Polyene phosphatidylcholine promotes tibial fracture healing in rats by stimulating angiogenesis dominated by the VEGFA/VEGFR2 signaling pathway.

One of the factors that predispose to fractures is liver damage. Interestingly, fractures are sometimes accompanied by abnormal liver function. Polyene phosphatidylcholine (PPC) is an important liver repair drug. We wondered if PPC had a role in promoting fracture healing. A rat model of tibial fracture was developed using the modified Einhorn model method. X-rays were used to detect the progression of fracture healing. Progress of ossification and angiogenesis at the fracture site were analyzed by Safranin O/fast green staining and CD31 immunohistochemistry. To investigate whether PPC has a direct angiogenesis effect, HUVECs were used. We performed MTT, wound healing, Transwell migration, and tube formation assays. Finally, RT-qPCR and Western blot analysis were used to study the underlying mechanism. The results showed that PPC significantly shortened the apparent recovery time of mobility in rats. PPC treatment significantly promoted the formation of cartilage callus, endochondral ossification, and angiogenesis at the fracture site. In vitro, PPC promoted the proliferative viability of HUVECs, their ability to heal wounds, and their ability to penetrate membranes in the Transwell apparatus and increased the tube formation of cells. The transcription of VEGFA, VEGFR2, PLCγ, RAS, ERK1/2 and MEK1/2 was significantly up regulated by PPC. Further, the protein level results demonstrated a significant increase in the expression of VEGFA, VEGFR2, MEK1/2, and ERK1/2 proteins. In conclusion, our findings suggest that PPC promotes angiogenesis by activating the VEGFA/VEGFR2 and downstream signaling pathway, thereby accelerating fracture healing.

The Discovery of Weddellamycin, a Tricyclic Polyene Macrolactam Antibiotic from an Antarctic Deep-Sea-Derived Streptomyces sp. DSS69, by Heterologous Expression.

Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO. Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10-0.83 µg/mL, and antifungal activity against Candida albicans, with an MIC value of 3.33 µg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC50 values ranging from 2.07 to 11.50 µM.

Shock absorption and dispersion capability of a novel five-layer mouthguard sheet material.

There is a growing need for a mouthguard sheet material with higher shock absorption and dispersion capacity than those obtained by conventional materials. A five-layer mouthguard sheet material was previously developed using laminated ethylene vinyl acetate and polyolefin copolymer resin. In this study, the shock absorption capacity and dispersion capability of the new sheet material were investigated and compared with those of other materials. Impact testing for the new sheet material showed that the force required to displace the sheet by 1 mm was significantly higher at all thicknesses (p<0.001), whereas the puncture energy and displacement were significantly lower than those for ethylene vinyl acetate (p<0.05). The five-layer mouthguard sheet material successfully absorbed and resisted shock. Therefore, the sheet material potentially increases resistance to applied deformation in teeth and alveolar bone and maintains structure. The five-layer sheet material could expand the range of mouthguard products and help prevent oral trauma.

Characterisation of Modular Polyketide Synthases Designed to Make Pentaene Analogues of Amphotericin B.

Glycosylated polyene macrolides are important antifungal agents that are produced by many actinomycete species. Development of new polyenes may deliver improved antibiotics. Here, Streptomyces nodosus was genetically re-programmed to synthesise pentaene analogues of the heptaene amphotericin B. These pentaenes are of interest as surrogate substrates for enzymes catalysing unusual, late-stage biosynthetic modifications. The previous deletion of amphotericin polyketide synthase modules 5 and 6 generated S. nodosus M57, which produces an inactive pentaene. Here, the chain-terminating thioesterase was fused to module 16 to generate strain M57-16TE, in which cycles 5, 6, 17 and 18 are eliminated from the biosynthetic pathway. Another variant of M57 was obtained by replacing modules 15, 16 and 17 with a single 15-17 hybrid module. This gave strain M57-1517, in which cycles 5, 6, 15 and 16 are deleted. M57-16TE and M57-1517 gave reduced pentaene yields. Only M57-1517 delivered its predicted full-length pentaene macrolactone in low amounts. For both mutants, the major pentaenes were intermediates released from modules 10, 11 and 12. Longer pentaene chains were unstable. The novel pentaenes were not glycosylated and were not active against Candida albicans. However, random mutagenesis and screening may yet deliver new antifungal producers from the M57-16TE and M57-1517 strains.

