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Aims and Background: The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake., Material Methods: The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, ''GOD-PAP'' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting., Results: According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group., Conclusion: Multiple mechanisms point to Rutin's role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Iodine (I 2 ) as a broad-spectrum antiseptic has been widely used for treating bacterial infections. However, I 2 has low water-solubility and sublimes under ambient conditions, which limits its practical antibacterial applications. The highly specific and sensitive reaction between I 2 and starch discovered 200 years ago has been extensively applied in analytical chemistry, but the antibacterial activity of the I 2 -starch complex is rarely investigated. Herein, we develop a novel type of iodine-based antiseptics, iodine-soluble starch (I 2 -SS) cryogel, which can dissolve in water instantly and almost completely kill bacteria in 10 min at 2 μg/mL of I 2 . Although KI 3 and the commercially available povidone‑iodine (I 2 -PVP) solutions show similar antibacterial efficacy, the high affinity of I 2 to SS largely enhances the shelf stability of the I 2 -SS solution with ∼73 % I 2 left after one-week storage at room temperature. In sharp contrast, ∼8.5 % and ∼2.5 % I 2 are detected in KI 3 and I 2 -PVP solutions, respectively. Mechanistic study reveals that the potent antibacterial effect of I 2 -SS originates from its attack on multiple bacterial targets. The outstanding antibacterial activity, capability of accelerating wound healing, and good biocompatibility of I 2 -SS are verified through further in vivo experiments. This work may promote the development of next-generation iodine-based antiseptics for clinical use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Biomaterial-associated infections caused by bacteria pose a great threat to human health, and therefore, various antibacterial coatings have been developed to control bacterial infections. Povidone iodine (PVP-I) is a broad-spectrum antimicrobial agent without drug resistance to most pathogenic microorganisms and has been widely used in the clinic. However, its applications in the field of coatings are limited due to its strong water solubility. Here, we used initiated Chemical Vapor Deposition (iCVD) technique to synthesize cross-linked poly( N -vinylpyrrolidone- co -ethylene glycol dimethacrylate) (PVE) coatings to firmly immobilize poly( N -vinylpyrrolidone) (PVP) on surfaces. After complexation with iodine, PVE-I coatings exhibited potent bacteria-killing and antifouling activities against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus in vitro owing to the antibacterial effect of iodine and the hydrophilicity of VP, respectively. The killing and antifouling effects were positively correlated with the VP content. The PVE-I-2 coating displayed excellent anti-infection performance in a rat subcutaneous implantation model in vivo . This study provided a simple method for preparing stable povidone iodine coatings on surfaces via solvent-free iCVD, and combined bacteria-killing and antifouling strategies to fabricate multifunctional antibacterial coatings against bacterial infections on biomaterial surfaces.

Metronomic chemotherapy with cyclophosphamide (Cpp) has shown promising results in cancer protocols. These lower and prolonged doses have antiangiogenic, pro-cytotoxic, and moderate secondary effects. Molecular iodine (I 2 ) reduces the viability of cancer cells and, with chemotherapeutic agents, activates the antitumoral immune response and diminishes side effects. The present work evaluates the adjuvant of oral I 2 with Cpp using a murine model of mammary cancer. Female Sprague Dawley rats with 7,12-dimethylbenzantracene-induced tumors received Cpp intraperitoneal (50 and 70 mg/kg two times/week, iCpp50 and iCpp70) and oral (0.03%; 50 mg/Kg; oCpp50) doses. I 2 (0.05%, 50 mg/100 mL) and oCpp50 were offered in drinking water for three weeks. iCpp70 was the most efficient antitumoral dose but generated severe body weight loss and hemorrhagic cystitis (HC). I 2 prevented body weight loss, exhibited adjuvant actions with Cpp, decreasing tumor growth, and canceled HC mechanisms, including decreases in vascular endothelial growth factor (VEGF) and Survivin expression. oCpp50 + I 2 diminished angiogenic signals (CD34, vessel-length, and VEGF content) and proinflammatory cytokines (interleukin-10 and tumor necrosis factor-alpha) and increased cytotoxic (lymphocytic infiltration, CD8 + cells, Tbet, and interferon-gamma) and antioxidant markers (nuclear erythroid factor-2 and glutathione peroxidase). I 2 enhances the effectiveness of oCpp, making it a compelling candidate for a clinical protocol.

Nanozyme-mediated antioxidative therapy is a promising star for treating a myriad of important diseases through eliminating excessive reactive oxygen species (ROS) such as O 2 ·- and H 2 O 2 , a critical mechanism for inflammatory bowel disease (IBD). This work provides a high biocompatibility iodine-copper-zinc covalent doped carbon dots (Cu,Zn,I-CDs) with the catalase (CAT)-, superoxide dismutase (SOD)- and glutathione peroxidase (GPx)-like catalytic activities for treating ulcerative colitis (UC) by scavenging overproduced ROS. We found that I dopant aids in counteracting the positive charge at Cu,Zn dopants brought on by low pH, enabling Cu,Zn,I-CDs to process strong triple antioxidant nanozyme activities rather than Cu,Zn-CDs. Vitro experiments displayed that the Cu,Zn,I-CDs could scavenge the excessive ROS to protect cellular against oxidative stress and reduce the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. In sodium dextran sulfate (DSS)-induced colitis mice models, Cu,Zn,I-CDs with excellent biocompatibility could effectively relieve the inflammation of the colon, containing the reduction of the colon length, the damaged epithelium, the infiltration of inflammatory cells, and upregulation of antioxidant genes. Therefore, the therapy of Cu,Zn,I-CD antioxidant nanozymes is an effective approach and provides a novel strategy for UC treatment.

Voice prostheses are known to fail in few weeks to several months of implantation due to the clogging mainly caused by microbial biofilm formation, which is a cause of concern. Iodine is a known broad-spectrum biocide and is reported to easily form complexes with various polymers. For long term device disinfection, strong iodine complexation that offers sustained iodine release for a prolonged period is essential. The present research work deals with the synthesis of a poly(methyl methacrylate- n -butyl acrylate- N -vinyl-2-pyrrolidone) (poly[MMA-BA-NVP]) tercopolymer through free radical polymerization for surface coating thermoplastic polyurethane (TPU) based voice prostheses. The NVP content in the tercopolymer was varied from 20% to 50% to optimise iodine loading and subsequent release. Base TPU coated with the tercopolymer was treated with 4% aqueous iodine solution at room temperature (28 ± 3 °C) for two hours. It was observed that the tercopolymer containing 35% N -vinyl-2-pyrrolidone (NVP), 32.5% methyl methacrylate (MMA) and 32.5% butyl acrylate ( n BA) gave a stable coating on TPUs together with sustained iodine release for a prolonged period. Furthermore, the tercopolymer coated and iodine loaded TPUs exhibited excellent antimicrobial activity against Candida albicans , Staphylococcus aureus and Escherichia coli .

The spread of upper respiratory tract (URT) infections harms people's health and causes social burdens. Developing targeted treatment strategies for URT infections that exhibit good biocompatibility, stability, and strong antimicrobial effects remains challenging. The dual antimicrobial and antiviral effects of iodine (I 2 ) in combination with the cooling sensation of l-menthol in the respiratory tract can simultaneously alleviate URT inflammation symptoms. However, as both I 2 and l-menthol are volatile, addressing stability issues is crucial. In this study, a potassium iodide β-cyclodextrin metal-organic framework [β-CD-POF(I)] with appropriate particle size was used to coload and deliver I 2 and l-menthol. Primarily, β-CD-POF(I) was employed as the most efficient carrier to significantly enhance the stability of I 2 , surpassing any other known protection strategies in the pharmaceutical field (CD complexations, PVP conjugations, and cadexomer iodine). The mechanism underlying the improvement in stability of I 2 by β-CD-POF(I) was investigated through scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular docking. The results revealed that the key processes involved in improving stability were the inclusion of I 2 by β-CD cavities in β-CD-POF(I) and the formation of polyiodide anion between iodine ions and I 2 . Furthermore, the potential of β-CD-POF(I) to load and deliver drugs was validated, and coloading of l-menthol and I 2 demonstrated reliable stability. β-CD-POF(I) achieved a rate of URT deposition ≥95% in vitro, and the combined antibacterial effects of coloaded I 2 and l-menthol was better than I 2 or PVP-I alone, with no irritation noted following URT administration in rabbits. Therefore, the stable coloading of drugs by β-CD-POF(I), leading to enhanced antimicrobial effects, provides a new strategy for treating URT infections.

