Core-Shell Structured Cobalt Sulfide/C. I. Pigment Yellow 53 Photocatalysts with Abundant Sulfur Vacancies for Efficient Photocatalytic Co-Production of Xylonic Acid and CO.

Photocatalytic biorefinery has been gaining increasing attention as a promising method for utilizing biomass and solar energy, yet it still faces the key challenge of designing stable, efficient, and cost-effective photocatalysts. In this study, cobalt sulfide/ C. I. Pigment Yellow 53 composite photocatalysts (CoS/PY53-CSx) with a core-shell structure, which has abundant sulfur (S) vacancies, are developed using a simple hydrothermal method. The CoS nanocage with S vacancies not only offers numerous active sites but also enhances the light-trapping performance of PY53. Moreover, the internal electric field within the core-shell CoS/PY53-CSx further enhances charge separation/transfer efficiency while reducing electron transfer resistance, thereby boosting photocatalytic activity. Remarkably, 75.2% of xylonic acid and 22.8 µmol of CO from xylose are obtained using CoS/PY53-CS0.1 in an air atmosphere. Recycling experiments demonstrate that CoS/PY53-CS0.1 exhibits excellent recyclability due to the strong bonding force between the core and shell. In addition, electron spin resonance characterization combined with poisoning experiments suggests that h+ and ·O2 - serve as the main oxidation active species during this system. This work presents a simple and cost-effective method for efficient photocatalytic biorefinery.

Association of HLA-DRB1 alleles with status of antibodies to hepatitis B surface and e antigen.

Antigen presentation by HLA class II molecules to CD4+ T cells is an essential step for generating antibodies to hepatitis B antigens. In this study, we investigated the association between the HLA-DRB1 gene and the status of antibodies to hepatitis B surface and e antigens. Our results revealed a significant association between the status of anti-HBsAg and HLA-DRB1*04:03 (OR = 4.11, 95% CI = 1.50-10.84, p = 0.005, Padj. = 0.05) as well as HLA-DRB1*15:01 (OR = 1.74, 95% CI = 1.20-2.50, p = 0.002, Padj. = 0.045). MHC II binding predictions and in silico docking demonstrated strong binding affinity of HBsAg peptides to these two HLA-DRB1 molecules. Conversely, the status of anti-HBeAg was inversely associated with HLA-DRB1*14:54 (OR = 0.34, 95% CI = 0.18-0.64, p = 0.001, Padj. = 0.011), and in silico analysis revealed weak binding affinity of HBeAg peptides to HLA-DRB1*14:54. In conclusion, these findings support the involvement of HLA-DRB1 in humoral immunity against HBV infection.

Manipulation and applications of ultrafast all-optical switching based on transient absorption and dispersion in KTN crystals.

Potassium tantalate niobate (KTN) represents a noteworthy category of optical crystals known for their superior nonlinear optical properties. In this study, we conducted measurements of femtosecond time-resolved transient absorption (TA) spectra in KTa0.57Nb0.43O3 crystals. Notably, a rapid and pronounced "plateau" phase, ∼1.5 ps in duration, was detected at the onset of the TA kinetics and succeeded by two distinct decay components, exhibiting lifetimes of ∼140 ps and over 10 ns, respectively. We attribute these observations to a decay process involving two-photon absorption, dispersion characteristics, and excited state absorption. Based on this unique TA characteristic of KTN crystals, an all-optical switching strategy was proposed and utilized to measure the ultrafast lasing dynamics of single-crystal CH3NH3PbBr3 nanowires. This polarization-independent TA gate approach offers an adjustable gate width combining ps and ns time scales and introduces a versatile tool for advanced optical applications.

Ultrathin endoscope equipped with ultrasonic miniprobe for upper GI US in a porcine model.

