长期暴露于红斑下的UVB不会影响小鼠的昼夜节律。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-03-26 DOI: 10.1111/php.14081
Adam J Greer, Sean J Cone, Rachel Bernstein, Elizabeth Schuetz, Narayani Prasad Kar, Bala S C Koritala, Shobhan Gaddameedhi

The International Agency for Research on Cancer (IARC) stated that circadian disruption is a potential carcinogen. However, the impact of environmental carcinogens, including sub-erythemal doses of UVB exposure, on circadian rhythms remains unclear. We evaluated the impact of long-term rotating shift, loss of Per1/2 genes, and chronic UVB exposure on the circadian rhythms of SKH-1 mice for up to 7 months. Real-time locomotion and circadian gene expression were measured in these animals. Mice under rotating shift exhibited a longer period of activity of up to 25.20 h, while those under standard light conditions had a clear 24-h rhythm. mPer1/mPer2 mice, conversely, displayed a shortened period of activity of 23.61 h. Interestingly, chronic UVB exposure had no impact on activity rhythms, though it induced skin tumors in all mice. Rotating shift and loss of mPer1/mPer2 led to circadian dysregulation of all core clock genes, with a notable phase difference in Cry1. These findings provide novel insights into environmental and genetic influences on circadian rhythms.

国际癌症研究机构(IARC)指出,昼夜节律紊乱是一种潜在的致癌物。然而,环境致癌物,包括亚红斑剂量的UVB暴露,对昼夜节律的影响尚不清楚。我们评估了长期轮班、Per1/2基因缺失和慢性UVB暴露对SKH-1小鼠昼夜节律长达7个月的影响。测量这些动物的实时运动和昼夜节律基因表达。旋转移位小鼠的活动周期较长,可达25.20 h,而标准光照条件下的小鼠具有明显的24小时节律。相反,mPer1/mPer2小鼠的活动时间缩短为23.61 h。有趣的是,长期暴露在UVB中对活动节律没有影响,尽管它会在所有小鼠中诱发皮肤肿瘤。mPer1/mPer2的旋转移位和缺失导致所有核心时钟基因的昼夜节律失调,其中Cry1的相位差显著。这些发现为环境和基因对昼夜节律的影响提供了新的见解。
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引用次数: 0
A skin explant model for studying UV-induced DNA damage and repair. 研究紫外线诱导DNA损伤及修复的皮肤外植体模型。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-02-03 DOI: 10.1111/php.14070
Hailey Payne, Christina Athans, Shiyong Wu, Veronica Bahamondes Lorca

There is a growing need for a skin model that combines the natural physiology of skin while reducing reliance on mice. Natural physiology is achieved by using fresh, intact skin explants sourced from living organisms such as humans or mice. This study focused on the standardization and characterization of an in vitro mouse skin explant model for investigating solar ultraviolet (sUV)-induced skin damage. We developed a protocol to use skin explants derived from the discarded tissue of mice after euthanasia. These explants consist of intact dermal and epidermal layers suspended in cell culture medium and maintained in vitro. To assess the viability of the skin explants, we evaluated tissue morphology (via hematoxylin and eosin [H&E] staining), viability markers, and DNA damage markers. Our ex vivo model preserves the key characteristics and physiological responses of in vivo skin for short incubation periods, while minimizing the use of mice. This model enables the study of DNA damage and repair, and it has broad applications, including studies on skin photoprotection, topical treatments, drug development, and cosmetics.

