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One of the challenges to enable targeted modification of lignocellulosic biomass from grasses for improved biofuel and biochemical production lies within our limited understanding of the transcriptional control of secondary cell wall biosynthesis. Here, we investigated the role of the maize MYB transcription factor ZmMYB167 in secondary cell wall biosynthesis and how modified ZmMYB167 expression in two distinct grass model species affects plant biomass and growth phenotypes. Heterologous expression of ZmMYB167 in the C 3 model system Brachypodium led to mild dwarf phenotypes, increased lignin (~7% to 13%) and S-lignin monomer (~11% to 16%) content, elevated concentrations of cell wall-bound p -coumaric acid (~15% to 24%) and reduced biomass sugar release (~20%) compared to controls. Overexpression of ZmMYB167 in the C 4 model system Zea mays increased lignin (~4% to 13%), p -coumaric acid (~8% to 52%) and ferulic acid (~13% to 38%) content but did not affect plant growth and development nor biomass recalcitrance. Taken together, modifying ZmMYB167 expression represents a target to alter lignin and phenolic content in grasses. The ZmMYB167 expression-induced discrepancies in plant phenotypic and biomass properties between the two grass model systems highlight the challenges and opportunities for MYB transcription factor-based genetic engineering approaches of grass biomass.

Background Perennial C 4 grasses from the genus Miscanthus are widely regarded as leading and promising dedicated bioenergy crops due to their high biomass accumulation on marginal land with low environmental impacts and maintenance requirements over its productive life. There is an urgent socio-political and environmental need to ramp up the production of alternative, affordable and green bioenergy sources and to re-direct the net zero carbon emissions trajectory. Hence, up-scaling of Miscanthus cultivation as a source of biomass for renewable energy could play an important role to strategically address sustainable development goals for a growing bio-based economy. Certain Miscanthus sinensis genotypes are particularly interesting for their biomass productivity across a wide range of locations. As the aromatic biomass component lignin exhibits a higher energy density than cell wall polysaccharides and is generally used as an indicator for heating or calorific value, genetic engineering could be a feasible strategy to develop M. sinensis biomass with increased lignin content and thus improving the energetic value of the biomass. Results For this purpose, transgenic M. sinensis were generated by Agrobacterium- mediated transformation for expression of ZmMYB167 , a MYB transcription factor known for regulating lignin biosynthesis in C 3 and C 4 grasses. Four independent transgenic ZmMYB167 Miscanthus lines were obtained. Agronomic traits such as plant height, tillering and above-ground dry weight biomass of the transgenic plants were not different to that of wild-type control plants. Total lignin content of the transgenic plants was ~ 15–24% higher compared with control plants. However, the structural carbohydrates, glucan and xylan, were decreased by ~ 2–7% and ~ 8–10%, respectively, in the transgenic plants. Moreover, expression of ZmMYB167 in transgenic plants did not alter lignin composition, phenolic compounds or enzymatic saccharification efficiency yields but importantly improved total energy levels in Miscanthus biomass, equivalent to 10% higher energy yield per hectare. Conclusions This study highlights ZmMYB167 as a suitable target for genetic lignin bioengineering interventions aimed at advancing and developing lignocellulosic biomass supply chains for sustainable production of renewable bioenergy.

This study investigated a traditionally brewed, organically produced kombucha, which may contain antioxidants, polyphenols, and bioactive compounds resulting from fermentation. While kombucha is marketed as a functional drink, there is limited empirical research on the drink's functional benefits. Additionally, much kombucha sold in the global marketplace is produced using instant mixes, pasteurization, filtration, and top carbonation, creating a shelf‐stable ambient product at significantly lower cost than fresh, refrigerated traditional Kombucha. An 8‐week randomized, double‐blinded, parallel trial investigated the effects of daily kombucha (330 mL) consumption on urinary and plasma metabolomics in healthy adults aged 18–71. Participants of mixed gender and ethnicity consumed either a trial canned kombucha or a placebo (flavored water). First Morning Void (FMV) urine and fasting venous blood samples were collected before and after the trial period. Urine samples were analyzed using Flow Infusion Electrospray Ionization Mass Spectrometry (FIE‐MS), while plasma short‐chain fatty acids (SCFAs) were quantified using Gas Chromatography–Flame Ionization Detection (GC‐FID). The urinary metabolomic profile showed an increase in metabolites linked to kombucha‐derived polyphenols and microbial fermentation, such as dihydroferulic acid and arabitol. Plasma analysis revealed a significant reduction in acetic acid and a marginal decrease in isoButyric acid after kombucha consumption. These findings highlight the complex interplay between fermented food consumption and human metabolism. An 8‐week randomized, double‐blind trial tested daily canned kombucha intake (330 mL) in healthy adults. Urinary metabolomics revealed increased polyphenol‐ and fermentation‐related metabolites, while plasma analysis showed reduced acetic acid and slightly lower isoButyric acid. Findings suggest kombucha consumption alters human metabolism, though health effects remain unclear.

