Lansoprazole (LPZ) reverses multidrug resistance (MDR) in cancer through impeding ATP-binding cassette (ABC) transporter-mediated chemotherapeutic drug efflux and lysosomal sequestration.

AIMS: Lansoprazole is one of the many proton pump inhibitors (PPIs) that acts more strongly with ABCB1 and ABCG2. The present study is to investigate the potential of lansoprazole on reversal of ABCB1/G2-mediated MDR in cancer, in vitro and in vivo. METHODS: Reversal studies and combination evaluation were conducted to determine the synergistic anti-MDR effects on lansoprazole. Lysosomal staining was used to determination of lansoprazole on ABCB1-mediated lysosomal sequestration. Substrate accumulation and efflux assays, ATPase activity, and molecular docking were conducted to evaluate lansoprazole on ABCB1/G2 functions. Western blot and immunofluorescence were used to detect lansoprazole on ABCB1/G2 expression and subcellular localization. MDR nude mice models were established to evaluate the effects of lansoprazole on MDR in vivo. RESULTS: Lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects with substrate drugs in MDR cells. In vivo experiments demonstrated that lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects that augmented the sensitivity of substrate anticancer drugs in ABCB1/G2-mediated settings without obvious toxicity. Lansoprazole impeded lysosomal sequestration mediated by ABCB1, leading to a substantial increase in intracellular accumulation of substrate drugs. The effects of lansoprazole were not attributable to downregulation or alterations in subcellular localization of ABCB1/G2. Lansoprazole promoted the ATPase activity of ABCB1/G2 and competitively bound to the substrate-binding region of ABCB1/G2. CONCLUSIONS: These findings present novel therapeutic avenues whereby the combination of lansoprazole and chemotherapeutic agents mitigates MDR mediated by ABCB1/G2 overexpression.

Nanoscale Spatiotemporal Dynamics of Microbial Adhesion: Unveiling Stepwise Transitions with Plasmonic Imaging.

Understanding bacterial adhesion at the nanoscale is crucial for elucidating biofilm formation, enhancing biosensor performance, and designing advanced biomaterials. However, the dynamics of the critical transition from reversible to irreversible adhesion has remained elusive due to analytical constraints. Here, we probed this adhesion transition, unveiling nanoscale, step-like bacterial approaches to substrates using a plasmonic imaging technique. This method reveals the discontinuous nature of adhesion, emphasizing the complex interplay between bacterial extracellular polymeric substances (EPS) and substrates. Our findings not only deepen our understanding of bacterial adhesion but also have significant implications for the development of theoretical models for biofilm management. By elucidating these nanoscale step-like adhesion processes, our work provides avenues for the application of nanotechnology in biosensing, biofilm control, and the creation of biomimetic materials.

Enhancing Clinical Predictive Modeling through Model Complexity-Driven Class Proportion Tuning for Class Imbalanced Data: An Empirical Study on Opioid Overdose Prediction.

Class imbalance issues are prevalent in the medical field and significantly impact the performance of clinical predictive models. Traditional techniques to address this challenge aim to rebalance class proportions. They generally assume that the rebalanced proportions are derived from the original data, without considering the intricacies of the model utilized. This study challenges the prevailing assumption and introduces a new method that ties the optimal class proportions to model complexity. This approach allows for individualized tuning of class proportions for each model. Our experiments, centered on the opioid overdose prediction problem, highlight the performance gains achieved by this approach. Furthermore, rigorous regression analysis affirms the merits of the proposed theoretical framework, demonstrating a statistically significant correlation between hyperparameters controlling model complexity and the optimal class proportions.

Remodeling ceramide homeostasis promotes functional maturation of human pluripotent stem cell-derived ß cells.

Human pluripotent stem cell-derived ß cells (hPSC-ß cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-ß cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-ß cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-ß cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome. Importantly, remodeling lipid metabolism, especially downregulating the metabolic activity of ceramides, the central hub of sphingolipid metabolism, is critical for ß cell maturation. Limiting intracellular accumulation of ceramides in hPSC-ß cells remarkably enhanced their function, as indicated by improvements in insulin processing and glucose-stimulated insulin secretion. In summary, our findings provide insights into the maturation of human pancreatic ß cells and highlight the importance of ceramide homeostasis in function acquisition.

Gastric cancer immune microenvironment score predicts neoadjuvant chemotherapy efficacy and prognosis.

