Root-exuded specialized metabolites reduce arsenic toxicity in maize.

By releasing specialized metabolites, plants modify their environment. Whether and how specialized metabolites protect plants against toxic levels of trace elements is not well understood. We evaluated whether benzoxazinoids, which are released into the soil by major cereals, can confer protection against arsenic toxicity. Benzoxazinoid-producing maize plants performed better in arsenic-contaminated soils than benzoxazinoid-deficient mutants in the greenhouse and the field. Adding benzoxazinoids to the soil restored the protective effect, and the effect persisted to the next crop generation via positive plant-soil feedback. Arsenate levels in the soil and total arsenic levels in the roots were lower in the presence of benzoxazinoids. Thus, the protective effect of benzoxazinoids is likely soil-mediated and includes changes in soil arsenic speciation and root accumulation. We conclude that exuded specialized metabolites can enhance protection against toxic trace elements via soil-mediated processes and may thereby stabilize crop productivity in polluted agroecosystems.

Memory effects of prior subculture may impact the quality of multiomic perturbation profiles.

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms.

The Duality of Arsenic Metabolism: Impact on Human Health.

Arsenic is a naturally occurring hazardous element that is environmentally ubiquitous in various chemical forms. Upon exposure, the human body initiates an elimination pathway of progressive methylation into relatively less bioreactive and more easily excretable pentavalent methylated forms. Given its association with decreasing the internal burden of arsenic with ensuing attenuation of its related toxicities, biomethylation has been applauded for decades as a pure route of arsenic detoxification. However, the emergence of detectable trivalent species with profound toxicity has opened a long-standing debate regarding whether arsenic methylation is a detoxifying or bioactivating mechanism. In this review, we approach the topic of arsenic metabolism from both perspectives to create a complete picture of its potential role in the mitigation or aggravation of various arsenic-related pathologies.

ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules.

Stress granules (SGs) are cytoplasmic assemblies of mRNPs stalled in translation initiation. They are induced by various stress conditions, including exposure to the environmental toxin and carcinogen arsenic. While perturbed SG turnover is linked to the pathogenesis of neurodegenerative diseases, the molecular mechanisms underlying SG formation and turnover are still poorly understood. Here, we show that ZFAND1 is an evolutionarily conserved regulator of SG clearance. ZFAND1 interacts with two key factors of protein degradation, the 26S proteasome and the ubiquitin-selective segregase p97, and recruits them to arsenite-induced SGs. In the absence of ZFAND1, SGs lack the 26S proteasome and p97, accumulate defective ribosomal products, and persist after arsenite removal, indicating their transformation into aberrant, disease-linked SGs. Accordingly, ZFAND1 depletion is epistatic to the expression of pathogenic mutant p97 with respect to SG clearance, suggesting that ZFAND1 function is relevant to the multisystem degenerative disorder IBMPFD/ALS.

Potassium jarosite seeding of soils decreases lead and arsenic bioaccessibility: A path toward concomitant remediation.

Soils are common sources of metal(loid) contaminant exposure globally. Lead (Pb) and arsenic (As) are of paramount concern due to detrimental neurological and carcinogenic health effects, respectively. Pb and/or As contaminated soils require remediation, typically leading to excavation, a costly and environmentally damaging practice of removing soil to a central location (e.g., hazardous landfill) that may not be a viable option in low-income countries. Chemical remediation techniques may allow for in situ conversion of soil contaminants to phases that are not easily mobilized upon ingestion; however, effective chemical remediation options are limited. Here, we have successfully tested a soil remediation technology using potted soils that relies on converting soil Pb and As into jarosite-group minerals, such as plumbojarosite (PLJ) and beudantite, possessing exceptionally low bioaccessibility [i.e., solubility at gastric pH conditions (pH 1.5 to 3)]. Across all experiments conducted, all new treatment methods successfully promoted PLJ and/or beudantite conversion, resulting in a proportional decrease in Pb and As bioaccessibility. Increasing temperature resulted in increased conversion to jarosite-group minerals, but addition of potassium (K) jarosite was most critical to Pb and As bioaccessibility decreases. Our methods of K-jarosite treatment yielded <10% Pb and As bioaccessibility compared to unamended soil values of approximately 70% and 60%, respectively. The proposed treatment is a rare dual remediation option that effectively treats soil Pb and As such that potential exposure is considerably reduced. Research presented here lays the foundation for ongoing field application.

