Integrated analysis of RNA methylation regulators crosstalk and immune infiltration for predictive and personalized therapy of diabetic nephropathy.

BACKGROUND: RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear. METHODS: The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro. RESULTS: We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose. CONCLUSION: Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN.

Ionic Hyperbranched Poly(amido-amine)-Incorporated Nanofiltration Membranes for High-Efficiency Dye Desalination.

High-efficiency dye desalination is crucial in the textile industry, considering its importance for human health, safe aquatic ecological systems, and resource recovery. In order to solve the problem of effective separation of univalent salt and ionic dye under the condition of high salt, ionic hyperbranched poly(amido-amine) (HBPs) were synthesized based on a simple and scalable one-step polycondensation method and then incorporated into the polyamide (PA) selective layers to construct charged nanochannels through interfacial polymerization (IP) on the surface of a polyvinyl chloride ultrafiltration (PVC-UF) hollow fiber membrane. Both the internal nanopores of HBPs (internal nanochannels) and the interfacial voids between HBPs and the PA matrix (external nanochannels) can be regarded as a fast water molecule transport pathway, while the terminal ionic groups of ionic HBPs endow the nanochannels with charge characteristics for improving ionic dye/salt selectivities. The permeate fluxes and dye/salt selectivities of HBP-TAC/PIP (57.3 L m-2 h-1 and rhodamine B (RB)/NaCl selectivity of 224.0) and HBP-PS/PIP (63.7 L m-2 h-1 and lemon yellow (LY)/NaCl selectivity of 664.0) membranes under 0.4 MPa operation pressure are much higher than PIP-only and HBP-NH2/PIP membranes. At the same time, this project also studied the membrane desalination process in a simulated high-salinity dye/salt mixture system to provide a theoretical basis and technical support for the actual dye desalination process.

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy.

The mechanisms underlying the complex correlation between immunoglobulin A nephropathy (IgAN) and inflammatory bowel disease (IBD) remain unclear. This study aimed to identify the optimal cross-talk genes, potential pathways, and mutual immune-infiltrating microenvironments between IBD and IgAN to elucidate the linkage between patients with IBD and IgAN. The IgAN and IBD datasets were obtained from the Gene Expression Omnibus (GEO). Three algorithms, CIBERSORTx, ssGSEA, and xCell, were used to evaluate the similarities in the infiltrating microenvironment between the two diseases. Weighted gene co-expression network analysis (WGCNA) was implemented in the IBD dataset to identify the major immune infiltration modules, and the Boruta algorithm, RFE algorithm, and LASSO regression were applied to filter the cross-talk genes. Next, multiple machine learning models were applied to confirm the optimal cross-talk genes. Finally, the relevant findings were validated using histology and immunohistochemistry analysis of IBD mice. Immune infiltration analysis showed no significant differences between IBD and IgAN samples in most immune cells. The three algorithms identified 10 diagnostic genes, MAPK3, NFKB1, FDX1, EPHX2, SYNPO, KDF1, METTL7A, RIDA, HSDL2, and RIPK2; FDX1 and NFKB1 were enhanced in the kidney of IBD mice. Kyoto Encyclopedia of Genes and Genomes analysis showed 15 mutual pathways between the two diseases, with lipid metabolism playing a vital role in the cross-talk. Our findings offer insights into the shared immune mechanisms of IgAN and IBD. These common pathways, diagnostic cross-talk genes, and cell-mediated abnormal immunity may inform further experimental studies.

Adaptive prediction for effluent quality of wastewater treatment plant: Improvement with a dual-stage attention-based LSTM network.

