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BACKGROUND AND PURPOSE: Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS (Panax notoginseng saponins), containing the main active ingredients of Panax notoginseng, exhibits anti-atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s). EXPERIMENTAL APPROACH: The anti-atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE-/- mice. In vitro, the anti-ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2-/- macrophages. Finally, the anti-atherogenic effect of USP2 knockout was determined by using USP2-/- mice treated with high-fat diet (HFD) and AAV-PCSK9. KEY RESULTS: PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis-aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis-aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro. CONCLUSION AND IMPLICATIONS: PNS reduced USP2-mediated Keap1 de-ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti-atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS.
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Listeriosis is highly prevalent in the animal farming industry, with Listeria monocytogenes as the causative pathogen. To identify potential therapeutic targets for LM infection, we investigated the mechanisms of LM infection in goat uteri. We inoculated a group of goats with LM via jugular vein injection, isolated and raised them, and subsequently collected sterile samples of their uterine tissue after they exhibited clinical symptoms of LM infection. We used Giemsa staining, immunohistochemical staining, real-time qPCR, and Western blotting as experimental methods.First, we investigated the mechanism of Listeria monocytogenes (LM) infection in the goat uterus by examining the expression levels of listeriolysin O, E-cadherin, and tyrosine kinase c-Met in the uterus.Furthermore, we investigated the impact of LM infection on uterine autophagy and cell apoptosis. The results indicate that the injection of LM into the goats' jugular veins leads to LM infection in the goats' uteri. During LM survival inside the goat uterine cells, there is a significant increase in the expression levels of LLO, E-cadherin, and c-Met in the host uterine tissue. This suggests that LM may potentially infect goat uteri through the InlA/E-cadherin and InlB/c-Met pathways. Furthermore, LM infection increases the levels of apoptosis and autophagy in goat uteri. Apoptosis genes Bcl-2 and Bax, as well as autophagy-related genes LC3B, PINK1, and Parkin, exhibit varying degrees of changes in localization and expression in goat uteri, mediating the occurrence of apoptotic and autophagic responses.
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Owing to their nontoxicity, environmental friendliness, and high biocompatibility, physically cross-linked hydrogels have become popular research materials; however, their high water content and high free volume, along with the weak bonding interactions inherent to ordinary physically cross-linked hydrogels, limit their application in fields such as flexible devices, packaging materials, and substance transport regulation. Here, a structural barrier approach based on directional freezing-assisted salting out was proposed, and the directional structure significantly enhanced the barrier performance of the hydrogel. When the direction of substance diffusion was perpendicular to the pore channel structure of the directional freezing-PVA hydrogel (DFPVA), the Cl- transmission rate was 57.2% for the uniform freezing-PVA hydrogel (UFPVA). By adjusting the concentration of the salting-out solution and the salting-out time, the crystallinity and crystal domain size of the hydrogel could be further changed, optimizing and regulating the barrier performance of the hydrogel, with the best Cl- unit permeability being 36.02 mg mm per cm2 per day. Additionally, DFPVA had excellent mechanical properties (stress of 6.47 ± 1.04 MPa, strain of 625.85 ± 61.58%, toughness of 25.77 ± 3.72 MPa). Due to the barrier and mechanical properties of the direct structure, DFPVA is suitable as a drug carrier for slow drug release in vitro.
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To eliminate the epidemic of coal-burning-borne endemic arsenism (CBBA), our study organized and implemented comprehensive measures including high-arsenic coal ban, improved cook-stoves, and health education. We also aimed to promote the application value of these measures in preventing and controlling CBBA to the world. From 2004 to 2005, through a stratified random sampling method, we selected 58,256 individuals to investigate the prevalence of CBBA and the arsenic levels in 1287 environmental and biological specimens. The prevalence of CBBA was 19.26 % and significantly associated with the arsenic levels in coal, pepper, corn and hair, which were at or exceeded national upper limits. To timely prevent and control the disease, the comprehensive measures have been implemented since 2005 to present. Comparison and correlation analyses were utilized to evaluate the effectiveness of these measures in reducing the prevalence of CBBA. According to statistics, 73 high-arsenic coal mines were banned and over 99 % households in endemic areas accepted stove improvements and diversified health education. Monitoring studies during 2010-2019 has confirmed that these measures led to a decrease in urine arsenic levels among endemic residents, and they developed novel dietary practices, such as properly drying, storage, and washing of food. Additionally, the awareness rate of CBBA increased from less than 70 % to over 95 %. Finally, the prevalence of CBBA has decreased to 0.153 % investigated by a census involving 2.076 million endemic residents in 2019. In summary, CBBA in northwest China has been successfully controlled through banning on high-arsenic coal, introducing improved cook-stoves, and providing health education.