Antimicrobial resistance (AMR) poses an emanating threat to humanity's future. The effectiveness of commonly used antibiotics against microbial infections is declining at an alarming rate. As a result, morbidity and mortality rates are soaring, particularly among immunocompromised populations. Exploring alternative solutions, such as medicinal plants and iodine, shows promise in combating resistant pathogens. Such antimicrobials could effectively inhibit microbial proliferation through synergistic combinations. In our study, we prepared a formulation consisting of Aloe barbadensis Miller (AV), Thymol, iodine (I 2 ), and polyvinylpyrrolidone (PVP). Various analytical methods including SEM/EDS, UV-vis, Raman, FTIR, and XRD were carried out to verify the purity, composition, and morphology of AV-PVP-Thymol-I 2 . We evaluated the inhibitory effects of this formulation against 10 selected reference strains using impregnated sterile discs, surgical sutures, gauze bandages, surgical face masks, and KN95 masks. The antimicrobial properties of AV-PVP-Thymol-I 2 were assessed through disc diffusion methods against 10 reference strains in comparison with two common antibiotics. The 25-month-old formulation exhibited slightly lower inhibitory zones, indicating changes in the sustained-iodine-release reservoir. Our findings confirm AV-PVP-Thymol-I 2 as a potent antifungal and antibacterial agent against the reference strains, demonstrating particularly strong inhibitory action on surgical sutures, cotton bandages, and face masks. These results enable the potential use of the formulation AV-PVP-Thymol-I 2 as a promising antimicrobial agent against wound infections and as a spray-on contact-killing agent.

Postoperative infection and subsequent device loss are serious complications in the use of titanium dental implants and plates for jawbone reconstruction. We have previously reported that NaOH-CaCl 2 -thermal-ICl 3 -treated titanium (NaCaThIo) has a nano-scale surface and exhibits antibacterial activity against Staphylococcus aureus. The present study examined the surface properties of mixed-acid treated and then iodine-treated titanium (MA-NaCaThIo), and evaluated oral antibacterial activity and cytotoxicity compared with the results obtained with NaCaThIo. MA-NaCaThIo formed a surface layer with a nano-scale network structure having microscale irregularities, and both the thickness of the surface layer (1.49 ± 0.16 μm) and the average surface roughness (0.35 ± 0.03 μm) were significantly higher than those of NaCaThIo. Furthermore, MA-NaCaThIo maintained high hydrophilicity with a contact angle of 7.5 ± 1.7° even after 4 weeks, as well as improved apatite formation, iodine ion release, and antibacterial activity against Prevotella intermedia compared to NaCaThIo. Cell culture test revealed that MA-NaCaThIo exhibited no cytotoxicity against MG-63 and Vero cells, while increased cell proliferation, ALP activity and mineralization of MG-63 compared to NaCaThIo. This treated titanium is expected to be useful for the development of next-generation titanium devices having both bone-bonding and antibacterial properties., (© 2023 Wiley Periodicals LLC.)

Waterborne coatings with intrinsic antibacterial attributes have attracted significant attention due to their potential in mitigating microbial contamination while simultaneously addressing the environmental drawbacks of their solvent-based counterparts. Typically, antimicrobial coatings are designed to resist and eliminate microbial threats, encompassing challenges such as biofilm formation, fungal contamination, and proliferation of black mold. Iodine, when solubilized using ethylene glycol and incorporated as a complex into waterborne latex dispersions, has shown remarkable antimicrobial activity. Here, we demonstrate the effect of the film formation process of these iodinated latex dispersions on their antimicrobial properties. The effect of iodine on the surface morphology and mechanical, adhesion, and antimicrobial properties of the generated films was investigated. Complete integration and uniform distribution of iodine in the films were confirmed through UV-vis spectrophotometry and a laser Raman imaging system (LRIS). In terms of properties, iodinated films showed improved mechanical strength and adhesion compared with blank films. Further, the presence of iodine rendered the films rougher, making them susceptible to bacterial adhesion, but interestingly provided enhanced antibiofilm activity. Moreover, thicker films had a lower surface roughness and reduced biofilm growth. These observations are elucidated through the complex interplay among film thickness, surface morphology, and iodine properties. The insights into the interlink between the film formation process and antimicrobial properties of iodinated latex dispersions will facilitate their enhanced application as sustainable alternatives to solvent-based coatings.

Objective: To evaluate the topical antiseptic activity of saline, chlorhexidine (CHX), and povidone-iodine (PI) scrubs on the skin of chickens with or without the addition of DuraPrep (DP)., Animals: 7 healthy adult Orpington hens (Gallus gallus domesticus)., Methods: The right apterium corporale laterale was swabbed for standard aerobic bacterial culture and colony-forming unit (CFU) determination. The apterium was divided into 3 areas and treated with sterile saline, CHX, or PI. Samples were collected by swabbing each area before and after additional treatment with DP. CFU's were counted after 48 hours of incubation. Statistical analysis was performed using a linear mixed model with a continuous outcome., Results: Compared to saline, CHX and PI treatment without DP decreased CFU count by 119 (95% CI, 55 to 183; P < .001) and 123 (95% CI, 58 to 187; P < .001), respectively. The application of DP after CHX and PI further decreased CFU counts by 6 (P = .01) and 9 (P = .01), respectively. DP after saline treatment decreased counts by 128 CFU (95% CI, 63 to 192; P < .001). No significant difference was detected between saline, PI, or CHX after DP application (-1.0 CFU; 95% CI, 63.4 to -65.4; P = .98 for both PI and CHX)., Clinical Relevance: CHX or PI provided greater reductions in bacterial CFU than saline, and all combinations with DP provided similar results. No notable cutaneous reactions were detected at any point. This data suggests that a scrub protocol including CHX or PI with DP is acceptable in surgical site preparation of chickens.

