Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 843
Filtrar
1.
Front Bioeng Biotechnol ; 12: 1466757, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39364265

RESUMO

Silk, traditionally acclaimed as the "queen of fiber," has been widely used thanks to its brilliant performance such as gentleness, smoothness and comfortableness. Owing to its mechanical characteristics and biocompatibility silk has a definitive role in biomedical applications, both as fibroin and fabric. In this work, the simultaneous dyeing and functionalization of silk fabric with pigments from Streptomyces anulatus BV365 were investigated. This strain produced high amounts of orange extracellular pigments on mannitol-soy flour agar, identified as actinomycin D, C2 and C3. The application of purified actinomycins in the dyeing of multifiber fabric was assessed. Actinomycins exhibited a high affinity towards protein fibers (silk and wool), but washing durability was maintained only with silk. Acidic condition (pH5) and high temperature (65°C) facilitated the silk dyeing. The morphologies and chemical components of the treated silk fabrics were analyzed using scanning electron microscopy and Fourier transform infrared spectroscopy. The results showed the pigments bind to the silk through interaction with the carbonyl group in silk fibroin rendering the functionalized, yet surface that does not cause skin irritation. The treated silk exhibited a remarkable antibacterial effect, while the biocompatibility test performed with 3D-reconstructed human epidermis model indicated safe biological properties, paving the way for future application of this material in medicine.

2.
Sci Total Environ ; : 176790, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39395503

RESUMO

Per- and poly-fluoroalkyl substances (PFAS) may threaten wildlife due to their high environmental persistence, toxicity potential and potential to bioaccumulate. Bioaccumulation may be particularly profound in long-lived animals inhabiting higher trophic niches. To date, there is a paucity of data on PFAS bioaccumulation potential in individual wild birds over their lifetime. In this study, we analysed within-individual PFAS contamination in a declining long-distance migratory shorebird, the ruddy turnstone (Arenaria interpres), and the variation in PFAS contamination with age by repeatedly sampling 19 individuals throughout their lives between 2007 and 2022. We found blood-sampled turnstones on their non-breeding grounds in King Island, Tasmania, exhibited no variation of PFAS contamination with age, with low overall circulating PFAS concentrations (<0.015-25 ng/g, median: 0.78 ng/g). Moreover, irrespective of the increased PFAS usage along the East Asian Australasian Flyway over the past two decades, ruddy turnstone survival remained consistent throughout the 15-year sampling period, with no temporal trend in percentage of juveniles in the population. From a conservation perspective, low concentrations of PFAS found in this study are good news as they suggest PFAS alone do not seem to threaten turnstone survival. However, the unknown effects of exposure to mixtures of pollutants may yet threaten turnstones.

