Correction: Zhao et al. Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN). Cells 2020, 9, 559.

In the original publication [...].

Risk of second primary thyroid cancer in cancer survivors.

A risk factor for thyroid cancer (TC) may be a history of former cancer and cancer therapy. The precise risk of a second primary thyroid carcinoma has not yet been revealed. In this study, we evaluated standardized incidence ratios (SIRs) of second primary thyroid cancer (SPTC) with consideration of different conditions and further analyzed the clinicopathological characteristics and survival of these patients. The cohort was selected from the US Surveillance, Epidemiology, and End Results (SEER) Program between 1975 and 2019. The standardized incidence ratios, morbidity risk, clinicopathological features, and survival of second primary thyroid carcinoma were analyzed. Propensity score matching (PSM) was used to balance covariates. Kaplan-Meier method was performed to assess the survival outcomes. Overall, 7066 patients with SPTC and 83,113 patients with primary TC were identified. The SIR of TC in tumor patients was 1.51/10,000, statistically higher than the natural population (0.94/10,000, P < 0.05). The most significant tumors contributing to the increased SIRs of SPTC were acute lymphocytic leukemia (3.49/10,000), Hodgkin's lymphoma-nodal (3.29/10,000), salivary gland cancer (3.23/10,000), and kidney and renal pelvis cancer (3.05/10,000). The incidence of TC increased significantly in tumor patients who received radiotherapy/chemotherapy before age 35. The age at diagnosis of the SPTC was much older than the primary TC (64.01 vs. 49.55 years, p < 0.001). The SPTC had a higher percentage of histological grades 3/4 (23.14% vs. 15.19%, p < 0.001). Survival analyses demonstrated a worse prognosis for the SPTC group compared to the primary TC group. But after PSM, the survival outcomes of the two groups tended to be equivalent (P = 0.584). The SIRs of TC are higher in tumor patients. The most significant factors contributing to the increased risk of SPTC were some specific former tumors and acceptance of radiotherapy/ chemotherapy before age 35. There was no significant difference in survival between SPTC and primary TC.

Super-Assembled Multilayered Mesoporous TiO2 Nanorockets for Light-Powered Space-Confined Microfluidic Catalysis.

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.

The survival after thyroidectomy versus lobectomy in multifocal papillary thyroid microcarcinoma patients.

BACKGROUND: The extent of thyroid surgery for multifocal papillary thyroid microcarcinoma (PTMC) remains controversial. Studies on the optimal surgical approach for a multifocal PTMC are scarce. This study aimed to compare the effectiveness of thyroidectomy and lobectomy for the treatment of multifocal PTMC. METHODS: A population-based retrospective cohort of patients with multifocal PTMC was analyzed using the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2017, and divided into two groups (thyroidectomy, lobectomy) based on the surgical approach. The clinicopathologic features and survival outcomes were compared between the two groups. Cox proportional hazards regression analysis to explore prognostic factors of survival. Propensity score matching (PSM) was used to balance covariates. RESULTS: Overall, a total of 9387 multifocal PTMC patients were included in the study. Among them, 8,107 (86.36%) patients received thyroidectomy, and 1280 (13.64%) patients underwent lobectomy. Compared to patients in the thyroidectomy group, patients in the lobectomy group were diagnosed with older age (50.47 years vs. 49.32 years, p = 0.003), a higher proportion of males (20.47% vs. 14.99%, p < 0.001), larger tumors (6.22 mm vs. 4.97 mm, p < 0.001), and more frequently underwent radiotherapy (35.40% vs. 10.16%, p < 0.001). Multivariate Cox regression analysis revealed that age was the only independent prognostic factor for thyroid cancer-specific survival (TCSS), and the determinants of overall survival (OS) were age and gender. Unadjusted survival analysis revealed no difference between the two treatment groups in TCSS (p = 0.598) and OS (p = 0.126). After 1:1 Propensity Score Matching (PSM), there was still no difference in TCSS (p = 0.368) or OS (p = 0.388). The stratified analysis revealed that for patients aged under or above 55, thyroidectomy was not associated with superior BCSS or OS (p > 0.05). CONCLUSIONS: Thyroidectomy was not associated with improved survival compared to thyroid lobectomy for patients with multifocal PTMC.

Identification of Chromosomal Regions and Candidate Genes for Round leaf Locus in Cucumis melo L.

