A polyamino acid-based phosphatidyl polymer library for in vivo mRNA delivery with spleen targeting ability.

A qualified delivery system is crucial for the successful application of messenger RNA (mRNA) technology. While lipid nanoparticles (LNPs) are currently the predominant platform for mRNA delivery, they encounter challenges such as high inflammation and difficulties in targeting non-liver tissues. Polymers offer a promising delivery solution, albeit with limitations including low transfection efficiency and potential high toxicity. Herein, we present a poly(L-glutamic acid)-based phosphatidyl polymeric carrier (PLG-PPs) for mRNA delivery that combines the dual advantages of phospholipids and polymers. The PLGs grafted with epoxy groups were firstly modified with different amines and then with alkylated dioxaphospholane oxides, which provided a library of PLG polymers grafted with various phosphatidyl groups. In vitro studies proved that PLG-PPs/mRNA polyplexes exhibited a significant increase in mRNA expression, peaking 14 716 times compared to their non-phosphatidyl parent polymer. Impressively, the subset PA8-PL3 not only facilitated efficient mRNA transfection but also selectively delivered mRNA to the spleen instead of the liver (resulting in 69.73% protein expression in the spleen) once intravenously administered. This type of phosphatidyl PLG polymer library provides a novel approach to the construction of mRNA delivery systems especially for spleen-targeted mRNA therapeutic delivery.

A hidden demethylation pathway removes mercury from rice plants and mitigates mercury flux to food chains.

Dietary exposure to methylmercury (MeHg) causes irreversible damage to human cognition and is mitigated by photolysis and microbial demethylation of MeHg. Rice (Oryza sativa L.) has been identified as a major dietary source of MeHg. However, it remains unknown what drives the process within plants for MeHg to make its way from soils to rice and the subsequent human dietary exposure to Hg. Here we report a hidden pathway of MeHg demethylation independent of light and microorganisms in rice plants. This natural pathway is driven by reactive oxygen species generated in vivo, rapidly transforming MeHg to inorganic Hg and then eliminating Hg from plants as gaseous Hg°. MeHg concentrations in rice grains would increase by 2.4- to 4.7-fold without this pathway, which equates to intelligence quotient losses of 0.01-0.51 points per newborn in major rice-consuming countries, corresponding to annual economic losses of US$30.7-84.2 billion globally. This discovered pathway effectively removes Hg from human food webs, playing an important role in exposure mitigation and global Hg cycling.

Nickel/photoredox dual catalyzed arylalkylation of nonactivated alkenes.

Alkene dicarbofunctionalization is an efficient strategy and operation-economic fashion for introducing complexity in molecules. A nickel/photoredox dual catalyzed arylalkylation of nonactivated alkenes for the simultaneous construction of one C(sp3)-C(sp3) bond and one C(sp3)-C(sp2) bond has been developed. The mild catalytic method provided valuable indanethylamine derivatives with wide substrate scope and good functional group compatibility. An enantioselective dicarbofunctionalization was also achieved with pyridine-oxazoline as a ligand. The efficiency of metallaphotoredox dicarbofunctionalization was demonstrated for the concise synthesis of pharmaceutically active compounds.

New insights into sulfur input induced methylmercury production and accumulation in paddy soil and rice.

Sulfur has a high affinity for mercury (Hg) and can serve as effective treating agent for Hg pollution. However, conflict effects between reducing Hg mobility and promoting Hg methylation by sulfur were found in recent studies, and there is a gap in understanding the potential mechanism of MeHg production under different sulfur-treated species and doses. Here, we investigated and compared the MeHg production in Hg-contaminated paddy soil and its accumulation in rice under elemental sulfur or sulfate treatment at a relatively low (500 mg·kg-1) or high (1000 mg·kg-1) level. The associated potential molecular mechanisms are also discussed with the help of density functional theory (DFT) calculation. Pot experiments demonstrate that both elemental sulfur and sulfate at high exposure levels increased MeHg production in soil (244.63-571.72 %) and its accumulation in raw rice (268.73-443.50 %). Coupling the reduction of sulfate or elemental sulfur and decrease of soil redox potential leads to the detachment of Hg-polysulfide complexes from the surface of HgS which can be explained by DFT calculations. Enhancement of free Hg and Fe release through reducing Fe(III) oxyhydroxides further promotes soil MeHg production. The results provide clues for understanding the mechanism by which exogenous sulfur promotes MeHg production in paddies and paddy-like environments and give new insights for decreasing Hg mobility by regulating soil conditions.

