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"Candidatus Accumulibacter" is the major polyphosphate-accumulating organism (PAO) in global wastewater treatment systems, and its phylogenetic and functional diversity have expanded in recent years. In addition to the widely recognized type I and II sublineages, we discovered a novel type enriched in laboratory bioreactors. Core gene and machine learning-based gene feature profiling supported the assertion that type III "Ca. Accumulibacter" is a potential PAO with the unique function of using dimethyl sulfoxide as an electron acceptor. Based on the correlation between ppk1 and genome similarity, the species-level richness of Accumulibacter was estimated to be over 100, suggesting that the currently recognized species are only the tip of the iceberg. Meanwhile, the interstrain transcriptional and morphological features of multiple "Ca. Accumulibacter" strains co-occurring in a bioreactor were investigated. Metatranscriptomics of seven co-occurring strains indicated that the expression level and interphasic dynamics of PAO phenotype-related genes had minimal correlation with their phylogeny. In particular, the expression of denitrifying and polyphosphate (poly-P) metabolism genes exhibited higher interstrain and interphasic divergence than expression of glycogen and polyhydroxyalkanoate metabolic genes. A strategy of cloning rRNA genes from different strains based on similar genomic synteny was successfully applied to differentiate their morphology via fluorescence in situ hybridization. Our study further expands the phylogenetic and functional diversity of "Ca. Accumulibacter" and proposes that deciphering the function and capability of certain "Ca. Accumulibacter" should be tailored to the environment and population in question. IMPORTANCE In the last 2 decades, "Ca. Accumulibacter" has garnered significant attention as the core functional but uncultured taxon for enhanced biological phosphorus removal due to its phylogenetic and functional diversity and intragenus niche differentiation. Since 2002, it has been widely known that this genus has two sublineages (type I and II). However, in this study, a metagenomic approach led to the discovery of a novel type (type III) with proposed novel functional features. By comparing the average nucleotide identity of "Ca. Accumulibacter" genomes and the similarity of ppk1, a phylogenetic biomarker largely deposited in databases, the global species-level richness of "Ca. Accumulibacter" was estimated for the first time to be over 100. Furthermore, we observed the co-occurrence of multiple "Ca. Accumulibacter" strains in a single bioreactor and found the simultaneous transcriptional divergence of these strains intriguing with regard to their niche differentiation within a single community. Our results indicated a decoupling feature between transcriptional pattern and phylogeny for co-occurring strains.
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Betaproteobacteria , Filogenia , Hibridização in Situ Fluorescente , Betaproteobacteria/genética , RNA Ribossômico 16S/genética , Fósforo/metabolismo , Reatores Biológicos , Polifosfatos/metabolismo , EsgotosRESUMO
We theoretically and experimentally investigate the wide-angle perfect absorptance in a photonic heterostructure composed of a metal film and a truncated photonic crystal (PC) with layered hyperbolic metamaterials (HMMs) in the near ultraviolet and visible regions. The wide-angle perfect optical absorption depends on the dispersionless Tamm plasmon polarition (TPP) under TM polarization, which originates from reflection phase compensation condition between the metal and the truncated PC with HMMs. Our experimental results show nearly perfect absorptance over 0.91 in an angle range of 0-45 degree, which facilitates the design of perfect optical absorbers working in a wide angle range.
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The efficacy of sonodynamic therapy (SDT) mainly relies on the sonosensitizers, which generate reactive oxygen species (ROS) upon ultrasound (US) stimulation. However, the limited availability of high-efficiency sonosensitizers hampers the therapeutic effectiveness of SDT as a standalone modality. In this work, a robust sonodynamic and gas cancer therapeutic platform is constructed based on strontium (Sr) doped barium titanate (BST) piezoelectric nanoparticles functionalized with L-arginine (BST@LA). The doping of Sr into A site of the ABO3 piezoelectric nanocrystals not only introduces oxygen vacancies into the nanoparticles and enhance the intrinsic piezoelectricity, but also narrows the semiconductor band gap and enhances charge carrier migration, all of which facilitate the sonodynamic production of superoxide anion (â¢O2 - ) and hydroxyl radical (â¢OH). In addition, the generated ROS promotes the decomposition of the surface-tethered LA, enabling the controlled release of nitric oxide (NO) gas at the tumor site, thereby achieving a combination therapeutic effect. In vivo experiments exhibit remarkable tumor suppression rate (89.5%) in 4T1 tumor mice model, demonstrating the effectiveness of this strategy. The ion doping and oxygen vacancy engineering to improve sonosensitizers, along with the synergistic combination of sonodynamic and gas therapy, provides promising avenues for improving cancer therapy.
