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Expert consensus on pediatric dry eye: Insights from a European Delphi study
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-04-05 DOI: 10.1016/j.jtos.2025.04.004
Edoardo Villani , Paolo Nucci , Jose Manuel Benitez-del-Castillo , Annegret Dahlmann-Noor , Wolf Alexander Lagrèze , Dominique Bremond-Gignac , PeDED Delphi Group

Context

Dry Eye Disease (DED) is a symptomatic multifactorial condition of the ocular surface, primarily characterized by tear film instability, which can lead to ocular surface damage. While traditionally associated with adults, recent studies have shown a significant prevalence of DED in pediatric populations, exacerbated by modern lifestyle changes such as increased screen time and environmental factors. Pediatric DED (PeDED) often goes underdiagnosed due to a lack of tailored diagnostic tools and the misattribution of symptoms to other conditions.

Methods

This Delphi study, conducted by a European panel of six ophthalmology experts sought to address expert consensus in pending challenges of PeDED.

Results

Over two rounds of surveys, 34 experts reached consensus on 39 of 46 statements, highlighting the need for age-specific diagnostic criteria and treatment protocols. The study identified environmental and lifestyle factors, such as screen time and ocular allergies, as significant risk factors for PeDED. There was strong consensus on the importance of adapting adult DED definitions and treatment approaches to better suit pediatric patients. The study also emphasized the cautious use of treatments like topical steroids or oral macrolides, especially in younger children.

Conclusion

The findings underscore the necessity for standardized clinical practices in diagnosing and managing PeDED, with a focus on improving the quality of life for affected children. Further research is required to validate these findings and develop comprehensive guidelines that cater to the unique needs of the pediatric population.
{"title":"Expert consensus on pediatric dry eye: Insights from a European Delphi study","authors":"Edoardo Villani ,&nbsp;Paolo Nucci ,&nbsp;Jose Manuel Benitez-del-Castillo ,&nbsp;Annegret Dahlmann-Noor ,&nbsp;Wolf Alexander Lagrèze ,&nbsp;Dominique Bremond-Gignac ,&nbsp;PeDED Delphi Group","doi":"10.1016/j.jtos.2025.04.004","DOIUrl":"10.1016/j.jtos.2025.04.004","url":null,"abstract":"<div><h3>Context</h3><div>Dry Eye Disease (DED) is a symptomatic multifactorial condition of the ocular surface, primarily characterized by tear film instability, which can lead to ocular surface damage. While traditionally associated with adults, recent studies have shown a significant prevalence of DED in pediatric populations, exacerbated by modern lifestyle changes such as increased screen time and environmental factors. Pediatric DED (PeDED) often goes underdiagnosed due to a lack of tailored diagnostic tools and the misattribution of symptoms to other conditions.</div></div><div><h3>Methods</h3><div>This Delphi study, conducted by a European panel of six ophthalmology experts sought to address expert consensus in pending challenges of PeDED.</div></div><div><h3>Results</h3><div>Over two rounds of surveys, 34 experts reached consensus on 39 of 46 statements, highlighting the need for age-specific diagnostic criteria and treatment protocols. The study identified environmental and lifestyle factors, such as screen time and ocular allergies, as significant risk factors for PeDED. There was strong consensus on the importance of adapting adult DED definitions and treatment approaches to better suit pediatric patients. The study also emphasized the cautious use of treatments like topical steroids or oral macrolides, especially in younger children.</div></div><div><h3>Conclusion</h3><div>The findings underscore the necessity for standardized clinical practices in diagnosing and managing PeDED, with a focus on improving the quality of life for affected children. Further research is required to validate these findings and develop comprehensive guidelines that cater to the unique needs of the pediatric population.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 189-197"},"PeriodicalIF":5.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pard3 promotes corneal epithelial stratification and homeostasis by regulating apical-basal polarity, cytoskeletal organization and tight junction-mediated barrier function Pard3 通过调节顶端-基底极性、细胞骨架组织和紧密连接介导的屏障功能,促进角膜上皮分层和平衡。
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-04-04 DOI: 10.1016/j.jtos.2025.04.001
Mehak Vohra , Simran Kumar , Peri Sohnen , Satinder Kaur , Sudha Swamynathan , Tomonori Hirose , Zbynek Kozmik , Shivalingappa K. Swamynathan

Purpose

To document the expression of apical-basal polarity (ABP) determinants in the mouse corneal epithelium (CE) and elucidate the functions of Pard3 in establishment and maintenance of ABP, stratification, homeostasis, and barrier function in the CE.

