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1.
Science ; 385(6709): 671-678, 2024 08 09.
Article in English | MEDLINE | ID: mdl-39116217

ABSTRACT

Prymnesium parvum are harmful haptophyte algae that cause massive environmental fish kills. Their polyketide polyether toxins, the prymnesins, are among the largest nonpolymeric compounds in nature and have biosynthetic origins that have remained enigmatic for more than 40 years. In this work, we report the "PKZILLAs," massive P. parvum polyketide synthase (PKS) genes that have evaded previous detection. PKZILLA-1 and -2 encode giant protein products of 4.7 and 3.2 megadaltons that have 140 and 99 enzyme domains. Their predicted polyene product matches the proposed pre-prymnesin precursor of the 90-carbon-backbone A-type prymnesins. We further characterize the variant PKZILLA-B1, which is responsible for the shorter B-type analog prymnesin-B1, from P. parvum RCC3426 and thus establish a general model of haptophyte polyether biosynthetic logic. This work expands expectations of genetic and enzymatic size limits in biology.


Subject(s)
Haptophyta , Polyether Toxins , Polyketide Synthases , Haptophyta/enzymology , Haptophyta/genetics , Polyenes/metabolism , Polyenes/chemistry , Polyether Toxins/biosynthesis , Polyketide Synthases/genetics , Polyketide Synthases/metabolism , Polyketides/metabolism , Protein Domains
2.
J Hazard Mater ; 477: 135381, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39088959

ABSTRACT

Recent studies have demonstrated superworms (larvae of Zophobas atratus) ability to degrade polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), and polypropylene (PP) within their digestive system. This study aimed to compare the ability of superworms to degrade the above four polyolefin plastics over a duration of 30 days. In this study, the degradation rate of PE was the highest, and the final average weight of superworms, as well as the final plastic mass loss consumed by them, significantly increased (73.38 % and 52.33 %, respectively) when PE was fed with wheat bran (1:1 [w/w]). FTIR and TGA indicated the occurrence of oxidation and biodegradation processes in the four polyolefin plastics when exposed to superworms. In addition, the molecular weights (Mw and Mn) of excreted polymer residues decreased by 3.1 % and 2.87 % in PE-fed superworms, suggesting that the depolymerization of PE was not entirely dependent on the gut microbial community. The analysis of the gut microbial communities revealed that the dominant microbial community were different for each type of plastic. The results indicate that the gut microbiome of superworms exhibited remarkable adaptability in degrading various types of plastics, and the intake preferences and efficiency of different plastics are associated with different dominant microbial community species.


Subject(s)
Biodegradation, Environmental , Gastrointestinal Microbiome , Larva , Polyenes , Animals , Gastrointestinal Microbiome/drug effects , Polyenes/metabolism , Larva/metabolism , Plastics/metabolism , Polychaeta/metabolism
3.
Sci Rep ; 14(1): 20300, 2024 08 31.
Article in English | MEDLINE | ID: mdl-39217210

ABSTRACT

Rampant industrialization has led to widespread reliance on hydrocarbon polymers for various commercial applications. While these synthetic polymers, commonly known as plastics, degrade in slowly in the environments, the toxic effects of their micro-sized particles remain underexplored. In this study, we synthesized polyisobutylene (PIB) microparticles in the lab and evaluated their toxicity and accumulation in a zebrafish model. Pristine and fluorescent PIB-microplastics (MPs), with particle sizes ranging from 2 to 10 µm, were synthesized using the solvent evaporation method. Fourier-transform infrared spectroscopy (FTIR) confirmed the stability of the suspensions. Zebrafish larvae exposed to various concentrations of PIB-MPs exhibited numerous morphological and molecular changes, including delayed hatching, impaired swimming behavior, increased reactive oxygen species levels, altered mRNA levels of genes encoding antioxidant proteins, and reduced survival rates. Dissections revealed PIB-MP accumulation in the guts of larvae and adult fish within 7-21 days, causing damage to the intestinal mucosa. These findings provide insights into how contaminants like PIB can induce pathophysiological defects in aquatic fauna and pose potential health hazards to humans.


