To evaluate the association of ultra-processed food (UPF) consumption with gains in weight and waist circumference, and incident overweight/obesity, in the Brazilian Longitudinal Study of Adult ...Health (ELSA-Brasil) cohort.
We applied FFQ at baseline and categorized energy intake by degree of processing using the NOVA classification. Height, weight and waist circumference were measured at baseline and after a mean 3·8-year follow-up. We assessed associations, through Poisson regression with robust variance, of UPF consumption with large weight gain (1·68 kg/year) and large waist gain (2·42 cm/year), both being defined as ≥90th percentile in the cohort, and with incident overweight/obesity.
Brazil.
Civil servants of Brazilian public academic institutions in six cities (n 11 827), aged 35-74 years at baseline (2008-2010).
UPF provided a mean 24·6 (sd 9·6) % of ingested energy. After adjustment for smoking, physical activity, adiposity and other factors, fourth (>30·8 %) v. first (<17·8 %) quartile of UPF consumption was associated (relative risk (95 % CI)) with 27 and 33 % greater risk of large weight and waist gains (1·27 (1·07, 1·50) and 1·33 (1·12, 1·58)), respectively. Similarly, those in the fourth consumption quartile presented 20 % greater risk (1·20 (1·03, 1·40)) of incident overweight/obesity and 2 % greater risk (1·02; (0·85, 1·21)) of incident obesity. Approximately 15 % of cases of large weight and waist gains and of incident overweight/obesity could be attributed to consumption of >17·8 % of energy as UPF.
Greater UPF consumption predicts large gains in overall and central adiposity and may contribute to the inexorable rise in obesity seen worldwide.
Nanozymes with inherent enzyme‐mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ...ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal–mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP‐mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP‐mSi, a lung‐cancer nanozymes probe (AP‐HAI) is ingeniously produced by removing the SiO2 template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase‐like catalytic process of H2O2. Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase‐like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung‐cancer synergetic catalytic therapy/immunogenic‐cell‐death‐based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.
Ultrasmall nPt nanozymes are innovatively fabricated upon AuP via a SiO2 spatial confinement strategy, and then modified with human serum albumin, followed by loading atovaquone molecules, and encapsulating IR780 in succession, to design AP‐HAI probes in which the IR780's PDT property and the nPt nanozymes' photoenhanced peroxidase‐like ability endow probes with a high reactive oxygen species (ROS) productivity, which results in outstanding lung‐cancer synergetic catalytic therapy/immunogenic‐cell‐death‐based immunotherapy.
Colloidal nanoparticles (NPs) have become versatile building blocks in a wide variety of fields. Here, we discuss the state-of-the-art, current hot topics, and future directions based on the ...following aspects: narrow size-distribution NPs can exhibit protein-like properties; monodispersity of NPs is not always required; assembled NPs can exhibit collective behavior; NPs can be assembled one by one; there is more to be connected with NPs; NPs can be designed to be smart; surface-modified NPs can directly reach the cytosols of living cells.
Due to the risks that water contamination implies for human health and environmental protection, monitoring the quality of water is a major concern of the present era. Therefore, in recent years ...several efforts have been dedicated to the development of fast, sensitive, and selective sensors for the detection of heavy metal ions. In particular, fluorescent sensors have gained in popularity due to their interesting features, such as high specificity, sensitivity, and reversibility. Thus, this review is devoted to the recent advances in fluorescent sensors for the monitoring of these contaminants, and special focus is placed on those devices based on fluorescent aptasensors, quantum dots, and organic dyes.
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Naturally occurring antimicrobial peptides (AMPs) hold promise as future therapeutics against multidrug resistant microorganisms. Recently, we have discovered that a derivative of the ...frog skin AMP esculentin-1a, Esc(1-21), is highly potent against both free living and biofilm forms of the bacterial pathogen Pseudomonas aeruginosa. However, bringing AMPs into clinics requires to overcome their low stability, high toxicity and inefficient delivery to the target site at high concentrations. Importantly, peptide conjugation to gold nanoparticles (AuNPs), which are among the most applied inorganic nanocarriers in biomedical sciences, represents a valuable strategy to solve these problems. Here we report that covalent conjugation of Esc(1-21) to soluble AuNPs AuNPs@Esc(1-21) via a poly(ethylene glycol) linker increased by ∼15-fold the activity of the free peptide against the motile and sessile forms of P. aeruginosa without being toxic to human keratinocytes. Furthermore, AuNPs@Esc(1-21) resulted to be significantly more resistant to proteolytic digestion and to disintegrate the bacterial membrane at very low concentration (5nM). Finally, we demonstrated for the first time the capability of peptide-coated AuNPs to display a wound healing activity on a keratinocytes monolayer. Overall, these findings suggest that our engineered AuNPs can serve as attractive novel biological-derived material for topical treatment of epithelial infections and healing of the injured tissue.