The ideal bone implant would effectively prevent aseptic as well as septic loosening by minimizing stress shielding, maximizing bone ingrowth, and preventing implant-associated infections. Here, a novel gradient-pore-size titanium scaffold was designed and manufactured to address these requirements. The scaffold features a larger pore size (900 μm) on the top surface, gradually decreasing to small sizes (600 μm to 300 μm) towards the center, creating a gradient structure. To enhance its functionality, the additively manufactured scaffolds were biofunctionalized using simple chemical and heat treatments so as to incorporate calcium and iodine ions throughout the surface. This unique combination of varying pore sizes with a biofunctional surface provides highly desirable mechanical properties, bioactivity, and notably, long-lasting antibacterial activity. The target mechanical aspects, including low elastic modulus, high compression, compression-shear, and fatigue strength, were effectively achieved. Furthermore, the biofunctional surface exhibits remarkable in vitro bioactivity and potent antibacterial activity, even under conditions specifically altered to be favorable for bacterial growth. More importantly, the integration of small pores alongside larger ones ensures a sustained high release of iodine, resulting in antimicrobial activity that persisted for over three months, with full eradication of the bacteria. Taken together, this gradient structure exhibits obvious superiority in combining most of the desired properties, making it an ideal candidate for orthopedic and dental implant applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The inconformity (IC) between pathological and imaging remissions after neoadjuvant immunotherapy in patients with NSCLC can affect the evaluation of curative effect of neoadjuvant therapy and the decision regarding the chance of surgery., Materials and Methods: Patients who achieved disease control(CR/PR/SD) after neoadjuvant chemoimmunotherapy from a clinical trial (NCT04326153) and after neoadjuvant chemotherapy during the same period were enrolled in this study. All patients underwent radical resection and systematic mediastinal lymphadenectomy after neoadjuvant treatments. The pathological remission, immunohistochemistry (CD4, CD8, CD20, CD56, FoxP3, CD68, CD163, CD11b tumor-infiltrating lymphocytes, or macrophages), and single-source dual-energy computed tomography (ssDECT) scans were assessed. The IC between imaging remission by CT and pathological remission was investigated. The underlying cause of IC, the correlation between IC and DFS, and prognostic biomarkers were explored., Results: After neoadjuvant immunotherapy, enhanced immune killing and reduced immunosuppressive performance were observed. 70 % of neoadjuvant chemoimmunotherapy patients were in high/medium IC level. Massive necrosis and repair around and inside the cancer nest were the main pathological changes observed 30-45 days post-treatment with PD1/PD-L1 antibody and were the main causes of IC between the pathology and imaging responses after neoadjuvant immunotherapy. High IC and preoperative CD8 expression (H score ≥ 3) indicate a high pathological response rate and prolonged DFS. Iodine material density ssDECT images showed that the iodine content in the lesion causes hyperattenuation in post-neoadjuvant lesion in PCR patient., Conclusions: Compared to chemotherapy and targeted therapy, the efficacy of neoadjuvant immunotherapy was underestimated based on the RECIST criteria due to the unique antitumor therapeutic mechanism. Preoperative CD8+ expression and ssDECT predict this IC and evaluate the residual tumor cells. This is of great significance for screening immune beneficiaries and making more accurate judgments about the timing of surgery., Competing Interests: Declaration of competing interest All authors declare no financial or non-financial competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Iodine is a vital microelement and a powerful antiseptic with a rapid and broad spectrum of action. The development of iodophor compounds to improve the solubility and stability of iodine is still challenging. Here, we report the synthesis of a novel cationic β-cyclodextrin bearing a choline-like pendant (β-CD-Chol) designed to complex and deliver iodine to bacterial cells. The characterization of β-CD-Chol and the investigation of the inclusion complex with iodine were performed by NMR spectroscopy, mass spectrometry, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. The functionalization with the positively charged unit conferred improved water-solubility, mucoadhesivity, and iodine complexation efficiency to the β-CD scaffold. The water-soluble β-CD-Chol/iodine complex efficiently formed both in solution and by solid-vapor reaction. The solid complex exhibited a significant stability for months. Iodine release from the inclusion complex was satisfactory and the bactericidal activity was proved against a Staphylococcus epidermidis strain. The absence of cytotoxicity tested on human keratinocytes and the improved mucoadhesivity make β-CD-Chol a promising drug delivery system and an appealing iodophor candidate for iodine-based antisepsis including mucosa disinfection., Competing Interests: Declaration of competing interest The Authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic wound infections are generally of polymicrobial nature with aerobic and anaerobic bacteria, as well as fungi frequently observed in them. Wound treatment involves a series of steps, including debridement of the wound, flushing, and often the use of multiple wound dressings many of which are antimicrobial. Yet, many wound dressings are tested versus single species of planktonic microbes, which fails to mirror the real-life presence of biofilms., Aims: Simple biofilm models are the first step to testing of any antimicrobial and wound dressing; therefore, the aim of this study was to develop and validate a simple polymicrobial colony biofilm wound model comprised of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on RPMI-1640 agar. The model was then used to evaluate the topical disinfectant chlorohexidine and four commercially available wound dressings using the polymicrobial model. The model used was as a starting point to mimic debridement in clinical care of wounds and the effectiveness of wound dressings evaluated afterwards., Methods and Results: Planktonic assessment using AATCC100-2004 demonstrated that all antimicrobial wound dressings reduced the planktonic microbial burden below the limit of detection; however, when challenged with polymicrobial colony biofilms, silver wound dressings showed limited effectiveness (1-2 log CFU reductions). In contrast, a single iodine releasing wound dressing showed potent antibiofilm activity reducing all species CFUs below the limit of detection (>6-10 log) depending on the species. A disrupted biofilm model challenge was performed to represent the debridement of a wound and wound silver-based wound dressings were found to be marginally more effective than in whole colony biofilm challenges while the iodine containing wound dressing reduced microbial recovery below the limit of detection., Conclusions: In this model, silver dressings were ineffective versus the whole colony biofilms but showed some recovery of activity versus the disrupted colony biofilm. The iodine wound dressing reduced the viability of all species below the level of detection. This suggests that mode of action of wound dressing should be considered for the type of biofilm challenge as should the clinical use, e.g. debridement., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Iodine-containing coatings were prepared on pure Ti surfaces via electrochemical deposition to enhance their antibacterial properties. The factors influencing iodine content were analyzed using an orthogonal experiment. The electrochemically deposited samples were characterized using scanning electron microscopy with energy dispersive spectroscopy and X-ray photoelectron spectroscopy, and their antibacterial properties and cytotoxicity were evaluated. The results showed that changing the deposition time is an effective way to control the iodine content. The iodine content, coating thickness, and adhesion of the samples increased with deposition time. Iodine in the coatings mainly exists in three forms, which are I 2 , I 3 - , and pentavalent iodine. For samples with iodine-containing coatings, the antibacterial ratios against E. coli and S. aureus were greater than 90% and increased with increasing iodine content. Although the samples with iodine-containing coatings showed some inhibition of the proliferation of MC3T3-E1 cells, the cell viabilities were all higher than 80%, suggesting that iodine-containing coatings are biosafe., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Investigating the development toxicity of perfluorinated iodine alkanes (PFIs) is critical, given their estrogenic effects through binding with estrogen receptors (ERs). In the present study, two PFIs, including dodecafluoro-1,6-diiodohexane (PFHxDI) and tridecafluorohexyl iodide (PFHxI), with binding preference to ERα and ERβ, respectively, were selected to evaluate their effects on proliferation and differentiation of the mouse embryonic stem cells (mESCs). The results revealed that, similar to E 2 , 50 µmol/L PFHxDI accelerated the cell proliferation of the mESCs. The PFI stimulation at the exposure concentrations of 2-50 µmol/L promoted the differentiation of the mESCs as characterized by the upregulation of differentiation-related biomarkers (i.e., Otx2 and Dnmt3β) and downregulation of pluripotency genes (i.e., Oct4, Nanog, Sox2, Prdm14 and Rex1). Comparatively, PFHxDI exhibited higher induction effect on the differentiation of the mESCs than did PFHxI . The tests on ER signaling indicated that both PFI compounds induced exposure concentration-dependent expressions of ER signaling-related biomarkers (i.e., ERα, ERβ and Caveolin-1) in the mESCs, and the downstream ER responsive genes (i.e., c-fos, c-myc and c-jun) well responded to PFHxI stimulation. The role of ER in PFI-induced effects on the mESCs was further validated by the antagonistic experiments using an ER inhibitor (ICI). The findings demonstrated that PFIs triggered ER signaling, and perturbed the differentiation program of the mESCs, causing the potential health risk during early stage of development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Bacterial infections have always been a major threat to public health, and the development of effective antibacterial substances from natural polymers is crucial. 2-Aminoisonicotinic acid (AN) was grafted onto chitosan by 1-ethyl-(3-dimethylaminopropyl)carbodiimide-mediated coupling reactions, and then modified chitosan‑iodine (CSAN-I) complexes were prepared by solvent-assisted grinding. The samples were characterized using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, proton nuclear magnetic resonance spectroscopy, and X-ray diffraction, confirming that CSAN-I complexes had been successfully prepared. Thermogravimetric (TG) analysis indicated that the chemical modification of chitosan and iodine complexation reduced the thermal stability; X-ray photoelectron spectroscopy (XPS) analysis revealed that 81 % of the iodine in CSAN-I complex was in the form of triiodide ions. The iodine contents of three CSAN-I complexes (CSAN-I-1, CSAN-I-2 and CSAN-I-3) were 1.59 ± 0.22 %, 3.18 ± 0.26 %, and 5.56 ± 0.41 %, respectively. The antibacterial effects were evaluated in vitro, and the results indicated that CSAN-I complexes had strong antibacterial activities against both E. coli and S. aureus. In particular, CSAN-I-3 exhibited the best antibacterial effect. In addition, CSAN-I-3 was nontoxic to L929 cells with good cytocompatibility. Therefore, CSAN-I complexes can be considered as promising candidates for wound management in clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Infections are still a major cause of morbidity in burn wounds. Although silver has been used strongly in past centuries as an anti-bacterial, it can lead to allergic reactions, bacterial resistance, and delayed wound healing. Iodine-based antibacterials are becoming an interesting alternative. In this work, the effect of complexation with poly(vinyl pyrrolidone) (PVP) and poly(ethylene oxide) (PEO)-based polymers is explored by using different acrylate-endcapped urethane-based poly(ethylene glycol) (AUP) polymers, varying the molar mass (MM) of the poly(ethylene glycol) (PEG) backbone, with possible addition of PVP. The higher MM AUP outperforms the swelling potential of commercial wound dressings such as Kaltostat, Aquacel Ag, and Hydrosorb and all MM show superior mechanical properties. The addition of iodine to the polymers is compared to Iso-Betadine Tulle (IBT). Interestingly, the addition of PVP does not lead to increased iodine complexation compared to the blank AUP polymers, while all have a prolonged iodine release compared to the IBT, which leads to a burst release. The observed prolonged release also leads to larger inhibition zones during antibacterial tests. Complexing iodine in AUP polymers with or without PVP leads to antimicrobial wound dressings which may hold potential for future application to treat infected wounds., (© 2023 Wiley-VCH GmbH.)