Background/Objectives: Cardiovascular diseases remain a leading cause of mortality and morbidity, and dyslipidaemia is one of the major risk factors. The widespread use of herbs and medicinal plants in traditional medicine has garnered increasing recognition as a valuable resource for increasing wellness and reducing the onset of disease. Several epidemiologic and clinical studies have shown that altering blood lipid profiles and maintaining gut homeostasis may protect against cardiovascular diseases. Methods: A randomised, active-controlled parallel human clinical trial (n = 52) with three herbal tea infusions (green (Camellia sinensis) tea with rhubarb root, green tea with senna, and active control green tea) daily for 21 days in a free-living healthy adult cohort was conducted to assess the potential for health benefits in terms of plasma lipids and gut health. Paired plasma samples were analysed using Afinion lipid panels (total cholesterol, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, triglycerides, and non-HDL cholesterol) and paired stool samples were analysed using 16S rRNA amplicon sequencing to determine bacterial diversity within the gut microbiome. Results: Among participants providing fasting blood samples before and after the intervention (n = 47), consumption of herbal rhubarb root tea and green tea significantly lowered total cholesterol, LDL-cholesterol, and non-HDL cholesterol (p < 0.05) in plasma after 21 days of daily consumption when compared with concentrations before the intervention. No significant change was observed in the senna tea group. In participants providing stool samples (n = 48), no significant differences in overall microbial composition were observed between pre- and post-intervention, even at the genus level. While no significant changes in overall microbial composition were observed, specific bacterial genera, such as Dorea spp., showed correlations with LDL cholesterol concentrations, suggesting potential microbiota-mediated effects of tea consumption. Diet and BMI was maintained in each of the three groups before and after the trial. Conclusions: It was found that drinking a cup of rhubarb root herbal or green tea infusion for 21 days produced beneficial effects on lipid profiles and maintained gut eubiosis without observable adverse effects in a healthy human cohort. More studies are needed to fully understand the effects of rhubarb root and green tea in fatty acid metabolism and gut microbial composition.

Together with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood. In human and mouse, C3AR1 in the liver is expressed primarily in Kupffer cells, but is downregulated in humans with MASLD compared to obese controls. To test the role of complement 3a receptor (C3aR1) on macrophages and liver resident macrophages in MASLD, we generated mice deficient in C3aR1 on all macrophages (C3aR1-MφKO) or specifically in liver Kupffer cells (C3aR1-KpKO) and subjected them to a model of metabolic steatotic liver disease. We show that macrophages account for the vast majority of C3ar1 expression in the liver. Overall, C3aR1-MφKO and C3aR1-KpKO mice have similar body weight gain without significant alterations in glucose homeostasis, hepatic steatosis and fibrosis, compared to controls on a MASLD-inducing diet. This study demonstrates that C3aR1 deletion in macrophages or Kupffer cells, the predominant liver cell type expressing C3ar1 , has no significant effect on liver steatosis, inflammation or fibrosis in a dietary MASLD model.

Together with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood. In human and mouse, C3AR1 in the liver is expressed primarily in Kupffer cells, but is downregulated in humans with MASLD compared to obese controls. To test the role of complement 3a receptor (C3aR1) on macrophages and liver resident macrophages in MASLD, we generated mice deficient in C3aR1 on all macrophages (C3aR1-MφKO) or specifically in liver Kupffer cells (C3aR1-KpKO) and subjected them to a model of metabolic steatotic liver disease. We show that macrophages account for the vast majority of C3ar1 expression in the liver. Overall, C3aR1-MφKO and C3aR1-KpKO mice have similar body weight gain without significant alterations in glucose homeostasis, hepatic steatosis and fibrosis, compared to controls on a MASLD-inducing diet. This study demonstrates that C3aR1 deletion in macrophages or Kupffer cells, the predominant liver cell type expressing C3ar1 , has no significant effect on liver steatosis, inflammation or fibrosis in a dietary MASLD model.

We present a 1:25,000 scale map of the coseismic surface ruptures following the 30 October 2016 M w 6.5 Norcia normal-faulting earthquake, central Italy. Detailed rupture mapping is based on almost 11,000 oblique photographs taken from helicopter flights, that has been verified and integrated with field data (>7000 measurements). Thanks to the common efforts of the Open EMERGEO Working Group (130 people, 25 research institutions and universities from Europe), we were able to document a complex surface faulting pattern with a dominant strike of N135°-160° (SW-dipping) and a subordinate strike of N320°-345° (NE-dipping) along about 28 km of the active Mt. Vettore-Mt. Bove fault system. Geometric and kinematic characteristics of the rupture were observed and recorded along closely spaced, parallel or subparallel, overlapping or step-like synthetic and antithetic fault splays of the activated fault systems, comprising a total surface rupture length of approximately 46 km when all ruptures were considered.

Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4·04 h (SE 0·65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2·14 h (0·66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference −1·91 h [95% CI −3·05 to −0·76]; p=0·0015). Mean on-time without troublesome dyskinesia increased by 4·11 h (SE 0·75) in the intestinal gel group and 2·24 h (0·76) in the immediate-release oral group (difference 1·86 [95% CI 0·56 to 3·17]; p=0·0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. AbbVie.

In 1996, the U.S. Environmental Protection Agency (USEPA) developed the Adult Lead Methodology (ALM) to provide an interim approach to assessing risks from non-residential exposures to lead. Because such exposures often involve occupational activities of adults, the ALM was directed at assessing soil-related lead risks to adults. Consistent with other approaches used in Superfund risk assessment, the ALM was designed to predict quasi-steady state blood lead concentrations (PbB) that might result from soil exposure. These predictions are converted to a risk estimate, expressed as the probability of exceeding a PbB level of concern. To examine the assumptions and variables in the ALM that have become available since 1996, a comparison was made of the attributes of seven alternative research models for which adequate documentation is available to understand and implement each approach. Several of these models have been used in regulatory decision-making; however, the USEPA has officially embraced none for general use. This analysis suggests that the ALM can continue to serve as a reasonable tool for assessing risks associated with non-residential exposures to soil. Under certain circumstances other models may be more applicable (i.e., for assessing acute or intensive exposures); however, the ALM is recommended for the majority of risk assessment applications.