OsbHLH6, a basic helix-loop-helix transcription factor, confers arsenic tolerance and root-to-shoot translocation in rice.

Arsenic (As) is extremely toxic to plants, posing a serious concern for food safety. Identification of genes responsive to As is significative for figuring out this issue. Here, we identified a bHLH transcription factor OsbHLH6 that was involved in mediating the processes of As tolerance, uptake, and root-to-shoot translocation in rice. The expression of OsbHLH6 gene was strongly induced after 3 and 48 h of arsenite [As(III)] treatment. The OsbHLH6-overexpressed transgenic rice (OE-OsbHLH6) was sensitive to, while the knockout mutant of OsbHLH6 gene (Osbhlh6) was tolerant to As(III) stress by affecting the contents of reactive oxygen species (ROS) and non-protein thiols (NPT), etc. Knockout of OsbHLH6 gene increased significantly the As concentration in roots, but decreased extensively As accumulation in shoots, compared to that in OE-OsbHLH6 and WT plants. The transcripts of phytochelatins (PCs) synthetase encoding genes OsPCS1 and OsPCS2, as well as As(III) transporter encoding genes OsLsi1 and OsABCC1 were greatly abundant in Osbhlh6 mutants than in OE-OsbHLH6 and WT plants under As(III) stress. In contrast, the expression of OsLsi2 gene was extensively suppressed by As(III) in Osbhlh6 mutants. OsbHLH6 acted as a transcriptional activator to bind directly to the promoter and regulate the expression of OsPrx2 gene that encodes a peroxidase precursor. Moreover, overexpression of OsbHLH6 gene resulted in significant change of expression of amounts of abiotic stress-related genes, which might partially contribute to the As sensitivity of OE-OsbHLH6 plants. These findings may broaden our understanding of the molecular mechanism of OsbHLH6-mediated As response in rice and provide novel useful genes for rice As stress-resistant breeding.

Arsenate reductase of Rufibacter tibetensis is a metallophosphoesterase evolved to catalyze redox reactions.

An arsenate reductase (Car1) from the Bacteroidetes species Rufibacter tibetensis 1351T was isolated from the Tibetan Plateau. The strain exhibits resistance to arsenite [As(III)] and arsenate [As(V)] and reduces As(V) to As(III). Here we shed light on the mechanism of enzymatic reduction by Car1. AlphaFold2 structure prediction, active site energy minimization, and steady-state kinetics of wild-type and mutant enzymes give insight into the catalytic mechanism. Car1 is structurally related to calcineurin-like metallophosphoesterases (MPPs). It functions as a binuclear metal hydrolase with limited phosphatase activity, particularly relying on the divalent metal Ni2+. As an As(V) reductase, it displays metal promiscuity and is coupled to the thioredoxin redox cycle, requiring the participation of two cysteine residues, Cys74 and Cys76. These findings suggest that Car1 evolved from a common ancestor of extant phosphatases by incorporating a redox function into an existing MPP catalytic site. Its proposed mechanism of arsenate reduction involves Cys74 initiating a nucleophilic attack on arsenate, leading to the formation of a covalent intermediate. Next, a nucleophilic attack of Cys76 leads to the release of As(III) and the formation of a surface-exposed Cys74-Cys76 disulfide, ready for reduction by thioredoxin.

Arsenite oxidase in complex with antimonite and arsenite oxyanions: Insights into the catalytic mechanism.

Arsenic contamination of groundwater is among one of the biggest health threats affecting millions of people in the world. There is an urgent need for efficient arsenic biosensors where the use of arsenic metabolizing enzymes can be explored. In this work, we have solved four crystal structures of arsenite oxidase (Aio) in complex with arsenic and antimony oxyanions and the structures determined correspond to intermediate states of the enzymatic mechanism. These structural data were complemented with density-functional theory calculations providing a unique view of the molybdenum active site at different time points that, together with mutagenesis data, enabled to clarify the enzymatic mechanism and the molecular determinants for the oxidation of As(III) to the less toxic As(V) species.

