Biosynthesized Selenium Nanoparticles as an Effective Tool to Combat Soil Metal Stresses in Rice (Oryza sativa L.).

Nanotechnology has demonstrated significant potential to improve agricultural production and increase crop tolerance to abiotic stress including exposure to heavy metals. The present study investigated the mechanisms by which aloe vera extract gel-biosynthesized (AVGE) selenium nanoparticles (Se NPs) alleviated cadmium (Cd)-induced toxicity to rice (Oryza sativa L.). AVGE Se NPs, chemically synthesized bare Se NPs, and NaSeO3 as an ionic control were applied to Cd-stressed rice seedlings via root exposure in both hydroponic and soil systems. Upon exposure to AVGE Se NPs at 15 mg Se/L, the fresh root biomass was significantly increased by 100.7% and 19.5% as compared to Cd control and conventional bare Se NPs. Transcriptional analyses highlighted that AVGE Se NPs activated stress signaling and defense related pathways, including glutathione metabolism, phenylpropanoid biosynthesis and plant hormone signal transduction. Specifically, exposure to AVGE Se NPs upregulated the expression of genes associated with the gibberellic acid (GA) biosynthesis by and 4.79- and 3.29-fold as compared to the Cd-alone treatment and the untreated control, respectively. Importantly, AVGE Se NPs restored the composition of the endophyte community and recruit of beneficial species under Cd exposure; the relative abundance of Azospirillum was significantly increased in roots, shoots, and the rhizosphere soil by 0.73-, 4.58- and 0.37-fold, respectively, relative to the Cd-alone treatment. Collectively, these findings highlight the significant potential of AVGE Se NPs to enhance plant growth and to minimize the Cd-induced toxicity in rice and provide a promising nanoenabled strategy to enhance food safety upon crop cultivation in contaminated agricultural soils.

Multiparametric MRI-based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

Nano-enabled strategies to promote safe crop production in heavy metal(loid)-contaminated soil.

Nanobiotechnology is a potentially safe and sustainable strategy for both agricultural production and soil remediation, yet the potential of nanomaterials (NMs) application to remediate heavy metal(loid)-contaminated soils is still unclear. A meta-analysis with approximately 6000 observations was conducted to quantify the effects of NMs on safe crop production in soils contaminated with heavy metal(loid) (HM), and a machine learning approach was used to identify the major contributing features. Applying NMs can elevate the crop shoot (18.2 %, 15.4-21.2 %) and grain biomass (30.7 %, 26.9-34.9 %), and decrease the shoot and grain HM concentration by 31.8 % (28.9-34.5 %) and 46.8 % (43.7-49.8 %), respectively. Iron-NMs showed a greater potential to inhibit crop HM uptake compared to other types of NMs. Our result further demonstrates that NMs application substantially reduces the potential health risk of HM in crop grains by human health risk assessment. The NMs-induced reduction in HM accumulation was associated with decreasing HM bioavailability, as well as increased soil pH and organic matter. A random forest model demonstrates that soil pH and total HM concentration are the two significant features affecting shoot HM accumulation. This analysis of the literature highlights the significant potential of NMs application in promoting safe agricultural production in HM-contaminated agricultural lands.

Towards realizing nano-enabled precision delivery in plants.

Nanocarriers (NCs) that can precisely deliver active agents, nutrients and genetic materials into plants will make crop agriculture more resilient to climate change and sustainable. As a research field, nano-agriculture is still developing, with significant scientific and societal barriers to overcome. In this Review, we argue that lessons can be learned from mammalian nanomedicine. In particular, it may be possible to enhance efficiency and efficacy by improving our understanding of how NC properties affect their interactions with plant surfaces and biomolecules, and their ability to carry and deliver cargo to specific locations. New tools are required to rapidly assess NC-plant interactions and to explore and verify the range of viable targeting approaches in plants. Elucidating these interactions can lead to the creation of computer-generated in silico models (digital twins) to predict the impact of different NC and plant properties, biological responses, and environmental conditions on the efficiency and efficacy of nanotechnology approaches. Finally, we highlight the need for nano-agriculture researchers and social scientists to converge in order to develop sustainable, safe and socially acceptable NCs.

