New Amphiphilic Terpolymers of N-Vinylpyrrolidone with Acrylic Acid and Triethylene Glycol Dimethacrylate as Promising Drug Delivery: Design, Synthesis and Biological Properties In Vitro.

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different molar composition (98:2:2, 95:5: 2 and 98:2:5) and their monomer composition, absolute molecular masses and hydrodynamic radii in aqueous media were determined. Using the MTT test, these terpolymers were established to be low toxic for non-tumor Vero cells and HeLa tumor cells. Polymer compositions of hydrophobic dye methyl pheophorbide a (MPP) based on studied terpolymers and linear polyvinylpyrrolidone (PVP) were obtained and characterized in water solution. Quantum-chemical modeling of the MPP-copolymer structures was conducted, and the possibility of hydrogen bond formation between terpolymer units and the MPP molecule was shown. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied, and an increase in the accumulation of MPP with both types of particles was found.

Distribution and accumulation of UV filters (UVFs) and conservation status of Posidonia oceanica seagrass meadows in a prominent Mediterranean coastal tourist hub.

This study investigates the presence and impact of UV filters in Posidonia oceanica meadows in Formentera, a Mediterranean tourist hotspot. It highlights the distribution of inorganic (TiO2 and ZnO) and organic UV filters (UVFs) in different environmental matrices, their accumulation in seagrass tissues and their impact on the seagrass health. In the overlying and canopy waters of P. oceanica, Zn concentrations surpassed Ti, with three organic UVFs (benzophenone-3 [BP-3], avobenzone and homosalate [HMS]) consistently detected. Ti concentrations were generally higher than Zn in rhizosphere sediments, along with recurrent presence of octocrylene, HMS, 2-ethylhexyl methoxycinnamate (EHMC), and 4-methylbenzylidene camphor (4-MBC). Maximum Zn concentrations were found in canopy waters (3052.9 ng L-1). Both Ti and Zn were found in all P. oceanica tissues and leaf epiphytes across all study sites. Additional UVFs like octocrylene, avobenzone, and BP-8 were also detected in P. oceanica tissues and epiphytes. Elevated levels of octocrylene in leaf epiphytes (2112.1 ng g-1 dw) and avobenzone in leaves (364.2 ng g-1 dw) and leaf epiphytes (199.6 ng g-1 dw) were observed in the Port of La Savina, the island's main entry port. Octocrylene concentrations (up to 2575 ng g-1 dw) in rhizosphere sediments near sewage discharge points exceeded reported maxima, highlighting wastewater treatment plants as significant sources of organic UVFs. Correlational analyses suggested that the accumulation of octocrylene, avobenzone, and BP-3 negatively impacted P. oceanica's conservation status, affecting global density, density at 100 % cover, and leaf morphometry. Positive correlations were observed between leaf polyphenols (antioxidants) and concentrations of avobenzone, benzophenone-8 (BP-8), and BP-3, indicating potential oxidative stress induced by UVFs in P. oceanica. Our study underscores the pervasive presence of UV filters in P. oceanica habitats, with implications for seagrass health and conservation, especially in areas of high tourism and sewage discharge.

Evaluation of a Covalent Library of Diverse Warheads (CovLib) Binding to JNK3, USP7, or p53.