The accurate effluent prediction plays a crucial role in providing early warning for abnormal effluent and achieving the adjustment of feedforward control parameters during wastewater treatment. This study applied a dual-staged attention mechanism based on long short-term memory network (DA-LSTM) to improve the accuracy of effluent quality prediction. The results showed that input attention (IA) and temporal attention (TA) significantly enhanced the prediction performance of LSTM. Specially, IA could adaptively adjust feature weights to enhance the robustness against input noise, with R2 increased by 13.18%. To promote its long-term memory ability, TA was used to increase the memory span from 96 h to 168 h. Compared to a single LSTM model, the DA-LSTM model showed an improvement in prediction accuracy by 5.10%, 2.11%, 14.47% for COD, TP, and TN. Additionally, DA-LSTM demonstrated excellent generalization performance in new scenarios, with the R2 values for COD, TP, and TN increasing by 22.67%, 20.06%, and 17.14% respectively, while the MAPE values decreased by 56.46%, 63.08%, and 42.79%. In conclusion, the DA-LSTM model demonstrated excellent prediction performance and generalization ability due to its advantages of feature-adaptive weighting and long-term memory focusing. This has forward-looking significance for achieving efficient early warning of abnormal operating conditions and timely management of control parameters.

Based on HPLC and HS-GC-IMS Techniques, the Changes in the Internal Chemical Components of Schisandra chinensis (Turcz.) Baill. Fruit at Different Harvesting Periods Were Analyzed.

Schisandra chinensis, as a traditional Chinese herbal medicine, has clear pharmacological effects such as treating asthma, protecting nerves and blood vessels, and having anti-inflammatory properties. Although the Schisandra chinensis fruit contain multiple active components, the lignans have been widely studied as the primary pharmacologically active compound. The volatile chemical components of Schisandra chinensis include a large amount of terpenes, which have been proven to have broad pharmacological activities. However, when to harvest to ensure the highest accumulation of pharmacologically active components in Schisandra chinensis fruits is a critical issue. The Schisandra chinensis fruit trees in the resource nursery were all planted in 2019 and began bearing fruit in 2021. Their nutritional status and tree vigor remain consistently good. The content of lignans and organic acids in the fruits of Schisandra chinensis over seven different harvest periods was tested, and the results of high-performance liquid chromatography (HPLC) indicated that the lignan content was higher, at 35 mg/g, in late July, and the organic acid content was higher, at 72.34 mg/g, in early September. If lignans and organic acids are to be selected as raw materials for pharmacological development, the harvest can be carried out at this stage. Using HS-GC-IMS technology, a total of 67 volatile flavor substances were detected, and the fingerprint of the volatile flavor substances in the different picking periods was established. It was shown by the results that the content of volatile flavor substances was the highest in early August, and 16 flavor substances were selected by odor activity value (OAV). The variable importance in projection (VIP) values of 16 substances were further screened, and terpinolene was identified as the key volatile flavor substance that caused the aroma characteristics of Schisandra chinensis fruit at different harvesting periods. If the aroma component content of Schisandra chinensis fruit is planned to be used as raw material for development and utilization, then early August, when the aroma component content is higher, should be chosen as the time for harvest. This study provides a theoretical basis for the suitable harvesting time of Schisandra chinensis for different uses, and promotes the high-quality development of the Schisandra chinensis industry.

LncRNA-protein interaction prediction with reweighted feature selection.

LncRNA-protein interactions are ubiquitous in organisms and play a crucial role in a variety of biological processes and complex diseases. Many computational methods have been reported for lncRNA-protein interaction prediction. However, the experimental techniques to detect lncRNA-protein interactions are laborious and time-consuming. Therefore, to address this challenge, this paper proposes a reweighting boosting feature selection (RBFS) method model to select key features. Specially, a reweighted apporach can adjust the contribution of each observational samples to learning model fitting; let higher weights are given more influence samples than those with lower weights. Feature selection with boosting can efficiently rank to iterate over important features to obtain the optimal feature subset. Besides, in the experiments, the RBFS method is applied to the prediction of lncRNA-protein interactions. The experimental results demonstrate that our method achieves higher accuracy and less redundancy with fewer features.

Identification of novel regulators required for early development of vein pattern in the cotyledons by single-cell RNA-sequencing.