3.
Transplant Cell Ther ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299503

RESUMO

BACKGROUND: Prophylactic antibiotics are still controversial during allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our transplant center, we suspended antibiotic prophylaxis during allo-HSCT in 2017. OBJECTIVE: The main objective of this study was the detailed analysis of the potentially beneficial impact of omittance of standard antibiotic prophylaxis during allo-HSCT in survival and Graft-versus-Host disease (GvHD) development, especially with consideration of confounding factors and competing events. Secondary objectives were the evaluation of the risk of severe infections and transplant-related mortality without antibiotic prophylaxis, the detailed assessment of bacterial and viral infections including multiresistant pathogens as well as occurrence of relapse in both groups. This study aims to support the development of future antibiotic strategies in allo-HSCT. STUDY DESIGN: We retrospectively analyzed patient outcome in the time periods before (between December 2012 and February 2017) and after suspension (between March 2017 and June 2020) of antibiotic prophylaxis during allo-HSCT. Relevant clinical outcome parameters of the patients (n = 221) were collected by chart-review in the two groups (with antibiotic prophylaxis n = 101 versus without antibiotic prophylaxis n = 120). All patients were 18 years or older. Propensity score methods were used to adjust for potentially confounding patient characteristics. To address competing events, transitions between moderate/severe acute and chronic GvHD, relapse and death were analyzed using an inverse-propensity score weighted multistate modeling approach. RESULTS: While we observed a trend towards an improved outcome in the cohort without antibiotic prophylaxis, the inverse-propensity-score-weighted analyses did not show significant differences between the two groups in overall survival (OS) (P = .811) or development of acute GvHD (aGvHD) grade 3/4 (P = .158) and chronic moderate/severe GvHD (cGvHD) (P = .686). Multistate analysis respecting competing events revealed comparable estimated probabilities without antibiotic prophylaxis versus with antibiotic prophylaxis in OS (35.0% [95% CI: 28.2%-42.7%] versus 35.3% [95% CI: 27.8%-41.1%]) as well as development of aGvHD grade 3/4 (7.7% [95% CI: 5.9%-12.2%] vs. 10.6% [95% CI: 7.7%-15.7%]) and moderate/severe cGvHD (21.0% [95% CI: 17.7%-30.0%] vs. 23.8% [95% CI: 19.6%-31.4%]). Similar analyses showed also no significant differences in relapse rate, transplant-related mortality, relapse-related mortality, or GvHD-free/relapse-free survival between the two groups. An observed increase in severe infections without antibiotic prophylaxis did not lead to a significantly higher mortality rate. Viral reactivation and detection of multiresistant bacteria were comparable, yet a higher incidence of Clostridioides difficile infections was observed in patients receiving antibiotic prophylaxis. CONCLUSION: Our study supports previous reports of noninferiority of allo-HSCT without use of antibiotic prophylaxis with close monitoring and rapid intervention, if infection is suspected. The trend towards improved outcomes without antibiotic prophylaxis, however, might not only be due to the absence of antibiotic prophylaxis but also due to additional progresses in the field over the recent years. While the present study is too small to draw definite conclusions, these results strongly warrant further multicenter studies addressing the potential benefit of omitting antibiotic prophylaxis during allo-HSCT.

4.
Cell Chem Biol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39332411

RESUMO

Biosynthesis of sodorifen with a unique C16-bicyclo[3.2.1]octene framework requires an S-adenosyl methionine-dependent methyltransferase SodC and terpene cyclase SodD. While bioinformatic analyses reveal a wide distribution of the sodCD genes organization in bacteria, their functional diversity remains largely unknown. Herein, two sodorifen-type gene clusters, pcch and pcau, from Pseudomonas sp. are heterologously expressed in Escherichia coli, leading to the discovery of two C16 terpenoids. Enzymatic synthesis of these compounds is achieved using the two (SodCD-like) pathway-specific enzymes. Enzyme assays using different combinations of methyltransferases and terpene synthases across the pcch, pcau, and sod pathways reveal a unifying biosynthetic mechanism: all three SodC-like enzymes methylate farnesyl pyrophosphate (FPP) with subsequent cyclization to a common intermediate, pre-sodorifen pyrophosphate. Structural diversification of this joint precursor solely occurs by the subsequently acting individual terpene synthases. Our findings expand basic biosynthetic understanding and structural diversity of unusual C16-terpenoids.