Purpose: Over the last few years, covalent fragment-based drug discovery has gained significant importance. Thus, striving for more warhead diversity, we conceived a library consisting of 20 covalently reacting compounds. Our covalent fragment library (CovLib) contains four different warhead classes, including five α-cyanoacacrylamides/acrylates (CA), three epoxides (EO), four vinyl sulfones (VS), and eight electron-deficient heteroarenes with a leaving group (SNAr/SN). Methods: After predicting the theoretical solubility of the fragments by LogP and LogS during the selection process, we determined their experimental solubility using a turbidimetric solubility assay. The reactivities of the different compounds were measured in a high-throughput 5,5'-dithiobis-(2-nitrobenzoic acid) DTNB assay, followed by a (glutathione) GSH stability assay. We employed the CovLib in a (differential scanning fluorimetry) DSF-based screening against different targets: c-Jun N-terminal kinase 3 (JNK3), ubiquitin-specific protease 7 (USP7), and the tumor suppressor p53. Finally, the covalent binding was confirmed by intact protein mass spectrometry (MS). Results: In general, the purchased fragments turned out to be sufficiently soluble. Additionally, they covered a broad spectrum of reactivity. All investigated α-cyanoacrylamides/acrylates and all structurally confirmed epoxides turned out to be less reactive compounds, possibly due to steric hindrance and reversibility (for α-cyanoacrylamides/acrylates). The SNAr and vinyl sulfone fragments are either highly reactive or stable. DSF measurements with the different targets JNK3, USP7, and p53 identified reactive fragment hits causing a shift in the melting temperatures of the proteins. MS confirmed the covalent binding mode of all these fragments to USP7 and p53, while additionally identifying the SNAr-type electrophile SN002 as a mildly reactive covalent hit for p53. Conclusion: The screening and target evaluation of the CovLib revealed first interesting hits. The highly cysteine-reactive fragments VS004, SN001, SN006, and SN007 covalently modify several target proteins and showed distinct shifts in the melting temperatures up to +5.1 °C and -9.1 °C.

Biodegradation by Cancer Cells of Magnetite Nanoflowers with and without Encapsulation in PS-b-PAA Block Copolymer Micelles.

Magnetomicelles were produced by the self-assembly of magnetite iron oxide nanoflowers and the amphiphilic poly(styrene)-b-poly(acrylic acid) block copolymer to deliver a multifunctional theranostic agent. Their bioprocessing by cancer cells was investigated in a three-dimensional spheroid model over a 13-day period and compared with nonencapsulated magnetic nanoflowers. A degradation process was identified and monitored at various scales, exploiting different physicochemical fingerprints. At a collective level, measurements were conducted using magnetic, photothermal, and magnetic resonance imaging techniques. At the nanoscale, transmission electron microscopy was employed to identify the morphological integrity of the structures, and X-ray absorption spectroscopy was used to analyze the degradation at the crystalline phase and chemical levels. All of these measurements converge to demonstrate that the encapsulation of magnetic nanoparticles in micelles effectively mitigates their degradation compared to individual nonencapsulated magnetic nanoflowers. This protective effect consequently resulted in better maintenance of their therapeutic photothermal potential. The structural degradation of magnetomicelles occurred through the formation of an oxidized iron phase in ferritin from the magnetic nanoparticles, leaving behind empty spherical polymeric ghost shells. These results underscore the significance of encapsulation of iron oxides in micelles in preserving nanomaterial integrity and regulating degradation, even under challenging physicochemical conditions within cancer cells.

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies.

BACKGROUND: Candesartan cilexetil (CC) is a selective angiotensin II receptor antagonist widely used to treat hypertension. CC is a substrate of P-glycoprotein (P-gp), causing its efflux to the intestinal lumen. It is also practically insoluble in water and has low oral bioavailability (14%). Thus, the current study aims to improve the in vitro dissolution of CC by developing solid dispersion systems (SDSs) and corroborating the in vitro results using a simulated pharmacokinetics study. METHODS: The SDSs were prepared using polyvinyl pyrrolidone (PVP) as a water-soluble polymer, Eudragit E100 (EE100) as a pH-dependent soluble carrier, and a combination of these two polymers. The saturation solubility and the dissolution rate studies of the prepared systems in three dissolution media were performed. The optimized system SE-EE5 was selected for further investigations, including DSC, XRD, FTIR, FESEM, DLS, TSEM, IVIVC convolution study, and stability studies. RESULTS: The solubility of CC significantly increased by a factor of 27,037.344 when formulated as a solid dispersion matrix using EE100 at a ratio of 1:5 (w/w) drug to polymer (SE-EE5 SD), compared to the solubility of the pure drug. The mechanism of solubility and dissolution rate enhancement of CC by the optimized SDS was found to be via the conversion of the crystalline CC into the amorphous form as well as nanoparticles formation upon dissolution at a pH below 5. The instrumental analysis tests showed good compatibility between CC and EE100 and there was no chemical interaction between the drug and the polymer. Moreover, the stability tests confirmed that the optimized system was stable after three months of storage at 25°C. CONCLUSION: The utilization of the solid dispersion technique employing EE 100 polymer as a matrix demonstrates significant success in enhancing the solubility, dissolution, and subsequently, the bioavailability of water-insoluble drugs like CC.