Oral arsenic administration to humanizedUDP-glucuronosyltransferase1 neonatal mice induces UGT1A1 through a dependence on Nrf2 and PXR.

Inorganic arsenic (iAs) is an environmental toxicant that can lead to severe health consequences, which can be exacerbated if exposure occurs early in development. Here, we evaluated the impact of oral iAs treatment on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) mice. We found that oral administration of iAs to neonatal hUGT1 mice that display severe neonatal hyperbilirubinemia leads to induction of intestinal UGT1A1 and a reduction in total serum bilirubin values. Oral iAs administration accelerates neonatal intestinal maturation, an event that is directly associated with UGT1A1 induction. As a reactive oxygen species producer, oral iAs treatment activated the Keap-Nrf2 pathway in the intestinal tract and liver. When Nrf2-deficient hUGT1 mice (hUGT1/Nrf2-/-) were treated with iAs, it was shown that activated Nrf2 contributed significantly toward intestinal maturation and UGT1A1 induction. However, hepatic UGT1A1 was not induced upon iAs exposure. We previously demonstrated that the nuclear receptor PXR represses liver UGT1A1 in neonatal hUGT1 mice. When PXR was deleted in hUGT1 mice (hUGT1/Pxr-/-), derepression of UGT1A1 was evident in both liver and intestinal tissue in neonates. Furthermore, when neonatal hUGT1/Pxr-/- mice were treated with iAs, UGT1A1 was superinduced in both tissues, confirming PXR release derepressed key regulatory elements on the gene that could be activated by iAs exposure. With iAs capable of generating reactive oxygen species in both liver and intestinal tissue, we conclude that PXR deficiency in neonatal hUGT1/Pxr-/- mice allows greater access of activated transcriptional modifiers such as Nrf2 leading to superinduction of UGT1A1.

Iron reprogrammes the root system architecture by regulating OsWRKY71 in arsenic-stressed rice (Oryza sativa L.).

Iron (Fe) has been critically reported to act as a signal that can be interpreted to activate the molecular mechanisms involved in root developmental processes. Arsenic (As) is a well-known metalloid that restricts the growth and productivity of rice plants by altering their root architecture. Since root system architecture (RSA) under As stress targets WRKY transcription factors (TFs) and their interaction partners, the current investigation was carried out to better understand the Fe-dependent dynamics of RSA and its participation in this process. Here, we analyzed the effects of As and Fe (alone or in combination) exposed to hydroponically grown rice roots of 12-day-old plants. Our research showed that adding As to Fe changed how OsWRKY71 was expressed and improved the morphology and anatomy of the rice roots in Ratna and Lalat varieties. As + Fe treatment also manifested the biochemical parameters. OsWRKY71, revealed an up-regulation (Fe alone and As + Fe conditions) and down-regulation (As stress) in both varieties, in comparison to the controls. The improved root anatomy and root oxidizability indicated the enhanced capability of Lalat over the Ratna variety to induce OsWRKY71 for the better development of RSA during As + Fe treatment. Further, OsWRKY71 has revealed the presence of gibberellin-responsive cis-regulatory elements (GAREs) in its promoter region, indicating the involvement of OsWRKY71 in the gibberellin pathway. Molecular docking revealed that OsWRKY71 and SLR1 (DELLA protein) interact positively, which supports the hypothesis that Fe alters RSA by regulating OsWRKY71 through the gibberellin pathway in As-stressed rice.

Arsenic: A Global Environmental Challenge.

Arsenic is a naturally occurring metalloid and one of the few metals that can be metabolized inside the human body. The pervasive presence of arsenic in nature and anthropogenic sources from agricultural and medical use have perpetuated human exposure to this toxic and carcinogenic element. Highly exposed individuals are susceptible to various illnesses, including skin disorders; cognitive impairment; and cancers of the lung, liver, and kidneys. In fact, across the globe, approximately 200 million people are exposed to potentially toxic levels of arsenic, which has prompted substantial research and mitigation efforts to combat this extensive public health issue. This review provides an up-to-date look at arsenic-related challenges facing the global community, including current sources of arsenic, global disease burden, arsenic resistance, and shortcomings of ongoing mitigation measures, and discusses potential next steps.