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Primary retroperitoneal liposarcoma (RLPS) is a rare heterogeneous tumor occurring within retroperitoneal space, and its overall survival has not improved much in the past few decades. Based on a small-sample clinical practice at our center, patients with RLPS can greatly benefit from anlotinib and eribulin combination. In this study, we investigated the combinational effect of anlotinib and eribulin on RLPS. In vitro experiments revealed that a low dose of anlotinib significantly enhances the cytotoxic effects of eribulin, leading to a remarkable suppression of RLPS cell proliferation, viability, colony formation, migration, and cell-cycle progression compared to individual drug treatments. At the organoid level, the combination treatment causes the spheroids in Matrigel to disintegrate earlier than the single-drug group. In vivo, RLPS patient-derived xenograft (PDX) models demonstrated that the combination of these two drugs can obviously exert a safe and effective anti-tumor effect. Through transcriptome analysis, we uncovered and validated that the synergistic effect mainly is induced by the endoplasmic reticulum stress (ERS) pathway both in vitro and in vivo. Further analyses indicate that anlotinib plus eribulin treatment results in micro-vessel density and PD-L1 expression alterations, suggesting a potential impact on the tumor microenvironment. This study extensively explored the combination regimen at multiple levels and its underlying molecular mechanism in RLPS, thus providing a foundation for translational medicine research.
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We designed two series of NIR-II PTAs with D-A or D-A-D structures, in which the introduction of thiophene promotes a bathochromic shift of emission into the NIR-II region, helps to improve the cellular uptake of the PTAs and facilitates NIR-II imaging-guided PDT/PTT cancer phototherapy.
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TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Tumor Suppressor Protein p53 , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Humans , Tumor Suppressor Protein p53/genetics , Prognosis , Mutation, Missense/genetics , Mutation/genetics , Tumor Microenvironment/genetics , Male , Female , Risk Factors , Middle AgedABSTRACT
The multiple relaxation processes of excited states are a bridge connecting molecular structures and properties, providing enormous application potential for organic luminogens. However, a systematic understanding and manipulation of the relationship between the molecular structure, excited state relaxation processes, and properties of organic luminogens is still lacking. Herein, we report a strategy for manipulating excited state electronic configurations through the regulation of the sulfur oxidation state to construct eminent organic type I PSs. Combined with the experimental results and theoretical calculations, we have successfully revealed the decisive role of high sulfur oxidation states in promoting ROS production capacity. Impressively, a higher sulfur oxidation state can reduce the singlet-triplet energy gap (ΔE ST), increase the matching degree of transition configurations, promote the changes of the excited state electronic configurations, and boost the effective ISC proportion by enhancing intramolecular interactions. Therefore, DBTS2O with the highest sulfur oxidation state exhibits the strongest type I ROS generation ability. Additionally, guided by our strategy, a water-soluble PS (2OA) is designed and synthesized, showing selective imaging capacity and photokilling ability against Gram-positive bacteria. This study broadens the horizons for both molecular design and mechanism study of high-performance organic type I PSs.
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The mislocalization of proteins leads to breast cancer, one of the world's most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.
Subject(s)
Breast Neoplasms , Deep Learning , Immunohistochemistry , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/diagnosis , Humans , Female , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/geneticsABSTRACT
Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.
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Nonadiabatic molecular dynamics (NA-MD) is a powerful tool to model far-from-equilibrium processes, such as photochemical reactions and charge transport. NA-MD application to condensed phase has drawn tremendous attention recently for development of next-generation energy and optoelectronic materials. Studies of condensed matter allow one to employ efficient computational tools, such as density functional theory (DFT) and classical path approximation (CPA). Still, system size and simulation timescale are strongly limited by costly ab initio calculations of electronic energies, forces, and NA couplings. We resolve the limitations by developing a fully machine learning (ML) approach in which all the above properties are obtained using neural networks based on local descriptors. The ML models correlate the target properties for NA-MD, implemented with DFT and CPA, directly to the system structure. Trained on small systems, the neural networks are applied to large systems and long timescales, extending NA-MD capabilities by orders of magnitude. We demonstrate the approach with dependence of charge trapping and recombination on defect concentration in MoS2. Defects provide the main mechanism of charge losses, resulting in performance degradation. Charge trapping slows with decreasing defect concentration; however, recombination exhibits complex dependence, conditional on whether it occurs between free or trapped charges, and relative concentrations of carriers and defects. Delocalized shallow traps can become localized with increasing temperature, changing trapping and recombination behavior. Completely based on ML, the approach bridges the gap between theoretical models and realistic experimental conditions and enables NA-MD on thousand-atom systems and many nanoseconds.