The leaf veins of higher plants contain a highly specialized vascular system comprised of xylem and phloem cells that transport water, organic compounds and mineral nutrients. The development of the vascular system is controlled by phytohormones that interact with complex transcriptional regulatory networks. Before the emergence of true leaves, the cotyledons of young seedlings perform photosynthesis that provides energy for the sustainable growth and survival of seedlings. However, the mechanisms underlying the early development of leaf veins in cotyledons are still not fully understood, in part due to the complex cellular composition of this tissue. To better understand the development of leaf veins, we analyzed 14 117 single cells from 3-day-old cotyledons using single-cell RNA sequencing. Based on gene expression patterns, we identified 10 clusters of cells and traced their developmental trajectories. We discovered multiple new marker genes and developmental features of leaf veins. The transcription factor networks of some cell types indicated potential roles of CYCLING DOF FACTOR 5 (CDF5) and REPRESSOR OF GA (RGA) in the early development and function of the leaf veins in cotyledons. These new findings lay a foundation for understanding the early developmental dynamics of cotyledon veins. The mechanisms underlying the early development of leaf veins in cotyledons are still not fully understood. In this study, we comprehensively characterized the early differentiation and development of leaf veins in 3-day-old cotyledons based on single-cell transcriptome analysis. We identified the cell types and novel marker genes of leaf veins and characterized the novel regulators of leaf vein.

Research strategies for single-cell transcriptome analysis in plant leaves.

The recent and continuous improvement in single-cell RNA sequencing (scRNA-seq) technology has led to its emergence as an efficient experimental approach in plant research. However, compared with single-cell research in animals and humans, the application of scRNA-seq in plant research is limited by several challenges, including cell separation, cell type annotation, cellular function analysis, and cell-cell communication networks. In addition, the unavailability of corresponding reliable and stable analysis methods and standards has resulted in the relative decentralization of plant single-cell research. Considering these shortcomings, this review summarizes the research progress in plant leaf using scRNA-seq. In addition, it describes the corresponding feasible analytical methods and associated difficulties and problems encountered in the current research. In the end, we provide a speculative overview of the development of plant single-cell transcriptome research in the future.

Self-Reconstructed Two-Dimensional Cluster-Based Co-Organic Layer Heterojunctions for Enhanced Oxygen Evolution Reactions.

When it comes to an efficient catalytic oxygen evolution reaction (OER) in the production of renewable energy and chemicals, the construction of heterogeneous structures is crucial to break the linear scalar relationship of a single catalyst. This heterogeneous structure construction helps creatively achieve high activity and stability. However, the synthesis process of heterogeneous crystalline materials is often complex and challenging to capture and reproduce, which limits their application. Here, the dynamic process of structural changes in Co-MOFs in alkali was captured by in situ powder X-ray diffraction, FT-IR spectroscopy, and Raman spectroscopy, and several self-reconfigured MOF heterogeneous materials with different structures were stably isolated. The created ß-Co(OH)2/Co-MOF heterojunction structure facilitates rapid mass-charge transfer and exposure of active sites, which significantly enhanced OER activity. Experimental results show that this heterogeneous structure achieves a low overpotential of 333 mV at 10 mA cm-2. The findings provide new insights and directions for the search for highly reactive cobalt-based MOFs for sustainable energy technologies.

Polyethylene glycol with dual three-dimensional porous carbon nanotube/diamond: a high thermal conductivity of composite PCM.

Polyethylene glycol (PEG) is widely used as a phase change material (PCM) in thermal energy storage systems due to its high latent heat and chemical stability. However, practical application has been hindered by its low thermal conductivity and leakage issues. Therefore, developing shape-stable high thermal conductivity PCM is of great importance. In this study, new shape-stable composite PCM with high thermal conductivity and leak-prevention capabilities were designed. The porous carbon skeleton of diamond foam (DF) and dual-3D carbon nanotube-diamond foam (CDF) were prepared using the microwave plasma chemical vapor deposition method. The composite materials (DF/PEG and CDF/PEG) were produced by vacuum impregnation with PEG and skeletons. The results showed that CDF/PEG had the highest thermal conductivity, measuring 2.30 W·m-1·K-1, which is 707% higher than that of pure PEG. The employing of 3D networks of CNTs, which can improve the phonon mean free path in DF/PEG (1.79 W·m-1·K-1) while reducing phonon dispersion.The phonon vibration of dual-3D CDF plays an important role in heat transfer. PEG was physically absorbed and well-distributed in CDF, alleviating leakage of liquid PEG. The weight loss of CDF/PEG was only 25% at 70 °C for 120 s. Using CDF is an attractive and efficient strategy to increase the heat transfer of PEG and improve heat storage efficiency, alleviate the problem of poor shape-stability.

