Metabolic Profiling of Genetically Modified Potato Periderm Tissues

Potato tubers are protected from dehydration and pathogens by a covering peel (periderm) impregnated with suberin, a complex cross-linked biopolymer that contains both polyaliphatic and lignin-like aromatic domains. Current models describing the macromolecular structure of suberin assume that ferulic acid cross-links both domains as it may form carboxyl ester bonds with aliphatic monomers and non-ester radical-coupled bonds with phenolics. Ferulic acid also links by ester bonds to glycans and acts in cross-linking polysaccharides and lignin. Fatty alcohol/ω-hydroxyacid hydroxycinnamoyl transferase (FHT) is a BADH acyltransferase responsible for the synthesis of akyl-ferulates that is necessary for suberin biosynthesis. Periderm from FHT-RNAi tubers showed a significant decrease in suberin ferulate esters and an increase in soluble phenolic breakdown products. This periderm also showed changes in texture and water permeability but, surprisingly, the suberin lamellar structure was not altered. The CYP86A gene is a strong candidate for aliphatic suberin biosynthesis. CYP86A33-RNAi potato periderm had a striking loss of suberin lamellar structure and diminished w-hydroxyacids and a,w-diacids. To obtain a more comprehensive molecular view of the consequences of gene silencing on potato periderm composition, metabolite profiling was conducted on soluble polar and nonv polar extracts from native and wound periderms of wild-type (WT) and FHT-RNAi silenced potato samples using liquid-chromatography mass-spectrometry (LC-MS), gas-chromatography mass-spectrometry (GC-MS) and 1H nuclear magnetic resonance spectroscopy (NMR). The solid interface was analyzed by solid-state NMR. FHT deficiency induced significant changes in the metabolite pool of both polar and non-polar extracts from native periderms. In particular, FHT silencing induced accumulation of phenolic amides such as caffeoylputrescine, feruloylputrescine, feruloyltyramine, and amide dimers in the polar extracts and long-chain saturated fatty acids (C22, C23, C24, C27), long-chain primary alcohols (C22, C26, C27, C28, C29), methyl esters (C17:0, C19:2) and 1-monohexadecanoyl glycerol in the non-polar extracts. Phenolic acids, glycoalkaloids, alkanes (C21, C23, C25, C27, C29) and fatty acids (C16:0, C18:0, C18:2) were down-regulated in FHT-RNAi native periderms. For the solid interfacial residue, the FHT-RNAi variety displayed higher arene-to-(CH2)n and oxygenated alkoxy-to-(CH2)n ratios compared to WT. In contrast to the native tissues, the WT and FHT-RNAi-silenced tissue extracts and solid interfacial residues from developing wound periderms each exhibited similar compositional progressions with time; their initially distinct metabolic profiles became overlapped and underwent a striking convergence. An analogous analysis was conducted on CYP86A33-RNAi native periderm. In CYP86A33 silenced native potato periderms, glycoalkaloids were highly abundant in polar extracts while polyamides were down-regulated compared with WT. Non-polar extracts are to be analyzed with GC-MS and LC-MS

Optimization of Offshore FPV Modules in Early Design Phase

Offshore Floating Photovoltaic (FPV) systems are gaining attention due to the high Technology Readiness Levels (TRL) of PV panels and offshore structures. Numerous offshore FPV design proposals exist, but none have yet met industrial standards. The designs fall into two main categories: membrane type supported by a floating collar/air cushion and modular structure type comprising interconnected FPV modules. This paper uses semi-analytical methods to optimize the modular structure type design, considering fabrication cost, module stability, and hydrodynamic response in waves.Optimization of Offshore FPV Modules in Early Design PhaseacceptedVersio