Effects of combined antibiotics on nitrification, bacteria and antibiotic resistance genes in activated sludge: Insights from legacy effect of antibiotics.

The effect of combined antibiotics exposure on nitrogen removal, microbial community assembly and proliferation of antibiotics resistance genes (ARGs) is a hotspot in activated sludge system. However, it is unclear that how the historical antibiotic stress affects the subsequent responses of microbes and ARGs to combined antibiotics. In this study, the effects of combined sulfamethoxazole (SMX) and trimethoprim (TMP) pollution on activated sludge under legacy of SMX or TMP stress with different doses (0.005-30 mg/L) were investigated to clarify antibiotic legacy effects. Nitrification activity was inhibited under higher level of combined exposure but a high total nitrogen removal (∼70%) occurred. Based on the full-scale classification, the legacy effect of past antibiotic stress had a marked effect on community composition of conditionally abundant taxa (CAT) and conditionally rare or abundant taxa (CRAT). Rare taxa (RT) were the keystone taxa in the microbial network, and the responses of hub genera were also affected by the legacy of antibiotic stress. Nitrifying bacteria and genes were inhibited by the antibiotics and aerobic denitrifying bacteria (Pseudomonas, Thaurea and Hydrogenophaga) were enriched under legacy of high dose, as were the key denitrifying genes (napA, nirK and norB). Furthermore, the occurrences and co-selection relationship of 94 ARGs were affected by legacy effect. While, some shared hosts (eg., Citrobacter) and hub ARGs (eg., mdtD, mdtE and acrD) were identified. Overall, antibiotic legacy could affect responses of activated sludge to combined antibiotic and the legacy effect was stronger at higher exposure levels.

Amendments of nitrogen and sulfur mitigate carbon-promoting effect on microbial mercury methylation in paddy soils.

The imbalance of nutrient elements in paddy soil could affect biogeochemical processes; however, how the key elements input influence microbially-driven conversion of mercury (Hg) to neurotoxic methylmercury (MeHg) remains virtually unknown. Herein, we conducted a series of microcosm experiments to explore the effects of certain species of carbon (C), nitrogen (N) and sulfur (S) on microbial MeHg production in two typical paddy soils (yellow and black soil). Results showed that the addition of C alone into the soils increased MeHg production approximately 2-13 times in the yellow and black soils; while the combined addition of N and C mitigated the C- promoting effect significantly. Added S also had a buffering effect on C-facilitated MeHg production in the yellow soil despite the extent being lower than that of N addition, whereas this effect was not obvious for the black soil. MeHg production was positively correlated with the abundance of Deltaproteobactera-hgcA in both soils, and the changes in MeHg production were related to the shifts of Hg methylating community resulting from C, N, and S imbalance. We further found that the changes in the proportions of dominant Hg methylators such as Geobacter and some unclassified groups could contribute to the variations in MeHg production under different treatments. Moreover, the enhanced microbial syntrophy with adding N and S might contribute to the reduced C-promoting effect on MeHg production. This study has important implications for better understanding of microbes-driven Hg conversion in paddies and wetlands with nutrient elements input.

Temporal changes of blood mercury concentrations in Chinese newborns and the general public from 1980s to 2020s.

Mercury (Hg) is a global pollutant that threatens the environment and human health. As a major producer, emitter and consumer of Hg, China is currently taking different measures to curb mercury pollution in accordance with the requirements of the Minamata Convention on Mercury. Blood Hg can reflect the human body's recent exposure to Hg. This review summarized the temporal changes in blood Hg concentrations in newborns and the general public in China from 1980 s to 2020 s. It was shown that the blood Hg concentrations of newborns showed the downward trend, although it was not significant. The general public Hg concentrations showed a trend of first increase and then decrease trend. Most of the cord blood Hg and venous blood Hg concentrations in China were lower than the USEPA reference concentration of 5.8 µg/L. Since low-dose prenatal Hg exposure can affect fetal and neonatal development, continuous attention needs to be paid to reduce maternal and neonatal Hg exposure. The information provided in this review may lay a basis for the effectiveness evaluation on the implementation of Minamata Convention on Mercury.

Gut as the target tissue of mercury and the extraintestinal effects.