5.
Behav Brain Res ; 476: 115254, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307287

RESUMO

The I-PACE model suggests that Internet-use disorders result from the interplay of individual vulnerabilities and cognitive and affective processes. As in substance use disorders, Pavlovian conditioning processes are attributed a key role. However, and despite progress in identifying individual vulnerabilities, factors influencing appetitive conditioning remain poorly understood. We therefore conducted a Pavlovian conditioning experiment in which individuals with risky as well as non-problematic use of either gaming or buying-shopping applications learned to associate different abstract stimuli with either gaming or buying-shopping. Regression analyses were used to identify individual characteristics influencing awareness of the experimental contingencies, speed of acquisition of awareness and the magnitude of the conditioned emotional responses regarding pleasantness and arousal ratings of the stimuli. Results demonstrated successful Pavlovian conditioning and an attentional bias towards reward-predicting cues. Awareness of the experimental contingencies was linked solely to cognitive abilities, while the speed of acquisition of awareness and the magnitude of conditioned responses was influenced by specific personality characteristics, experiences of compensation from using the application and severity of problematic use. Importantly, certain characteristics specifically predicted the magnitude of the conditioned response towards gaming, while others specifically predicted the response towards buying-shopping, highlighting differing vulnerabilities. These findings underscore the importance of targeted interventions and prevention strategies tailored to these specific vulnerability factors. Further implications and limitations are discussed.

6.
Nat Commun ; 15(1): 8261, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327438

RESUMO

The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies.


Assuntos
Metagenoma , Metagenômica , Microbiota , Humanos , Microbiota/genética , Metagenoma/genética , Metagenômica/métodos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/classificação , Fezes/microbiologia , Masculino , Feminino , Família Multigênica , Saliva/microbiologia , Adulto
7.
World Neurosurg ; 191: 234-244, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39181237

RESUMO

BACKGROUND: The use of bibliometric analysis studies allows for the precise assessment of high impact contributions to various fields of study. A bibliometric assessment of academic works cited in filed patents enables tracking the academic studies which have been most influential in the development of new technologies in spine surgery. METHODS: The Lens database was utilized to retrieve scholarly articles related to the field of spine surgery, with special focus on spinal fusion and biologics. Scholarly works cited in patents were organized by publishing journal, article topic, study type, publishing institution, and authors information. Such publications were also categorized by country of origin and, for U.S. patents, region of origin. RESULTS: The employed search criteria yielded 37,005 scholarly works related to spine surgery published between 1889 and 2022 and a total of 947 scholarly works cited in patents from 1968 to 2022. Many of the top contributing authors were orthopedic surgeons while the top 3 authors were biomedical engineers. The region in the U.S. with the most citations in patents and the most scholarly work overall was the middle-Atlantic region. CONCLUSIONS: This patent bibliometric analysis provides a general overview of trends in publications impacting spine surgery innovation over time. Our results highlight top instutions and regional contributions to spine surgery innovation within the United States and worldwide. As the first patent bibliometric study providing data on the most technologically impactful scholarly work in spine surgery, this study has not only historical value in terms of documenting the scientific and intellectual property developments in spine surgery in the past 50 years, but also practical relevance insofar as the identified trends and research hotspots that may provide researchers valuable insights regarding future decisions involving research efforts and resources allocation.

8.
Obes Surg ; 34(10): 3579-3591, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134834

RESUMO

PURPOSE: Previous research on obesity surgery (OS) showed that patients do not only experience weight loss but also improvements in certain mental health outcomes (e.g., depression) after OS. However, self-harm behaviors might increase after OS. Regarding self-harm, the literature is mostly limited to studies using data from hospital or emergency room charts. This longitudinal study examined self-reported self-harm behaviors and potential psychopathological correlates before and after OS. MATERIALS AND METHODS: Pre-surgery patients (N = 220) filled out a set of questionnaires before and approximately six months after OS. Self-harm behaviors were captured with the Self-Harm Inventory. The assessments further included standardized instruments to measure symptoms of depression, anxiety, eating disorders, alcohol use, and suicidal ideations. RESULTS: Any self-harm was reported by 24.6% before and by 25.0% after OS. No differences in the number of self-harm behaviors or prevalence of any self-harm before and after OS were found. Overall, 11.4% experienced self-harm behaviors at both times. A subset showed self-harm behaviors only before (13.2%) OS and another subset only after OS (13.6%). These two groups were about the same size. Self-harm behaviors showed strong associations with psychopathology after OS, especially with depression and suicidal ideation. CONCLUSION: No increase in self-harm behaviors after OS emerged. Still, a subgroup showed self-harm behaviors after OS closely linked to further psychopathology. This mirrors the need to implement screening for self-harm before and after OS into OS care. Further studies with longer follow up periods are needed to extend these findings.