Nitrifier adaptation to low energy flux controls inventory of reduced nitrogen in the dark ocean.

Ammonia oxidation to nitrite and its subsequent oxidation to nitrate provides energy to the two populations of nitrifying chemoautotrophs in the energy-starved dark ocean, driving a coupling between reduced inorganic nitrogen (N) pools and production of new organic carbon (C) in the dark ocean. However, the relationship between the flux of new C production and the fluxes of N of the two steps of oxidation remains unclear. Here, we show that, despite orders-of-magnitude difference in cell abundances between ammonia oxidizers and nitrite oxidizers, the two populations sustain similar bulk N-oxidation rates throughout the deep waters with similarly high affinities for ammonia and nitrite under increasing substrate limitation, thus maintaining overall homeostasis in the oceanic nitrification pathway. Our observations confirm the theoretical predictions of a redox-informed ecosystem model. Using balances from this model, we suggest that consistently low ammonia and nitrite concentrations are maintained when the two populations have similarly high substrate affinities and their loss rates are proportional to their maximum growth rates. The stoichiometric relations between the fluxes of C and N indicate a threefold to fourfold higher C-fixation efficiency per mole of N oxidized by ammonia oxidizers compared to nitrite oxidizers due to nearly identical apparent energetic requirements for C fixation of the two populations. We estimate that the rate of chemoautotrophic C fixation amounts to ∼1 × 1013 to ∼2 × 1013 mol of C per year globally through the flux of ∼1 × 1014 to ∼2 × 1014 mol of N per year of the two steps of oxidation throughout the dark ocean.

Broadband similariton generation in a mode-locked Yb-doped fiber laser.

We experimentally demonstrated a broadband similariton generated from a mode-locked Yb-doped fiber laser with dispersion compensation. The broadest spectrum was obtained by pushing the net dispersion to its limitation and fully exploiting the gain bandwidth. The spectrum was 115 nm broad in 10 dB bandwidth and 36 nm broad in 3 dB bandwidth. The output was 105 mW optical power at 545 mW pump power. Simulation combined with experiment was performed to investigate and confirm the mode-locking regime of the laser. Experimental observations agreed well with the numerical simulation. We believe our study provides a practical route for designing broadband mode-locked fiber lasers.

Pharmacological characterization and biological function of the interleukin-8 receptor, CXCR2, in largemouth bass (Micropterus salmoides).

Interleukin-8 (IL-8 or C-X-C motif chemokine ligand 8, CXCL8) is a cytokine secreted by numerous cell types and is best known for its functional roles in inflammatory response by binding to specific receptors (the interleukin-8 receptors, IL-8Rs). From the transcriptomic data of largemouth bass (Micropterus salmoides), we identified an IL-8R that is highly homologous to the functionally validated teleost IL-8Rs. The M. salmoides IL-8 receptor (MsCXCR2) was further compared with the C-X-C motif chemokine receptor 2 subfamily by phylogenetic analysis. Briefly, the full-length CDS sequence of MsCXCR2 was cloned into the pEGFP-N1 plasmid, and the membrane localization of fusion expressing MsCXCR2-EGFP was revealed in HEK293 cells. To determine the functional interaction between IL-8 and MsCXCR2, secretory expressed Larimichthys crocea IL-8 (LcIL-8) was used to stimulate MsCXCR2 expressing cells. MsCXCR2 was demonstrated to be activated by LcIL-8, leading to receptor internalization, which was further revealed by the detection of extracellular regulated protein kinase (ERK) phosphorylation. Quantitative real-time PCR was used to evaluate the expressional distribution and variation of MsCXCR2 in healthy and Nocardia seriolae infected fish. Based on our findings, MsCXCR2 was constitutively expressed in all examined tissues, despite at different levels. Furthermore, gene expression was found to be significantly upregulated in the liver and head kidney of diseased fish. Collectively, our findings reveal the molecular activity of MsCXCR2 and indicate the functional involvement of this IL-8R in the immune response induced by N. seriolae in M. salmoides.