Mercury (Hg) is harmful to the environment and human health. The gut plays important roles as the biological, chemical, mechanical, and immune barriers in animals and human beings. It has been known that Hg can be absorbed and methylated/demethylated in the gut, on the other hand, the impacts of Hg to the gut (especially the gut microbiota) is less studied. This review paper summarizes the impacts of inorganic Hg (IHg) and methyl Hg (MeHg) on gut barriers and the extraintestinal effects (damage to other organs such as the liver and brain). Both IHg and MeHg were found to cause intestinal microbial disorders, abnormal metabolites production, tight junction damage, and immune responses in the gut. The damage to the gut also contributed to the extraintestinal effects like the hepatotoxicity by IHg and the neurotoxicity by MeHg. In all, it is proposed that the gut should be considered as an important target tissue of Hg exposure, and the regulation of gut microbiota may have the potential for the prevention and control of the toxicity of Hg.

In Situ Reprogramming of Tumors for Activating the OX40/OX40 Ligand Checkpoint Pathway and Boosting Antitumor Immunity.

OX40 (CD134, TNFRSF4) is a member of the tumor necrosis factor receptor superfamily that can be activated by its cognate ligand OX40L (CD252, TNFSF4) and functions as a pair of T cell costimulatory molecules. The interaction between OX40 and OX40L (OX40/OX40L) plays a critical role in regulating antitumor immunity, including promoting effector T cells expansion and survival, blocking natural regulatory T cells (Treg) activity, and antagonizing inducible Treg generation. However, current OX40 agonists including anti-OX40 monoclonal antibodies (aOX40) have serious side effects after systemic administration, which limits their clinical success and application. Herein, we propose a strategy to reprogram tumor cells into OX40L-expressing "artificial" antigen-presenting cells (APCs) by OX40L plasmid-loaded nanoparticles for boosting antitumor immunity in situ. A novel gene transfection carrier was prepared by a modular hierarchical assembly method, which could efficiently transfect various tumor cells and express OX40L proteins on their surface. These surface-decorated OX40L proteins were proved to stimulate T cell proliferation in vitro while stimulating strong antitumor immune responses in vivo. Importantly, this in situ reprogramming strategy did not induce any toxicity as observed in aOX40 treatment, thus providing a novel method for immune checkpoint stimulator application.

[Historical Antibiotic Stress Changed the Effects of Sulfamethoxazole and Trimethoprim on Activated Sludge: ARGs and Potential Hosts].

The co-exposure of antibiotics has important effects on antibiotic resistance genes (ARGs) and microbial community aggregation in wastewater treatment plants (WWTPs). However, it is unclear whether differences in historical antibiotic exposure stress can determine responses of microbes and ARGs to combined antibiotics. By selecting a high concentration (30 mg·L-1) of sulfamethoxazole (SMX) and trimethoprim (TMP) as historical exposure stress conditions, the effects of SMX and TMP-combined pollution on ARGs, bacterial communities, and their interactions were explored in short-term experiments. Based on high-throughput quantitative PCR, a total of 13 ARGs were detected, and the absolute abundance was 2.21-5.42 copies·µL-1 (logarithm, DNA, the same below). Among them, sul2, ermB, mefA, and tetM-01 were the main subtypes in the samples, and the absolute abundance was between 2.95 and 5.40 copies·µL-1. The combined contamination of SMX and TMP could cause the enrichment of ARGs and mobile genetic elements (MGEs); however, their effects on each subtype were different, and the historical legacy effect of SMX was higher than that of TMP. Under the different exposure histories, the co-occurrence and co-exclusion patterns existed between ARGs. Moreover, MGEs (especially intI-1) were significantly correlated with sulfonamides (sul1 and sul2), tetracyclines[tet(32)], and macrolide-lincosamide-streptogramin (MLSB) resistance genes (ermB). Based on the full-scale classification of microorganisms, it was found that the microbial community structure of various groups responded differently to combined pollution, and the conditionally abundant taxa (CAT) were obviously enriched. Thauera, Pseudoxanthomonas, and Paracoccus were the dominant resistant bacterial genera. Furthermore, a total of 31 potential hosts of ARGs were identified with network analysis, which were dominated with conditionally rare taxa (CRT). Particularly, Candidatus_Alysiosphaera and Fusibacter were positively correlated with most of the ARGs, being the common protentional hosts. Importantly, some rare genera (RT, Variibacter, Aeromonas, Cloacibacterium, etc.) were potential hosts of transposon IS613, which played an important role in the proliferation and spread of ARGs. In conclusion, this study revealed the legacy effects of historical antibiotic stress on ARGs and their hosts, which could provide new ideas and theoretical basis for reducing ARGs pollution in WWTPs.