Hybrid-genome sequence analysis of Enterobacter cloacae FACU and morphological characterization: insights into a highly arsenic-resistant strain.

Many organisms have adapted to survive in environments with high levels of arsenic (As), a naturally occurring metalloid with various oxidation states and a common element in human activities. These organisms employ diverse mechanisms to resist the harmful effects of arsenic compounds. Ten arsenic-resistant bacteria were isolated from contaminated wastewater in this study. The most efficient bacterial isolate able to resist 15,000 ppm Na2HAsO4·7H2O was identified using the 16S rRNA gene and whole genome analysis as Enterobacter cloacae FACU. The arsenic E. cloacae FACU biosorption capability was analyzed. To further unravel the genetic determinants of As stress resistance, the whole genome sequence of E. cloacae FACU was performed. The FACU complete genome sequence consists of one chromosome (5.7 Mb) and two plasmids, pENCL 1 and pENCL 2 (755,058 and 1155666 bp, respectively). 7152 CDSs were identified in the E. cloacae FACU genome. The genome consists of 130 genes for tRNA and 21 for rRNAs. The average G + C content was found to be 54%. Sequencing analysis annotated 58 genes related to resistance to many heavy metals, including 16 genes involved in arsenic efflux transporter and arsenic reduction (five arsRDABC genes) and 42 genes related to lead, zinc, mercury, nickel, silver, copper, cadmium and chromium in FACU. Scanning electron microscopy (SEM) confirmed the difference between the morphological responses of the As-treated FACU compared to the control strain. The study highlights the genes involved in the mechanism of As stress resistance, metabolic pathways, and potential activity of E. cloacae FACU at the genetic level.

Leucocytosis during all-trans retinoic acid and arsenic trioxide treatment in acute promyelocytic leukaemia.

In patients with acute promyelocytic leukaemia (APL), differentiation syndrome (DS) is a life-threatening complication caused by the differentiating effect of all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). Leucocytosis is frequently observed during induction therapy for APL and is intimately associated with the development of DS and its severity. The management of DS is particularly important due to the high likelihood of excellent outcomes for APL patients who successfully complete induction therapy. Commentary on: Cicconi et al. Leukocytosis during induction therapy with all-trans-retinoic acid and arsenic trioxide in acute promyelocytic leukemia predicts for differentiation syndrome and treatment-related complications. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19759.

Pseudochrobactrum asaccharolyticum mitigates arsenic induced oxidative stress of maize plant by enhancing water status and antioxidant defense system.