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Background: Traumatic heterotopic ossification (HO) is a devastating sequela of orthopedic surgeries and traumatic injuries; however, few studies have explored the effects of the estrogen-deficient state on HO formation. In the present study, we investigated the impact of estrogen deficiency on ectopic cartilage and bone formation in tendon after Achilles tenotomy in an ovariectomized mouse model. Methods: A total of 45 female C57BL/6 mice were randomly divided into three groups: sham-operated (control), estrogen depletion by ovariectomy (OVX) and OVX with 17ß-estradiol supplementation (OVX + E2), with 15 animals in each group. Three weeks after OVX, all mice were subjected to an Achilles tenotomy using a posterior midpoint approach to induce HO. At 1, 3 and 9 weeks after tenotomy, the left hind limbs were harvested for histology, immunohistochemistry and immunofluorescence evaluations. The volume of ectopic bone was assessed by micro-CT. Results: Mice in the OVX group formed more ectopic cartilage 3 weeks after tenotomy, as well as ectopic bone 9 weeks after tenotomy, compared to the control group. Estrogen deficiency resulted in more severe inflammatory infiltration at the injury sites 1 week after tenotomy, involving the recruitment of more macrophages and mast cells, as well as increasing the expressions of pro-inflammatory mediators, including IL-1ß, IL-6, and TNF-α. Moreover, the local TGF-ß/SMAD signaling pathway was dysregulated after OVX, which manifested as upregulated expressions of TGF-ß and pSMAD2/3. E2 supplementation protected against OVX-induced HO deterioration, inhibited inflammatory infiltration, and downregulated the TGF-ß/SMAD signaling pathway. Conclusion: Estrogen deficiency exacerbated HO formation in the Achilles tenotomy model. These findings might be attributable to the disturbance of the inflammatory response and the activation of TGF-ß/SMAD signaling at the injury sites during the early stages of HO development.
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Concise and scalable formal syntheses of (-)-quinocarcinamide and (-)-quinocarcin have been achieved in 9 steps with 9% overall yield from simple commercially available chemicals. The synthetic strategy features an ortho-regioselective Pictet-Spengler cyclization for the construction of the tetrahydroisoquinoline skeleton, a stereoselective formal intramolecular [3 + 2] cross cycloaddition of cyclopropane 1,1-diester with an imine for the construction of the 3,8-diazabicyclo[3.2.1]octane skeleton.
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Zero-dimensional (0D) hybrid metal halides have been emerged as room-temperature phosphorescence (RTP) materials, but synchronous optimization of multiple phosphorescence performance in one structural platform remains less resolved, and stable RTP activity in aqueous medium is also unrealized due to serious instability toward water and oxygen. Herein, we demonstrated a photophysical tuning strategy in a new 0D hybrid zinc halide family of (BTPP)2ZnX4 (BTPP = benzyltriphenylphosphonium, X = Cl and Br). Infrequently, the delicate combination of organic and inorganic species enables this family to display multiple ultralong green afterglow and efficient self-trapped exciton (STE) associated cyan phosphorescence. Compared with inert luminescence of [BTPP]+ cation, incorporation of anionic [ZnX4]2- effectively enhance the spin-orbit coupling effect, which significantly boosts the photoluminescence quantum yield (PLQY) up to 30.66% and 54.62% for afterglow and phosphorescence, respectively. Synchronously, the corresponding luminescence lifetime extend to 143.94 ms and 0.308 µs surpassing the indiscernible phosphorescence of [BTPP]X salt. More importantly, this halide family presents robust RTP emission with nearly unattenuated PLQY in water and harsh condition (acid and basic aqueous solution) over half a year. The highly efficient integrated afterglow and STE phosphorescence as well as ultrahigh aqueous state RTP realize multiple anti-counterfeiting applications in wide chemical environments.
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BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.
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Tetracycline (TC) is widely present in the environment, and adsorption technology is a potential remediation method. S/N co-doped tea residue biochar (SNBC) was successfully prepared by hydrothermal carbonization method using tea residue as raw material. S was doped by Na2S2O3·5H2O, and N was doped by N in tea residue. The adsorption efficiency of SNBC could reach 94.16% when the concentration of TC was 100 mg L-1. The adsorption effect of SNBC on TC was 9.38 times more than that of unmodified biochar. Tea biochar had good adsorption effect at pH 4-9. The maximum adsorption capacity of 271 mg g-1 was calculated by the Langmuir isotherm model. The adsorption mechanism involved many mechanisms such as pore filling, π-π interaction and hydrogen bonding. The adsorbent prepared in this study could be used as an effective adsorbent in the treatment of TC wastewater.
