Recent advances in sulfur dioxide releasing nanoplatforms for cancer therapy.

Sulfur dioxide (SO2), long considered to be a harmful atmospheric pollutant, has recently been posited as the fourth gasotransmitter, as it is produced endogenously in mammals and has important pathophysiological effects. The field of tumor therapy has witnessed a paradigm shift with the emergence of SO2-based gas therapy. This has been possible because SO2 is a potent glutathione consumer that can promote the production of reactive oxygen species, eventually leading to oxidative-stress-induced cancer cell death. Nevertheless, this therapeutic gas cannot be directly administrated in gaseous form. Thus, various nano formulations incorporating SO2 donors or prodrugs capable of storing and releasing SO2 have been developed in an attempt to achieve active/passive intratumoral accumulation and SO2 release in the tumor microenvironment. In this review article, the advances over the past decade in nanoplatforms incorporating sulfur SO2 prodrugs to provide controlled release of SO2 for cancer therapy are summarized. We first describe the synthesis of polypeptide SO2 prodrugs to overcome multiple drug resistance that was pioneered by our group, followed by other macromolecular SO2 prodrug structures that self-assemble into nanoparticles for tumor therapy. Second, we describe nanoplatforms composed of various small-molecule SO2 donors with endogenous or exogenous stimuli responsiveness, including thiol activated, acid-sensitive, and ultraviolet or near-infrared light-responsive SO2 donors, which have been used for tumor inhibition. Combinations of SO2 gas therapy with photodynamic therapy, chemotherapy, photothermal therapy, sonodynamic therapy, and nanocatalytic tumor therapy are also presented. Finally, we discuss the current limitations and challenges and the future outlook for SO2-based gas therapy. STATEMENT OF SIGNIFICANCE: Gas therapy is attracting increasing attention in the scientific community because it is a highly promising strategy against cancer owing to its inherent biosafety and avoidance of drug resistance. Sulfur dioxide (SO2) is recently found to be produced endogenously in mammals with important pathophysiological effects. This review summarizes recent advances in SO2 releasing nanosystems for cancer therapy, including polymeric prodrugs, endogenous or exogenous stimulus-activated SO2 donors delivered by nanoplatform and combination therapy strategies.

QTL mapping reveals novel genes and mechanisms underlying variations in H2S production during alcoholic fermentation in Saccharomyces cerevisiae.

Saccharomyces cerevisiae requirement for reduced sulfur to synthesize methionine and cysteine during alcoholic fermentation, is mainly fulfilled through the sulfur assimilation pathway. Saccharomyces cerevisiae reduces sulfate into sulfur dioxide (SO2) and sulfide (H2S), whose overproduction is a major issue in winemaking, due to its negative impact on wine aroma. The amount of H2S produced is highly strain-specific and also depends on SO2 concentration, often added to grape must. Applying a bulk segregant analysis to a 96-strain-progeny derived from two strains with different abilities to produce H2S, and comparing allelic frequencies along the genome of pools of segregants producing contrasting H2S quantities, we identified two causative regions involved in H2S production in the presence of SO2. A functional genetic analysis allowed the identification of variants in four genes able to impact H2S formation, viz; ZWF1, ZRT2, SNR2, and YLR125W, and involved in functions and pathways not associated with sulfur metabolism until now. These data point out that, in wine fermentation conditions, redox status, and zinc homeostasis are linked to H2S formation while providing new insights into the regulation of H2S production, and a new vision of the interplay between the sulfur assimilation pathway and cell metabolism.

A near-infrared AIE fluorescent probe for accurate detection of sulfur dioxide derivatives and visualization of fingerprints.

