A "Two-Pronged" Strategy to Boost Hydrogen Evolution Kinetics on NiFe-Based (Oxy)hydroxides via Oxygen Deficient Ni-Mo-Fe Coordinate Structures for Ultra-Stable Ampere-Level Alkaline Overall Water Splitting.

NiFe (oxy)hydroxides have been regarded as one of the state-of-the-art catalysts for oxygen evolution reaction (OER). Unfortunately, the sluggish hydrogen evolution reaction (HER) kinetics limit its application as bifunctional electrocatalyst for alkaline overall water splitting (OWS). Herein, a "two-pronged" strategy is proposed to construct highly active oxygen deficient Ni-Mo-Fe coordinate structures in NiFe (oxy)hydroxide (NFM-OVR/NF), which simultaneously reduces the energy barrier of Volmer and Heyrovsky steps during alkaline HER process and significantly accelerate the reaction kinetics. Consequently, NFM-OVR/NF delivers overpotentials as low as 25 and 234 mV to achieve 10 and 1000 mA cm-2 in 1.0 M KOH, respectively. Furthermore, benefiting from excellent HER and OER activity, NFM-OVR/NF exhibits a remarkable OWS activity with cell voltages of 1.44 V and 1.77 V at 10 and 1000 mA cm-2 in 1.0 M KOH, and displays ultralong-term stability for 600 h at 500 mA cm-2, while remaining durable for 300 h in an alkaline water electrolyzer in 30% KOH at 80 °C. The calculated price per gallon of gasoline equivalent for the produced H2 is $ 0.92, which is much lower than 2026 U.S. Department of Energy target ($ 2.00), demonstrating feasibility and practicability of NFM-OVR/NF for industrial applications.

Amorphous/Crystalline Phases Mixed Nanosheets Array Rich in Oxygen Vacancies Boost Oxygen Evolution Reaction of Spinel Oxides in Alkaline Media.

As promising oxygen evolution reaction (OER) catalysts, spinel-type oxides face the bottleneck of weak adsorption for oxygen-containing intermediates, so it is challenging to make a further breakthrough in remarkably lowering the OER overpotential. In this study, a novel strategy is proposed to substantially enhance the OER activity of spinel oxides based on amorphous/crystalline phases mixed spinel FeNi2O4 nanosheets array, enriched with oxygen vacancies, in situ grown on a nickel foam (NF). This unique architecture is achieved through a one-step millisecond laser direct writing method. The presence of amorphous phases with abundant oxygen vacancies significantly enhances the adsorption of oxygen-containing intermediates and changes the rate-determining step from OH*→O* to O*→OOH*, which greatly reduces the thermodynamic energy barrier. Moreover, the crystalline phase interweaving with amorphous domains serves as a conductive shortcut to facilitate rapid electron transfer from active sites in the amorphous domain to NF, guaranteeing fast OER kinetics. Such an anodic electrode exhibits a nearly ten fold enhancement in OER intrinsic activity compared to the pristine counterpart. Remarkably, it demonstrates record-low overpotentials of 246 and 315 mV at 50 and 500 mA cm-2 in 1 m KOH with superior long-term stability, outperforming other NiFe-based spinel oxides catalysts.

Construction of Co-Se-W at Interfaces of Phase-Mixed Cobalt Selenide via Spontaneous Phase Transition for Platinum-Like Hydrogen Evolution Activity and Long-Term Durability in Alkaline and Acidic Media.

Cost-effective transition metal chalcogenides are highly promising electrocatalysts for both alkaline and acidic hydrogen evolution reactions (HER). However, unsatisfactory HER kinetics and stability have severely hindered their applications in industrial water electrolysis. Herein, a nanoflowers-shaped W-doped cubic/orthorhombic phase-mixed CoSe2 catalyst ((c/o)-CoSe2-W) is reported. The W doping induces spontaneous phase transition from stable phase cubic CoSe2 (c-CoSe2) to metastable phase orthorhombic CoSe2, which not only enables precise regulation of the ratio of two phases but also realizes W doping at the interfaces of two phases. The (c/o)-CoSe2-W catalyst exhibits a Pt-like HER activity in both alkaline and acidic media, with record-low HER overpotentials of 29.8 mV (alkaline) and 35.9 mV (acidic) at 10 mA cm-2, respectively, surpassing the vast majority of previously reported non-precious metal electrocatalysts for both alkaline and acidic HER. The Pt-like HER activities originate from the formation of Co-Se-W active species on the c-CoSe2 side at the phase interface, which effectively modulates electron structures of active sites, not only enhancing H2O adsorption and dissociation at Co sites but also optimizing H* adsorption to ΔGH* ≈ 0 at W sites. Benefiting from the abundant phase interfaces, the catalyst also displays outstanding long-term durability in both acidic and alkaline media.