Decatungstate Catalyzed Photochemical Acetylation of C(sp3)-H Bonds.

A direct acetylation of inert C(sp3)-H bonds was developed that was catalyzed by decatungstate under visible light irradiation and was followed by radical addition-disassociation with phenylsulfonyl ethanone oxime. The reaction displays site-selectivity in multiple C(sp3)-H bonds without prefunctionalization and directing groups. Various functional groups are well-tolerated and natural molecules are structurally feasible. CF3-modified phenylsulfonyl ethanone oxime was discovered to be necessary for enhancing the electrophilicity of imine and lowering the C-S bond cleavage energy.

Fates of antibiotic resistance genes and bacterial/archaeal communities of activated sludge under stress of copper: Gradient increasing/decreasing exposure modes.

Effect of copper (Cu) on antibiotic resistance genes (ARGs) and bacterial/archaeal community of activated sludge under gradient increasing (0.5-10 mg/L) or decreasing exposure (10-0.5 mg/L) modes was explored. Here, 29 genes were detected among 48 selected ARGs and mobile gene elements (MGEs). Two exposure modes showed dissimilar effects on ARGs and distribution was more affected by environmental concentrations of Cu, which promoted transmission of ARGs (multiple drug resistance and sulfonamide). Cellular protection was main resistance mechanism, which was less inhibited than efflux pumps. The tnpA-02, as main MGE, interacted closely with ARGs (sul2, floR, etc.). Gradient increasing exposure mode had more effects on bacterial/archaeal structure and composition. Bacteria were main hosts for specific ARGs and tnpA-02, while archaea carried multiple ARGs (cmx(A), adeA, etc.), and bacteria (24.24 %) contributed more to changes of ARGs than archaea (19.29 %). This study clarified the impacts of Cu on the proliferation and transmission of ARGs.

Mechanistic insights into sulfate and phosphate-mediated hexavalent chromium removal by tea polyphenols wrapped nano-zero-valent iron.

Nano zero-valent iron via green synthesis (g-nZVI) has great potential in removing toxic hexavalent Cr(VI) from industrial wastewater. Sulfate and phosphate in wastewater can influence Cr(VI) removal by g-nZVI. In this study, the Cr(VI) removal kinetics by different g-nZVI materials were investigated with the existence of sulfate and/or phosphate, and the corresponding mechanisms were first revealed using multiple characterizations, including X-ray absorption near-edge spectra (XANES) and X-ray photoelectron spectroscopy (XPS). The results showed that Cr(OH)3 was the dominant species initially formed on the surface of g-nZVI particles before transforming to Cr2O3 during the reaction of g-nZVI with Cr(VI). Sulfate in wastewater can promote the reduction from Cr(VI) to Cr(OH)3 by g-nZVI, because sulfate triggers the release of Fe(II) and tea polyphenols (from tea extracts) from the g-nZVI surface due to the corrosion of Fe0 core, which is in line with an obvious increase in pseudo-second-order rate constant (k2) and subtle change in Cr(VI) removal capacity (qe). However, phosphate impedes the g-nZVI corrosion and inhibits qe because of the inner-sphere complexation of phosphate onto g-nZVI decreasing the released Fe(II) for Cr2O3 production. When sulfate and phosphate coexisted in contaminated water, the inhibition effect of phosphate in Cr(VI) removal by g-nZVI was stronger than the promotion of sulfate. Accordingly, qe value of g-nZVI declined from 93.4 mg g-1 to 77.5 mg g-1, while k2 remained constant as the molar ratio of phosphate/sulfate increased from 0.1 to 10 in water. This study provides new insights into applying g-nZVI in efficient Cr(VI) removal from contaminated water with enrichment of sulphates and phosphates.

Diabetic Retinopathy Grading by Deep Graph Correlation Network on Retinal Images Without Manual Annotations.