Acrylated adhesive proteinic microneedle patch for local drug delivery and stable device implantation.

Microneedle patches have been developed as favorable platforms for delivery systems, such as the locoregional application of therapeutic drugs, and implantation systems, such as electronic devices on visceral tissue surfaces. However, the challenge lies in finding materials that can achieve both biocompatibility and stable fixation on the target tissue. To address this issue, utilizing a biocompatible adhesive biomaterial allows the flat part of the patch to adhere as well, enabling double-sided adhesion for greater versatility. In this work, we propose an adhesive microneedle patch based on mussel adhesive protein (MAP) with enhanced mechanical strength via ultraviolet-induced polyacrylate crosslinking and Coomassie brilliant blue molecules. The strong wet tissue adhesive and biocompatible nature of engineered acrylated-MAP resulted in the development of a versatile wet adhesive microneedle patch system for in vivo usage. In a mouse tumor model, this microneedle patch effectively delivered anticancer drugs while simultaneously sealing the skin wound. Additionally, in an application of rat subcutaneous implantation, an electronic circuit was stably anchored using a double-sided wet adhesive microneedle patch, and its signal location underneath the skin did not change over time. Thus, the proposed acrylated-MAP-based wet adhesive microneedle patch system holds great promise for biomedical applications, paving the way for advancements in drug delivery therapeutics, tissue engineering, and implantable electronic medical devices.

Environmental implications and nanotechnological advances in octocrylene-enriched sunscreen formulations: A comprehensive review.

Ultraviolet (UV) radiation is a major contributor to skin aging, cancer, and other detrimental health effects. Sunscreens containing FDA-approved UV filters, like avobenzone, offer protection but suffer from photodegradation and potential phototoxicity. Encapsulation, antioxidants, and photostabilizers are strategies employed to combat these drawbacks. Octocrylene, an organic UV filter, utilizes nanotechnology to enhance sun protection factor (SPF). This review examines recent literature on octocrylene-enriched sunscreens, exploring the interplay between environmental impact, nanotechnological advancements, and clinical trial insights. A critical focus is placed on the environmental consequences of sunscreen use, particularly the potential hazards UV filters pose to marine ecosystems. Research in the Mediterranean Sea suggests bacterial sensitivity to these filters, raising concerns about their integration into the food chain. This review aims to guide researchers in developing effective strategies for photostabilization of UV filters. By combining encapsulation, photostabilizers, and antioxidants, researchers can potentially reduce phototoxic effects and contribute to developing more environmentally friendly sunscreens.

Coordinative Compounds Based on Unsaturated Carboxylate with Versatile Biological Applications.

This review presents an overview of the biological applications of coordinative compounds based on unsaturated carboxylates accompanied by other ligands, usually N-based heterocyclic species. The interest in these compounds arises from the valuable antimicrobial and antitumor activities evidenced by some species, as well as from their ability to generate metal-containing polymers suitable for various medical purposes. Therefore, we describe the recently discovered aspects related to the synthesis, structure, and biological activity of a wide range of unsaturated carboxylate-containing species and metal ions, originating mostly from 3d series. The unsaturated carboxylates encountered in coordinative compounds are acrylate, methacrylate, fumarate, maleate, cinnamate, ferulate, coumarate, and itaconate. Regarding the properties of the investigated compounds, it is worth mentioning the good ability of some to inhibit the development of resistant strains or microbial biofilms on inert surfaces or, even more, exert antitumor activity against resistant cells. The ability of some species to intercalate into DNA strands as well as to scavenge ROS species is also addressed.

