Poly(Propylene Carbonate)-Based Biodegradable and Environment-Friendly Materials for Biomedical Applications.

Poly(propylene carbonate) (PPC) is an emerging "carbon fixation" polymer that holds the potential to become a "biomaterial of choice" in healthcare owing to its good biocompatibility, tunable biodegradability and safe degradation products. However, the commercialization and wide application of PPC as a biomedical material are still hindered by its narrow processing temperature range, poor mechanical properties and hydrophobic nature. Over recent decades, several physical, chemical and biological modifications of PPC have been achieved by introducing biocompatible polymers, inorganic ions or small molecules, which can endow PPC with better cytocompatibility and desirable biodegradability, and thus enable various applications. Indeed, a variety of PPC-based degradable materials have been used in medical applications including medical masks, surgical gowns, drug carriers, wound dressings, implants and scaffolds. In this review, the molecular structure, catalysts for synthesis, properties and modifications of PPC are discussed. Recent biomedical applications of PPC-based biomaterials are highlighted and summarized.

Optimizing the Ion Conductivity and Mechanical Stability of Polymer Electrolyte Membranes Designed for Use in Lithium Ion Batteries: Combining Imidazolium-Containing Poly(ionic liquids) and Poly(propylene carbonate).

State-of-the-art Li batteries suffer from serious safety hazards caused by the reactivity of lithium and the flammable nature of liquid electrolytes. This work develops highly efficient solid-state electrolytes consisting of imidazolium-containing polyionic liquids (PILs) and lithium bis(trifluoromethane sulfonyl)imide (LiTFSI). By employing PIL/LiTFSI electrolyte membranes blended with poly(propylene carbonate) (PPC), we addressed the problem of combining ionic conductivity and mechanical properties in one material. It was found that PPC acts as a mechanically reinforcing component that does not reduce but even enhances the ionic conductivity. While pure PILs are liquids, the tricomponent PPC/PIL/LiTFSI blends are rubber-like materials with a Young's modulus in the range of 100 MPa. The high mechanical strength of the material enables fabrication of mechanically robust free-standing membranes. The tricomponent PPC/PIL/LiTFSI membranes have an ionic conductivity of 10-6 S·cm-1 at room temperature, exhibiting conductivity that is two orders of magnitude greater than bicomponent PPC/LiTFSI membranes. At 60 °C, the conductivity of PPC/PIL/LiTFSI membranes increases to 10-5 S·cm-1 and further increases to 10-3 S·cm-1 in the presence of plasticizers. Cyclic voltammetry measurements reveal good electrochemical stability of the tricomponent PIL/PPC/LiTFSI membrane that potentially ranges from 0 to 4.5 V vs. Li/Li+. The mechanically reinforced membranes developed in this work are promising electrolytes for potential applications in solid-state batteries.

K2CO3-Modified Smectites as Basic Catalysts for Glycerol Transcarbonation to Glycerol Carbonate.

A novel and cost-effective heterogeneous catalyst for glycerol carbonate production through transesterification was developed by impregnating smectite clay with K2CO3. Comprehensive structural and chemical analyses, including X-ray diffraction Analysis (XRD), Scanning Electron Microscopy (SEM)-Electron Dispersion Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) surface area analysis measurements, were employed to characterize the catalysts. Among the various catalysts prepared, the one impregnated with 40 wt% K2CO3 on smectite and calcined at 550 °C exhibited the highest catalytic activity, primarily due to its superior basicity. To enhance the efficiency of the transesterification process, several reaction parameters were optimized, including the molar ratio between propylene carbonate and glycerol reactor loading of the catalyst and reaction temperature. The highest glycerol carbonate conversion rate, approximately 77.13% ± 1.2%, was achieved using the best catalyst under the following optimal conditions: 2 wt% reactor loading, 110 °C reaction temperature, 2:1 propylene carbonate to glycerol molar ratio, and 6h reaction duration. Furthermore, both the raw clay and the best calcined K2CO3-impregnated catalysts demonstrated remarkable stability, maintaining their high activity for up to four consecutive reaction cycles. Finally, a kinetic analysis was performed using kinetic data from several runs employing raw clay and the most active K2CO3-modified clay at different temperatures, observing that a simple reversible second-order potential kinetic model of the quasi-homogeneous type fits perfectly to such data in diverse temperature ranges.