The efficacy of neoadjuvant chemotherapy (NACT) in patients with advanced gastric cancer (GC) varies greatly. Thus, we aimed to verify the predictive value of tumor-infiltrating immune cells (TIICs) on the treatment response to NACT and the prognosis of patients with advanced GC, and to explore the impact of NACT on the tumor immune microenvironment (TIME). Paired tumor tissues (pre- and post-NACT) from patients with advanced GC were collected for this study. TIICs were assessed using immunohistochemistry staining and analyzed using logistic regression to establish an immune microenvironment score for GC (ISGC score) and predict NACT efficacy. Kaplan-Meier curves were used to evaluate the survival outcome of patients. The results showed that TIME was dramatically heterogeneous between NACT response and nonresponse patients. In the validation cohort, the ISGC score demonstrated good predictive performance for treatment response to NACT. Moreover, high ISGC indicated better long-term survival in patients with advanced GC. Furthermore, tumor-infiltrated T cells (CD3+ and CD8+) and CD11c+ macrophages were significantly increased in the response group, while CD163+ macrophages and FOXP3+ Treg cells were decreased after NACT. However, opposite results were exhibited in the nonresponse group. Finally, we found that the percentage of programmed cell death ligand 1 (PD-L1)-positive tumors was 31% (32/104) pre-NACT and 49% (51/104) post-NACT, and almost all patients with elevated PD-L1 were in the NACT response group. The ISGC model accurately predicted NACT efficacy and classified patients with GC into different survival groups. NACT regulates the TIME in GC, which may provide strategies for personalized immunotherapy.

A Shape Memory Polymeric Shield for Protecting Corneal Endothelium During Phacoemulsification.

Background: The purpose of this study was to explore the protective effect of a shape memory polymeric shield on corneal endothelium during phacoemulsification in rabbits. Methods: Poly-(glycerol dodecanedioate) (PGD) with a transition temperature of 24.416°C was prepared to make a shape memory shield with a thickness of 100 µm, an arc length of 14 mm, and a radius of curvature of 8.8 mm. In the control group, a phaco-tip with bevel-down was used to simulate injury to the corneal endothelium by phacoemulsification in rabbits. In the experimental group, the pre-cooled and curled shape memory shield was injected into and removed from the anterior chamber before and after phaco-power release. Anterior segment optical coherence tomography (AS-OCT), confocal microscope, trypan blue/alizarin red staining, and scanning electron microscope were performed to measure endothelial damage after surgery. Results: One day postoperatively, the lost cell ratio of the control group and the experimental group were 28.08 ± 5.21% and 3.50 ± 1.43%, respectively (P < 0.0001), the damaged cell ratios were 11.83 ± 2.30% and 2.55 ± 0.52%, respectively (P < 0.0001), and the central corneal thicknesses (CCT) were 406.75 ± 16.74 µm and 340. 5 ±13.48 µm, respectively (P < 0.0001). Seven days postoperatively, the endothelial cell density (ECD) of the control group and the experimental group were 1674 ± 285/mm2 and 2561 ± 554/mm2, respectively (P < 0.05). The above differences were all statistically significant. Conclusions: This PGD based shape memory shield has a protective effect on corneal endothelium during phacoemulsification. It reduces postoperative corneal edema and ECD decrease in the short term after surgery. Translational Relevance: The shape memory PGD "shield" in this study may have a use in certain human patients with vulnerable corneas of low endothelial cell count or shallow anterior chambers.

Early changes in cardiac troponin T and NT-proBNP levels in neonates receiving ECMO support: a single-center experience.

OBJECTIVE: This study aimed to examine the changes in absolute value and decline rate of early serum cardiac troponin T (cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in neonates who received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support therapy within the first week of life. METHODS: We retrospectively collected clinical data and laboratory test results of 18 neonates who underwent V-A ECMO support within one week of birth, from July 2021 to June 2023, using the electronic medical record system. These patients were categorized into survival and death groups. Comparative analyses of the absolute values and decline rates of cTnT and NT-proBNP were made between the groups at baseline, and at 24, 48, and 72 h post-ECMO initiation. RESULTS: Out of the 18 neonates, 12 survived (survival rate: 66.7%), while 6 succumbed. The survival group exhibited significantly lower absolute values of cTnT and NT-proBNP than the death group, and their decline rates were significantly higher. Notably, all neonates without an early decline in cTnT and NT-proBNP levels were in the death group. CONCLUSION: The early changes in the absolute value and decline rate of serum cTnT and NT-proBNP in neonates undergoing V-A ECMO may serve as predictors of their prognosis.

A Method for Prediction of High-Water-Production Areas in Coalbed Methane Blocks Based on γ Logging Data: A Case Study of the Taiyuan Formation in Liulin Area, Eastern Ordos Basin, China.