Background: Diabetic retinopathy, as a severe public health problem associated with vision loss, should be diagnosed early using an accurate screening tool. While many previous deep learning models have been proposed for this disease, they need sufficient professional annotation data to train the model, requiring more expensive and time-consuming screening skills. Method: This study aims to economize manual power and proposes a deep graph correlation network (DGCN) to develop automated diabetic retinopathy grading without any professional annotations. DGCN involves the novel deep learning algorithm of a graph convolutional network to exploit inherent correlations from independent retinal image features learned by a convolutional neural network. Three designed loss functions of graph-center, pseudo-contrastive, and transformation-invariant constrain the optimisation and application of the DGCN model in an automated diabetic retinopathy grading task. Results: To evaluate the DGCN model, this study employed EyePACS-1 and Messidor-2 sets to perform grading results. It achieved an accuracy of 89.9% (91.8%), sensitivity of 88.2% (90.2%), and specificity of 91.3% (93.0%) on EyePACS-1 (Messidor-2) data set with a confidence index of 95% and commendable effectiveness on receiver operating characteristic (ROC) curve and t-SNE plots. Conclusion: The grading capability of this study is close to that of retina specialists, but superior to that of trained graders, which demonstrates that the proposed DGCN provides an innovative route for automated diabetic retinopathy grading and other computer-aided diagnostic systems.

Non-targeted metallomics through synchrotron radiation X-ray fluorescence with machine learning for cancer screening using blood samples.

Cancer is the leading cause of death in many countries. The development of new methods for early screening of cancers is highly desired. Targeted metallomics has been successfully applied in the screening of cancers through quantification of elements in the matrix, which is time consuming and requires combined techniques for the quantification due to the large elemental difference in the matrix. This work proposed a non-targeted metallomics (NTM) approach through synchrotron radiation based X-ray fluorescence (SRXRF) and machine learning algorithms (MLAs) for the screening of cancers. One hundred serum samples were collected from cancer patients who were confirmed by pathological examination with 100 matched serum samples from healthy volunteers. The serum samples were studied with SRXRF and the spectra from both groups were directly clarified through MLAs, which did not require the quantification of elements. The NTM approach through SRXRF and MLAs is fast (5s for data collection for one sample) and accurate (over 96% accuracy) for cancer screening. Besides, this approach can also identify the most affected elements in cancer samples like Ca, Zn and Ti as we found, which may shed lights on the drug development for cancer treatment. This NTM approach can also be applied through commercially available XRF instruments or ICP-TOF-MS with MLAs. It has the potential for the screening and prediction of other diseases like COVID-19 and neurodegenerative diseases in a high throughput and least invasive way.

Mercury Reduction, Uptake, and Species Transformation by Freshwater Alga Chlorella vulgaris under Sunlit and Dark Conditions.

As a major entry point of mercury (Hg) to aquatic food webs, algae play an important role in taking up and transforming Hg species in aquatic ecosystems. However, little is known how and to what extent Hg reduction, uptake, and species transformations are mediated by algal cells and their exudates, algal organic matter (AOM), under either sunlit or dark conditions. Here, using Chlorella vulgaris (CV) as one of the most prevalent freshwater model algal species, we show that solar irradiation could enhance the reduction of mercuric Hg(II) to elemental Hg(0) by both CV cells and AOM. AOM reduced more Hg(II) than algal cells themselves due to cell surface adsorption and uptake of Hg(II) inside the cells under solar irradiation. Synchrotron radiation X-ray absorption near-edge spectroscopy (SR-XANES) analyses indicate that sunlight facilitated the transformation of Hg to less bioavailable species, such as ß-HgS and Hg-phytochelatins, compared to Hg(Cysteine)2-like species formed in algal cells in the dark. These findings highlight important functional roles and potential mechanisms of algae in Hg reduction and immobilization under varying lighting conditions and how these processes may modulate Hg cycling and bioavailability in the aquatic environment.

Roles of plant-associated microorganisms in regulating the fate of Hg in croplands: A perspective on potential pathways in maintaining sustainable agriculture.

In heavy metal-contaminated croplands, plant-associated microorganisms play important roles in the adaptation of crops to heavy metals. Plant-associated microbes can interact with Hg and stimulate plant resistance to Hg toxicity, which is crucial for impeding Hg accumulation along the food chain. The roles of rhizosphere microorganisms for the improvement of plant growth and Hg resistance have drawn great research attention. However, the interactions among plant-endophyte-Hg have been neglected although they might be important for in vivo Hg detoxification. In this study, we systematically summarized 1) the roles of plant-associated microorganisms in Hg detoxification and plant growth, 2) Hg methylation and demethylation driven by plant-associated microbes, 3) the relationships between plant-associated microbes and Hg biogeochemical cycling. The possible mechanisms underlying crop-endophyte-Hg interactions were discussed, although limited studies on this aspect are available to date. The challenges and perspectives of plant-endophytes in dampening Hg phytotoxicity and controlling Hg accumulation in croplands were proposed on the basis of the present knowledge. Taken together, this work provides evidence for further understanding the interactions between soil-plant-endophyte-Hg systems and as well as new interpretations and perspectives into regulating the fate of Hg in croplands.