Human health risk assessment of volatile organic compounds in oil-based drill cuttings of shale gas.

Waste oil-based drill cuttings contain dioxins and volatile organic compounds (VOCs), which have the potential to cause serious health effects in humans. Therefore, this paper took oil-based drill cuttings (OBDCs) as the research object and carried out the testing of VOCs and dioxins content by using GC-MS and HRGCS-HRMS and comprehensively evaluated the content, composition and distribution pattern of VOCs and dioxins and the risk to human health posed by the two pollutants in OBDCs. The results showed that the VOCs did not exceed the emission limits in ESPPI (GB 31571-2015), but it is vital to recognise that 1,2-dichloropropane has the potential to cause cancer risk, with soil and groundwater risk control values of 662.95 mg·kg-1 and 0.066 mg·kg-1, respectively. Benzene, 1,2-dichloropropane and 8 other VOCs pose a non-carcinogenic risk to humans. The levels of polychlorinated dibenzofurans (PCDFs) exceeded those of polychlorinated dibenzo-p-dioxins (PCDDs), which accounted for 95.76 percent of the total PCDD/Fs, 2,3,4,7,8-P5CDF (56.00%), 2,3,7,8-T4CDF (9.20%), 1,2,3,6,7,8-H6CDF (8.80%) and 1,2,3,7,8-P5CDF (8.00%) were the main contributing monomers. The findings of the assessment on exposure risk indicate that there is a respiratory risk to oil-based drill cuttings dioxins for adults and children exceeded the World Health Organisation (WHO) acceptable daily intake (ADI) (1-4 pgTEQ/kg/d). Finally, three aspects of solid waste pre-treatment prior to incineration, the incineration process and post incineration were used to reduce the environmental and human health risks from dioxins.

Multiple spectrophotometric determinations of Chlorthalidone and Cilnidipine using propylene carbonate - As a step towards greenness.

Analyzing a drug based on its overlapping spectra requires the use of sophisticated equipment and more hazardous solvents, which is detrimental to ecological sustainability. There is a critical need to create a simple, unique, and cost-effective approach for detecting a mixture of compounds in a safer environment. The aim was to develop an eco-friendly, stability-indicating assay method to determine Chlorthalidone (CLD) and Cilnidipine (CIL) in bulk and tablet dosage form using four different Ultra-Violet (UV) spectrophotometric methods. The ratio difference method showed absorbance peaks at 256.01 nm, 220.87 nm, first ratio difference spectra at 267.21 nm, 288.03 nm, and second ratio difference spectra at 309.2 nm, 280.03 nm. The area under curve techniques showed an absorbance range of around 224-232 nm for CIL and 218-227 nm for CLD. Further, the spectral changes have been assessed at various conditions like acid, base, oxidation, and UV radiation, and it has been found that CLD tends to lose its spectral property by more than 45%. The method developed for two drugs has obeyed Beers law with the selected concentration range of 7-13 µg/mL for CLD and 8.75-16.25 µg/mL for CIL. The developed method was finally evaluated using four tools, and the results showed green pictographically representation in the GAPI and score near to 100 for AES and closer to 1 for AGREE indicated that the method was found to be most eco-friendly. The findings were easy to replicate, adoptive with major regulatory requirements, environmentally friendly, fast, and inexpensive to perform. This approach does not require any specific expensive equipment, and it might be inexpensive to use in the future to assess laboratory and commercial mixtures.

