TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.

BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. CONCLUSIONS: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Low-dose ionizing radiation-induced RET/PTC1 rearrangement via the non-homologous end joining pathway to drive thyroid cancer.

Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled-coil domain containing 6 [CCDC6]-rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N-thy-ori-3-1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low-dose IR-induced RET/PTC1 rearrangement in a dose-dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI-1, and Olaparib were employed to inhibit non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR-induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) decreased the efficiency of NHEJ and thus reduced IR-induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR-induced RET/PTC1 rearrangement. Targeting DNA-PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR-induced RET/PTC1 rearrangement in PTC.

DNA-PKcs/AKT1 inhibits epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1.

INTRODUCTION: Radiation-induced pulmonary fibrosis (RIPF) is a chronic, progressive, irreversible lung interstitial disease that develops after radiotherapy. Although several previous studies have focused on the mechanism of epithelial-mesenchymal transition (EMT) in lung epithelial cells, the essential factors involved in this process remain poorly understood. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) exhibits strong repair capacity when cells undergo radiation-induced damage; whether DNA-PKcs regulates EMT during RIPF remains unclear. OBJECTIVES: To investigate the role and molecular mechanism of DNA-PKcs in RIPF and provide an important theoretical basis for utilising DNA-PKcs-targeted drugs for preventing RIPF. METHODS: DNA-PKcs knockout (DPK-/-) mice were generated via the Cas9/sgRNA technique and subjected to whole chest ionizing radiation (IR) at a 20 Gy dose. Before whole chest IR, the mice were intragastrically administered the DNA-PKcs-targeted drug VND3207. Lung tissues were collected at 1 and 5 months after IR. RESULTS: The expression of DNA-PKcs is low in pulmonary fibrosis (PF) patients. DNA-PKcs deficiency significantly exacerbated RIPF by promoting EMT in lung epithelial cells. Mechanistically, DNA-PKcs deletion by shRNA or inhibitor NU7441 maintained the protein stability of Twist1. Furthermore, AKT1 mediated the interaction between DNA-PKcs and Twist1. High Twist1 expression and EMT-associated changes caused by DNA-PKcs deletion were blocked by insulin-like growth factor-1 (IGF-1), an AKT1 agonist. The radioprotective drug VND3207 prevented IR-induced EMT and alleviated RIPF in mice by stimulating the kinase activity of DNA-PKcs. CONCLUSION: Our study clarified the critical role and mechanism of DNA-PKcs in RIPF and showed that it could be a potential target for preventing RIPF.

Activable Photodynamic DNA Probe with an "AND" Logic Gate for Precision Skin Cancer Therapy.

Photodynamic therapy (PDT) has emerged as a promising approach for squamous cell carcinoma treatment but hindered by tumor hypoxia, acquired resistance, phototoxicity, and so on. To address these issues, we developed a smart strategy utilizing activable photosensitizers delivered by an aptamer-functionalized DNA probe (ADP). The ADP incorporated an AS1411 aptamer for tumor targeting and a linear antisense oligonucleotide (ASO) for recognition of Survivin mRNA. In the absence of the target, PDT remained quenched, thereby avoiding phototoxicity during circulation and nonselective distribution. With the aid of the aptamer, ADP achieved selective targeting of tumors. Upon internalization, ADP targeted recognized Survivin mRNA, triggering PDT activation, and releasing ASO to down-regulate Survivin expression and reverse tumor resistance. Consequently, the activable photosensitizers exhibited an "AND" logic gate, combining tumor-targeting delivery and tumor-related gene activation, thus enhancing its specificity. Additionally, the incorporation of hemin into the ADP provided catalase activity, converting tumor-abundant H2O2 into O2, thereby ameliorating tumor hypoxia. The resulting functionalized G-quadruplex/hemin-DNA probe complex demonstrated targeted delivery and activation, minimized side effects, and enhanced PDT efficacy in both xenograft tumor-bearing mice and patient-derived xenograft models. This study offers a unique and promising platform for efficient and safe PDT, thus holding great potential for future clinical translation and improved cancer therapy.

Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.