Assessment of the Bioavailability of Mercury Sulfides in Paddy Soils Using Sodium Thiosulfate Extraction - Results from Microcosm Experiments.

Mercury sulfides (HgS), one of the largest Hg sinks in the lithosphere, has long been considered to be highly inert. Recently, several HgS speciation (e.g., nano- or micro-sized HgS particles) in paddy soils have been found to be reactive and bioavailable, increasing the possibility of methylation and bioaccumulation and posing a potential risk to humans. However, a simple and uniform method for investigating HgS bioavailability is still lacking. To address this issue, we extracted dissolved Hg from HgS particles by sodium thiosulfate (Na2S2O3) in paddy soils and analyzed the correlation between extracted Hg and soil methylmercury (MeHg). Results showed that the amounts of Hg extracted by Na2S2O3 had a strong positive correlation with the levels of soil MeHg (R 2 adj = 0.893, p < 0.05). It is suggested that Na2S2O3 extraction may be a good method of predicting Hg bioavailability in paddy soils. Our results would help to give clues in better predicting Hg risk in natural environments.

The dissimilarity of antibiotic and quorum sensing inhibitor on activated sludge nitrification system: Microbial communities and antibiotic resistance genes.

Effects of antibiotics (azithromycin, AZM, 1-40 mg/L) and quorum sensing inhibitor (QSI, 2(5H)-furanone, 1-40 mg/L) combined pollution with environmental concentration of copper on bacterial/archaeal community and antibiotic resistance genes (ARGs) in activated sludge system were explored. QSI inhibited nitrification more obviously than AZM. AZM and QSI were synergistic inhibitions on bacterial diversity, and AZM inhibited bacterial compositions more than QSI. While, QSI had more impacts on archaeal diversity/compositions. Less interactions among bacteria and archaea communities with Aquimonas as keystone genus. Functional differences in bacteria/archaea communities were little, and AZM had more effects on metabolism. AZM mainly affected nitrifying bacteria (Candidatus Nitrospira nitrificans and Nitrosomonas). Specific denitrifying bacteria were enriched by AZM (Brevundimonas, 1.76-31.69%) and QSI (Comamonas, 0.61-9.61%), respectively. AZM enriched ARGs more easily than QSI and they were antagonistic to proliferation of ARGs. Bacteria were main hosts of ARGs (macrolide-lincosamide-streptogramin B, other/efflux, etc.) and archaea (Methanosphaerula, Methanolobus) carried multiple ARGs.

Mobilization and methylation of mercury with sulfur addition in paddy soil: Implications for integrated water-sulfur management in controlling Hg accumulation in rice.

Sulfur-fertilizer is commonly applied in croplands and in immobilizing Hg in contaminated soil. However, there is still great uncertainty and controversy concerning Hg transportability and transformation when supplying sulfur in paddies with complex conditions. Herein, we explored the effect of adding sulfate in paddy soil at different rice growth stages on soil Hg release and MeHg accumulation in rice and uncovered the correlation between sulfur induced MeHg production and the dynamically changed soil Eh, dissolved Fe, and dissolved organic carbon (DOC). In specific, sulfate addition at early stages (flooding period) triggered the decrease of Eh and increase of DOC and dissolved Fe, which in turn promoted Hg release and favored MeHg generation (increased by 235.19-555.07% vs control). Interestingly, adding sulfate at late stages (drainage condition), as compared with that at early stages, alleviated Hg release and MeHg production accompanied by the increase of Eh and decrease of dissolved Fe and DOC. The microcosmic experiment further confirmed the reduction of sulfate to sulfide promoted the change of Eh, thereby stimulating HgS dissolution in soil extract. The results give clues on the rational application of sulfur-fertilizer and through the water-sulfur fertilizer management considering the correspondingly changed soil conditions to diminish Hg bioavailability and MeHg production in paddies and paddy-like environments.