Enhanced cadmium phytoremediation capacity of poplar is associated with increased biomass and Cd accumulation under nitrogen deposition conditions.

Nitrogen (N) deposition plays a significant role in soil cadmium (Cd) phytoremediation, and poplar has been considered for the remediation of contaminated soil because of its enormous biomass and strong Cd resistance. To reveal the underlying physiological and root phenotypic mechanisms of N deposition affecting Cd phytoextraction in poplar, we assessed root phenotypic characteristics, Cd absorption and translocation, chlorophyll fluorescence performance, and antioxidant enzyme activities of a clone of Populus deltoides × P. nigra through combined greenhouse Cd and N experiments. Our results showed that Cd significantly changed the root phenotype by reducing root length, tip number, and diameter. Cd also caused the peroxidation of lipids, damaged the photosystem II (PSII) reaction centre, and reduced photosynthetic capacity, resulting in a decrease in biomass accumulation in poplar. The N60 (60 kg N·ha-1·yr-1) and N90 (90 kg N·ha-1·yr-1) treatments promoted the net photosynthetic rate of poplar by increasing the activity of antioxidant enzymes and proline content and repairing the PSII reaction centre, thus increasing the biomass accumulation of poplar exposed to Cd stress. Simultaneously, the N60 and N90 treatments might have increased Cd uptake from the soil by upregulating total root length, root tips, and fine root length. Cd mainly accumulated in roots and stems but not in leaves. The N30 (30 kg N·ha-1·yr-1) treatment had no obvious effects on these parameters compared with the single Cd treatment. Consequently, our study suggested that adequate N can improve biomass and Cd accumulation to enhance the phytoremediation capacity of poplar for Cd, which might be related to the improvement of leaf physiological defence and the change in root phenotypic characteristics.

Genome-wide prediction and comparative transcriptomic analysis reveals the G protein-coupled receptors involved in gonadal development of Apostichopus japonicus.

The sea cucumber Apostichopus japonicus is dioecious, with seasonal reproduction. G protein-coupled receptor (GPCR)-mediated signaling systems might play critical roles in the reproductive control of A. japonicus. Here, we classified GPCR from the genome in silico and used transcriptomic analyses to further mine those that function in gonadal-development control. Totally, 487 GPCRs were predicted from A. japonicus, and 183 of these were further annotated to molecular pathways. Transcriptome analysis revealed 327 GPCRs expressed in gonads, and these were classified into four families and 19 subfamilies. Three pathways were apparently associated with reproduction, including neuroactive ligand-receptor interaction, the mTOR and Wnt signaling pathways. Seven and eight ovary- and testis-specific GPCRs were filtered, and the gene expression profiles were determined in multiple tissues and gonads at different developmental stages by qPCR. These results provide new insights into the discovery of GPCR-mediated signaling control in sea cucumber reproduction, especially in gonadal development control.

Nonconventional luminophores: characteristics, advancements and perspectives.

Nonconventional luminophores devoid of remarkable conjugates have attracted considerable attention due to their unique luminescence behaviors, updated luminescence mechanism of organics and promising applications in optoelectronic, biological and medical fields. Unlike classic luminogens consisting of molecular segments with greatly extended electron delocalization, these unorthodox luminophores generally possess nonconjugated structures based on subgroups such as ether (-O-), hydroxyl (-OH), halogens, carbonyl (CO), carboxyl (-COOH), cyano (CN), thioether (-S-), sulfoxide (SO), sulfone (OSO), phosphate, and aliphatic amine, as well as their grouped functionalities like amide, imide, anhydride and ureido. They can exhibit intriguing intrinsic luminescence, generally featuring concentration-enhanced emission, aggregation-induced emission, excitation-dependent luminescence and prevailing phosphorescence. Herein, we review the recent progress in exploring these nonconventional luminophores and discuss the current challenges and future perspectives. Notably, different mechanisms are reviewed and the clustering-triggered emission (CTE) mechanism is highlighted, which emphasizes the clustering of the above mentioned electron rich moieties and consequent electron delocalization along with conformation rigidification. The CTE mechanism seems widely applicable for diversified natural, synthetic and supramolecular systems.

