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Skin injuries caused by accidents and acute or chronic diseases place a heavy burden on patients and health care systems. Current treatments mainly depend on preventing infection, debridement, and hemostasis and on supplementing growth factors, but patients will still have scar tissue proliferation or difficulty healing and other problems after treatment. Conventional treatment usually focuses on a single factor or process of wound repair and often ignores the influence of the wound pathological microenvironment on the final healing effect. Therefore, it is of substantial research value to develop multifunctional therapeutic methods that can actively regulate the wound microenvironment and reduce the oxidative stress level at the wound site to promote the repair of skin wounds. In recent years, various bioactive nanomaterials have shown great potential in tissue repair and regeneration due to their properties, including their unique surface interface effect, small size effect, enzyme activity and quantum effect. This review summarizes the mechanisms underlying skin wound repair and the defects in traditional treatment methods. We focus on analyzing the advantages of different types of nanomaterials and comment on their toxicity and side effects when used for skin wound repair.

Worldwide, the rapid increase in the incidence of diabetes and its complications poses a serious threat to human health. Ferroptosis, which is a new nonapoptotic form of cell death, has been proven to be closely related to the occurrence and development of diabetes and its complications. In recent years, lncRNAs have been confirmed to be involved in the occurrence and development of diabetes and play an important role in regulating ferroptosis. An increasing number of studies have shown that lncRNAs can affect the occurrence and development of diabetes and its complications by regulating ferroptosis. Therefore, lncRNAs have great potential as therapeutic targets for regulating ferroptosis-mediated diabetes and its complications. This paper reviewed the potential impact and regulatory mechanism of ferroptosis on diabetes and its complications, focusing on the effects of lncRNAs on the occurrence and development of ferroptosis-mediated diabetes and its complications and the regulation of ferroptosis-inducing reactive oxygen species, the key ferroptosis regulator Nrf2 and the NF-κB signaling pathway to provide new therapeutic strategies for the development of lncRNA-regulated ferroptosis-targeted drugs to treat diabetes.

The mechanism of lignin degradation via white rot fungi was studied. Phanerochaete chrysosporium and Pleurotus ostreatus were used for all the experiments, i.e., measuring the concentration and structure of alkali lignins and studying the effect of the substrate concentration and enzyme activity on the removal. Gas chromatography-mass spectrometry was performed on the reaction liquid of the lignin degradation enzyme system. Alkali lignin had a characteristic absorption spectrum with a peak at approximately 280 nm. Precipitation in the laccase (Lac) degradation system occurred earlier, as well as being more obvious than that in the manganese peroxidase (Mnp) degradation system. The maximum removal was 29.4% in the Mnp degradation system at a concentration of 40 mg/L. The removal increased in a concentration-dependent manner in the Lac degradation system. The increase in Mnp and Lac enzyme activity led to an increased alkali lignin removal. The removal of the control group was significantly lower than the experimental degradation systems. The degradation mainly produced organic acids, esters, and aromatic substances. In conclusion, white rot fungi could effectively remove alkali lignin, in which precipitation played a major role, followed by enzymolysis; the enzymolysis was associated with the alkali lignin concentration and enzyme activity.

Large amounts of enriched cadmium (Cd) in the environment seriously threatens the healthy and sustainable development of the aquaculture industry and greatly restricts the development of the food processing industry. Studying the distribution and toxic effects of Cd in fish, as well as the possible toxic effects of Cd on the human body, is very significant. A large number of studies have shown that the accumulation and distribution of Cd in fish are biologically specific, cause tissue differences, and seriously damage the integrity of tissue structure and function, the antioxidant defense system, the reproductive regulation system, and the immune system. The physiological, biochemical, enzyme, molecular, and gene expression levels change with different concentrations and times of Cd exposure, and these changes are closely related to the target sites of Cd action and tissues in fish. Therefore, the toxic effects of Cd on fish occur with multiple tissues, systems, and levels.