Intrinsic Atomic-Scale Antiferroelectric VOF3 Nanowire with Ultrahigh-Energy Storage Properties.

Antiferroelectrics with antiparallel dipoles are receiving tremendous attention for their technological importance and fundamental interest. However, intrinsic one-dimensional (1D) materials harboring antiferroelectric ordering have rarely been reported despite the promise of novel paradigms for miniaturized and high-density electronics. Herein, based on first- and second-principles calculations, we demonstrate the VOF3 atomic wire, exfoliated from an experimentally synthesized yet underexplored 1D van der Waals (vdW) bulk, as a new 1D antiferroelectric material. The energetic, thermal, and dynamic stabilities of the nanowire are confirmed theoretically. Moreover, the temperature-dependent phase transitions and double-hysteresis polarization-field loops are computed for the VOF3 nanowire by constructing the second-principles model. According to the hysteresis loops, high energy densities and efficiencies can be obtained simultaneously at room temperature in the VOF3 nanowire under moderate applied fields. Our identified 1D atomic wire not only expands the family of antiferroelectricity but also holds potential for novel high-power energy storage nanodevices.

A Strongly Coupled Ag(S)@NiO/Nickel Foam Electrode Induced by Laser Direct Writing for Hydrogen Evolution at Ultrahigh Current Densities with Long-Term Durability.

Highly active, durable, and cost-effective electrodes for hydrogen evolution reaction (HER) at ultrahigh current densities (≥1 A cm-2 ) are extremely demanded for industrial high-rate hydrogen production, but challenging. Here, a robust strongly coupled Ag(S)@NiO/nickel foam (NF) electrode is reported. Taking advantage of millisecond laser direct writing in liquid nitrogen technique, lattice-matched and coherent interfaces are formed between Ag nanoparticles with stacking faults (denoted by Ag(S)) and NiO nanosheets, leading to strong interfacial electronic coupling, not only promoting H2 O adsorption and dissociation on Ni2+ but also enhancing H* adsorption on intrinsically inactive but most electrically conductive Ag. Strong chemical bonding is established at NiO/NF interface, guaranteeing rapid electron transfer and excellent mechanical durability under high-rate hydrogen evolution. The physicochemically stable electrode achieves record-low alkaline HER overpotential of 167 and 180 mV at 1 and 1.5 A cm-2 , respectively, along with negligible activity decay after 120 h test at ≈1.5 A cm-2 , surpassing reported non-platinum group metal electrocatalysts.

Rare-earth control of phase transitions in infinite-layer nickelates.

Perovskite nickelates RNiO3 (R = rare-earth ion) exhibit complex rare-earth ion dependent phase diagram and high tunability of various appealing properties. Here, combining first- and finite-temperature second-principles calculations, we explicitly demonstrate that the superior merits of the interplay among lattice, electron, and spin degrees of freedom can be passed to RNiO2, which recently gained significant interest as superconductors. We unveil that decreasing the rare-earth size directly modulates the structural, electronic, and magnetic properties and naturally groups infinite-layer nickelates into two categories in terms of the Fermi surface and magnetic dimensionality: compounds with large rare-earth sizes (La, Pr) closely resemble the key properties of CaCuO2, showing quasi-two-dimensional (2D) antiferromagnetic (AFM) correlations and strongly localized dx2-y2 orbitals around the Fermi level; the compounds with small rare-earth sizes (Nd-Lu) are highly analogous to ferropnictides, showing three-dimensional (3D) magnetic dimensionality and strong kz dispersion of d3z2-r2 electrons at the Fermi level. Additionally, we highlight that RNiO2 with R = Nd-Lu exhibit on cooling a structural transition with the appearance of oxygen rotation motion, which is softened by the reduction of rare-earth size and enhanced by spin-rotation couplings. The rare-earth control of kz dispersion and structural phase transition might be the key factors differentiating the distinct upper critical field and resistivity in different compounds. The established original phase diagram summarizing the temperature and rare-earth controlled structural, electronic, and magnetic transitions in RNiO2 compounds provides rich structural and chemical flexibility to tailor the superconducting property.