In most biophysiological processes, sulfur dioxide (SO2) is an important intracellular signaling molecule that plays an important role. The change of SO2 in cells are closely related to various diseases such as neurological disorders and lung cancer, so it is necessary to develop fluorescent probes with the ability to accurately detect SO2 during physiological processes. In this work, we designed and synthesized a multifunctional fluorescent probe TIS. TIS has excellent properties such as near-infrared emission, large stokes shift, excellent SO2 detection capabilities, low detection limit, high specificity and visualization of color change before and after reaction. Simultaneously, TIS has low cytotoxicity, good biocompatibility, clear cell imaging capability and mitochondrial targeting ability. In addition, the ability of TIS to be applied to different material surfaces for latent fingerprint fluorescence imaging was also explored. TIS provides an excellent method for the accurate detection of SO2 derivatives and shows great potential applications in near-infrared cellular imaging and latent fingerprint fluorescence imaging.

[Regulative effects of endogenous sulfur dioxide on oxidant stress in myocardium of rat with sepsis].

OBJECTIVE: To explore the modulating effect of endogenous sulfur dioxide (SO2) on the ba-lance of oxidation/reduction in the cecal-ligation-and-puncture-induced septic rat myocardium. METHODS: Forty male Sprague Dawley rats were randomized into control group, SO2group, sepsis group and sepsis + SO2group. The levels of procalcitonin (PCT), creatine kinase isoenzyme (CK-MB), cardiac troponin Ⅰ (cTn Ⅰ) and fatty acid binding protein (FABP) in plasma in each group of the rats were measured; The level of hydrogen peroxide (H2O2), level of nitric oxide (NO), activity of myeloperoxidase (MPO), activity of hydroxyl free radical (·OH) and level of malondialdehyde (MDA) in myocardial tissue were measured; Total antioxidant capacity (T-AOC), activity of catalase (CAT), level of cytochrome oxidase (CO), level of glutathione (GSH), level of glutathione oxidase (GSH-px) and activity of superoxide dismutase (SOD) in myocardial tissue were measured. RESULTS: The level of PCT in plasma in the rats with sepsis increased from (0.93±0.26) µg/L to (2.45±0.52) µg/L (P < 0.01), and decreased to (1.58±0.36) µg/L after the intervention of sulfur dioxide donor (P < 0.01). In sepsis, the plasma CK-MB, cTn Ⅰ and FABP levels in the rats increased respectively from (14.46±6.48) µg/L, (151.25±30.14) ng/L and (2.72±0.65) µg/L to (23.72±7.72) µg/L, (272.78±52.70) ng/L and (5.22±1.01) µg/L (P all < 0.01), and decreased to (16.74±3.63) µg/L, (184.86±37.72) µg/L and (3.31±0.84) µg/L (all P < 0.05) after the intervention of sulfur dioxide donor. The level of H2O2, level of NO, activity of MPO, activity of ·OH and level of MDA in myocardial tissue in the rats with sepsis increased respectively from (67.26±8.77) mmol/g, (38.39±6.93) µmol/g, (358.25±68.12) U/g, (648.42±93.69) U/ mg and (4.55±0.96) µmol/g to (111.45±17.35) mmol/g, (51.04±5.91) µmol/g, (465.88±76.76) U/g, (873.75±123.47) U/mg and (7.25±0.86) µmol/g (all P < 0.01), and decreased respectively to (75.99±10.52) mmol/g, (39.39±7.80) µmol/g, (393.17±51.5) U/g, (710.54±106.33) U/mg and (5.16±0.65) µmol/g after the intervention of the sulfur dioxide donor (all P < 0.05). The activity of T-AOC, activity of CAT, level of CO, level of GSH, level of GSH-px and activity of SOD in myocardial tissue in the rats with sepsis increased respectively from (2.07±0.37) U/mg, (169.25±36.86) U/g, (1.35±0.32) µmol/g, (103.51±16.62) µmol/g, (38.40±7.97) µmol/g and (38.50±8.30) U/mg to (1.42±0.39) U/mg, (98.44±26.56) U/g, (0.96±0.21) µmol/g, (68.05±7.35) µmol/ g, (23.83±5.04) µmol/g and (23.11±4.63) U/mg (P all < 0.01), and increased respectively to (1.83±0.37) U/mg, (146.14±31.63) U/g, (1.28±0.20) µmol/g, (92.10±11.84) µmol/g, (37.16±3.01) µmol/g and (37.29±2.62) U/mg (P all < 0.05) after the intervention of the sulfur dioxide donor. CONCLUSION: Endogenous SO2 can protect rat myocardium in sepsis by modulating the ba-lance of oxidation and reduction.