Subject(s)
Homeostasis , Larva , Polymers , Zebrafish , Animals , Zebrafish/metabolism , Polymers/chemistry , Larva/drug effects , Larva/metabolism , Homeostasis/drug effects , Microplastics/toxicity , Reactive Oxygen Species/metabolism , Particle Size , Water Pollutants, Chemical/toxicity , Polyenes
4.
Nature ; 632(8026): 795-801, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39085607

ABSTRACT

Polyene cyclizations are among the most complex and challenging transformations in biology. In a single reaction step, multiple carbon-carbon bonds, ring systems and stereogenic centres are constituted from simple, acyclic precursors1-3. Simultaneously achieving this kind of precise control over product distribution and stereochemistry poses a formidable task for chemists. In particular, the polyene cyclization of (3E,7E)-homofarnesol to the valuable naturally occurring ambergris odorant (-)-ambrox is recognized as a longstanding challenge in chemical synthesis1,4-7. Here we report a diastereoselective and enantioselective synthesis of (-)-ambrox and the sesquiterpene lactone natural product (+)-sclareolide by a catalytic asymmetric polyene cyclization by using a highly Brønsted-acidic and confined imidodiphosphorimidate catalyst in the presence of fluorinated alcohols. Several experiments, including deuterium-labelling studies, suggest that the reaction predominantly proceeds through a concerted pathway in line with the Stork-Eschenmoser hypothesis8-10. Mechanistic studies show the importance of the enzyme-like microenvironment of the imidodiphosphorimidate catalyst for attaining exceptionally high selectivities, previously thought to be achievable only in enzyme-catalysed polyene cyclizations.


Subject(s)
Catalysis , Cyclization , Diterpenes , Farnesol , Furans , Naphthalenes , Polyenes , Alcohols/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Diterpenes/chemical synthesis , Diterpenes/chemistry , Farnesol/analogs & derivatives , Farnesol/chemistry , Fluorine/chemistry , Furans/chemical synthesis , Furans/chemistry , Lactones/chemistry , Lactones/chemical synthesis , Naphthalenes/chemical synthesis , Naphthalenes/chemistry , Polyenes/chemistry , Stereoisomerism
5.
Environ Microbiol Rep ; 16(4): e13283, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39075734

ABSTRACT

Plastic waste, especially positively buoyant polymers known as polyolefins, are a major component of floating debris in the marine environment. While plastic colonisation by marine microbes is well documented from environmental samples, the succession of marine microbial community structure over longer time scales (> > 1 month) and across different types and shapes of plastic debris is less certain. We analysed 16S rRNA and 18S rRNA amplicon gene sequences from biofilms on polyolefin debris floating in a flow-through seawater tank in Hawai'i to assess differences in microbial succession across the plastic types of polypropylene (PP) and both high-density polyethylene (HDPE) and low-density polyethylene (LDPE) made of different plastic shapes (rod, film and cube) under the same environmental conditions for 1 year. Regardless of type or shape, all plastic debris were dominated by the eukaryotic diatom Nitzschia, and only plastic type was significantly important for bacterial community structure over time (p = 0.005). PE plastics had higher differential abundance when compared to PP for 20 bacterial and eight eukaryotic taxa, including the known plastic degrading bacterial taxon Hyphomonas (p = 0.01). Results from our study provide empirical evidence that plastic type may be more important for bacterial than eukaryotic microbial community succession on polyolefin pollution under similar conditions.


Subject(s)
Bacteria , RNA, Ribosomal, 16S , Seawater , Seawater/microbiology , Hawaii , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 18S/genetics , Microbiota , Polyenes/metabolism , Polyenes/chemistry , Biofilms/growth & development , Polyethylene/chemistry , Biofouling , Diatoms/classification , Diatoms/growth & development , Phylogeny
6.
Int J Mol Sci ; 25(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38928007

ABSTRACT

Three types of starch with different amylose content were esterified and blended with polybutylene succinate (PBS) to obtain esterified manioc starch/PBS (EMS/PBS), esterified corn starch/PBS (ECS/PBS), and esterified waxy corn starch/PBS (EWS/PBS) composites. The EMS/PBS and ECS/PBS composites with high amylose content displayed typical V-type crystal structures. The original crystals of EWS, which had low amylose content, were disrupted during the esterification process. EWS exhibited the strongest interaction with PBS and the most favorable interface compatibility. The pyrolysis temperature was in order of EMS/PBS < ECS/PBS < EWS/PBS. The elongation at break of the three blends was higher than that of pure PBS. The esterification and plasticization of the EWS/PBS composite were the most comprehensive. The EWS/PBS composite showed the lowest storage modulus (G') and complex viscosity (η*). The interfacial bonding force of the composite materials increased with more amylopectin, decreasing intermolecular forces and destroying crystal structures, which decreased G' and η* and increased toughness. The EWS/PBS composite, with the least amylose content, had the best hydrophobicity and degradation performance.