BACKGROUND AND AIMS: Ultrathin EGD (UT-EGD) is an ideal tool for unsedated upper GI examination and pediatric gastroenterology but is rarely competent for EUS miniprobe (EUS-MP). We developed a UT-EGD US method (UT-EUS) and verified its clinical application value through animal experiments. METHODS: Five Bama miniature pigs were selected. Using an acoustic medium, we performed US on the duodenum, stomach, and esophagus, respectively, with conventional 20-MHz EUS miniprobe (EUS-MP-20), 20-MHz UT-EUS (UT-EUS-20), and 30-MHz UT-EUS (UT-EUS-30). The times to acquire 5 consecutive stable US images, number of identifiable wall layers, and quality and penetration depth of the images were recorded. RESULTS: No significant differences were found in the time required to obtain images between EUS-MP-20 and UT-EUS-20 at each site (P > .05). UT-EUS-30 showed more wall levels than UT-EUS-20 (P < .05). No significant differences were noted between EUS-MP-20 and UT-EUS-20 in imaging quality and penetration depth (P > .05). CONCLUSIONS: The UT-EUS is easy to use with a satisfactory image quality and has potential clinical application value.

Which productivity can promote clean energy transition -total factor productivity or green total factor productivity?

Developing clean energy is a key pathway and an inevitable choice for achieving the goals of carbon peak and carbon neutrality. From a global perspective, technology is increasingly affecting the trajectory of energy transition, driving clean energy into a stage of rapid development. Therefore, this paper focuses on exploring the dynamic evolutionary characteristics of clean energy transitions driven by different productivity. Using panel data from 171 economies from 1990 to 2019, this paper systematically examines the impact of Total Factor Productivity (TFP) and Green Total Factor Productivity (GTFP) on clean energy transitions. The empirical results indicate that both TFP and GTFP positively impact clean energy transition. Specifically, clean energy consumption increases by 3.35% and 6.03%with a one standard deviation change in TFP and GTFP respectively. Upon decomposing TFP and GTFP, it was found that Green Efficiency Change (GECH) and Green Technical Change (GHCH), especially GECH, are the main factors driving the clean energy transition. Heterogeneity analysis shows that, in developed economies, GTFP has a larger positive impact on clean energy transition than TFP. Furthermore, GTFP demonstrates a significant positive impact on the clean energy transition both before and after the 2008 financial crisis, whereas TFP's positive impact is only evident before the crisis. Our findings emphasize the social benefits of further investments in GTFP.

Bidirectional Decoupled Distillation for Heterogeneous Federated Learning.

Federated learning enables multiple devices to collaboratively train a high-performance model on the central server while keeping their data on the devices themselves. However, due to the significant variability in data distribution across devices, the aggregated global model's optimization direction may differ from that of the local models, making the clients lose their personality. To address this challenge, we propose a Bidirectional Decoupled Distillation For Heterogeneous Federated Learning (BDD-HFL) approach, which incorporates an additional private model within each local client. This design enables mutual knowledge exchange between the private and local models in a bidirectional manner. Specifically, previous one-way federated distillation methods mainly focused on learning features from the target class, which limits their ability to distill features from non-target classes and hinders the convergence of local models. To solve this limitation, we decompose the network output into target and non-target class logits and distill them separately using a joint optimization of cross-entropy and decoupled relative-entropy loss. We evaluate the effectiveness of BDD-HFL through extensive experiments on three benchmarks under IID, Non-IID, and unbalanced data distribution scenarios. Our results show that BDD-HFL outperforms state-of-the-art federated distillation methods across five baselines, achieving at most 3% improvement in average classification accuracy on the CIFAR-10, CIFAR-100, and MNIST datasets. The experiments demonstrate the superiority and generalization capability of BDD-HFL in addressing personalization challenges in federated learning.

Layered Cathode Materials: Precursors, Synthesis, Microstructure, Electrochemical Properties, and Battery Performance.

The exploitation of clean energy promotes the exploration of next-generation lithium-ion batteries (LIBs) with high energy-density, long life, high safety, and low cost. Ni-rich layered cathode materials are one of the most promising candidates for next-generation LIBs. Numerous studies focusing on the synthesis and modifications of the layered cathode materials are published every year. Many physical features of precursors, such as density, morphology, size distribution, and microstructure of primary particles pass to the resulting cathode materials, thus significantly affecting their electrochemical properties and battery performance. This review focuses on the recent advances in the controlled synthesis of hydroxide precursors and the growth of particles. The essential parameters in controlled coprecipitation are discussed in detail. Some innovative technologies for precursor modifications and for the synthesis of novel precursors are highlighted. In addition, future perspectives of the development of hydroxide precursors are presented.