Sulfur is in the Air: Cyanolichen Marriages and Pollution.

Cyanolichens are symbiotic organisms involving cyanobacteria and fungi (bipartite) or with the addition of an algal partner (tripartite). Cyanolichens are known for their heightened susceptibility to environmental pollution. We focus here on the impacts on cyanolichens due to rising air pollution; we are especially interested in the role of sulfur dioxide on cyanolichen biology. Cyanolichens due to air pollution including sulfur dioxide exposure, show symptomatic changes including degradation of chlorophyll, lipid membrane peroxidation, decrease in ATP production, changes in respiration rate, and alteration of endogenous auxins and ethylene production, although symptoms are known to vary with species and genotype. Sulfur dioxide has been shown to be damaging to photosynthesis but is relatively benign on nitrogen fixation which proposes as a hypothesis that the algal partner may be more in harm's way than the cyanobiont. In fact, the Nostoc cyanobiont of sulfur dioxide-susceptible Lobaria pulmonaria carries a magnified set of sulfur (alkane sulfonate) metabolism genes capable of alkane sulfonate transport and assimilation, which were only unraveled by genome sequencing, a technology unavailable in the 1950-2000 epoch, where most physiology- based studies were performed. There is worldwide a growing corpus of evidence that sulfur has an important role to play in biological symbioses including rhizobia-legumes, mycorrhizae-roots and cyanobacteria-host plants. Furthermore, the fungal and algal partners of L. pulmonaria appear not to have the sulfonate transporter genes again providing the roles of ambient-sulfur (alkanesulfonate metabolism etc.) mediated functions primarily to the cyanobacterial partner. In conclusion, we have addressed here the role of the atmospheric pollutant sulfur dioxide to tripartite cyanolichen viability and suggest that the weaker link is likely to be the photosynthetic algal (chlorophyte) partner and not the nitrogen-fixing cyanobiont.

Bifunctional Single-Molecular Fluorescent Probe: Visual Detection of Mitochondrial SO2 and Membrane Potential.

Mitochondrial membrane potential (MMP) and sulfur dioxide (SO2) significantly affect the mitochondrial state. In this work, TC-2 and TC-8 were constructed through side-chain engineering, in which TC-2 bearing the poorer hydrophobicity could localize on mitochondria better. Interestingly, short-wave emission was captured due to the sensitive response of TC-2 to SO2 (LOD = 13.8 nM). Meanwhile, the probe could bind with DNA, presenting enhanced long-wave emission. Encouragingly, TC-2 could migrate from mitochondria to the nucleus when MMP was decreased, accompanied by the increase of fluorescence lifetime (9-fold). Hence, TC-2 could be used for dual-channel monitoring of mitochondrial SO2 and MMP, which showed a completely different pathway from the commercial MMP detectors JC-1/JC-10. The cellular experiments showed that MMP was gradually decreased due to reactive oxygen species-triggered oxidative stress, and the SO2 level was up-regulated simultaneously. Overall, this work proposed a new method to investigate and diagnose the mitochondrial-related diseases.

Sulfur dioxide derivatives aggravated ovalbumin-induced asthma through targeting TRPV1 and tight junctions.

This study aimed to investigate the effects of sulfur dioxide (SO2) derivatives on asthma induced by ovalbumin (OVA). Sprague Dawley rats were sensitized to and challenged with OVA and SO2 derivatives (NaHSO3 and Na2SO3, 1:3 M/M) to establish 28-day (short-term) and 42-day (long-term) asthma models. Exposure to SO2 derivatives aggravated asthma and hence, promoted lung injury in OVA-induced asthma. In addition, it upregulated the protein expression of TRPV1 and downregulated the expression of tight junctions (TJs). These changes were dose-dependent and were more pronounced in the presence of a high concentration of SO2 derivatives. In vitro, SO2 derivatives also increased the calcium influx and TRPV1 protein expression, and decreased TJ expression. Besides, no significant difference in the TJ expression was found between the WT and TRPV1-/- mice. The underlying mechanism might be related to regulating the effects of TRPV1 and TJs.

