Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard ...reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE-RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE-RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of "metabolic memory", the "French paradox", and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects.
A sum-frequency spectroscopy scheme is developed that allows the measurement of vibrational spectra of the interfacial molecular structure of charged water interfaces. The application of this scheme ...to a prototype lipid-aqueous interface as a demonstration reveals an interfacial hydrogen-bonding water layer structure that responds sensitively to the charge state of the lipid headgroup and its interaction with specific ions. This novel technique provides unique opportunities to search for better understanding of electrochemistry and biological aqueous interfaces at a deeper molecular level.
Plant polysaccharides have prebiotic properties for gut microbiota and immune modulation. This study aimed to investigate the prevention abilities of edible Rhinacanthus nasutus polysaccharide (RNP) ...and okara polysaccharide (OP) in Sprague–Dawley rats with acetic acid‐induced colitis. The characterizations of RNP and OP were analyzed, including Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, and monosaccharide composition. The prebiotic properties of RNP and OP were determined in vitro. In addition, the pathological features of colon length and inflammatory cytokine levels in acetic acid‐induced colitis were improved by intragastric preadministration of RNP and OP for 3 weeks. There was no nephrotoxicity or hepatotoxicity in rats via histopathological assessment after RNP and OP intake. Moreover, the abundance of short‐chain fatty acids‐producing bacteria (Lachnospiraceae, Lactobacilli, and Prevotellaceae) were increased after RNP supplementation. In conclusion, intragastric gavage of RNP and OP significantly modulated the gut microbiota and immune response, consequently alleviating the symptoms of colitis. This novel finding provides an alternative strategy and potential application of these two polysaccharides for colitis prevention and treatment.
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
Polymorphonuclear neutrophils (PMNs) are traditionally regarded as professional phagocytic and acute inflammatory cells that engulf the microbial pathogens. However, accumulating data have suggested ...that PMNs are multi-potential cells exhibiting many important biological functions in addition to phagocytosis. These newly found novel activities of PMN include production of different kinds of cytokines/chemokines/growth factors, release of neutrophil extracellular traps (NET)/ectosomes/exosomes and trogocytosis (membrane exchange) with neighboring cells for modulating innate, and adaptive immune responses. Besides, PMNs exhibit potential heterogeneity and plasticity in involving antibody-dependent cellular cytotoxicity (ADCC), cancer immunity, autoimmunity, inflammatory rheumatic diseases, and cardiovascular diseases. Interestingly, PMNs may also play a role in ameliorating inflammatory reaction and wound healing by a subset of PMN myeloid-derived suppressor cells (PMN-MDSC). Furthermore, PMNs can interact with other non-immune cells including platelets, epithelial and endothelial cells to link hemostasis, mucosal inflammation, and atherogenesis. The release of low-density granulocytes (LDG) from bone marrow initiates systemic autoimmune reaction in systemic lupus erythematosus (SLE). In clinical application, identification of certain PMN phenotypes may become prognostic factors for severe traumatic patients. In the present review, we will discuss these newly discovered biological and pathobiological functions of the PMNs.
Aim
Long‐distance dispersal (LDD) plays an important role in shaping the distribution of global biodiversity. Polyploidy could favour invasion and thereby facilitate LDD. However, how and to what ...extent polyploidy interacts with LDD remain unclear. Here, we test the putative role of polyploidy in the global dispersal of a cosmopolitan genus Rorippa.
Location
Global.
Time Period
Late Miocene to present.
Major Taxa Studied
Rorippa Scop., Brassicaceae.
Methods
We traced the biogeographical and speciation history for 17 diploids and 41 polyploids of Rorippa using variation from plastid genomes and multiple nuclear loci. The ploidy role in dispersal rate difference was demonstrated using trait‐dependent biogeographical modelling.
Results
LDD shaped the amphitropical disjunction of Rorippa, during which polyploids showed higher dispersal rates than those of diploids, with 5.6× increase under the best‐fitted model. Five diploids and 21 polyploids were identified as products of transoceanic speciation events. Polyploidy‐involved LDD was more common in terms of polyploidization following LDD than those preceding LDD.
Main Conclusions
We demonstrate that polyploidy would be not only a driver but also a responder of LDD in Rorippa, highlighting a synergistic relationship between them. Our results provide a framework to uncover the biogeographical consequences of polyploidization and the joint roles of polyploidy and LDD in shaping the distribution of biodiversity.