Methods

Pard3Δ/ΔC mice (Pard3LoxP/LoxP; Aldh3A1-Cre/+) with cornea-specific Pard3 ablation were generated by breeding Aldh3A1-Cre/+ with Pard3LoxP/LoxP mice. The control (Aldh3A1-Cre/+ or Pard3LoxP/LoxP alone) and Pard3Δ/ΔC corneal histology, ocular surface properties, barrier function, and actin cytoskeleton were assessed by Haematoxylin and Eosin staining of paraformaldehyde-fixed, paraffin-embedded tissues, scanning electron microscopy, fluorescein staining, and phalloidin staining, respectively. The expression of specific markers of interest was evaluated by qRT-PCR, immunoblots and immunofluorescent staining.

Results

Dynamic changes were observed in the expression and localization of ABP determinants as the CE stratified and matured between post-natal day 5 (PN5) and PN52. Adult Pard3Δ/ΔC CE contained fewer cell layers with rounded basal cells, and loosely adherent superficial cells lacking microplicae. Adult Pard3Δ/ΔC CE also displayed impaired barrier function with decreased expression of tight junction, adherens junction, and desmosome components, disrupted actin cytoskeletal organization, increased proliferation, and upregulation of transcription factors that drive epithelial-mesenchymal transition (EMT).

Conclusions

Disruption of ABP in Pard3Δ/ΔC CE, altered expression of cell junction complex components and disorganized actin cytoskeleton, increased cell proliferation, and upregulated EMT transcription factors suggest that the ABP-determinant Pard3 promotes CE features while suppressing mesenchymal cell fate. Collectively, these results elucidate that Pard3-mediated ABP is essential for CE stratification, homeostasis and barrier function.
{"title":"Pard3 promotes corneal epithelial stratification and homeostasis by regulating apical-basal polarity, cytoskeletal organization and tight junction-mediated barrier function","authors":"Mehak Vohra ,&nbsp;Simran Kumar ,&nbsp;Peri Sohnen ,&nbsp;Satinder Kaur ,&nbsp;Sudha Swamynathan ,&nbsp;Tomonori Hirose ,&nbsp;Zbynek Kozmik ,&nbsp;Shivalingappa K. Swamynathan","doi":"10.1016/j.jtos.2025.04.001","DOIUrl":"10.1016/j.jtos.2025.04.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To document the expression of apical-basal polarity (ABP) determinants in the mouse corneal epithelium (CE) and elucidate the functions of Pard3 in establishment and maintenance of ABP, stratification, homeostasis, and barrier function in the CE.</div></div><div><h3>Methods</h3><div><em>Pard3</em><sup>Δ/ΔC</sup> mice (<em>Pard3</em><sup><em>LoxP/LoxP</em></sup>; <em>Aldh3A1-Cre/+</em>) with cornea-specific <em>Pard3</em> ablation were generated by breeding <em>Aldh3A1-Cre/+</em> with <em>Pard3</em><sup><em>LoxP/LoxP</em></sup> mice. The control (<em>Aldh3A1-Cre/+</em> or <em>Pard3</em><sup><em>LoxP/LoxP</em></sup> alone) and <em>Pard3</em><sup>Δ/ΔC</sup> corneal histology, ocular surface properties, barrier function, and actin cytoskeleton were assessed by Haematoxylin and Eosin staining of paraformaldehyde-fixed, paraffin-embedded tissues, scanning electron microscopy, fluorescein staining, and phalloidin staining, respectively. The expression of specific markers of interest was evaluated by qRT-PCR, immunoblots and immunofluorescent staining.</div></div><div><h3>Results</h3><div>Dynamic changes were observed in the expression and localization of ABP determinants as the CE stratified and matured between post-natal day 5 (PN5) and PN52. Adult <em>Pard3</em><sup>Δ/ΔC</sup> CE contained fewer cell layers with rounded basal cells, and loosely adherent superficial cells lacking microplicae. Adult <em>Pard3</em><sup>Δ/ΔC</sup> CE also displayed impaired barrier function with decreased expression of tight junction, adherens junction, and desmosome components, disrupted actin cytoskeletal organization, increased proliferation, and upregulation of transcription factors that drive epithelial-mesenchymal transition (EMT).</div></div><div><h3>Conclusions</h3><div>Disruption of ABP in <em>Pard3</em><sup>Δ/ΔC</sup> CE, altered expression of cell junction complex components and disorganized actin cytoskeleton, increased cell proliferation, and upregulated EMT transcription factors suggest that the ABP-determinant Pard3 promotes CE features while suppressing mesenchymal cell fate. Collectively, these results elucidate that Pard3-mediated ABP is essential for CE stratification, homeostasis and barrier function.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 201-215"},"PeriodicalIF":5.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A tribute to Gary N. Foulks, M.D. (1944–2025) and his contributions to the ocular surface
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-04-02 DOI: 10.1016/j.jtos.2025.03.009
Michael H. Goldstein , Deepinder Dhaliwal , Ed Isbey , Stephen Pflugfelder , Mark J. Mannis , Gary D. Novack
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引用次数: 0
Corneal epithelial cells upregulate macropinocytosis to engulf metabolically active axonal mitochondria released by injured axons
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-04-01 DOI: 10.1016/j.jtos.2025.03.007
Sonali Pal-Ghosh , Himani Datta-Majumdar , Soneha Datta , Shelly Dimri , Jordan Hally , Hugo Wehmeyer , Zhong Chen , Mitchell Watsky , Jian-Xing Ma , Wentao Liang , Mary Ann Stepp

