Cyanobacterial blooms, which are increasingly exacerbated by eutrophication and climate change, pose threats to ecosystems and public health. This paper systematically reviews recent advances in microbial intervention strategies for controlling cyanobacterial blooms. Current approaches primarily comprise direct lysis methods, indirect suppression methods, and integrated strategies. Direct algicide methods rapidly lyse cyanobacterial cells and degrade toxins, although their application is constrained by environmental sensitivity and host specificity. Indirect approaches offer sustainable preventive strategies by inhibiting cyanobacterial growth, yet require careful environmental management. Integrated methods combine microbial strategies with other technologies, enhancing both the efficiency and ecological safety of managing cyanobacterial blooms. While microbial strategies demonstrate significant potential, practical implementation faces challenges, including environmental adaptability, ecological safety, and regulatory frameworks. Future research should focus on integrating synthetic biology, intelligent delivery systems, and multi-omics technologies to achieve more effective and environmentally friendly management of cyanobacterial blooms.
{"title":"Microorganism-Based Strategies for the Control of Cyanobacterial Blooms: A Review of Recent Progress.","authors":"Wangle Zhang, Shiyuan Meng, Xiaoxu Wu, Hong Shen, Dongqin Wang, Tong Qiu, Weijie Li, Jiping Chen, Ling Li, Bingbing Liang, Mengdi Zhao, Xuwei Deng, Chi Zhou","doi":"10.3390/toxins17120604","DOIUrl":"10.3390/toxins17120604","url":null,"abstract":"<p><p>Cyanobacterial blooms, which are increasingly exacerbated by eutrophication and climate change, pose threats to ecosystems and public health. This paper systematically reviews recent advances in microbial intervention strategies for controlling cyanobacterial blooms. Current approaches primarily comprise direct lysis methods, indirect suppression methods, and integrated strategies. Direct algicide methods rapidly lyse cyanobacterial cells and degrade toxins, although their application is constrained by environmental sensitivity and host specificity. Indirect approaches offer sustainable preventive strategies by inhibiting cyanobacterial growth, yet require careful environmental management. Integrated methods combine microbial strategies with other technologies, enhancing both the efficiency and ecological safety of managing cyanobacterial blooms. While microbial strategies demonstrate significant potential, practical implementation faces challenges, including environmental adaptability, ecological safety, and regulatory frameworks. Future research should focus on integrating synthetic biology, intelligent delivery systems, and multi-omics technologies to achieve more effective and environmentally friendly management of cyanobacterial blooms.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carla de Sanctis Pecora, Martina Kerscher, Mariana Muniz, Ada Trindade de Almeida
Recent advances in the understanding of facial anatomy have contributed significantly to the refinement of injection techniques for the treatment of dynamic forehead lines. A comprehensive assessment of eyebrow shape, position, and the aging process is essential, as the latter are closely linked to the functional balance between the frontalis muscle and the upper facial depressors. Optimal outcomes also depend on the accurate determination of dosage per injection point, injection depth, and strategic distribution of injection sites within the frontalis, which should be carefully considered and tailored to the individual's anatomical characteristics and therapeutic goals-whether the aim is neuromodulation for muscle activity reduction or intradermal application for skin quality enhancement. A round table discussion session among three experienced international dermatology experts in aesthetic botulinum toxin type A was performed during a MERZ LATAM-sponsored medical education session. Recent insights in facial anatomy, including the precise location and distribution of motor endplates, as well as the direction of muscular force vectors during contraction; aging processes; and interindividual variability in facial musculature and mimicry patterns are discussed, and the results are described herein. These factors play a critical role in customizing personalized injection strategies and improving aesthetic outcomes in the treatment of forehead lines.