Quasi-Solid Electrolyte Interphase Boosting Charge and Mass Transfer for Dendrite-Free Zinc Battery.

The practical applications of zinc metal batteries are plagued by the dendritic propagation of its metal anodes due to the limited transfer rate of charge and mass at the electrode/electrolyte interphase. To enhance the reversibility of Zn metal, a quasi-solid interphase composed by defective metal-organic framework (MOF) nanoparticles (D-UiO-66) and two kinds of zinc salts electrolytes is fabricated on the Zn surface served as a zinc ions reservoir. Particularly, anions in the aqueous electrolytes could be spontaneously anchored onto the Lewis acidic sites in defective MOF channels. With the synergistic effect between the MOF channels and the anchored anions, Zn2+ transport is prompted significantly. Simultaneously, such quasi-solid interphase boost charge and mass transfer of Zn2+, leading to a high zinc transference number, good ionic conductivity, and high Zn2+ concentration near the anode, which mitigates Zn dendrite growth obviously. Encouragingly, unprecedented average coulombic efficiency of 99.8% is achieved in the Zn||Cu cell with the proposed quasi-solid interphase. The cycling performance of D-UiO-66@Zn||MnO2 (~ 92.9% capacity retention after 2000 cycles) and D-UiO-66@Zn||NH4V4O10 (~ 84.0% capacity retention after 800 cycles) prove the feasibility of the quasi-solid interphase.

Enhancing the Performance of PVDF/GO Ultrafiltration Membrane via Improving the Dispersion of GO with Homogeniser.

In this study, PVDF/GO-h composite membranes were synthesised using a homogeniser to improve the dispersion of GO nanosheets within the composite membrane's structure, and then characterised and contrasted to PVDF/GO-s control samples, which were synthesised via traditional blending method-implementing a magnetic stirrer. By characterizing membrane via X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), water contact angle (WCA) and membrane performance. SEM results showed that the number of the finger-like structure channels and pores in the sponge like structure of PVDF/GO-h composite membranes become more compared with PVDF/GO-s membranes. Water contact angle tests showed that the PVDF/GO-h composite membranes have lower contact angle than PVDF/GO-s control, which indicated the PVDF/GO-h composite membranes are more hydrophilic. Results also showed that composite membranes blended using homogeniser exhibited both improved water flux and rejection of target pollutants. In summary, it was shown that the performance of composite membranes could be improved significantly via homogenisation during synthesis, thus outlining the importance of further research into proper mixing.

Ultrahigh Energy Storage Performance of Flexible BMT-Based Thin Film Capacitors.

Ferroelectric thin film capacitors have attracted increasing attention because of their high energy storage density and fast charge-discharge speed, but less attention has been paid to the realization of flexible capacitors for wearable electronics and power systems. In this work, flexible xMn-BiMg0.5 Ti0.7 O3 (xMn-BMT0.7 ) thin film capacitors with ultrahigh energy storage density and good stability are deposited on mica substrate. The introduction of excess TiO2 with an amorphous structure contributes to the forming of the polar nano regions, resulting in the reduced ferroelectric hysteresis. In order to further improve the energy storage performance, Mn doping increases the polarization by regulating chemical pressure in the lattices and inhibits the valence change of Ti4+ . Especially in the 1.5% Mn-BMT0.7 film capacitor, an ultrahigh energy storage density of 124 J cm-3 and an outstanding efficiency of 77% are obtained, which is one of the best energy storage performances recorded for ferroelectric capacitors. In addition, the flexible ferroelectric film capacitor also exhibits good thermal stability (25-200 °C), high frequency reliability (500 Hz-10 kHz), excellent electrical (108 cycles), and mechanical (104 cycles) fatigue properties. This work is expected to pave the way for the application of BMT-based thin film capacitors in flexible energy storage systems.

Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer.

BACKGROUND: Chemotherapy and/or immunotherapy are first-line treatments for advanced muscle-invasive bladder cancer (BCa), but the unsatisfactory objective response rate to these treatments yields poor 5-year patient survival. Discovery of therapeutic targets essential for BCa maintenance is critical to improve therapy response in clinic. This study evaluated the role of targeting WD repeat domain 5 (WDR5) with the small molecule compound OICR-9429 and whether it could be used to treat bladder cancer. METHODS: We analysed the expression and clinical prognosis of WDR5 in a TCGA cohort. The pharmacological role of OICR-9429 was further investigated in vitro and in vivo. RNA sequencing, western blot, and chromatin immunoprecipitation (ChIP) were utilized to explored the mechanism underlying OICR-9429-induced WDR5 inhibition. RESULTS: First, we found that WDR5 expression was upregulated in BCa and was associated with histologic grade, metastasis status, histologic subtype, and molecular subtype. High WDR5 expression level was also correlated with shorter overall survival (OS) in BCa. The WDR5 inhibitor OICR-9429 reduced cell viability by decreasing H3K4me3 levels but not WDR5 levels in T24, UM-UC-3, and TCCSUP BCa cells. OICR-9429 suppressed the proliferation of BCa cells by blocking the G1/S phase transition. Next, OICR-9429 enhanced apoptosis and chemosensitivity to cisplatin in BCa cells. In addition, OICR-9429 independently inhibited the motility and metastatic behaviour of BCa cells. In vivo experiments further revealed that OICR-9429 suppressed tumour growth, enhanced chemosensitivity, and reduced the toxicity of cisplatin in BCa. Notably, WDR5 was positively correlated with programmed death-ligand 1 (PD-L1) expression, and OICR-9429 suppressed immune evasion by blocking PD-L1 induced by IFN-γ. Mechanistically, some cell cycle-, antiapoptosis-, DNA repair-, metastasis-, and immune evasion-related genes, including BIRC5, XRCC2, CCNB1, CCNE2, PLK1, AURKA, FOXM1, and PD-L1 were identified to be directly regulated by OICR-9429 in a H3K4me3-dependent manner. CONCLUSIONS: Our novel finding is that the WDR5 inhibitor, OICR-9429, suppressed proliferation, metastasis and PD-L1-based immune evasion while enhancing apoptosis and chemosensitivity to cisplatin in BCa by blocking the WDR5-MLL complex mediating H3K4me3 in target genes. Hence, our findings offer insight into a multipotential anticancer compound, OICR-9429, which enhances the antitumour effect of cisplatin or immunotherapy in BCa.

A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer.

BACKGROUND: Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. METHODS: A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. RESULTS: The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7-77.8% vs. 0.0-22.2%, 0.0-22.2%), Ta tumor (83.3% vs. 22.2-41.2%, 44.4-52.9%) and non-muscle invasive BC (NMIBC) (80.0-89.7% vs. 51.5-52.0%, 59.4-72.0%) in both cohorts. The assay also had higher accuracies (88.9-95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6-70.8%) and FISH (72.2-77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. CONCLUSIONS: The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer.