The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs' histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.

Synthesis of ultrathin hybrid membranes via the co-polymerization of acrylic acid, styrene and molybdenum disulfide and their high adsorption selectivity for lead(II) in the mixture of metal ions.

Lead(II) is a potential carcinogen of heavy-metal ions (HIs). With the wide application of Pb-bearing products including lead alloy products, and new-energy lead-ion batteries, lead pollution has become a tricky problem. To solve such a difficulty, novel ultrathin MoS2-vinyl hybrid membranes (MVHMs) with a "spring" effect were synthesized via co-polymerization of acrylic acid, styrene and molybdenum disulfide (MoS2) and their adsorptions for HIs were explored. The "spring" effect derived from the interaction between the tendency of the short polyacrylic acid (PAA) chain connected with MoS2 to spread outward and the coulomb force between layers from MoS2 (s-MoS2), which enlarge the spacing of MoS2 layers without changing the number of layers after membrane formation, which changes the swelling membrane to a dense membrane and reduces the original thickness from 0.5 cm to 0.011 mm in the thickness direction. The adsorption experiment revealed that these MVHMs had super adsorption performance and high selectivity for Pb2+ by comparison with other five metal ions: Cu2+, Cd2+, Ni2+, Cr3+ and Zn2+. Especially, the adsorption quantity of MVHMs for Pb2+ could approach 2468 mg/g and the maximum adsorption ratio of qe[Pb2+]/qe[Cu2+] can reach 10.909. These values were much larger than the data obtained with the adsorbents reported in the last decade. A variety of models are applied to evaluate the effect of ionic groups. It was confirmed that -COOH plays a key role in adsorption of HIs and s-MoS2 also has a certain contribution. Conversely, ion exchange plays only a minor role during the period of adsorption process. Effective diffusion coefficient (Deff) of Pb(II) had the largest values among these metal ions. Hence, these hybrid membranes are promising adsorbents for the removal of Pb2+ from water containing various ions.

Effect of oxygen-containing functional group contents on sorption of lead ions by acrylate-functionalized hydrochar.

The surface functional groups of hydrochar are crucial to its surface properties, and their contents are strongly positively correlated with the adsorption performance. In this study, acrylate-functionalized hydrochar (AHC) with varying contents of O-containing functional groups (OFGs) was synthesized via hydrothermal carbonization (HTC) of bamboo, acrylic acid and an initiator, and then deprotonated with NaOH. The AHCs were analyzed by various characterization techniques. During HTC, the higher amount of acrylic acid added led to higher carbon, oxygen and carboxyl contents, and to the larger specific surface area and pore volume of AHC. The adsorption kinetics, isotherms, thermodynamic, ionic strength and pH effects of Pb(II) on AHC were studied. Adsorption isotherms and kinetics obeyed Langmuir and pseudo-second-order models, respectively, indicating adsorption is monolayer chemical process. The adsorptive ability was well linearly related to the OFG contents of AHC. When acrylic acid was added to 25 mL during HTC, the adsorbing ability of AHC over Pb(II) reached 193.90 mg g-1. Hence, direct HTC of acrylic acid, biomass and an initiator can prepare hydrochar with controllable OFG contents, which is a prospective adsorbent for treating metal cations.

Enhanced sun protection factor of octocrylene with green tea and bhringraj extracts.