{"title":"Why, When, and How to Treat Dynamic Forehead Lines with Botulinum Toxin Type A.","authors":"Carla de Sanctis Pecora, Martina Kerscher, Mariana Muniz, Ada Trindade de Almeida","doi":"10.3390/toxins17120603","DOIUrl":"10.3390/toxins17120603","url":null,"abstract":"<p><p>Recent advances in the understanding of facial anatomy have contributed significantly to the refinement of injection techniques for the treatment of dynamic forehead lines. A comprehensive assessment of eyebrow shape, position, and the aging process is essential, as the latter are closely linked to the functional balance between the frontalis muscle and the upper facial depressors. Optimal outcomes also depend on the accurate determination of dosage per injection point, injection depth, and strategic distribution of injection sites within the frontalis, which should be carefully considered and tailored to the individual's anatomical characteristics and therapeutic goals-whether the aim is neuromodulation for muscle activity reduction or intradermal application for skin quality enhancement. A round table discussion session among three experienced international dermatology experts in aesthetic botulinum toxin type A was performed during a MERZ LATAM-sponsored medical education session. Recent insights in facial anatomy, including the precise location and distribution of motor endplates, as well as the direction of muscular force vectors during contraction; aging processes; and interindividual variability in facial musculature and mimicry patterns are discussed, and the results are described herein. These factors play a critical role in customizing personalized injection strategies and improving aesthetic outcomes in the treatment of forehead lines.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiale Wang, Xunyuan Jiang, Zemiao Xiao, Xuemei Tang, Kai Wan
Parasitoid wasp venoms represent highly specialized biochemical arsenals that evolved to manipulate host physiology and ensure successful development of the parasitoid offspring. However, the molecular targets and mechanisms underlying this complex host modulation remain poorly understood. To address this, we employed an AI-driven discovery pipeline, integrating the sequence-based predictor D-SCRIPT with the structural modeler AlphaFold3, to characterize LjSPI-1, a venom serpin from Liragathis javana. This computational workflow highlighted a previously unreported candidate partner-a host serine carboxypeptidase (Chr09G02510). Crucially, we detected a direct physical interaction between these two proteins through both in vitro pull-down and in vivo yeast two-hybrid assays, supporting this AI-prioritized interaction under experimental conditions. Our study identifies a high-priority molecular pairing and demonstrates the utility of an AI-guided strategy for uncovering candidate targets of venom proteins. In addition, guided by the predicted biochemical role of Chr09G02510, we propose several plausible physiological hypotheses linking this interaction to host peptide metabolism and immune modulation. These hypotheses serve as a conceptual basis for future mechanistic and toxicological investigations.
{"title":"Ai-Assisted Discovery of a Direct Physical Interaction Between a Venom Serpin from the Parasitoid Wasp <i>Liragathis javana</i> and a Host Serine Carboxypeptidase.","authors":"Jiale Wang, Xunyuan Jiang, Zemiao Xiao, Xuemei Tang, Kai Wan","doi":"10.3390/toxins17120600","DOIUrl":"10.3390/toxins17120600","url":null,"abstract":"<p><p>Parasitoid wasp venoms represent highly specialized biochemical arsenals that evolved to manipulate host physiology and ensure successful development of the parasitoid offspring. However, the molecular targets and mechanisms underlying this complex host modulation remain poorly understood. To address this, we employed an AI-driven discovery pipeline, integrating the sequence-based predictor D-SCRIPT with the structural modeler AlphaFold3, to characterize LjSPI-1, a venom serpin from <i>Liragathis javana</i>. This computational workflow highlighted a previously unreported candidate partner-a host serine carboxypeptidase (Chr09G02510). Crucially, we detected a direct physical interaction between these two proteins through both in vitro pull-down and in vivo yeast two-hybrid assays, supporting this AI-prioritized interaction under experimental conditions. Our study identifies a high-priority molecular pairing and demonstrates the utility of an AI-guided strategy for uncovering candidate targets of venom proteins. In addition, guided by the predicted biochemical role of Chr09G02510, we propose several plausible physiological hypotheses linking this interaction to host peptide metabolism and immune modulation. These hypotheses serve as a conceptual basis for future mechanistic and toxicological investigations.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huijuan Lu, Guowen Zhang, Lin Zhao, Ying Yuan, Bing Gong, Bin Han, Wen-Hui Lee
The preparation of an antibody to treat snake envenomation requires a large amount of snake venom. In China, only four types of anti-snake venom sera are clinically available, and the production and immunization strategies for clinically approved anti-snake venom sera still mainly rely on detoxified antigens, which is a mature technical route commonly adopted by domestic pharmaceutical enterprises. At present, researchers immunize animals with low doses of certain snake venom toxic components or prokaryotically expressed toxic components to reduce the amount of venom needed, and use prepared antisera for their specific investigation purposes. However, it is unclear if low-dose immunized antibody titers and toxin-neutralizing activities are consistent with those of high-dose detoxified crude venom immunized antibodies. In this study, we developed a method for the preparation of highly effective rabbit polyclonal antisera while saving a large amount of toxin. Rabbit polyclonal antisera prepared by low-dose natural α-bungarotoxin (α-BGT) had strong neutralizing effects on the toxin itself and achieved the same antibody titers as antisera prepared with high doses of detoxified α-BGT. Antigen of A maltose binding protein (MBP) fused with α-BGT (MBP-α-BGT) expressed in prokaryotes had low antibody titer and low neutralizing activity. This study provides an effective dosage selection guide and methods for the preparation of polyclonal antibodies and antiserum for investigation purposes.
