Boosting Electrochemical Urea Synthesis via Constructing Ordered Pd-Zn Active Pair.

Electrochemical co-reduction of nitrate (NO3-) and carbon dioxide (CO2) has been widely regarded as a promising route to produce urea under ambient conditions, however the yield rate of urea has remained limited. Here, we report an atomically ordered intermetallic pallium-zinc (PdZn) electrocatalyst comprising a high density of PdZn pairs for boosting urea electrosynthesis. It is found that Pd and Zn are responsible for the adsorption and activation of NO3- and CO2, respectively, and thus the co-adsorption and co-activation NO3- and CO2 are achieved in ordered PdZn pairs. More importantly, the ordered and well-defined PdZn pairs provide a dual-site geometric structure conducive to the key C-N coupling with a low kinetical barrier, as demonstrated on both operando measurements and theoretical calculations. Consequently, the PdZn electrocatalyst displays excellent performance for the co-reduction to generate urea with a maximum urea Faradaic efficiency of 62.78% and a urea yield rate of 1274.42 µg mg-1 h-1, and the latter is 1.5-fold larger than disordered pairs in PdZn alloys. This work paves new pathways to boost urea electrosynthesis via constructing ordered dual-metal pairs.

Isoxazolyl-urea derivative evokes apoptosis and paraptosis by abrogating the Wnt/ß-catenin axis in colon cancer cells.

Deregulated activation of the Wnt/ß-catenin pathway is observed in many types of human malignancies including colon cancer. Abrogation of the Wnt/ß-catenin pathway has been demonstrated as an effective way of inducing cancer cell death. Herein, a new isoxazolyl-urea (QR-5) was synthesized and examined its efficacy on the viability of colon cancer cell lines. QR-5 displayed selective cytotoxicity towards colon cancer cells over normal counterparts. QR-5 induced apoptosis as evidenced by elevation in sub-G1 cells, decrease in Bcl-2, MMP-9, COX-2, VEGF and cleavage of PARP and caspase-3. QR-5 reduced the mitochondrial membrane potential, decreased the expression of Alix and elevated the expression of ATF4 and CHOP indicating the induction of paraptosis. The inhibitor of apoptosis (Z-DEVD-FMK) and paraptosis (CHX) could not restore Alix expression and PARP cleavage in QR-5 treated cells, respectively suggesting the complementation between the two cell death pathways. QR-5 suppressed the expression of Wnt/ß-catenin pathway proteins which was also evidenced by the downregulation of nuclear and cytoplasmic ß-catenin. The dependency of QR-5 on ß-catenin for inducing apoptosis and paraptosis was demonstrated using knockdown experiments using ß-catenin specific siRNA. Overall, QR-5 induces apoptosis as well as paraptosis by mitigating the Wnt/ß-catenin axis in colon cancer cells.

Non-isocyanate Synthesis of Covalent Adaptable Networks Based on Dynamic Hindered Urea Bonds: Sequential Polymerization and Chemical Recycling.

The development of environmentally sustainable processes for polymer recycling is of paramount importance in the polymer industry. In particular, the implementation of chemical recycling for thermoset polymers via covalent adaptable networks (CANs), particularly those based on the dynamic hindered urea bond (HUB), has garnered intensive attention from both the academic and industrial sectors. This interest stems from its straightforward chemical structure and reaction mechanism, which are well-suited for commercial polyurethane and polyurea applications. However, a substantial drawback of these CANs is the requisite use of toxic isocyanate curing agents for their synthesis. Herein, we propose a new HUB synthesis pathway involving thiazolidin-2-one and a hindered amine. This ring-opening reaction facilitates the isocyanate-free formation of a HUB and enables sequential reactions with acrylate and epoxide monomers via thiol-Michael and thiol-epoxy click chemistry. The CANs synthesized using this methodology exhibit superior reprocessability, chemical recyclability, and reutilizability, facilitated by specific catalytic and solvent conditions, through the reversible HUB, thiol-Michael addition, and transesterification processes.

Hyponatremia - Treatment standard 2024.

