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• Iron (Fe) from rice grains is an important source of dietary intake; however, the molecular mechanisms responsible for loading of Fe to the grains are poorly understood. • We functionally characterized a vacuolar iron transporter gene, OsVIT2 in terms of expression pattern, cellular localization, and mutant phenotypes. • OsVIT2 was expressed in the parenchyma cell bridges of nodes, in the mestome sheath of leaf sheath and aleurone of the caryopsis. Mutation of OsVIT2 resulted in decreased Fe distribution to the leaf sheath, nodes, and aleurone, but increased Fe to the leaf blade and grains. Furthermore, Fe was heavily deposited in the parenchyma cell bridges, mestome sheath and aleurone in the wild-type rice, but this accumulation was decreased in the knockout lines. Conversely, heavier deposition of Fe was observed in the embryo and endosperm of the grains of knockout lines compared with the wild-type rice, resulting in increased Fe accumulation in the polished rice without yield penalty. • These results indicate that OsVIT2 is involved in the distribution of Fe to the grains through sequestering Fe into vacuoles in mestome sheath, nodes, and aleurone layer and that knockout of this gene provides a potential way for Fe biofortification without yield penalty.

Background and Objectives: Malnutrition among older hospitalized adults with chronic heart failure (CHF) is associated with adverse clinical outcomes, yet reliable early risk stratification tools remain lacking. This study aimed to develop and validate a machine learning (ML) model for malnutrition risk stratification in this population. Methods and Study Design: Malnutrition among older hospitalized adults with chronic heart failure (CHF) is associated with adverse clinical outcomes, yet reliable early risk stratification tools remain lacking. This study aimed to develop and validate a machine learning (ML) model for malnutrition risk stratification in this population. Results: Malnutrition prevalence was 44.1% (348/790). In the internal testing, CatBoost (CAT) achieved superior performance with an AUC of 0.901 (95% confidence interval [CI]: 0.858-0.943), accuracy of 0.840, recall of 0.753, and the lowest Brier score of 0.113. This model demonstrated strong calibration, clinical utility, and the highest composite score (62/64). External validation confirmed CAT's generalizability (AUC: 0.916, 95% CI: 0.887-0.945). SHAP analysis identified body mass index (BMI), calf circumference, New York Heart Association (NYHA) classification, age, and diabetes as significant contributors to malnutrition risk. Conclusions: The CAT-based model effectively stratifies malnutrition risk in older hospitalized CHF patients, offering a tool for early intervention to improve outcomes. Further multicenter prospective studies are needed to validate its real-world applicability.

Essential metals, such as iron (Fe) and zinc (Zn), in grains are important sources for seed germination and nutritional requirements, but the molecular mechanisms underlying their loading into grains are poorly understood. Recently, nodes in rice (Oryza sativa) were reported to play an important role in the preferential distribution of mineral elements to the grains. In this study, we functionally characterized a rice gene highly expressed in nodes, OsVMT (VACUOLAR MUGINEIC ACID TRANSPORTER), belonging to a major facilitator superfamily. OsVMT is highly expressed in the parenchyma cell bridges of node I, where Fe and Zn are highly deposited. The expression of OsVMT was induced by Fe deficiency in the roots but not in the shoot basal region and uppermost node. OsVMT localized to the tonoplast and showed efflux transport activity for 2ʹ-deoxymugineic acid (DMA). At the vegetative stage, knockout of OsVMT resulted in decreased DMA but increased ferric Fe in the root cell sap. As a result, the concentration of DMA in the xylem sap increased but that of ferric Fe decreased in the xylem sap in the mutants. In the polished rice grain, the mutants accumulated 1.8- to 2.1-fold, 1.5- to 1.6-fold, and 1.4- to 1.5-fold higher Fe, Zn, and DMA, respectively, than the wild type. Taken together, our results indicate that OsVMT is involved in sequestering DMA into the vacuoles and that knockout of this gene enhances the accumulation of Fe and Zn in polished rice grains through DMA-increased solubilization of Fe and Zn deposited in the node.

Drug–target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug–drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user’s molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75–100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug–drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

Mineral elements required for plant growth and development must first be taken up by the roots from soil. Plants have developed an efficient uptake system for the radial transport of mineral elements from soil to central stele through the allocation of various transporters at different root cells. These transporters are regulated at transcriptional, translational and/or post-translational level to cope with the fluctuation of mineral elements in soil. In this insight, we describe an efficient uptake system for mineral elements formed by influx and efflux transporters, regulatory mechanisms and polarity of these transporters, and sensing and signal pathways, in response to spatial and temporal changes of mineral elements in soil. An understanding of the mineral element uptake system in different plant species, and its regulatory network, will contribute to high and safe crop production under varying environments.

Silicon (Si) alleviates cadmium (Cd) toxicity and accumulation in a number of plant species, but the exact molecular mechanisms responsible for this effect are still poorly understood. Here, we investigated the effect of Si on Cd toxicity and accumulation in rice (Oryza sativa) by using two mutants (lsi1 and lsi2) defective in Si uptake and their wild types (WTs). Root elongation was decreased with increasing external Cd concentrations in both WTs and mutants, but Si did not show an alleviative effect on Cd toxicity in all lines. By contrast, the Cd concentration in both the shoots and roots was decreased by Si in the WTs, but not in the mutants. Furthermore, Si supply resulted in a decreased Cd concentration in the root cell sap and xylem sap in the WTs, but not in the mutants. Pre-treatment with Si also decreased Cd accumulation in the WTs, but not in the mutants. Silicon slightly decreased Cd accumulation in the cell wall of the roots. The expression level of OsNramp5 and OsHMA2 was down-regulated by Si in the WTs, but not in the mutants. These results indicate that the Si-decreased Cd accumulation was caused by down-regulating transporter genes involved in Cd uptake and translocation in rice.