Purpose

To determine the mechanisms used to internalize mitochondria by corneal epithelial cells after in vivo corneal trephine injury and in vitro in corneal epithelial cells.

Methods

Male and female mice were subjected to trephine injury and euthanized immediately, 6, and 24 h after injury. Macropinocytosis was quantified in vivo using 70 kD fluorescent dextran. Mitochondrial content was assessed by immunofluorescence and metabolic activity quantified by Seahorse assay immediately and 6 h after injury. In vitro experiments using human corneal and limbal epithelial (HCLE) cells and isolated mitochondria were performed to assess mitochondrial transfer in the presence of the gap junction inhibitor 18α-glycyrrhetinc acid and the macropincytosis inhibitor ethylisopropylamiloride.

Results

Mitochondria accumulate within apical epithelial cell layers within minutes of trephine injury. Macropinocytosis also increases within minutes of trephine injury. Oxygen Consumption Rates increase in the corneal epithelium 6 h after trephine injury in males and females. Inhibiting gap junctions increases mitochondrial engulfment while inhibiting macropinocytosis prevents engulfment of mitochondria by corneal epithelial cells in vitro.

Conclusions

Molecules released by injured cells and severed axons induce macropinocytosis in corneal epithelial cells within minutes of trephine injury. An increase in oxygen consumption rate in the corneal epithelium after trephine injury indicates that axonal mitochondria can evade lysosomal degradation for at least 6 h. In vitro studies using isolated labeled and unlabeled mitochondria and control and mechanically stressed human corneal epithelial cells confirm the involvement of macropinocytosis in the engulfment of free and vesicle bound mitochondria by corneal epithelial cells.
{"title":"Corneal epithelial cells upregulate macropinocytosis to engulf metabolically active axonal mitochondria released by injured axons","authors":"Sonali Pal-Ghosh ,&nbsp;Himani Datta-Majumdar ,&nbsp;Soneha Datta ,&nbsp;Shelly Dimri ,&nbsp;Jordan Hally ,&nbsp;Hugo Wehmeyer ,&nbsp;Zhong Chen ,&nbsp;Mitchell Watsky ,&nbsp;Jian-Xing Ma ,&nbsp;Wentao Liang ,&nbsp;Mary Ann Stepp","doi":"10.1016/j.jtos.2025.03.007","DOIUrl":"10.1016/j.jtos.2025.03.007","url":null,"abstract":"<div><h3>Purpose</h3><div>To determine the mechanisms used to internalize mitochondria by corneal epithelial cells after <em>in vivo</em> corneal trephine injury and <em>in vitro</em> in corneal epithelial cells.</div></div><div><h3>Methods</h3><div>Male and female mice were subjected to trephine injury and euthanized immediately, 6, and 24 h after injury. Macropinocytosis was quantified <em>in vivo</em> using 70 kD fluorescent dextran. Mitochondrial content was assessed by immunofluorescence and metabolic activity quantified by Seahorse assay immediately and 6 h after injury. <em>In vitro</em> experiments using human corneal and limbal epithelial (HCLE) cells and isolated mitochondria were performed to assess mitochondrial transfer in the presence of the gap junction inhibitor 18α-glycyrrhetinc acid and the macropincytosis inhibitor ethylisopropylamiloride.</div></div><div><h3>Results</h3><div>Mitochondria accumulate within apical epithelial cell layers within minutes of trephine injury. Macropinocytosis also increases within minutes of trephine injury. Oxygen Consumption Rates increase in the corneal epithelium 6 h after trephine injury in males and females. Inhibiting gap junctions increases mitochondrial engulfment while inhibiting macropinocytosis prevents engulfment of mitochondria by corneal epithelial cells <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>Molecules released by injured cells and severed axons induce macropinocytosis in corneal epithelial cells within minutes of trephine injury. An increase in oxygen consumption rate in the corneal epithelium after trephine injury indicates that axonal mitochondria can evade lysosomal degradation for at least 6 h. <em>In vitro</em> studies using isolated labeled and unlabeled mitochondria and control and mechanically stressed human corneal epithelial cells confirm the involvement of macropinocytosis in the engulfment of free and vesicle bound mitochondria by corneal epithelial cells.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 173-188"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The association between personality and dry eye disease: A large cross-sectional study
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-03-26 DOI: 10.1016/j.jtos.2025.03.005
Morten S. Magno , Laura E. Wolpert , Mathias K. Morthen , Tor P. Utheim , Christopher J. Hammond , Jelle Vehof