OBJECTIVES: The aim of this study of sun protection factor boosting effect sunscreen compositions with herbal extract and combination with octocrylene. MATERIALS AND METHODS: The standardized herbal extracts procured and studied their sun protection Factors. Camellia Sinensis (Green tea) leaf Extract, Eclipta prostrata (bhringraj) leaf extract are selected for the development of the herbal sunscreen composition along with octocrylene as synthetic sunscreen. The developed sunscreen composition contains defined concentration of herbal extracts and octocrylene were evaluated for their different physicochemical properties and stability. Sun protection factor boosting effect of herbal extracts is studied combination with octocrylene. RESULTS: Invitro SPF studied for herbal extract individually and combination with octocrylene. The results of Invitro SPF study revealed the presence of green tea extract and, Eclipta prostrata (bhringraj) leaf extract shows excellent sun protection factor (SPF) boosting value of sunscreen composition containing 5% concentration of herbal extract and octocrylene. The sunscreen formulation containing 5% herbal extracts are stable for 12 weeks in an oven (45 °C). CONCLUSION: The findings of this in-vitro SPF study revealed a sun protection boosting capacity of green tea extract and bhringraj extract confirmed. SUMMARY: The over exposure of human skin to Ultra-Violet Radiation (UVR) can trigger photodamage, UV burn, pigmentation, erythema, and enhance the chance of dermal carcinoma. UVR causes DNA damage, which leads to dermal cancer. Daily sunscreens protect the skin from the adverse effects of sun rays, especially UVB (290-320 nm) and UVA (320-400 nm). The ozone layer filters UVC (200-290 nm) radiation when it enters into atmosphere of the earth. UVB causes sunburn, photo damage and cause mutagenic changes in nucleic acids. UVA increases ROS (Reactive Oxygen Species) accumulation. ROS is responsible for cell repair which leads to carcinogenesis, and the cause of photodamage. Herbal extracts contain polyphenols, and flavonoids act as a natural sunscreen that will filter Ultra-Violet (UVB) light and contain antioxidant characteristics to modulate the photo-oxidative damage that results from UV-induced Reactive Oxygen Species production. The UVR protection of most herbal extracts are required to attain the higher UV protection in the sun care products. The approaches for preparing sun care products with higher Sun Protection Factor (SPF) possible through Oil in water formulation with herbal extract combinations of octocrylene. The developed sunscreen composition containing different concentration of herbal extracts were evaluated for their other physicochemical properties and stability. Invitro SPF was studied for Camellia Sinensis (Green tea) Leaf Extract and Eclipta prostrata (bhringraj) leaf extract individually and in combination with octocrylene. The results of the Invitro SPF study revealed the Camellia Sinensis (Green tea) Leaf Extract with octocrylene shows better Sun protection factor than Eclipta prostrata (bhringraj) leaf extract with octocrylene. The Sun Protection Factor (SPF) enhancement value of sunscreen compositions was compared to both sunscreen macroemulsion and nanoemulsion.

Water-compatible cross-linked pyrrolidone acrylate pressure-sensitive adhesives with persistent adhesion for transdermal delivery: Synergistic effect of hydrogen bonding and electrostatic force.