Diabetes mellitus (DM) is an endocrine and metabolic disease caused by a variety of pathogenic factors, including genetic factors, environmental factors and behavior. In recent decades, the number of cases and the prevalence of diabetes have steadily increased, and it has become one of the most threatening diseases to human health in the world. Currently, insulin is the most effective and direct way to control hyperglycemia for diabetes treatment at a low cost. However, hypoglycemia is often a common complication of insulin treatment. Moreover, with the extension of treatment time, insulin resistance, considered the typical adverse symptom, can appear. Therefore, it is urgent to develop new targets and more effective and safer drugs for diabetes treatment to avoid adverse reactions and the insulin tolerance of traditional hypoglycemic drugs.In recent years, it has been found that some fibroblast growth factors (FGFs), including FGF1, FGF19 and FGF21, can safely and effectively reduce hyperglycemia and have the potential to be developed as new drugs for the treatment of diabetes. FGF23 is also closely related to diabetes and its complications, which provides a new approach for regulating blood glucose and solving the problem of insulin tolerance.This article reviews the research progress on the physiology and pharmacology of fibroblast growth factor in the treatment of diabetes. We focus on the application of FGFs in diabetes care and prevention.

Cancer immunotherapy is a promising approach that has recently gained its importance in treating cancer. Despite various approaches of immunotherapies being used to target cancer cells, they are either not effective against all types of cancer or for all patients. Although efforts are being made to improve the cancer immunotherapy in all possible ways, one important hindrance that lowers the immune response to kill cancer cells is the infiltration of Regulatory T (Treg) cells into the tumor cells, favoring tumor progression, on one hand, and inhibiting the activation of T cells to respond to cancer cells, on the other hand. Therefore, new anti-cancer drugs and vaccines fail to show promising results against cancer. This is due to the infiltration of Treg cells into the tumor region and suppression of anti-cancer activity. Thus, regardless of various types of immunotherapies being practiced, understanding the mechanisms of how Treg cells favor tumor progression and inhibition of anti-cancer activity is worthwhile. Therefore, the review highlights the importance of Tregs cells and how depletion of Treg cells can pave the way to an effective immunotherapy by activating the immune responses against cancer.

In recent decades, diabetes mellitus has become a major chronic disease threatening human health worldwide, and the age of patients tends to be younger; however, the pathogenesis remains unclear, resulting in many difficulties in its treatment. As an ideal model animal, zebrafish can simulate the processes of human diabetes well. In this study, we successfully established a model of diabetic zebrafish larvae in a previous work. Furthermore, transcriptome analysis was completed, and the results suggested that 10.59% of differentially expressed genes (DEGs) related to the apoptosis pathway need to be considered. Then, glucose-induced developmental toxicity, reactive oxygen species (ROS) accumulation, antioxidant system function, apoptosis and mitochondrial dysfunction were measured in zebrafish larvae. We hope that this study will provide valuable reference information for type 2 juvenile diabetes treatment.

Gallinacin-3 (Gal-3) is a newly discovered epithelial beta-defensin that acts as cationic antimicrobial peptides, and plays an important role in chicken innate immunity. However, the gallinacin-3 precursor containeda lengthy C-terminal region, which often hindered itsexpression. After codon optimization of Gal-3 and construction of an expression vector, the transgenic plants of Medicago sativa were obtained. Transgenic plants were validated and expression of proteins was detected. The antimicrobial activity of chicken β Gal-3 was analyzed and effects of chicken β Gal-3 on the body weight and intestinal microflora of mice were described. Our results demonstrated that the codon optimized chicken Gal-3 was stably expressed in transgenic Medicago sativa using the pCAMBIA3301 expression vector under the control of protein phosphatase (Ppha) promoter. Five transgenic plants with the highest expression of chicken β Gal-3 were selected, and were evaluated for the in vitro antimicrobial activity against Escherichia coli, Staphylococcus aureus and Salmonella typhi. Our findings confirmed that the Minimum Inhibitory Concentration (MIC) of the three bacterial strains were 32, 16 and 128 μg/mL, respectively. In addition, the effect of chicken Gal-3 on the body weight of mice fed with transgenic plants showed no significant deviation compared with that of the control group. Similarly, no loss of intestinal microflora was evident in the experimental group compared with the control group. Together, our findings demonstrate an alternative method for the stable expression of chicken Gal-3 withsignificant antibacterial effects and potential probiotics uses. In addition, this study may also be useful in the development of resistant M. sativa plants against pathogenic bacteria in future studies.

In recent decades, diabetes mellitus has become a major chronic disease threatening human health worldwide, and the age of patients tends to be younger; however, the pathogenesis remains unclear, resulting in many difficulties in its treatment. As an ideal model animal, zebrafish can simulate the processes of human diabetes well. In this study, we successfully established a model of diabetic zebrafish larvae in a previous work. Furthermore, transcriptome analysis was completed, and the results suggested that 10.59% of differentially expressed genes (DEGs) related to the apoptosis pathway need to be considered. Then, glucose-induced developmental toxicity, reactive oxygen species (ROS) accumulation, antioxidant system function, apoptosis and mitochondrial dysfunction were measured in zebrafish larvae. We hope that this study will provide valuable reference information for type 2 juvenile diabetes treatment.