Transcriptome analysis of human cholangiocytes exposed to carcinogenic 1,2-dichloropropane in the presence of macrophages in vitro.

1,2-Dichloropropane (1,2-DCP), a synthetic organic solvent, has been implicated in causality of cholangiocarcinoma (bile duct cancer). 1,2-DCP-induced occupational cholangiocarcinoma show a different carcinogenic process compared to common cholangiocarcinoma, but its mechanism remains elusive. We reported previously that exposure of MMNK-1 cholangiocytes co-cultured with THP-1 macrophages, but not monocultured MMNK-1 cholangiocytes, to 1,2-DCP induced activation-induced cytidine deaminase (AID) expression, DNA damage and ROS production. The aim of this study was to identify relevant biological processes or target genes expressed in response to 1,2-DCP, using an in vitro system where cholangiocytes are co-cultured with macrophages. The co-cultured cells were exposed to 1,2-DCP at 0, 0.1 or 0.4 mM for 24 h, and then the cell lysates were assessed by transcriptome analysis. 1,2-DCP upregulated the expression of base excision repair genes in MMNK-1 cholangiocytes in the co-cultures, whereas it upregulated the expression of cell cycle-related genes in THP-1 macrophages. Activation of the base excision repair pathway might result from the previously observed DNA damage in MMNK-1 cholangiocytes co-cultured with THP-1 macrophages, although involvement of other mechanisms such as DNA replication, cell death or other types of DNA repair was not disproved. Cross talk interactions between cholangiocytes and macrophages leading to DNA damage in the cholangiocytes should be explored.

Sphingopyxis yananensis sp. nov., a novel 2-nitropropane degrading bacterium isolated from a microbial fermentation bed substrate.

A rod-shaped, Gram-negative staining strain, FBM22T, was isolated from a microbial fermentation bed substrate from a pig farm. Its colonies appeared yellow and were 0.5-1.2 mm in diameter. Cells were 0.3-0.5 µm wide, 0.5-0.83 µm long. Optimal growth occurred at 30 °C and pH 7.0-8.0; NaCl was not required for growth. The strain performed denitrification and nitrate reduction functions. And it could produce catalase. FBM22-1T utilized the following organic substrates for growth: tyrosine, glutamic acid, D-glucose, and galactose. The novel isolate could degrade 2-nitropropane as carbon and nitrogen source. The dominant respiratory quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. C18:1 ω7c, C16:1 ω7c and/ or C16:1 ω6c, and C14:0 2-OH were the major (≥ 8%) fatty acids. The G+C content was 56.8 mol%. FBM22T was found to be a member of the genus Sphingopyxis in the family Sphingomonadaceae of the class Alphaproteobacteria. It had the highest sequence similarity with the type strains Sphingopyxis terrae subsp. ummariensis UI2T (96.47%) and Sphingopyxis terrae subsp. terrae NBRC 15098T (96.40%). Furthermore, FBM22T had 18.7% and 18.4% relatedness (based on digital DNA-DNA hybridization) with its two relatives (S. terrae subsp. ummariensis UI2T and S. terrae subsp. terrae NBRC 15098T). The morphological, physiological, and genotypic differences identified in this study support the classification of FBM22T as a novel species within the genus Sphingopyxis, for which the name Sphingopyxis yananensis sp. nov. is proposed. The type strain is FBM22T (= KCTC 82290T = CCTC AB2020286T).

Patch testing with the European baseline series and 10 added allergens: Single-centre study of 748 patients.