Purpose

Personality influences health and wellbeing. The purpose of this large, cross-sectional study was to clarify the association between personality traits and dry eye disease (DED).

Methods

78,610 participants from the Lifelines cohort were included. DED was assessed using the Women's Health Study (WHS) dry eye disease questionnaire. Three of the Big Five personality domains (neuroticism, extraversion, conscientiousness) were assessed using an abbreviated NEO Personality Inventory. Logistic regressions including age, sex, BMI, physical activity, smoking, education, income, and 48 medical comorbidities were used to examine the association between personality and DED. The main outcome was WHS-defined DED, with highly symptomatic DED as a secondary outcome. Results are presented as odds ratios per standard deviation increase in personality score.

Results

DED was present in 8.7 % of participants. In the fully corrected model including all demographics and comorbidities, higher neuroticism was associated with greater odds of DED (OR 1.10, P < 0.001), while higher conscientiousness was tied to lower odds of DED (OR 0.97, P = 0.014). For highly symptomatic DED, these associations were especially strong: OR 1.23 (P < 0.001) and 0.90 (P < 0.001) for neuroticism and conscientiousness, respectively. Higher extraversion was associated with lower odds of highly symptomatic DED (OR 0.93, P = 0.031), but showed no significant relationship with WHS-defined DED. Additionally, participants diagnosed with DED who had higher neuroticism scores experienced a greater symptom burden.

