UNASSIGNED: Analytical methods to measure trace and toxic elements are essential to evaluate exposure and nutritional status. A ten-element panel was developed and validated for clinical testing in whole blood. Retrospective data analysis was conducted on patient samples performed at ARUP Laboratories.
UNASSIGNED: A method was developed and validated to quantify ten elements in whole blood by ICP-MS. Fifty microliters of sample were extracted with 950 μL of diluent containing 1 % ammonium hydroxide, 0.1 % Triton X-100, 1.75 % EDTA along with spiked internal standards. Four calibrators were used for each element and prepared in goat blood to match the patient specimen matrix. Samples were analyzed with an Agilent 7700 ICP-MS with a Cetac MVX 7100 μL Workstation autosampler.
UNASSIGNED: The assay was linear for all elements with inter- and intra-assay imprecision less than or equal to 11% CV at the low end of the analytical measurement range (AMR) and less than or equal to 4% CV at the upper end of the AMR for all elements. Accuracy was checked with a minimum of 40 repeat patient samples, proficiency testing samples, and matrix-matched spikes. The linear slopes for the ten elements ranged from 0.94 to 1.03 with intercepts below the AMR and R2 ranging from 0.97 to 1.00.
UNASSIGNED: The multi-element panel was developed to analyze ten elements in whole blood to unify the sample preparation and increase batch run efficiency. The improved analytical method utilized matrix-matched calibrators for accurate quantification to meet regulatory requirements. The assay was validated according to guidelines for CLIA-certified clinical laboratories and was suitable for clinical testing to assess nutritional status and toxic exposure.

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.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) is the most dangerous form of the coronavirus, which causes COVID-19. In patients with severe COVID-19, the immune system becomes markedly overactive. There is evidence that supplementation with select micronutrients may play a role in maintaining immune system function in this patient population. Throughout the COVID-19 pandemic, significant emphasis has been placed on the importance of supplementing critical micronutrients such as Vitamin C and Zinc (Zn) due to their immunomodulatory effects. Viral infections, like COVID-19, increase physiological demand for these micronutrients. Therefore, the purpose of this review was to provide comprehensive information regarding the potential effectiveness of Vitamin C and Zn supplementation during viral infection and specifically COVID-19. This review demonstrated a relation between Vitamin C and Zn deficiency and a reduction in the innate immune response, which can ultimately make patients with COVID-19 more vulnerable to viral infection. As such, adequate intake of Vitamin C and Zn, as an adjunctive therapeutic approach with any necessary pharmacological treatment(s), may be necessary to mitigate the adverse physiological effects of COVID-19. To truly clarify the role of Vitamin C and Zn supplementation in the management of COVID-19, we must wait for the results of ongoing randomized controlled trials. The toxicity of Vitamin C and Zn should also be considered to prevent over-supplementation. Over-supplementation of Vitamin C can lead to oxalate toxicity, while increased Zn intake can reduce immune system function. In summary, Vitamin C and Zn supplementation may be useful in mitigating COVID-19 symptomology.

Coronaviruses have received worldwide attention following several severe acute respiratory syndrome (SARS) epidemics. In 2019, the first case of coronavirus disease (COVID-19) caused by a novel coronavirus (SARS-coronavirus 2 [CoV-2]) was reported. SARS-CoV-2 employs RNA-dependent RNA polymerase (RdRp) for genome replication and gene transcription. Recent studies have identified a sulfur (S) metal-binding site in the zinc center structures of the RdRp complex. This metal-binding site is essential for the proper functioning of the viral helicase. We hypothesize that the use of essential nutrients can permeabilize the cell membranes. The oxidation of the metal-binding site occurs via analogs of the essential S-containing amino acid, l-Methionine. l-Methionine can operate as a carrier, and its binding would cause the potential disassembly of RdRp via the S complex and drive methyl donors via a possible countercurrent exchange mechanism and electrical-chemical gradient leading to SARS-CoV-2 replication failure. Our previously published hypothesis on the control of cancer cell proliferation suggests that the presence of a novel disulfide/methyl- adenosine triphosphate pump as an energy source would allow this process. The S binding site in l-Methionine serves as a potential target cofactor for SARS-CoV RdRp, thus providing a possible avenue for the future development of vaccines and antiviral therapeutic strategies to combat COVID-19.

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.