Purpose: Advanced prostate cancer (PCa) has limited treatment regimens and shows low response to chemotherapy and immunotherapy, leading to poor prognosis. Histone modification is a vital mechanism of gene expression and a promising therapy target. In this study, we characterized WD repeat domain 5 (WDR5), a regulator of histone modification, and explored its potential therapeutic value in PCa. Experimental Design: We characterized specific regulators of histone modification, based on TCGA data. The expression and clinical features of WDR5 were analyzed in two dependent cohorts. The functional role of WDR5 was further investigated with siRNA and OICR-9429, a small molecular antagonist of WDR5, in vitro and in vivo. The mechanism of WDR5 was explored by RNA-sequencing and chromatin immunoprecipitation (ChIP). Results: WDR5 was overexpressed in PCa and associated with advanced clinicopathological features, and predicted poor prognosis. Both inhibition of WDR5 by siRNA and OICR-9429 could reduce proliferation, and increase apoptosis and chemosensitivity to cisplatin in vitro and in vivo. Interestingly, targeting WDR5 by siRNA and OICR-9429 could block IFN-γ-induced PD-L1 expression in PCa cells. Mechanistically, we clarified that some cell cycle, anti-apoptosis, DNA repair and immune related genes, including AURKA, CCNB1, E2F1, PLK1, BIRC5, XRCC2 and PD-L1, were directly regulated by WDR5 and OICR-9429 in H3K4me3 and c-Myc dependent manner. Conclusions: These data revealed that targeting WDR5 suppressed proliferation, enhanced apoptosis, chemosensitivity to cisplatin and immunotherapy in PCa. Therefore, our findings provide insight into OICR-9429 is a multi-potency and promising therapy drug, which improves the antitumor effect of cisplatin or immunotherapy in PCa.

NONO Inhibits Lymphatic Metastasis of Bladder Cancer via Alternative Splicing of SETMAR.

Bladder cancer patients with lymph node (LN) metastasis have an extremely poor prognosis and no effective treatment. The alternative splicing of precursor (pre-)mRNA participates in the progression of various tumors. However, the precise mechanisms of splicing factors and cancer-related variants in LN metastasis of bladder cancer remain largely unknown. The present study identified a splicing factor, non-POU domain-containing octamer-binding protein (NONO), that was significantly downregulated in bladder cancer tissues and correlated with LN metastasis status, tumor stage, and prognosis. Functionally, NONO markedly inhibited bladder cancer cell migration and invasion in vitro and LN metastasis in vivo. Mechanistically, NONO regulated the exon skipping of SETMAR by binding to its motif, mainly through the RRM2 domain. NONO directly interacted with splicing factor proline/glutamine rich (SFPQ) to regulate the splicing of SETMAR, and it induced metastasis suppression of bladder cancer cells. SETMAR-L overexpression significantly reversed the metastasis of NONO-knockdown bladder cancer cells, both in vitro and in vivo. The further analysis revealed that NONO-mediated SETMAR-L can induce H3K27me3 at the promotor of metastatic oncogenes and inhibit their transcription, ultimately resulting in metastasis suppression. Therefore, the present findings uncover the molecular mechanism of lymphatic metastasis in bladder cancer, which may provide novel clinical markers and therapeutic strategies for LN-metastatic bladder cancer.

Mitochondrial DNA diversity and population structure of Laodelphax striatellus across a broad geographic area in China.

The small brown planthopper (SBPH), Laodelphax striatellus Fallén (Hemiptera: Delphacidae), is a crucial devastating rice pest in East Asia. To effectively control this pest, we investigate the genetic diversity, genetic differentiation and genetic structure of 49 populations in China based on a 596 bp fragment of the mitochondrial DNA cytochrome c oxidase subunit I (mtDNA COI) gene. Overall, 83 haplotypes were detected in 1253 mtDNA COI sequences. High levels of genetic variability (Hd = 0.756 ± 0.009, π = 0.00416 ± 0.00011) and genetic differentiation (FST = 0.262, p < .001) were observed. Bayesian inference phylogenetic and median-joining haplotype network analyses indicated no obvious geographical distribution pattern among haplotypes. Hierarchical AMOVA and SAMOVA revealed no genetically distinct groups and lack of obvious phylogeographic structure. Isolation by distance (IBD) analysis results demonstrated no correlation between genetic differentiation and geographic distance. Finally, the demographic history of SBPH examined by neutrality tests and mismatch distribution analyses illustrated a sudden population expansion at the large spatial scale in China.

Correction: Two-dimensional polar metal of a PbTe monolayer by electrostatic doping.

Correction for 'Two-dimensional polar metal of a PbTe monolayer by electrostatic doping' by Tao Xu et al., Nanoscale Horiz., 2020, 5, 1400-1406, DOI: .