BACKGROUND: Oxidative stress mediated by reactive oxygen species (ROS) is a common denominator in arsenic toxicity. Arsenic stress in soil affects the water absorption, decrease stomatal conductance, reduction in osmotic, and leaf water potential, which restrict water uptake and osmotic stress in plants. Arsenic-induced osmotic stress triggers the overproduction of ROS, which causes a number of germination, physiological, biochemical, and antioxidant alterations. Antioxidants with potential to reduce ROS levels ameliorate the arsenic-induced lesions. Plant growth promoting rhizobacteria (PGPR) increase the total soluble sugars and proline, which scavenging OH radicals thereby prevent the oxidative damages cause by ROS. The main objective of this study was to evaluate the potential role of Arsenic resistant PGPR in growth of maize by mitigating arsenic stress. METHODOLOGY: Arsenic tolerant PGPR strain MD3 (Pseudochrobactrum asaccharolyticum) was used to dismiss the 'As' induced oxidative stress in maize grown at concentrations of 50 and 100 mg/kg. Previously isolated arsenic tolerant bacterial strain MD3 "Pseudochrobactrum asaccharolyticum was used for this experiment. Further, growth promoting potential of MD3 was done by germination and physio-biochemical analysis of maize seeds. Experimental units were arranged in Completely Randomized Design (CRD). A total of 6 sets of treatments viz., control, arsenic treated (50 & 100 mg/kg), bacterial inoculated (MD3), and arsenic stress plus bacterial inoculated with three replicates were used for Petri plates and pot experiments. After treating with this MD3 strain, seeds of corn were grown in pots filled with or without 50 mg/kg and 100 mg/kg sodium arsenate. RESULTS: The plants under arsenic stress (100 mg/kg) decreased the osmotic potential (0.8 MPa) as compared to control indicated the osmotic stress, which caused the reduction in growth, physiological parameters, proline accumulation, alteration in antioxidant enzymes (Superoxide dismutase-SOD, catalase-CAT, peroxidase-POD), increased MDA content, and H2O2 in maize plants. As-tolerant Pseudochrobactrum asaccharolyticum improved the plant growth by reducing the oxidation stress and antioxidant enzymes by proline accumulation. PCA analysis revealed that all six treatments scattered differently across the PC1 and PC2, having 85.51% and 9.72% data variance, respectively. This indicating the efficiency of As-tolerant strains. The heatmap supported the As-tolerant strains were positively correlated with growth parameters and physiological activities of the maize plants. CONCLUSION: This study concluded that Pseudochrobactrum asaccharolyticum reduced the 'As' toxicity in maize plant through the augmentation of the antioxidant defense system. Thus, MD3 (Pseudochrobactrum asaccharolyticum) strain can be considered as bio-fertilizer.

Application of CuNPs and AMF alleviates arsenic stress by encompassing reduced arsenic uptake through metabolomics and ionomics alterations in Elymus sibiricus.

Recent studies have exhibited a very promising role of copper nanoparticles (CuNPs) in mitigation of abiotic stresses in plants. Arbuscular mycorrhizae fungi (AMF) assisted plants to trigger their defense mechanism against abiotic stresses. Arsenic (As) is a non-essential and injurious heavy-metal contaminant. Current research work was designed to elucidate role of CuNPs (100, 200 and 300 mM) and a commercial inoculum of Glomus species (Clonex® Root Maximizer) either alone or in combination (CuNPs + Clonex) on physiology, growth, and stress alleviation mechanisms of E. sibiricus growing in As spiked soils (0, 50, and 100 mg Kg- 1 soil). Arsenic induced oxidative stress, enhanced biosynthesis of hydrogen peroxide, lipid peroxidation and methylglyoxal (MG) in E. sibiricus. Moreover, As-phytotoxicity reduced photosynthetic activities and growth of plants. Results showed that individual and combined treatments, CuNPs (100 mM) as well as soil inoculation of AMF significantly enhanced root growth and shoot growth by declining As content in root tissues and shoot tissues in As polluted soils. E. sibiricus plants treated with CuNPs (100 mM) and/or AMF alleviated As induced phytotoxicity through upregulating the activity of antioxidative enzymes such as catalase (CAT) and superoxide dismutase (SOD) besides the biosynthesis of non-enzymatic antioxidants including phytochelatin (PC) and glutathione (GSH). In brief, supplementation of CuNPs (100 mM) alone or in combination with AMF reduced As uptake and alleviated the As-phytotoxicity in E. sibiricus by inducing stress tolerance mechanism resulting in the improvement of the plant growth parameters.

Optimizing biochar, vermicompost, and duckweed amendments to mitigate arsenic uptake and accumulation in rice (Oryza sativa L.) cultivated on arsenic-contaminated soil.