Dimensional accuracy and simulation-based optimization of polyolefins and biocopolyesters for extrusion-based additive manufacturing and steam sterilization.

Polyolefins exhibit robust mechanical and chemical properties and can be applied in the medical field, e.g. for the manufacturing of dentures. Despite their wide range of applications, they are rarely used in extrusion-based printing due to their warpage tendency. The aim of this study was to investigate and reduce the warpage of polyolefins compared to commonly used filaments after additive manufacturing (AM) and sterilization using finite element simulation. Three types of filaments were investigated: a medical-grade polypropylene (PP), a glass-fiber reinforced polypropylene (PP-GF), and a biocopolyester (BE) filament, and they were compared to an acrylic resin (AR) for material jetting. Square specimens, standardized samples prone to warpage, and denture bases (n = 10 of each group), as clinically relevant and anatomically shaped reference, were digitized after AM and steam sterilization (134 °C). To determine warpage, the volume underneath the square specimens was calculated, while the deviations of the denture bases from the printing file were measured using root mean square (RMS) values. To reduce the warpage of the PP denture base, a simulation of the printing file based on thermomechanical calculations was performed. Statistical analysis was conducted using the Kruskal-Wallis test, followed by Dunn's test for multiple comparisons. The results showed that PP exhibited the greatest warpage of the square specimens after AM, while PP-GF, BE, and AR showed minimal warpage before sterilization. However, warpage increased for PP-GF, BE and AR during sterilization, whereas PP remained more stable. After AM, denture bases made of PP showed the highest warpage. Through simulation-based optimization, warpage of the PP denture base was successfully reduced by 25%. In contrast to the reference materials, PP demonstrated greater dimensional stability during sterilization, making it a potential alternative for medical applications. Nevertheless, reducing warpage during the cooling process after AM remains necessary, and simulation-based optimization holds promise in addressing this issue.

Chromophore-Protein Interactions Affecting the Polyene Twist and π-π* Energy Gap of the Retinal Chromophore in Schizorhodopsins.

The properties of a prosthetic group are broadened by interactions with its neighboring residues in proteins. The retinal chromophore in rhodopsins absorbs light, undergoes structural changes, and drives functionally important structural changes in proteins during the photocycle. It is therefore crucial to understand how chromophore-protein interactions regulate the molecular structure and electronic state of chromophores in rhodopsins. Schizorhodopsin is a newly discovered subfamily of rhodopsins found in the genomes of Asgard archaea, which are extant prokaryotes closest to the last common ancestor of eukaryotes and of other microbial species. Here, we report the effects of a hydrogen bond between a retinal Schiff base and its counterion on the twist of the polyene chain and the color of the retinal chromophore. Correlations between spectral features revealed the unexpected fact that the twist of the polyene chain is reduced as the hydrogen bond becomes stronger, suggesting that the twist is caused by tight atomic contacts between the chromophore and nearby residues. In addition, the strength of the hydrogen bond is the primary factor affecting the color-tuning of the retinal chromophore in schizorhodopsins. The findings of this study are valuable for manipulating the molecular structure and electronic state of the chromophore by controlling chromophore-protein interactions.

Multi-color polymer carbon dots synthesized from waste polyolefins through phenylenediamine-assisted hydrothermal processing.