Subject(s)
Amylose , Amylose/chemistry , Esterification , Starch/chemistry , Polymers/chemistry , Viscosity , Polyenes/chemistry , Zea mays/chemistry , Butylene Glycols/chemistry
7.
Int J Mol Sci ; 25(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38891775

ABSTRACT

One useful technique for increasing the efficiency of organic dye-sensitized solar cells (DSSCs) is to extend the π-conjugated bridges between the donor (D) and the acceptor (A) units. The present study used the DFT and TD-DFT techniques to investigate the effect of lengthening the polyene bridge between the donor N, N-dimethyl-anilino and the acceptor dicyanovinyl. The results of the calculated key properties were not all in line with expectations. Planar structure was associated with increasing the π-conjugation linker, implying efficient electron transfer from the donor to the acceptor. A smaller energy gap, greater oscillator strength values, and red-shifted electronic absorption were also observed when the number of polyene units was increased. However, some results indicated that the potential of the stated dyes to operate as effective dye-sensitized solar cells is limited when the polyene bridge is extended. Increasing the polyene units causes the HOMO level to rise until it exceeds the redox potential of the electrolyte, which delays regeneration and impedes the electron transport cycle from being completed. As the number of conjugated units increases, the terminal lobes of HOMO and LUMO continue to shrink, which affects the ease of intramolecular charge transfer within the dyes. Smaller polyene chain lengths yielded the most favorable results when evaluating the efficiency of electron injection and regeneration. This means that the charge transfer mechanism between the conduction band of the semiconductor and the electrolyte is not improved by extending the polyene bridge. The open circuit voltage (VOC) was reduced from 1.23 to 0.70 V. Similarly, the excited-state duration (τ) decreased from 1.71 to 1.23 ns as the number of polyene units increased from n = 1 to n = 10. These findings are incompatible with the power conversion efficiency requirements of DSSCs. Therefore, the elongation of the polyene bridge in such D-π-A configurations rules out its application in solar cell devices.


Subject(s)
Coloring Agents , Polyenes , Solar Energy , Polyenes/chemistry , Coloring Agents/chemistry , Density Functional Theory , Aniline Compounds/chemistry , Electron Transport
8.
ACS Appl Bio Mater ; 7(7): 4442-4453, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38888242

ABSTRACT

Silicone rubber tissue expanders and breast implants are associated with chronic inflammation, leading to the formation of fibrous capsules. If the inflammation is left untreated, the fibrous capsules can become hard and brittle and lead to formation of capsular contracture. When capsular contracture occurs, implant failure and reoperation is unavoidable. Fibrous capsule formation to medical grade silicone rubber breast implants and polyisobutylene-based electrospun fiber mats attached to silicone rubber with and without an anti-inflammatory therapeutic were compared. A linear polyisobutylene (PIB)-based thermoplastic elastomer is currently applied as a polymer coating for drug release on coronary stents to reduce restenosis. Recent work has created a drug releasing electrospun fiber mat from PIB-based materials. Important to this study, poly(alloocimene-b-isobutylene-b-alloocimene) (AIBA) was electrospun with zafirlukast (ZAF). ZAF is an anti-inflammatory drug that is able to reduce capsule formation and complications to silicone breast implants. Fiber mats are advantageous for local drug delivery because of their high porosity and surface area for drug release. The chief hypothesis was that local release of ZAF from AIBA would lower inflammatory signaling and resulting capsular formation after 90 days in vivo. Electrospun AIBA mats locally released ZAF, lowering inflammation and fibrous capsule development compared to medical grade silicone rubber. Locally and orally released ZAF led to similar results, but the former had much lower concentration that highlights local delivery's therapeutic potential. Released ZAF from AIBA fiber mats mitigated inflammation and serves as an alternative to existing clinical approaches.


Subject(s)
Breast Implants , Materials Testing , Polyenes , Breast Implants/adverse effects , Polyenes/chemistry , Tosyl Compounds/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals , Particle Size , Female , Polymers/chemistry , Humans , Xylenes/chemistry , Indoles , Sulfonamides , Phenylcarbamates
9.
Macromol Rapid Commun ; 45(16): e2400226, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38837553

