UNASSIGNED: Micrometer-sized spherules formed of hydroxyapatite or whitlockite were identified within extracellular deposits that accumulate in the space between the basal lamina (BL) of retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch\'s membrane (sub-RPE-BL space). This investigation aimed to characterize the morphologic features, structure, and distribution of these spherules in aged human eyes with and without clinical indications of age-related macular degeneration (AMD).
UNASSIGNED: Experimental study.
UNASSIGNED: Five human eyes with varying degrees of sub-RPE-BL deposits were obtained from the University College London Institute of Ophthalmology and Moorfield\'s Eye Hospital Tissue Repository or the Advancing Sight Network. Two eyes were reported as having clinical indications of AMD (age, 76-87 years), whereas 3 were considered healthy (age, 69-91 years).
UNASSIGNED: Cadaveric eyes with sub-RPE-BL deposits were embedded in paraffin wax and sectioned to a thickness of 4-10 μm. Spherules were identified and characterized using high-resolution scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy, and time-of-flight secondary ion mass spectroscopy.
UNASSIGNED: High-resolution scanning electron micrographs of spherules, the size-frequency distribution of spherules including average diameter, and the distribution of particles across the central-peripheral axis. Elemental maps and time-of-flight secondary ion mass spectra also were obtained.
UNASSIGNED: The precipitation of spherules is ubiquitous across the central, mid-peripheral, and far-peripheral axis in aged human eyes. No significant difference was found in the frequency of spherules along this axis. However, statistical analysis indicated that spherules exhibited significantly different sizes in these regions. In-depth analysis revealed that spherules in the sub-RPE-BL space of eyes with clinical signs of AMD were significantly larger (median diameter, 1.64 μm) than those in healthy aged eyes (median diameter, 1.16 μm). Finally, spherules showed great variation in surface topography and internal structure.
UNASSIGNED: The precipitation of spherules in the sub-RPE-BL space is ubiquitous across the central-peripheral axis in aged human eyes. However, a marked difference exists in the size and frequency of spherules in eyes with clinical signs of AMD compared to those without, suggesting that the size and frequency of spherules may be associated with AMD.

Implantation of cardiovascular stents is an important therapeutic method to treat coronary artery diseases. Bare-metal and drug-eluting stents show promising clinical outcomes, however, their permanent presence may create complications. In recent years, numerous preclinical and clinical trials have evaluated the properties of bioresorbable stents, including polymer and magnesium-based stents. Three-dimensional (3D) printed-shape-memory polymeric materials enable the self-deployment of stents and provide a novel approach for individualized treatment. Novel bioresorbable metallic stents such as iron- and zinc-based stents have also been investigated and refined. However, the development of novel bioresorbable stents accompanied by clinical translation remains time-consuming and challenging. This review comprehensively summarizes the development of bioresorbable stents based on their preclinical/clinical trials and highlights translational research as well as novel technologies for stents (e.g., bioresorbable electronic stents integrated with biosensors). These findings are expected to inspire the design of novel stents and optimization approaches to improve the efficacy of treatments for cardiovascular diseases.

Multiple studies have shown strong relationships between different nutrients in plants, and the important role of N in Zn acquisition and translocation has been recognized.
The aim of this study was to estimate the effect of Zn on N uptake, translocation, and distribution in rice as well as the corresponding molecular mechanisms. We also aimed to evaluate the impact of N on the Zn content in rice grains which is closely related to the Zn nutrition in humans with rice-based diets.
We conducted both field trials and hydroponic cultures of two rice cultivars to analyze the growth and yield, the uptake, translocation, and distribution of N and Zn, as well as the expression of N transport and assimilation genes, and the Zn transporter genes under different combined applications of N and Zn.
Zn supply promoted the root-to-shoot translocation (12-70% increasing) and distribution of N into the leaves (19-49% increasing) and brown rice (6-9% increasing) and increased the rice biomass (by 14-35%) and yield (by 13-63%). Zn supply induced the expression of OsNRTs and OsAMTs in both roots and shoots, but repressed the expression of OsNiR2, OsGS1;2, and OsFd-GOGAT in roots, whereas it activated the expression of OsNiR2, OsGS1;1, OsGS2, and OsFd-GOGAT in the shoots. Moreover, the enzyme activities of nitrite reductase, nitrate reductase, and glutamine synthetase increased and the free NO3 - concentration decreased, but the soluble protein concentration increased significantly in the shoots after Zn supply. Synergistically, N significantly facilitated the root-to-shoot translocation (1.68-11.66 fold) and distribution of Zn into the leaves (1.68-6.37 fold) and brown rice (7-12% increasing) and upregulated the expression levels of Zn transporter genes in both the roots and shoots.
We propose a working model of the cross-talk between Zn and N in rice plants, which will aid in the appropriate combined application of Zn and N fertilizers in the field to improve both N utilization in plants and Zn nutrition in humans with rice-based diets.