The accumulation of arsenic (As) in rice (Oryza sativa L.) grain poses a significant health concern in Bangladesh. To address this, we investigated the efficacy of various organic amendments and phytoremediation techniques in reducing As buildup in O. sativa. We evaluated the impact of five doses of biochar (BC; BC0.1: 0.1%, BC0.28: 0.28%, BC0.55: 0.55%, BC0.82: 0.82% and BC1.0: 1.0%, w/w), vermicompost (VC; VC1.0: 1.0%, VC1.8: 1.8%, VC3.0: 3.0%, VC4.2: 4.2% and VC5.0: 5.0%, w/w), and floating duckweed (DW; DW100: 100, DW160: 160, DW250: 250, DW340: 340 and DW400: 400 g m- 2) on O. sativa cultivated in As-contaminated soil. Employing a three-factor five-level central composite design and response surface methodology (RSM), we optimized the application rates of BC-VC-DW. Our findings revealed that As contamination in the soil negatively impacted O. sativa growth. However, the addition of BC, VC, and DW significantly enhanced plant morphological parameters, SPAD value, and grain yield per pot. Notably, a combination of moderate BC-DW and high VC (BC0.55VC5DW250) increased grain yield by 44.4% compared to the control (BC0VC0DW0). As contamination increased root, straw, and grain As levels, and oxidative stress in O. sativa leaves. However, treatment BC0.82VC4.2DW340 significantly reduced grain As (G-As) by 56%, leaf hydrogen peroxide by 71%, and malondialdehyde by 50% compared to the control. Lower doses of BC-VC-DW (BC0.28VC1.8DW160) increased antioxidant enzyme activities, while moderate to high doses resulted in a decline in these activities. Bioconcentration and translocation factors below 1 indicated limited As uptake and translocation in plant tissues. Through RSM optimization, we determined that optimal doses of BC (0.76%), VC (4.62%), and DW (290.0 g m- 2) could maximize grain yield (32.96 g pot- 1, 44% higher than control) and minimize G-As content (0.189 mg kg- 1, 54% lower than control). These findings underscore effective strategies for enhancing yield and reducing As accumulation in grains from contaminated areas, thereby ensuring agricultural productivity, human health, and long-term sustainability. Overall, our study contributes to safer food production and improved public health in As-affected regions.

As(III)-oxidizing and plant growth-promoting bacteria increase the starch biosynthesis-related enzyme activity, 2-AP levels, and grain quality of arsenic-stressed rice plants.

BACKGROUND: Grain quality is an important index of rice production, particularly when plants are grown under stress. Arsenic (As) contamination in paddy fields severely affects rice grain yield and quality. Here, the effects of As and combinations of As(III)-oxidizing bacteria (Pseudomonas stutzeri 4.25, 4.27, and 4.44) and plant growth-promoting bacteria (Delftia acidovorans KKU2500-12 and Cupriavidus taiwanensis KKU2500-3) on enzymes related to starch accumulation in grains and the grain quality of Khao Dawk Mali 105 rice cultivated in As-contaminated soil under greenhouse conditions were investigated. RESULTS: Arsenic affected the activities of starch biosynthesis-related enzymes, and decreases of up to 76.27%, 71.53%, 49.74%, 73.39%, and 47.46% in AGPase, SSS, GBSS, SBE, and SDBE activities, respectively, and 9.42-61.07% in starch accumulation in grains were detected after growth in As-contaminated soil. However, the KKU2500-3/4.25 and KKU2500-3/4.44 combinations yielded the greatest enzyme activities in grains, and compared with the results observed in uninoculated seedlings, increases in starch accumulation of up to 51.16% and 23.81% were found in the inoculated seedlings after growth in medium- and high-As-contaminated soils, at 10-17 and 10-24 days after anthesis, respectively. The bacteria increased the 2-AP content in rice under As stress, possibly via the induction of proline, a 2-AP substrate. Bacterium-inoculated rice had significantly greater 2-AP levels than uninoculated rice, and 2.16-9.93% and 26.57-42.04% increases were detected in rice plants grown in medium- and high-As-contaminated soils, respectively. CONCLUSIONS: Arsenic toxicity can be mitigated in rice growing under greenhouse conditions by maintaining starch biosynthesis, accumulating amylose, and increasing 2-AP content. The effectiveness of these bacteria should be validated in paddy fields; hence, safe rice grains with a good starch content and aroma could be produced.

Synergistic Gas Therapy and Targeted Interventional Ablation With Size-Controllable Arsenic Sulfide (As2S3) Nanoparticles for Effective Elimination of Localized Cancer Pain.