SO2 and copper tolerance exhibit an evolutionary trade-off in Saccharomyces cerevisiae.

Copper tolerance and SO2 tolerance are two well-studied phenotypic traits of Saccharomyces cerevisiae. The genetic bases of these traits are the allelic expansion at the CUP1 locus and reciprocal translocation at the SSU1 locus, respectively. Previous work identified a negative association between SO2 and copper tolerance in S. cerevisiae wine yeasts. Here we probe the relationship between SO2 and copper tolerance and show that an increase in CUP1 copy number does not always impart copper tolerance in S. cerevisiae wine yeast. Bulk-segregant QTL analysis was used to identify variance at SSU1 as a causative factor in copper sensitivity, which was verified by reciprocal hemizygosity analysis in a strain carrying 20 copies of CUP1. Transcriptional and proteomic analysis demonstrated that SSU1 over-expression did not suppress CUP1 transcription or constrain protein production and provided evidence that SSU1 over-expression induced sulfur limitation during exposure to copper. Finally, an SSU1 over-expressing strain exhibited increased sensitivity to moderately elevated copper concentrations in sulfur-limited medium, demonstrating that SSU1 over-expression burdens the sulfate assimilation pathway. Over-expression of MET 3/14/16, genes upstream of H2S production in the sulfate assimilation pathway increased the production of SO2 and H2S but did not improve copper sensitivity in an SSU1 over-expressing background. We conclude that copper and SO2 tolerance are conditional traits in S. cerevisiae and provide evidence of the metabolic basis for their mutual exclusivity. These findings suggest an evolutionary driver for the extreme amplification of CUP1 observed in some yeasts.

Elucidating the role of circNFIB in myocardial fibrosis alleviation by endogenous sulfur dioxide.

BACKGROUND: To investigate the role of circNFIB in the alleviation of myocardial fibrosis by endogenous sulfur dioxide (SO2). METHODS: We stimulated cultured neonatal rat cardiac fibroblasts with transforming growth factor-ß1 (TGF-ß1) and developed an in vitro myocardial fibrosis model. Lentivirus vectors containing aspartate aminotransferase 1 (AAT1) cDNA were used to overexpress AAT1, and siRNA was used to silence circNFIB. The SO2, collagen, circNFIB, Wnt/ß-catenin, and p38 MAPK pathways were examined in each group. RESULTS: In the in vitro TGF-ß1-induced myocardial fibrosis model, endogenous SO2/AAT1 expression was significantly decreased, and collagen levels in the cell supernatant and type I and III collagen expression, as well as α-SMA expression, were all significantly increased. TGF-ß1 also significantly reduced circNFIB expression. AAT1 overexpression significantly reduced myocardial fibrosis while significantly increasing circNFIB expression. Endogenous SO2 alleviated myocardial fibrosis after circNFIB expression was blocked. We discovered that circNFIB plays an important role in the alleviation of myocardial fibrosis by endogenous SO2 by inhibiting the Wnt/ß-catenin and p38 MAPK pathways. CONCLUSION: Endogenous SO2 promotes circNFIB expression, which inhibits the Wnt/ß-catenin and p38 MAPK signaling pathways, consequently alleviating myocardial fibrosis.

Using the aluminum decorated graphitic-C3N4 quantum dote (QD) as a sensor, sorbent, and photocatalyst for artificial photosynthesis; a DFT study.