Leaf morphology plays a crucial role in plant classification and provides a significant model for studying plant diversity while directly impacting photosynthetic efficiency. In the case of melons, leaf shape not only influences production and classification but also represents a key genetic trait that requires further exploration. In this study, we utilized forward genetics to pinpoint a recessive locus, dubbed Cmrl (Round leaf), which is responsible for regulating melon leaf shape. Through bulked segregant analysis sequencing and extensive evaluation of a two-year F2 population, we successfully mapped the Cmrl locus to a 537.07 kb region on chromosome 8 of the melon genome. Subsequent genetic fine-mapping efforts, leveraging a larger F2 population encompassing 1322 plants and incorporating F2:3 phenotypic data, further refined the locus to an 80.27 kb interval housing five candidate genes. Promoter analysis and coding sequence cloning confirmed that one of these candidates, MELO3C019152.2 (Cmppr encoding a pentatricopeptide repeat-containing family protein, Cmppr), stands out as a strong candidate gene for the Cmrl locus. Notably, comparisons of Cmrl expressions across various stages of leaf development and different leaf regions suggest a pivotal role of Cmrl in the morphogenesis of melon leaves.

Selection of the Dominant Endophytes Based on Illumina Sequencing Analysis for Controlling Bacterial Wilt of Patchouli Caused by Ralstonia solanacearum.

Bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating diseases in patchouli (Pogostemon cablin [Blanco] Benth.), which results in low yield and quality of patchouli. However, no stable and effective control methods have been developed yet. To evaluate the potential of dominant bacterial endophytes in biocontrol, the endophytic bacterial diversity of patchouli was investigated based on Illumina sequencing analysis, and the ability of isolates belonging to the dominant bacterial genera to control RS wilt of patchouli was explored in pot experiments. A total of 245 bacterial genera were detected in patchouli plants, with the highest relative abundance of operational taxonomic units belonging to the genus Pseudomonas detected in roots, leaves, and stems. The Pseudomonas isolates S02, S09, and S26 showed antagonistic activity against RS in vitro and displayed many plant growth-promoting characteristics, including production of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylic acid deaminase and phosphate- and potassium-solubilizing capability. Inoculation of patchouli plants with the isolates S02, S09, and S26 significantly improved shoot growth and decreased the incidence of bacterial wilt caused by RS. The results suggest that screening of dominant bacterial endophytes for effective biocontrol agents based on Illumina sequencing analysis is more efficient than random isolation and screening procedures.

Characterization of a novel T cell-engaging bispecific antibody for elimination of L1CAM-positive tumors.

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.

Computational modelling of articular joints with biphasic cartilage: recent advances, challenges and opportunities.

Biphasic models have been widely used to simulate the time-dependent biomechanical response of soft tissues. Modelling techniques of joints with biphasic weight-bearing soft tissues have been markedly improved over the last decade, enhancing our understanding of the function, degenerative mechanism and outcomes of interventions of joints. This paper reviews the recent advances, challenges and opportunities in computational models of joints with biphasic weight-bearing soft tissues. The review begins with an introduction of the function and degeneration of joints from a biomechanical aspect. Different constitutive models of articular cartilage, in particular biphasic materials, are illustrated in the context of the study of contact mechanics in joints. Approaches, advances and major findings of biphasic models of the hip and knee are presented, followed by a discussion of the challenges awaiting to be addressed, including the convergence issue, high computational cost and inadequate validation. Finally, opportunities and clinical insights in the areas of subject-specific modeling and tissue engineering are provided and discussed.

Oncolytic mineralized bacteria as potent locally administered immunotherapeutics.

Oncolytic bacteria can trigger innate immune activity. However, the antitumour efficacy of inactivated bacteria is poor, and attenuated live bacteria pose substantial safety risks. Here we show that intratumourally injected paraformaldehyde-fixed bacteria coated with manganese dioxide potently activate innate immune activity, modulate the immunosuppressive tumour microenvironment and trigger tumour-specific immune responses and abscopal antitumour responses. A single intratumoural administration of mineralized Salmonella typhimurium suppressed the growth of multiple types of subcutaneous and orthotopic tumours in mice, rabbits and tree shrews and protected the cured animals against tumour rechallenge. We also show that mineralized bacteria can be administered via arterial embolization to treat orthotopic liver cancer in rabbits. Our findings support the further translational testing of oncolytic mineralized bacteria as potent and safe antitumour immunotherapeutics.