Hyponatremia is the most common electrolyte disorder in hospital patients associated with increased morbidity, mortality, hospital stay and financial burden. The speed of a correction with 3% sodium chloride as 100 mL IV bolus or continuous infusion depends on the severity and persistence of the symptoms, and needs frequent biochemical monitoring. The rapid intermittent administration of hypertonic saline is preferred for treatment of symptomatic hyponatremia. In asymptomatic mild hyponatremia, an adequate solute intake with an initial fluid restriction (FR) of 500 mL/d adjusted according to the serum sodium levels is preferred. Almost half of the syndrome of inappropriate diuresis hormone (SIADH) patients do not respond to FR as first-line therapy. At present, urea and tolvaptan are considered as most effective second-line therapies in SIADH. However, the evidence for guidance on the choice of second-line therapy of hypotonic hyponatremia is lacking. Oral urea is considered as very effective and safe treatment. Mild and asymptomatic hyponatremia is treated with adequate solute intake (salt and protein) and an initial FR with adjustments based on serum sodium levels. Specific treatment with vaptans may be considered in either euvolemic or hypervolemic patients with high ADH activity. In order to ensure optimal patient outcome, a close monitoring and readiness for administration of either hypotonic fluids or desmopressin may be crucial in decision making process for specific treatment and eventual overcorrection consequences. According to the guidelines, a gradual correction and clinical evaluation is preferable over the rapid normalization of serum sodium towards the laboratory reference ranges.

Risk management and loss prevention strategies for fertilizer industries.

Various toxic and flammable gases exist in the fertilizer industry whose release quantification is very important regarding emergency preparedness, planning and response, and well-being of the community. ALOHA threat zones and threat at a point coupled with MARPLOT are evaluated for ammonia, methane, carbon dioxide and hydrogen release, and outdoor and indoor concentrations of these gases in nearby residences and highways calculated. These footprints are calculated using ALOHA which requires inputs such as site data, site location, building type, gas name, atmospheric inputs, release source information and dispersion model to display the threat zone, which can then be shown on MARPLOT. Potential impact of these releases on the community is mitigated through releasing equipment isolations, water sprays for dilutions, dilutions through steam or air and emergency sirens for information. This article covers hazards in the fertilizer industry, and provides general guidelines for operational staff of any industry to mitigate hazards.

Association between blood urea nitrogen to serum albumin ratio and in-hospital mortality in critical patients with diabetic ketoacidosis: a retrospective analysis of the eICU database.

Background: This study aimed to investigate the association between blood urea nitrogen to serum albumin ratio (BAR) and the risk of in-hospital mortality in patients with diabetic ketoacidosis. Methods: A total of 3,962 diabetic ketoacidosis patients from the eICU Collaborative Research Database were included in this analysis. The primary outcome was in-hospital death. Results: Over a median length of hospital stay of 3.1 days, 86 in-hospital deaths were identified. One unit increase in LnBAR was positively associated with the risk of in-hospital death (hazard ratio [HR], 1.82 [95% CI, 1.42-2.34]). Furthermore, a nonlinear, consistently increasing correlation between elevated BAR and in-hospital mortality was observed (P for trend =0.005 after multiple-adjusted). When BAR was categorized into quartiles, the higher risk of in-hospital death (multiple-adjusted HR, 1.99 [95% CI, (1.1-3.6)]) was found in participants in quartiles 3 to 4 (BAR≥6.28) compared with those in quartiles 1 to 2 (BAR<6.28). In the subgroup analysis, the LnBAR-hospital death association was significantly stronger in participants without kidney insufficiency (yes versus no, P-interaction=0.023). Conclusion: There was a significant and positive association between BAR and the risk of in-hospital death in patients with diabetic ketoacidosis. Notably, the strength of this association was intensified among those without kidney insufficiency.

Nano-hydroxyapatite-assisted enzyme-induced carbonate precipitation enhances Pb-contaminated aqueous solution and loess remediation.

Intensive agricultural activities could cause lead (Pb) bioaccumulation, threatening human health. Although the enzyme-induced carbonate precipitation (EICP) technology has been applied to tackle the aforesaid problem, the urease may denature or even lose its activity when subjected to a significant Pb2+ toxicity effect. To this end, the nano-hydroxyapatite (nHAP)-assisted EICP was proposed to reduce the mobility of Pb2+. Results indicated that a below 30% immobilization efficiency at 60 mM Pb2+ was attained under EICP. nHAP adsorbed the majority of Pb2+, preventing Pb2+ attachment to urease. Further, hydroxylphosphohedyphane or hydroxylpyromorphite was formed at 60 mM Pb2+, followed by the formation of cerussite, allowing hydroxylphosphohedyphane or hydroxylpyromorphite to be wrapped by cerussite. By contrast, carbonate-bearing hydroxylpyromorphite of higher stability (Pb10(PO4)6CO3) was developed at 20 mM Pb2+ as CO3 2- substituted the hydroxyl group in hydroxylpyromorphite. Moreover, nHAP helped EICP to form nucleated minerals. As a result, the EICP-nHAP technology raised the immobilization efficiency at 60 mM Pb2+ up to 70%. The findings highlight the potential of applying the EICP-nHAP technology to Pb-containing water bodies remediation.