Assuntos
Cirurgia Bariátrica , Depressão , Obesidade Mórbida , Comportamento Autodestrutivo , Ideação Suicida , Humanos , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Feminino , Masculino , Adulto , Estudos Longitudinais , Pessoa de Meia-Idade , Cirurgia Bariátrica/psicologia , Depressão/epidemiologia , Obesidade Mórbida/cirurgia , Obesidade Mórbida/psicologia , Inquéritos e Questionários , Redução de Peso , Ansiedade/epidemiologia , Prevalência , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia
9.
World Neurosurg ; 191: 156-164, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39098502

RESUMO

OBJECTIVE: Postural abnormalities are a debilitating symptom of Parkinson disease (PD) that may require spinal intervention. Camptocormia is a unique abnormality most seen in PD, defined by a severe forward flexion of the trunk that completely resolves when supine. The condition presents a challenge due to an undefined pathophysiology and optimal therapeutic approach in a high-risk patient population. In this study, we systematically reviewed the literature regarding the use of spine surgery for the treatment of camptocormia in PD. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically queried for studies involving spine surgery as treatment of PD-associated camptocormia. Studies involving nonsurgical management, involving deep brain stimulation, involving noncamptocormic PD patients undergoing surgery, or were out of scope were excluded. RESULTS: The search resulted in 5 studies, with a total of 19 patients with PD with camptocormia who underwent spine surgery (73.7% women). The mean age was 69.5 years (range, 59-83), and the mean PD duration was 69.5 months (range, 36-84). Of 19 patients, 11 required surgical revision (57.9%), with an average of 0.68 revisions per patient (range, 0-2). Radiographic and patient-reported outcomes were inconsistently reported yet showed improvement. Ultimately, 18 patients were reported to have positive outcomes. CONCLUSIONS: Despite an increased risk of complication and revision that is inherent to patients with PD, spine surgery has been proven as a reasonable alternative that should be prospectively studied further because 18 of 19 patients had favorable outcomes.

10.
G3 (Bethesda) ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39197015

RESUMO

The ability to predict the outcome of selection and mating decisions enables breeders to make strategically better selection decisions. To improve genetic progress, those individuals need to be selected whose offspring can be expected to show high genetic variance next to high breeding values. Previously published approaches enable to predict the variance of descendants of two future generations for up to 4 founding haplotypes, or 2 outbred individuals, based on phased genotypes, allele effects and recombination frequencies. The purpose of this study was to develop a general approach for the analytical calculation of the genetic variance in any future generation. The core development is an equation for the prediction of the variance of double haploid lines, under the assumption of no selection and negligible drift, stemming from an arbitrary number of founder haplotypes. This double haploid variance can be decomposed into gametic Mendelian sampling variances (MSV) of ancestors of the double haploid lines allowing usage for non-double haploid genotypes which enables application in animal breeding programs as well as in plant breeding programs. Together with the breeding values of the founders, the gametic MSV may be used in new selection criteria. We present our idea of such a criterion that describes the genetic level of selected individuals in four generations. Since breeding programs do select, the assumption made for predicting variances is clearly violated which decreases the accuracy of predicted gametic MSV caused by changes in allele frequency and linkage disequilibrium. Despite violating the assumption, we found high predictive correlations of our criterion to the true genetic level which was obtained by means of simulation for the "corn" and "cattle" genome models tested in this study (0.90 and 0.97). In practice, the genotype phases, genetic map and allele effects all need to be estimated meaning inaccuracies in their estimation will lead to inaccurate variance prediction. Investigation of variance prediction accuracy when input parameters are estimated was not part of this study.