Objectives: To measure the absorbed dose to the thyroid in patients injected with 123 I-Ioflupane where the thyroid was not blocked with prophylaxis to investigate whether thyroid blocking should be limited to younger patients. This risk from the additional absorbed dose to the thyroid was then compared to the risk from iodine overdose through ingestion of the iodide prophylaxis, resulting in iodine-induced hyper/hypothyroidism (IIH)., Methods: A cohort of patients (n = 30) who did not receive thyroid prophylaxis underwent static thyroid imaging 3 h after 123 I-Ioflupane administration. The measured thyroidal uptake of free 123 I was then extrapolated to peak uptake time (24 h post-administration). This value was used to calculate cumulated activity in the thyroid and thus thyroid-thyroid absorbed dose D(rthy←rthy ) using the relevant S-value in the MIRD method., Results: Mean D(rthy←rthy ) was found to be 13.6 mGy with an SD of 8.8 mGy; this would contribute an additional 0.5 mSv to the effective dose., Conclusion: ARSAC recommends in its Notes for Guidance prophylactic thyroid blocking if the absorbed dose to the thyroid is >50 mGy; the maximum thyroid dose in this study cohort was 36.3 mGy. With risk from IIH and its associated cardiac complications increasing with age, this study suggests that iodide prophylaxis with 123 I-Ioflupane should be reconsidered for elderly patient., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Meeting the diverse requirements of effective wound repair while surpassing the single-function limitations of traditional wound dressings is a significant challenge. In this study, we successfully synthesized an inclusion complex of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and iodine using the saturated aqueous solution method. Additionally, dialdehyde cellulose (DAC) was extracted from fat-free cotton through oxidation. To enhance wound healing, l-glutamine (l-glu) was utilized as a functional molecule, resulting in composite hydrogels with hemostatic, sterilizing, and wound-healing-promoting properties that were achieved by adsorbing the resulting inclusion complex. Through TG and SEM analysis, we confirmed that iodine was effectively accommodated by cyclodextrin and was uniformly attached to the hydrogel. The hydrogel exhibits exceptional long-term moisturizing and bactericidal properties, while also demonstrating excellent swelling, oxygen permeability, hemolytic, and mechanical properties, fully satisfying the requirements of wound treatment. External coagulation tests revealed that the hydrogel can rapidly coagulate 4.5 times its own weight of blood. Moreover, in a full-thickness scald mouse model, the hydrogel effectively promotes wound healing. The development of this multifunctional composite hydrogel presents a novel approach to advance wound dressing research, holding substantial potential for practical applications.

Microbial biofilms are a major hindrance in the wound healing process, prolonging the inflammatory response phase, thus making them a target in treatment. The aim of this study is to assess the antibacterial properties of commercially available wound dressings, of various material composition and antibacterial agents, towards multiple in vitro microbial and biofilm models. A variety of in vitro microbial and biofilm models were utilised to evaluate the ability of wound dressing materials to sequester microbes, prevent dissemination and manage bioburden. Sequestering and dissemination models were used to evaluate the ability of wound dressing materials to prevent the biofilm-forming bacterium, Pseudomonas aeruginosa, from migrating through dressing materials over a 24-72 h challenge period. Additionally, Centre for Disease Control (CDC) Bioreactor and Drip Flow models were used to evaluate antibacterial killing efficacy towards established P. aeruginosa and Staphylococcus aureus biofilms using more challenging, wound-like models. Controlled-release iodine foam and silver-impregnated carboxymethylcellulose (CMC) wound dressing materials demonstrated potent biofilm management properties in comparison to a methylene blue and gentian violet-containing foam dressing. Both the iodine-containing foam and silver-impregnated CMC materials effectively prevented viable P. aeruginosa dissemination for up to 72 h. In addition, the controlled-release iodine foam and silver-impregnated CMC materials reduced P. aeruginosa bioburden in the Drip Flow model. The controlled-release iodine foam demonstrated superiority in the CDC Bioreactor model, as both the silver- and iodine-containing materials reduced S. aureus to the limit of detection, but P. aeruginosa growth was only completely reduced by controlled-release iodine foam dressing materials. The data generated within the in vitro biofilm models supports the clinical data available in the public domain for the implementation of iodine foam dressings for effective biofilm management and control in wound care., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Purpose: To investigate the virucidal effects of a polyvinyl alcohol iodine, Saniode, against 16 types of human mastadenovirus (HAdV) causing ophthalmic, respiratory, gastrointestinal, urinary, and systemic infections., Study Design: Laboratory investigation METHODS: Fifty microliters of Saniode were exposed to 10 μL each containing HAdV virus stock solution of 1 × 10 6  copies/μL of HAdV-1, -2, -3, -4, 5, -6, -7, -8, -11, -37, -53, -54, -56, -64, -81, and -85 for 10 s, 30 s, 1 min, and 3 min. After neutralization with 0.5% sodium thiosulfate, the mixture was diluted by ten-fold serial dilution and inoculated into 24 wells containing confluent A549 cell monolayers. Virucidal effects were calculated relative to the positive control on days 7-10 and observed until 30 days post-infection., Results: Saniode satisfied the EN-14476 criterion for virucidal effects (>99.99%) for all HAdV types at all exposure times, including at 10 s on days 7 to 10 post-infection. All types of HAdVs that reacted for > 1 min achieved 99.99% reduction, including after 30 days., Conclusion: Saniode displayed virucidal effects against all tested HAdV types. Currently, with no specific medication available for HAdVs in ocular infection, this could be an option to prevent the spread of keratoconjunctivitis., (© 2023. Japanese Ophthalmological Society.)

Background: Implant-related infections are a challenging complication of orthopedic surgery, primarily due to the formation of bacterial biofilms on the implant surface. An antibacterial coating for titanium implants was developed to provide novel insights into the prevention and treatment of implant-related infections., Methods: Titanium plates were coated with TiO 2 nanotubes by anodization, and iodine was doped onto the coating via electrophoretic deposition. The obtained plates were characterized using a range of analytical techniques. Subsequently, Staphylococcus aureus was inoculated onto the surfaces of untreated titanium plates (control group), TiO 2 -nanocoated titanium plates (TiO 2 group), and iodine-doped TiO 2 -nanocoated titanium plates (I-TiO 2 group) to compare their antibacterial properties., Results: Twenty-four hour in vitro antimicrobial activity test of the I-TiO 2 group against Staphylococcus aureus was superior to those of the other groups, and this difference was statistically significant (P < 0.05)., Conclusions: This coating technology provides a new theoretical basis for the development of anti-infective implants against Staphylococcus aureus in orthopedics., (© 2023. The Author(s).)

The growing incidence of thyroid disease triggered by excess iodine uptake poses a severe health threat throughout the world. Extracellular interference therapies impede iodine transport across the sodium-iodide symporter (NIS) membrane protein and thus prevent excessive iodine uptake by thyroid cells, which may lessen the occurrence of disease. Herein, we for the first time utilized nano-starch particles (St NPs) to regulate iodine transport across the NIS protein of thyroid cells by using extracellular interference therapy. By precisely encapsulating iodine within the cavity of a glucan α-helix via hydrogen bonding, extracellular St NPs prevented excess iodine uptake by thyroid cells in vitro and in vivo; this down-regulated the expression of NIS protein (0.06-fold) and autophagy protein LC3B-II (0.35-fold). We also found that St NPs regulated the metabolic pathway of iodine in zebrafish. We believe this proposed strategy offers a novel insight into controlling iodine uptake by the thyroid and indicates a new direction for preventing iodine-induced thyroid disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Molecular iodine (I 2 ) prevents oxidative stress and prostate hyperplasia induced by hyperandrogenism and reduces cell viability in prostate cancer cell lines. Here, we aimed to evaluate the protective effect of I 2 and testosterone (T) on hyperestrogenism-induced prostate inflammation. Additionally, the effects of I 2 and/or tumor necrosis factor (TNF) on cell viability and interleukin 6 (IL6) secretion were evaluated in a prostate cancer cell line (DU145). We also investigated whether the effects of I 2 on viability are peroxisome proliferator-activated receptor gamma (PPARG)-dependent. Castrated (Cx) rats received pellets of either 17β estradiol (E 2 ) or E 2 and T and were treated with I 2 (0.05%) in the drinking water for four weeks. The experimental groups were sham, Cx, Cx + E 2 , Cx + E 2 +I 2 , Cx + E 2 +T, and Cx + E 2 +T + I 2 . As expected, inflammation was triggered in the Cx + E 2 group (high inflammation score; increase in TNF and transcriptional activity of RELA [nuclear factor-kappa B p65 subunit]), and this effect was diminished in the Cx + E 2 +T group (medium inflammation score and decrease in TNF). The lowest inflammation score (decrease of TNF and RELA and increase of PPARG) was obtained in the Cx + E 2 +T + I 2 group. In DU145 cells, I 2 (400 μM) and TNF (10 ng/ml) additively reduced cell viability, and I 2 reduced the production of TNF-stimulated IL6. The PPARG antagonist (GW9662) did not inhibit the effects of I 2 on the loss of cell viability. In summary, our data suggest that I 2 and T exert a synergistic anti-inflammatory action on the normal prostate, and the interrelationship between I 2 and TNF leads to anti-proliferative effects in DU145 cells. PPARG does not seem to participate in the I 2 -induced cell viability loss in the prostate., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The instability and volatility of iodine is high, however, effective iodine biocidal species can be readily stored in iodinated azoles and then be released upon decomposition or detonation. Iodine azoles with high iodine content and high thermal stability are highly desired. In this work, the strategy of methylene bridging with asymmetric structures of 3,4,5-triiodo-1-H-pyrazole (TIP), 2,4,5-triiodo-1H-imidazol (TIM), and tetraiodo-1H-pyrrole (TIPL) are proposed. Two highly stable fully iodinated methylene-bridged azole compounds 3,4,5-triiodo-1-((2,4,5-triiodo-1H-imidazol-1-yl)methyl)-1H-pyrazole ( 3 ) and 3,4,5-triiodo-1-((tetraiodo-1H-pyrrol-1-yl)methyl)-1H-pyrazole ( 4 ) were obtained with high iodine content and excellent thermal stability (iodine content: 84.27% for compound 3 and 86.48% for compound 4 ; T d : 3 : 285 °C, 4 : 260 °C). Furthermore, their composites with high-energy oxidant ammonium perchlorate (AP) were designed. The combustion behavior and thermal decomposition properties of the formulations were tested and evaluated. This work may open a new avenue to develop advanced energetic biocidal materials with well-balanced energetic and biocidal properties and versatile functionality.