Evaluation of short-term (16-week) effectiveness and safety of guselkumab in patients with psoriasis: A prospective real-life study on the Chinese population.

Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4+ CD25+ Foxp3+ regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4+ CD25+ Foxp3+ Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.

3MTox: A motif-level graph-based multi-view chemical language model for toxicity identification with deep interpretation.

Toxicity identification plays a key role in maintaining human health, as it can alert humans to the potential hazards caused by long-term exposure to a wide variety of chemical compounds. Experimental methods for determining toxicity are time-consuming, and costly, while computational methods offer an alternative for the early identification of toxicity. For example, some classical ML and DL methods, which demonstrate excellent performance in toxicity prediction. However, these methods also have some defects, such as over-reliance on artificial features and easy overfitting, etc. Proposing novel models with superior prediction performance is still an urgent task. In this study, we propose a motifs-level graph-based multi-view pretraining language model, called 3MTox, for toxicity identification. The 3MTox model uses Bidirectional Encoder Representations from Transformers (BERT) as the backbone framework, and a motif graph as input. The results of extensive experiments showed that our 3MTox model achieved state-of-the-art performance on toxicity benchmark datasets and outperformed the baseline models considered. In addition, the interpretability of the model ensures that the it can quickly and accurately identify toxicity sites in a given molecule, thereby contributing to the determination of the status of toxicity and associated analyses. We think that the 3MTox model is among the most promising tools that are currently available for toxicity identification.

Efferocytosis-Inspired Biomimetic Nanoplatform for Targeted Acute Lung Injury Therapy.

Acute lung injury (ALI) is a serious inflammatory disease that causes impairment of pulmonary function. Phenotypic modulation of macrophage in the lung using fibroblast growth factor 21 (FGF21) may be a potential strategy to alleviate lung inflammation. Consequently, achieving specific delivery of FGF21 to the inflamed lung and subsequent efficient FGF21 internalization by macrophages within the lung becomes critical for effective ALI treatment. Here, an apoptotic cell membrane-coated zirconium-based metal-organic framework UiO-66 is reported for precise pulmonary delivery of FGF21 (ACM@U-FGF21) whose design is inspired by the process of efferocytosis. ACM@U-FGF21 with apoptotic signals is recognized and internalized by phagocytes in the blood and macrophages in the lung, and then the intracellular ACM@U-FGF21 can inhibit the excessive secretion of pro-inflammatory cytokines by these cells to relieve the inflammation. Utilizing the homologous targeting properties inherited from the source cells and the spontaneous recruitment of immune cells to inflammatory sites, ACM@U-FGF21 can accumulate preferentially in the lung after injection. The results prove that ACM@U-FGF21 effectively reduces inflammatory damage to the lung by modulating lung macrophage polarization and suppressing the excessive secretion of pro-inflammatory cytokines by activated immune cells. This study demonstrates the usefulness of efferocytosis-inspired ACM@U-FGF21 in the treatment of ALI.

A strategy for oral delivery of FGF21 for mitigating inflammation and multi-organ damage in sepsis.

Fibroblast growth factor 21 (FGF21) shows great therapeutic potential in metabolic, neurodegenerative and inflammatory diseases. However, current FGF21 administration predominantly relies on injection rather than oral ingestion due to its limited stability and activity post-gastrointestinal transit, thereby hindering its clinical utility. Milk-derived exosomes (mEx) have emerged as a promising vehicle for oral drug delivery due to their ability to maintain structural integrity in the gastrointestinal milieu. To address the challenge associated with oral delivery of FGF21, we encapsulated FGF21 within mEx (mEx@FGF21) to protect its activity post-oral administration. Additionally, we modified the surface of mEx@FGF21 by introducing transferrin (TF) to enhance intestinal absorption and transport, designated TF-mEx@FGF21. In vitro results demonstrated that the surface modification of TF promoted FGF21 internalization by intestinal epithelial cells. Orally administered TF-mEx@FGF21 showed promising therapeutic effects in septic mice. This study represents a practicable strategy for advancing the clinical application of oral FGF21 delivery.