Conclusions

Higher neuroticism and lower conscientiousness are associated with increased odds of DED. These personality traits may contribute to increased subjective symptoms and are important to consider in clinical management and care.
{"title":"The association between personality and dry eye disease: A large cross-sectional study","authors":"Morten S. Magno ,&nbsp;Laura E. Wolpert ,&nbsp;Mathias K. Morthen ,&nbsp;Tor P. Utheim ,&nbsp;Christopher J. Hammond ,&nbsp;Jelle Vehof","doi":"10.1016/j.jtos.2025.03.005","DOIUrl":"10.1016/j.jtos.2025.03.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Personality influences health and wellbeing. The purpose of this large, cross-sectional study was to clarify the association between personality traits and dry eye disease (DED).</div></div><div><h3>Methods</h3><div>78,610 participants from the Lifelines cohort were included. DED was assessed using the Women's Health Study (WHS) dry eye disease questionnaire. Three of the Big Five personality domains (neuroticism, extraversion, conscientiousness) were assessed using an abbreviated NEO Personality Inventory. Logistic regressions including age, sex, BMI, physical activity, smoking, education, income, and 48 medical comorbidities were used to examine the association between personality and DED. The main outcome was WHS-defined DED, with highly symptomatic DED as a secondary outcome. Results are presented as odds ratios per standard deviation increase in personality score.</div></div><div><h3>Results</h3><div>DED was present in 8.7 % of participants. In the fully corrected model including all demographics and comorbidities, higher neuroticism was associated with greater odds of DED (OR 1.10, P &lt; 0.001), while higher conscientiousness was tied to lower odds of DED (OR 0.97, P = 0.014). For highly symptomatic DED, these associations were especially strong: OR 1.23 (P &lt; 0.001) and 0.90 (P &lt; 0.001) for neuroticism and conscientiousness, respectively. Higher extraversion was associated with lower odds of highly symptomatic DED (OR 0.93, P = 0.031), but showed no significant relationship with WHS-defined DED. Additionally, participants diagnosed with DED who had higher neuroticism scores experienced a greater symptom burden.</div></div><div><h3>Conclusions</h3><div>Higher neuroticism and lower conscientiousness are associated with increased odds of DED. These personality traits may contribute to increased subjective symptoms and are important to consider in clinical management and care.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 132-139"},"PeriodicalIF":5.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bringing ophthalmology into the scientific world: Novel nanoparticle-based strategies for ocular drug delivery
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-03-25 DOI: 10.1016/j.jtos.2025.03.004
Milad Abbasi , Hossein Aghamollaei , Ahmad Vaez , Ali Mohammad Amani , Hesam Kamyab , Shreeshivadasan Chelliapan , Sajad Jamalpour , Renato Zambrano-Dávila
The distinctive benefits and drawbacks of various drug delivery strategies to supply corneal tissue improvement for sense organs have been the attention of studies worldwide in recent decades. Static and dynamic barriers of ocular tissue prevent foreign chemicals from entering and inhibit the active absorption of therapeutic medicines. The distribution of different medications to ocular tissue is one of the most appealing and demanding tasks for investigators in pharmacology, biomaterials, and ophthalmology, and it is critical for cornea wound healing due to the controlled release rate and increased drug bioavailability. It should be mentioned that the transport of various types of medications into the different sections of the eye, particularly the cornea, is exceedingly challenging because of its distinctive structure and various barriers throughout the eye. Nanoparticles are being studied to improve medicine delivery strategies for ocular disease. Repetitive corneal drug delivery using biodegradable nanocarriers allows a medicine to remain in different parts of the cornea for extended periods of time and thus improve administration route effectiveness. In this review, we discussed eye anatomy, ocular delivery barriers, as well as the emphasis on the biodegradable nanomaterials ranging from organic nanostructures, such as nanomicelles, polymers, liposomes, niosomes, nanowafers, nanoemulsions, nanosuspensions, nanocrystals, cubosomes, olaminosomes, hybridized NPs, dendrimers, bilosomes, solid lipid NPs, nanostructured lipid carriers, and nanofiber to organic nanomaterials like silver, gold, and mesoporous silica nanoparticles. In addition, we describe the nanotechnology-based ophthalmic medications that are presently on the market or in clinical studies. Finally, drawing on current trends and therapeutic approaches, we discuss the challenges that innovative optical drug delivery systems confront and propose future research routes. We hope that this review will serve as a source of motivation and inspiration for developing innovative ophthalmic formulations.
近几十年来,为改善感官器官角膜组织而采用的各种给药策略的独特益处和弊端一直是全球研究的焦点。眼组织的静态和动态屏障会阻止外来化学物质进入,并抑制治疗药物的有效吸收。对于药理学、生物材料学和眼科学研究人员来说,将不同药物分配到眼部组织是最吸引人也是最艰巨的任务之一,而且由于可控释放率和药物生物利用度的提高,这对角膜伤口愈合至关重要。值得一提的是,由于角膜的独特结构和整个眼球的各种屏障,将各种药物输送到眼球的不同部分,尤其是角膜,是一项极具挑战性的工作。目前正在对纳米颗粒进行研究,以改进眼部疾病的给药策略。使用可生物降解的纳米载体在角膜上重复给药,可使药物在角膜的不同部位停留较长时间,从而提高给药途径的有效性。在这篇综述中,我们讨论了眼部解剖、眼部给药屏障,并重点介绍了可生物降解的纳米材料,包括有机纳米结构,如纳米细胞、聚合物、脂质体、niosomes、纳米晶片、纳米乳液、纳米悬浮液、纳米晶体、立方体、橄榄体、杂化 NPs、树枝状分子、双体、固态脂质 NPs、纳米结构脂质载体和纳米纤维,以及银、金和介孔二氧化硅纳米粒子等有机纳米材料。此外,我们还介绍了目前已上市或正在进行临床研究的基于纳米技术的眼科药物。最后,我们借鉴当前的趋势和治疗方法,讨论了创新型光学给药系统所面临的挑战,并提出了未来的研究路线。我们希望这篇综述能成为开发创新眼科制剂的动力和灵感来源。
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引用次数: 0
Endoplasmic reticulum stress contributes to the development of ocular graft-vs-host disease in the eyelids and the ocular surface
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-03-22 DOI: 10.1016/j.jtos.2025.03.003
Shinri Sato , Yoko Ogawa , Eisuke Shimizu , Kazuki Asai , Kazuno Negishi , Kazuo Tsubota , Masatoshi Hirayama

Background

While endoplasmic reticulum (ER) stress has been implicated in various aspects of graft-versus-host disease (GVHD), its effects on the eyelids and ocular surface in patients with chronic GVHD (cGVHD) remains poorly understood. We aimed to investigate the relationship between ER stress and ocular GVHD using the ER stress suppressor, 4-phenylbutyric acid (PBA).

Methods

The study used allogeneic bone marrow transplantation (BMT) and syngeneic BMT to establish a cGVHD mouse model. cGVHD mice were treated with either intraperitoneal administration of PBA or 2 % PBA eye drops following BMT.