BACKGROUND: The European baseline series (EBS) of contact allergens is subject to change. An allergen is considered for inclusion when routine patch testing of patients with suspected contact dermatitis results in ≥0.5% prevalence rate. OBJECTIVES: We aimed to determine the frequency of sensitizations to 30 EBS allergens and 10 locally added allergens. Additionally, we assessed the strength and evolution of reactions to all tested allergens and co-reactivity of additional allergens. METHODS: Patch testing with our baseline series of 40 allergens was done in 748 consecutive adults. Tests were applied to the upper back and removed by patients after 48 h. Readings were done on Day 3 (D3) and D6 or D7 (D6/7). Positive reactions fulfilled the criteria of at least one plus (+) reaction. A retrospective analysis was done. RESULTS: Eight allergens not listed in the EBS had ≥0.5% prevalence rate (i.e., cocamidopropyl betaine, thiomersal, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, propylene glycol, Compositae mix II and dexamethasone-21-phosphate), and 16.6% of positive reactions would have been missed without D6/7 readings. CONCLUSION: We propose further studies to evaluate whether cocamidopropyl betaine, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea and Compositae mix II need to be added to the EBS.

Improving Cyclability of All-Solid-State Batteries via Stabilized Electrolyte-Electrode Interface with Additive in Poly(propylene carbonate) Based Solid Electrolyte.

In this study, tetraethylene glycol dimethyl ether (TEGDME) is demonstrated as an effective additive in poly(propylene carbonate) (PPC) polymers for the enhancement of ionic conductivity and interfacial stability and a tissue membrane is used as a backbone to maintain the mechanical strength of the solid polymer electrolytes (SPEs). TEGDME in the PPC allows the uniform distribution of conductive LiF species throughout the cathode electrolyte interface (CEI) layer which plays a critically important role in the formation of a stable and efficient CEI. In addition, the high modulus of SPEs suppresses the formation of a protrusion-type CEI on the cathode. The SPE with the optimized TEGDME content exhibits a high ionic conductivity of 0.89 mS cm-1 , an adequate potential stability of up to 4.89 V, and a high Li-ion transference number of 0.81 at 60 °C. Moreover, the Li/SPE/Li cell demonstrates excellent cycling stability for 1650 h, and the Li/SPE/LFP full cell exhibits an initial reversible capacity of 103 mAh g-1 and improved stability over 500 cycles at a rate of 1 C. The TEGDME additive improves the electrochemical properties of the SPEs and promotes the creation of a stable interface, which is crucial for ASSLIBs.

A novel sustained release fluoride strip based Poly(propylene carbonate) for preventing caries.

Low-level fluoride in the oral environment for a long sustained period is more effective for preventing caries. However, the current fluoride delivery methods have a short fluoride retention time and high-dose fluoride administration may increase the risk of dental fluorosis. This study developed a novel fluoride strip based poly(propylene carbonate) (PPC), which can improve oral fluoride retention for desirable anticaries effect with minimal side effects. The fluoride strips based PPC (NaF-PPC strips) with different fluoride contents (0, 1.25, 2.5 and 5 wt.%) were developed by melt-blending method. The physico-chemical characteristics, drug loading, drug release properties, remineralization and antibacterial efficacy and biocompatibility of NaF-PPC strips were investigated. The in vitro drug release studies indicated that fluoride release in a sustained manner with no initial burst release and approximately 100% of fluoride ions were released from PPC strips over 24 days. NaF-PPC strips exhibited excellent remineralization and antibacterial potential when fluoride content up to 5%. Combination with biocompatibility, 2.5% NaF-PPC strips could be a promising fluoride application for preventing caries. This work provides an effective and novel topical fluoride delivery for general use.

Can fig and olive ameliorate the toxicity induced by 2-nitropropane in some organs of mice? Role of inflammatory versus anti-inflammatory gene.