2D Amino-Functionalized Black Phosphorus: A New Approach to Improve Hydrogen Gas Detection Performance.

In recent years, hydrogen has gained attention as a potential solution to replace fossil fuels, thus reducing greenhouse gas emissions. The development of ever improving hydrogen sensors is a topic that is constantly under study due to concerns about the inherent risk of leaks of this gas and potential explosions. In this work, a new, long-term, stable phosphorene-based sensor was developed for hydrogen detection. A simple functionalization of phosphorene using urea was employed to synthesize an air-stable material, subsequently used to prepare films for gas sensing applications, via the drop casting method. The material was deeply characterized by different techniques (scanning electron microscopy, X-ray diffraction, X-ray photoelectron, and Raman spectroscopy), and the stability of the material in a noninert atmosphere was evaluated. The phosphorene-based sensor exhibited high sensitivity (up to 700 ppm) and selectivity toward hydrogen at room temperature, as well as long-term stability over five months under ambient conditions. To gain further insight into the gas sensing mechanism over the surface, we employed a dedicated apparatus, namely operando diffuse reflectance infrared Fourier transform, by exposing the chemoresistive sensor to hydrogen gas under dry air conditions.

Preparation of a Highly Flame-Retardant Urea-Formaldehyde Resin and Flame Retardance Mechanism.

Urea-formaldehyde (UF) resin is the most widely used adhesive resin. However, it is necessary to improve its flame-retardant performance to expand its applications. In this study, exploiting electrostatic interactions, anionic phytic acid and cationic chitosan were combined to form a bio-based intumescent flame-retardant, denoted phytic acid-chitosan polyelectrolyte (PCS). The molecular structure of the urea-formaldehyde resin was optimized by crosslinking with melamine and plasticizing with polyvinyl alcohol-124. Thus, by combining PCS with the urea-formaldehyde resin and with ammonium polyphosphate and ammonium chloride as composite curing agents, flame-retardant urea-formaldehyde resins (FRUFs) were prepared. Compared to traditional UF resin, FRUF showed excellent flame retardancy and not only reached the UL-94 V-0 level, but the limit of oxygen index was also as high as 36%. Compared to those of UF, the total heat release and peak heat release rate of FRUF decreased by 86.44% and 81.13%, respectively. The high flame retardancy of FRUF originates from the combination of oxygen and heat isolation by the dense carbon layer, quenching of phosphorus free radicals, and dilution of oxygen by a non-flammable gas. In addition, the mechanical properties of the FRUF remained good, even after modification. The findings of this study provide a reference for the flame-retardant application of FRUF for applications in multiple fields.

Sustainable All-Cellulose Biocomposites from Renewable Biomass Resources Fabricated in a Water-Based Processing System by the Vacuum-Filtration-Assisted Impregnation Method.

The increasing awareness of global ecological concerns and the rising sustainability consciousness associated with the manufacturing of non-renewable and non-biodegradable composite materials have led to extensive research on product and process developments of more sustainable, environmentally friendly, and fully biodegradable biocomposites for higher-value end-use applications. All-cellulose composites (ACCs) are an emerging class of biocomposites, which are produced utilizing solely cellulose as a raw material that is derived from various renewable biomass resources, such as trees and plants, and are assessed as fully biodegradable. In this study, sustainable ACCs were fabricated for the first time based on the full dissolution of commercially available sulfite dissolving (D) pulps as a matrix with concentrations of 1.5 wt.% and 2.0 wt.% in an aqueous NaOH-urea solvent, and they were then impregnated on/into the pre-fabricated birch (B), abaca (A), and northern softwood (N) fiber sheets as reinforcements by the vacuum-filtration-assisted impregnation approach. This research aimed to investigate the effects of the impregnated cellulose matrix concentrations and types of the utilized cellulose fiber reinforcements (B, A, N) on the morphological, crystalline, structural, and physio-mechanical properties of the ACCs. The highest degrees of improvements were achieved for tensile strength (+532%, i.e., from 9.24 MPa to 58.04 MPa) and strain at break of the B fiber-reinforced ACC B1.5 (+446%, i.e., from 1.36% to 4.62%) fabricated with vacuum impregnation of the 1.5 wt.% cellulose matrix. Noticeably, the greatest improvements were attained in strain at break of the A and N fiber-reinforced ACCs A2.0 (+218%, i.e., from 4.44 % to 14.11%) and N2.0 (+466%, i.e., 2.59% to 14.65%), respectively, produced with vacuum impregnation of the 2.0 wt.% cellulose matrix. The study highlights the diverse properties of the all-cellulose biocomposite materials that could, expectedly, lead to further development and research for upscaled production of the ACCs.