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Neoplasias , Estrôncio , Animais , Camundongos , Óxido Nítrico , Espécies Reativas de Oxigênio , Ácido Linoleico , Oxigênio , Neoplasias/terapiaRESUMO
The low cultivability of environmental bacteria has been widely acknowledged, but most previous estimates focused on the proportion of cultivable cells rather than cultivable taxa. Here, we estimate the proportions of cultivable cells and cultivable taxa for two sample types (soil and activated sludge) using cell counting, 16S rRNA gene amplicon sequencing, metagenomics, and cultivation on agar plates under various conditions. We find that the proportion of cultivable taxa exceeds that of cultivable cells at the sample level. A large proportion of cultivable taxa are taxonomically novel but tend to be present at very low abundance on agar plates, forming microcolonies, and some of them cease to grow during subculture. Compared with uncultivable taxa (under the conditions used in our study), cultivatable taxa tend to display higher metabolic activity as inferred by measuring rRNA copies per cell. Finally, we use the generated taxonomic and genomic information as a guide to isolate a strain representing a yet-uncultured class within the Bacteroidota and to enhance the cultivable diversity of Burkholderiales from activated sludge.
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Bactérias , Metagenômica , RNA Ribossômico 16S , Esgotos , Microbiologia do Solo , RNA Ribossômico 16S/genética , Esgotos/microbiologia , Metagenômica/métodos , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Filogenia , DNA Bacteriano/genética , Análise de Sequência de DNARESUMO
INTRODUCTION: Postoperative delirium (POD) is the most common acute fluctuating mental state change after hip fractures in older adults. Postoperative pain is a Grade A risk factor for POD and is closely related to the prognosis of patients undergoing hip fracture surgery. The fascia iliac block has a definite analgesic effect and few side effects, and several studies have reported that it reduces the occurrence of POD in patients undergoing general anaesthesia for hip fracture surgery. Liposomal bupivacaine is a local anaesthetic with a long half-life that significantly reduces the use of opioids and is conducive to patient prognosis and recovery. However, whether regional nerve block analgesia can decrease the occurrence of POD in elderly patients undergoing hip fracture surgery has not been reported. METHODS AND ANALYSIS: This is a single-blinded, randomised, parallel-controlled prospective clinical study. Participants will be randomly assigned preoperatively to either the liposomal bupivacaine (ie, Exparel) or ropivacaine groups by block randomisation. Then, the occurrence of POD (primary outcome) and postoperative pain (secondary outcome) will be evaluated. ETHICS AND DISSEMINATION: This research protocol complies with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 guidelines and is approved by the Ethics Committee of Shanghai General Hospital (ID 2023-437). The original data are expected to be released in July 2029 on the ResMan original data-sharing platform (IPD-sharing platform) of the China Clinical Trial Registry, which can be viewed on the following website: http://www.medresman.org.cn. PROSPERO REGISTRATION NUMBER: ChiCTR2300074022.
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Delírio , Fraturas do Quadril , Idoso , Humanos , Estudos Prospectivos , China , Fraturas do Quadril/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Anestésicos Locais/uso terapêutico , Bupivacaína/uso terapêutico , Delírio/etiologia , Delírio/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Electric-field-based stimulation is emerging as a new cancer therapeutic modality through interfering with cell mitosis. To address its limitations of complicated wire connections, bulky devices, and coarse spatial resolution, an improved and alternative method is proposed for wirelessly delivering electrical stimulation into tumor tissues through designing an implantable, biodegradable, and wirelessly controlled therapeutic triboelectric nanogenerator (ET-TENG). With the excitation of ultrasound (US) to the ET-TENG, the implanted ET-TENG can generate an alternating current voltage and concurrently release the loaded anti-mitotic drugs into tumor tissues, which synergistically disrupts the assembly of microtubules and filament actins, induces cell cycle arrest, and finally enhances cell death. With the assistance of US, the device can be completely degraded after the therapy, getting free of a secondary surgical extraction. The device can not only work around those unresectable tumors, but also provides a new application of wireless electric field in cancer therapy.