Fish not only constitute an important trophic level in aquatic ecosystems but also serve as an important source of protein for human beings. The health of fish is related to the sustained and healthy development of their entire aquatic ecosystem. Due to the widespread use, mass production, high disposal frequency, and degradation resistance of plastics, these pollutants are released into aquatic environments on a large scale. They have become one of the fastest growing pollutants and have a substantial toxic effect on fish. Microplastics have intrinsic toxicity and can absorb heavy metals discharged into water. The adsorption of heavy metals onto microplastics in aquatic environments is affected by many factors and serves as a convenient way for heavy metals to migrate from the environment to organisms. Fish are exposed to both microplastics and heavy metals. In this paper, the toxic effects of heavy metal adsorption by microplastics on fish are reviewed, and the focus is on the toxic effects at the individual (survival, feeding activity and swimming, energy reserves and respiration, intestinal microorganisms, development and growth, and reproduction), cellular (cytotoxicity, oxidative damage, inflammatory response, neurotoxicity, and metabolism) and molecular (gene expression) levels. This facilitates an assessment of the pollutants’ impact on ecotoxicity and contributes to the regulation of these pollutants in the environment.

In recent years, with the aggravation of environmental pollution, the study of aquatic ecotoxicology has become a hot topic. Some aquatic organisms, such as large fleas, toads, and zebrafish, have been developed and applied as model organisms. They have been increasingly used to study the bioaccumulation and toxicity of environmental pollutants due to the advantages of their small size, easy reproduction, short life cycle, low maintenance cost, and ability to combine genetic, cellular, and whole organism endpoints. This review summarizes the methods of zebrafish, as a model in aquatic ecotoxicology, using its developmental toxicity, biomarkers, genomics, and phenotype analysis to evaluate the toxicity of environmental pollutants, providing a reference value for researchers to select model animals for aquatic ecotoxicology research.

Diabetes is a metabolic disease characterized by high blood glucose levels. With economic development and lifestyle changes, the prevalence of diabetes is increasing yearly. Thus, it has become an increasingly serious public health problem in countries around the world. The etiology of diabetes is complex, and its pathogenic mechanisms are not completely clear. The use of diabetic animal models is helpful in the study of the pathogenesis of diabetes and the development of drugs. The emerging vertebrate model of zebrafish has many advantages, such as its small size, large number of eggs, short growth cycle, simple cultivation of adult fish, and effective improvement of experimental efficiency. Thus, this model is highly suitable for research as an animal model of diabetes. This review not only summarizes the advantages of zebrafish as a diabetes model, but also summarizes the construction methods and challenges of zebrafish models of type 1 diabetes, type 2 diabetes, and diabetes complications. This study provides valuable reference information for further study of the pathological mechanisms of diabetes and the research and development of new related therapeutic drugs.

Plants have evolved many strategies for adaptation to extreme environments. Ca

Hydrogen sulfide (H

Hydrogen sulfide (H2S) is considered the third gas signal molecule in recent years. A large number of studies have shown that H2S not only played an important role in animals but also participated in the regulation of plant growth and development and responses to various environmental stresses. Waterlogging, as a kind of abiotic stress, poses a serious threat to land-based waterlogging-sensitive plants, and which H2S plays an indispensable role in response to. In this review, we summarized that H2S improves resistance to waterlogging stress by affecting lateral root development, photosynthetic efficiency, and cell fates. Here, we reviewed the roles of H2S in plant resistance to waterlogging stress, focusing on the mechanism of its promotion to gained hypoxia tolerance. Finally, we raised relevant issues that needed to be addressed.