Iodine, as a typical haloid element in group VIIA, has been extensively applied as antiseptics clinically, thanks to its effective and wide-spectrum antimicrobial activity against bacteria, fungi, and viruses. Nevertheless, current iodic sterilizing agents are still limited to topical applications such as instrument sterilization and treatments of skin or mucous membrane infection due to its unsatisfactory stability and biocompatibility. Here, we propose an emerging two-dimensional iodine nanomaterial (noted as iodinene) for the treatment of infection diseases in vivo . Iodinene nanosheets were fabricated by a facile and environmentally friendly approach via sonication-assisted liquid exfoliation, which present an intriguing layered structure and negligible toxicity. The as-synthesized iodinene would experience an in situ allotropic transformation spontaneously to release active HIO and I 2 molecules by reacting with H 2 O 2 in the infectious microenvironment. By the in situ production of active HIO and I 2 molecules via allotropic transformation, iodinene presents enhanced antibacterial efficacy against Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa . In vivo outcome demonstrates the desirable antibacterial efficacy of iodinene in treating bacterial wound infection and pneumonia. This study thus offers an alternative to conventional sterilizing agents against hard-to-treat bacterial infections.

Recurrent infection of chronic wounds remains a major clinical challenge. Recently, the hydrogel antibacterial materials have attracted extensive attention for preventing infection in wound healing. In this study, a hybrid hydrogel made of polyvinyl alcohol - iodine (PAI), sodium carboxymethyl cellulose (CMC), and carbamino quantum dot (CQDs) was prepared by the cross-linking of hydrogen bonds, named as polyvinyl alcohol‑iodine/sodium carboxymethyl cellulose/carbon quantum dots (PAI/CMC/CQDs). The composite hydrogels exhibited the outstanding photothermal conversion efficiency with near infrared (NIR) light irradiation, and the high antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Meanwhile, the elevated temperature of the composite hydrogels up to ∼45 °C was able to stimulate the migration of epidermal cell to accelerate skin repair. Given that PAI and CQDs could respond to different pH values (5-8), the real-time would pH information was provided by the visible light and fluorescent light dual monitoring system by naked eye. Moreover, the visible-fluorescent images could be collected and transformed into RGB signals to quantify the would pH levels, avoiding secondary injuries caused by frequent dressing changes. PAI/CMC/CQDs was demonstrated the significant therapeutic effect on chronic wounds by eliminating bacterial infections and promoting skin repair under the smart RGB monitoring system., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Iodine-containing formulations have been widely used to treat iodine deficiency and as antiseptics. Lecithin-bound iodine (LBI) has been approved to treat allergic diseases in Japan; however, its underlying mechanism remains unknown. In this study, we show that LBI ameliorated disease symptoms in an ovalbumin (OVA)-induced allergic rhinitis mouse model. LBI suppressed OVA-specific IgE production by attenuating germinal center (GC) reaction in the draining lymph nodes. The antiallergic effect of LBI is most likely attributed to increased serum iodine levels but not thyroid hormone levels. In vitro treatment of activated B cells with potassium iodide induced ferroptosis by increasing intracellular reactive oxygen species (ROS) and ferrous iron in a concentration-dependent manner. Accordingly, LBI diets increased ROS levels in GC B cells of the draining lymph nodes. This study suggests that iodine directly promotes ferroptosis in activated B cells and attenuates GC reactions, leading to the alleviation of allergic symptoms., (© 2023. The Author(s).)

We analyzed the fractal dimension (Df) of lung gas and blood distribution imaged with synchrotron radiation K-edge subtraction (KES), in six anesthetized adult New Zealand White rabbits. KES imaging was performed in upright position during stable Xe gas (64% in O 2 ) inhalation and iodine infusion (Iomeron, 350 mg/mL), respectively, at baseline and after induced bronchoconstriction by aerosolized methacholine (125 mg/mL, 90 s) and bronchodilator (salbutamol, 10 mg/mL, 90 s) inhalation, at two axial image levels. Lung Xe and iodine images were segmented, and maps of regional lung gas and blood fractions were computed. The Df of lung gas (Df Xe ) and blood (Df Iodine ) distribution was computed based on a log-log plot of variation coefficient as a function of region volume. Df Xe decreased significantly during bronchoconstriction ( P < 0.0001), and remained low after salbutamol. Df Iodine depended on the axial image level ( P < 0.0001), but did not change with bronchoconstriction. Df Xe was significantly associated with arterial [Formula: see text] ( R = 0.67, P = 0.002), and negatively associated with [Formula: see text] ( R = -0.62, P = 0.006), respiratory resistance ( R = -0.58, P = 0.011), and elastance ( R = -0.55, P = 0.023). These data demonstrate the reduced Df of gas distribution during acute bronchoconstriction, and the association of this parameter with physiologically meaningful variables. This finding suggests a decreased complexity and space-filling properties of lung ventilation during bronchoconstriction, and could serve as a functional imaging biomarker in obstructive airway diseases. NEW & NOTEWORTHY Here, we used an energy-subtractive imaging technique to assess the fractal dimension (Df) of lung gas and blood distribution and the effect of acute bronchoconstriction. We found that Df of gas significantly decreases in bronchoconstriction. Conversely, Df of blood exhibits gravity-dependent changes only, and is not affected by acute bronchoconstriction. Our data show that the fractal dimension of lung gas detects the emergence of clustered rather than scattered loss of ventilatory units during bronchoconstriction.

Ensuring optimal iodine nutrition in pregnant women is a global public health concern. However, there is no direct data on safe tolerable upper intake levels (ULs) for pregnant women. A cross-sectional study was performed to determine the ULs of pregnant women. A total of 744 pregnant women were enrolled in this study. The median (IQR) urinary iodine concentration (UIC) in pregnant women was 150.2 (87.6, 268.0) μg/L, and the urinary iodine excretion (UIE) over 24 h was 204.2 (116.0, 387.0) μg/day. Compared with those with a UIE figure of between 150-250 μg/day, the reference group, the prevalence of thyroid dysfunction was 5.7 times higher (95%CI: 1.7, 19.2) in pregnant women with a UIE figure of between 450-550 μg/day, and 3.9 times higher (95%CI: 1.5, 10.3) in pregnant women with a UIE figure of ≥550 μg/day. Compared with an estimated iodine intake (EII) of between 100-200 μg/day, the reference group, the prevalence of thyroid dysfunction was 4.3 times higher (95%CI: 1.3, 14.4) in pregnant women with a UIE figure of between 500-600 μg/day, and 3.6 times higher (95%CI: 1.5, 8.9) in pregnant women with UIE of ≥600 μg/day. In general, our cross-sectional study found that excessive iodine intake during pregnancy appears to directly increase the risk of thyroid dysfunction. Avoiding chronic iodine intakes of 500 μg/day or higher or having a UIE figure of ≥450 μg/day is recommended for pregnant women in China.

Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I 2 ), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I 2 Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits., (© 2023 Steins et al.)

Sulfonamides are a conventional class of antibiotics that are well-suited to combat infections. However, their overuse leads to antimicrobial resistance. Porphyrins and analogs have demonstrated excellent photosensitizing properties and have been used as antimicrobial agents to photoinactivate microorganisms, including multiresistant Staphylococcus aureus (MRSA) strains. It is well recognized that the combination of different therapeutic agents might improve the biological outcome. In this present work, a novel meso -arylporphyrin and its Zn(II) complex functionalized with sulfonamide groups were synthesized and characterized and the antibacterial activity towards MRSA with and without the presence of the adjuvant KI was evaluated. For comparison, the studies were also extended to the corresponding sulfonated porphyrin TPP(SO 3 H) 4 . Photodynamic studies revealed that all porphyrin derivatives were effective in photoinactivating MRSA (>99.9% of reduction) at a concentration of 5.0 μM upon white light radiation with an irradiance of 25 mW cm -2 and a total light dose of 15 J cm -2 . The combination of the porphyrin photosensitizers with the co-adjuvant KI during the photodynamic treatment proved to be very promising allowing a significant reduction in the treatment time and photosensitizer concentration by six times and at least five times, respectively. The combined effect observed for TPP(SO 2 NHEt) 4 and ZnTPP(SO 2 NHEt) 4 with KI seems to be due to the formation of reactive iodine radicals. In the photodynamic studies with TPP(SO 3 H) 4 plus KI, the cooperative action was mainly due to the formation of free iodine (I 2 ).

Herein, we report a facile approach for the preparation of two-dimensional iodine nanosheets (2D iodine NSs) with good stability and high biocompatibility via an aqueous solvent-assisted ultrasonic route. Due to the large specific surface area of the 2D morphology, iodine NSs effectively interact with bacterial membranes and destroy bacterial integrity, as well as further damaging intracellular DNA, showing prominent antibacterial activity against S. aureus in vitro and in vivo .

Iodine-V ((C26H39N4O15)x * (I2)y) demonstrates an in vitro virucidal activity by deactivating SARS-CoV-2 viral titers. It combines elemental iodine (I2) and fulvic acid (C14H12O8), forming a clathrate compound. The antiviral properties of Iodine-V reduce viral load in the air to inhibit viral transmission indoors. This antiviral property was applied to form a disinfectant solution called SAFEAIR-X Aerosol. The current study evaluates the antiviral efficacy of Iodine-V in aerosol form in a prototype called SAFEAIR-X Aerosol. The experiment measured the antiviral efficacy of SAFEAIR-X following exposure to the Vaccinia virus (VACV) samples as a confirmed surrogate for SARS-CoV-2. The SAFEAIR-X showed 96% effectiveness, with 2 seconds of spraying duration and 60 seconds of contact time releasing less than 0.0001 ppm of iodine into the air, and a log reduction value of 1.50 at 60 seconds in 2 out of 3 tests was observed. Therefore, this study demonstrates SAFEAIR-X aerosol as a potential indoor surface and air disinfectant., Competing Interests: The author has read the journal’s policy and the author of this manuscript has the following competing interests: KZ is a paid employee of IOI Investment Zrt, the manufacturing company of Iodine-V. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents associated with this research to declare., (Copyright: © 2023 Zoltán Köntös. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As an emerging antibacterial strategy, photothermal disinfection attracts increasing attention due to its advantages of high efficacy, wide pertinence, and non-drug resistance. However, the unavoidable shielding of observation by photothermal components and the possible damage to normal tissue caused by hyperthermia restrict its applications. Herein, we propose a composite hydrogel with the ability of on-demand generation of photothermal components and mild-temperature photothermal disinfection by elegantly tuning the binding and release of iodine and starch. The composite hydrogel is obtained by blending iodine-adsorbed pH-responsive ZIF-8 nanoparticles (NPs) with a starch-based hydrogel matrix. Through a convenient pH response, the composite hydrogel leverages the triple functions of iodine, which serves as a disinfectant and reacts with starch to generate a photothermal agent and color indicator, allowing photothermal-chemotherapy combined disinfection on demand. In vitro antibacterial experiments show that the composite hydrogel can respond to the acidification of the microenvironment caused by bacterial metabolism and produce corresponding color changes, realizing naked-eye observation. Meanwhile, under the combined treatment of heating/I 2 /Zn 2+ , the composite hydrogel can completely kill Escherichia coli and Staphylococcus aureus at a mild temperature of ∼41 °C. This study represents a breakthrough in on-demand generation of photothermal hydrogels for mild-temperature photothermal disinfection.

Iodine is anessential micronutrient that plays a crucial role in male reproduction (sexual behavior and semen production performance) by modulating thyroid function and the antioxidant status of the animal. Nonetheless, in Bos indicus bulls, a thorough evaluation of the effects of dietary iodine supplementation on antioxidant status, seminal quality parameters, and its interaction with other minerals is not documented. Twelve Bos indicus (Sahiwal) bulls were distributed into three groups (n = 4 in each group) viz. T 1 (control), T 2 , and T 3 and fed diets containing 0.250, 0.375, and 0.500 ppm iodine/ kg dry matter intake, corresponding to 0%, 50%, and 100% higher than ICAR (2013) recommendations, respectively. The experimental feeding was carried out for 60 days and the effects on nutrient utilization, hormonal and antioxidant status, and sperm function tests were investigated. Results revealed that body weight, dry matter intake, and nutrient digestibility remained unaffected by dietary supplementation of iodine. Testosterone and thyroxine hormone concentrations were improved (p<0.05) in T 2 and T 3 groups. Blood and seminal iodine content were also higher (p<0.05) in both the supplemented groups (T 2 and T 3 ). Sperm functions viz. viability, physical membrane integrity, acrosomal integrity, motility, and mitochondrial membrane potential were improved (p<0.05) due to iodine supplementation. Furthermore, lipid peroxidation and membrane scrambling in spermatozoa were reduced (p<0.05) in T 2 and T 3 groups. Blood antioxidant status (total antioxidant activity and GPx levels) was improved (p<0.05) in T 2 and T 3 . Sexual behavior was also improved (p<0.05) in iodine-supplemented groups. Hence, it can be concluded that iodine supplementation at the dose rate of 0.500 ppm in the Bos indicus bull diet is beneficial in improving hormonal status, antioxidant status, and semen quality., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the case of nuclear incidents, radioiodine may be released. After incorporation, it accumulates in the thyroid and enhances the risk of thyroidal dysfunctions and cancer occurrence by internal irradiation. Pregnant women and children are particularly vulnerable. Therefore, thyroidal protection by administering a large dose of stable (non-radioactive) iodine, blocking radioiodide uptake into the gland, is essential in these subpopulations. However, a quantitative estimation of the protection conferred to the maternal and fetal thyroids in the different stages of pregnancy is difficult. We departed from an established biokinetic model for radioiodine in pregnancy using first-order kinetics. As the uptake of iodide into the thyroid and several other tissues is mediated by a saturable active transport, we integrated an uptake mechanism described by a Michaelis-Menten kinetic. This permits simulating the competition between stable and radioactive iodide at the membrane carrier site, one of the protective mechanisms. The Wollf-Chaikoff effect, as the other protective mechanism, was simulated by adding a total net uptake block for iodide into the thyroid, becoming active when the gland is saturated with iodine. The model's validity was confirmed by comparing predicted values with results from other models and sparse empirical data. According to our model, in the case of radioiodine exposure without thyroid blocking, the thyroid equivalent dose in the maternal gland increases about 45% within the first weeks of pregnancy to remain in the same range until term. Beginning in the 12th pregnancy week, the equivalent dose in the fetal thyroid disproportionately increases over time and amounts to three times the dose of the maternal gland at term. The maternal and fetal glands' protection increases concomitantly with the amount of stable iodine administered to the mother simultaneously with acute radioiodine exposure. The dose-effect curves reflecting the combined thyroidal protection by the competition at the membrane carrier site and the Wolff-Chaikoff effect in the mother are characterized by a mean effective dose (ED 50 ) of roughly 1.5 mg all over pregnancy. In the case of the fetal thyroid, the mean effective doses for thyroid blocking, taking into account only the competition at the carrier site are numerically lower than in the mother. Taking into account additionally the Wolff-Chaikoff effect, the dose-effect curves for thyroidal protection in the fetus show a shift to the left over time, with a mean effective dose of 12.9 mg in the 12th week of pregnancy decreasing to 0.5 mg at term. In any case, according to our model, the usually recommended dose of 100 mg stable iodine given at the time of acute radioiodine exposure confers a very high level of thyroidal protection to the maternal and fetal glands over pregnancy. For ethical reasons, the possibilities of experimental studies on thyroid blocking in pregnant women are extremely limited. Furthermore, results from animal studies are associated with the uncertainties related to the translation of the data to humans. Thus model-based simulations may be a valuable tool for better insight into the efficacy of thyroidal protection and improve preparedness planning for uncommon nuclear or radiological emergencies., (© 2022. The Author(s).)