Two-dimensional polar metal of a PbTe monolayer by electrostatic doping.

Polar metals characterized by the simultaneous coexistence of a polar structure and metallicity have been a long-sought goal due to the promise of novel electronic devices. Developing such materials at low dimensions remains challenging since both conducting electrons and reduced dimensions are supposed to quench the polar state. Here, based on first-principles calculations, we report the discovery of a non-centrosymmetric polar structure in two-dimensional (2D) metallic materials with electrostatic doping, even though ferroelectricity is unconventional at the atomic scale. We revealed that the PbTe monolayer is intrinsically ferroelectric with pronounced out-of-plane electric polarization originating from its non-centrosymmetric buckled structure. Moreover, the polar distortions can be preserved with carrier doping in the monolayer, which further enables the doped PbTe monolayer to act as a 2D polar metal. With an effective Hamiltonian extracted from the parametrized energy space, we found that the special elastic-polar mode interaction is of great importance for the existence of robust polar instability (i.e., soft phonon mode associated with polar distortion) in the doped system. The application of this doping strategy is not specific to the present crystal, but is rather general to other 2D ferroelectrics to bring about the fascinating non-centrosymmetric metallic state. Our findings thus change the conventional knowledge in 2D materials and will facilitate the development of multifunctional materials in low dimensions.

Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer.

BACKGROUNDCurrent methods for the detection and surveillance of bladder cancer (BCa) are often invasive and/or possess suboptimal sensitivity and specificity, especially in early-stage, minimal, and residual tumors.METHODSWe developed an efficient method, termed utMeMA, for the detection of urine tumor DNA methylation at multiple genomic regions by MassARRAY. We identified the BCa-specific methylation markers by combined analyses of cohorts from Sun Yat-sen Memorial Hospital (SYSMH), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) database. The BCa diagnostic model was built in a retrospective cohort (n = 313) and validated in a multicenter, prospective cohort (n = 175). The performance of this diagnostic assay was analyzed and compared with urine cytology and FISH.RESULTSWe first discovered 26 significant methylation markers of BCa in combined analyses. We built and validated a 2-marker-based diagnostic model that discriminated among patients with BCa with high accuracy (86.7%), sensitivity (90.0%), and specificity (83.1%). Furthermore, the utMeMA-based assay achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early-stage (stage Ta and low-grade tumor, 64.5% vs. 11.8%, 15.8%), minimal (81.0% vs. 14.8%, 37.9%), residual (93.3% vs. 27.3%, 64.3%), and recurrent (89.5% vs. 31.4%, 52.8%) tumors. The urine diagnostic score from this assay was better associated with tumor malignancy and burden.CONCLUSIONUrine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in BCa is a rapid, high-throughput, noninvasive, and promising approach, which may reduce the burden of cystoscopy and blind second surgery.FUNDINGThis study was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.

Loss of GATA6 expression promotes lymphatic metastasis in bladder cancer.

Lymph node metastasis is associated with tumor relapse and poor patient prognosis in bladder cancer. However, the mechanisms by which bladder carcinoma cells induce lymphangiogenesis and further promote metastasis in the lymphatic system remain unclear. Here, we show that the transcription factor GATA-binding factor 6 (GATA6) was substantially downregulated in bladder cancer via promoter hypermethylation. Low-level GATA6 expression significantly correlated with lymph node metastasis positivity and was able to predict earlier relapse and shorter survival of bladder cancer. Reconstitution of GATA6 inhibited lymphangiogenesis and lymph node metastasis in GATA6-low bladder cancer cells, while silencing of GATA6 rendered lymphatic metastasis in GATA6-high bladder cancer cells. Additionally, we demonstrated that GATA6 bound to the promoter of vascular endothelial growth factor (VEGF)-C, a lymphangiogenic factor, and acted as a transcriptional repressor. This GATA6/VEGF-C axis was essential for GATA6-mediated lymphatic metastasis. In bladder cancer patients, low GATA6 correlated with high VEGF-C and reduced overall survival. These findings indicate GATA6 as a pivotal regulator in the lymphatic dissemination of bladder cancer and suggest a new therapeutic target for the disease.