ABSTRACT

Coordinative chain transfer polymerization (CCTP) of ethylene and its copolymerization with 1,3-butadiene is conducted in toluene at 80 °C using a combination of {(Me2Si(C13H8)2)Nd(µ-BH4)[(µ-BH4)Li(THF)]}2 (1) metal complex and various organomagnesium compounds used as chain transfer agents including n-butyl-n-octyl-magnesium (BOMAG), n-butyl-mesityl-magnesium (n-BuMgMes), n-butyl-magnesium chloride (n-BuMgCl), n-pentyl-magnesium bromide (n-C5H11MgBr), pentanediyl-1,5-di(magnesium bromide) (PDMB) and isobutyl-magnesium chloride (i-BuMgCl). Kinetics and performance in terms of control of the (co)polymerization are comparatively discussed particularly considering the presence of ether and the nature of the organomagnesium compounds employed. Taking advantage of the well-known reactivity between nitrile and molecular organomagnesium compounds, the functionalization of the chains is further carried out by deactivation of the polymerization medium with benzonitrile or methoxybenzonitrile compounds leading to ketone ω-functionalized chains. The success of the functionalizations is extended to coupling strategies using dinitrile reagents and to the functionalization of high molar mass ethylene butadiene rubber (EBR).


Subject(s)
Butadienes , Nitriles , Polymerization , Nitriles/chemistry , Butadienes/chemistry , Molecular Structure , Ethylenes/chemistry , Polyenes/chemistry , Kinetics
10.
IEEE Trans Biomed Eng ; 71(10): 2877-2888, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38728123

ABSTRACT

Histotripsy is a non-thermal focused ultrasound therapy in development for the non-invasive ablation of cancerous tumors. Intracranial histotripsy has been limited by significant pressure attenuation through the skull, requiring large, complex array transducers to overcome this effect. OBJECTIVE: Recently, a biocompatible, polyolefin-based cranioplasty device was developed to allow ultrasound (US) transmission into the intracranial space with minimal distortion. In this study, we investigated the in vitro feasibility of applying US-guided histotripsy procedures across the prosthesis. METHODS: Pressure waveforms and beam profiles were collected for single- and multi-element histotripsy transducers. Then, high-speed optical images of the bubble cloud with and without the prosthesis were collected in water and tissue-mimicking agarose gel phantoms. Finally, red blood cell (RBC) tissue phantom and excised brain tissue experiments were completed to test the ablative efficacy across the prosthesis. RESULTS: Single element tests revealed increased pressure loss with increasing transducer frequency and increasing transducer-to-prosthesis angle. Array transducer measurements at 1 MHz showed average pressure losses of >50% across the prosthesis. Aberration correction recovered up to 18% of the pressure lost, and high-speed optical imaging in water, agarose gels, and RBC phantoms demonstrated that histotripsy bubble clouds could be generated across the prosthesis at pulse repetition frequencies of 50-500 Hz. Histologic analysis revealed a complete breakdown of brain tissue treated across the prosthesis. Conclusion & Significance: Overall, the results of this study demonstrate that the cranial prosthesis may be used as an acoustic window through which intracranial histotripsy can be applied under US guidance without the need for large transcranial array transducers.


Subject(s)
High-Intensity Focused Ultrasound Ablation , Phantoms, Imaging , Polyenes , High-Intensity Focused Ultrasound Ablation/instrumentation , High-Intensity Focused Ultrasound Ablation/methods , Polyenes/chemistry , Skull/surgery , Skull/diagnostic imaging , Humans , Transducers , Equipment Design , Animals , Brain/diagnostic imaging , Brain/surgery
11.
Biochem Biophys Res Commun ; 719: 150100, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38763043

ABSTRACT

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.


Subject(s)
Fracture Healing , Human Umbilical Vein Endothelial Cells , Neovascularization, Physiologic , Phosphatidylcholines , Rats, Sprague-Dawley , Signal Transduction , Tibial Fractures , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2 , Animals , Fracture Healing/drug effects , Vascular Endothelial Growth Factor Receptor-2/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Tibial Fractures/metabolism , Tibial Fractures/drug therapy , Tibial Fractures/pathology , Signal Transduction/drug effects , Neovascularization, Physiologic/drug effects , Humans , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Rats , Male , Phosphatidylcholines/pharmacology , Polyenes/pharmacology , Angiogenesis
12.
J Antibiot (Tokyo) ; 77(8): 540-543, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38750248

ABSTRACT

A new polyene macrolide, machidamycin (1), and a known compound YS-822A (2), were obtained by physicochemical screening from a culture broth of Streptomyces sp. K22-0017. The structures were elucidated using MS and 1D/2D NMR analyses. Compound 1 exhibited weak antifungal activity against Candida albicans and Mucor racemosus. Furthermore, 1 showed stronger antileishmanial activity than the existing drug paromomycin.