Salt-inducible kinase 2 (SIK2) belongs to the serine/threonine protein kinases of the AMPK/SNF1 family, which has important roles in cell cycle, tumor, melanogenesis, neuronal damage repair and apoptosis. Recent studies showed that SIK2 regulates the macrophage polarization to make a balance between inflammation and macrophage. Macrophage is critical to initiate immune regulation, however, whether SIK2 can be involved in immune regulation is not still well understood. Here, we revealed that the protein of SIK2 was highly expressed in thymus, spleen, lung, and brain. And SIK2 protein content increased in RAW264.7 and AHH1 cells with a time and dose-dependent after-ionizing radiation (IR). Inhibition of SIK2 could promote AHH1 cells apoptosis Moreover, we used the Cre-LoxP system to construct the SIK2+/- mice, and the research on function suggested that the deficiency of SIK2 could promote the sensitivity of IR. The deficiency of SIK2 promoted the immune injury via inhibiting the maturation of T cells and B cells. Furthermore, the TCRß rearrangement was inhibited by the deficiency of SIK2. Collectively, this study demonstrated that SIK2 provides an essential function of regulating immune injury, which will provide new ideas for the treatment of immune injury-related diseases.

Research progress of LINE-1 in the diagnosis, prognosis, and treatment of gynecologic tumors.

The retrotransposon known as long interspersed nuclear element-1 (LINE-1), which is currently the sole autonomously mobile transposon in the human genome, can result in insertional mutations, chromosomal rearrangements, and genomic instability. In recent years, numerous studies have shown that LINE-1 is involved in the development of various diseases and also plays an important role in the immune regulation of the organism. The expression of LINE-1 in gynecologic tumors suggests that it is expected to be an independent indicator for early diagnosis and prognosis, and also, as a therapeutic target, LINE-1 is closely associated with gynecologic tumor prognosis. This article discusses the function of LINE-1 in the diagnosis, treatment, and prognosis of ovarian, cervical, and endometrial malignancies, as well as other gynecologic malignancies. It offers fresh perspectives on the early detection of tumors and the creation of novel anti-tumor medications.

Targeting lncRNA DDIT4-AS1 Sensitizes Triple Negative Breast Cancer to Chemotherapy via Suppressing of Autophagy.

In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both in vitro and in vivo. Using a self-activatable siRNA/drug core-shell nanoparticle system, which effectively deliver both DDIT4-AS1 siRNA and paclitaxel to the tumor-bearing mice, a significantly enhanced antitumor activity is achieved. Importantly, the codelivery nanoparticles exert a stronger antitumor effect on breast cancer patient-derived organoids. These findings indicate that lncRNA DDIT4-AS1-mediated activation of autophagy promotes progression and chemoresistance of TNBC, and targeting of DDIT4-AS1 may be exploited as a new therapeutic approach to enhancing the efficacy of chemotherapy against TNBC.

Hemostatic effects of FmocF-ADP hydrogel consisted of Fmoc-Phenylalanine and ADP.

During trauma and surgery, bleeding is a major concern. One of the crucial strategies for hemostasis is the use of biological hemostatic material. Herein, we reported an amino acid-based hydrogel FmocF-ADP hydrogel, which consisted of N-[(9H-fluoren-9-ylmethoxy) carbonyl]-3-phenyl-L-alanine (FmocF) and adenosine diphosphate (ADP) sodium solution. The hydrogel was created by FmocF self-assembling to nanofiber in ADP sodium solution and then cross-linking to hydrogel. FmocF-ADP hydrogel showed good in vitro coagulation activity as measured by whole blood clotting assays, platelet clotting assays, platelet activation assays, and platelet adhesion assays. Further, it was noted to reveal an exceptional in vivo hemostatic effect in a mouse liver bleeding model. Together with the previous report of the good biocompatibility and antimicrobial activity of FmocF hydrogel, our study would extend the biomedical application of FmocF hydrogel. In conclusion, the present study would provide a constructive strategy for the development of new antimicrobial and hemostatic materials or develop a potential hemostatic material.

LANA regulates miR-155/GATA3 signaling axis by enhancing c-Jun/c-Fos interaction to promote the proliferation and migration of KSHV-infected cells.

Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA-binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV-infected cells, while microRNA-155 (miR-155) was highly expressed in KS serum and KSHV-infected cells. miR-155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV-encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV-infected cells by regulating the miR-155/GATA3 axis. Regarding the molecular mechanism, c-Jun and c-Fos interact to form a complex. LANA upregulates the expression of c-Jun and c-Fos and enhances the formation of c-Jun/c-Fos complex. The complex binds to the -95∼-100 bp site of miR-155 promoter and transcriptionally activates miR-155. All in all, LANA enhances the c-Jun/c-Fos interaction, resulting in enhanced transcriptional regulation of miR-155 by the c-Jun/c-Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV-infected cells. The discovery of LANA/c-Jun/c-Fos/miR-155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS.