4D-QSAR, ADMET properties, and molecular dynamics simulations for designing N-substituted urea/thioureas as human glutaminyl cyclase inhibitors.

Human glutaminyl cyclase (hQC) inhibitors have great potential to be used as anti- Alzheimer's disease (AD) agents by reducing the toxic pyroform of ß-amyloid in the brains of AD patients. The four-dimensional quantitative structure activity relationship (4D-QSAR) model of N-substituted urea/thioureas was established with satisfying predictive ability and statistical reliability (Q2 = 0.521, R2 = 0.933, R2prep = 0.619). By utilizing the developed 4D-QSAR model, a set of new N-substituted urea/thioureas was designed and evaluated for their Absorption Distribution Metabolism Excretion and Toxicity (ADMET) properties. The results of molecular dynamics (MD) simulations, Principal component analysis (PCA), free energy landscape (FEL), dynamic cross-correlation matrix (DCCM) and molecular mechanics generalized Born Poisson-Boltzmann surface area (MM-PBSA) free energy calculations, revealed that the designed compounds were remained stable in protein binding pocket and compounds b ∼ f (-35.1 to -44.55 kcal/mol) showed higher binding free energy than that of compound 14 (-33.51 kcal/mol). The findings of this work will be a theoretical foundation for further research and experimental validation of urea/thiourea derivatives as hQC inhibitors.

Electron-Delocalization Across High Surface Entropy Sub-1 nm Nanobelts Toward Enhanced Electrocatalytic Urea Oxidation.

Integration of inherently incompatible elements into a single sublattice, resulting in the formation of monophasic metal oxide, holds great scientific promise; it unveils that the overlooked surface entropy in subnanometer materials can thermodynamically facilitate the formation of homogeneous single-phase structures. Here a facile approach is proposed for synthesizing multimetallic oxide subnanometer nanobelts (MMO-PMA SNBs) by harnessing the potential of phosphomolybdic acid (PMA) clusters to capture inorganic nuclei and inhibiting their subsequent growth in solvothermal reactions. Experimental and theoretical analyses show that PMA in MMO-PMA SNBs not only aids subnanometer structure formation but also induces in situ modifications to catalytic sites. The electron transfer from PMA, coupled with the loss of elemental identity of transition metals, leads to electron delocalization, jointly activating the reaction sites. The unique structure makes pentametallic oxide (PMO-PMA SNBs) achieve a current density of 10 mA cm-2 at a low potential of 1.34 V and remain stable for 24 h at 10 mA cm-2 on urea oxidation reaction (UOR). The exceptional UOR catalytic activity suggests a potential for utilizing multimetallic subnanometer nanostructures in energy conversion and environmental remediation.

The search for pyruvate kinase-R activators; from a HTS screening hit via an impurity to the discovery of a lead series.

Pyruvate kinase (PK) is an essential component of cellular metabolism, converting ADP and phosphoenolpyruvate (PEP) to pyruvate in the final step of glycolysis. Of the four unique isoforms of pyruvate kinase, R (PKR) is expressed exclusively in red blood cells and is a tetrameric enzyme that depends on fructose-1,6-bisphosphate (FBP) for activation. PKR deficiency leads to hemolysis of red blood cells resulting in anemia. Activation of PKR in both sickle cell disease and beta-thalassemia patients could lead to improved red blood cell fitness and survival. The discovery of a novel series of substituted urea PKR activators, via the serendipitous identification and diligent characterization of a minor impurity in an High Throughput Screening (HTS) hit will be discussed.

FeCu bimetallic clusters for efficient urea production via coupling reduction of carbon dioxide and nitrate.