Evidence for autotrophic growth of purple sulfur bacteria using pyrite as electron and sulfur source.

Purple sulfur bacteria (PSB) are capable of anoxygenic photosynthesis via oxidizing reduced sulfur compounds and are considered key drivers of the sulfur cycle in a range of anoxic environments. In this study, we show that Allochromatium vinosum (a PSB species) is capable of autotrophic growth using pyrite as the electron and sulfur source. Comparative growth profile, substrate characterization, and transcriptomic sequencing data provided valuable insight into the molecular mechanisms underlying the bacterial utilization of pyrite and autotrophic growth. Specifically, the pyrite-supported cell cultures ("py"') demonstrated robust but much slower growth rates and distinct patterns from their sodium sulfide-amended positive controls. Up to ~200-fold upregulation of genes encoding various c- and b-type cytochromes was observed in "py," pointing to the high relevance of these molecules in scavenging and relaying electrons from pyrite to cytoplasmic metabolisms. Conversely, extensive downregulation of genes related to LH and RC complex components indicates that the electron source may have direct control over the bacterial cells' photosynthetic activity. In terms of sulfur metabolism, genes encoding periplasmic or membrane-bound proteins (e.g., FccAB and SoxYZ) were largely upregulated, whereas those encoding cytoplasmic proteins (e.g., Dsr and Apr groups) are extensively suppressed. Other notable differentially expressed genes are related to flagella/fimbriae/pilin(+), metal efflux(+), ferrienterochelin(-), and [NiFe] hydrogenases(+). Characterization of the biologically reacted pyrite indicates the presence of polymeric sulfur. These results have, for the first time, put the interplay of PSB and transition metal sulfide chemistry under the spotlight, with the potential to advance multiple fields, including metal and sulfur biogeochemistry, bacterial extracellular electron transfer, and artificial photosynthesis. IMPORTANCE: Microbial utilization of solid-phase substrates constitutes a critical area of focus in environmental microbiology, offering valuable insights into microbial metabolic processes and adaptability. Recent advancements in this field have profoundly deepened our knowledge of microbial physiology pertinent to these scenarios and spurred innovations in biosynthesis and energy production. Furthermore, research into interactions between microbes and solid-phase substrates has directly linked microbial activities to the surrounding mineralogical environments, thereby enhancing our understanding of the relevant biogeochemical cycles. Our study represents a significant step forward in this field by demonstrating, for the first time, the autotrophic growth of purple sulfur bacteria using insoluble pyrite (FeS2) as both the electron and sulfur source. The presented comparative growth profiles, substrate characterizations, and transcriptomic sequencing data shed light on the relationships between electron donor types, photosynthetic reaction center activities, and potential extracellular electron transfer in these organisms capable of anoxygenic photosynthesis. Furthermore, the findings of our study may provide new insights into early-Earth biogeochemical evolutions, offering valuable constraints for understanding the environmental conditions and microbial processes that shaped our planet's history.

Exogenous selenium promotes cadmium reduction and selenium enrichment in rice: Evidence, mechanisms, and perspectives.