11.
Org Biomol Chem ; 22(34): 7035-7038, 2024 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-39145461

RESUMO

The menaquinone-pathway (men) is widespread in bacteria and key to the biosynthesis of intriguing small molecules such as the essential vitamin menaquinone and the natural dye lawsone. The violet molecule brevinic acid is another proposed product of men, but its direct biosynthetic precursor has remained doubtful. In this study, we isolated brevinic acid from E. coli and confirmed its non-enzymatic formation from lawsone and homocysteine involving an intermediate acetylation or phosphorylation step. We furthermore compared our proposed substrates in a non-enzymatic assay against the previously hypothesized precursor DHNA and showed that the reaction with activated lawsone derivatives proceeded faster, more selective, and with complete turnover. This supports our proposed biosynthesis of brevinic acid from lawsone and enables a cost effective, larger-scale synthesis of brevinic acid.


Assuntos
Escherichia coli , Naftoquinonas , Escherichia coli/metabolismo , Naftoquinonas/química , Naftoquinonas/metabolismo , Estrutura Molecular
12.
Chemistry ; : e202402801, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39189945

RESUMO

A hitherto unknown modification of I2O5 was obtained from high-pressure/high-temperature syntheses in a Walker-type multianvil device at 8 GPa and 250 °C. HP-I2O5 crystallizes in the monoclinic crystal system in the space group P21/c (no. 14) with the unit cell parameters a = 12.0612(3) Å, b = 4.8613(2) Å, c = 6.9585(2) Å, ß = 100.10(1)° (at 173 K), and four formula units per cell. The single-crystal structure data are accompanied by powder X-ray diffraction data at ambient and elevated temperatures. Furthermore, DFT calculations were carried out to investigate the phase transition between the ambient-pressure polymorph NP-I2O5 to the newly synthesized high-pressure phase.

13.
N Am Spine Soc J ; 19: 100510, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39114407
14.
J Immunother Cancer ; 12(7)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39038917

RESUMO

RATIONALE OF THE TRIAL: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors. TRIAL DESIGN: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of 16 patients. IMA202 consists of autologous genetically modified cytotoxic CD8+ T cells expressing a T cell receptor (TCR), which is specific for a nine amino acid peptide derived from MAGEA1. Eligible patients underwent leukapheresis, T cells were isolated, transduced with lentiviral vector carrying MAGEA1-specific TCR and following lymphodepletion (fludarabine/cyclophosphamide), infused with a median of 1.4×109 specific T cells (range, 0.086×109-2.57×109) followed by interleukin 2. SAFETY OF IMA202: No DLT was observed. The most common grade 3-4 adverse events were cytopenias, that is, neutropenia (81.3%), lymphopenia (75.0%), anemia (50.0%), thrombocytopenia (50.0%) and leukopenia (25.0%). 13 patients experienced cytokine release syndrome, including one grade 3 event. Immune effector cell-associated neurotoxicity syndrome was observed in two patients and was grade 1 in both. EFFICACY OF IMA202: Of the 16 patients dosed, 11 (68.8%) patients had stable disease (SD) as their best overall response (Response Evaluation Criteria in Solid Tumors V.1.1). Five patients had initial tumor shrinkage in target lesions and one patient with SD experienced continued shrinkage in target lesions for 3 months in total but had to be classified as progressive disease due to progressive non-target lesions. IMA202 T cells were persistent in peripheral blood for several weeks to months and were also detectable in tumor tissue. Peak persistence was higher in patients who received higher doses. CONCLUSION: In conclusion, IMA202 had a manageable safety profile, and it was associated with biological and potential clinical activity of MAGEA1-targeting genetically engineered TCR-T cells in a poor prognosis, multi-indication solid tumor cohort. TRIAL REGISTRATION NUMBERS: NCT04639245, NCT05430555.