Cu-OFF/ERI Zeolite: Intergrowth Structure Synergistically Boosting Selective Catalytic Reduction of NOx with NH3.

Cu-SSZ-13 has been commercialized for selective catalytic reduction with ammonia (NH3-SCR) to remove NOx from diesel exhaust. As its synthesis usually requires toxic and costly organic templates, the discovery of alternative Cu-based zeolite catalysts with organotemplate-free synthesis and comparable or even superior NH3-SCR activity to that of Cu-SSZ-13 is of great academic and industrial significance. Herein, we demonstrated that Cu-T with an intergrowth structure of offretite (OFF) and erionite (ERI) synthesized by an organotemplate-free method showed better catalytic performance than Cu-ERI and Cu-OFF as well as Cu-SSZ-13. Structure characterizations and density functional theory calculations indicated that the intergrowth structure promoted more isolated Cu2+ located at the 6MR of the intergrowth interface, resulting in a better hydrothermal stability of Cu-T than Cu-ERI and Cu-OFF. Strikingly, the low-temperature activity of Cu-T significantly increased after hydrothermal aging, while that of Cu-ERI and Cu-OFF substantially decreased. Based on in situ diffuse reflectance infrared Fourier transform spectra analysis and density functional theory calculations, the reason can be attributed to the fact that NH4NO3 formed on the CuxOy species within ERI polymorph of Cu-T underwent a fast SCR reaction pathway with the assistance of Brønsted acid sites at the intergrowth interfaces under standard SCR reaction conditions. Significantly, Cu-T exhibited a wider temperature window at a catalytic activity of over 90% than Cu-SSZ-13 (175-550 vs 175-500 °C for fresh and 225-500 vs 250-400 °C for hydrothermal treatment). This work provides a new direction for the design of high-performance NH3-SCR catalysts in terms of the interplay of the intergrowth structure of zeolites.

Research progress of periostin and osteoporosis.

Periostin, as a unique extracellular matrix, is mainly produced during ontogeny and in adult connective tissues that bear mechanical loads, such as heart valves, skin, periodontal ligaments, tendons, and bones. By binding to the integrin on the cell surface and activating Wnt/ß-catenin, NF-κB, Fak and other signaling pathways, it regulates the tissues in vivo positively or negatively, and also has different effects on the occurrence and development of various diseases. Periostin is an important factor, which can promote cell proliferation, stimulate tissue repair and maintain the integrity of the structure and function of connective tissue. It also promotes the formation, regeneration and repairation of bone. Recent studies have shown that periostin is important in bone metabolic diseases. The increased expression of periostin can affect bone mineral density at different sites, and its relationship with traditional biochemical markers of bone turnover has not been conclusively established. This article reviews the research results and potential applications of periostin in osteoporosis.

CircCPA4 induces ASCT2 expression to promote tumor property of non-small cell lung cancer cells in a miR-145-5p-dependent manner.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a type of lung cancer that occurs in the cells of the respiratory tract, and its development is influenced by the regulation of circular RNAs (circRNAs). However, the role of circRNA carboxypeptidase A4 (circCPA4) in the progression of NSCLC and the underlying mechanism remain relatively clear. METHODS: The study utilized both real-time quantitative polymerase chain reaction (RT-qPCR) and western blot techniques to evaluate the levels of circCPA4, microRNA-145-5p (miR-145-5p), alanine, serine, or cysteine-preferring transporter 2 (ASCT2). To assess cell proliferation, cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed. Apoptosis was determined using flow cytometry, while cell migration and invasive capacity were evaluated through transwell and wound-healing assays. Intracellular levels of glutamine, glutamate, and α-KG were measured using specific kits. The relationship between miR-145-5p and circCPA4 or ASCT2 was confirmed using dual-luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: CircCPA4 and ASCT2 RNA levels were elevated, while miR-145-5p was downregulated in both NSCLC tissues and cells. Depletion of circCPA4 significantly inhibited NSCLC cell proliferation, migration, invasion, and intracellular levels of glutamine, glutamate, and α-KG, and promoted apoptosis. Moreover, circCPA4 knockdown delayed tumor growth in vivo. Furthermore, circCPA4 was found to bind to miR-145-5p, thereby regulating the progression of NSCLC in vitro. ASCT2 was also identified as a downstream target of miR-145-5p, and its upregulation rescued the effects of miR-145-5p overexpression on NSCLC cell processes. CONCLUSION: CircCPA4 knockdown inhibited tumor property of NSCLC cells by modulating the miR-145-5p/ASCT2 axis.