OBJECTIVE: To investigate the efficacy of Fig fruit powder and olive on hepatic, renal and splenic injury induced by 2-nitropropane (2-NP) in mice, especially if they were used in combination. METHODS: A total of 40 adult BALB/c male mice weighting 25-30 g/each. Mice were categorized into five groups (8 each). Group 1 as negative control. Group 2 as positive control group intraperitoneally injected with 2-NP (100 mg/kg b. w.) 3 times/weekly for eight weeks. Group 3 injected with 2-NP and were orally supplemented with Fig (300 mg/kg). Group 4 injected with 2-NP and were orally supplemented with olive (100 mg/kg). Group 5 injected with 2-NP and were orally supplemented with mixture of Fig and olive (3:1 respectively). RESULTS: Histopathological observation of liver in mice treated with 2-NP showed cellular degeneration, pyknosis, and congestion of the portal vein. In kidney there were disorganization of the cortical tissues, cellular necrosis and plenty of inflammatory lymphocytic aggregation. Significant elevations in liver function parameters (alanine aminotransferase and aspartate aminotransferase), mRNA expression levels of tumor necrosis factor-α, nicotinamide adenine dinucleotide phosphate oxidase and cyclooxygenase were detected as anti-inflammatory markers and 5-lipoxygenase, interleukin-1α and interleukin-6 as inflammatory biomarkers for liver and spleen, also significant elevations was detected in lipid peroxidation levels. The levels of antioxidants, glutathione, glutathione peroxidase, catalase and superoxide dismutase were significantly decreased. CONCLUSION: our findings indicated that Fig fruit powder and olive protected against hepatic, renal and splenic injury induced with 2-NP in mice, especially if they were used in combination.

[Advances in degradation mechanisms of 1,2,3-trichloropropane and remediation technology of contaminated sites].

1,2,3-trichloropropane (TCP) is an industrially synthesized aliphatic chlorinated hydrocarbon and an intermediate product in the industrial production of epichlorohydrin, which can be used as a precursor for the manufacture of soil fumigant and organic solvents. Due to its biological toxicity, environmental persistence and strong environmental migration ability, 1,2,3-TCP is listed as an emerging organochlorine pollutant in the environment and regulated by many international organizations. Currently, the degradation of 1,2,3-TCP and the remediation of 1,2,3-TCP-contaminated sites receive great attention, but the degradation mechanism of 1,2,3-TCP has not been summarized in depth. This article discussed the origin of 1,2,3-TCP, its environmental impact and ecological effects, and the physical and chemical degradation techniques. This was followed by summarizing the degradation mechanisms of 1,2,3-TCP (e.g., aerobic co-biodegradation, anaerobic biodegradation). Specially, the pathways and mechanisms of microbial biodegradation and transformation of 1,2,3-TCP in anoxic environments (e.g., groundwater) were thoroughly reviewed. The feasibility of using 1,2,3-TCP as an electron acceptor by organohalide-respiring bacteria under anoxic conditions was predicted based on thermodynamic analysis. Last but not least, in situ bioremediation of 1,2,3-TCP contaminated sites was summarized, and prospects for future research were discussed.

Enhanced dechlorination of 1,2-dichloropropane to propene in a bioelectrochemical system mediated by Dehalogenimonas.

Bioelectrochemical systems (BES) are promising technologies to enhance the growth of organohalide-respiring bacteria and to treat chlorinated aliphatic hydrocarbons. In this study, two carbon-based cathodic electrode materials, a graphite brush and a carbon cloth, were used as hydrogen suppliers to couple growth of Dehalogenimonas and dechlorination of 1,2-DCP to nontoxic propene in the cathode vessel. The BES with graphite brush electrode consumed ~4000 µM 1,2-DCP during 110 days and exhibited a degradation rate 5.6-fold higher than the maximum value obtained with the carbon cloth electrode, with a cathode potential set at -0.7 V. Quantitative PCR confirmed that Dehalogenimonas gene copies increased by two orders of magnitude in the graphite brush BES, with an average yield of 1.2·108±5·107 cells per µmol of 1,2-DCP degraded. The use of a pulsed voltage operation (cathode potential set at -0.6 V for 16 h and -1.1 V for 8 h) increased the coulombic efficiency and degradation of 1,2-DCP when compared with a continuous voltage operation of -1.1 V. Bacterial cell aggregates were observed in the surface of the graphite brush electrodes by electron scanning microscopy, suggesting biofilm formation. This study expands the range of chlorinated compounds degradable and organohalide-respiring bacteria capable of growing in BES.