The large accumulation and low recycling rates of polyolefin waste have posed a threat to the environment and human health. The shortage of chemical recycling methods for polyolefins strongly demands the development of new and sustainable treatment technologies for hydrocarbon plastics to improve their waste management. In this study, polyethylene (PE) and polypropylene (PP) were utilized for the preparation of multi-color polymer carbon dots (PCDs) via a two-step hydrothermal (HT) synthesis involving (i) thermo-oxidative degradation of polyolefins to precursors containing plentiful oxygen-based functional groups, and (ii) modification with phenylenediamine (PDA). The fluorescence of PCDs depends on the structure of isomeric PDA and PCDs modified by ortho-, meta-, and para-PDA emit blue, green, and yellow color fluorescence, respectively. The formation mechanism of PCDs, involving dehydrative condensation and amination of PE or PP-derived precursors by PDA, was proposed. The obtained PCDs were utilized for the detection and quantification of Fe3+ ions at ppm concentrations. The proposed strategy here aims to broaden the scope of the chemical recycling methods for polyolefin plastic waste as well as to develop a conversion route of polyolefin to value-added materials.

Absolute Configuration of Oxabornyl Polyenes Prugosenes A1-A3 and Structural Revision of Prugosene A2.

Oxabornyl polyenes represent a unique group of polyketides characterized by a central polyene core flanked by a conserved oxabornyl moiety and a structurally diverse oxygen heterocyclic ring. They are widely distributed in fungi and possess a variety of biological activities. Due to the significant spatial separation between the two stereogenic ring systems, it is difficult to establish their overall relative configurations. Here, we isolated three oxabornyl polyenes, prugosenes A1-A3 (1-3), from Talaromyces sp. JNU18266-01. Although these compounds were first reported from Penicillium rugulosum, their overall relative and absolute configurations remained unassigned. By employing ozonolysis in combination with ECD calculations, we were able to establish their absolute configurations, and additionally obtained seven new chemical derivatives (4-10). Notably, through NMR data analysis and quantum chemical calculations, we achieved the structural revision of prugosene A2. Furthermore, prugosenes A1-A3 exhibited potent antiviral activity against the respiratory syncytial virus, with compound 1 displaying an IC50 value of 6.3 µM. Our study thus provides a valuable reference for absolute configuration assignment of oxabornyl polyene compounds.

Development and validation of a novel risk classification tool for predicting long length of stay in NICU blood transfusion infants.

Newborns are as the primary recipients of blood transfusions. There is a possibility of an association between blood transfusion and unfavorable outcomes. Such complications not only imperil the lives of newborns but also cause long hospitalization. Our objective is to explore the predictor variables that may lead to extended hospital stays in neonatal intensive care unit (NICU) patients who have undergone blood transfusions and develop a predictive nomogram. A retrospective review of 539 neonates who underwent blood transfusion was conducted using median and interquartile ranges to describe their length of stay (LOS). Neonates with LOS above the 75th percentile (P75) were categorized as having a long LOS. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to screen variables and construct a risk model for long LOS. A multiple logistic regression prediction model was then constructed using the selected variables from the LASSO regression model. The significance of the prediction model was evaluated by calculating the area under the ROC curve (AUC) and assessing the confidence interval around the AUC. The calibration curve is used to further validate the model's calibration and predictability. The model's clinical effectiveness was assessed through decision curve analysis. To evaluate the generalizability of the model, fivefold cross-validation was employed. Internal validation of the models was performed using bootstrap validation. Among the 539 infants who received blood transfusions, 398 infants (P75) had a length of stay (LOS) within the normal range of 34 days, according to the interquartile range. However, 141 infants (P75) experienced long LOS beyond the normal range. The predictive model included six variables: gestational age (GA) (< 28 weeks), birth weight (BW) (< 1000 g), type of respiratory support, umbilical venous catheter (UVC), sepsis, and resuscitation frequency. The area under the receiver operating characteristic (ROC) curve (AUC) for the training set was 0.851 (95% CI 0.805-0.891), and for the validation set, it was 0.859 (95% CI 0.789-0.920). Fivefold cross-validation indicates that the model has good generalization ability. The calibration curve demonstrated a strong correlation between the predicted risk and the observed actual risk, indicating good consistency. When the intervention threshold was set at 2%, the decision curve analysis indicated that the model had greater clinical utility. The results of our study have led to the development of a novel nomogram that can assist clinicians in predicting the probability of long hospitalization in blood transfused infants with reasonable accuracy. Our findings indicate that GA (< 28 weeks), BW(< 1000 g), type of respiratory support, UVC, sepsis, and resuscitation frequency are associated with a higher likelihood of extended hospital stays among newborns who have received blood transfusions.

