Tumor microenvironment(TME) and single-source dual-energy CT(ssDECT) on assessment of inconformity between RECIST1.1 and pathological remission in neoadjuvant immunotherapy of NSCLC.

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.

Development, characterization, and evaluation of a simple polymicrobial colony biofilm model for testing of antimicrobial wound dressings.

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.

Mechanical, bioactive, and long-lasting antibacterial properties of a Ti scaffold with gradient pores releasing iodine ions.

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.

Preparation and characterizations of antibacterial iodine-containing coatings on pure Ti.

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 I2, I3-, 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.

Chitosan­iodine complexes: Preparation, characterization, and antibacterial activity.

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 chitosan­iodine (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.

A novel cationic ß-cyclodextrin decorated with a choline-like pendant exhibits Iodophor, Mucoadhesive and bactericidal properties.

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 ß-cyclodextrin bearing a choline-like pendant (ß-CD-Chol) designed to complex and deliver iodine to bacterial cells. The characterization of ß-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 ß-CD scaffold. The water-soluble ß-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 ß-CD-Chol a promising drug delivery system and an appealing iodophor candidate for iodine-based antisepsis including mucosa disinfection.

Development of a Multifunctional Composite Hydrogel for Enhanced Wound Healing: Hemostasis, Sterilization, and Long-Term Moisturizing Properties.

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-ß-cyclodextrin (HP-ß-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.

Should we reconsider blocking the thyroid for 123 I-Ioflupane studies in elderly patients: quantifying radiation dose to the unblocked thyroid and implications for clinical practice.

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.

Evaluation of anti-adenoviral effects of the polyvinyl alcohol iodine ophthalmic solution.

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 × 106 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.

In vitro prevention and inactivation of biofilms using controlled-release iodine foam dressings for wound healing.

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.

Iodine-doped TiO2 nanotube coatings: a technique for enhancing the antimicrobial properties of titanium surfaces against Staphylococcus aureus.

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 TiO2 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), TiO2-nanocoated titanium plates (TiO2 group), and iodine-doped TiO2-nanocoated titanium plates (I-TiO2 group) to compare their antibacterial properties. RESULTS: Twenty-four hour in vitro antimicrobial activity test of the I-TiO2 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.

Biological regulation on iodine using nano-starch for preventing thyroid dysfunction.

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.

Asymmetrical Methylene-Bridge Linked Fully Iodinated Azoles as Energetic Biocidal Materials with Improved Thermal Stability.

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; Td: 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.

Iodinene Nanosheet-to-Iodine Molecule Allotropic Transformation for Antibiosis.

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 I2 molecules by reacting with H2O2 in the infectious microenvironment. By the in situ production of active HIO and I2 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.

Protective effects of iodine on rat prostate inflammation induced by sex hormones and on the DU145 prostate cancer cell line treated with TNF.

Molecular iodine (I2) 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 I2 and testosterone (T) on hyperestrogenism-induced prostate inflammation. Additionally, the effects of I2 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 I2 on viability are peroxisome proliferator-activated receptor gamma (PPARG)-dependent. Castrated (Cx) rats received pellets of either 17ß estradiol (E2) or E2 and T and were treated with I2 (0.05%) in the drinking water for four weeks. The experimental groups were sham, Cx, Cx + E2, Cx + E2+I2, Cx + E2+T, and Cx + E2+T + I2. As expected, inflammation was triggered in the Cx + E2 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 + E2+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 + E2+T + I2 group. In DU145 cells, I2 (400 µM) and TNF (10 ng/ml) additively reduced cell viability, and I2 reduced the production of TNF-stimulated IL6. The PPARG antagonist (GW9662) did not inhibit the effects of I2 on the loss of cell viability. In summary, our data suggest that I2 and T exert a synergistic anti-inflammatory action on the normal prostate, and the interrelationship between I2 and TNF leads to anti-proliferative effects in DU145 cells. PPARG does not seem to participate in the I2-induced cell viability loss in the prostate.

Dietary iodine attenuates allergic rhinitis by inducing ferroptosis in activated B cells.

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.

Adverse Effects on the Thyroid of Chinese Pregnant Women Exposed to Long-Term Iodine Excess: Optimal and Safe Tolerable Upper Intake Levels of Iodine.

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.

Cell death and barrier disruption by clinically used iodine concentrations.

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 (I2), 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 I2 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.

Fractal dimension of pulmonary gas and blood distribution assessed by synchrotron K-edge subtraction imaging: effect of bronchoconstriction.

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 O2) 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 (DfXe) and blood (DfIodine) distribution was computed based on a log-log plot of variation coefficient as a function of region volume. DfXe decreased significantly during bronchoconstriction (P < 0.0001), and remained low after salbutamol. DfIodine depended on the axial image level (P < 0.0001), but did not change with bronchoconstriction. DfXe 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.

Integrated photo-inspired antibacterial polyvinyl alcohol/carboxymethyl cellulose hydrogel dressings for pH real-time monitoring and accelerated wound healing.

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 alcohol­iodine/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.