Poor skin adhesion and mechanical properties are common problems of pressure-sensitive adhesive (PSA) in transdermal drug delivery system (TDDS). Its poor water compatibility also causes the patch to fall off after sweating or soaking in the application site. To solve this problem, poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl)acrylamide) (PENH), a cross-linked pyrrolidone polyacrylate PSA, was designed to improve the adhesion and water resistance of PSA through electrostatic force and hydrogen bonding system. The structure of PENH was characterized by 1H NMR, FTIR, DSC, and other methods. The mechanism was studied by FTIR, rheological test, and molecular simulation. The results showed that the PENH patch could adhere to human skin for more than 10 days without cold flow, and it could still adhere after sweating or water contact. In contrast, the commercial PSA Duro-Tak® 87-4098 and Duro-Tak® 87-2852 fell off completely on the 3rd and 6th day, respectively, and Duro-Tak® 87-2510 showed a significant dark ring on the second day. Mechanism studies have shown that the hydrogen bond formed by 2-ethylhexyl acrylate (2-EHA), N-vinyl-2-pyrrolidinone (NVP), and N-(2-Hydroxyethyl)acrylamide (HEAA) enhances cohesion, the interaction with skin improves skin adhesion, and the electrostatic interaction with water or drug molecules enhances the ability of water absorption and drug loading. Due to the synergistic effect of hydrogen bonds and electrostatic force, PENH can maintain high cohesion after drug loading or water absorption. PENH provides a choice for the development of water-compatible patches with long-lasting adhesion. STATEMENT OF SIGNIFICANCE: Based on the synergistic effect of hydrogen bonding and electrostatic force, a hydrogen-bonded, cross-linked pyrrolidone acrylate pressure-sensitive adhesive for transdermal drug delivery was designed and synthesized, which has high adhesion and cohesive strength and is non-irritating to the skin. The patch can be applied on the skin surface continuously for more than 10 days without the phenomenon of "dark ring", and the patch can remain adherent after the patient sweats or bathes. This provides a good strategy for choosing a matrix for patches that require prolonged administration.

Efficient photocatalytic remediation of lerui acid brilliant blue dye using radiation- prepared carboxymethyl cellulose/acrylic acid hydrogel supported by ZnO@Ag.

Organic dye pollution from textiles and other industries presents a substantial risk to people and aquatic life. The use of photocatalysis to decolorize water using the strength of UV light is one of the most important remediation techniques. In the present study, a novel nanocomposites hydrogel including carboxymethyl cellulose (CMC), acrylic acid (AAc), Zinc oxide (ZnO), and silver (Ag) nanoparticles was produced using an eco-friendly γ-irradiation technique for photocatalytic decolorization applications. ZnO and Ag nanoparticles were distributed in the CMC/AAc hydrogel matrix without significant aggregation. SEM, XRD, EDX, TEM, and FTIR analyses were used to assess the physicochemical characteristics of the nanocomposite samples. Carboxymethyl cellulose/acrylic acid/Zinc oxide doped silver (CMC/PAAc/ZnO@Ag) nanocomposite hydrogels were developed and utilized in the photocatalytic decolorization of the lerui acid brilliant blue dye (LABB) when exposed to ultraviolet (UV) radiation. UV- Vis spectrophotometry was utilized to analyze the optical properties of the produced nanostructure. Regarding the decolorization of the LABB, the impacts of operational variables were investigated. The optimum conditions for decolorization (93 %) were an initial concentration of 50 mg/L, pH = 4, catalyst dosage of 50 g/L, and exposure time of 90 min. The results illustrated that the LABB acidic dye from wastewater was remarkably decolored.

Determination of breast cancer biomarkers with poly acrylic acid/ MIL-88(Fe)-NH2 hydrogel as a coating for stir bar sorptive extraction.

The Poly acrylic acid/MIL-88(Fe)-NH2 composite material, carefully prepared, is employed as a sorbent for the stir bar. The best formula of the composite was selected by investigation of two parameters including the cross-linker of PAA and MIL-88(Fe)-NH2 content. The prepared stir bar was used for extraction of 2-pentanone, 2-heptanone, ethyl propionate, para-xylene, 1,2,4-trimethylbenzene, o-cresol, m-cresol in urine samples as breast cancer biomarkers with gas chromatography-flame ionization detector. The prepared Poly acrylic acid / MIL-88(Fe)-NH2 as sorbent for the stir bar demonstrate good repeatability of one bar (relative standard deviation (RSD%) < 4.61 %) and satisfactory reproducibility between two bars (RSD% < 6.85 %). The central composite design method was applied for the optimization of extraction parameters. Under the optimum conditions, linear dynamic ranges for compounds were in the acceptable range with correlation coefficients higher than 0.99. Detection limits of them were less than 1.71 µg L-1.

