The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS‐CoV) calls for the development of novel vaccine technology that offers ...safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus‐like fashion. STING agonists are first encapsulated into capsid‐like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH‐responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen‐specific T cell responses in mice immunized with a MERS‐CoV nanoparticle vaccine candidate. Using a MERS‐CoV‐permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle‐based MERS‐CoV vaccine are protected against a lethal challenge of MERS‐CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.
To improve vaccination efforts against Middle East respiratory syndrome coronavirus (MERS‐CoV), a virus‐mimicking vaccine is herein prepared with a capsid‐like hollow polymeric nanoparticle loaded with STING agonists and coated in MERS‐CoV antigens. The viromimetic nanoparticle facilitates safe and effective vaccination against the lethal virus and offers a versatile platform for combatting emerging infectious threats.
Concerns have been raised regarding the potential association between proton pump inhibitor (PPI) use and dementia.
This study aimed to examine this association in an Asian population.
Patients ...initiating PPI therapy between January 1, 2000 and December 31, 2003 without a prior history of dementia were identified from Taiwan's National Health Insurance Research Database. The outcome of interest was all-cause dementia. Cox regression models were applied to estimate the hazard ratio (HR) of dementia. The cumulative PPI dosage stratified by quartiles of defined daily doses and adjusted for baseline disease risk score served as the primary variables compared against no PPI use.
We analyzed the data of 15726 participants aged 40 years or older and free of dementia at baseline. PPI users (n = 7863; average follow-up 8.44 years) had a significantly increased risk of dementia over non-PPI users (n = 7863; average follow-up 9.55 years) (adjusted HR aHR 1.22; 95% confidence interval: 1.05-1.42). A significant association was observed between cumulative PPI use and risk of dementia (P for trend = .013). Subgroup analysis showed excess frequency of dementia in PPI users diagnosed with depression (aHR 2.73 1.91-3.89), hyperlipidemia (aHR 1.81 1.38-2.38), ischemic heart disease (aHR 1.55 1.12-2.14), and hypertension (aHR 1.54 1.21-1.95).
An increased risk for dementia was identified among the Asian PPI users. Cumulative PPI use was significantly associated with dementia. Further investigation into the possible biological mechanisms underlying the relationship between dementia and PPI use is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This work first demonstrates the improved electromagnetic interference (EMI) shielding performance of monolayer graphene on highly transparent metal-meshes of random pattern. Metal-meshes are ...fabricated on quartz substrate by lift-off based on self-cracking template and CVD graphene is directly transferred onto thin metal-meshes to construct the hierarchical graphene/metal-mesh film, by which considerable improvements both in microwave reflection and absorption can be realized in thin metal-meshes. The shielding effectiveness (SE) of the hierarchical film even exceeds the summation of those of the monolayer graphene and the metal-mesh film. Detailed analyses reveal that absorption dominates the improvement in SE for a graphene/50 nm Ag-mesh film, with a three-fold absorption coefficient as well as a slightly increased reflectivity compared to the Ag-mesh itself. The as-prepared hierarchical film primely inherits the excellent optical transmission properties from random-pattern metal-meshes with high transmittance in visual-IR spectrum, low haze and faint diffraction. Moreover, the chemical stability of metal-meshes is highly improved with the protection of graphene. We anticipate that the hierarchical graphene/metal-mesh film can be a promising material to play a great role in realization of high-performance EMI shielding in emerging optoelectronic devices such as touch panels, displays, airborne optoelectronic pods, and aviation camcorders.
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Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature ...concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.
Abstract
Defects can induce drastic changes of the electronic properties of two-dimensional transition metal dichalcogenides and influence their applications. It is still a great challenge to ...characterize small defects and correlate their structures with properties. Here, we show that tip-enhanced Raman spectroscopy (TERS) can obtain distinctly different Raman features of edge defects in atomically thin MoS
2
, which allows us to probe their unique electronic properties and identify defect types (e.g., armchair and zigzag edges) in ambient. We observed an edge-induced Raman peak (396 cm
−1
) activated by the double resonance Raman scattering (DRRS) process and revealed electron–phonon interaction in edges. We further visualize the edge-induced band bending region by using this DRRS peak and electronic transition region using the electron density-sensitive Raman peak at 406 cm
−1
. The power of TERS demonstrated in MoS
2
can also be extended to other 2D materials, which may guide the defect engineering for desired properties.
In recent years, several publications reported that nanoparticles larger than the kidney filtration threshold were found intact in the urine after being injected into laboratory mice. This ...theoretically should not be possible, as it is widely known that the kidneys prevent molecules larger than 6-8 nm from escaping into the urine. This is interesting because it implies that some nanoparticles can overcome the size limit for renal clearance. What kinds of nanoparticles can "bypass" the glomerular filtration barrier and cross into the urine? What physical and chemical characteristics are essential for nanoparticles to have this ability? And what are the biomolecular and cellular mechanisms that are involved? This review attempts to answer those questions and summarize known reports of renal-clearable large nanoparticles.