Subject(s)
Antifungal Agents , Candida albicans , Macrolides , Magnetic Resonance Spectroscopy , Polyenes , Streptomyces , Streptomyces/metabolism , Candida albicans/drug effects , Macrolides/pharmacology , Macrolides/chemistry , Macrolides/isolation & purification , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Polyenes/pharmacology , Polyenes/chemistry , Polyenes/isolation & purification , Mucor/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Microbial Sensitivity Tests , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Mass Spectrometry
13.
Macromol Rapid Commun ; 45(16): e2400195, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38713145

ABSTRACT

This communication reports an effective strategy helping address the long-troubling melt processing issue of isotactic polybutene-1 (i-PB) caused by its extremely slow II-I crystal phase transition. The solution lies in a facile synthesis of i-PB containing H-shape long-chain-branching structures (LCB-i-PB) by applying a so-called ω-alkenylmethyldichlorosilane copolymerization-hydrolysis (ACH) chemistry to butene-1 polymerization with Ziegler-Natta or metallocene catalysts. It is evident that the H-shape LCB structures effectively enhance chain entanglements of i-PB and induce an over-the-board acceleration of the overall melt crystallization process including nucleation, form II crystallization, and form II-form I phase transition. As i-PB usually requires up to a week to reach equilibrium of the II-I phase transition, it is found that with LCB-i-PB such a transition is almost finished within as short as 24 h to even higher degrees.


Subject(s)
Crystallization , Phase Transition , Polyenes/chemistry , Molecular Structure , Polymerization , Catalysis
14.
Macromol Rapid Commun ; 45(14): e2400102, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38648071

ABSTRACT

The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces are introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (Tc) and shear temperature (Tshear) on crystallization and phase transition are explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high Tc (105 °C). Besides, the shear-induced Form II can transit to Form I faster than the unsheared one. In addition, the phase transition rate increases as the Tshear decreases, with the fastest rate occurring at Tshear of 120 °C. The half transition time (t1/2) is measured as 6.3 h when Tc = 105 °C, Tshear = 120 °C, which is much shorter than the 20.7 h required for unsheared samples. The accelerated phase transition of iPBu can be attributed to the stretching of molecular chains, resulting from shear treatment. This study provides a quantitative analysis of the influence of the shear treatment and the Tshear on the II-I phase transition rate. It also presents a cost-effective and straightforward approach for expediting the phase transition process.


Subject(s)
Phase Transition , Polyenes/chemistry , Crystallization , Temperature , Polymers/chemistry , Shear Strength
15.
Mar Drugs ; 22(4)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38667806

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Lactams, Macrocyclic , Microbial Sensitivity Tests , Multigene Family , Streptomyces , Streptomyces/genetics , Streptomyces/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Humans , Lactams, Macrocyclic/pharmacology , Lactams, Macrocyclic/chemistry , Lactams, Macrocyclic/isolation & purification , Polyenes/pharmacology , Polyenes/isolation & purification , Polyenes/chemistry , Candida albicans/drug effects , Cell Line, Tumor , Antarctic Regions , Animals , Porifera/microbiology , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification
16.
Dent Mater J ; 43(3): 367-374, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38583997

ABSTRACT

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.


Subject(s)
Materials Testing , Mouth Protectors , Polyenes/chemistry , Vinyl Compounds/chemistry , Equipment Design , Polyvinyls/chemistry , Stress, Mechanical , Dental Stress Analysis
17.
Molecules ; 29(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38543033

ABSTRACT

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.


Subject(s)
Amphotericin B , Polyketide Synthases , Amphotericin B/pharmacology , Polyketide Synthases/genetics , Polyketide Synthases/metabolism , Polyenes/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Macrolides/metabolism , Anti-Bacterial Agents
18.
J Mech Behav Biomed Mater ; 153: 106507, 2024 May.
Article in English | MEDLINE | ID: mdl-38503082

ABSTRACT

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.


Subject(s)
Polypropylenes , Steam , Polyenes , Acrylic Resins/chemistry , Sterilization
19.
Sci Rep ; 14(1): 6877, 2024 03 22.
Article in English | MEDLINE | ID: mdl-38519538

ABSTRACT

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.


Subject(s)
Intensive Care Units, Neonatal , Polyenes , Pyrones , Sepsis , Infant, Newborn , Infant , Humans , Length of Stay , Hospitalization , Birth Weight , Blood Transfusion , Nomograms , Retrospective Studies
20.
Chemosphere ; 354: 141685, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38513957

ABSTRACT

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.


Subject(s)
Plastics , Polyenes , Polymers , Humans , Carbon , Polypropylenes , Polyethylene
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