Iodine-containing systems show broad antiseptic properties that can be an invaluable tool in controlling infections in humans and animals. Here, we describe the first proof-of-concept studies on biocidal active polyamide- and polyurethane-iodine complexes that are produced in situ directly during the fabrication and/or polymerization process at laboratory and commercially relevant scales. These polymer-iodine materials are active against a broad range of microorganisms, including bacteria and fungi. It is suggested that the ease of manufacture and subsequent commercialization make said systems especially suited for applications as base materials for medical devices to reduce infection risks and control the spread of pathogens. IMPORTANCE Infectious diseases are of mounting medical and public concern. A major contributor to this trend is the proliferation of medical implants, which are inherently vulnerable to microbial contamination and the subsequent onset of hospital-acquired infections. Moreover, implant-associated infections in humans are often difficult to diagnose and treat and are associated with substantial health care costs. Here, we present the development of biocidal active polyamide- and polyurethane-iodine complexes that are generated in situ during fabrication. We show that the excellent antiseptic properties of water-soluble povidone-iodine can be similarly realized in water-insoluble engineering plastics, specifically polyamide- and polyurethane-iodine. These complexes have inherent biocidal activity against major pathogenic bacteria and fungi.

Considering the growing number of cancer cases around the world, natural products from the diet that exhibit potential antitumor properties are of interest. Our previous research demonstrated that fortification with iodine compounds is an effective way to improve the antioxidant potential of lettuce. The purpose of the present study was to evaluate the effect of iodine-biofortified lettuce on antitumor properties in human gastrointestinal cancer cell lines, gastric AGS and colon HT-29. Our results showed that extracts from iodine-biofortified lettuce reduce the viability and proliferation of gastric and colon cancer cells. The extracts mediated cell cycle arrest which was accompanied by inactivation of anti-apoptotic Bcl-2 and activation of caspases, as assessed by flow cytometry. However, extracts from lettuce fortified with organic forms of iodine acted more effectively than extracts from control and KIO 3 -enriched plants. Using quantitative PCR, we detected the increase in pro-apoptotic genes BAD, BAX and BID in AGS cells whereas up-regulation of cell cycle progression inhibitor CDKN2A and downregulation of pro-proliferative MDM2 in HT-29 cells. Interestingly, lettuce extracts led to down-regulation of pro-survival AKT1 and protooncogenic MDM2 , which was consistent for extracts of lettuce fortified with organic form of iodine, 5-ISA, in both cell lines. MDM2 downregulation in HT-29 colon cancer cells was associated with RB1 upregulation upon 5-ISA-fortified lettuce extracts, which provides a link to the epigenetic regulation of tumor suppressor genes by RB/MDM2 pathway. Indeed, SEMA3A tumor suppressor gene was hypomethylated and upregulated in HT-29 cells treated with 5-ISA-fortified lettuce. Control lettuce exerted similar effects on RB/MDM2 pathway and SEMA3A epigenetic activation in HT-29 cells. Our findings suggest that lettuce as well as lettuce fortified with organic form of iodine, 5-ISA, may exert epigenetic anti-cancer effects that can be cancer type-specific.

Iodine is an essential trace element in the human body. Severe maternal iodine deficiency during pregnancy leads to obvious intellectual disability in the offspring. The effects of iodine deficiency on brain development have been demonstrated, but there is no clear evidence of the effects of iodine excess on brain development. To clarify the effects of iodine excess on the brain development of offspring and to provide clues to the mechanisms underlying the effects of iodine deficiency and iodine excess on the brain development of offspring. In this study, animal models with different iodine intakes were constructed using potassium iodate (KIO 3 ). The models included four experimental groups (low-iodine group one (LI, 0μg/L iodine), low-iodine group two (LII, 5μg/L iodine), high-iodine group one (HI, 3000μg/L iodine), and high-iodine group two (HII, 10000μg/L iodine)) and one control group (NI, 100μg/L iodine). There were 20 female rats in each group, and 8 offspring were chosen from each group following birth to assess metabolic alterations. The metabolites of subsets of brain hippocampal tissue were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and the results were subjected to multivariate data analysis. Differential substances were screened by t test (p<0.05), principal component analysis (PCA), and partial least squares analysis (PLS-DA, VIP>1). The thyroid function of the female rats in the experimental group was abnormally changed. Metabolic analysis showed that the five groups were separated which revealed significant differences in hippocampal tissue metabolism among the five groups of offspring. A total of 12 potential metabolites were identified, with the majority of them being related to amino acid and energy metabolism. These metabolites are involved in various metabolic pathways, are interrelated, and may play a function in brain development. Our study highlights changes in metabolites and metabolic pathways in the brain hippocampus of offspring rats with different iodine intakes compared to controls, revealing new insights into hippocampal metabolism in offspring rats and new relevant targets., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Embryo surface disinfection in either an iodine or sodium hypochlorite (NaOCl) solution is commonly performed on imported zebrafish embryos to decrease pathogen introduction into a facility. The impact of the consecutive use of these disinfectants and the conductivity of the culture media on embryo survival and development post-disinfection have not been evaluated. Iodine (12.5-25 ppm) is effective at eliminating several Mycobacterium species, whereas NaOCl (50-100 ppm) reduces the number of viable Pseudoloma neurophilia spores. Casper and T5D (tropical 5D wild type) embryos reared in media of differing conductivities (0-10, 100-200, 750-950, and 1500-2000 μS) with and without exposure to NaOCl 100 ppm at 6 h post-fertilization were evaluated for survival, hatching success, and morphological defects at 5 days post-fertilization. Additionally, the consecutive use of iodine (12.5 ppm for 2 min) followed by NaOCl (75 or 100 ppm for 10 min), as well as the inverse, was evaluated. Embryo survival was not impacted by embryo rearing media alone; however, survival significantly decreased when embryos were disinfected with 100 ppm NaOCl in media with a conductivity >750-950 μS. Iodine (12 ppm) and NaOCl (75 ppm) used sequentially resulted in >50% survival, whereas the use of 100 ppm NaOCl resulted in high levels of embryo mortality.

Streptococcus mutans ( S. mutans ) and Candida albicans ( C. albicans ) are prominent microbes associated with rapid and aggressive caries. In the present study, we investigated the antimicrobial efficacy, cytotoxicity, and mechanism of toluidine blue O (TBO)-mediated antimicrobial photodynamic therapy (aPDT) and potassium iodide (KI). The dependence of KI concentration, TBO concentration and light dose on the antimicrobial effect of aPDT plus KI was determined. The cytotoxicity of TBO-mediated aPDT plus KI was analyzed by cell counting kit-8 (CCK-8) assay. A singlet oxygen ( 1 O 2 ) probe test, time-resolved 1 O 2 detection, and a 1 O 2 quencher experiment were performed to evaluate the role of 1 O 2 during aPDT plus KI. The generation of iodine and hydrogen peroxide (H 2 O 2 ) were analyzed by an iodine starch test and Amplex red assay. The anti-biofilm effect of TBO-mediated aPDT plus KI was also evaluated by counting forming unit (CFU) assay. KI could potentiate TBO-mediated aPDT against S. mutans and C. albicans in planktonic and biofilm states, which was safe for human dental pulp cells. 1 O 2 measurement showed that KI could quench 1 O 2 signals, implicating that 1 O 2 may act as a principal mediator to oxidize excess iodide ions to form iodine and H 2 O 2 . KI could highly potentiate TBO-mediated aPDT in eradicating S. mutans and C. albicans due to the synergistic effect of molecular iodine and H 2 O 2 .