Regiodivergent Radical Termination for Intermolecular Biocatalytic C-C Bond Formation.

Radical hydrofunctionalizations of electronically unbiased dienes are challenging to render regioselective, because the products are nearly identical in energy. Here, we report two engineered FMN-dependent "ene"-reductases (EREDs) that catalyze regiodivergent hydroalkylations of cyclic and linear dienes. While previous studies focused exclusively on the stereoselectivity of alkene hydroalkylation, this work highlights that EREDs can control the regioselectivity of hydrogen atom transfer, providing a method for selectively preparing constitutional isomers that would be challenging to prepare using traditional synthetic methods. Engineering the ERED from Gluconabacter sp. (GluER) furnished a variant that favors the γ,δ-unsaturated ketone, while an engineered variant from a commercial ERED panel favors the δ,ε-unsaturated ketone. The effect of beneficial mutations has been investigated using substrate docking studies and the mechanism probed by isotope labeling experiments. A variety of α-bromo ketones can be coupled with cyclic and linear dienes. These interesting building blocks can also be further modified to generate difficult-to-access heterocyclic compounds.

Molecular epidemiology and antimicrobial resistance of vaginal Candida glabrata isolates in Namibia.

Candida glabrata is the most common non-albicans Candida species that causes vulvovaginal candidiasis (VVC). Given the intrinsically low susceptibility of C. glabrata to azole drugs, investigations into C. glabrata prevalence, fungal susceptibility profile, and molecular epidemiology are necessary to optimise the treatment of VVC. This molecular epidemiological study was conducted to determine antifungal drug profile, single nucleotide polymorphisms (SNPs) associated with phenotypic antifungal resistance and epidemic diversity of C. glabrata isolates from women with VVC in Namibia. Candida glabrata isolates were identified using phenotypic and molecular methods. Antifungal susceptibility of strains was determined for fluconazole, itraconazole, amphotericin B, and anidulafungin. Whole genome sequencing was used to determine SNPs in antifungal resistance genes and sequence type (ST) allocation. Among C. glabrata isolates, all (20/20; 100%) exhibited phenotypic resistance to the azole class antifungal drug, (fluconazole), and phenotypic susceptibility to the polyene class (amphotericin B), and the echinocandins (anidulafungin). Non-synonymous SNPs were identified in antifungal resistance genes of all fluconazole-resistant C. glabrata isolates including ERG6 (15%), ERG7 (15%), CgCDR1 (25%), CgPDR1 (60%), SNQ2 (10%), FKS1 (5.0%), FKS2 (5.0%), CgFPS1 (5.0%), and MSH2 (15%). ST15 (n = 8/20, 40%) was predominant. This study provides important insight into phenotypic and genotypic antifungal resistance across C. glabrata isolates from women with VVC in Namibia. In this study, azole resistance is determined by an extensive range of SNPs, while the observed polyene and echinocandin resistance-associated SNPs despite phenotypic susceptibility require further investigation.

Candida glabrata is inherently resistant to azole drugs. In this study, we identified a clone that was predominant in women with vulvovaginal candidiasis in Namibia, and that harboured various mutations in resistance-associated genes. This study provides important insight into antifungal resistance across C. glabrata isolates in a sub-Sahara African setting.

Effect of migration on the functionality of zinc oxide nanoparticle in polybutylene adipate terephthalate/thermoplastic starch films: A food simulant study.