人们越来越需要一种结合皮肤自然生理学的皮肤模型,同时减少对小鼠的依赖。自然生理学是通过使用新鲜的、完整的皮肤外植体来实现的,这些皮肤外植体来自于活的有机体,如人类或老鼠。本研究的重点是研究太阳紫外线(sUV)诱导的皮肤损伤的小鼠皮肤外植体模型的标准化和表征。我们制定了一项方案,使用来自安乐死后小鼠丢弃组织的皮肤外植体。这些外植体由完整的真皮和表皮层组成,悬浮在细胞培养基中并在体外维持。为了评估皮肤外植体的活力,我们评估了组织形态(通过苏木精和伊红[H&E]染色)、活力标记和DNA损伤标记。我们的体外模型在短潜伏期内保留了体内皮肤的关键特征和生理反应,同时最大限度地减少了小鼠的使用。该模型能够研究DNA损伤和修复,并且具有广泛的应用,包括皮肤光保护,局部治疗,药物开发和化妆品的研究。
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引用次数: 0
Spectral comparison between diffuse PAR irradiance received under the shade of nine trees in different heights and a cloudy day in summer. 9棵树不同高度树荫下与夏季阴天的漫射PAR辐照度光谱比较。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-01-27 DOI: 10.1111/php.14074
Gonzalo Gurrea-Ysasi, Vicente Blanca-Gimenez

Spectral Solar Photosynthetically Photon Flux Density (PPFD) (380-780 nm) reaching the surface in different tree shade conditions and heights has been analyzed in order to better understand the different photosynthetic performance of plants depending on their spatial situation, the canopy density and height with respect to the floor. A comparison between the shadow of nine different trees in a sunny day and the case of a cloudy day in an open space has been studied. A poplar, laurel, amber tree, pine, olive tree, fir tree, cypress, elm tree and magnolia tree have been analyzed. The study has been developed in Valencia (Spain) during July and August 2022. Conditions with higher PPFD received are found to be, apart from those of a sunny day, those for cloudy day, and those for the shade of cypress. The case in which less amount of PPFD is received is that under the shade of olive tree. Both with a spectral maximum in the Blue region. It is also remarkable that the PPFD radiation is proportional to the height of measurement at 10 h, but this relationship changes, and at 13 h the relationship between irradiance received and height of measurement is inversely proportional.

为了更好地了解植物在不同的空间环境、冠层密度和相对于地面的高度下的不同光合作用性能,我们分析了在不同树荫条件和高度下到达地表的光谱太阳光合作用光子通量密度(PPFD) (380-780 nm)。对晴天和阴天在空地上九棵不同树木的阴影进行了比较研究。对杨树、月桂树、琥珀树、松树、橄榄树、冷杉树、柏树、榆树和木兰树进行了分析。该研究于2022年7月和8月在西班牙瓦伦西亚进行。得到较高PPFD的条件除晴天外,还有阴天和柏树树荫。在橄榄树树荫下,收到的PPFD量较少。两者的光谱最大值都在蓝色区域。同样值得注意的是,PPFD辐射在10 h时与测量高度成正比,但这种关系发生了变化,在13 h时,接收到的辐照度与测量高度成反比。
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引用次数: 0
Ozone as a method for decontamination of dissolving microneedles for clinical use. 臭氧作为临床用溶解性微针的去污方法。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-01-29 DOI: 10.1111/php.14068
Michelle B Requena, Thaila Q Corrêa, Dianeth Sara L Bejar, Juliana C Barreiro, Kelly T de Paula, Vanderlei S Bagnato

Dissolving microneedles (DMNs) is a promising technology for transdermal and intradermal drug delivery. However, effective decontamination protocols are necessary to ensure safety and efficacy in clinical applications. The challenge is to use a technique that preserves mechanical properties, does not introduce chemicals, and can decontaminate DMNs without affecting the drug. With its potent antimicrobial properties and minimal residual effects, ozone presents a novel and safe method for decontaminating DMNs. Specifically, the present study assesses ozone's efficacy in decontaminating DMNs loaded with aminolevulic acid, intended for photodynamic therapy in skin cancer treatment. The results showed that it effectively decontaminates E. coli and S. aureus without compromising the polymer properties or promoting drug degradation. Overall, ozone represents an approach that can be adopted to decontaminate DMNs, offering a safer and effective strategy that enhances their potential to translate to clinical application.