Evaluation of Arctic sea ice simulation of CMIP6 models from China

Nine coupled climate models from China participating in the Coupled Model Intercomparison Project Phase 6 (CMIP6) were evaluated in terms of their capability in ensemble historical Arctic sea ice simulation in the context of 56 CMIP6 models. We evaluated these nine models using satellite observations from 1980 to 2014. This evaluation was conducted comprehensively using 12 metrics covering different aspects of the seasonal cycle and long-term trend of sea ice extent (SIE) and sea ice concentration (SIC). The nine Chinese models tended to overestimate SIE, especially in March, and underestimate its long-term decline trend. There was less spread in model skill in reproducing the spatial pattern of March SIC than in reproducing the spatial pattern of September SIC. The error of March SIC simulation was distributed at the margins of sea ice cover, such as in the Nordic Seas, the Barents Sea, the Labrador Sea, the Bering Sea, and the Sea of Okhotsk. However, the error of September SIC was distributed both at the margins of sea ice cover and in the central part of the Arctic Basin. Five of these nine models had capabilities comparable with the majority of the CMIP6 models in reproducing the seasonal cycle and long-term trend of Arctic sea ice

Association of heavy metals exposure with lower blood pressure in the population aged 8–17 years: a cross-sectional study based on NHANES

BackgroundThe existing evidence regarding the joint effect of heavy metals on blood pressure (BP) in children and adolescents is insufficient. Furthermore, the impact of factors such as body weight, fish consumption, and age on their association remains unclear.MethodsThe study utilized original data from the National Health and Nutrition Examination Survey, encompassing 2,224 children and adolescents with complete information on 12 urinary metals (barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, tungsten, uranium, mercury and arsenic), BP, and core covariates. Various statistical methods, including weighted multiple logistic regression, linear regression, and Weighted Quantile Sum regression (WQS), were employed to evaluate the impact of mixed metal exposure on BP. Sensitivity analysis was conducted to confirm the primary analytical findings.ResultsThe findings revealed that children and adolescents with low-level exposure to lead (0.40 μg/L, 95%CI: 0.37, 0.42), mercury (0.38 μg/L, 95%CI: 0.35, 0.42) and molybdenum (73.66 μg/L, 95%CI: 70.65, 76.66) exhibited reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP). Conversely, barium (2.39 μg/L, 95%CI: 2.25, 2.54) showed a positive association with increased SBP. A 25th percentile increase in the WQS index is significantly associated with a decrease in SBP of 0.67 mmHg (95%CI, −1.24, −0.10) and a decrease in DBP of 0.59 mmHg (95% CI, −1.06, −0.12), which remains statistically significant even after adjusting for weight. Furthermore, among individuals who consume fish, heavy metals have a more significant influence on SBP. A 25 percentile increase in the WQS index is significantly associated with a decrease of 3.30 mmHg (95% CI, −4.73, −1.87) in SBP, primarily attributed to mercury (27.61%), cadmium (27.49%), cesium (17.98%), thallium (8.49%). The study also identified a declining trend in SBP among children aged 10–17, whereas children aged 11–18 exhibited lower levels of systolic and diastolic blood pressure, along with a reduced risk of hypertension.ConclusionSome heavy metals demonstrate an inverse association with the BP of children and adolescents, particularly notable in groups with fish consumption and older children and adolescents. Future studies are warranted to validate these findings and delve deeper into the interplay of heavy metals

Low Cost Industrial Production of Coagulation Factor IX Bioencapsulated in Lettuce Cells for Oral Tolerance Induction in Hemophilia B

Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (~1mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ~2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP+ regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft2 per annum yielding 24,000–36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs

Circulating tumor DNA determining hyperprogressive disease after CAR-T therapy alarms in DLBCL: a case report and literature review

Chimeric antigen receptor T-cell therapy (CAR-T) has been widely applied in the clinical practice of relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) due to its promising effects. Hyperprogressive disease (HPD) has gained attention for rapid tumor progression and has become a therapeutic and prognostic challenge. Here, we present a patient who had suffered from several recurrences previously and controlled well with a very small tumor lesion left was infused with CD19/CD22 bispecific CAR-T, with no immune effector cell-associated neurotoxicity syndrome, or cytokine release syndrome observed. However, rapid deterioration, subsequent imaging examination, circulating tumor DNA, and serum biomarkers detection identified HPD. The patient did not respond to salvage treatment and died 40 days after infusion. To our knowledge, only one case of HPD in DLBCL after CAR-T therapy has been reported. This fatal case alarmed the risk of HPD and the ctDNA profile monitoring we used was performed as a non-invasive method to diagnose HPD, providing far-reaching practical instruction for CAR-T therapy