In this project, we have investigated the possibility of mimicking the natural photosynthesis, as well as sensing and adsorption application of aluminum decorated graphitic C3N4 (Al-g-C3N4) QDs (toward some air pollutants containing CO, CO2, and SO2). The results of the potential energy surface (PES) studies show that in all three adsorption processes, the energy changes are negative (-10.70 kcal mol-1, -16.81 kcal mol-1, and -79.97 kcal mol-1 for CO, CO2, and SO2 gasses, respectively). Thus, all of the adsorption processes (mainly SO2) are spontaneous. Moreover, the frontier molecular orbital (FMO) investigations indicate that the Al-g-C3N4 QD could be used as a suitable semiconductor sensor for detection of CO, and CO2 (as carbon oxides) in one hand, and SO2 gaseous species on the other hand. Finally, the results reveal that those QDs could be applied for artificial photosynthesis (in presence of CO2; Δµh-e = 1.43 V), and for water splitting process for the H2 generation (Δµh-e = 1.23 V) as a clean fuel for near future.

Mass transfer characteristics and effect of flue gas used in microalgae culture.

Flue gas not only contains carbon dioxide (CO2) but also air pollutants (sulfur oxides (SOx) and nitrogen oxides (NOx)). The effective utilization of flue gas could help us to reduce the cost of microalgal biomass production. This study assessed and explored the utilization of flue gas for the absorption characteristics of different components and their biological effect in microalgal culture systems. In abiotic absorption experiments, the absorptivity of CO2 was reduced by a maximum of 3.1%, and the concentration of the available carbon source in the culture medium was decreased by 6.7% when sulfur dioxide (SO2, at 100 mg/m3) was presented in the flue gas. Meanwhile, the presence of oxygen (O2, at 4%) in the flue gas improved the absorptivity of nitric oxide (NO). When Scenedesmus dimorphus was cultured using bisulfites and nitrites (at 10 mmol/L and 8 mmol/L, respectively) as the sulfur and nitrogen sources, SOx and NOx in the flue gas did not significantly affect growth of microalgal cells and the carbohydrate, lipid, and protein content. The consumption rates of nutrient elements were calculated, which could provide an adjustment strategy for the initial gas source when culturing microalgae with the flue gas. This study indicates that the flue gas used for microalgal culture should be partially desulfurized, so that the SOx and CO2 concentrations can optimize growth of microalgal cells, while the denitrification might not be needed since the flue gas can be oxidized to utilize the NO. KEY POINTS: • The concentration of the available carbon source in the culture medium was decreased when SO2 was presented in the flue gas, and the presence of O2 in the flue gas improved the absorptivity of NO. • An adjustment strategy for the initial gas source when culturing microalgae with the flue gas was firstly proposed. • For flue gas containing 10% CO2 and 60 mg/m3 of SO2, growth of Scenedesmus dimorphus showed no difference in cell growth in normal culture conditions.

Mitochondria-targetable colorimetric and far-red fluorescent sensor for rapid detection of SO2 derivatives in food samples and living cells.

Sulfur dioxide (SO2) derivatives are intertwined with many physiological and pathological processes in living systems, and excess intake of them are associated with various diseases. Herein, we have rationally constructed a novel colorimetric and far-red fluorescent probe for HSO3- based on a rhodamine analogue skeleton bearing a 3-quinolinium carboxaldehyde moiety. The novel probe exhibited a significant far-red fluorescence "Turn-on" response to HSO3-, along with obvious color change from reddish to purple via the specific 1,4-nucleophilic addition reaction of HSO3- with the quinolinium moiety in 3-(4-(2-carboxyphenyl)-7-(diethylamino)chromenylium-2-yl)-1-methylquinolin-1-ium hypochlorite trifluoromethanesulfonate (AQCB). The AQCB had excellent water-solubility, and presented rapid response (<15 s),highsensibility(LOD = 49 nM) and selectivity toward HSO3-. In addition, the probe was able to detect the content of HSO3- in food samples with satisfactory results. Furthermore, the probe possessed good cell membrane and could be successfully applied for imaging HSO3- in the mitochondria of living cells.

Role of hydrogen sulfide in sulfur dioxide production and vascular regulation.