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Actinas , Neoplasias , Humanos , Morte Celular , Estimulação Elétrica , Microtúbulos , Neoplasias/tratamento farmacológicoRESUMO
Ultrasound (US)-triggered sonodynamic therapy (SDT) is an emerging method for treating cancer due to its non-invasive nature and high-depth tissue penetration ability. However, current sonosensitizers commonly have unsatisfactory quantum yields of free radicals. In this work, we have developed unique organic semiconductor π-conjugated covalent organic framework nanocages (COFNs) as highly efficient sonosensitizers to boost free radical (1O2 and â¢OH) production and cancer therapy. With the hollow and porous structure and band transport behavior, COFNs displayed remarkably improved SDT performance through enhanced electron utilization and cavitation effect, with a 1.8-fold increase in US pressure and a 64.8% increase in 1O2 production relative to the core-shell-structured COF under US irradiation. The in vitro and in vivo experimental results verified the elevated SDT performance, showing a high tumor suppression of 91.4% against refractory breast cancer in mice. This work provides a promising strategy to develop high-performance sonosensitizers for cancer therapy.
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Estruturas Metalorgânicas , Neoplasias , Terapia por Ultrassom , Camundongos , Animais , Estruturas Metalorgânicas/farmacologia , Terapia por Ultrassom/métodos , Neoplasias/terapia , Neoplasias/patologia , Ultrassonografia , Radicais Livres , Linhagem Celular Tumoral , Espécies Reativas de OxigênioRESUMO
The efficacy of cancer catalytic therapy is still hindered by the inefficient generation of reactive oxygen species (ROS). Herein, we report a self-driven electrical stimulation-promoted cancer catalytic therapy and chemotherapy by integrating a human-driven triboelectric nanogenerator (TENG) with an implantable and biodegradable nanofibrous patch. The gelatin/polycaprolactone nanofibrous patch incorporates doxorubicin (DOX) and graphitic carbon nitride (g-C3N4), in which the peroxidase (POD)-like activity of g-C3N4 to produce hydroxyl radical (â¢OH) can be distinctly enhanced by the self-driven electrical stimulation for 4.12-fold, and simultaneously DOX can be released to synergize the therapy, especially under a weakly acidic tumor microenvironment (TME) condition. The in vitro and in vivo experimental results on a mouse breast cancer model demonstrate superior tumor suppression outcome. The self-powered electrical stimulation-enhanced catalytic therapy and chemotherapy via multifunctional nanofibrous patches proposes a new complementary strategy for the catalytic therapy of solid tumors.
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Nanofibras , Neoplasias , Camundongos , Animais , Humanos , Próteses e Implantes , Eletricidade , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Estimulação Elétrica , Microambiente TumoralRESUMO
BACKGROUND: Foot and lower limb health complications are common among patients undergoing dialysis; but a summary of prevention and management evidence is not available. The aim of this scoping review was to summarise study characteristics and the nature of results regarding strategies to prevent and manage peripheral arterial disease (PAD), foot ulceration, amputation, associated infection and associated hospital admission in adults undergoing dialysis. METHODS: MEDLINE, Embase, CINAHL and AMED databases were searched for longitudinal experimental and observational studies. Eligible studies included adults undergoing dialysis (≥10 dialysis patients, with separate results or ≥ 75% of the cohort). Any interventions relating to PAD, foot ulceration, amputation, associated infection, and associated hospital admission were included. RESULTS: The review included 212 studies, of which 199 were observational (94%) and 13 were experimental (6%). Sixteen studies (8%) addressed the prevention of foot and lower limb health complications, 43 (20%) addressed management, and 153 (72%) addressed both. The main intervention type in each study was surgery (n = 159, 75%), care from one or more health professionals (n = 13, 6%), screening by a health professional (n = 10, 5%), medication (n = 9, 4%) and rehabilitation (n = 5, 2%). No studies were identified where exercise, offloading or education were the main intervention. Results for PAD were reported in 137 (65%) studies, foot ulceration in 54 (25%), amputation in 171 (81%), infection in 7 (3%), and admission in 26 studies (12%). Results for more than one foot or lower limb outcome were reported in 141 studies (67%), with each study reporting on average two outcomes. Results varied and spanned positive, negative, and neutral outcomes following intervention. CONCLUSIONS: Identified studies frequently aimed to both prevent and manage foot and lower limb health complications. A variety of interventions were identified and studies often reported results for more than one foot or lower limb health outcome. Findings from this review can be used to guide future research, with a goal to support improved patient outcomes.