Cadmium (Cd) accumulation in rice, a global environmental issue, poses a significant threat to human health due to its widespread presence and potential transfer through the food chain. Selenium (Se), an essential micronutrient for humans and plants, can reduce Cd uptake in rice and alleviate Cd-induced toxicity. However, the effects and mechanisms of Se supplementation on rice performance in Cd-contaminated soil remain largely unknown. Here, a global meta-analysis was conducted to evaluate the existing knowledge on the effects and mechanisms by which Se supplementation impacts rice growth and Cd accumulation. The result showed that Se supplementation has a significant positive impact on rice growth in Cd-contaminated soil. Specifically, Se supplementation decreased Cd accumulation in rice roots by 16.3 % (11.8-20.6 %), shoots by 24.6 % (19.9-29.1 %), and grain by 37.3 % (33.4-40.9 %), respectively. The grain Cd reduction was associated with Se dose and soil Cd contamination level but not Se type or application method. Se influences Cd accumulation in rice by regulating the expression of Cd transporter genes (OSLCT1, OSHMA2, and OSHMA3), enhancing Cd sequestration in the cell walls, and reducing Cd bioavailability in the soil. Importantly, Se treatment promoted Se enrichment in rice and alleviated oxidative damage associated with Cd exposure by stimulating photosynthesis and activating antioxidant enzymes. Overall, Se treatment mitigated the health hazard associated with Cd in rice grains, particularly in lightly contaminated soil. These findings reveal that Se supplementation is a promising strategy for simultaneous Cd reduction and Se enrichment in rice.

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

Nano- and Microplastics Increase the Occurrence of Bacterial Wilt in Tomato (Solanum lycopersicum L.).

Concern over nano- and microplastic contamination of terrestrial ecosystems has been increasing. However, little is known about the effect of nano- and microplastics on the response of terrestrial ecosystems already under biotic stress. Here, nano- and microplastics at 150-500 mg·kg-1 were exposed to tomatoes (Solanum lycopersicum L.), and the results demonstrate that the presence of nano- and microplastics increased the occurrence of bacterial wilt caused by Ralstonia solanacearum in tomatoes as a function of contaminant concentration, surface modification, and size. Our work shows that nanoplastics (30 nm, 250 mg·kg-1) increased the disease incidence by 2.19-fold. The disease severities in amino- and carboxyl-modified nanoplastic treatments were 30.4 and 21.7% higher than that in unmodified nanoplastic treatment, respectively. The severity of disease under the influence of different-sized nano- and microplastic treatments followed the order 30 > 100 nm > 1 > 50 µm. Mechanistically, nanoplastics disrupted the structure of the tomato rhizosphere soil bacterial community and suppressed the induced systemic resistance in tomato; nanoplastics in planta decreased the salicylic acid and jasmonic acid content in tomatoes, thus inhibiting systemic acquired resistance; and microplastics increased the soil water retention, leading to increased pathogen abundance in the rhizosphere. Additionally, the leachates from nano- and microplastics had no effect on disease occurrence or the growth of tomatoes. Our findings highlight a potential risk of nano- and microplastic contamination to agriculture sustainability and food security.

The environmental risk threshold (HC5) for Cd remediation in Chinese agricultural soils.

Given the increasing concern over Cd contamination of agricultural soils in China, reducing the availability of the toxic metal has become an important remedial strategy. However, the lack of a unified evaluation framework complicates the assessment of remediation efficiency of different practices. Here, we evaluated the general extraction method (GEM) of available Cd in nine typical soil types by comparing extraction agents, including CaCl2, EDTA, Mehlich-Ⅲ, HCl and DTPA. The safe grain concentration of different agricultural products from National Food Safety Standards Limits of Contaminants in Food (GB 2762-2022) was then applied to understand soil limited available Cd concentration based on dose-response curves. We also derived environmental risk threshold (HC5) values for Cd remediation in agricultural soils by constructing species sensitivity distribution (SSD) curves. The results showed that Mehlich-Ⅲ best predicted Cd accumulation in crops (with 76.5% of explanation of grain Cd) and was selected as the GEM of soil available Cd for subsequent analyses. The regression coefficient (R2) of dose-response curves fitting between Cd absorption in crop tissues and soil available Cd extracted by GEM based on 30 different crop species varied from 51.0% to 79.5%, and the derived limit concentration of soil available Cd based on standard GB 2762-2022 was 0.18-0.76 mg‧kg-1. An HC5 of 0.19 mg‧kg-1 was then calculated, meaning that a concentration of available Cd in agricultural soil below 0.19 mg‧kg-1 ensures that 95% of agricultural products meet the quality and safety requirements of standard GB 2762-2022. The prediction model was well verified in the field test, indicating that can correctly estimate the soil available Cd based on the content of Cd in plant. This study provides a robust scientific framework for deriving the risk threshold for Cd remediation in agricultural soils and could be quite useful for establishing soil remediation standards.