Numerous harmful microorganisms and insect pests have the ability to cause plant infections or damage, which is mostly controlled by toxic chemical agents. These chemical compounds and their derivatives exhibit hazardous effects on habitats and human life too. Hence, there\'s a need to develop novel, more effective and safe bio-control agents. A variety of microbes such as viruses, bacteria, and fungi possess a great potential to fight against phytopathogens and thus can be used as bio-control agents instead of harmful chemical compounds. These naturally occurring microorganisms are applied to the plants in order to control phytopathogens. Moreover, practicing them appropriately for agriculture management can be a way towards a sustainable approach. The MBCAs follow various modes of action and act as elicitors where they induce a signal to activate plant defense mechanisms against a variety of pathogens. MBCAs control phytopathogens and help in disease suppression through the production of enzymes, antimicrobial compounds, antagonist activity involving hyper-parasitism, induced resistance, competitive inhibition, etc. Efficient recognition of pathogens and prompt defensive response are key factors of induced resistance in plants. This resistance phenomenon is pertaining to a complex cascade that involves an increased amount of defensive proteins, salicylic acid (SA), or induction of signaling pathways dependent on plant hormones. Although, there\'s a dearth of information about the exact mechanism of plant-induced resistance, the studies conducted at the physiological, biochemical and genetic levels. These studies tried to explain a series of plant defensive responses triggered by bio-control agents that may enhance the defensive capacity of plants. Several natural and recombinant microorganisms are commercially available as bio-control agents that mainly include strains of Bacillus, Pseudomonads and Trichoderma. However, the complete understanding of microbial bio-control agents and their interactions at cellular and molecular levels will facilitate the screening of effective and eco-friendly bio-agents, thereby increasing the scope of MBCAs. This article is a comprehensive review that highlights the importance of microbial agents as elicitors in the activation and regulation of plant defense mechanisms in response to a variety of pathogens.

The availability of multi-omics data sets and genome-scale metabolic models for various organisms provide a platform for modeling and analyzing genotype-to-phenotype relationships. Flux balance analysis is the main tool for predicting flux distributions in genome-scale metabolic models and various data-integrative approaches enable modeling context-specific network behavior. Due to its linear nature, this optimization framework is readily scalable to multi-tissue or -organ and even multi-organism models. However, both data and model size can hamper a straightforward biological interpretation of the estimated fluxes. Moreover, flux balance analysis simulates metabolism at steady-state and thus, in its most basic form, does not consider kinetics or regulatory events. The integration of flux balance analysis with complementary data analysis and modeling techniques offers the potential to overcome these challenges. In particular machine learning approaches have emerged as the tool of choice for data reduction and selection of most important variables in big data sets. Kinetic models and formal languages can be used to simulate dynamic behavior. This review article provides an overview of integrative studies that combine flux balance analysis with machine learning approaches, kinetic models, such as physiology-based pharmacokinetic models, and formal graphical modeling languages, such as Petri nets. We discuss the mathematical aspects and biological applications of these integrated approaches and outline challenges and future perspectives.

Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.