Advances in Exosomal microRNAs and Proteins in Ovarian Cancer Diagnosis, Prognosis, and Treatment.

Late diagnosis, postoperative recurrence, and chemotherapy resistance are the main causes of the high mortality rate in ovarian cancer (OC). Understanding the molecular mechanisms in the pathogenesis and progression of OC may contribute to discovering new tumor biomarkers and therapeutic targets for OC. Exosomes are small extracellular vesicles derived from different types of cells that carry cargos, including nucleic acids, proteins, and lipids, and are pivotal mediators of intercellular communication in the tumor microenvironment. There is emerging evidence that exosomal proteins and nucleic acids play pivotal roles in facilitating the progression and drug resistance of OC. Identification of these factors may aid in the future diagnosis of OC. Furthermore, they also have promising value as OC therapeutic targets that can improve the prognosis. In the current review, we summarize the progress of exosomal research in OC, especially highlighting the most updated roles of exosomal microRNAs and proteins in the diagnosis, prognosis, therapy, and drug resistance of OC in order to facilitate future studies in this area.

Alveolar type 2 epithelial cell senescence and radiation-induced pulmonary fibrosis.

Radiation-induced pulmonary fibrosis (RIPF) is a chronic and progressive respiratory tract disease characterized by collagen deposition. The pathogenesis of RIPF is still unclear. Type 2 alveolar epithelial cells (AT2), the essential cells that maintain the structure and function of lung tissue, are crucial for developing pulmonary fibrosis. Recent studies indicate the critical role of AT2 cell senescence during the onset and progression of RIPF. In addition, clearance of senescent AT2 cells and treatment with senolytic drugs efficiently improve lung function and radiation-induced pulmonary fibrosis symptoms. These findings indicate that AT2 cell senescence has the potential to contribute significantly to the innovative treatment of fibrotic lung disorders. This review summarizes the current knowledge from basic and clinical research about the mechanism and functions of AT2 cell senescence in RIPF and points to the prospects for clinical treatment by targeting senescent AT2 cells.

Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review.

Background and Objective: The adeno-associated virus (AAV) is a member of the Parvoviridae family and has emerged as one of the most popular and promising approaches for gene therapy due to its low toxicity, low immunogenicity, and excellent safety after optimization. Advances in gene therapy methods have allowed novel treatments such as using AAV to knock out or repair target genes. AAV-mediated gene therapy has been used in numerous tumor studies, including lymphatic metastasis of prostate cancer, liver cancer, and renal cell carcinoma in mice. Ovarian cancer is an extremely aggressive malignancy which is prone to recurrence, and AAV vector-based gene therapy may be a potential treatment strategy. Methods: Herein, we reviewed the current research to provide an update on the role of AAV-mediated gene therapy in tumor research, especially in ovarian cancer. To find recent developments in pertinent research, we examined the PubMed database. Key Content and Findings: AAV vectors may produce steady and effective gene expression without becoming harmful, making it a viable gene delivery technique. AAV-based gene therapy products have been widely used in preclinical research and some have achieved marketing approval. Conclusions: Due to its affinity for various organs, reliable integration, and long-lasting expression, certain AAV serotypes have been widely used in gene therapy. However, there are also some challenges. Extensive research on the role of AAV in disease and gene therapy has shown great potential. Herein, we examined the literature to better understand the function of the AAV in tumor research, particularly in ovarian cancer research.

Photothermal Nano-Vaccine Promoting Antigen Presentation and Dendritic Cells Infiltration for Enhanced Immunotherapy of Melanoma via Transdermal Microneedles Delivery.

Immunotherapy has demonstrated the potential to cure melanoma, while the current response rate is still unsatisfactory in clinics. Extensive evidence indicates the correlation between the efficacy and pre-existing T-cell in tumors, whereas the baseline T-cell infiltration is lacking in low-response melanoma patients. Herein, we demonstrated the critical contribution of dendritic cells (DCs) on melanoma survival and baseline T-cell level, as well as the efficacy of immunotherapy. Capitalized on this fact, we developed a photothermal nano-vaccine to simultaneously promote tumor antigens presentation and DCs infiltration for enhanced immunotherapy. The nano-vaccine was composed of polyserotonin (PST) core and tannic acid (TA)/Mn2+ coordination-based metal-organic-framework (MOF) shell for ß-catenin silencing DNAzyme loading, which was further integrated into dissolving microneedles to allow noninvasive and transdermal administration at melanoma skin. The nano-vaccine could rapidly penetrate skin upon microneedles insertion and exert a synergistically amplified photothermal effect to induce immunogenic cell death (ICD). The MOF shell then dissociated and released Mn2+ as a cofactor to self-activate DNAzyme for ß-catenin suppression, which in turn caused a persistent CCL4 excretion to promote the infiltration of DCs into the tumor. Meanwhile, the liberated PST core could effectively capture and facilitate tumor antigens presentation to DCs. As a result, potent antitumor efficacies were achieved for both primary and distal tumors without any extra treatment, indicating the great promise of such a nano-vaccine for on-demand personalized immunotherapy of melanoma.