Results

The Intraperitoneal PBA-treated (PBAip) group retained a larger meibomian gland (MG) area and corneal epithelial damage and inflammatory and fibrotic cell infiltration in the ocular surface was attenuated compared to vehicle-treated cGVHD mice. The expression of unfolded protein response markers was significantly elevated in the vehicle group compared to the syngeneic control and the PBAip group. Electron microscopy and immunohistochemistry revealed that fibroblasts and macrophages infiltrated the eyelids and ocular surface of cGVHD mice under ER stress. The corneal fluorescein staining score was significantly lower in the PBA eye drop-treated group than in the vehicle-treated group. The numbers of leukocyte marker CD45-, T cell marker CD4-, and macrophage marker F4/80-positive cells were significantly reduced in the PBA eye drop-treated group compared to the vehicle group.

Conclusions

The study suggests that the ER stress response, which is triggered by cGVHD in ocular surface tissues, can be suppressed by PBA, an ER stress suppressor, potentially offering therapeutic benefits in ocular GVHD.
{"title":"Endoplasmic reticulum stress contributes to the development of ocular graft-vs-host disease in the eyelids and the ocular surface","authors":"Shinri Sato ,&nbsp;Yoko Ogawa ,&nbsp;Eisuke Shimizu ,&nbsp;Kazuki Asai ,&nbsp;Kazuno Negishi ,&nbsp;Kazuo Tsubota ,&nbsp;Masatoshi Hirayama","doi":"10.1016/j.jtos.2025.03.003","DOIUrl":"10.1016/j.jtos.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>While endoplasmic reticulum (ER) stress has been implicated in various aspects of graft-versus-host disease (GVHD), its effects on the eyelids and ocular surface in patients with chronic GVHD (cGVHD) remains poorly understood. We aimed to investigate the relationship between ER stress and ocular GVHD using the ER stress suppressor, 4-phenylbutyric acid (PBA).</div></div><div><h3>Methods</h3><div>The study used allogeneic bone marrow transplantation (BMT) and syngeneic BMT to establish a cGVHD mouse model. cGVHD mice were treated with either intraperitoneal administration of PBA or 2 % PBA eye drops following BMT.</div></div><div><h3>Results</h3><div>The Intraperitoneal PBA-treated (PBAip) group retained a larger meibomian gland (MG) area and corneal epithelial damage and inflammatory and fibrotic cell infiltration in the ocular surface was attenuated compared to vehicle-treated cGVHD mice. The expression of unfolded protein response markers was significantly elevated in the vehicle group compared to the syngeneic control and the PBAip group. Electron microscopy and immunohistochemistry revealed that fibroblasts and macrophages infiltrated the eyelids and ocular surface of cGVHD mice under ER stress. The corneal fluorescein staining score was significantly lower in the PBA eye drop-treated group than in the vehicle-treated group. The numbers of leukocyte marker CD45-, T cell marker CD4-, and macrophage marker F4/80-positive cells were significantly reduced in the PBA eye drop-treated group compared to the vehicle group.</div></div><div><h3>Conclusions</h3><div>The study suggests that the ER stress response, which is triggered by cGVHD in ocular surface tissues, can be suppressed by PBA, an ER stress suppressor, potentially offering therapeutic benefits in ocular GVHD.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 115-131"},"PeriodicalIF":5.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Smoking negatively impacts ocular surface health and corneal nerve metrics
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-03-13 DOI: 10.1016/j.jtos.2025.03.002
Ansa Anam , Mingyi Yu , Chang Liu , Isabelle Xin Yu Lee , Juanita Yang , A.V. Shanmathi , Ching-Yu Cheng , Yu-Chi Liu

Purpose

To evaluate the effects of smoking on ocular surface through comprehensive analysis of corneal nerves, corneal epithelium, dendritic cells (DCs), and clinical assessments.

Methods

This cross-sectional study included 250 healthy smokers and 272 healthy non-smokers. Patients’ smoking status and duration were recorded. In vivo confocal microscopy was performed to assess 7 quantitative corneal nerves parameters, 3 corneal neuroma parameters, 3 DCs parameters, and 3 epithelial parameters. Ocular surface evaluations included tear break-up time (TBUT), ocular surface and corneal staining, corneal sensitivity, and Schirmer test. Ocular Surface Disease Index questionnaire was used for symptom assessment.

