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.

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.

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.

Double Hydroxide Nanocatalysts for Urea Electrooxidation Engineered toward Environmentally Benign Products.

Recent advancements in the electrochemical urea oxidation reaction (UOR) present promising avenues for wastewater remediation and energy recovery. Despite progress toward optimized efficiency, hurdles persist in steering oxidation products away from environmentally unfriendly products, mostly due to a lack of understanding of structure-selectivity relationships. In this study, the UOR performance of Ni and Cu double hydroxides, which show marked differences in their reactivity and selectivity is evaluated. CuCo hydroxides predominantly produce N2, reaching a current density of 20 mA cmgeo -2 at 1.04 V - 250 mV less than NiCo hydroxides that generate nitrogen oxides. A collection of in-situ spectroscopies and scattering experiments reveal a unique in situ generated Cu(2-x)+-OO-• active sites in CuCo, which initiates nucleophilic substitution of NH2 from the amide, leading to N-N coupling between *NH on Co and Cu. In contrast, the formation of nitrogen oxides on NiCo is primarily attributed to the presence of high-valence Ni3+ and Ni4+, which facilitates N-H activation. This process, in conjunction with the excessive accumulation of OH- ions on Jahn-Teller (JT) distorted Co sites, leads to the generation of NO2 - as the primary product. This work underscores the importance of catalyst composition and structural engineering in tailoring innocuous UOR products.

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.

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 by 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.

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.

The association between blood urea nitrogen to albumin ratio and the 28 day mortality in tuberculosis patients complicated by sepsis.

The relationship between blood urea nitrogen to albumin ratio (BAR) and the prognosis of patients with tuberculosis (TB) complicated by sepsis remains unclear. This study aimed to explore the association between BAR and overall patient prognosis. This was a retrospective cohort study of patients with TB complicated by sepsis who were admitted to the intensive care unit (ICU) of the Public Health Clinical Center of Chengdu between January 2019 and February 2023. The relationship between BAR values and prognosis in these patients was investigated using multivariate Cox regression, stratified analysis with interaction, restricted cubic spline (RCS), and threshold effect analysis. Sensitivity analyses were conducted to assess the robustness of the results. Our study included 537 TB patients complicated by sepsis admitted in the ICU, with a median age of 63.0 (48.0, 72.0) years; 76.7% of whom were men. The multivariate-restricted cubic spline analysis showed a non-linear association between BAR and patient prognosis. In the threshold analysis, we found that TB patients complicated by sepsis and a BAR < 7.916 mg/g had an adjusted hazard ratio (HR) for prognosis of 1.163 (95% CI 1.038-1.303; P = 0.009). However, when the BAR was ≥ 7.916 mg/g, there was no significant increase in the risk of death. The results of the sensitivity analysis were stable.

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.

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.

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.

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.

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.

Insights into in situ surface reconstruction in cobalt perovskite oxides for enhanced catalytic activity.

An depth understanding of the fundamental interactions between surface termination and catalytic activity is crucial to prompt the properties of functional perovskite materials. The elastic energy due to size mismatch and electrostatic attraction of the charged Sr dopant by positively charged oxygen vacancies induced inert A-site surface enrichment rearrangement for perovskites. Lower temperatures could reduce A-site enrichment, but it is difficult to form perovskite crystals. La0.8Sr0.2CoO3-δ (LSCO) as a model perovskite oxide was modified with additive urea to reduce the crystallization temperature, and suppress Sr segregation. The LSCO catalysts with 600 °C annealing temperature (LSCO-600) exhibited a 19.4-fold reaction reactivity of toluene oxidation than that with 800 °C annealing temperature (LSCO-800). Combined surface-sensitive and depth-resolved techniques for surface and sub-surface analysis, surface Sr enrichment was effectively suppressed due to decreased oxygen vacancy concentration and smaller electrostatic driving force. DFT calculations and in-situ DRIFTs spectra well revealed that tuning the surface composition/termination affected the intrinsic reactivity. The catalyst surface with lower Sr enrichment could easily adsorb toluene, cleave, and decompose benzene rings, thus contributing to toluene degradation to CO2. This work demonstrates a green and efficient way to control surface composition and termination at the atomic scale for higher catalytic activity.

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.

A hydrogel sensor based on cellulose nanofiber/polyvinyl alcohol with colorimetric-fluorescent bimodality for non-invasive detection of urea in sweat.

The concentration of urea in sweat serves as a valuable indicator of an individual's overall health. In this study, we present a novel hydrogel sensor (BAF-CPu), based on cellulose nanofiber and polyvinyl alcohol, designed to achieve non-invasive in situ and highly sensitive detection of urea in sweat by combining the dual-mode response of colorimetric and ratiometric fluorescence techniques. The bright red fluorescent gold­copper bimetallic nanoclusters and green fluorescent fluorescein isothiocyanate-modified cellulose nanofibers endowed BAF-CPu with proportional fluorescence responsive properties. Under the catalytic action of urease, the hydrolysis of urea raises the pH, resulting in diminished red fluorescence along with enhanced green fluorescence, and the fluorescence color of BAF-CPu changes from red to green. Moreover, BAF-CPu hydrogel encapsulates pH-responsive bromothymol blue (BTB), which changes from yellow to blue in the presence of urea. Importantly, BAF-CPu absorbs sweat by adhering directly to the skin surface, avoiding the complicated sampling process and improving the maneuverability of the detection process. With both ratiometric fluorescence and colorimetric modes, BAF-CPu is not only able to detect sweat in situ, but also can reduce the interference of the complex sweat environment on the urea detection, and realize the high sensitivity detection of urea in sweat.

Clinical factors associated with hyponatremia correction during treatment with oral Urea.

BACKGROUND AND HYPOTHESIS: Oral urea is being used more commonly to treat hyponatremia, but factors contributing to the correction rate are unknown. We hypothesized that clinically relevant factors can be identified to help guide hyponatremia correction with oral urea. METHODS: Retrospective study in two university hospitals including hospitalized patients with hyponatremia (plasma sodium < 135 mmol/L) treated with oral urea. Linear mixed-effects models were used to identify factors associated with hyponatremia correction. Rates of overcorrection, osmotic demyelination and treatment discontinuation were also assessed. RESULTS: We included 161 urea treatment episodes in 140 patients (median age 69 years, 46% females, 93% syndrome of inappropriate antidiuresis). Oral urea succeeded fluid restriction in 117 treatment episodes (73%), was combined with fluid restriction in 104 treatment episodes (65%) and was given as only treatment in 27 treatment episodes (17%). A median dose of 30 grams/day of urea for 4 days (interquartile range 2-7 days) increased plasma sodium from 127 to 134 mmol/L and normalized hyponatremia in 47% of treatment episodes. Older age (ß 0.09, 95%CI 0.02 to 0.16), lower baseline plasma sodium (ß -0.65, 95%CI -0.78 to -0.62), and higher cumulative urea dose (ß 0.03, 95%CI -0.02 to -0.03) were independently associated with a greater rise in plasma sodium. Concurrent fluid restriction was associated with a greater rise in plasma sodium only during the first 48 h of treatment (ß 1.81, 95%CI 0.40 to 3.08). Overcorrection occurred in 5 cases (3%), no cases of osmotic demyelination were identified, and oral urea was discontinued in 11 cases (11%) due to side-effects. CONCLUSION: During treatment with oral urea, older age, higher cumulative dose, lower baseline plasma sodium and initial fluid restriction are associated with a greater correction rate of hyponatremia. These factors may guide clinicians to achieve a gradual correction of hyponatremia with oral urea.

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.