Precision nitrogen fertilizer application depends on accurate estimation of plant nitrogen content. However, the assessment of plant nitrogen content at early growth stages of paddy rice through ...remote sensed images is complicated by the compound effects of backgrounds (e.g. flood water, bare soil, algae, etc.) on the band reflectance. The rapid changing of plant nitrogen content during the vegetative phase makes the development of an operational prediction model very difficult. In this study, aerial images acquired by a quadcopter unmanned aerial vehicle (UAV) equipped with a multispectral sensor were used to estimate plant nitrogen content at vegetative phase of rice crops. The experiments were conducted at the experimental farm of Taiwan Agricultural Research Institute (TARI) from 2018 to 2020. A variable, N-index (ratio between N content of plants to be evaluated and plants not receiving N fertilizers), was introduced to resolve the issues related to rapid changing of plant N content during the vegetative phase. After removing the interference on band reflectance by background from the aerial images, the most appropriate vegetation indices and period that can capture the variations of N-index of rice plants were identified. It was found that a normalized difference red edge index (NDRI) and red edge chlorophyll index (RECI) based model correlated well with the N-index values from c.a. 30 days after transplanting (DAT) to 55 DAT (i.e., the most crucial period for rice yield and grain quality). The developed model was then used to display the spatial and temporal heterogeneity in plant nitrogen status within an experimental field as an example to illustrate how to use the model. In the example, soil plant analysis development (SPAD) meter values at locations of various levels of estimated N-index were collected as surrogates of plant nitrogen content at various DATs to build relationships for converting N-index maps to SPAD maps for potential variable rate fertilizer application management.
This study presents investigations into the fabrication, characterization, and performance analysis of stretchable white random lasers based on 2D glutamine(GLN)‐functionalized WS2 quantum dots (QDs) ...enhanced by the integration of Au nanoparticles (NPs) and a wrinkled graphene structure. Wrinkled graphene holds the potential for achieving transient population inversion through electron collisions. Incorporating Au NPs introduces localized surface plasmon resonance (LSPR), which enhances the light‐matter interaction, resulting in reduced lasing thresholds. The GLN‐functionalized WS2 QDs exhibit strong photoluminescence emission, and their integration with a wrinkled graphene structure and Au NPs creates a synergistic effect that enhances the emission efficiency and enables the realization of white random lasing. The extensive characterization and analysis of the emission spectra under different deformation ratios provide valuable insights into the tunability and reliability of these devices, as well as the importance of light trapping due to the wrinkled graphene structure. The findings of this study underscore the significant potential of LSPR and wrinkled graphene structure induced stretchable and white random lasers based on 2D GLN‐functionalized WS2 QDs. These lasers may have a promising application in the field of flexible and wearable photonics, which is a critical step towards the development of next‐generation optoelectronic devices with improved performance.
Wrinkled graphene structure and localized surface plasmon resonance induced stretchable white random lasers have been demonstrated and their excellent capability for potential applications in the next‐generation information technology.
Phase-sensitive sum-frequency vibrational spectroscopy was used to probe interfaces of a long-chain alcohol monolayer with various electrolytic solutions, chosen as a prototype for nonionic ...organic/water interfaces. Spectra in the OH stretching range were observed to be under the influence of ions emerging at the interfaces. Analysis of the spectra with the help of Levin’s theory allowed us to quantitatively find the surface densities of various ions and, hence, the ion affinities and surface pH/pOH at the alcohol/water interface. For the ions studied, the interface affinity has the ranking order of OH– > I– > Cl– ∼ H3O+ > Na+, the same as that at the air/water interface except that OH– and H3O+ have their places interchanged. Significantly stronger affinity of OH– than H3O+ with the result of surface pH/pOH extrapolating to bulk pH 7 suggests that the alcohol/neutral water interface is weakly basic.
Transition metal dichalcogenides (TMDCs) have recently attracted a tremendous amount of attention owing to their superior optical and electrical properties as well as the interesting and various ...nanostructures that are created by different synthesis processes. However, the atomic thickness of TMDCs limits the light absorption and results in the weak performance of optoelectronic devices, such as photodetectors. Here, we demonstrate the approach to increase the surface area of TMDCs by a one-step synthesis process of TMDC nanowalls from WO x into three-dimensional (3D) WS2 nanowalls. By utilizing a rapid heating and rapid cooling process, the formation of 3D nanowalls with a height of approximately 150 nm standing perpendicularly on top of the substrate can be achieved. The combination of core–shell colloidal quantum dots (QDs) with three different emission wavelengths and 3D WS2 nanowalls further improves the performance of WS2-based photodetector devices, including a photocurrent enhancement of 320–470% and shorter response time. The significant results of the core–shell QD–WS2 hybrid devices can be contributed by the high nonradiative energy transfer efficiency between core–shell QDs and the nanostructured material, which is caused by the spectral overlap between the emission of core–shell QDs and the absorption of WS2. Besides, outstanding NO2 gas-sensing performance of core–shell QDs/WS2 devices can be achieved with an extremely low detection limit of 50 ppb and a fast response time of 26.8 s because of local p–n junctions generated by p-type 3D WS2 nanowalls and n-type core–shell CdSe-ZnS QDs. Our work successfully reveals the energy transfer phenomenon in core–shell QD–WS2 hybrid devices and shows great potential in commercial multifunctional sensing applications.
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