The elimination of localized cancer pain remains a globally neglected challenge. A potential solution lies in combining gas therapy with targeted interventional ablation therapy. In this study, HA-As2S3 nanoparticles with controlled sizes are synthesized using different molecular weights of sodium hyaluronate (HA) as a supramolecular scaffold. Initially, HA co-assembles with arsenic ions (As3+) via coordinate bonds, forming HA-As3+ scaffold intermediates. These intermediates, varying in size, then react with sulfur ions to produce size-controlled HA-As2S3 particles. This approach demonstrates that different molecular weights of HA enable precise control over the particle size of arsenic sulfide, offering a straightforward and environmentally friendly method for synthesizing metal sulfide particles. In an acidic environment, HA-As2S3 nanoparticles release hydrogen sulfide(H2S) gas and As3+. The released As3+ directly damage tumor mitochondria, leading to substantial reactive oxygen species (ROS) production from mitochondria. Concurrently, the H2S gas inhibits the activity of catalase (CAT) and complex IV, preventing the beneficial decomposition of ROS and disrupting electron transfer in the mitochondrial respiratory chain. Consequently, it is found that H2S gas significantly enhances the mitochondrial damage induced by arsenic nanodrugs, effectively killing local tumors and ultimately eliminating cancer pain in mice.

Carbon Dots-Embedded Silica Tubes: An Excitation-Independent Yellow-Emitting Turn-On Probe for Simultaneous Detection and Removal of Inorganic Arsenic with In Vivo Tracking in Living Organisms.

The environmental monitoring and remediation of highly toxic inorganic arsenic species in natural water are needed for the benefit of the ecosystem. Current studies on arsenic detection and removal often employ separate materials, which exhibit blue luminescence with fluorescence quenching, making them unsuitable for biological and environmental samples. In this study, carbon dot-embedded mesoporous silica tubes functionalized with melamine are synthesized to address these limitations and enable specific and turn-on probing of inorganic arsenic. The newly synthesized material demonstrates excitation-independent yellow luminescence and can effectively detect both As (III) and As (V) at low detection limits (11 × 10-9 m, 11.2 × 10-9 m), well below the prescribed threshold limits in drinking water. It also exhibits a high adsorption capacity (≈125, 159 mg g-1 ) with fast kinetics. The material's applicability in environmental samples is validated through the successful quantification of arsenic in real samples with satisfactory recoveries. Moreover, the material shows recyclability for reuse, as demonstrated by its arsenic adsorption and desorption for several cycles under basic conditions. Additionally, the material's capability for monitoring arsenic in a biological sample (Artemia salina) is demonstrated through fluorescence imaging. The encouraging outcomes underscore the material's potential use in monitoring and mitigating arsenic in aqueous systems.

Synergistic rescue of temperature-sensitive p53 mutants by hypothermia and arsenic trioxide.

The p53 tumor suppressor is inactivated by mutations in about 50% of tumors. Rescuing the transcriptional function of mutant p53 has potential therapeutic benefits. Approximately 15% of p53 mutants are temperature sensitive (TS) and regain maximal activity at 32°C. Proof of concept study showed that induction of 32°C hypothermia in mice restored TS mutant p53 activity and inhibited tumor growth. However, 32°C is the lower limit of therapeutic hypothermia procedures for humans. Higher temperatures are preferable but result in suboptimal TS p53 activation. Recently, arsenic trioxide (ATO) was shown to rescue the conformation of p53 structural mutants by stabilizing the DNA binding domain. We examined the responses of 17 frequently observed p53 TS mutants to functional rescue by temperature shift and ATO. The results showed that ATO only rescued mild p53 TS mutants with high basal activity at 37°C. Mild TS mutants showed a common feature of regaining significant activity at the semi-permissive temperature of 35°C and could be further stimulated by ATO at 35°C. TS p53 rescue by ATO was antagonized by the cellular redox mechanism and was rapidly reversible. Inhibition of glutathione (GSH) biosynthesis enhanced ATO rescue efficiency and sustained p53 activity after ATO washout. The results suggest that mild TS p53 mutants are uniquely responsive to functional rescue by ATO due to small thermostability deficits and inherent potential to regain active conformation. Combining mild hypothermia and ATO may provide an effective and safe procedure for targeting tumors with p53 TS mutations.