Both hydrogen sulfide (H2S) and sulfur dioxide (SO2) are produced endogenously from the mammalian metabolic pathway of sulfur-containing amino acids and play important roles in several vascular diseases. However, their interaction during the control of vascular function has not been fully clear. Here, we investigated the potential role of H2S in SO2 production and vascular regulation in vivo and in vitro. Wistar rats were divided into the vehicle, SO2, DL-propargylglycine (PPG) + SO2, ß-cyano-L-alanine (BCA) + SO2 and sodium hydrosulfide (NaHS) + SO2 groups. SO2 donor was administered with or without pre-administration of PPG, BCA or NaHS for 30 min after blood pressure was stabilized for 1 h, and then, the change in blood pressure was detected by catheterization via the common carotid artery. Rat plasma SO2 and H2S concentrations were measured by high performance liquid chromatography and sensitive sulfur electrode, respectively. The isolated aortic rings were prepared for the measurement of changes in vasorelaxation stimulated by SO2 after PPG, BCA or NaHS pre-incubation. Results showed that the intravenous injection of SO2 donors caused transient hypotension in rats compared with vehicle group. After PPG or BCA pretreatment, the plasma H2S content decreased but the SO2 content increased markedly, and the hypotensive effect of SO2 was significantly enhanced. Conversely, NaHS pretreatment upregulated the plasma H2S content but reduced SO2 content, and attenuated the hypotensive effect of SO2. After PPG or BCA pre-incubation, the vasorelaxation response to SO2 was enhanced significantly. While NaHS pre-administration weakened the SO2-induced relaxation in aortic rings. In conclusion, our in vivo and in vitro data indicate that H2S negatively controls the plasma content of SO2 and the vasorelaxant effect under physiological conditions.

Insight into sulfur dioxide and its derivatives metabolism in living system with visualized evidences via ultra-sensitive fluorescent probe.

Sulfur dioxide (SO2) and its derivatives have long been considered as hazardous environmental pollutants but commonly used as food additives in safe dose range. They also could be produced from biological metabolism process of sulfur-containing amino acids. However, their physiological roles remain extremely obscure mainly due to lack of efficient tools for monitoring and imaging strategy establishment. Furthermore, most of current studies of this aspect focus on novel probe design or just imaging them rather than on the ins and outs. Therefore, there is a high significance of establishing highly sensitive detection strategy for monitoring SO2 derivatives in living systems, food and environment. Herein, we design a fluorescent probe MS-Bindol for sensitively detecting SO2 derivatives with a low detection limit (0.2 nM). We have established an imaging strategy for investigation of SO2 derivatives metabolism in living cells and zebrafish, providing visualize evidences and verified that SO2 derivatives could be synthetized from thiosulfate and glutathione(GSH) and be hardly consumed by using sulfite oxidase inhibitors (ferricyanide or arsenite). Moreover, the probe also exhibits excellent practicability in food as well as environmental samples. Our studies may help biologist for better understanding SO2 derivatives metabolism and deeply explore their physiological roles in biological systems.

Sulfur Dioxide: Endogenous Generation, Biological Effects, Detection, and Therapeutic Potential.

Significance: Previously, sulfur dioxide (SO2) was recognized as an air pollutant. However, it is found to be endogenously produced in mammalian tissues. As a new gasotransmitter, SO2 is involved in regulating the structure and function of blood vessels, heart, lung, gastrointestinal tract, nervous system, etc.Recent Advances: Increasing evidence showed that endogenous SO2 regulates cardiovascular physiological processes, such as blood pressure control, vasodilation, maintenance of the normal vascular structure, and cardiac negative inotropy. Under pathological conditions including hypertension, atherosclerosis, vascular calcification, aging endothelial dysfunction, myocardial injury, myocardial hypertrophy, diabetic myocardial fibrosis, sepsis-induced cardiac dysfunction, pulmonary hypertension, acute lung injury, colitis, epilepsy-related brain injury, depression and anxiety, and addictive drug reward memory consolidation, endogenous SO2 protects against the pathological changes via different molecular mechanisms and the disturbed SO2/aspartate aminotransferase pathway is likely involved in the mechanisms for the earlier mentioned pathologic processes. Critical Issues: A comprehensive understanding of the biological effects of endogenous SO2 is extremely important for the development of novel SO2 therapy. In this review, we summarized the biological effects, mechanism of action, SO2 detection methods, and its related prodrugs. Future Directions: Further studies should be conducted to understand the effects of endogenous SO2 in various physiological and pathophysiological processes and clarify its underlying mechanisms. More efficient and accurate SO2 detection methods, as well as specific and effective SO2-releasing systems should be designed for the treatment and prevention of clinical related diseases. The translation from SO2 basic medical research to its clinical application is also worthy of further study. Antioxid. Redox Signal. 36, 256-274.