Maize straw increases while its biochar decreases native organic carbon mineralization in a subtropical forest soil.

Organic soil amendments have been widely adopted to enhance soil organic carbon (SOC) stocks in agroforestry ecosystems. However, the contrasting impacts of pyrogenic and fresh organic matter on native SOC mineralization and the underlying mechanisms mediating those processes remain poorly understood. Here, an 80-day experiment was conducted to compare the effects of maize straw and its derived biochar on native SOC mineralization within a Moso bamboo (Phyllostachys edulis) forest soil. The quantity and quality of SOC, the expression of microbial functional genes concerning soil C cycling, and the activity of associated enzymes were determined. Maize straw enhanced while its biochar decreased the emissions of native SOC-derived CO2. The addition of maize straw (cf. control) enhanced the O-alkyl C proportion, activities of ß-glucosidase (BG), cellobiohydrolase (CBH) and dehydrogenase (DH), and abundances of GH48 and cbhI genes, while lowered aromatic C proportion, RubisCO enzyme activity, and cbbL abundance; the application of biochar induced the opposite effects. In all treatments, the cumulative native SOC-derived CO2 efflux increased with enhanced O-alkyl C proportion, activities of BG, CBH, and DH, and abundances of GH48 and cbhI genes, and with decreases in aromatic C, RubisCO enzyme activity and cbbL gene abundance. The enhanced emissions of native SOC-derived CO2 by the maize straw were associated with a higher O-alkyl C proportion, activities of BG and CBH, and abundance of GH48 and cbhI genes, as well as a lower aromatic C proportion and cbbL gene abundance, while biochar induced the opposite effects. We concluded that maize straw induced positive priming, while its biochar induced negative priming within a subtropical forest soil, due to the contrasting microbial responses resulted from changes in SOC speciation and compositions. Our findings highlight that biochar application is an effective approach for enhancing soil C stocks in subtropical forests.

Benfotiamine improves dystrophic pathology and exercise capacity in mdx mice by reducing inflammation and fibrosis.

Duchenne Muscular Dystrophy (DMD) is a progressive and fatal neuromuscular disease. Cycles of myofibre degeneration and regeneration are hallmarks of the disease where immune cells infiltrate to repair damaged skeletal muscle. Benfotiamine is a lipid soluble precursor to thiamine, shown clinically to reduce inflammation in diabetic related complications. We assessed whether benfotiamine administration could reduce inflammation related dystrophic pathology. Benfotiamine (10 mg/kg/day) was fed to male mdx mice (n = 7) for 15 weeks from 4 weeks of age. Treated mice had an increased growth weight (5-7 weeks) and myofibre size at treatment completion. Markers of dystrophic pathology (area of damaged necrotic tissue, central nuclei) were reduced in benfotiamine mdx quadriceps. Grip strength was increased and improved exercise capacity was found in mdx treated with benfotiamine for 12 weeks, before being placed into individual cages and allowed access to an exercise wheel for 3 weeks. Global gene expression profiling (RNAseq) in the gastrocnemius revealed benfotiamine regulated signalling pathways relevant to dystrophic pathology (Inflammatory Response, Myogenesis) and fibrotic gene markers (Col1a1, Col1a2, Col4a5, Col5a2, Col6a2, Col6a2, Col6a3, Lum) towards wildtype levels. In addition, we observed a reduction in gene expression of inflammatory gene markers in the quadriceps (Emr1, Cd163, Cd4, Cd8, Ifng). Overall, these data suggest that benfotiamine reduces dystrophic pathology by acting on inflammatory and fibrotic gene markers and signalling pathways. Given benfotiamine's excellent safety profile and current clinical use, it could be used in combination with glucocorticoids to treat DMD patients.