Arabinogalactan proteins (AGPs) are essential members of hyperglycosylated glycoproteins and are critical for the sexual reproduction of plants. To our knowledge, currently Arabodopsis FLA3 and Brassica BcMF8 are the only two members of AGPs reported concerning pollen intine formation. Previously, the orthologue of AtAGP6 in B. campestris, BcMF18, was isolated and proved to affect microspore development. In this study, western blot assay and subcellular localization showed that BcMF18 encoded an approximately 19.5 kDa secretory AGP protein which anchored to extracellular matrices. Ectopic overexpression of BcMF18 (OE) in Arabodopsis caused reduced male fertility and resulted in short siliques with low seed set. Approximately 46% of OE pollen grains were aborted and lacked viability, without all cytoplasmic materials and nuclei. Pollen abortion which led to defective microspore production with no cellulose was observed to start at the bicellular stage. At this point, intine layer displayed abnormalities and degraded from the bicellular stage, which led to the failure in keeping the internal environment stability and resulted in hollow remnants of microspores. However, the basic structure and patterning of the exine layer of collapsed pollen grains seemed unaffected, completed with intact nexine, baculum, and tectum to constitute a pronounced reticulate structure filled with typhine. Based on these results presented here, it is proposed that BcMF18 functions in Arabodopsis and is associated with pollen intine formation, possibly through participating in the formation of proteoglycan structures, which provide strong evidence for subfunctionalization from AtAGP6 to BcMF18.

Cancer immunotherapy is a promising approach that has recently gained its importance in treating cancer. Despite various approaches of immunotherapies being used to target cancer cells, they are either not effective against all types of cancer or for all patients. Although efforts are being made to improve the cancer immunotherapy in all possible ways, one important hindrance that lowers the immune response to kill cancer cells is the infiltration of Regulatory T (Treg) cells into the tumor cells, favoring tumor progression, on one hand, and inhibiting the activation of T cells to respond to cancer cells, on the other hand. Therefore, new anti-cancer drugs and vaccines fail to show promising results against cancer. This is due to the infiltration of Treg cells into the tumor region and suppression of anti-cancer activity. Thus, regardless of various types of immunotherapies being practiced, understanding the mechanisms of how Treg cells favor tumor progression and inhibition of anti-cancer activity is worthwhile. Therefore, the review highlights the importance of Tregs cells and how depletion of Treg cells can pave the way to an effective immunotherapy by activating the immune responses against cancer.

Cancer remains a daunting and cureless disease, which is responsible for one-sixth of human deaths worldwide. These mortality rates have been expected to rise in the future due to the side effects of conventional treatments (chemotherapy, radiotherapy, and surgery), which can be addressed by applying nanomedicine. In order to escape from biological barriers, such nanomedicine should be mimicked and designed to be stealthy while navigating in the bloodstream. To achieve this, scientists take advantage of erythrocytes (red blood cells; RBCs) as drug carriers and develop RBC membrane (RBCm) coating nanotechnology. Thanks to the significant advances in nanoengineering, various facile surface functionalization methods can be applied to arm RBCm with not only targeting moieties, but also imaging agents, therapeutic agents, and nanoparticles, which are useful for theranostic nanomedicine. This review focuses on refunctionalization of erythrocyte-based nanomedicine for enhancing cancer-targeted drug delivery.

Plants have evolved many strategies for adaptation to extreme environments. Ca2+, acting as an important secondary messenger in plant cells, is a signaling molecule involved in plants’ response and adaptation to external stress. In plant cells, almost all kinds of abiotic stresses are able to raise cytosolic Ca2+ levels, and the spatiotemporal distribution of this molecule in distant cells suggests that Ca2+ may be a universal signal regulating different kinds of abiotic stress. Ca2+ is used to sense and transduce various stress signals through its downstream calcium-binding proteins, thereby inducing a series of biochemical reactions to adapt to or resist various stresses. This review summarizes the roles and molecular mechanisms of cytosolic Ca2+ in response to abiotic stresses such as drought, high salinity, ultraviolet light, heavy metals, waterlogging, extreme temperature and wounding. Furthermore, we focused on the crosstalk between Ca2+ and other signaling molecules in plants suffering from extreme environmental stress.