Induced sulfur metabolism by sulfur dioxide maintains postharvest quality of 'Thompson Seedless' grape through increasing sulfite content.

BACKGROUND: The commercial preservation of table grapes largely depends on the application of sulfur dioxide (SO2 ). However, little is known about whether SO2 participates in sulfur metabolism to improve the postharvest quality of table grapes. In this study, the contents of sulfur-containing compounds, activities of enzymes, and expression of genes involved in sulfur metabolism in table grapes (Vitis vinifera cv. Thompson Seedless) were evaluated. RESULTS: The results indicated that SO2 treatment maintained the postharvest quality of table grapes. The sulfite content in rachises and berries, but not the sulfate content, increased in response to SO2 treatment. SO2 caused high activities of sulfite reductase, O-acetylserine (thiol)-lyase, and γ-glutamylcysteine synthetase, thereby increasing the contents of cysteine, hydrogen sulfide, and glutathione in the rachises and berries. The expression of VvSURTL, VvATPS1, VvATPS2, and VvAPR3 decreased in response to SO2 treatment; however, the transcript levels of VvSiR1 and VvOASTL exhibited the opposite tendency. CONCLUSION: These findings indicated that the sulfite converted from SO2 participated in sulfur metabolism and maintained the postharvest quality of table grapes by modulating the contents of metabolites, activities of enzymes, and expression of genes related to sulfur metabolism. © 2021 Society of Chemical Industry.

Dual-Targeting into the Mitochondria of Cancer Cells for Ratiometric Investigation of the Dynamic Fluctuation of Sulfur Dioxide and Formaldehyde with Two-Photon Integrated Semiconducting Polymer Dots.

Mitochondrial sulfur dioxide (SO2) and formaldehyde (FA) in cancer cells serve as important signal molecules in mediating multiple physiological and pathological activities. Accurate monitoring of the dynamic fluctuation of SO2 and FA in the mitochondria of cancer cells is important for insight into their relationships and functions in cancer, understanding cancer mechanism, and the role of mitochondrial homeostasis in cancer invasion and metastasis. Herein, a novel integrated two-photon semiconducting polymer dot (BF@Pdots) with dual-targeting (cancer cells and mitochondrial) and dual-emission in green and red regions, which is rationally designed through a four-step engineering strategy by using two newly synthesized functionalized polymers PFNA and FD-PSMA as precursors, has been developed for accurate tracking of the dynamic variation of SO2 and FA in the mitochondria of cancer cells. The sensing mechanism is on the basis of the fluorescence resonance energy transfer (FRET) process in BF@Pdots tuned by the reversible Michael addition reaction between the sensing-groups and SO2 (or FA). The integrated BF@Pdots nanoprobes display excellent performances in the accurate detection of the dynamic fluctuation of SO2 and FA such as precise positioning in the mitochondria of cancer cells, self-calibrating ratiometric, two-photon emission with long wavelength excitation, and fast reversible response. The BF@Pdots nanoprobes are also applied to the ratiometric detection of the dynamic fluctuation of exogenous and endogenous SO2 and FA in the mitochondria of cancer cells for the first time with satisfactory results. Taken together, this work will provide an attractive way to develop versatile integrated Pdots-based fluorescent probes through flexible molecular engineering for applications in accurate imaging of biomolecules in living systems.