Sources and human health risks associated with potentially toxic elements (PTEs) in urban dust: A global perspective.

Long-term exposure to urban dust containing potentially toxic elements (PTEs) poses detrimental impacts on human health. However, studies estimating human health risks in urban dusts from a global perspective are scarce. We evaluated data for twelve PTEs in urban dusts across 59 countries from 463 published articles, including their concentrations, input sources, and probabilistic risks to human health. We found that 34.1 and 60.3% of those investigated urban dusts have been heavily contaminated with As and Cd, respectively. The input of PTEs was significantly correlated with economic structure due to emissions of industrial activities and traffic emissions being the major sources. Based on the Monte Carlo simulation, we found that the mean hazard index below the safe threshold (1.0) could still cause non-negligible risks to human health. Arsenic and Cr were the major PTEs threatening human health, and relatively high risk levels were observed in cities in China, Korea, Chile, Malaysia, and Australia. Importantly, our analysis suggested that PTEs threaten the health of approximately 92 million adults and 280 million children worldwide. Overall, our study provides important foundational understanding and guidance for policy decision-making to reduce the potential risks associated with PTE exposure and to promote sustainable development of urban economies.

Epigenetic Modulation of GPER Expression in Gastric and Colonic Smooth Muscle of Male and Female Non-Obese Diabetic (NOD) Mice: Insights into H3K4me3 and H3K27ac Modifications.

Type 1 diabetes (T1D) affects gastrointestinal (GI) motility, favoring gastroparesis, constipation, and fecal incontinence, which are more prevalent in women. The mechanisms are unknown. Given the G-protein-coupled estrogen receptor's (GPER) role in GI motility, we investigated sex-related diabetes-induced epigenetic changes in GPER. We assessed GPER mRNA and protein expression levels using qPCR and Western blot analyses, and quantified the changes in nuclear DNA methyltransferases and histone modifications (H3K4me3, H3Ac, and H3K27Ac) by ELISA kits. Targeted bisulfite and chromatin immunoprecipitation assays were used to evaluate DNA methylation and histone modifications around the GPER promoter by chromatin immunoprecipitation assays in gastric and colonic smooth muscle tissues of male and female control (CTR) and non-obese diabetic (NOD) mice. GPER expression was downregulated in NOD, with sex-dependent variations. In the gastric smooth muscle, not in colonic smooth muscle, downregulation coincided with differences in methylation ratios between regions 1 and 2 of the GPER promoter of NOD. DNA methylation was higher in NOD male colonic smooth muscle than in NOD females. H3K4me3 and H3ac enrichment decreased in NOD gastric smooth muscle. H3K4me3 levels diminished in the colonic smooth muscle of NOD. H3K27ac levels were unaffected, but enrichment decreased in NOD male gastric smooth muscle; however, it increased in the NOD male colonic smooth muscle and decreased in the female NOD colonic smooth muscle. Male NOD colonic smooth muscle exhibited decreased H3K27ac levels, not female, whereas female NOD colonic smooth muscle demonstrated diminished enrichment of H3ac at the GPER promoter, contrary to male NOD. Sex-specific epigenetic mechanisms contribute to T1D-mediated suppression of GPER expression in the GI tract. These insights advance our understanding of T1D complications and suggest promising avenues for targeted therapeutic interventions.

Interfacial Interactions between Nanoplastics and Biological Systems: toward an Atomic and Molecular Understanding of Plastics-Driven Biological Dyshomeostasis.