Subject(s)
Charcoal , Tea , Tetracycline , Water Pollutants, Chemical , Charcoal/chemistry , Tetracycline/chemistry , Adsorption , Tea/chemistry , Water Pollutants, Chemical/chemistry , Nitrogen/chemistry , Water Purification/methods , Hydrogen-Ion Concentration , Wastewater/chemistryABSTRACT
The field of mechanobiology is gaining prominence due to recent findings that show cells sense and respond to the mechanical properties of their environment through a process called mechanotransduction. The mechanical properties of cells, cell organelles, and the extracellular matrix are understood to be viscoelastic. Various technologies have been researched and developed for measuring the viscoelasticity of biological materials, which may provide insight into both the cellular mechanisms and the biological functions of mechanotransduction. Here, we explain the concept of viscoelasticity and introduce the major techniques that have been used to measure the viscoelasticity of various soft materials in different length- and timescale frames. The topology of the material undergoing testing, the geometry of the probe, the magnitude of the exerted stress, and the resulting deformation should be carefully considered to choose a proper technique for each application. Lastly, we discuss several applications of viscoelasticity in 3D cell culture and tissue models for regenerative medicine, including organoids, organ-on-a-chip systems, engineered tissue constructs, and tunable viscoelastic hydrogels for 3D bioprinting and cell-based therapies.
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Introduction: Ascaris lumbricoides and Ascaris suum are parasitic nematodes that primarily infest the small intestines of humans and pigs, respectively. Ascariasis poses a significant threat to human health and swine health. Understanding Ascaris larval development is crucial for developing novel therapeutic interventions that will prevent ascariasis in both humans and pigs. This study aimed to characterize the excretory-secretory (ES) proteome of different Ascaris suum larval stages (L3-egg, L3-lung, L3-trachea) to identify potential targets for intervention to prevent Ascaris -induced global morbidity. Methods: Stage-specific larvae were isolated, cultured in vitro and ES-product was collected. Third-stage Ascaris larvae (L3) were isolated from embryonated eggs (L3-egg), isolated from the lungs of Balb/c mice infected with Ascaris suum eggs at day 8 post infection (L3-lungs) and isolated from the trachea of Balb/c mice infected with Ascaris suum eggs at day 12 post infection (L3-trachea). ES products were obtained by culturing larvae. Proteomic analysis was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatic tools including MaxQuant, Perseus, and Andromeda, following a detailed protocol available on GitHub. The analysis encompassed peptide identification, scoring, and quantification against an organism-specific database, with subsequent quality control, correlation assessment, and differential abundance determination using the Amica algorithm. Results: A total of 58 unique proteins were identified in the ES products. Fourteen proteins were common across all stages, while others were stage-specific. Principal component analysis revealed distinct protein profiles for each stage, suggesting qualitatively different proteomes. Gene ontology analysis indicated stage-specific GO enrichment of specific protein classes, such as nuclear proteins in L3-egg ES products and metabolic enzymes in L3-lung and L3-trachea ES products. Discussion: This study revealed stage-specific differences in the composition of Ascaris ES products. Further investigation into the functional roles of these proteins and their interactions with host cells is crucial for developing novel therapeutic and diagnostic strategies against ascariasis.
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BACKGROUND: Implicit rationing of nursing care is defined as the withholding of necessary nursing measures for patients because of a lack of nursing resources. However, no studies have explored the experience of decision-making about implicit rationing of nursing care in an intensive care unit (ICU). AIM: To explore the process of ICU nurses' decisions and judgement based on the conceptual framework of implicit rationing of nursing care. STUDY DESIGN: A qualitative study was undertaken between June 2020 and September 2020. The data collection methods were participative observation and interview. Eighteen ICU nurses participated in interviews. A thematic analysis was performed for the data analysis. RESULTS: The following five themes emerged: assessment of the condition and nature of nursing and time taken; strategies for setting personal priorities; plan implementation under mitigation strategy; existing nursing in reality; evaluation of the implementation of implicit rationing care. Nurses choose different strategies during plan implementation. CONCLUSIONS: In the absence of explicit guidelines on rationing nursing care, nurses often rely on intuitive and situational decision-making processes for setting priorities. Given the vulnerability of ICU patients and the absence of family caregivers, nurses bear a heightened ethical responsibility to provide care. Establishing a positive nursing culture is essential. It is both reasonable and effective to organize work by accurately quantifying workload, improving staffing levels and optimizing scheduling methods. These themes align with the decision-making process outlined in the conceptual framework and offer fresh perspectives. RELEVANCE TO CLINICAL PRACTICE: Nurses have a greater responsibility to provide care in an ethical manner and to increase awareness of the importance of holistic nursing care for the patient, that is to raise awareness of the importance of care that is often missed. Nurses actively adopt strategies to reduce implicit rationing of nursing care, including teamwork, organized nursing, working overtime and ignoring quality. The findings highlight the importance of creating a positive nursing culture that encourages nurses to adopt positive strategies.