Assuntos
Antígenos de Neoplasias , Imunoterapia Adotiva , Neoplasias , Humanos , Feminino , Masculino , Antígenos de Neoplasias/imunologia , Pessoa de Meia-Idade , Idoso , Neoplasias/terapia , Neoplasias/imunologia , Adulto , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/genética
15.
Postepy Biochem ; 70(1): 4-7, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-39016222

RESUMO

70 Years - from DNA Double Helix via Approaching Systems Genomics to a Generalized Unified Evolution Theory.


Assuntos
DNA , Genômica , Evolução Biológica , DNA/genética , Evolução Molecular , Genômica/métodos , História do Século XX , História do Século XXI
16.
Ann Surg Open ; 5(2): e452, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911625

RESUMO

Up to hundreds of billions of dollars are annually lost to fraud and abuse in the US health care, making it a significant burden on the system. This study investigates a specific instance of health care fraud in spine surgery, in which a medical device company ended up paying $75 million to settle violations of the False Claims Act. We review the surgical background regarding the kyphoplasty procedure, as well as its billing and reimbursement details. We also explore the official legal complaint brought by the US Department of Justice to tell the story of how one of the most significant medical innovations in spine surgery in the 21st century turned into a widespread fraudulent marketing scheme. In the sequence, we provide a detailed root cause analysis of this scandal and propose some proactive measures that can be taken to avoid such type of unfortunate events. Ultimately, this historical health care scandal constitutes a valuable lesson to surgeons, health care administrators, medical device companies, and policymakers on how misaligned incentives and subsequent unscrupulous practices can transform a medical innovation into an unfortunate tale of fraud and deceit.

17.
J Am Chem Soc ; 146(23): 16203-16212, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38829274

RESUMO

Baeyer-Villiger monooxygenases (BVMOs) play crucial roles in the core-structure modification of natural products. They catalyze lactone formation by selective oxygen insertion into a carbon-carbon bond adjacent to a carbonyl group (Baeyer-Villiger oxidation, BVO). The homologous bacterial BVMOs, BraC and PxaB, thereby process bicyclic dihydroindolizinone substrates originating from a bimodular nonribosomal peptide synthetase (BraB or PxaA). While both enzymes initially catalyze the formation of oxazepine-dione intermediates following the identical mechanism, the final natural product spectrum diverges. For the pathway involving BraC, the exclusive formation of lipocyclocarbamates, the brabantamides, was reported. The pathway utilizing PxaB solely produces pyrrolizidine alkaloids, the pyrrolizixenamides. Surprisingly, replacing pxaB within the pyrrolizixenamide biosynthetic pathway by braC does not change the product spectrum to brabantamides. Factors controlling this product selectivity have remained elusive. In this study, we set out to solve this puzzle by combining the total synthesis of crucial pathway intermediates and anticipated products with in-depth functional in vitro studies on both recombinant BVMOs. This work shows that the joint oxazepine-dione intermediate initially formed by both BVMOs leads to pyrrolizixenamides upon nonenzymatic hydrolysis, decarboxylative ring contraction, and dehydration. Brabantamide biosynthesis is enzyme-controlled, with BraC efficiently transforming all the accepted substrates into its cognate final product scaffold. PxaB, in contrast, shows only considerable activity toward brabantamide formation for the substrate analog with a natural brabantamide-type side chain structure, revealing substrate-controlled product selectivity.


Assuntos
Oxigenases de Função Mista , Oxigenases de Função Mista/metabolismo , Oxigenases de Função Mista/química , Alcaloides/química , Alcaloides/metabolismo , Biocatálise , Estrutura Molecular , Especificidade por Substrato
18.
Angew Chem Int Ed Engl ; 63(34): e202406742, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-38842522