There is a critical need to understand the health risks associated with vaping e-cigarettes, which has reached epidemic levels among teens. Juul is currently the most popular type of e-cigarette on the market. Using the Comparative Toxicogenomics Database (CTD; http://ctdbase.org), a public resource that integrates chemical, gene, phenotype and disease data, we aimed to analyze the potential molecular mechanisms of eight chemicals detected in the aerosols generated by heating Juul e-cigarette pods: nicotine, acetaldehyde, formaldehyde, free radicals, crotonaldehyde, acetone, pyruvaldehyde, and particulate matter. Curated content in CTD, including chemical-gene, chemical-phenotype, and chemical-disease interactions, as well as associated phenotypes and pathway enrichment, were analyzed to help identify potential molecular mechanisms and diseases associated with vaping. Nicotine shows the most direct disease associations of these chemicals, followed by particulate matter and formaldehyde. Together, these chemicals show a direct marker or mechanistic relationship with 400 unique diseases in CTD, particularly in the categories of cardiovascular diseases, nervous system diseases, respiratory tract diseases, cancers, and mental disorders. We chose three respiratory tract diseases to investigate further, and found that in addition to cellular processes of apoptosis and cell proliferation, prioritized phenotypes underlying Juul-associated respiratory tract disease outcomes include response to oxidative stress, inflammatory response, and several cell signaling pathways (p38MAPK, NIK/NFkappaB, calcium-mediated).

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.

UNASSIGNED: Exposure to particulate matter (PM) emitted from vehicle exhaust might disrupt systemic function and elevate the risk of cardiovascular disease. In this study, we examined the changes of cardiometabolic biomarkers among vehicle inspectors exposed daily to PM0.25 and components.
UNASSIGNED: This cross-sectional study was conducted at two vehicle inspection centers, Pulogadung and Ujung Menteng, located in East Jakarta, Indonesia. The exposed respondents were 43 workers from vehicle inspection centers, and the unexposed group consisted of 22 staff officers working in the same locations. Vehicle exhaust particulate matter was measured for eight hours using a Leland Legacy personal pump attached to a Sioutas Cascade Impactor. The used filters were 25 and 37-mm quartz filters. The particulate matter concentration was analyzed using a gravimetric method, whereas trace elements were analyzed using energy dispersive X-ray fluorescence. An EEL Smoke Stain Reflectometer analyzed black carbon.
UNASSIGNED: The personal exposure concentrations of PM0.25 were 10.4-fold higher than those in unexposed groups. Calcium and sulfur were the major components in the obtained dust, and their levels were 3.3- and 7.2-fold higher, respectively, in the exposed group. Based on an independent-samples t-test, high-density lipoprotein, triglyceride, HbA1c, total immunoglobulin E, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and nitric oxide levels were significantly different between the groups.
UNASSIGNED: In summary, it was suggested that PM0.25 exposure from vehicle exhaust might affect cardiometabolic biomarkers change.

The advent of new technologies has paved the rise of various chemicals that are being employed in industrial as well as consumer products. This leads to the accumulation of these xenobiotic compounds in the environment where they pose a serious threat to both target and non-target species. miRNAs are one of the key epigenetic mechanisms that have been associated with toxicity by modulating the gene expression post-transcriptionally. Here, we provide a comprehensive view on miRNA biogenesis, their mechanism of action and, their possible role in xenobiotic toxicity. Further, we review the recent in vitro and in vivo studies involved in xenobiotic exposure induced miRNA alterations and the mRNA-miRNA interactions. Finally, we address the challenges associated with the miRNAs in toxicological studies.

Clarifying the mechanisms of heavy metal (HM) accumulation and translocation from soil-root-leaf is crucial to coping with soil HM pollution. In this study, we analysed copper (Cu), manganese (Mn), zinc (Zn) and cadmium (Cd) accumulation characteristics in Chinese turnips and the effect of soil physicochemical properties on both HM accumulation and translocation. Our results indicate that Chinese turnips absorb and translocate Mn, Zn, and Cd at much higher levels than they do Cu. When we measured bioconcentration factors in Chinese turnips for different HMs in the same soil, we found Chinese turnip capacities for HM accumulation decrease from Zn > Mn > Cd > Cu. In addition, the translocation factor for these HMs decreases from Mn > Cd > Zn > Cu. Correlation analysis indicates that soil pH and various soil components are either negatively or positively correlated with Mn, Zn, and Cd accumulation; also, soil properties are correlated with Mn translocation from root to leaf. These findings may help evaluate HM accumulation and translocation mechanisms as well as artificially regulate HM uptake levels from soils to turnips.