Active packaging relies on controlled release of antimicrobials for food protection; however, uncontrolled migration due to environmental factors poses safety and functionality challenges. This study investigated the stability of zinc oxide nanoparticle (ZnONP) in poly(butylene-adipate-co-terephthalate)/thermoplastic starch (PBAT/TPS) biopolymer film for active food packaging applications. While incorporating ZnONP significantly enhanced the properties and active functionalities (UV-light blocking, antimicrobial activity) of PBAT/TPS film, food simulants posed significant stability challenges. Notably, exposure to 3 % acetic acid (acidic food simulant) triggered complete detachment and dissolution of ZnONPs from the film surface, leading to pore formation and subsequent internal ZnO dissolution. This resulted in dramatic alterations to the bionanocomposite films, including increased opacity, water vapor permeability, and decreased thermal stability, mechanical properties, and active functionalities. In contrast, 10 % ethanol (aqueous food simulant) had minimal impact, suggesting higher ZnO stability in neutral environments. Importantly, ZnO migration analysis revealed thresholds for safe application: 1 % ZnONP for acidic food contact and up to 5 % for aqueous foodstuffs. These findings highlight the critical role of environmental factors in ZnONP stability and emphasize the need for strategic optimization of ZnO content for achieving both functionality and safety in active biopolymer packaging.

In-vitro assessment of a novel intraocular lens made of crosslinked polyisobutylene.

PURPOSE: To describe and analyse the particularities of the material and the optical quality of the first intraocular lens (IOL) (Eyedeal® lens) made of crosslinked polyisobutylene (xPIB). METHODS: We assessed the material quality using an accelerated ageing process (to provoke glistenings) and compared values with a control, AcrySof® lens. Using the sessile drop method, the contact angle of the new IOL was measured. Images of the lens surface were recorded by scanning electron microscopy (SEM). Optical quality was assessed by measuring the labeled power and modulation transfer function (MTF) using standard metrology equipment (OptiSpheric IOL PRO2). RESULTS: The Eyedeal® lens had an average glistening density result of 7.46 ± 3.78 MV/mm2 compared to the control AcrySof® whose glistenings number was 142.42 ± 72.47 MV/mm2. The contact angle was 97.2° whereas the angle of AcrySof material is between 73.3 ± 2.4° and 84.4 ± 0.1°. Using SEM, Eyedeal® lenses were examined and all appeared to be comparable to modern IOLs made of acrylic materials. The power and MTF values were normal and conformed to ISO standards. CONCLUSIONS: In the laboratory, the new Eyedeal® lens showed equivalence to current hydrophobic- or hydrophilic-acrylic lens models. It showed superiority in its glistening density result compared to the control lens.

Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion.

Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space-time yield of 4.22 g·L-1·day-1. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. KEY POINTS: • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.

Antibiotic Skeletal Diversification via Differential Enoylreductase Recruitment and Module Iteration in trans-Acyltransferase Polyketide Synthases.

Microorganisms are remarkable chemists capable of assembling complex molecular architectures that penetrate cells and bind biomolecular targets with exquisite selectivity. Consequently, microbial natural products have wide-ranging applications in medicine and agriculture. How the "blind watchmaker" of evolution creates skeletal diversity is a key question in natural products research. Comparative analysis of biosynthetic pathways to structurally related metabolites is an insightful approach to addressing this. Here, we report comparative biosynthetic investigations of gladiolin, a polyketide antibiotic from Burkholderia gladioli with promising activity against multidrug-resistant Mycobacterium tuberculosis, and etnangien, a structurally related antibiotic produced by Sorangium cellulosum. Although these metabolites have very similar macrolide cores, their C21 side chains differ significantly in both length and degree of saturation. Surprisingly, the trans-acyltransferase polyketide synthases (PKSs) that assemble these antibiotics are almost identical, raising intriguing questions about mechanisms underlying structural diversification in this important class of biosynthetic assembly line. In vitro reconstitution of key biosynthetic transformations using simplified substrate analogues, combined with gene deletion and complementation experiments, enabled us to elucidate the origin of all the structural differences in the C21 side chains of gladiolin and etnangien. The more saturated gladiolin side chain arises from a cis-acting enoylreductase (ER) domain in module 1 and in trans recruitment of a standalone ER to module 5 of the PKS. Remarkably, module 5 of the gladiolin PKS is intrinsically iterative in the absence of the standalone ER, accounting for the longer side chain in etnangien. These findings have important implications for biosynthetic engineering approaches to the creation of novel polyketide skeletons.