RESUMO

A selective deelectronation reagent with very high potential of +2.00 (solution)/+2.41 V (solid-state) vs. Fc+/0 and based on a room temperature stable perfluoronaphthalene (naphthaleneF) radical cation salt was developed and applied. The solid-state deelectronation of commercial naphthaleneF with [NO]+[F{Al(ORF)3}2]- generates [naphthaleneF]+⋅[F{Al(ORF)3}2]- (ORF=OC(CF3)3) in gram scale. Thermochemical analysis unravels the solid-state deelectronation potential of the starting [NO]+-reagent to be +2.34 V vs. Fc+/0 with [F{Al(ORF)3}2]- counterion, but only +1.14 V vs. Fc+/0 with the small [SbF6]- ion. Selective reactions demonstrate the selectivity of [naphthaleneF]+⋅ for deelectronation of a multitude of organ(ometall)ic molecules and elements in solution: providing the molecular structures of the acene dications [tetracene]2+, [pentacene]2+ or spectroscopic evidence for the carbonyl complex of the ferrocene dication [Fc(CO)]2+, the [P9]+ cation from white phosphorus, the solvent-free copper(I) salt starting from copper metal and the dicationic Fe(IV)-scorpionate complex [Fe(sc)2]2+.

19.
J Colloid Interface Sci ; 674: 560-575, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38945024

RESUMO

The present paper reports the fabrication of novel types of hybrid fibrous photocatalysts by combining block copolymer (BCP) templating, sol-gel processing, and coaxial electrospinning techniques. Coaxial electrospinning produces core-shell nanofibers (NFs), which are converted into hollow porous TiO2 NFs using an oxidative calcination step. Hybrid BCP micelles comprising a single plasmonic nanoparticle (NP) in their core and thereof derived silica-coated core-shell particles are utilized as precursors to generate yolk-shell type particulate inclusions in photocatalytically active NFs. The catalytic and photocatalytic activity of calcined NFs comprising different types of yolk-shell particles is systematically investigated and compared. Interestingly, calcined NFs comprising silica-coated yolk-shells demonstrate enhanced catalytic and photocatalytic performance despite the presence of silica shell separating plasmonic NP from the TiO2 matrix. Electromagnetic simulations indicate that this enhancement is caused by a localized surface plasmon resonance and a confinement effect in silica-coated yolk-shells embedded in porous TiO2 NFs. Utilization of the coaxially electrospun TiO2 NFs in combination with yolk-shells comprising plasmonic NPs reveals to be a potent method for the photocatalytic decomposition of numerous pollutants. It is worth noting that this study stands as the first occurrence of combining yolk-shells (Au@void@SiO2) with porous electrospun NFs (TiO2) for photocatalytic purposes and gaining an understanding of plasmon and confinement effects for photocatalytic performance. This approach represents a promising route for fabricating highly active and up-scalable fibrous photocatalytic systems.

20.
Commun Biol ; 7(1): 655, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806706

RESUMO

The gut microbiota influences human health and the development of chronic diseases. However, our understanding of potentially protective or harmful microbe-host interactions at the molecular level is still in its infancy. To gain further insights into the hidden gut metabolome and its impact, we identified a cryptic non-ribosomal peptide BGC in the genome of Bacillus cereus DSM 28590 from the mouse intestine ( www.dsmz.de/miBC ), which was predicted to encode a thiazol(in)e substructure. Cloning and heterologous expression of this BGC revealed that it produces bacillamide D. In-depth functional evaluation showed potent cytotoxicity and inhibition of cell migration using the human cell lines HCT116 and HEK293, which was validated using primary mouse organoids. This work establishes the bacillamides as selective cytotoxins from a bacterial gut isolate that affect mammalian cells. Our targeted structure-function-predictive approach is demonstrated to be a streamlined method to discover deleterious gut microbial metabolites with potential effects on human health.


Assuntos
Bacillus cereus , Microbioma Gastrointestinal , Bacillus cereus/metabolismo , Bacillus cereus/genética , Animais , Camundongos , Humanos , Células HEK293 , Citotoxinas/metabolismo , Citotoxinas/genética , Células HCT116 , Intestinos/microbiologia , Movimento Celular , Organoides/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...