Rice is a major dietary source of the toxic metalloid arsenic. Reducing arsenic accumulation in rice grain is important for food safety. We generated transgenic rice overexpressing two aquaporin genes, OsNIP1;1 and OsNIP3;3, under the control of a maize ubiquitin promoter or the rice OsLsi1 promoter, and tested the effect on arsenite uptake and translocation. OsNIP1;1 and OsNIP3;3 were highly permeable to arsenite in Xenopus oocyte assays. Both transporters were localized at the plasma membrane. Knockout of either gene had little effect on arsenite uptake or translocation. Overexpression of OsNIP1;1 or OsNIP3;3 in rice did not affect arsenite uptake but decreased root-to-shoot translocation of arsenite and shoot arsenic concentration markedly. The overexpressed OsNIP1;1 and OsNIP3;3 proteins were localized in all root cells without polarity. Expression of OsNIP1;1 driven by the OsLsi1 promoter produced similar effects. When grown in two arsenic-contaminated paddy soils, overexpressing lines contained significantly lower arsenic concentration in rice grain than the wild-type without compromising plant growth or the accumulation of essential nutrients. Overexpression of OsNIP1;1 or OsNIP3;3 provides a route for arsenite to leak out of the stele, thus restricting arsenite loading into the xylem. This strategy is effective in reducing arsenic accumulation in rice grain.

High aluminum (Al) tolerance in rice (Oryza sativa) is controlled by a Cys2His2-type zinc finger transcription factor ART1 (Al resistance transcription factor 1). There are five close homologs of ART1 in the rice genome, but the role of these homologs is unknown. We functionally characterized one of the ART1 homologs, ART2, in terms of tissue and spatial expression, subcellular localization, transcriptional activation activity, and phenotypic analysis of the knockout lines. ART2 was localized to the nucleus and showed a transcriptional activation potential in yeast. ART2 was mainly expressed in the roots, but the expression level was much lower than that of ART1. The ART2 expression was rapidly induced by Al in the roots of the wild-type rice, but not in art1 mutant. Knockout of ART2 resulted in increased sensitivity to Al toxicity, but did not alter sensitivity to different pH values. Expression profile analysis by RNA-sequencing showed that ART2 was not involved in activation of genes regulated by ART1; however, four genes seems to be regulated by ART2, which are implicated in Al tolerance. These results indicate that ART1 and ART2 regulate different pathways leading to Al tolerance, and ATR2 plays a supplementary role in Al tolerance in rice.

Silicon (Si) is known to alleviate manganese (Mn) toxicity in a number of plant species; however, the mechanisms responsible for this effect are poorly understood. Here, we investigated the interaction between Si and Mn in rice (Oryza sativa) by using a mutant defective in Si uptake. Silicon alleviated Mn toxicity in the wild-type (WT) rice, but not in the mutant exposed to high Mn. The Mn concentration in the shoots was decreased, but that in the roots was increased by Si in the WT. In contrast, the Mn concentration in the roots and shoots was unaffected by Si in the mutant. Furthermore, Si supply resulted in an increased Mn in the root cell sap, decreased Mn in the xylem sap in the WT, but these effects of Si were not observed in the mutant. A short-term labelling experiment with 54Mn showed that the uptake of Mn was similar between plants with and without Si and between WT and the mutant. However, Si decreased root-to-shoot translocation of Mn in the WT, but not in the mutant. The expression of a Mn transporter gene for uptake, OsNramp5, was unaffected by a short exposure (<1 d) to Si, but down-regulated by relatively long-term exposure to Si in WT. In contrast, the expression of OsNramp5 was unaffected by Si in the mutant. These results indicated that Si-decreased Mn accumulation results from both Si-decreased root-to-shoot translocation of Mn, probably by the formation of Mn-Si complex in root cells, and uptake by down-regulating Mn transporter gene.

Cyrtodactylus species are the most diverse of the geckos and are widely distributed in Southeast Asia, including Thailand. However, their patterns of distribution, especially in northern and western parts of Thailand, remain unknown because few Cyrtodactylus species in these regions have been described. Thus, a data set of mitochondrial NADH dehydrogenase 2 ( ND2 ) gene and flanking tRNAs from Cyrtodactylus found in northern and western Thailand, including contiguous areas, was assembled to elucidate phylogenetic relationships and identify the distribution patterns of these geckos. The results showed four well-supported clades, a northwestern clade (A), a northern clade (B), a western clade (C), and a special clade characterized by specific morphological features (D). Clades A–C were grouped with strong support by the geography of their localities from northern Thailand (Mae Hong Son and Chiang Mai Provinces) along the Tenasserim mountain ranges to Phang-Nga Province, Thailand. Clade D is a distinct clade of Cyrtodactylus species characterized by a tuberculate and prehensile tail and distributed widely in mainland Southeast Asia. Overall, the results suggest a pattern of geographic separation and distribution of Cyrtodactylus in northern and western Thailand. Additionally, this study provides evidence of a hidden biodiversity of Cyrtodactylus in these regions.