Erythrocyte membrane biomimetic EGCG nanoparticles attenuate renal injury induced by diquat through the NF-κB/NLRP3 inflammasome pathway.

Diquat (DQ) poisoning can cause multiple organ damage, and the kidney is considered to be the main target organ. Increasing evidence shows that alleviating oxidative stress and inflammatory response has promising application prospects. Epigallocatechin gallate (EGCG) has potent antioxidant and anti-inflammatory effects. In this study, red blood cell membrane (RBCm)-camouflaged polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) were synthesized to deliver EGCG (EGCG-RBCm/NPs) for renal injury induced by DQ. Human renal tubular epithelial cells (HK-2 cells) were stimulated with 600 µM DQ for 12 h and mice were intraperitoneally injected with 50 mg/kg b.w. DQ, followed by 20 mg/kg b.w./day EGCG or EGCG-RBCM/NPs for 3 days. The assessment of cellular vitality was carried out using the CCK-8 assay, while the quantification of reactive oxygen species (ROS) was performed through ROS specific probes. Apoptosis analysis was conducted by both flow cytometry and TUNEL staining methods. Pathological changes in renal tissue were observed. The expressions of NLRP3, IL-1ß, IL-18, NFκB and Caspase1 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, immunofluorescence, and Western blot. The results showed that the DQ group had increased ROS expression, increased the level of oxidative stress, and increased apoptosis rate compared with the control group. Histopathological analysis of mice in the DQ group showed renal tubular injury and elevated levels of blood urea nitrogen (BUN), serum creatinine (SCr), kidney injury molecule-1 (KIM-1), and cystatin C (Cys C). Furthermore, the DQ group exhibited heightened expression of NLRP3, p-NFκB p65, Caspase1 p20, IL-1ß, and IL-18. However, EGCG-RBCm/NPs treatment mitigated DQ-induced increases in ROS, apoptosis, and oxidative stress, as well as renal toxicity and decreases in renal biomarker levels. Meanwhile, the expression of the above proteins were significantly decreased, and the survival rate of mice was ultimately improved, with an effect better than that of the EGCG treatment group. In conclusion, EGCG-RBCm/NPs can improve oxidative stress, inflammation, and apoptosis induced by DQ. This effect is related to the NF-κB/NLRP3 inflammasome pathway. Overall, this study provides a new approach for treating renal injury induced by DQ.

Chitosan-amidated lignin aerogel beads efficiently loaded with lanthanum hydroxide for phosphate removal from aqueous solutions.

Developing phosphorus removal adsorbents with high adsorption performance and excellent structural stability remains a challenge. Herein, a chitosan (CS) - amidated lignin (AL) gel-bead adsorbent with high efficiency in immobilizing lanthanum hydroxide (La(OH)3) was fabricated via an in situ precipitation and freeze-drying strategy (abbreviated as La@ALCSx). The abundant hydroxyl and amino groups in CS promoted excellent loading of La(OH)3 on the surface and inside of the adsorbent. The introduction of lignin enhanced the structural stability of the beads along with the mass transfer efficiency. Owing to the porous structure and high La utilization, the adsorption capacity of La@ALCS2 reached 130.52 mg P g-1. Intra-sphere complexation of La(OH)3 with phosphate resulted in high adsorption selectivity of La@ALCS2. Moreover, the millimeter-sized of La@ALCS2 has favourable recoverability and maintains high adsorption performance after five adsorption-desorption cycles. Characterization analysis indicated that electrostatic attraction and ligand exchange were the main adsorption mechanisms. The excellent phosphorus removal efficiency, separation efficiency and recyclability of La@ALCSx provide a viable solution for the remediation of phosphate contaminated waters.