Urea electrosynthesis has appeared to meet the nitrogen cycle and carbon neutrality with energy-saving features. Copper can co-electrocatalyze among CO2 and nitrogen species to generate urea, however developing effective electrocatalysts is still an obstacle. Here, we developed a nitrogen-doped porous carbon loaded with FeCu clusters that convert CO2 and NO3- into urea, with the highest Faradaic efficiency of 39.8 % and yield rate of 1024.6 µg h-1 mgcat.-1, under optimized ambient conditions, exceeding that at the Fe or Cu homogeneous sites. Furthermore, a favorable CN coupling pathway originates from *NHCO and *NHCONO two intermediates with lower free energy barriers on FeCu dual active sites are verified through in-situ Fourier transform infrared spectroscopy and theoretical calculations. This research might provide deep insights into coupling mechanisms and investigation of efficient catalysts for green urea production.

Urea production via photocatalytic coupling of mixed gases (CO2/NH3) using Mo(MnO4)5 supported on Ce-BTC as nano-composite catalyst.

Urea used in fertilization and feed supplement, as well as a starting material for the manufacture of plastics and drugs. Urea is most commonly produced by reacting carbon dioxide with ammonia at high temperature. Photocatalysis has gained attention as a sustainable pathway for performing urea. This work focus on designing very active photocatalysts based on cerium organic framework (Ce-BTC) doped with metal oxide nanoparticles (molybdenum permanganate, Mo(MnO4)5) for production of urea from coupling of ammonia with carbon dioxide. The prepared materials were characterized using different spectral analysis and the morphology was analysed using microscopic data. The effect of catalyst loading on the production rate of urea was investigated and the obtained results showed speed rate of urea production with high production yield at low temperature. The recyclability tests confirmed the sustainability of the prepared photocatlysts (Mo(MnO4)5@Ce-BTC) which supported the beneficial of the photocatalysis process in urea production.

Recent advances in the development of tumor microenvironment-activatable nanomotors for deep tumor penetration.

Cancer represents a significant threat to human health, with the use of traditional chemotherapy drugs being limited by their harsh side effects. Tumor-targeted nanocarriers have emerged as a promising solution to this problem, as they can deliver drugs directly to the tumor site, improving drug effectiveness and reducing adverse effects. However, the efficacy of most nanomedicines is hindered by poor penetration into solid tumors. Nanomotors, capable of converting various forms of energy into mechanical energy for self-propelled movement, offer a potential solution for enhancing drug delivery to deep tumor regions. External force-driven nanomotors, such as those powered by magnetic fields or ultrasound, provide precise control but often necessitate bulky and costly external equipment. Bio-driven nanomotors, propelled by sperm, macrophages, or bacteria, utilize biological molecules for self-propulsion and are well-suited to the physiological environment. However, they are constrained by limited lifespan, inadequate speed, and potential immune responses. To address these issues, nanomotors have been engineered to propel themselves forward by catalyzing intrinsic "fuel" in the tumor microenvironment. This mechanism facilitates their penetration through biological barriers, allowing them to reach deep tumor regions for targeted drug delivery. In this regard, this article provides a review of tumor microenvironment-activatable nanomotors (fueled by hydrogen peroxide, urea, arginine), and discusses their prospects and challenges in clinical translation, aiming to offer new insights for safe, efficient, and precise treatment in cancer therapy.

Highly Efficient Electrosynthesis of Urea from CO2 and Nitrate by a Metal-Organic Framework with Dual Active Sites.

Electrosynthesis of urea from CO2 and NO3- is a sustainable alternative to energy-intensive industrial processes. The challenge hindering the progress is the development of advanced electrocatalysts that yield urea with both high Faradaic efficiency (FE) and current density. In this work, we designed a new two-dimensional MOF, namely PcNi-Fe-O, constructed by nickel-phthalocyanine (NiPc) ligands and square-planar FeO4 nodes. PcNi-Fe-O exhibits remarkable performance to yield urea at a high current density of 10.1 mA cm-2 with a high FE(urea) of 54.1% in a neutral aqueous solution, surpassing those of most reported electrocatalysts. No obvious performance degradation was observed over 20 hours of continuous operation at the current density of 10.1 mA cm-2. By expanding the electrode area to 25 cm2 and operating for 8 hours, we obtained 0.164 g of high-purity urea, underscoring its potential for industrial applications. Mechanism study unveiled the enhanced performance might be ascribed to the synergistic interaction between NiPc and FeO4 sites. Specifically, NH3 produced at the FeO4 site can efficiently migrate and couple with the *NHCOOH intermediate adsorbed on the urea-producing site (NiPc). This synergistic effect results in a lower energy barrier for C-N bond formation than those of the reported catalysts with single active sites.