{"title":"Characterization of Alpha-Bungarotoxin Antibodies Prepared by Different Strategies.","authors":"Huijuan Lu, Guowen Zhang, Lin Zhao, Ying Yuan, Bing Gong, Bin Han, Wen-Hui Lee","doi":"10.3390/toxins17120601","DOIUrl":"10.3390/toxins17120601","url":null,"abstract":"<p><p>The preparation of an antibody to treat snake envenomation requires a large amount of snake venom. In China, only four types of anti-snake venom sera are clinically available, and the production and immunization strategies for clinically approved anti-snake venom sera still mainly rely on detoxified antigens, which is a mature technical route commonly adopted by domestic pharmaceutical enterprises. At present, researchers immunize animals with low doses of certain snake venom toxic components or prokaryotically expressed toxic components to reduce the amount of venom needed, and use prepared antisera for their specific investigation purposes. However, it is unclear if low-dose immunized antibody titers and toxin-neutralizing activities are consistent with those of high-dose detoxified crude venom immunized antibodies. In this study, we developed a method for the preparation of highly effective rabbit polyclonal antisera while saving a large amount of toxin. Rabbit polyclonal antisera prepared by low-dose natural α-bungarotoxin (α-BGT) had strong neutralizing effects on the toxin itself and achieved the same antibody titers as antisera prepared with high doses of detoxified α-BGT. Antigen of A maltose binding protein (MBP) fused with α-BGT (MBP-α-BGT) expressed in prokaryotes had low antibody titer and low neutralizing activity. This study provides an effective dosage selection guide and methods for the preparation of polyclonal antibodies and antiserum for investigation purposes.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bacteria encode a broad range of survival and defence systems, including CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems, restriction-modification systems, and toxin-antitoxin (TA) systems, which are involved in bacterial regulation and immunity. The traditional view holds that CRISPR-Cas systems and TA systems are two independent defense lines in prokaryotes. However, groundbreaking studies in recent years have revealed multi-level functional coupling between them. This review systematically elaborates on this mechanism, focusing on three types of TA systems that mediate the core correlation of CRISPR-Cas systems: CreTA maintains the evolutionary stability of CRISPR-Cas systems through an addiction mechanism; CreR enables self-regulation of CRISPR-Cas expression; and CrePA provides herd immunity by triggering abortive infection after the CRISPR-Cas system has been destroyed by Anti-CRISPRS protein. Additionally, we discuss the evolutionary homology between the type III toxin AbiF and the type VI CRISPR effector Cas13, offering a new perspective for understanding the origin of CRISPR-Cas systems. These findings not only reveal the functional coupling of prokaryotic defense systems but also provide a powerful theoretical framework and practical solutions for addressing stability challenges in CRISPR technology applications.