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Úlcera do Pé , Doença Arterial Periférica , Humanos , Adulto , Diálise Renal/efeitos adversos , Fatores de Risco , Extremidade Inferior , Úlcera do Pé/etiologia , Amputação Cirúrgica , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/prevenção & controleRESUMO
The experiments on cellulose dissolution/regeneration have made some achievements to some extent, but the mechanism of cellulose regeneration in ionic liquids (ILs) and anti-solvent mixtures remains elusive. In this work, the cellulose regeneration mechanism in different anti-solvents, and at different temperatures and concentrations, has been studied with molecular dynamics (MD) simulations. The IL considered is 1-ethyl-3-methylimidazolium acetate (EmimOAc). In addition, to investigate the microcosmic effects of ILs and anti-solvents, EmimOAc-nH2O (n = 0-6) clusters have been optimized by Density Functional Theory (DFT) calculations. It can be found that water is beneficial to the regeneration of cellulose due to its strong polarity. The interactions between ILs and cellulose will become strong with the increase in temperature. The H-bonds of cellulose chains would increase with the rising concentrations of anti-solvents. The interaction energies between cellulose and the anions of ILs are stronger than that of cations. Furthermore, the anti-solvents possess a strong affinity for ILs, cation-anion pairs are dissociated to form H-bonds with anti-solvents, and the H-bonds between cellulose and ILs are destroyed to promote cellulose regeneration.
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Cellulose can be dissolved in ionic liquids (ILs), and it can be recovered by adding antisolvent such as water or alcohol. In addition, the regenerated cellulose can be used for textiles, degradable membranes, hydrogels/aerogels, etc. However, the regenerated mechanism of cellulose remains ambiguous. In this work, density functional theory (DFT) calculation is reported for the cellulose regeneration from a cellulose/1-n-butyl-3-methylimidazolium acetate (BmimOAc)/water mixture. To investigate the microscopic effects of the antisolvents, we analyzed the structures and H-bonds of BmimOAc-nH2O and cellobiose-ILs-nH2O (n = 0-6) clusters. It can be found that when n ≥ 5 in the BmimOAc-nH2O clusters, the solvent-separated ion pairs (SIPs) play a dominant position in the system. With the increasing numbers of water molecules, the cation-anion interaction can be separated by water to reduce the effects of ILs on cellulose dissolution. Furthermore, the BmimOAc-nH2O and cellobiose-ILs (n = 0-6) clusters tend to be a more stable structure with high hydration in an aqueous solution. When the water molecules were added to the system, H-bonds can be formed among H2O, the hydroxyl of cellulose, and the oxygen of OAc. Therefore, the interactions between cellulose and ILs will be decreased to promote cellulose regeneration. This work would provide some help to understand the mechanism of cellulose regeneration from the view of theoretical calculation.
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Gas therapy is an emerging technology for improving cancer therapy with high efficiency and low side effects. However, due to the existence of the gatekeeper of the blood-brain barrier (BBB) and the limited availability of current drug delivery systems, there still have been no reports on gas therapy for intracranial neuroglioma. Herein, an integrated, self-powered, and wirelessly controlled gas-therapy system is reported, which is composed of a self-powered triboelectric nanogenerator (TENG) and an implantable nitric oxide (NO) releasing device for intracranial neuroglioma therapy. In the system, the patient self-driven TENG converts the mechanical energy of body movements into electricity as a sustainable and self-controlled power source. When delivering energy to light a light-emitting diode in the implantable NO releasing device via wireless control, the encapsulated NO donor s-nitrosoglutathione (GSNO) can generate NO gas to locally kill the glioma cells. The efficacy of the proof-of-concept system in subcutaneous 4T1 breast cancer model in mice and intracranial glioblastoma multiforme in rats is verified. This self-powered gas-therapy system has great potential to be an effective adjuvant treatment modality to inhibit tumor growth, relapse, and invasion via teletherapy.
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Nanotecnologia , Óxido Nítrico , Ratos , Camundongos , Animais , Recidiva Local de Neoplasia , Fontes de Energia Elétrica , EletricidadeRESUMO
Inferring the properties of a scattering objective by analyzing the optical far-field responses within the framework of inverse problems is of great practical significance. However, it still faces major challenges when the parameter range is growing and involves inevitable experimental noises. Here, we propose a solving strategy containing robust neural-networks-based algorithms and informative photonic dispersions to overcome such challenges for a sort of inverse scattering problem-reconstructing grating profiles. Using two typical neural networks, forward-mapping type and inverse-mapping type, we reconstruct grating profiles whose geometric features span hundreds of nanometers with nanometric sensitivity and several seconds of time consumption. A forward-mapping neural network with a parameters-to-point architecture especially stands out in generating analytical photonic dispersions accurately, featured by sharp Fano-shaped spectra. Meanwhile, to implement the strategy experimentally, a Fourier-optics-based angle-resolved imaging spectroscopy with an all-fixed light path is developed to measure the dispersions by a single shot, acquiring adequate information. Our forward-mapping algorithm can enable real-time comparisons between robust predictions and experimental data with actual noises, showing an excellent linear correlation (R2 > 0.982) with the measurements of atomic force microscopy. Our work provides a new strategy for reconstructing grating profiles in inverse scattering problems.