Improving grain filling in the presernt farming systems is crucial where grain filling is a concern due to the extreme use of chemical fertilizers (CF). A field experiment was conducted at the experimental station of Guangxi University, China in 2019 to test the hypothesis that cattle manure (CM) and poultry manure (PM) combined with CF could improve rice grain filling rate, yield, biochemical and qualitative attributes. A total of six treatments, i.e., no fertilizer (T1), 100% CF (T2), 60% CM + 40% CF (T3), 30% CM + 70% CF (T4), 60% PM + 40% CF (T5), and 30% PM + 70% CF (T6) were used in this study. Results showed that the combined treatment T6increased starch metabolizing enzymes activity (SMEs), such as ADP-glucose phosphorylase (ADGPase) by 8 and 12%, soluble starch synthase (SSS) by 7 and 10%, granule bound starch synthesis (GBSS) by 7 and 9%, and starch branching enzyme (SBE) by 14 and 21% in the early and late seasons, respectively, compared with T2. Similarly, higher rice grain yield, grain filling rate, starch, and amylose content were also recorded in combined treatments. In terms of seasons, higher activity of SMEs , grain starch, and amylose content was noted in the late-season compared to the early season. The increment in these traits was mainly attributed to a lower temperature in the late season during the grain filling period. Furthermore, our results suggested that an increment in starch accumulation and grain filling rate were mainly associated with the enhanced sink capacity by regulating key enzyme activities involved in Suc-to-starch conversion. In-addition, RT-qPCR analysis showed higher expression levels of AGPS2b, SSS1, GBSS1, and GBSE11b genes, which resultantly increased the activities of SMEs during the grain filling period under combined treatments. Linear regression analysis revealed that the activity of ADGPase, SSS, GBSS, and SBE were highly positively correlated with starch and amylose accumulation. Thus, we concluded that a combination of 30% N from PM or CM with 70% N from CF is a promising option in terms of improving rice grain yield and quality. Our study provides a sustainable fertilizer management strategy to enhance rice grain yield and quality at the lowest environmental cost.

The rich content of nutrients in human waste provides an outlook for turning it from pollutants to potential resources. The pilot-scale resource-oriented toilet with forward osmosis technology was demonstrated to have advantages to recover clean water, nitrogen, phosphorus, potassium, biogas, and heat from urine and feces. For the possibility of further full-scale implementation in different scenarios, six resource-oriented toilet systems and one conventional toilet system were designed in this study. The methodology of cost-benefit analysis and life cycle assessment were applied to analyze the life cycle economic feasibility and environmental sustainability of these systems. As results indicated, resource-oriented toilets with forward osmosis technology concentrating urine proved to have both economic and environmental benefit. The economic net present value results of new resource-oriented toilets were much better than conventional toilet. The energy consumption in resource-oriented toilets contributes a lot to the environmental impacts while resource recovery such as the fertilizer production and fresh water harvest in resource-oriented toilet systems offsets a lot. Taking both life cycle economic feasibility and environmental sustainability into consideration, the partial resource-oriented toilet (only recovering nutrients from urine) is the best choice, and the totally independent resource-oriented toilet could be applied to replace conventional toilets in areas without any external facilities such as sewer and water supply system etc.

This paper describes data of nitrous oxides (N2O) emissions from open-field and greenhouse systems in Chinese vegetable production. The data also describes the potential soil and management factors to identify the effective measures to mitigate N2O emissions. The data were collected from 21 peer-reviewed papers, covering 153 N2O emission field measurements as affected by fertilizer nitrogen (N) management. This data were subjected to meta-analysis for a comprehensive assessment on N2O emission and applied N based emission factor in Chinese vegetable production.

Nitrate (NO3(-)) and ammonium (NH4(+)) are the main forms of nitrogen available in the soil for plants. Excessive NH4(+) accumulation in tissues is toxic for plants and exclusive NH4(+)-based nutrition enhances this effect. Ammonium toxicity syndrome commonly includes growth impairment, ion imbalance and chlorosis among others. In this work, we observed high intraspecific variability in chlorophyll content in 47 Arabidopsis thaliana natural accessions grown under 1 mM NH4(+) or 1 mM NO3(-) as N-source. Interestingly, chlorophyll content increased in every accession upon ammonium nutrition. Moreover, this increase was independent of ammonium tolerance capacity. Thus, chlorosis seems to be an exclusive effect of severe ammonium toxicity while mild ammonium stress induces chlorophyll accumulation.