细菌编码了广泛的生存和防御系统,包括参与细菌调节和免疫的CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas系统、限制性修饰系统和毒素-抗毒素(TA)系统。传统观点认为,CRISPR-Cas系统和TA系统是原核生物中两条独立的防线。然而,近年来突破性的研究揭示了它们之间多层次的功能耦合。本文系统阐述了这一机制,重点介绍了介导CRISPR-Cas系统核心相关性的三种TA系统:CreTA通过成瘾机制维持CRISPR-Cas系统的进化稳定性;CreR能够自我调节CRISPR-Cas的表达;在CRISPR-Cas系统被Anti-CRISPRS蛋白破坏后,CrePA通过触发流产感染提供群体免疫。此外,我们讨论了III型毒素AbiF与VI型CRISPR效应物Cas13之间的进化同源性,为理解CRISPR- cas系统的起源提供了新的视角。这些发现不仅揭示了原核防御系统的功能耦合,而且为解决CRISPR技术应用中的稳定性挑战提供了强大的理论框架和实践解决方案。
{"title":"Functional Coupling and Evolutionary Relationships Between Toxin-Antitoxin Systems and CRISPR-Cas Systems.","authors":"Yibo Meng, Jiyun Chen, Liang Liu","doi":"10.3390/toxins17120602","DOIUrl":"10.3390/toxins17120602","url":null,"abstract":"<p><p>Bacteria encode a broad range of survival and defence systems, including CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems, restriction-modification systems, and toxin-antitoxin (TA) systems, which are involved in bacterial regulation and immunity. The traditional view holds that CRISPR-Cas systems and TA systems are two independent defense lines in prokaryotes. However, groundbreaking studies in recent years have revealed multi-level functional coupling between them. This review systematically elaborates on this mechanism, focusing on three types of TA systems that mediate the core correlation of CRISPR-Cas systems: CreTA maintains the evolutionary stability of CRISPR-Cas systems through an addiction mechanism; CreR enables self-regulation of CRISPR-Cas expression; and CrePA provides herd immunity by triggering abortive infection after the CRISPR-Cas system has been destroyed by Anti-CRISPRS protein. Additionally, we discuss the evolutionary homology between the type III toxin AbiF and the type VI CRISPR effector Cas13, offering a new perspective for understanding the origin of CRISPR-Cas systems. These findings not only reveal the functional coupling of prokaryotic defense systems but also provide a powerful theoretical framework and practical solutions for addressing stability challenges in CRISPR technology applications.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The interaction between gut microbiota dysbiosis and CKD progression via the "gut-kidney axis" is increasingly recognized. Gut-derived uremic toxins (e.g., indoxyl sulfate and p-cresyl sulfate) accumulate systemically, while beneficial metabolites like short-chain fatty acids (SCFAs) decrease, contributing to inflammation, oxidative stress, and kidney fibrosis. Traditional Chinese Medicine (TCM), including complex formulae, single herbs, and active ingredients, has long been used to manage CKD. Emerging evidence-primarily from animal studies-highlights its potential to alleviate the disease by modulating the gut microbiota. This review summarizes how TCM interventions re-establish gut microbial symbiosis by regulating microbial composition, reducing toxin load, and reinforcing intestinal barrier integrity, thereby ameliorating systemic inflammation and protecting kidney function. Targeting the gut microbiota represents a promising therapeutic frontier for CKD, and TCM offers a rich resource for developing novel microbiota-modulating strategies. However, future research must focus on validating molecular mechanisms, standardizing TCM preparations, and conducting rigorous clinical trials to facilitate clinical translation.