Confinement of CsPbBr3 Perovskite Nanocrystals into Extra-large-pore Zeolite for Efficient and Stable Photocatalytic Hydrogen Evolution.

Metal halide perovskites (MHPs), renowned for their outstanding optoelectronic properties, hold significant promise as photocatalysts for hydrogen evolution reaction (HER). However, the low stability and insufficient exposure of catalytically active sites of bulky MHPs seriously impair their catalytic efficiency. Herein, we utilized an extra-large-pore zeolite ZEO-1 (JZO) as a host to confine and stabilize the CsPbBr3 nanocrystals (3.4 nm) for boosting hydrogen iodide (HI) splitting. The as-prepared CsPbBr3@ZEO-1 featured sufficiently exposed active sites, superior stability in acidic media, along with intrinsic extra-large pores of ZEO-1 that were favorable for molecule/ion adsorption and diffusion. Most importantly, the unique nanoconfinement effect of ZEO-1 led to the narrowing of the band gap of CsPbBr3, allowing for more efficient light utilization. As a result, the photocatalytic HER rate of the as-prepared CsPbBr3@ZEO-1 photocatalyst was increased to 1734 µmol ⋅ h-1 ⋅ g-1 (CsPbBr3) under visible light irradiation compared with bulk CsPbBr3 (11 µmol ⋅ h-1 ⋅ g-1 (CsPbBr3)), and the long-term durability (36 h) can be achieved. Furthermore, Pt was incorporated with well-dispersed CsPbBr3 nanocrystals into ZEO-1, resulting in a significant enhancement in activity (4826 µmol ⋅ h-1 ⋅ g-1 (CsPbBr3)), surpassing most of the Pt-integrated perovskite-based photocatalysts. Density functional theory (DFT) calculations and charge-carrier dynamics investigation revealed that the dramatically boosted photocatalytic performance of Pt/CsPbBr3@ZEO-1 could be attributed to the promotion of charge separation and transfer, as well as to the substantially lowered energy barrier for HER. This work highlights the advantage of extra-large-pore zeolites as the nanoscale platform to accommodate multiple photoactive components, opening up promising prospects in the design and exploitation of novel zeolite-confined photocatalysts for energy harvesting and storage.

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma.

Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

Ferroptosis Exists in Ischemia Reperfusion Injury after Cardiac Surgery with Cardiopulmonary Bypass.

Ischemia-reperfusion (IR) injury commonly arises during cardiac surgery involving Cardiopulmonary Bypass (CPB), and it has relationship with ferroptosis in mice. However, the exact role of ferroptosis in the human cardiac damage caused by cardiac surgery remains unclear. Basic patient data and perioperative period information were collected, and clinic indicators related to cardiac function were detected to assess the extent of cardiac injury. Cardiac tissue samples were collected to determine histopathological changes, ultrastructure of mitochondrial and hallmarks of ferroptosis. 25 patients were involved in this study. In the present study, we observed a significant increase in the clinical indicator hs-cTnT, with levels rising more than 1393 ± 242 folds (P < 0.0001) following the cardiac surgery. Masson staining revealed a notable increase in fibrosis levels by 2.282 ± 0.259% (P = 0.0009). Furthermore, there was a significant elevation in lipid peroxidation, as evidenced by a 61.42 ± 17.33% increase in MDA (P = 0.0006). Additionally, we observed notable swelling, decreased mitochondrial crista, and even fragmented mitochondria. Notably, changes in the marker gene of ferroptosis were observed, with PTGS2 showing a 6.437 ± 0.81 folds increase (P < 0.0001). Furthermore, key regulators such as SLC7A11 and GPX4 proteins exhibited a reduction of 97.33 ± 25.78% (P = 0.0068) and 60.59 ± 14.93% (P = 0.0071), respectively, indicating the occurrence of ferroptosis following the surgery. Ferroptosis exists in myocardial IR injury caused by cardiac surgery with CPB, indicating that targeting ferroptosis could serve as a potential strategy for myocardial protection against CPB-induced IR injury. The trial has been registered in Chinese Clinical Trial Registry (ChiCTR, No. ChiCTR2200061995) on July 16th, 2022.

Construction and validation of a nomogram for predicting lateral lymph node metastasis in pediatric and adolescent with differentiated thyroid carcinoma.