Block Copolymers of Polyolefins with Polyacrylates: Analyzing and Improving the Blocking Efficiencies Using MILRad/ATRP Approach.

Despite their industrial ubiquity, polyolefin-polyacrylate block copolymers are challenging to synthesize due to the distinct polymerization pathways necessary for respective blocks. This study utilizes MILRad, metal-organic insertion light-initiated radical polymerization, to synthesize polyolefin-b-poly(methyl acrylate) copolymer by combining palladium-catalyzed insertion-coordination polymerization and atom transfer radical polymerization (ATRP). Brookhart-type Pd complexes used for the living polymerization of olefins are homolytically cleaved by blue-light irradiation, generating polyolefin-based macroradicals, which are trapped with functional nitroxide derivatives forming ATRP macroinitiators. ATRP in the presence of Cu(0), that is, supplemental activators and reducing agents , is used to polymerize methyl acrylate. An increase in the functionalization efficiency of up to 71% is demonstrated in this study by modifying the light source and optimizing the radical trapping condition. Regardless of the radical trapping efficiency, essentially quantitative chain extension of polyolefin-Br macroinitiator with acrylates is consistently demonstrated, indicating successful second block formation.

Polar Molecules Regulating the Regio- and Stereoselectivity of Polymerization of Conjugated Dienes Catalyzed by CGC-Type Rare-Earth Metal Catalysts.

Herein, a concise, effective, and scalable strategy is reported that the introduction of polar molecules (PMs) (e.g., anisole (PhOMe), phenetole (PhOEt), 2-methoxynaphthalene (NaphOMe), thioanisole (PhSMe), and N,N-dimethylaniline (PhNMe2)) as continuously coordinated neutral ligand of cationic active species in situ generated from the constrain-geometry-configuration-type rare-earth metal complexes A-F/AliBu3/[Ph3C][B(C6F5)4] ternary systems can easily switch the regio- and stereoselectivity of the polymerization of conjugated dienes (CDs, including 2-subsituted CDs such as isoprene (IP) and myrcene (MY), 1,2-disubstituted CD ocimene (OC), and 1-substituted polar CD 1-(para-methoxyphenyl)-1,3-butadiene (p-MOPB)) from poor selectivities to high selectivities (for IP and MY: 3,4-selectivity up to 99%; for OC: trans-1,2-selectivity up to 93% (mm up to 90%); for p-MOPB: 3,4-syndioselectivity (3,4- up to 99%, rrrr up to 96%)). DFT calculations explain the continuous coordination roles of PMs on the regulation of the regio- and stereoselectivity of the polymerization of CDs. In comparison with the traditional strategies, this strategy by adding some common PMs is easier and more convenient, decreasing the synthetic cost and complex operation of new metal catalyst and cocatalyst. Such regio- and stereoselective regulation method by using PMs is not reported for the coordination polymerization of olefins catalyzed by rare-earth metal and early transition metal complexes.

Recent advances in liquid fuel production from plastic waste via pyrolysis: Emphasis on polyolefins and polystyrene.