溶解微针(DMNs)是一种很有前途的经皮和皮内给药技术。然而,有效的去污方案是必要的,以确保在临床应用的安全性和有效性。挑战在于使用一种既能保持机械特性,又不引入化学物质,又能在不影响药物的情况下净化dmn的技术。臭氧具有强大的抗菌性能和最小的残留效应,是一种新的、安全的净化DMNs的方法。具体地说,本研究评估了臭氧在净化含有氨基乙酰酸的DMNs中的功效,该DMNs用于皮肤癌的光动力治疗。结果表明,它能有效地去除大肠杆菌和金黄色葡萄球菌,而不影响聚合物的性质或促进药物的降解。总的来说,臭氧代表了一种可以用来净化DMNs的方法,提供了一种更安全有效的策略,提高了它们转化为临床应用的潜力。
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引用次数: 0
Effect of the naphthylene linker on the J-aggregation abilities of chlorophyll-a derivatives. 萘链对叶绿素-a 衍生物 J-聚集能力的影响。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-02-13 DOI: 10.1111/php.14076
Yuma Hisahara, Takeo Nakano, Hitoshi Tamiaki

Chlorophyll(Chl)-a derivatives inserting an ethynylene-naphthylene linker between the chlorin π-skeleton and hydroxymethyl group were prepared as models of chlorosomal Chls. Their syntheses were achieved via Sonogashira coupling reaction. Their J-aggregation behaviors were investigated by electronic absorption and circular dichroism spectroscopic measurements. These studies revealed that the 2,6-naphthylene inserted Chl-a derivatives gave the single J-aggregation species in an aqueous Triton X-100 micellar solution with a larger red-shift value (1270 cm-1) of the Qy band in spite of its longer linker compared with p-phenylene inserted Chl-a derivative (970 cm-1). These unique optical properties were also discussed based on the computational studies, which indicated the different positional relation of chlorin rings in the assemblies by the linker structure.

制备了在氯π骨架和羟甲基之间插入乙烯-萘连接体的叶绿素(Chl)衍生物作为叶绿体Chl的模型。它们是通过Sonogashira偶联反应合成的。通过电子吸收和圆二色光谱测量研究了它们的j聚集行为。这些研究表明,在Triton X-100胶束水溶液中,2,6-萘插入的Chl-a衍生物与对苯基插入的Chl-a衍生物(970 cm-1)相比,其连接体较长,但其Qy波段的红移值(1270 cm-1)更大。在计算的基础上对这些独特的光学性质进行了讨论,揭示了连接体结构对氯环在组装体中的不同位置关系的影响。
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引用次数: 0
Reactive oxygen species are involved in inhibition of photoreactivation of Staphylococcus aureus irradiated with 222-nm Far ultraviolet C. 活性氧参与了222nm远紫外C辐射对金黄色葡萄球菌光活化的抑制作用。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-02-03 DOI: 10.1111/php.14065
Risako Fukushi, Kouji Narita, Kyosuke Yamane, Toru Koi, Krisana Asano, Akio Nakane

Ultraviolet-C (UV-C) at a wavelength of 254 nm is used for disinfection but cannot be used in dwelling space because it is harmful to the human body, while 222-nm Far UV-C shows germicidal effect and poses little hazardous effect to human. Formation of cyclobutane pyrimidine dimers (CPD) of DNA is a main mechanism of UV-C germicidal effect. CPD formed by irradiation with 254-nm UV-C is repaired and bacterial proliferation is recovered by photoreactivation. In this study, we investigated photoreactivation of Staphylococcus aureus irradiated with 222-nm Far UV-C. The proliferative effect of 222-nm Far UV-C irradiated S. aureus by photoreactivation was inferior to that of irradiated with 254-nm UV-C. The 254-nm UV-C wavelength and 222-nm Far UV-C induced CPD in S. aureus cells, and the same level of CPD was repaired in cells irradiated with either UV-C after photoreactivation. It has been reported that UV-C induces generation of reactive oxygen species (ROS) in bacteria and that ROS oxidize and inactivate a variety of biomolecules in bacteria. This study showed that more ROS-producing S. aureus were observed after irradiation with 222-nm Far UV-C compared with 254-nm UV-C. These results indicate that ROS may be involved in lower recovery of 222-nm Far UV-C irradiated S. aureus by photoreactivation.