BACKGROUND: Limited research has been conducted to specifically investigate the identification of risk factors and the development of prediction models for lateral lymph node metastasis (LNM) in pediatric and adolescent differentiated thyroid carcinoma (DTC) populations, despite its significant association with unfavorable prognosis. METHODS: This study entails a retrospective analysis of the clinical characteristics exhibited by pediatric and adolescent patients who have been diagnosed with DTC. The data utilized for this analysis was sourced from the Surveillance, Epidemiology, and End Results (SEER) database, spanning the time frame from 2000 to 2020. Furthermore, the study incorporates patients who were treated at the Departments of Breast and Thyroid Surgery in the Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, as well as The General Hospital of Western Theater Command, during the period from 2010 to 2020. RESULTS: A cohort of 2631 patients from the SEER database, along with an additional 339 patients from our departments who met the specified inclusion criteria, were included in this study. Subsequently, four clinical variables, namely age, tumor size, multifocality, and extrathyroidal invasion, were identified as being significantly associated with lateral LNM in pediatric and adolescent DTC patients. These variables were then utilized to construct a nomogram, which demonstrated effective discrimination with a concordance index (C-index) of 0.731. Furthermore, the performance of this model was validated through both internal and external assessments, yielding C-index values of 0.721 and 0.712, respectively. Afterward, a decision curve analysis was conducted to assess the viability of this nomogram in predicting lymph node metastasis. CONCLUSION: The current investigation has effectively constructed a nomogram model utilizing visualized multipopulationsal data. Our findings demonstrate a significant association between various clinical characteristics and lateral LNM in pediatric and adolescent DTC patients. These outcomes hold substantial significance for healthcare practitioners, as they can employ this model to inform individualized clinical judgments for the pediatric and adolescent cohorts.

Phenotypic and transcriptome profiling of spikes reveals the regulation of light regimens on spike growth and fertile floret number in wheat.

The spike growth phase is critical for the establishment of fertile floret (grain) numbers in wheat (Triticum aestivum L.). Then, how to shorten the spike growth phase and increase grain number synergistically? Here, we showed high-resolution analyses of floret primordia (FP) number, morphology and spike transcriptomes during the spike growth phase under three light regimens. The development of all FP in a spike could be divided into four distinct stages: differentiation (Stage I), differentiation and morphology development concurrently (Stage II), morphology development (Stage III), and polarization (Stage IV). Compared to the short photoperiod, the long photoperiod shortened spike growth and stimulated early flowering by shortening Stage III; however, this reduced assimilate accumulation, resulting in fertile floret loss. Interestingly, long photoperiod supplemented with red light shortened the time required to complete Stages I-II, then raised assimilates supply in the spike and promoted anther development before polarization initiation, thereby increasing fertile FP number during Stage III, and finally maintained fertile FP development during Stage IV until they became fertile florets via a predicted dynamic gene network. Our findings proposed a light regimen, critical stages and candidate regulators that achieved a shorter spike growth phase and a higher fertile floret number in wheat.

Synthesis, antitumor activity evaluation of 2-selenocyano-3-selenocyanoalkyloxyestradiols with a bisselenocyanate structure.

The combination of steroid structure and selenocyano group offers high potential for the design and synthesis of new potential anti-tumor drugs. Beginning with estradiol, a series of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives with remarkable antiproliferative activity was synthesized. Additionally, a 2,4-bisselenocyanoestradiol was synthesized by directly selenocyanating estradiol diacetate. It was found that the cytotoxicity of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives was significantly increased in comparison to the corresponding monoselenocyanate precursor, whereas the cytotoxicity of the 2, 4-bisselenocyanoestradiol derivative was significantly reduced compared to the respective monosubstituted precursor. The introduction of the second selenocyano group at different locations of estradiol shows a various impact on the cytotoxicity of the compounds. Among them, compound 3e showed the best cytotoxicity, with an IC50 value of less than 5 µM against the tested tumor cells, and strong inhibitory activities against HeLa and MCF-7 cell xenograft tumors in zebrafish, suppressing tumor cell migration and neovascularization. Notably, compound 3e was more effective at inhibiting neovascularization of MCF-7 cell xenograft tumors than the positive control 2-methoxyestradiol. Furthermore, compound 3e showed excellent anti-oxidative stress effect in zebrafish. Therefore, these estrogen bisselenocyanate compounds may be promising anti-tumor agents, warranting further investigation.