18ß-Glycyrrhetinic acid monoglucuronide (GAMG) alleviates single-walled carbon nanotubes (SWCNT)-induced lung inflammation and fibrosis in mice through PI3K/AKT/NF-κB signaling pathway.

Carbon nanotubes (CNTs) have become far and wide used in a number of technical and merchant applications as a result of substantial advances in nanotechnology, therein single-walled carbon nanotubes (SWCNT) are one of the most promising nanoparticles. Inhaling CNTs has been linked to a variety of health problems, including lung fibrosis. Glycyrrhetinic acid 3-O-mono-ß-D-glucuronide (GAMG), a natural sweetener, has anti-inflammatory and antioxidant capacities. The purpose of this study was to evaluate the potential for GAMG to alleviate SWCNT-induced lung inflammation and fibrosis. During days 3-28 after SWCNT intratracheal administration, we observed a remarkable increase of IL-1ß, IL-6 and TNF-α in bronchoalveolar lavage fluid (BALF) on day 3 and collagen deposition on day 28. GAMG treatment remarkably ameliorated SWCNT-induced pulmonary fibrosis and attenuated SWCNT-induced inflammation and collagen deposition, and suppressed the activation of PI3K/AKT/NF-κB signaling pathway in the lungs. Therefore, GAMG has a therapeutic potential for the treatment of SWCNT-induced pulmonary fibrosis. Targeting PI3K/AKT/NF-κB signaling pathway may be a potential therapeutic approach to treat pulmonary fibrosis in mice with SWCNT.

Polyserotonin as a versatile coating with pH-responsive degradation for anti-tumor therapy.

Through self-polymerization of serotonin monomer, polyserotonin (PST) can coat on arbitrary surfaces with pH-responsive degradation, which was employed for nanoparticle coating and controlled drug release, achieving a robust anti-tumor effect when combined with its intrinsic photothermal effect.

Inhibition of lncRNA RET enhances radio-sensitivity of tumor cells via miR-3179/Slug/PTEN axis.

Radioresistance is one of the key obstacles that may lead to the failure of cancer treatment. The underlying mechanisms of radioresistance remain largely unknown; however, increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in radiotherapy resistance of several cancers. In the present study, we demonstrated that radiation-elevated transcript (RET), a newly identified lnRNA, was highly expressed in cancer cells. Knockdown of RET significantly inhibited the proliferation and colony formation of cancer cells and markedly inhibited apoptosis. Furthermore, downregulation of RET in cancer cells significantly inhibited cell growth, decreased colony survival fractions, and promoted apoptosis in response to radiation treatment, indicating a role in radiation resistance. Moreover, RET knockdown significantly increased the expression of γ-H2AX, an indicator of DNA double strand damage, and reversed radiation-induced EMT, both of which contributed to its radiation resistance. In addition, a negative correlation was found between the expression of RET and PTEN. Rescue assays confirmed RET knockdown enhanced radiosensitivity of cancer cells by upregulating the expression of PTEN. Mechanistically, RET positively regulated Slug, a repressor of PTEN transcription, by acting as a molecular sponge of miR-3179. Our present study showed that RET conferred radioresistance by regulating miR-3179/Slug/PTEN axis, indicating that RET may be a potential target for the clinical application in cancer patients with radioresistance.

Transcriptional inhibition of miR-486-3p by BCL6 upregulates Snail and induces epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis.