通过“肠肾轴”,肠道菌群失调与CKD进展之间的相互作用越来越被认识到。肠道源性尿毒症毒素(如硫酸吲哚酚和对甲酚硫酸盐)在全身积累,而有益的代谢物如短链脂肪酸(SCFAs)减少,导致炎症、氧化应激和肾纤维化。中药(Traditional Chinese Medicine, TCM),包括复方、单药和有效成分,长期以来被用于治疗慢性肾病。新出现的证据——主要来自动物研究——强调了它通过调节肠道微生物群来减轻疾病的潜力。本文综述了中医药干预如何通过调节微生物组成、减少毒素负荷、增强肠道屏障完整性,从而改善全身炎症和保护肾功能,重建肠道微生物共生关系。针对肠道菌群是CKD治疗的一个有前景的前沿,中医药为开发新的微生物群调节策略提供了丰富的资源。然而,未来的研究必须集中在验证分子机制,规范中药制剂,并进行严格的临床试验,以促进临床翻译。
{"title":"Targeting the Gut-Kidney Axis: Modulation of Gut Microbiota by Traditional Chinese Medicine for Chronic Kidney Disease Management.","authors":"Yijing Xin, Libin Pan","doi":"10.3390/toxins17120599","DOIUrl":"10.3390/toxins17120599","url":null,"abstract":"<p><p>The interaction between gut microbiota dysbiosis and CKD progression via the \"gut-kidney axis\" is increasingly recognized. Gut-derived uremic toxins (e.g., indoxyl sulfate and p-cresyl sulfate) accumulate systemically, while beneficial metabolites like short-chain fatty acids (SCFAs) decrease, contributing to inflammation, oxidative stress, and kidney fibrosis. Traditional Chinese Medicine (TCM), including complex formulae, single herbs, and active ingredients, has long been used to manage CKD. Emerging evidence-primarily from animal studies-highlights its potential to alleviate the disease by modulating the gut microbiota. This review summarizes how TCM interventions re-establish gut microbial symbiosis by regulating microbial composition, reducing toxin load, and reinforcing intestinal barrier integrity, thereby ameliorating systemic inflammation and protecting kidney function. Targeting the gut microbiota represents a promising therapeutic frontier for CKD, and TCM offers a rich resource for developing novel microbiota-modulating strategies. However, future research must focus on validating molecular mechanisms, standardizing TCM preparations, and conducting rigorous clinical trials to facilitate clinical translation.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baozhu Guo, Idrice Carther Kue Foka, Dongliang Wu, Josh P Clevenger, Rong Di, Jake C Fountain
The year 2025 marks two significant milestones for aflatoxin research: 65 years since aflatoxin was first identified in 1960, and 50 years of focused research on preharvest aflatoxin contamination since it was first recognized in 1975. Studies in the 1970s revealed that A. flavus could infect crops like maize and produce aflatoxin in the field before harvest and made it possible to investigate the potential genetic resistance in crops to mitigate the issues. Tremendous efforts have been made to learn about the process and regulation of aflatoxin production along with interactions between A. flavus and host plants as influenced by environmental factors. This has allowed for the breeding of more resistant crops and investigations into the underlying genetic and genomic components of resistance mechanisms in crops like maize and peanut. However, despite decades of studies, many questions remain. One established "dogma" is that drought stress, especially when combined with high temperatures, is the single greatest contributing factor to preharvest aflatoxin contamination and is a perennial risk faced throughout the major agricultural production regions of the world. Although there are many reviews summarizing the decades' long wealth of information about A. flavus, aflatoxin biosynthesis, management and host plant resistance, there are few reports that put the spotlight on why aflatoxin contamination is exacerbated by drought stress, which places plants under severe physiological stress and weakens immune systems. Therefore, here we will focus on three major areas of research in maize: the "living embryo" theory and host resistance mechanisms, the "Key Largo hypothesis" and the causes of drought-exacerbated aflatoxin contamination, and recent advancements in CRISPR-based genome editing for enhancing drought tolerance and increasing plant immune responses. This will highlight key breakthroughs and future prospects for the continuing development of superior crop germplasm and cultivars and for mitigating aflatoxin contamination in food and feed supply chains.