Allergic contact dermatitis due to 1,6-hexanediol diacrylate in ostomy patients.

BACKGROUND: Many people live with ostomies after life-saving surgery. Ostomy patients often suffer from peristomal dermatitis. Allergic contact dermatitis (ACD) has been reported, mostly due to contact allergy (CA) to topical agents. OBJECTIVES: We present three patients with therapy resistant peristomal dermatitis, suggesting ACD caused by different stoma products. METHODS: Patch testing was performed with baseline series, additional series, and selected allergens. They were also tested with their own ostomy products as is and separate extracts of the products. Extracts were analysed using Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: In all three patients we diagnosed CA to 1,6-hexanediol diacrylate (HDDA), +++ in case (C) 1 and 3, ++ in C 2. HDDA was detected in C 2's ostomy pouch adhesive and in C 1's and 3's flange extenders used to improve the adhesion of the ostomy pouches. CONCLUSION: Therapy resistant peristomal dermatitis should always be suspected of ACD and patch testing, especially with the patient's own products, should be performed.

Fluacrypyrim Protects Hematopoietic Stem and Progenitor Cells against Irradiation via Apoptosis Prevention.

Ionizing radiation (IR)-induced hematopoietic injury has become a global concern in the past decade. The underlying cause of this condition is a compromised hematopoietic reserve, and this kind of hematopoietic injury could result in infection or bleeding, in addition to lethal mishaps. Therefore, developing an effective treatment for this condition is imperative. Fluacrypyrim (FAPM) is a recognized effective inhibitor of STAT3, which exhibits anti-inflammation and anti-tumor effects in hematopoietic disorders. In this context, the present study aimed to determine whether FAPM could serve as a curative agent in hematopoietic-acute radiation syndrome (H-ARS) after total body irradiation (TBI). The results revealed that the peritoneally injection of FAPM could effectively promote mice survival after lethal dose irradiation. In addition, promising recovery of peripheral blood, bone marrow (BM) cell counts, hematopoietic stem cell (HSC) cellularity, BM colony-forming ability, and HSC reconstituting ability upon FAPM treatment after sublethal dose irradiation was noted. Furthermore, FAPM could reduce IR-induced apoptosis in hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo. Specifically, FAPM could downregulate the expressions of p53-PUMA pathway target genes, such as Puma, Bax, and Noxa. These results suggested that FAPM played a protective role in IR-induced hematopoietic damage and that the possible underlying mechanism was the modulation of apoptotic activities in HSCs.

Digital light 4D printing of bioresorbable shape memory elastomers for personalized biomedical implantation.

Four-dimensional (4D) printing unlocks new potentials for personalized biomedical implantation, but still with hurdles of lacking suitable materials. Herein, we demonstrate a bioresorbable shape memory elastomer (SME) with high elasticity at both below and above its phase transition temperature (Ttrans). This SME can be digital light 3D printed by co-polymerizing glycerol dodecanoate acrylate prepolymer (pre-PGDA) with acrylic acid monomer to form crosslinked Poly(glycerol dodecanoate acrylate) (PGDA)-Polyacrylic acid (PAA), or PGDA-PAA network. The printed complex, free-standing 3D structures with high-resolution features exhibit shape programming properties at a physiological temperature. By tuning the pre-PGDA weight ratios between 55 wt% and 70 wt%, Ttrans varies between 39.2 and 47.2 ℃ while Young's moduli (E) range 40-170 MPa below Ttrans with fractural strain (εf) of 170 %-200 %. Above Ttrans, E drops to 1-1.82 MPa which is close to those of soft tissue. Strikingly, εf of 130-180 % is still maintained. In vitro biocompatibility test on the material shows > 90 % cell proliferation and great cell attachment. In vivo vascular grafting trials underline the geometrical and mechanical adaptability of these 4D printed constructs in regenerating the aorta tissue. Biodegradation of the implants shows the possibility of their full replacement by natural tissue over time. To highlight its potential for personalized medicine, a patient-specific left atrial appendage (LAA) occluder was printed and implanted endovascularly into an in vitro heart model. STATEMENT OF SIGNIFICANCE: 4D printed shape-memory elastomer (SME) implants particularly designed and manufactured for a patient are greatly sought-after in minimally invasive surgery (MIS). Traditional shape-memory polymers used in these implants often suffer from issues like unsuitable transition temperatures, poor biocompatibility, limited 3D design complexity, and low toughness, making them unsuitable for MIS. Our new SME, with an adjustable transition temperature and enhanced toughness, is both biocompatible and naturally degradable, particularly in cardiovascular contexts. This allows implants, like biomedical scaffolds, to be programmed at room temperature and then adapt to the body's physiological conditions post-implantation. Our studies, including in vivo vascular grafts and in vitro device implantation, highlight the SME's effectiveness in aortic tissue regeneration and its promising applications in MIS.