Prediction of Poor Outcome Using the Urea to Albumin Ratio in Thoracic Empyema.

Purpose: The prognostic performance of urea-to-albumin ratio (UAR) has been assessed in various pulmonary and nonpulmonary conditions, but never in thoracic empyema. Therefore, our aim was to determine whether this marker has the ability to predict outcome in such patients. Methods: A single-center retrospective study was conducted in a Clinic of Thoracic Surgery at a University Hospital between January 2021 and October 2023. A total of 84 patients who underwent emergency surgery due to thoracic empyema were involved. Serum levels of urea and albumin at admission were used to calculate UAR. We analyzed area under receiver operating characteristics (AUROC) curves of UAR, systemic inflammatory response syndrome (SIRS) and quick-sequential organ failure assessment (qSOFA), and compared their prognostic performance. Results: The identified in-hospital mortality was 10.7%. The UAR showed the best ability to prognosticate mortality compared to qSOFA (AUROC = 0.828 vs 0.747) and SIRS (AUROC = 0.828 vs 0.676). We established a sensitivity of 87.5% and specificity of 74.2% at optimal cut-off value UAR > 51.1 for prediction of adverse outcome. Conclusion: In patients with thoracic empyema urea-to-albumin ratio showed significant prognostic performance and a potential for clinical application as a low cost and widely available predictor of death.

The impact of dialysate flow rate on haemodialysis adequacy: a systematic review and meta-analysis.

Background: Patients with kidney failure treated with maintenance haemodialysis (HD) require appropriate small molecule clearance. Historically, a component of measuring 'dialysis adequacy' has been quantified using urea kinetic modelling that is dependent on the HD prescription. However, the impact of dialysate flow rate on urea clearance remains poorly described in vivo and its influence on other patient-important outcomes of adequacy is uncertain. Methods: We searched Embase, MEDLINE and the Cochrane Library from inception until April 2022 for randomized controlled trials and observational trials comparing a higher dialysate flow rate (800 ml/min) and lower dialysate flow rate (300 ml/min) with a standard dialysis flow rate (500 ml/min) in adults (age ≥18 years) treated with maintenance HD (>90 consecutive days). We conducted a random effects meta-analysis to estimate the pooled mean difference in dialysis adequacy as measured by Kt/V or urea reduction ratio (URR). Results: A total of 3118 studies were identified. Of those, nine met eligibility criteria and four were included in the meta-analysis. A higher dialysate flow rate (800 ml/min) increased single-pool Kt/V by 0.08 [95% confidence interval (CI) 0.05-0.10, P < .00001] and URR by 3.38 (95% CI 1.97-4.78, P < .00001) compared with a dialysate flow rate of 500 ml/min. Clinically relevant outcomes including symptoms, cognition, physical function and mortality were lacking and studies were generally at a moderate risk of bias due to issues with randomization sequence generation, allocation concealment and blinding. Conclusion: A higher dialysate flow increased urea-based markers of dialysis adequacy. Additional high-quality research is needed to determine the clinical, economic and environmental impacts of higher dialysate flow rates.

Plasma proteome analysis implicates novel proteins as potential therapeutic targets for chronic kidney disease: A proteome-wide association study.

Chronic kidney disease (CKD) is prevalent globally with limited therapeutic drugs available. To systemically identify novel proteins involved in the pathogenesis of CKD and possible therapeutic targets, we integrated human plasma proteomes with the genome-wide association studies (GWASs) of CKD, estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) to perform proteome-wide association study (PWAS), Mendelian Randomization and Bayesian colocalization analyses. The single-cell RNA sequencing data of healthy human and mouse kidneys were analyzed to explore the cell-type specificity of identified genes. Functional enrichment analysis was conducted to investigate the involved signaling pathways. The PWAS identified 22 plasma proteins significantly associated with CKD. Of them, the significant associations of three proteins (INHBC, LMAN2, and SNUPN) were replicated in the GWASs of eGFR, and BUN. Mendelian Randomization analyses showed that INHBC and SNUPN were causally associated with CKD, eGFR, and BUN. The Bayesian colocalization analysis identified shared causal variants for INHBC in CKD, eGFR, and BUN (all PP4 > 0.75). The single-cell RNA sequencing revealed that the INHBC gene was sparsely scattered within the kidney cells. This proteomic study revealed that INHBC, LMAN2, and SNUPN may be involved in the pathogenesis of CKD, which represent novel therapeutic targets and warrant further exploration in future research.