Cytoplasmic male sterility (CMS) is a widely used trait in angiosperms caused by perturbations in nucleus-mitochondrion interactions that suppress the production of functional pollen. MicroRNAs (miRNAs) are small non-coding RNAs that act as regulatory molecules of transcriptional or post-transcriptional gene silencing in plants. The discovery of miRNAs and their possible implications in CMS induction provides clues for the intricacies and complexity of this phenomenon. Previously, we characterized an Ogura-CMS line of turnip (Brassica rapa ssp. rapifera) that displays distinct impaired anther development with defective microspore production and premature tapetum degeneration. In the present study, high-throughput sequencing was employed for a genome-wide investigation of miRNAs. Six small RNA libraries of inflorescences collected from the Ogura-CMS line and its maintainer fertile (MF) line of turnip were constructed. A total of 120 pre-miRNAs corresponding to 89 mature miRNAs were identified, including 87 conversed miRNAs and 33 novel miRNAs. Among these miRNAs, the expression of 10 differentially expressed mature miRNAs originating from 12 pre-miRNAs was shown to have changed by more than two-fold between inflorescences of the Ogura-CMS line and inflorescences of the MF line, including 8 down- and 2 up-regulated miRNAs. The expression profiles of the differentially expressed miRNAs were confirmed by stem-loop quantitative real-time PCR. In addition, to identify the targets of the identified miRNAs, a degradome analysis was performed. A total of 22 targets of 25 miRNAs and 17 targets of 28 miRNAs were identified as being involved in the reproductive development for Ogura-CMS and MF lines of turnip, respectively. Negative correlations of expression patterns between partial miRNAs and their targets were detected. Some of these identified targets, such as squamosa promoter-binding-like transcription factor family proteins, auxin response factors and pentatricopeptide repeat-containing proteins, were previously reported to be involved in reproductive development in plants. Taken together, our results can help improve the understanding of miRNA-mediated regulatory pathways that might be involved in CMS occurrence in turnip.

Atherosclerosis (AS), a typical chronic inflammatory vascular disease, is the main pathological basis of ischemic cardio/cerebrovascular disease (CVD). Long-term administration was characterized with low efficacy and serious side effects, while the macrophages with attractive intrinsic homing target have great potential in the efficient and safe management of AS. In this review, we focused on the systematical summary of the macrophage-based therapies in AS management, including macrophage autophagy, polarization, targeted delivery, microenvironment-triggered drug release, and macrophage- or macrophage membrane-based drug carrier. In conclusion, macrophage-based therapies have great promise to effectively manage AS in future research and clinic translation.

Our data present H 2 S in a new role, serving as a multi-faceted transducer to different response mechanisms during NO-induced acquisition of tolerance to flooding-induced hypoxia in maize seedling roots. Nitric oxide (NO), serving as a secondary messenger, modulates physiological processes in plants. Recently, hydrogen sulfide (H2S) has been demonstrated to have similar signaling functions. This study focused on the effects of treatment with H2S on NO-induced hypoxia tolerance in maize seedlings. The results showed that treatment with the NO donor sodium nitroprusside (SNP) enhanced survival rate of submerged maize roots through induced accumulation of endogenous H2S. The induced H2S then enhanced endogenous Ca2+ levels as well as the Ca2+-dependent activity of alcohol dehydrogenase (ADH), improving the capacity for antioxidant defense and, ultimately, the hypoxia tolerance in maize seedlings. In addition, NO induced the activities of key enzymes in H2S biosynthesis, such as l-cysteine desulfhydrases (l-CDs), O-acetyl-l-serine (thiol)lyase (OAS-TL), and β-Cyanoalanine Synthase (CAS). SNP-induced hypoxia tolerance was enhanced by the application of NaHS, but was eliminated by the H2S-synthesis inhibitor hydroxylamine (HA) and the H2S-scavenger hypotaurine (HT). H2S concurrently enhanced the transcriptional levels of relative hypoxia-induced genes. Together, our findings indicated that H2S serves as a multi-faceted transducer that enhances the nitric oxide-induced hypoxia tolerance in maize (Zea mays L.)

Flooding stress constrains crop growth and yield because most agricultural species are flood-sensitive. However, many of the plant species that live in permanently or temporarily flooded habitats have evolved specific traits to cope with these harsh conditions. Grass pea (Lathyrus sativus L.) is a legume that tolerates stresses such as drought, diseases, and pests; however, it is unclear whether grass pea has a tolerance mechanism for flooding stress. To understand if grass pea tolerates hypoxia and how it deals with hypoxic stress, the effects of hypoxia on root tip death, physiological, and morpho-anatomical alterations in grass pea and pea (Pisum sativum), which is sensitive to hypoxia, were compared. The results showed that activities of antioxidant enzymes, namely superoxide dismutase, catalase, ascorbate peroxidase, and glutathione content in grass pea were greater than in pea during hypoxia, which protected the root tip from oxidative damage and reduced ion leakage, which helped maintain membrane integrity. Furthermore, aerenchyma and lateral root development accompanied by ethylene production, moderate ROS accumulation-mediated cell death, and Ca2+ spatial-temporal heterogeneity developed well in grass pea compared to pea, which may not only facilitate internal gas diffusion but also promote removal of toxic by-products under hypoxic conditions. These results demonstrate that grass pea is more tolerant to hypoxic stress induced by flooding than garden pea seedlings. This discovery not only provides significant information for understanding the hypoxia-tolerant mechanisms in plants, but also promotes the usability of grass pea in flood-prone areas.