Micro- and nano-plastics (NPs) are found in human milk, blood, tissues, and organs and associate with aberrant health outcomes including inflammation, genotoxicity, developmental disorders, onset of chronic diseases, and autoimmune disorders. Yet, interfacial interactions between plastics and biomolecular systems remain underexplored. Here, we have examined experimentally, in vitro, in vivo, and by computation, the impact of polystyrene (PS) NPs on a host of biomolecular systems and assemblies. Our results reveal that PS NPs essentially abolished the helix-content of the milk protein ß-lactoglobulin (BLG) in a dose-dependent manner. Helix loss is corelated with the near stoichiometric formation of ß-sheet elements in the protein. Structural alterations in BLG are also likely responsible for the nanoparticle-dependent attrition in binding affinity and weaker on-rate constant of retinol, its physiological ligand (compromising its nutritional role). PS NP-driven helix-to-sheet conversion was also observed in the amyloid-forming trajectory of hen egg-white lysozyme (accelerated fibril formation and reduced helical content in fibrils). Caenorhabditis elegans exposed to PS NPs exhibited a decrease in the fluorescence of green fluorescent protein-tagged dopaminergic neurons and locomotory deficits (akin to the neurotoxin paraquat exposure). Finally, in silico analyses revealed that the most favorable PS/BLG docking score and binding energies corresponded to a pose near the hydrophobic ligand binding pocket (calyx) of the protein where the NP fragment was found to make nonpolar contacts with side-chain residues via the hydrophobic effect and van der Waals forces, compromising side chain/retinol contacts. Binding energetics indicate that PS/BLG interactions destabilize the binding of retinol to the protein and can potentially displace retinol from the calyx region of BLG, thereby impairing its biological function. Collectively, the experimental and high-resolution in silico data provide new insights into the mechanism(s) by which PS NPs corrupt the bimolecular structure and function, induce amyloidosis and onset neuronal injury, and drive aberrant physiological and behavioral outcomes.

Selenium Nanomaterials Enhance Sheath Blight Resistance and Nutritional Quality of Rice: Mechanisms of Action and Human Health Benefit.

In the current work, the foliar application of selenium nanomaterials (Se0 NMs) suppressed sheath blight in rice (Oryza sativa). The beneficial effects were nanoscale specific and concentration dependent. Specifically, foliar amendment of 5 mg/L Se0 NMs decreased the disease severity by 68.8% in Rhizoctonia solani-infected rice; this level of control was 1.57- and 2.20-fold greater than that of the Se ions with equivalent Se mass and a commercially available pesticide (Thifluzamide). Mechanistically, (1) the controlled release ability of Se0 NMs enabled a wider safe concentration range and greater bioavailability to Se0 NMs, and (2) transcriptomic and metabolomic analyses demonstrated that Se0 NMs simultaneously promoted the salicylic acid- and jasmonic-acid-dependent acquired disease resistance pathways, antioxidative system, and flavonoid biosynthesis. Additionally, Se0 NMs improved rice yield by 31.1%, increased the nutritional quality by 6.4-7.2%, enhanced organic Se content by 44.8%, and decreased arsenic and cadmium contents by 38.7 and 42.1%, respectively, in grains as compared with infected controls. Human simulated gastrointestinal tract model results showed that the application of Se0 NMs enhanced the bioaccessibility of Se in grains by 22.0% and decreased the bioaccessibility of As and Cd in grains by 20.3 and 13.4%, respectively. These findings demonstrate that Se0 NMs can serve as an effective and sustainable strategy to increase food quality and security.

Seven-years of alcohol consumption in Australia by wastewater analysis: Exploring patterns by remoteness and socioeconomic factors.