Pd Nanoclusters-Sensitized MIL-125/TiO2 Nanochannel Arrays for Sensitive and Humidity-Resistant Formaldehyde Detection at Room Temperature.

Among the various hazardous substances, formaldehyde (HCHO), produced worldwide from wood furniture, dyeing auxiliaries, or as a preservative in consumer products, is harmful to human health. In this study, a sensitive room-temperature HCHO sensor, MTiNCs/Pd, has been developed by integrating Pd nanoclusters (PdNCs) into mesoporous MIL-125(Ti)-decorated TiO2 nanochannel arrays (TiNCs). Thanks to the enrichment effect of the mesoporous structure of MIL-125 and the large surface area offered by TiNCs, the resulting gas sensor accesses significantly enhanced HCHO adsorption capacity. The sufficient energetic active defects formed on PdNCs further allow an electron-extracting effect, thus effectively separating the photogenerated electrons and holes at the interface. The resulting HCHO sensor exhibits a short response/recovery time (37 s/12 s) and excellent sensitivity with a low limit of detection (4.51 ppb) under ultraviolet (UV) irradiation. More importantly, the cyclic redox reactions of Pdδ+ in PdNCs facilitated the regeneration of O2-(ads), thus ensuring a stable and excellent gas sensing performance even under a high-humidity environment. As a proof-of-principle of this design, a wearable gas sensing band is developed for the real-time and on-site detection of HCHO in cigarette smoke, with the potential as an independent device for environmental monitoring and other smart sensing systems.

Intelligent drugs based on notch protein remodeling: a defensive targeting strategy for tumor therapy.

In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple "wisdom" by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

Solute carrier family 16 member 1 as a potential prognostic factor for pancreatic ductal adenocarcinoma and its influence on tumor immunity.

Background: Solute carrier family 16 member 1 (SLC16A1) serves as a biomarker in numerous types of cancer. Tumor immune infiltration has drawn increasing attention in cancer progression and treatment. The objective of our study was to explore the association between SLC16A1 and the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). Methods: Data were obtained from The Cancer Genome Atlas. The xCell web tool was used to calculate the proportion of immune cells according to SLC16A1 expression. To further explore the mechanism of SLC16A1, immunity-related genes were screened from differentially expressed genes through weighted gene coexpression network analysis, examined via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and filtrated using univariate Cox regression and least absolute shrinkage and selection operator regression model combined correlation analysis (P<0.05). Next, CIBERSORT was used to analyze the correlation between immune cells and five important genes. SLC16A1 expression and its clinical role in pancreatic cancer was clarified via immunohistochemical staining experiments. Finally, the effects of SLC16A1 on the results of cancer immunity were evaluated by in vitro experiments. Results: SLC16A1 was overexpressed in PDAC tissues and could be an independent prognostic factor. SLC16A1 was significantly negatively correlated with overall survival and suppressed the tumor immunity of PDAC. In clinic, SLC16A1 expression was significantly positively correlated with tumor progression and poor prognosis. We also found that SLC16A1 could suppress the antitumor ability of CD8+ T cells. Conclusions: SLC16A1 is a biomarker for the prognosis of PDAC and can influence the immune environment of PDAC. These findings provide new insights into the treatment of PDAC.

Liquid-free ionic conductive elastomers with high mechanical properties and ionic conductivity for multifunctional sensors and triboelectric nanogenerators.

Liquid-free ionic conductive elastomers (ICEs) are ideal materials for constructing flexible electronic devices by avoiding the limitations of liquid components. However, developing all-solid-state ionic conductors with high mechanical strength, high ionic conductivity, excellent healing, and recyclability remains a great challenge. Herein, a series of liquid-free polyurethane-based ICEs with a double dynamic crosslinked structure are reported. As a result of interactions between multiple dynamic bonds (multi-level hydrogen bonds, disulfide bonds, and dynamic D-A bonds) and lithium-oxygen bonds, the optimal ICE exhibited a high mechanical strength (1.18 MPa), excellent ionic conductivity (0.14 mS cm-1), desirable healing capacity (healing efficiency >95%), and recyclability. A multi-functional wearable sensor based on the novel ICE enabled real-time and rapid detection of various human activities and enabled recognizing writing signals and encrypted information transmission. A triboelectric nanogenerator based on the novel ICE exhibited an excellent open-circuit voltage of 464 V, a short-circuit current of 16 µA, a transferred charge of 50 nC, and a power density of 720 mW m-2, enabling powering of small-scale electronic products. This study provides a feasible strategy for designing flexible sensor products and healing, self-powered devices, with promising prospects for application in soft ionic electronics.