Micro(nano)plastics in human urine: A surprising contrast between Chongqing's urban and rural regions.

Microplastics (100 nm-5 mm) and nanoplastics (<100 nm) collectively referred to as micro(nano)plastics (MNPs), which are emerging pollutants all over the world. Environmental differences affect its distribution. The content of MNPs differs between urban and rural environments, according to previous studies. To understand the actual situation of human exposure to MNPs in various environments, this study collected 12 urine samples from volunteers in urban and rural regions of Chongqing and used pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and laser direct infrared spectroscopy (LDIR) to detect and analyze MNPs in urine. With an average abundance of 1.50 (2.31) mg/kg, MNPs were found in 9 samples by Py-GC/MS. Polyethylene (PE), polyvinyl chloride (PVC) and polyamide 66 (PA66), three different types of MNPs were found, with PE content being the highest among them. By using LDIR, MNPs were found in 7 samples, with an average abundance of 15.17 (23.13) particles/kg. Five different types of MNPs were found, with acrylates (ACR) being the main type, followed by polymethylmethacrylate (PMMA), polyurethane (PU), polypropylene (PP), polyethylene terephthalate (PET). The findings demonstrated that urban region had much greater levels and more types of MNPs in human urine than rural. Additionally, regular contact with plastic toys and the use of personal care products are linked to the presence of MNPs. The influence of environmental factors on the actual exposure of the human body to MNPs was preliminary explored in this study, and two different methods were used for the first time to simultaneously detect and analyze MNPs in human urine. This allowed for the feasibility of comprehensively and effectively quantitatively analyzing the actual exposure of the human body to MNPs, and also provided the theoretical foundation for further research on the harm of MNPs to human health in different environments.

Derivation of no significant risk levels for three lower acrylates: Conclusions and recommendations from an expert panel.

A panel of toxicology, mode of action (MOA), and cancer risk assessment experts was engaged to derive no-significant-risk-levels (NSRLs) for three lower acrylates: methyl acrylate (MA), ethyl acrylate (EA), and 2-ethylhexyl acrylate (2EHA) using the best available science, data, and methods. The review was structured as a five-round, modified Delphi format, a systematic process for collecting independent and deliberative input from panel members, and it included several procedural elements to reduce potential sources of bias and groupthink. Input from the panel for key decisions in the dose-response assessments resulted in NSRL values of 530 µg/day (330-800 µg/day), 640 µg/day (280-670 µg/day), and 1700 µg/day (1300-2700 µg/day) for MA, EA, and 2EHA, respectively. Novel to this approach were the use of nonneoplastic lesions reported at point of contact where tumors have been reported in laboratory rodents, along with nonlinear extrapolation to low doses (uncertainty factor approach) based upon panel recommendations. Confidence in these values is considered medium to high for exposures applied to the routes of exposure tested (inhalation for MA and EA, dermal for 2EHA), but confidence is considered lower when applied to other routes of exposure.