BACKGROUND: Wastewater analysis provides a complementary measure of alcohol use in whole communities. We assessed absolute differences and temporal trends in alcohol consumption by degree of remoteness and socioeconomics indicators in Australia from 2016 to 2023. METHODS: Alcohol consumption estimates from 50 wastewater treatment plants (WWTP) in the Australian National Wastewater Drug Monitoring Program were used. Trends were analysed based on 1) site remoteness: Major Cities, Inner Regional and a combined remoteness category of Outer Regional and Remote, and 2) using two socioeconomic indexes from the Australian Bureau of Statistics (ABS) relating to advantage and disadvantage for Income, education, occupation, and housing. RESULTS: Consumption estimates were similar for Major Cities and Inner Regional areas (14.3 and 14.4L/day/1000 people), but significantly higher in Outer Regional and Remote sites (18.6L/day/1000 people). Consumption was decreasing in Major cities by 4.5% annually, Inner Regional by 2.4%, and 3.5% in the combined Outer Regional and Remote category. Consumption estimates were higher in socioeconomically advantaged quartiles than those of lower advantage (0%-25% mean = 13.0, 75%-100% mean = 17.4). Consumption in all quartiles decreased significantly over the 7 year period with annual rates of decrease of 0.9%, 3.7%, 3.6%, and 3.0% for the lowest to highest quartile, respectively. CONCLUSIONS: Declines in Australian alcohol consumption have been steeper in large urban areas than regional and remote areas. There were smaller annual decreases in the most socioeconomically disadvantaged areas. If continued, these trends may increase Australian health inequalities. Policy and prevention work should be appropriately targeted to produce more equitable long-term outcomes.

Multiomic foundations of human prefrontal cortex tissue function.

The prefrontal cortex (PFC) is a region of the brain that in humans is involved in the production of higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission in the PFC produces higher-order functions by integrating information from other areas of the brain. At the foundation of neurotransmission, and by extension at the foundation of higher-order brain functions, are an untold number of coordinated molecular processes involving the DNA sequence variants in the genome, RNA transcripts in the transcriptome, and proteins in the proteome. These "multiomic" foundations are poorly understood in humans, perhaps in part because most modern studies that characterize the molecular state of the human PFC use tissue obtained when neurotransmission and higher-order brain functions have ceased (i.e., the postmortem state). Here, analyses are presented on data generated for the Living Brain Project (LBP) to investigate whether PFC tissue from individuals with intact higher-order brain function has characteristic multiomic foundations. Two complementary strategies were employed towards this end. The first strategy was to identify in PFC samples obtained from living study participants a signature of RNA transcript expression associated with neurotransmission measured intracranially at the time of PFC sampling, in some cases while participants performed a task engaging higher-order brain functions. The second strategy was to perform multiomic comparisons between PFC samples obtained from individuals with intact higher-order brain function at the time of sampling (i.e., living study participants) and PFC samples obtained in the postmortem state. RNA transcript expression within multiple PFC cell types was associated with fluctuations of dopaminergic, serotonergic, and/or noradrenergic neurotransmission in the substantia nigra measured while participants played a computer game that engaged higher-order brain functions. A subset of these associations - termed the "transcriptional program associated with neurotransmission" (TPAWN) - were reproduced in analyses of brain RNA transcript expression and intracranial neurotransmission data obtained from a second LBP cohort and from a cohort in an independent study. RNA transcripts involved in TPAWN were found to be (1) enriched for RNA transcripts associated with measures of neurotransmission in rodent and cell models, (2) enriched for RNA transcripts encoded by evolutionarily constrained genes, (3) depleted of RNA transcripts regulated by common DNA sequence variants, and (4) enriched for RNA transcripts implicated in higher-order brain functions by human population genetic studies. In PFC excitatory neurons of living study participants, higher expression of the genes in TPAWN tracked with higher expression of RNA transcripts that in rodent PFC samples are markers of a class of excitatory neurons that connect the PFC to deep brain structures. TPAWN was further reproduced by RNA transcript expression patterns differentiating living PFC samples from postmortem PFC samples, and significant differences between living and postmortem PFC samples were additionally observed with respect to (1) the expression of most primary RNA transcripts, mature RNA transcripts, and proteins, (2) the splicing of most primary RNA transcripts into mature RNA transcripts, (3) the patterns of co-expression between RNA transcripts and proteins, and (4) the effects of some DNA sequence variants on RNA transcript and protein expression. Taken together, this report highlights that studies of brain tissue obtained in a safe and ethical manner from large cohorts of living individuals can help advance understanding of the multiomic foundations of brain function.