Kidney targeting peptide-modified biomimetic nanoplatforms for treatment of acute kidney injury.

The management of acute kidney injury (AKI) imposes a significant medical burden. Due to the lack of effective drug transport vehicles, the administration of therapeutic agents for AKI cannot obtain the desired therapeutic effects. Kidney-targeted nanoparticles for renal delivery of drugs have shown promising potential as an emerging strategy for AKI therapy. However, these exogenous nanoparticles are rapidly cleared in the body and fail to achieve the expected renal targeting efficiency. Herein, we prepared the kidney targeting peptide-modified renal tubular epithelial cell membrane to coat zeolite imidazolate framework-8 nanoparticles for FGF21 delivery (KMZ@FGF21) for AKI treatment. KMZ@FGF21 could be efficiently internalized by renal cells and exhibited antioxidative, antiapoptotic and anti-inflammatory effects. A septic AKI murine model was established to assess the in vivo performance of KMZ@FGF21. The results showed that injected KMZ@FGF21 specifically accumulated in the injured kidney and exerted good renoprotective effects. This study provides an innovative thread for precise drug delivery in the treatment of various renal diseases.

Simultaneous photocatalytic biomass conversion and CO2 reduction over high crystalline oxygen-doped carbon nitride.

Simultaneous photocatalytic biorefinery and CO2 reduction to co-produce fuels and high value-added chemicals have recently attracted significant attention; however, comprehensive studies are still lacking. Herein, we report the preparation of highly crystalline oxygen-doped carbon nitride nanotubes (O-CNNTs-x) using an ammonium fluoride-assisted hydrothermal/calcination strategy. The hollow structure, high crystallinity, and O incorporation endowed the O-CNNTs-x with photocatalytic activity by considerably improving optical absorption and modulating the charge carrier motion. The lactic acid yield and CO evolution rate over O-CNNTs-2.0 reached 82.08% and 67.95 µmol g-1 h-1, which are 1.57- and 7.37-fold times higher than those of CN, respectively. Moreover, ·OH plays a key role in the oxidation half-reaction. This study offers a facile approach for fabricating highly crystalline element-doped CN with a customizable morphology and electronic properties and demonstrates the viability of co-photocatalytic CO2 reduction and biomass selective oxidation.

METTL14 regulates chromatin bivalent domains in mouse embryonic stem cells.

METTL14 (methyltransferase-like 14) is an RNA-binding protein that partners with METTL3 to mediate N6-methyladenosine (m6A) methylation. Recent studies identified a function for METTL3 in heterochromatin in mouse embryonic stem cells (mESCs), but the molecular function of METTL14 on chromatin in mESCs remains unclear. Here, we show that METTL14 specifically binds and regulates bivalent domains, which are marked by trimethylation of histone H3 lysine 27 (H3K27me3) and lysine 4 (H3K4me3). Knockout of Mettl14 results in decreased H3K27me3 but increased H3K4me3 levels, leading to increased transcription. We find that bivalent domain regulation by METTL14 is independent of METTL3 or m6A modification. METTL14 enhances H3K27me3 and reduces H3K4me3 by interacting with and probably recruiting the H3K27 methyltransferase polycomb repressive complex 2 (PRC2) and H3K4 demethylase KDM5B to chromatin. Our findings identify an METTL3-independent role of METTL14 in maintaining the integrity of bivalent domains in mESCs, thus indicating a mechanism of bivalent domain regulation in mammals.