Bacterial cellulose (BC), produced by bacteria and fungi, is a promising material in the biomedical field. However, non-antibacterial activity limits its broad applications. Herein, antibacterial composites (BC/ZIF-8-iodine) were prepared by loading iodine into zeolitic imidazolate framework-8 (ZIF-8) modified BC (BC/ZIF-8). BC/ZIF-8-iodine was well characterized by SEM, XRD, FTIR, XPS, Raman and contact angle analyses. The increase of ZIF-8 content augmented the loading capacity of iodine in BC/ZIF-8-iodine. Meanwhile, the adsorbed iodine can be released from BC/ZIF-8-iodine composites, following the Higuchi equation. A reduced sublimation of iodine was observed in BC/ZIF-8-iodine composites, indicating their good iodine preservation ability. BC/ZIF-8-iodine composites exhibited strong antibacterial activity towards Escherichia coli , Staphylococcus aureus and Candida albicans . XPS and Raman analyses indicated that the adsorbed iodine of BC/ZIF-8-iodine composites was in the form of I 3 - . The expected iodine loading, release and preservation behaviors of BC/ZIF-8-iodine composites ensure their antibacterial performance and suggest potential clinical applications.

Although photothermal therapy (PTT) can effectively eliminate tumors, the normal tissues near tumors are inevitably damaged by heat and infected by bacteria, which greatly limits the therapeutic effect. In this work, an injectable thermosensitive hydrogel based on iodine-loaded starch-g-poly(N-isopropylacrylamide) (PNSI) is developed to overcome this problem. FTIR, 1 H NMR, and UV-vis spectra confirm the graft copolymerization of poly(N-isopropylacrylamide) with starch and the formation of "iodine-starch" complex. Transmission electron microscope images show PNSI polymer self-assembles into regular spherical nanogel with a size of ≈50 nm. The concentrated nanogel dispersion is a sol at room temperature and transforms to hydrogel at body temperature. Under NIR laser irradiation for 10 min, the ΔT of the nanogel dispersion approachs about 20 °C with excellent thermal stability and high cytotoxicity due to the photothermal effect of the "iodine-starch" complex. After intratumor injection, this injectable hydrogel efficiently inhibites the tumor growth under 808 nm laser irradiation. Furthermore, it can also suppress Staphylococcus aureus infection in the wound post-PTT due to the release of iodine, which promotes wound healing. Therefore, this injectable thermosensitive "iodine-starch" composite hydrogel with advantages of good biocompatible and easy preparation possesses potential application for tumor photothermal therapy and antibacterial infection., (© 2022 Wiley-VCH GmbH.)

Objective: Surgical site infection is a common complication of surgery, especially in orthopedics. Povidone-Iodine (PI) is one of the oldest and most commonly used disinfectants in surgery. However, the toxicity and antimicrobial effect of PI have not been discussed. In addition, no study has explored the optimum PI concentration for sterilization and tissue healing. This study explores the germicidal efficacy of different concentrations PI, in addition, the toxicity and antibacterial effects of PI irrigation in fracture surgery are also discussed., Methods: Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa (P. aeruginosa) were used to evaluate the germicidal efficacy of PI in vitro and in vivo. In vitro, the effects of PI on bacterial growth were analyzed. 2.5%, 1.25%, 0.5%, 0.25%, 0.05%, 0.025%, 0.005%, 0.0025% and 0% PI was added into the bacterial suspension, besides, the bacterial algebra and growth rate were tested. Meanwhile, the fluorescence intensity of viable bacteria was also tested to evaluate the effects of PI on bacterial survival. In vivo, first, femoral fracture with wound infection rat models were established. Second, thyroid gland sections, blood thyroxine, urinary iodine, wound local skin, muscle and bone tissue sections, serum creatinine and alanine aminotransferase, serum and bone local tissue interleukin-6 (IL-6), interleukin-10 (IL-10), bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF-β1) were detected in rat femoral shaft fracture model with 5%, 2.5%, 0.5%, 0.05%, and 0% PI irrigation. Third, tissue bacteria culture was tested in rat femoral fracture with wound infection model with different concentrations PI irrigation., Results: In vitro, 2.5%, 1.25%, 0.5% PI inhibited the growth of bacteria. 1.25%, 0.5% PI killed all the bacteria, while 0.25%, 0.05% PI had not killed bacteria after about 10 min. The iodine absorption of 5%, 2.5%, 0.5% PI irrigation did not cause thyroid injury. The 5%, 2.5%, 0.5% PI irrigation did not make serum creatinine and alanine aminotransferase abnormal and can remove bacteria from wounds. The 0.5%, 2.5% PI irrigation can promote tissue healing and increase BMP-2, VEGF, TGF-β1, IL-10, in addition, decrease IL-6. 5% PI irrigation would inhibit tissue healing, and increase IL-6, decrease BMP-2, VEGF, TGF-β1, IL-10., Conclusions: Povidone-Iodine was a widely used disinfectant and 2.5%, 1.25% and 0.5% PI could effectively kill bacteria. Five percent and lower concentration PI irrigation was safe and could not cause thyroid, kidney and liver damage. The 0.5% PI irrigation was beneficial for tissue healing but 5% PI irrigation was the opposite., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Healthcare-associated infections (HAIs) are a persistent clinical challenge caused primarily by bacteria on the skin. Proper utilization of optimized antiseptic skin preparation solutions helps reduce the prevalence and impact of HAIs by decreasing patient skin microorganisms preoperatively. The purpose of this study was to evaluate the efficacy of 2 antimicrobial solutions containing iodine and isopropyl alcohol (IPA): Povidone iodine (PVP-I) with IPA (ie, PVP-I+IPA, PurPrep) and Iodine Povacrylex+IPA (DuraPrep)., Methods: The antimicrobial activity of the test solutions was evaluated in vitro by determinations of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against 1105 diverse microbial isolates and a time-kill assay to evaluate efficacy against 120 strains of Gram-positive and Gram-negative bacteria and yeasts. Peel tests were performed between skin samples treated with test solutions and representative drape/dressing materials to determine effects of test solutions on the biomechanical adhesion properties. Finally, an Institutional Review Board (IRB)-approved, randomized, controlled, single-center, partially blinded in vivo study was performed to assess the immediate and persistent antimicrobial activity of the test solutions on the abdomen and groin., Results: Both PVP-I+IPA and Iodine Povacrylex+IPA solutions demonstrated broad-spectrum antimicrobial activity with MIC and MBC at less than 1% of the full-strength concentration of each product against a wide variety of microorganisms. In the time-kill tests, both solutions were able to successfully reduce all microbial populations by 99.99% (ie, 4 log 10 ) at the contact times of 30 seconds, 2 minutes and 10 minutes. The 2 solutions showed relatively similar adhesion results when tested with 3 representative operating room materials. Both PVP-I+IPA and Iodine Povacrylex+IPA met the expected Food and Drug Administration (FDA) efficacy requirements at 10 minutes and 6 hours post-treatment for both anatomic sites (ie, groin, and abdomen) in the clinical study, with no safety issues or adverse events., Conclusions: Analysis of the in vitro antimicrobial activity, biomechanical adhesive strength, and in vivo efficacy of PVP-I+IPA demonstrated similar results compared to Iodine Povacrylex+IPA. Both products were efficacious at reducing or eliminating a wide range of clinically-relevant microorganisms in lab-based and clinical settings, supporting their use as antiseptic skin preparation solutions to reduce bacteria on the skin that can cause infection., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Developing antimicrobial biomaterials is a major challenge in the fields of orthopaedic and dental implants. In this study, we evaluated the bone-bonding ability and antibacterial activity of a novel biomaterial for preventing implant-associated infections. We have previously reported that NaOH heat treatment improved the bone-bonding ability of titanium, which was later modified to release target ions from the calcium titanate surface. Iodine, an essential nutrient, exhibits broad-spectrum antimicrobial activity; hence, we designed a calcium titanate that releases iodine ions (Ca-I-Ti). The material was prepared from a simple solution using heat treatments as well as inexpensive devices and chemical agents. MC3T3-E1 cells seeded on Ca-I-Ti displayed high degrees of bioactivity and viability, and Ca-I-Ti exhibited antibacterial activity against methicillin-susceptible Staphylococcus aureus. In vivo biomechanical and histological experiments showed that Ca-I-Ti had excellent bone-bonding ability at 8 weeks after implantation. In a subcutaneous infection model in rats, methicillin-susceptible Staphylococcus aureus on the implant was reduced by approximately 95% compared to that on commercially pure titanium, indicating that Ca-I-Ti has antibacterial effects in vivo. In addition, no local or systemic complications were observed, and active infection in the surrounding tissues was histologically inhibited. Thus, iodine-containing calcium titanate is a safe biomaterial with excellent bioactivity and antibacterial properties, indicating its potential in preventing implant-associated infections., (Copyright © 2022 Elsevier B.V. All rights reserved.)