Results

Compared to non-smokers, smokers exhibited significantly lower corneal nerve fiber density (CNFD), nerve branch density, nerve fiber length, nerve total branch density, corneal nerve fiber area (CNFA), and corneal nerve fractal dimension (CFracDim; all p < 0.001). Smokers also presented with a significantly swollen corneal nerve fiber (p < 0.001). Longer smoking duration was significantly associated with lower CNFD (β = −0.04, P = 0.010), lower CNFA (β = −0.00002, P = 0.033), and lower CFracDim (β = −0.0008, P = 0.016). Additionally, a significantly larger neuroma total area (p = 0.040), size (p < 0.001) and perimeter (p < 0.001), as well as a significantly higher DCs density (p < 0.001), DCs count (p = 0.003), and lower DCs elongation which suggested higher DCs maturity (p < 0.001), were observed in the smoking group. Smokers demonstrated significantly higher ocular surface staining scores (p < 0.001) and reduced TBUT (p = 0.001). Corneal epithelial circularity was borderline higher in the smoking subjects (p = 0.059).

Conclusions

Smoking is associated with significant alterations in corneal nerve morphology and quantity, increased immunological cells, and compromised ocular surface integrity.
{"title":"Smoking negatively impacts ocular surface health and corneal nerve metrics","authors":"Ansa Anam ,&nbsp;Mingyi Yu ,&nbsp;Chang Liu ,&nbsp;Isabelle Xin Yu Lee ,&nbsp;Juanita Yang ,&nbsp;A.V. Shanmathi ,&nbsp;Ching-Yu Cheng ,&nbsp;Yu-Chi Liu","doi":"10.1016/j.jtos.2025.03.002","DOIUrl":"10.1016/j.jtos.2025.03.002","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the effects of smoking on ocular surface through comprehensive analysis of corneal nerves, corneal epithelium, dendritic cells (DCs), and clinical assessments.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 250 healthy smokers and 272 healthy non-smokers. Patients’ smoking status and duration were recorded. In vivo confocal microscopy was performed to assess 7 quantitative corneal nerves parameters, 3 corneal neuroma parameters, 3 DCs parameters, and 3 epithelial parameters. Ocular surface evaluations included tear break-up time (TBUT), ocular surface and corneal staining, corneal sensitivity, and Schirmer test. Ocular Surface Disease Index questionnaire was used for symptom assessment.</div></div><div><h3>Results</h3><div>Compared to non-smokers, smokers exhibited significantly lower corneal nerve fiber density (CNFD), nerve branch density, nerve fiber length, nerve total branch density, corneal nerve fiber area (CNFA), and corneal nerve fractal dimension (CFracDim; all p &lt; 0.001). Smokers also presented with a significantly swollen corneal nerve fiber (p &lt; 0.001). Longer smoking duration was significantly associated with lower CNFD (β = −0.04, P = 0.010), lower CNFA (β = −0.00002, P = 0.033), and lower CFracDim (β = −0.0008, P = 0.016). Additionally, a significantly larger neuroma total area (p = 0.040), size (p &lt; 0.001) and perimeter (p &lt; 0.001), as well as a significantly higher DCs density (p &lt; 0.001), DCs count (p = 0.003), and lower DCs elongation which suggested higher DCs maturity (p &lt; 0.001), were observed in the smoking group. Smokers demonstrated significantly higher ocular surface staining scores (p &lt; 0.001) and reduced TBUT (p = 0.001). Corneal epithelial circularity was borderline higher in the smoking subjects (p = 0.059).</div></div><div><h3>Conclusions</h3><div>Smoking is associated with significant alterations in corneal nerve morphology and quantity, increased immunological cells, and compromised ocular surface integrity.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 105-114"},"PeriodicalIF":5.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A masked study to differentiate in vivo confocal microscopic features of Pythium insidiosum and fungal filaments 通过掩蔽研究来区分体内白粉菌和真菌菌丝的共聚焦显微特征。
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-03-12 DOI: 10.1016/j.jtos.2025.03.001
Bhupesh Bagga , Md Hasnat Ali , K Shreeya Jain , Tanmay Gokhale , Joveeta Joseph , Pabitra Duwal , Amrita Mohanty , Lakshminarayanan Gowtham , Savitri Sharma

Purpose

To describe in vivo confocal microscopic features of Pythium insidiosum in patients with Pythium keratitis and compare with those observed in fungal keratitis.

Method

We collected in vivo confocal images of the cornea from patients with microbiologically confirmed Pythium and fungal keratitis, analysing five putative distinguishing features: filament width (broad or thin), granularity within the filament (present or absent), filament continuity or traceability, the presence or absence of loops, and the double track sign. Three masked observers were shown images with concealed identities and tasked with detecting Pythium filaments. After initial assessment and training, their detection rates were calculated and compared before and after training. We did perform imageJ (Open Source software project Fiji) analysis of all the images for objectively assessment.