Strategies for Enhancing Plant Immunity and Resilience Using Nanomaterials for Sustainable Agriculture.

Research on plant-nanomaterial interactions has greatly advanced over the past decade. One particularly fascinating discovery encompasses the immunomodulatory effects in plants. Due to the low doses needed and the comparatively low toxicity of many nanomaterials, nanoenabled immunomodulation is environmentally and economically promising for agriculture. It may reduce environmental costs associated with excessive use of chemical pesticides and fertilizers, which can lead to soil and water pollution. Furthermore, nanoenabled strategies can enhance plant resilience against various biotic and abiotic stresses, contributing to the sustainability of agricultural ecosystems and the reduction of crop losses due to environmental factors. While nanoparticle immunomodulatory effects are relatively well-known in animals, they are still to be understood in plants. Here, we provide our perspective on the general components of the plant's immune system, including the signaling pathways, networks, and molecules of relevance for plant nanomodulation. We discuss the recent scientific progress in nanoenabled immunomodulation and nanopriming and lay out key avenues to use plant immunomodulation for agriculture. Reactive oxygen species (ROS), the mitogen-activated protein kinase (MAPK) cascade, and the calcium-dependent protein kinase (CDPK or CPK) pathway are of particular interest due to their interconnected function and significance in the response to biotic and abiotic stress. Additionally, we underscore that understanding the plant hormone salicylic acid is vital for nanoenabled applications to induce systemic acquired resistance. It is suggested that a multidisciplinary approach, incorporating environmental impact assessments and focusing on scalability, can expedite the realization of enhanced crop yields through nanotechnology while fostering a healthier environment.

Targeting neddylation and sumoylation in chemoresistant triple negative breast cancer.

Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC.

Co-exposure to tire wear particles and nickel inhibits mung bean yield by reducing nutrient uptake.

Soil and terrestrial contamination with microplastics and nanoplastics has been discussed extensively, while tire wear particles (TWPs) have been largely overlooked. We investigated the root-surface interactions and growth response of mung bean (Vigna radiata L.) plants exposed to tire wear particles (TWPs) (0.05, 0.1, and 0.25% w/w) and nickel sulfate (50 and 100 mg kg-1 NiSO4) alone and in co-exposure scenarios for the full life cycle (105 days) under soil conditions. The results show that TWPs adhered to the root surface and reduced the water and nutrient uptake by the plant, particularly at higher concentrations of TWPs (0.25% w/w), without any observed organic contaminant accumulation in the root tissue. TWPs alone at 0.01, 0.1, and 0.25% (w/w) decreased mung bean yield by 11, 28, and 52%, respectively. Co-exposure to TWPs at 0.01, 0.1 and 0.25% w/w with 100 mg kg-1 NiSO4 decreased yield by 73, 79 and 88%, respectively. However, co-exposure to TWPs at 0.01 and 0.1% w/w with 50 mg kg-1 NiSO4 enhanced the yield by 32% and 7%, respectively. These changes in yield and nutritional aspects appear to be linked to Ni's regulatory influence on mineral homeostasis. Moreover, exposure to NiSO4 at 100 mg kg-1 increased Ni uptake in the root, shoot, and grain by 9, 26, and 20-fold, respectively as compared to the unamended control; this corresponded to increased antioxidant enzyme activity (10-127%) as compared to the control. TWPs caused blockages, significantly reducing plant yield and altering nutrient dynamics, highlighting emerging risks to plant health.