{"title":"Fifty Years and Counting: Searching for the \"Silver Bullet\" or the \"Silver Shotgun\" to Mitigate Preharvest Aflatoxin Contamination.","authors":"Baozhu Guo, Idrice Carther Kue Foka, Dongliang Wu, Josh P Clevenger, Rong Di, Jake C Fountain","doi":"10.3390/toxins17120596","DOIUrl":"10.3390/toxins17120596","url":null,"abstract":"<p><p>The year 2025 marks two significant milestones for aflatoxin research: 65 years since aflatoxin was first identified in 1960, and 50 years of focused research on preharvest aflatoxin contamination since it was first recognized in 1975. Studies in the 1970s revealed that <i>A. flavus</i> could infect crops like maize and produce aflatoxin in the field before harvest and made it possible to investigate the potential genetic resistance in crops to mitigate the issues. Tremendous efforts have been made to learn about the process and regulation of aflatoxin production along with interactions between <i>A. flavus</i> and host plants as influenced by environmental factors. This has allowed for the breeding of more resistant crops and investigations into the underlying genetic and genomic components of resistance mechanisms in crops like maize and peanut. However, despite decades of studies, many questions remain. One established \"dogma\" is that drought stress, especially when combined with high temperatures, is the single greatest contributing factor to preharvest aflatoxin contamination and is a perennial risk faced throughout the major agricultural production regions of the world. Although there are many reviews summarizing the decades' long wealth of information about <i>A. flavus</i>, aflatoxin biosynthesis, management and host plant resistance, there are few reports that put the spotlight on why aflatoxin contamination is exacerbated by drought stress, which places plants under severe physiological stress and weakens immune systems. Therefore, here we will focus on three major areas of research in maize: the \"living embryo\" theory and host resistance mechanisms, the \"Key Largo hypothesis\" and the causes of drought-exacerbated aflatoxin contamination, and recent advancements in CRISPR-based genome editing for enhancing drought tolerance and increasing plant immune responses. This will highlight key breakthroughs and future prospects for the continuing development of superior crop germplasm and cultivars and for mitigating aflatoxin contamination in food and feed supply chains.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Uwe Martin, Jürgen Frevert, Je-Young Park, Haiyan Cui, Andy Curry, Wei Qi Loh
Recent botulinum neurotoxin type A (BoNT/A) formulations have shifted towards the use of polysorbate 20 (PS20) and polysorbate 80 (PS80) as a non-human-derived excipient to enhance product stability. Polysorbates are a distinct class of synthetic non-ionic surfactants with high heterogeneity in chemical structure and properties. Accumulating mechanistic and clinical evidence suggests that they may trigger immunological reactions, including hypersensitivity and immunogenicity. Such risks are largely associated with their susceptibility to degradation via hydrolysis and oxidation, forming reactive byproducts that can interact with proteins and immune pathways. Despite these mechanistic insights, data on the association between polysorbate excipients and observed immune outcomes in practice is relatively sparse and excipient-related immunogenicity and hypersensitivity is often underrecognized in practice. This review provides a summary of polysorbate excipients in BoNT/A formulations, focusing on their chemical properties and degradation pathways, characterizing downstream immune effects and appraising available clinical data of polysorbate-containing BoNT/A formulations. Finally, we discuss potential risk mitigation strategies including process modifications that could prevent degradation, and consideration of alternative excipients, such as human serum albumin, that has been shown to be immunologically inert and has an established safety profile. By integrating chemical, mechanistic, and clinical perspectives, this review seeks to clarify the implications of polysorbate use in BoNT/A formulations and inform both clinical practice and future formulation strategies.
{"title":"Immunological Considerations of Polysorbate as an Excipient in Botulinum Neurotoxin Type A Formulations: A Narrative Review.","authors":"Michael Uwe Martin, Jürgen Frevert, Je-Young Park, Haiyan Cui, Andy Curry, Wei Qi Loh","doi":"10.3390/toxins17120598","DOIUrl":"10.3390/toxins17120598","url":null,"abstract":"<p><p>Recent botulinum neurotoxin type A (BoNT/A) formulations have shifted towards the use of polysorbate 20 (PS20) and polysorbate 80 (PS80) as a non-human-derived excipient to enhance product stability. Polysorbates are a distinct class of synthetic non-ionic surfactants with high heterogeneity in chemical structure and properties. Accumulating mechanistic and clinical evidence suggests that they may trigger immunological reactions, including hypersensitivity and immunogenicity. Such risks are largely associated with their susceptibility to degradation via