The major concept of "oxidative stress" is an excess elevated level of reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption of oxygen. The precise harmonization ...of oxidative stresses between mitochondria and other organelles in the cell is absolutely vital to cell survival. Under oxidative stress, ROS produced from mitochondria and are the major mediator for tumorigenesis in different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, and immunoescape to allow cancer cells to adapt to the rigorous environment. Accordingly, the dynamic balance of oxidative stresses not only orchestrate complex cell signaling events in cancer cells but also affect other components in the tumor microenvironment (TME). Immune cells, such as M2 macrophages, dendritic cells, and T cells are the major components of the immunosuppressive TME from the ROS-induced inflammation. Based on this notion, numerous strategies to mitigate oxidative stresses in tumors have been tested for cancer prevention or therapies; however, these manipulations are devised from different sources and mechanisms without established effectiveness. Herein, we integrate current progress regarding the impact of mitochondrial ROS in the TME, not only in cancer cells but also in immune cells, and discuss the combination of emerging ROS-modulating strategies with immunotherapies to achieve antitumor effects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Wafer‐scale fabrication of high‐performance uniform organic electronic materials is of great challenge and has rarely been realized before. Previous large‐scale fabrication methods always lead to ...different layer thickness and thereby poor film and device uniformity. Herein, the first demonstration of 4 in. wafer‐scale, uniform, and high‐performance n‐type polymer monolayer films is reported, enabled by controlling the multi‐level self‐assembly process of conjugated polymers in solution. Since the self‐assembly process happened in solution, the uniform 2D polymer monolayers can be facilely deposited on various substrates, and theoretically without size limitations. Polymer monolayer transistors exhibit high electron mobilities of up to 1.88 cm2 V−1 s−1, which is among the highest in n‐type monolayer organic transistors. This method allows to easily fabricate n‐type conjugated polymers with wafer‐scale, high uniformity, low contact resistance, and excellent transistor performance (better than the traditional spin‐coating method). This work provides an effective strategy to prepare large‐scale and uniform 2D polymer monolayers, which could enable the application of conjugated polymers for wafer‐scale sophisticated electronics.
Using a multi‐level self‐assembly strategy, an n‐type polymer monolayer field‐effect transistor is obtained on wafer‐scale. These devices offers high performance, high air‐stability, and high uniformity. The strategy enhances the formation of wafer‐scale and uniform polymer monolayers. Transistor arrays on a 4 in. wafer exhibit electron mobilities of up to 1.88 cm2 V−1 s−1, among the highest reported until now for n‐type monolayer organic transistors.
Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are the two most common immune checkpoints targeted in triple-negative breast cancer (BC). Refining patient selection for immunotherapy ...is non-trivial and finding an appropriate digital pathology framework for spatial analysis of theranostic biomarkers for PD-1/PD-L1 inhibitors remains an unmet clinical need.
We describe a novel computer-assisted tool for three-dimensional (3D) imaging of PD-L1 expression in immunofluorescence-stained and optically cleared BC specimens (n = 20). The proposed 3D framework appeared to be feasible and showed a high overall agreement with traditional, clinical-grade two-dimensional (2D) staining techniques. Additionally, the results obtained for automated immune cell detection and analysis of PD-L1 expression were satisfactory.
The spatial distribution of PD-L1 expression was heterogeneous across various BC tissue layers in the 3D space. Notably, there were six cases (30%) wherein PD-L1 expression levels along different layers crossed the 1% threshold for admitting patients to PD-1/PD-L1 inhibitors. The average PD-L1 expression in 3D space was different from that of traditional immunohistochemistry (IHC) in eight cases (40%). Pending further standardization and optimization, we expect that our technology will become a valuable addition for assessing PD-L1 expression in patients with BC.
Via a single round of immunofluorescence imaging, our approach may provide a considerable improvement in patient stratification for cancer immunotherapy as compared with standard techniques.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metalenses consist of an array of optical nanoantennas on a surface capable of manipulating the properties of an incoming light wavefront. Various flat optical components, such as polarizers, optical ...imaging encoders, tunable phase modulators and a retroreflector, have been demonstrated using a metalens design. An open issue, especially problematic for colour imaging and display applications, is the correction of chromatic aberration, an intrinsic effect originating from the specific resonance and limited working bandwidth of each nanoantenna. As a result, no metalens has demonstrated full-colour imaging in the visible wavelength. Here, we show a design and fabrication that consists of GaN-based integrated-resonant unit elements to achieve an achromatic metalens operating in the entire visible region in transmission mode. The focal length of our metalenses remains unchanged as the incident wavelength is varied from 400 to 660 nm, demonstrating complete elimination of chromatic aberration at about 49% bandwidth of the central working wavelength. The average efficiency of a metalens with a numerical aperture of 0.106 is about 40% over the whole visible spectrum. We also show some examples of full-colour imaging based on this design.
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