波长为254纳米的紫外线c (UV-C)用于消毒,但对人体有害,不能用于居住空间;而波长为222纳米的远紫外线c则具有杀菌作用,对人体的危害很小。DNA的环丁烷嘧啶二聚体(CPD)的形成是UV-C杀菌作用的主要机制。在254 nm UV-C照射下形成的CPD被修复,细菌增殖通过光再激活恢复。在本研究中,我们研究了222nm远紫外辐射对金黄色葡萄球菌的光活化作用。222nm远紫外- c光活化对金黄色葡萄球菌的增殖作用不如254nm远紫外- c。波长为254 nm的UV-C和222 nm的远紫外- c诱导金黄色葡萄球菌细胞发生CPD,两种UV-C照射的细胞在光活化后均可修复相同水平的CPD。据报道,UV-C诱导细菌产生活性氧(ROS), ROS氧化和灭活细菌中的多种生物分子。本研究表明,222 nm的远紫外- c比254 nm的远紫外- c照射后,金黄色葡萄球菌产生ros的数量更多。这些结果表明,活性氧可能参与了222 nm远紫外- c照射下金黄色葡萄球菌的光活化低回收率。
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引用次数: 0
Optimized LED phototherapy induces ROS-mediated membrane damage in Trichophyton rubrum for effective onychomycosis treatment. 优化的LED光疗诱导红毛癣ros介导的膜损伤,有效治疗甲真菌病。
IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-02-17 DOI: 10.1111/php.14079
Angze Li, Yi Ren, Zhenjian Peng, Shangfeng Liu, Muqing Liu

Onychomycosis, predominantly induced by Trichophyton rubrum, is a pervasive nail disorder within dermatology known for its high relapse rates and suboptimal patient adherence to treatment regimens. While photomedicine has emerged as a promising therapeutic modality, efficiency reductions are common due to deck obstruction in conventional light therapy. The spectral flexibility of LEDs offers a compelling solution, allowing for deeper deck penetration while maintaining efficacy. We have developed an advanced LED system with optimized optical parameters and have elucidated the antimicrobial mechanisms underlying this technology. Our research shows that an optimal wavelength of 405 nm, an energy density of 396 J/cm2, and an average light intensity of 140 mW/cm2 demonstrate superior efficacy in treating onychomycosis. The antifungal mechanism of our pulsed LED system involves the induction of reactive oxygen species (ROS) within fungal mycelia, ultimately resulting in membrane damage. These insights highlight the potential of LED lighting systems as a novel antimicrobial strategy, offering a promising avenue for the treatment of onychomycosis.

甲真菌病主要由红毛癣菌引起,是一种普遍存在于皮肤科的指甲疾病,以其高复发率和患者对治疗方案的依从性不佳而闻名。虽然光医学已经成为一种很有前途的治疗方式,但由于传统光疗法的甲板阻塞,效率降低是常见的。led的光谱灵活性提供了一个令人信服的解决方案,允许更深的甲板穿透,同时保持效率。我们开发了一种先进的LED系统,优化了光学参数,并阐明了该技术的抗菌机制。我们的研究表明,最佳波长为405 nm,能量密度为396 J/cm2,平均光强为140 mW/cm2,治疗甲真菌病的效果较好。我们的脉冲LED系统的抗真菌机制涉及在真菌菌丝体内诱导活性氧(ROS),最终导致膜损伤。这些见解突出了LED照明系统作为一种新型抗菌策略的潜力,为治疗甲癣提供了一条有希望的途径。
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引用次数: 0
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Photochemistry and Photobiology
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