hydrolysis and oxidation, forming reactive byproducts that can interact with proteins and immune pathways. Despite these mechanistic insights, data on the association between polysorbate excipients and observed immune outcomes in practice is relatively sparse and excipient-related immunogenicity and hypersensitivity is often underrecognized in practice. This review provides a summary of polysorbate excipients in BoNT/A formulations, focusing on their chemical properties and degradation pathways, characterizing downstream immune effects and appraising available clinical data of polysorbate-containing BoNT/A formulations. Finally, we discuss potential risk mitigation strategies including process modifications that could prevent degradation, and consideration of alternative excipients, such as human serum albumin, that has been shown to be immunologically inert and has an established safety profile. By integrating chemical, mechanistic, and clinical perspectives, this review seeks to clarify the implications of polysorbate use in BoNT/A formulations and inform both clinical practice and future formulation strategies.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seraina L C Müller, Chantal Zeier, Pablo Pfister, Nadia Menzi, Bita Tafrishi, Dirk J Schaefer, Jan A Plock, Tarek Ismail, Holger J Klein
Facial palsy affects millions worldwide. Botulinum toxin Type A (BoNT-A) is an established treatment for non-flaccid facial palsy, yet objective evidence remains limited. This study evaluates the effects of BoNT-A using AI-based tools and patient-reported outcome measures (PROMs). In this prospective observational study, patients with non-flaccid facial palsy received individualized BoNT-A injections. Exclusion criteria included age < 18, hypersensitivity to BoNT-A, or lack of follow-up. Assessments were conducted before and 3 weeks after treatment, including facial symmetry (Emotrics®), emotion expression (FaceReader™), and PROMs (FaCE and FDI). Eleven patients (mean age 50.1 ± 18 years) were included. BoNT-A significantly improved dynamic facial symmetry: eyebrow raising (p = 0.032), smile angle (p = 0.005), and lower lip height (p = 0.042). Emotion analysis showed no significant changes. PROMs revealed improvements in social well-being (FDI, p = 0.004) and aesthetic satisfaction (FaCE, p = 0.035), while functional FDI scores remained unchanged (p = 0.406). BoNT-A improves objective symmetry and patient satisfaction in non-flaccid facial palsy. The lack of change in emotional expression may reflect improved symmetry at the cost of dynamic muscle activation.
面瘫影响着全世界数百万人。A型肉毒毒素(BoNT-A)是一种治疗非弛缓性面瘫的方法,但客观证据仍然有限。本研究使用基于人工智能的工具和患者报告的结果测量(PROMs)评估BoNT-A的效果。在这项前瞻性观察研究中,非弛缓性面瘫患者接受个体化BoNT-A注射。排除标准包括年龄< 18岁,对BoNT-A过敏或缺乏随访。在治疗前和治疗后3周进行评估,包括面部对称性(Emotrics®)、情绪表达(FaceReader™)和PROMs (FaCE和FDI)。纳入11例患者(平均年龄50.1±18岁)。BoNT-A显着改善了动态面部对称性:眉毛抬起(p = 0.032),微笑角度(p = 0.005)和下唇高度(p = 0.042)。情绪分析显示无明显变化。PROMs显示了社会幸福感(FDI, p = 0.004)和审美满意度(FaCE, p = 0.035)的改善,而功能FDI得分保持不变(p = 0.406)。BoNT-A改善非弛缓性面瘫的客观对称性和患者满意度。情绪表达的缺乏变化可能反映了以动态肌肉激活为代价的对称性的改善。
{"title":"Artificial Intelligence Analysis of Symmetry and Emotions in Facial Palsy Patients After Botulinum Toxin A Injections.","authors":"Seraina L C Müller, Chantal Zeier, Pablo Pfister, Nadia Menzi, Bita Tafrishi, Dirk J Schaefer, Jan A Plock, Tarek Ismail, Holger J Klein","doi":"10.3390/toxins17120597","DOIUrl":"10.3390/toxins17120597","url":null,"abstract":"<p><p>Facial palsy affects millions worldwide. Botulinum toxin Type A (BoNT-A) is an established treatment for non-flaccid facial palsy, yet objective evidence remains limited. This study evaluates the effects of BoNT-A using AI-based tools and patient-reported outcome measures (PROMs). In this prospective observational study, patients with non-flaccid facial palsy received individualized BoNT-A injections. Exclusion criteria included age < 18, hypersensitivity to BoNT-A, or lack of follow-up. Assessments were conducted before and 3 weeks after treatment, including facial symmetry (Emotrics<sup>®</sup>), emotion expression (FaceReader™), and PROMs (FaCE and FDI). Eleven patients (mean age 50.1 ± 18 years) were included. BoNT-A significantly improved dynamic facial symmetry: eyebrow raising (<i>p</i> = 0.032), smile angle (<i>p</i> = 0.005), and lower lip height (<i>p</i> = 0.042). Emotion analysis showed no significant changes. PROMs revealed improvements in social well-being (FDI, <i>p</i> = 0.004) and aesthetic satisfaction (FaCE, <i>p</i> = 0.035), while functional FDI scores remained unchanged (<i>p</i> = 0.406). BoNT-A improves objective symmetry and patient satisfaction in non-flaccid facial palsy. The lack of change in emotional expression may reflect improved symmetry at the cost of dynamic muscle activation.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dominika Jaguś, Anna Pawłowska, Robert Krzysztof Mlosek
Background: Botulinum toxin injection is one of the most common esthetic procedures, yet complications may occur due to anatomical variability or suboptimal injection technique. This study aimed to evaluate the upper facial muscles using ultrasound, focusing on inter- and intraindividual variability.