Growth factors (GFs) act as important active molecules for the treatment of skin wounds. However, their clinical translation is seriously restrained due to single function and short half-life. Besides, the underlying GFs-mediated wound healing mechanism remains elusive. Therefore, we aimed to develop a thermo-sensitive chitosan hydrogel embedding with poly lactic-co-glycolic acid (PLGA) microspheres which can deliver platelet-derived growth factor receptor (PDGF) for wound healing. The generated PDGF-PLGA hydrogel was systematically evaluated for its wound healing efficiency by the in vivo experiments, including biocompatibility testing, cell proliferation and migration, wound closure rate, granulation tissue formation and collagen deposition. Further, the expression levels of autophagy-related proteins were detected. The results showed that the PDGF-PLGA hydrogel exhibited excellent cell compatibility, cell proliferation and migration. The PDGF-PLGA hydrogel was superior to PDGF alone and control groups in promoting wound closure, granulation tissue formation and collagen synthesis. In addition, the autophagy levels were significantly decreased by PDGF hydrogel in wound tissue of treated mice as compared with PDGF alone and control groups. We also found that the autophagy activator rapamycin delayed PDGF hydrogel-mediated wound healing. This study provides a novel mechanism for the beneficial effects of PDGF-PLGA hydrogel on the wound repair.

Ogura-type cytoplasmic male sterility (Ogura-CMS) has been widely used in the hybrid breeding industry for cruciferous vegetables. Turnip (Brassica rapa ssp. rapifera) is one of the most important local cruciferous vegetables in China, cultivated for its fleshy root as a flat disc. Here, morphological characteristics of an Ogura-CMS line 'BY10-2A' and its maintainer fertile (MF) line 'BY10-2B' of turnip were investigated. Ogura-CMS turnip showed a reduction in the size of the fleshy root, and had distinct defects in microspore development and tapetum degeneration during the transition from microspore mother cells to tetrads. Defective microspore production and premature tapetum degeneration during microgametogenesis resulted in short filaments and withered white anthers, leading to complete male sterility of the Ogura-CMS line. Additionally, the mechanism regulating Ogura-CMS in turnip was investigated using inflorescence transcriptome analyses of the Ogura-CMS and MF lines. The de novo assembly resulted in a total of 84,132 unigenes. Among them, 5,117 differentially expressed genes (DEGs) were identified, including 1,339 up- and 3,778 down-regulated genes in the Ogura-CMS line compared to the MF line. A number of functionally known members involved in anther development and microspore formation were addressed in our DEG pool, particularly genes regulating tapetum programmed cell death (PCD), and associated with pollen wall formation. Additionally, 185 novel genes were proposed to function in male organ development based on GO analyses, of which 26 DEGs were genotype-specifically expressed. Our research provides a comprehensive foundation for understanding anther development and the CMS mechanism in turnip.

Flooding of soils often results in hypoxic conditions surrounding plant roots, which is a harmful abiotic stress to crops. Hydrogen sulfide (H2S) is a highly diffusible, gaseous molecule that modulates cell signaling and is involved in hypoxia signaling in animal cells. However, there have been no previous studies of H2S in plant cells in response to hypoxia. The effects of H2S on hypoxia-induced root tip death were studied in pea (Pisum sativum) via analysis of endogenous H2S and reactive oxygen species (ROS) levels. The activities of key enzymes involved in antioxidative and H2S metabolic pathways were determined using spectrophotometric assays. Ethylene was measured by gas chromatography. We found that exogenous H2S pretreatment dramatically alleviated hypoxia-induced root tip death by protecting root tip cell membranes from ROS damage induced by hypoxia and by stimulating a quiescence strategy through inhibiting ethylene production. Conversely, root tip death induced by hypoxia was strongly enhanced by inhibition of the key enzymes responsible for endogenous H2S biosynthesis. Our results demonstrated that exogenous H2S pretreatment significantly alleviates hypoxia-induced root tip death in pea seedlings and, therefore, enhances the tolerance of the plant to hypoxic stress.