Results

Sixty confocal images of Pythium (n = 32,15 patients) and fungal (n = 28,12 patients) keratitis were analysed. The continuity of filaments and the presence of loops emerged as strong predictors of Pythium, with adjusted odds ratios (OR) of 18.1 and 19.29, respectively, based on multivariate logistic regression and decision tree splits. Pre-training accuracy was 0.51, 0.52, and 0.56, but post-training (95 % CI) improved to 0.75 (0.62–0.85), 0.80 (0.67–0.89), and 0.86 (0.75–0.94). Correct identification rates for Pythium were 27, 28, and 29 (84–89 %) out of 32, and for fungus were 16, 21, and 24 (57.4–85.7 %) out of 28 images with sensitivity and specificity ranging from 70.7 to 87.5 % and 80–85 % respectively. ImageJ analysis revealed a significant difference between Pythium and fungal filaments in both width (9.30 ± 1.21 μ vs. 6.20 ± 0.88 μ, p < 0.001) and branching angle (83.92 ± 13.57° vs. 55.10 ± 6.03°, p < 0.001).

Conclusions

Based on our analysis, these features may be indicative of Pythium and could serve as a helpful reference for future prospective studies. However, further large scale studies and validation are needed to strengthen these observations.
{"title":"A masked study to differentiate in vivo confocal microscopic features of Pythium insidiosum and fungal filaments","authors":"Bhupesh Bagga ,&nbsp;Md Hasnat Ali ,&nbsp;K Shreeya Jain ,&nbsp;Tanmay Gokhale ,&nbsp;Joveeta Joseph ,&nbsp;Pabitra Duwal ,&nbsp;Amrita Mohanty ,&nbsp;Lakshminarayanan Gowtham ,&nbsp;Savitri Sharma","doi":"10.1016/j.jtos.2025.03.001","DOIUrl":"10.1016/j.jtos.2025.03.001","url":null,"abstract":"<div><h3>Purpose</h3><div>To describe <em>in vivo</em> confocal microscopic features of <em>Pythium insidiosum</em> in patients with <em>Pythium</em> keratitis and compare with those observed in fungal keratitis.</div></div><div><h3>Method</h3><div>We collected <em>in vivo</em> confocal images of the cornea from patients with microbiologically confirmed <em>Pythium</em> and fungal keratitis, analysing five putative distinguishing features: filament width (broad or thin), granularity within the filament (present or absent), filament continuity or traceability, the presence or absence of loops, and the double track sign. Three masked observers were shown images with concealed identities and tasked with detecting <em>Pythium</em> filaments<em>.</em> After initial assessment and training, their detection rates were calculated and compared before and after training. We did perform imageJ (Open Source software project Fiji) analysis of all the images for objectively assessment.</div></div><div><h3>Results</h3><div>Sixty confocal images of <em>Pythium</em> (n = 32,15 patients) and fungal (n = 28,12 patients) keratitis were analysed. The continuity of filaments and the presence of loops emerged as strong predictors of <em>Pythium</em>, with adjusted odds ratios (OR) of 18.1 and 19.29, respectively, based on multivariate logistic regression and decision tree splits. Pre-training accuracy was 0.51, 0.52, and 0.56, but post-training (95 % CI) improved to 0.75 (0.62–0.85), 0.80 (0.67–0.89), and 0.86 (0.75–0.94). Correct identification rates for <em>Pythium</em> were 27, 28, and 29 (84–89 %) out of 32, and for fungus were 16, 21, and 24 (57.4–85.7 %) out of 28 images with sensitivity and specificity ranging from 70.7 to 87.5 % and 80–85 % respectively. ImageJ analysis revealed a significant difference between <em>Pythium</em> and fungal filaments in both width (9.30 ± 1.21 μ vs. 6.20 ± 0.88 μ, <em>p</em> &lt; 0.001) and branching angle (83.92 ± 13.57° vs. 55.10 ± 6.03°, <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Based on our analysis, these features may be indicative of <em>Pythium</em> and could serve as a helpful reference for future prospective studies. However, further large scale studies and validation are needed to strengthen these observations.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 99-104"},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Readership awareness series – Paper 15: How the ICMJE 2025 recommendations update impact the scientific community?
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-03-04 DOI: 10.1016/j.jtos.2025.02.009
Mohammad Javed Ali MD, PhD, FRCS (Editor-in-Chief) , Ali Djalilian MD (Former Editor-in-Chief)
{"title":"Readership awareness series – Paper 15: How the ICMJE 2025 recommendations update impact the scientific community?","authors":"Mohammad Javed Ali MD, PhD, FRCS (Editor-in-Chief) ,&nbsp;Ali Djalilian MD (Former Editor-in-Chief)","doi":"10.1016/j.jtos.2025.02.009","DOIUrl":"10.1016/j.jtos.2025.02.009","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 97-98"},"PeriodicalIF":5.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Ocular Surface
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