1,2-Dichloropropane induces γ-H2AX expression in human cholangiocytes only in the presence of macrophages.

Recent epidemiological studies reported cases of cholangiocarcinoma in workers exposed to 1,2-dichloropropane (1,2-DCP) in an offset proof printing factory in Japan. The present study investigated the effects of 1,2-DCP on the expression of histone family member X (H2AX) phosphorylated on Ser 139 (γ-H2AX), a marker of DNA double strand break, in human immortalized cholangiocytes MMNK-1 cells. Mono-cultures of MMNK-1 cells and co-cultures of MMNK-1 cells with THP-1 macrophages were exposed to 1,2-DCP at concentrations of 100 and 500 µM for 24 h. Expression of γ-H2AX was visualized by immunofluorescence staining. Exposure to 1,2-DCP had no effect on the expression of γ-H2AX in mono-cultured MMNK-1 cells, but significantly increased the number of nuclear foci stained by γ-H2AX in MMNK-1 cells co-cultured with THP-1 macrophages. Exposure to 1,2-DCP also significantly increased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in co-cultured MMNK-1 cells. The results suggest that macrophages play a critical role by producing cytokines in 1,2-DCP-induced DNA double strand break in MMNK-1 cells.

Chitosan scaffolds with enhanced mechanical strength and elastic response by combination of freeze gelation, photo-crosslinking and freeze-drying.

In this study, a new scaffold fabrication method based on the combination of a series of stabilization processes was set up to obtain chitosan scaffolds with improved mechanical properties for regeneration of load-bearing tissues. Specifically, thermally induced phase separation (TIPS) of chitosan solutions was used to obtain an open structure which was then stabilized by freeze-gelation and photo cross-linking. Freeze-gelation combined with freeze-drying permitted to obtain a porous structure with a 95 µm-mean pore size suitable for osteoblast cells' housing. Photo-crosslinking improved by ca. three times the scaffold compressive modulus, passing from 0,8 MPa of the uncrosslinked scaffolds to 2,2 MPa of the crosslinked one. Hydrated crosslinked scaffolds showed a good elastic response, with an 80% elastic recovery for at least 5 consecutive compressive cycles. The herein reported method has the advantage to not require the use of potentially toxic cross-linking agents and may be extended to other soft materials.

Chitosan nanoparticles as a promising candidate for liver injury induced by 2-nitropropane: Implications of P53, iNOS, VEGF, PCNA, and CD68 pathways.

The current article was designed to assess the role of chitosan nanoparticles (CNPs) in the management of hepatic injury induced by the hepatocarcinogen 2-nitropropane (2-NP). Rats were divided into three groups. The first group served as a control, the second group was injected with 2-NP, while the third group was treated with CNPs 1 h before 2-NP injection every other day for 4 weeks. The 2-NP injection upregulated serum AST and ALT activities, as well as hepatic TNF- α, IL-6, and MDA levels and the expression of vascular endothelial growth factor (VEGF) and caspase-3, whereas GSH contents and SOD activity were decreased. Immunohistochemistry investigations revealed that the hepatic protein expression of collagen I, inducible nitric oxide synthetase, proliferating cell nuclear antigen, cluster of differentiation, and p53 were upregulated. hematoxylin and eosin (H&E) and Masson's trichrome stains supported the previous parameters, and CNPs ameliorated most of the previous biochemical parameters. CNPs achieved promising results in the limitation of 2-NP hepatotoxicity.

Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis.

The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.

Hazard characterization of carcinogenicity, mutagenicity, and reproductive toxicity for short chain primary nitroalkanes.