The management of plastic waste (PW) has become an indispensable worldwide issue because of the enhanced accumulation and environmental impacts of these waste materials. Thermo-catalytic pyrolysis has been proposed as an emerging technology for the valorization of PW into value-added liquid fuels. This review provides a comprehensive investigation of the latest advances in thermo-catalytic pyrolysis of PW for liquid fuel generation, by emphasizing polyethylene, polypropylene, and polystyrene. To this end, the current strategies of PW management are summarized. The various parameters affecting the thermal pyrolysis of PW (e.g., temperature, residence time, heating rate, pyrolysis medium, and plastic type) are discussed, highlighting their significant influence on feed reactivity, product yield, and carbon number distribution of the pyrolysis process. Optimizing these parameters in the pyrolysis process can ensure highly efficient energy recovery from PW. In comparison with non-catalytic PW pyrolysis, catalytic pyrolysis of PW is considered by discussing mechanisms, reaction pathways, and the performance of various catalysts. It is established that the introduction of either acid or base catalysts shifts PW pyrolysis from the conventional free radical mechanism towards the carbonium ion mechanism, altering its kinetics and pathways. This review also provides an overview of PW pyrolysis practicality for scaling up by describing techno-economic challenges and opportunities, environmental considerations, and presenting future outlooks in this field. Overall, via investigation of the recent research findings, this paper offers valuable insights into the potential of thermo-catalytic pyrolysis as an emerging strategy for PW management and the production of liquid fuels, while also highlighting avenues for further exploration and development.

Aliskiren-Loaded Nanoparticles Downregulate (Pro)renin Receptor and ACE Gene Expression in the Heart of Spontaneously Hypertensive Rats: Effect on NADPH Oxidase.

We aimed to determine effects of aliskiren, a direct renin inhibitor, loaded onto polymeric nanoparticles on the (pro)renin receptor (Atp6ap2), angiotensin II type 1 receptor (Agtr1), and angiotensin-converting enzyme (ACE) gene expression in the heart of spontaneously hypertensive rats (SHR). Twelve-week-old male SHRs were divided into an untreated group and groups treated with powdered aliskiren or aliskiren-loaded nanoparticles (25 mg/kg/day). After three weeks, the accumulation of aliskiren, distribution of polymeric nanoparticles, gene expression of Atp6ap2 and Agtr1 receptors and ACE, and protein expression of NADPH oxidase along with the conjugated diene (CD) concentration were analyzed. The accumulation of aliskiren in the heart was higher in the aliskiren-loaded nanoparticle group than in the powdered group. The fluorescent signals of nanoparticles were visible in cardiomyocytes, vessel walls, and erythrocytes. Aliskiren-loaded nanoparticles decreased the gene expression of Atp6ap2 and ACE, while not affecting Agtr1. Both forms of aliskiren decreased the protein expression of NADPH oxidase, with a more pronounced effect observed in the aliskiren-loaded nanoparticle group. CD concentration was decreased only in the aliskiren-loaded nanoparticle group. We hypothesize that aliskiren-loaded nanoparticle-mediated downregulation of Atp6ap2 and ACE may contribute to a decrease in ROS generation with beneficial effects in the heart. Moreover, polymeric nanoparticles may represent a promising tool for targeted delivery of aliskiren.

Outcomes of ECMO support with polypropylene membrane during pandemic times: a retrospective cohort study.

BACKGROUND: The SARS-CoV-2 pandemic resulted in shortages of supplies, which limited the use of extracorporeal membrane oxygenation (ECMO) support. As a contingency strategy, polypropylene (PP) oxygenation membranes were used. This study describes the clinical outcomes in patients on ECMO with PP compared to poly-methylpentene (PMP) oxygenation membranes. METHODS: Retrospective cohort of patients in ECMO support admitted between 2020 and 2021. RESULTS: A total of 152 patients with ECMO support were included, 71.05% were men with an average age of 42 (SD 9.91) years. Veno-venous configuration was performed in 75.6% of cases. The PP oxygenation membranes required more changes 22 (63.1%), than the PMP Sorin® 24 (32,8%) and Euroset® 15 (31,9%) (p.0.022). The main indication for membrane change was low oxygen transfer for PP at 56.2%, Sorin® at 50%, and Euroset® at 14.8%. Renal replacement therapy was the most frequent complication with PP membrane in 22 patients (68.7%) Sorin® 25 patients (34.2%), and Euroset® 15 patients (31.9%) (p 0.001) without statistically significant differences in mortality. CONCLUSION: PP oxygenation membranes was a useful and feasible strategy. It allowed a greater disponibility of ECMO support for critically ill in a situation of great adversity during the SARS-CoV-2 pandemic.