Despite conjugation of AMPs to AuNPs represents a worthwhile solution to face some limitations for their development as new therapeutics, only a very limited number of studies is available on peptide-coated AuNPs. Importantly, this is the first report showing that a covalent binding of a linear AMP via a poly(ethylene glycol) linker to AuNPs highly enhances antipseudomonal activity, preserving the same mode of action of the free peptide, without being harmful. Furthermore, AuNPs@Esc(1-21) are expected to accelerate recovery of an injured skin layer. All together, these findings suggest our peptide-coated AuNPs as attractive novel nanoscale formulation to treat bacterial infections and to heal the injured tissue.
The blood–brain barrier (BBB) is a formidable physical and enzymatic barrier that tightly controls the passage of molecules from the blood to the brain. In fact, less than 2 % of all potential ...neurotherapeutics are able to cross it. Here, by applying the retro‐enantio approach to a peptide that targets the transferrin receptor, a full protease‐resistant peptide with the capacity to act as a BBB shuttle was obtained and thus enabled the transport of a variety of cargos into the central nervous system.
Jumping hurdles: The retro‐enantio approach has been applied to a peptide that targets the transferrin receptor. The stability and permeability of the peptide across the blood–brain barrier (BBB) were notably increased. This new protease‐resistant peptide was tested as a BBB shuttle, and it does facilitate the transport of cargo across the BBB, both in vitro and in vivo, as demonstrated by intravital microscopy in living mice.
The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid ...malignancies.
The investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling-based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients.
On the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods.
Gene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias.
Too hot to handle: The surroundings of magnetic nanoparticles can be heated by applying a magnetic field. Polymer‐coated magnetic nanoparticles were functionalized with single‐stranded DNA molecules ...and further hybridized with DNA modified with different fluorophores. By correlating the denaturation profiles of the DNA with the local temperature, temperature gradients for the vicinity of the excited nanoparticles were determined.
Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. ...Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that couple pre-mRNA processing to mRNA export. Consistent with this proposal, >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo. To address the mechanism, transcriptome-wide RNA-binding profiles of NXF1 and SRSF1-7 were determined in parallel by individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP). Quantitative comparisons of RNA-binding sites showed that NXF1 and SR proteins bind mRNA targets at adjacent sites, indicative of cobinding. SRSF3 emerged as the most potent NXF1 adaptor, conferring sequence specificity to RNA binding by NXF1 in last exons. Interestingly, SRSF3 and SRSF7 were shown to bind different sites in last exons and regulate 3' untranslated region length in an opposing manner. Both SRSF3 and SRSF7 promoted NXF1 recruitment to mRNA. Thus, SRSF3 and SRSF7 couple alternative splicing and polyadenylation to NXF1-mediated mRNA export, thereby controlling the cytoplasmic abundance of transcripts with alternative 3' ends.
Force exertion is an integral part of cellular behavior. Traction force microscopy (TFM) has been instrumental for studying such forces, providing spatial force measurements at subcellular ...resolution. However, the applications of classical TFM are restricted by the typical planar geometry. Here, we develop a particle-based force sensing strategy for studying cellular interactions. We establish a straightforward batch approach for synthesizing uniform, deformable and tuneable hydrogel particles, which can also be easily derivatized. The 3D shape of such particles can be resolved with superresolution (<50 nm) accuracy using conventional confocal microscopy. We introduce a reference-free computational method allowing inference of traction forces with high sensitivity directly from the particle shape. We illustrate the potential of this approach by revealing subcellular force patterns throughout phagocytic engulfment and force dynamics in the cytotoxic T-cell immunological synapse. This strategy can readily be adapted for studying cellular forces in a wide range of applications.
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