Nitroalkanes are organic aliphatic hydrocarbon compounds with a nitro moiety that are commonly used as solvents or intermediates to synthesize a variety of organic compounds due to their inherent reactivity. In June 2020, a harmonized classification and labeling (CLH) proposal was submitted to the European Chemicals Agency (ECHA) for the following harmonized carcinogenicity, mutagenicity, and reproductive toxicity ("CMR") classifications for nitromethane (NM), nitroethane (NE), and 1-nitropropane (1-NP): NM Carc. 1B and Repr. 1B; NE Repr. 1B; and 1-NP Repr. 2. In this assessment, a weight of evidence (WoE) evaluation of studies on animal carcinogenicity and reproductive and developmental toxicity, genotoxicity, and mode of action for these three nitroalkanes was performed to critically assess the relevance of the proposed CMR classifications. Overall, the WoE indicates that NM, NE, and 1-NP are not carcinogenic, genotoxic, nor selective reproductive or developmental toxicants. Based on our analysis, classifying NM, NE, and 1-NP as Category 2 reproductive toxicants is most appropriate. Furthermore, not classifying NE and 1-NP with respect to their carcinogenicity is appropriate based on the available studies for this endpoint coupled with negative results in genotoxicity studies, metabolism data, and in silico predictions. We determined that the classification for NM of Carc. 1B is not appropriate, based on the fact that rat mammary and harderian tumors are likely not relevant to humans and lung and liver tumors reported in mice were equivocal in their dose-response and statistical significance.

Gelatin Methacryloyl-Riboflavin (GelMA-RF) Hydrogels for Bone Regeneration.

Gelatin methacryloyl (GelMA) is a versatile biomaterial that has been used in various biomedical fields. UV light is commonly used to photocrosslink such materials; however, its use has raised several biosafety concerns. We investigated the mechanical and biological properties of a visible-wavelength (VW)-light-crosslinked gelatin-based hydrogel to evaluate its viability as a scaffold for bone regeneration in bone-destructive disease treatment. Irgacure2959 or riboflavin was added as a photoinitiator to create GelMA solutions. GelMA solutions were poured into a mold and exposed to either UV or VW light. KUSA-A1 cell-laden GelMA hydrogels were crosslinked and then cultured. Mechanical characterization revealed that the stiffness range of GelMA-RF hydrogel was suitable for osteoblast differentiation. KUSA-A1 cells encapsulated in GelMA hydrogels photopolymerized with VW light displayed significantly higher cell viability than cells encapsulated in hydrogels photopolymerized with UV light. We also show that the expression of osteogenesis-related genes at a late stage of osteoblast differentiation in osteoblasts encapsulated in GelMA-RF hydrogel was markedly increased under osteoblast differentiation-inducing conditions. The GelMA-RF hydrogel served as an excellent scaffold for the encapsulation of osteoblasts. GelMA-RF hydrogel-encapsulated osteoblasts have the potential not only to help regenerate bone mass but also to treat complex bone defects associated with bone-destructive diseases such as periodontitis.

Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1-(Pyrrolidin-2-yl)propan-2-one Derivatives.

Deoxyribonuclease I (DNase I) inhibitory properties of two 1-(pyrrolidin-2-yl)propan-2-one derivatives were examined in vitro. Determined IC50 values of 1-[1-(4-methoxyphenyl)pyrrolidin-2-yl]propan-2-one (1) (192.13±16.95 µM) and 1-[1-(3,4,5-trimethoxyphenyl)pyrrolidin-2-yl]propan-2-one (2) (132.62±9.92 µM) exceed IC50 value of crystal violet, used as a positive control, 1.89- and 2.73-times, respectively. Compounds are predicted to be nontoxic and to have favorable pharmacokinetic profiles, with high gastrointestinal absorption and blood-brain barrier permeability. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, Glu 78, Arg 111, Pro 137, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Determined inhibitory properties along with predicted ADMET profiles and observed interactions would be beneficial for the discovery of new active 1-(pyrrolidin-2-yl)propan-2-one-based inhibitors of DNase I.