Methods: The study involved volunteers aged 21-40 years, excluding those with prior facial treatments, trauma, or muscle disorders. The muscles examined included the occipitofrontalis (frontal belly), procerus, corrugator supercilii, and orbicularis oculi. Muscle thickness and distance from the epidermis were measured using high-frequency ultrasound. Statistical analyses included descriptive statistics, correlation with age and BMI, sex comparisons, and symmetry assessment.
Results: A total of 127 participants (103 women and 24 men) were enrolled, with a mean age of 28.8 ± 4.4 years. Age showed no significant correlation with muscle thickness or depth, supporting the internal consistency of the studied age group. BMI showed moderate correlations with the depth of the selected forehead muscles. Males showed greater thickness in the frontal and procerus muscles. Relative side-to-side asymmetry coefficients reached 40% for both thickness and depth, indicating notable individual laterality.
Conclusions: The study provides normative ultrasound parameters for the upper facial muscle in healthy adults. The results demonstrate significant anatomical variability depending on sex, BMI, and facial laterality, supporting individualized ultrasound-guided approaches for botulinum toxin injection.
{"title":"Ultrasound Evaluation of Upper Facial Muscles to Guide Botulinum Toxin Application.","authors":"Dominika Jaguś, Anna Pawłowska, Robert Krzysztof Mlosek","doi":"10.3390/toxins17120595","DOIUrl":"10.3390/toxins17120595","url":null,"abstract":"<p><strong>Background: </strong>Botulinum toxin injection is one of the most common esthetic procedures, yet complications may occur due to anatomical variability or suboptimal injection technique. This study aimed to evaluate the upper facial muscles using ultrasound, focusing on inter- and intraindividual variability.</p><p><strong>Methods: </strong>The study involved volunteers aged 21-40 years, excluding those with prior facial treatments, trauma, or muscle disorders. The muscles examined included the occipitofrontalis (frontal belly), procerus, corrugator supercilii, and orbicularis oculi. Muscle thickness and distance from the epidermis were measured using high-frequency ultrasound. Statistical analyses included descriptive statistics, correlation with age and BMI, sex comparisons, and symmetry assessment.</p><p><strong>Results: </strong>A total of 127 participants (103 women and 24 men) were enrolled, with a mean age of 28.8 ± 4.4 years. Age showed no significant correlation with muscle thickness or depth, supporting the internal consistency of the studied age group. BMI showed moderate correlations with the depth of the selected forehead muscles. Males showed greater thickness in the frontal and procerus muscles. Relative side-to-side asymmetry coefficients reached 40% for both thickness and depth, indicating notable individual laterality.</p><p><strong>Conclusions: </strong>The study provides normative ultrasound parameters for the upper facial muscle in healthy adults. The results demonstrate significant anatomical variability depending on sex, BMI, and facial laterality, supporting individualized ultrasound-guided approaches for botulinum toxin injection.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 12","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}