Medicinal Chemistry Strategies Towards SO2 Donors as Research Tools and Potential Therapeutics.

SO2 is emerging as a possible endogenous signaling molecule in mammals. In addition, SO2 has also shown pharmacological effects, presenting SO2 as a promising potential therapeutic agent. The past decade has witnessed steady advances in the development of small molecule-based SO2 prodrugs/donors with varied release mechanisms. Herein, we summarize various strategies employed for SO2 prodrug design. The remaining challenges and issues will also be discussed.

Sulfur dioxide promotes seed germination by modulating reactive oxygen species production in maize.

Sulfur dioxide (SO2) is generally considered to be toxic to cells, but recent studies have shown that SO2 has positive roles in stress defense responses in plants. However, whether SO2 functions as a signaling molecule in the developmental process, especially in seed germination, is yet to be studied. Here, we present data supporting the role of SO2 in seed germination and possible molecular mechanisms. SO2 treatment significantly promoted the seed germination and seed vigor in maize. The germinating seeds treated with SO2 treatment exhibited higher reactive oxygen species (ROS) levels and NADPH oxidase activities. Furthermore, the specific NADPH oxidase inhibitor diphenyleneiodinium (DPI) strongly inhibited ROS accumulations, and SO2-promoted seed germination and vigor. Meanwhile, α-Amylase activity and transcripts in germinating seeds treated with SO2 were significantly elevated. These data have demonstrated that NADPH oxidase-dependent ROS production contributes to the induction of α-Amylase activity, thereby promoting seed germination upon SO2 exposure. SO2 might function as a signaling molecule in plant growth and development, especially in seed germination. This study might provide a theoretical foundation for the potential exploitation of hydrated SO2 in seed germination control in crop management.

Endogenous sulfur dioxide is a novel inhibitor of hypoxia-induced mast cell degranulation.

Introduction: Mast cell (MC) degranulation is an important step in the pathogenesis of inflammatory reactions and allergies; however, the mechanism of stabilizing MC membranes to reduce their degranulation is unclear. Methods: SO2 content in MC culture supernatant was measured by HPLC-FD. The protein and mRNA expressions of the key enzymes aspartate aminotransferase 1 (AAT1) and AAT2 and intracellular AAT activity were detected. The cAMP level in MCs was detected by immunofluorescence and ELISA. The release rate of MC degranulation marker ß-hexosaminidase was measured. The expression of AAT1 and cAMP, the MC accumulation and degranulation in lung tissues were detected. Objectives: To exam whether an endogenous sulfur dioxide (SO2) pathway exists in MCs and if it serves as a novel endogenous MC stabilizer. Results: We firstly show the existence of the endogenous SO2/AAT pathway in MCs. Moreover, when AAT1 was knocked down in MCs, MC degranulation was significantly increased, and could be rescued by a SO2 donor. Mechanistically, AAT1 knockdown decreased the cyclic adenosine monophosphate (cAMP) content in MCs, while SO2 prevented this reduction in a dose-independent manner. Pretreatment with the cAMP-synthesizing agonist forskolin or the cAMP degradation inhibitor IBMX significantly blocked the increase in AAT1 knockdown-induced MC degranulation. Furthermore, in hypoxia-stimulated MCs, AAT1 protein expression and SO2 production were markedly down regulated, and MC degranulation was activated, which were blunted by AAT1 overexpression. The cAMP synthesis inhibitor SQ22536 disrupted the suppressive effect of AAT1 overexpression on hypoxia-induced MC degranulation. In a hypoxic environment, mRNA and protein expression of AAT1 was significantly reduced in lung tissues of rats. Supplementation of SO2 elevated the cAMP level and reduced perivascular MC accumulation and degranulation in lung tissues of rats exposed to a hypoxic environment in vivo. Conclusion: SO2 serves as an endogenous MC stabilizer via upregulating the cAMP pathway under hypoxic circumstance.