Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. ...Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 10
, 4.10 × 10
and 1.03 × 10
CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p < 0.05). We believe that PL-02 can be used as a supplement to improve exercise performance and for its anti-fatigue effect.
Type IVa pili are filamentous cell surface structures observed in many bacteria. They pull cells forward by extending, adhering to surfaces, and then retracting. We used cryo-electron tomography of ...intact Myxococcus xanthus cells to visualize type IVa pili and the protein machine that assembles and retracts them (the type IVa pilus machine, or T4PM) in situ, in both the piliated and nonpiliated states, at a resolution of 3 to 4 nanometers. We found that T4PM comprises an outer membrane pore, four interconnected ring structures in the periplasm and cytoplasm, a cytoplasmic disc and dome, and a periplasmic stem. By systematically imaging mutants lacking defined T4PM proteins or with individual proteins fused to tags, we mapped the locations of all 10 T4PM core components and the minor pilins, thereby providing insights into pilus assembly, structure, and function.
The delivery of proteins into cells is a potential game changer for a wide array of therapeutic purposes, including cancer therapy, immunomodulation and treatment of inherited diseases. In this ...review, we present recently developed nanoassemblies for protein delivery that utilize strategies that range from direct assembly, encapsulation and composite formation. We will discuss factors that affect the efficacy of nanoassemblies for delivery from the perspective of both nanoparticles and proteins. Challenges in the field, particularly achieving effective cytosolar protein delivery through endosomal escape or evasion are discussed.
Direct intracellular delivery of proteins using inorganic nanoparticle-protein supramolecular assemblies.
Genome editing through the delivery of CRISPR/Cas9-ribonucleoprotein (Cas9-RNP) reduces unwanted gene targeting and avoids integrational mutagenesis that can occur through gene delivery strategies. ...Direct and efficient delivery of Cas9-RNP into the cytosol followed by translocation to the nucleus remains a challenge. Here, we report a remarkably highly efficient (∼90%) direct cytoplasmic/nuclear delivery of Cas9 protein complexed with a guide RNA (sgRNA) through the coengineering of Cas9 protein and carrier nanoparticles. This construct provides effective (∼30%) gene editing efficiency and opens up opportunities in studying genome dynamics.
The successful use of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based gene editing for therapeutics requires efficient in vivo delivery of the CRISPR components. There ...are, however, major challenges on the delivery front. In this Topical Review, we will highlight recent developments in CRISPR delivery, and we will present hurdles that still need to be overcome to achieve effective in vivo editing.
Abstract
As one of the most ideal display approaches, holographic 3-dimensional (3D) display has always been a research hotspot since the holographic images reproduced in such system are very similar ...to what humans see the actual environment. However, current holographic 3D displays suffer from critical bottlenecks of narrow viewing angle and small size. Here, we propose a tunable liquid crystal grating-based holographic 3D display system with wide viewing angle and large size. Our tunable liquid crystal grating, providing an adjustable period and the secondary diffraction of the reconstructed image, enables to simultaneously implement two different hologram generation methods in achieving wide viewing angle and enlarged size, respectively. By using the secondary diffraction mechanism of the tunable liquid crystal grating, the proposed system breaks through the limitations of narrow viewing angle and small size of holographic 3D display. The proposed system shows a viewing angle of 57.4°, which is nearly 7 times of the conventional case with a single spatial light modulator, and the size of the reconstructed image is enlarged by about 4.2. The proposed system will have wide applications in medical diagnosis, advertising, education and entertainment and other fields.
Objective
We utilized human midbrain‐like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α‐synuclein (α‐syn; SNCA) perturbations to ...investigate genotype‐to‐phenotype relationships in Parkinson disease, with the particular aim of recapitulating α‐syn– and Lewy body–related pathologies and the process of neurodegeneration in the hMLO model.
Methods
We generated and characterized hMLOs from GBA1−/− and SNCA overexpressing isogenic embryonic stem cells and also generated Lewy body–like inclusions in GBA1/SNCA dual perturbation hMLOs and conduritol‐b‐epoxide–treated SNCA triplication hMLOs.
Results
We identified for the first time that the loss of glucocerebrosidase, coupled with wild‐type α‐syn overexpression, results in a substantial accumulation of detergent‐resistant, β‐sheet–rich α‐syn aggregates and Lewy body–like inclusions in hMLOs. These Lewy body–like inclusions exhibit a spherically symmetric morphology with an eosinophilic core, containing α‐syn with ubiquitin, and can also be formed in Parkinson disease patient–derived hMLOs. We also demonstrate that impaired glucocerebrosidase function promotes the formation of Lewy body–like inclusions in hMLOs derived from patients carrying the SNCA triplication.
Interpretation
Taken together, the data indicate that our hMLOs harboring 2 major risk factors (glucocerebrosidase deficiency and wild‐type α‐syn overproduction) of Parkinson disease provide a tractable model to further elucidate the underlying mechanisms for progressive Lewy body formation. ANN NEUROL 2021;90:490–505
Inorganic nanoparticles provide multipurpose platforms for a broad range of delivery applications. Intrinsic nanoscopic properties provide access to unique magnetic and optical properties. Equally ...importantly, the structural and functional diversity of gold, silica, iron oxide, and lanthanide-based nanocarriers provide unrivalled control of nanostructural properties for effective transport of therapeutic cargos, overcoming biobarriers on the cellular and organismal level. Taken together, inorganic nanoparticles provide a key addition to the arsenal of delivery vectors for fighting disease and improving human health.
Display omitted
Correlation of the surface physicochemical properties of nanoparticles with their interactions with biosystems provides key foundational data for nanomedicine. We report here the systematic synthesis ...of 2, 4, and 6 nm core gold nanoparticles (AuNP) featuring neutral (zwitterionic), anionic, and cationic headgroups. The cellular internalization of these AuNPs was quantified, providing a parametric evaluation of charge and size effects. Contrasting behavior was observed with these systems: with zwitterionic and anionic particles, uptake decreased with increasing AuNP size, whereas with cationic particles, uptake increased with increasing particle size. Through mechanistic studies of the uptake process, we can attribute these opposing trends to a surface-dictated shift in uptake pathways. Zwitterionic NPs are primarily internalized through passive diffusion, while the internalization of cationic and anionic NPs is dominated by multiple endocytic pathways. Our study demonstrates that size and surface charge interact in an interrelated fashion to modulate nanoparticle uptake into cells, providing an engineering tool for designing nanomaterials for specific biological applications.
Nocardial Brain Abscesses Lee, Yi-Wei; Liu, Hsin-Yi
The New England journal of medicine,
10/2021, Letnik:
385, Številka:
16
Journal Article
Recenzirano
An 80-year-old immunocompromised man presented to the emergency department with confusion. He later became obtunded, and magnetic resonance imaging of the head revealed ring-enhancing lesions. A ...cerebrospinal fluid culture grew
Nocardia farcinica
.
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