BACKGROUND: Ionizing radiation (IR) can induce pulmonary fibrosis by causing epithelial mesenchymal transition (EMT), but the exact mechanism has not been elucidated. To investigate the molecular mechanism of how radiation induces pulmonary fibrosis by altering miR-486-3p content and thus inducing EMT. METHODS: The changes of miR-486-3p in cells after irradiation were detected by RT-qPCR. Western blot was used to detect the changes of cellular epithelial marker protein E-cadherin, mesenchymal marker N-cadherin, Vimentin and other proteins. The target gene of miR-486-3p was predicted by bioinformatics method and the binding site was verified by dual luciferase reporter system. In vivo experiments, adeno-associated virus (AAV) was used to carry miR-486-3p mimic to lung. Radiation-induced pulmonary fibrosis (RIPF) model was constructed by 25Gy60Co γ-rays. The structural changes of mouse lung were observed by HE and Masson staining. The expression of relevant proteins in mice was detected by immunohistochemistry. RESULTS: IR could decrease the miR-486-3p levels in vitro and in vivo, and that effect was closely correlated to the occurrence of RIPF. The expression of Snail, which induces EMT, was shown to be restrained by miR-486-3p. Therefore, knockdown of Snail blocked the EMT process induced by radiation or knockdown of miR-486-3p. In addition, the molecular mechanism underlying the IR-induced miRNA level reduction was explored. The increased in BCL6 could inhibit the formation of pri-miR-486-3p, thereby reducing the levels of miR-486-3p in the alveolar epithelial cells, which would otherwise promote EMT and contribute to RIPF by targeting Snail. CONCLUSION: IR can exacerbate RIPF in mice by activating the transcription factor BCL6, which inhibits the transcription of miR-486-3p and decreases its content, which in turn increases the content of the target gene slug and triggers EMT.

Surface Coating of Pulmonary siRNA Delivery Vectors Enabling Mucus Penetration, Cell Targeting, and Intracellular Radical Scavenging for Enhanced Acute Lung Injury Therapy.

Pulmonary delivery of anti-inflammatory siRNA presents a promising approach for localized therapy of acute lung injury (ALI), while polycationic vectors can be easily trapped by the negatively charged airway mucin glycoproteins and arbitrarily internalized by epithelial cells with nontargetability for immunological clearance. Herein, we report a material, the dopamine (DA)-grafted hyaluronic acid (HA-DA), coating on an anti-TNF-α vector to address these limitations. HA-DA was simply synthesized and facilely coated on poly(ß-amino ester) (BP)-based siRNA vectors via electrostatic attraction. The resulting HA-DA/BP/siRNA displayed significantly enhanced mucus penetration, attributable to the charge screen effect of HA-DA and the bioadhesive nature of the grafting DA. After transmucosal delivery, the nanosystem could target diseased macrophages via CD44-mediated internalization and rapidly escape from endo/lysosomes through the proton sponge effect, resulting in effective TNF-α regulation. Meanwhile, DA modification endowed the coating material with robust antioxidative capability to scavenge a broad spectrum of reactive oxygen/nitrogen species (RONS), which protected the lung tissue from oxidative damage and synergized with anti-TNF-α to inhibit a cytokine storm. As a result, a remarkable amelioration of ALI was achieved in a lipopolysaccharide (LPS)-stimulated mice model. This study provides a multifunctional coating material to facilitate pulmonary drug delivery for the treatment of lung diseases.

Selenium inhibits cadmium uptake and accumulation in the shoots of winte wheat by altering the transformation of chemical forms of cadmium in soil.

This study aimed to investigate the effects of selenium application on cadmium absorption, transport, and soil cadmium forms of winter wheat at different stages. A pot experiment with one Cd application (6 mg·kg-1) and five Se application levels (0, 1, 2, 5, and 10 mg·kg-1) was conducted. The results showed that Se application increased the grain yield of winter wheat, especially at 5 mg·kg-1 under Cd stress. As Se was supplied at 5 (Se5) and 10 (Se10) mg·kg-1, the Cd concentrations in roots and shoots, including stems, spikes, glumes, and grains, decreased at different growth stages, and the decreases in grain were 46.1% and 70.9% respectively. Se5 and Se10 also significantly decreased the translocation factors of Cd from roots to shoots, roots to stems, stems to spikes, and glumes to grains, promoted the accumulation of Cd in roots, and inhibited the accumulation of Cd in shoots and final grains at different growth stages, and the accumulation of Cd in grains decreased by 16.9% and 68.1%, respectively. High levels of Se application (Se5 and Se10) decreased the concentrations and proportions of exchangeable Cd (EXC-Cd) and iron (Fe)-manganese (Mn) oxide-bound Cd (R2O3-Cd) but increased the concentration and proportion of residual Cd (RES-Cd) in both soils with wheat and fallow soil at different growth stages. Therefore, under Cd stress, high levels of Se application reduced the shoot Cd concentration by inhibiting the uptake and transport of Cd from roots to shoots, and decreased the bioavailability of Cd in both soil with wheat and fallow by enhancing the transformation and distribution of RES-Cd from EXC-Cd and R2O3-Cd.