Identification of the Regulators of Epidermis Development under Drought- and Salt-Stressed Conditions by Single-Cell RNA-Seq.

As sessile organisms, plants constantly face challenges from the external environment. In order to meet these challenges and survive, plants have evolved a set of sophisticated adaptation strategies, including changes in leaf morphology and epidermal cell development. These developmental patterns are regulated by both light and hormonal signaling pathways. However, our mechanistic understanding of the role of these signaling pathways in regulating plant response to environmental stress is still very limited. By applying single-cell RNA-Seq, we determined the expression pattern of PHYTOCHROME INTERACTING FACTOR (PIF) 1, PIF3, PIF4, and PIF5 genes in leaf epidermal pavement cells (PCs) and guard cells (GCs). PCs and GCs are very sensitive to environmental stress, and our previous research suggests that these PIFs may be involved in regulating the development of PCs, GCs, and leaf morphology under environmental stress. Growth analysis showed that pif1/3/4/5 quadruple mutant maintained tolerance to drought and salt stress, and the length to width ratio of leaves and petiole length under normal growth conditions were similar to those of wild-type (WT) plants under drought and salt treatment. Analysis of the developmental patterns of PCs and GCs, and whole leaf morphology, further confirmed that these PIFs may be involved in mediating the development of epidermal cells under drought and salt stress, likely by regulating the expression of MUTE and TOO MANY MOUTHS (TMM) genes. These results provide new insights into the molecular mechanism of plant adaptation to adverse growth environments.

Correction to: Well­Being Reduces COVID­19 Anxiety: A Three­Wave Longitudinal Study in China.

[This corrects the article DOI: 10.1007/s10902-021-00385-2.].

Unprecedented and Readily Tunable Photoluminescence from Aliphatic Quaternary Ammonium Salts.

Compounds bearing aliphatic amines can be emissive under appropriate conditions. However, their ionized counterparts, namely, quaternary ammonium salts (QASs), which are widely used as phase-transfer catalysts, ionic liquids, disinfectants, and surfactants, are known as luminescence quenchers and considered nonemissive. Herein, unprecedented intrinsic fluorescence/phosphorescence dual emissions from various QASs are reported, which can be finely regulated by changing the excitation wavelength, alkyl chain length, counterion, and mechanical stimuli. The bright photoluminescence along with distinct afterglow and tunable multicolor emissions enables the application of QAS solids in advanced multimode anticounterfeiting. This finding refreshes the understanding of QASs and may inspire emerging applications based on the utilization of the intrinsic luminescences of QASs. Furthermore, it opens opportunities for the investigation of QAS-related processes and functions via a photophysical approach and affords strong implications for the fabrication of novel nonconventional luminophores.

Bioinspired Ti3 C2 Tx MXene-Based Ionic Diode Membrane for High-Efficient Osmotic Energy Conversion.

Bioinspired asymmetric nanofluidic ion channels with ionic diode behavior that can boost the osmotic energy (so-called blue energy) conversion are highly desirable, especially if they can be easily constructed and modified. Two-dimensional (2D) metal carbides and nitrides, known as MXenes, combine hydrophilic surfaces and tunable surface charge properties, providing a shortcut to prepare asymmetric nanofluidic ion channels. Here, we report a mechanically robust, flexible, and scale-up-friendly asymmetric Ti3 C2 Tx MXene-based ionic diode membrane with a highly rectified current and demonstrate its potential use in reverse electrodialysis osmotic energy conversion. Under the salinity gradient of synthetic seawater and river water, our ionic diode membrane-based generator's power density is 8.6 W m-2 and up to 17.8 W m-2 at a 500-fold salinity gradient, outperforming the state-of-the-art membranes. The design of MXene-based ionic diode-type membrane provides a facile and general strategy in developing large-scale 2D nanofluidics and selective ion transport.