The roof aquifer of the Carboniferous Taiyuan Formation coal beds in the Liulin area severely restricts the development and utilization of coalbed methane (CBM). A method for quantitatively predicting high-water-production areas was established by analyzing the relationship between the geophysical logging data and water production. The results showed that the logging profile of the limestone aquifers in high-water-production wells was unique, with high acoustic velocity (AC), high γ-ray values (GR), and low resistivity (Rd). The developed pores and fractures in the roof limestone increase the interval transit time. The formation water in the pores and fractures of the roof limestone decreases the resistivity. The clay filling in the pores and fractures of the roof limestone originated from the dissolution product of limestone and hydrodynamic transportation, which resulted in increased GR values. Furthermore, the representative natural GR log data were used to calculate the clay content in limestone, which indicated that the clay content in limestone had a positive correlation with the water yield of the CBM wells. The water-bearing characteristics of roof limestone showed that the water content was higher in the northern area and decreased gradually toward the south. The method for predicting the high-water-production area was helpful for the CBM exploration and production.

Boosted Electrocatalytic Degradation of Levofloxacin by Chloride Ions: Performances Evaluation and Mechanism Insight with Different Anodes.

As chloride (Cl-) is a commonly found anion in natural water, it has a significant impact on electrocatalytic oxidation processes; yet, the mechanism of radical transformation on different types of anodes remains unexplored. Therefore, this study aims to investigate the influence of chlorine-containing environments on the electrocatalytic degradation performance of levofloxacin using BDD, Ti4O7, and Ru-Ti electrodes. The comparative analysis of the electrode performance demonstrated that the presence of Cl- improved the removal and mineralization efficiency of levofloxacin on all the electrodes. The enhancement was the most pronounced on the Ti4O7 electrode and the least significant on the Ru-Ti electrode. The evaluation experiments and EPR characterization revealed that the increased generation of hydroxyl radicals and active chlorine played a major role in the degradation process, particularly on the Ti4O7 anode. The electrochemical performance tests indicated that the concentration of Cl- affected the oxygen evolution potentials of the electrode and consequently influenced the formation of hydroxyl radicals. This study elucidates the mechanism of Cl- participation in the electrocatalytic degradation of chlorine-containing organic wastewater. Therefore, the highly chlorine-resistant electrocatalytic anode materials hold great potential for the promotion of the practical application of the electrocatalytic treatment of antibiotic wastewater.

Ginseng-Sanqi-Chuanxiong (GSC) extracts attenuate d-galactose-induced vascular aging in mice via inhibition of endothelial progenitor cells senescence.

Vascular aging is an independent risk factor for age-related diseases and a specific type of organic aging. Endothelial progenitor cells (EPCs), a type of bone marrow stem cell, has been linked to vascular aging. The purpose of this study is to investigate if Ginseng-Sanqi-Chuanxiong (GSC) extract, a traditional Chinese medicine, can delay aortic aging in mice by enhancing the performance and aging of EPCs in vivo and to analyze the potential mechanisms through a d-Galactose (D-gal)-induced vascular aging model in mice. Our study revealed that GSC extracts not only enhanced the aortic structure, endothelial function, oxidative stress levels, and aging in mice, but also enhanced the proliferation, migration, adhesion, and secretion of EPCs in vivo, while reducing the expression of p53, p21, and p16. To conclude, GSC can delay vascular senescence by enhancing the function and aging of EPCs, which could be linked to a decrease in p16 and p53/p21 signaling. Consequently, utilizing GSC extracts to enhance the function and senescence of autologous EPCs may present a novel avenue for enhancing autologous stem cells in alleviating senescence.

Quantitative Characterization of Inorganic Pores in Sinian Doushantou Dolomitic Shale Based on FIB-SEM in Western Hubei Province, China.

Unlike traditional shale gas reservoirs, where organic matter pores dominate, inorganic pores are the primary reservoir space in the Sinian (Ediacaran) high-maturity Doushantou dolomitic shale in western Hubei Province, China. The inorganic pore characteristics of Doushantuo shale and its influence on shale gas aggregation were investigated by examining the TOC content, thermal maturity, mineralogical composition, and field-emission scanning electron microscopy (SEM) and focused ion beam scanning electron microscopy (FIB-SEM) of drill cores. The results show that the shale mineral composition in the study area is primarily dolomite and plate-shaped interparticle-intercrystalline pores associated with dolomite are widespread inorganic pores in dolomitic shale. Interparticle-intercrystalline pores account for 75% of the total pores, with a pore size distribution mainly between 50 and 300 nm, as extracted from the 3D pore network model (PNM). Compared with organic pores, interparticle-intercrystalline pores provide greater space for gas storage and have a strong coupling relationship with the hydrocarbon generation and evolution of organic matter. Therefore, the inorganic pores in the Doushantuo Formation play a vital role in the enrichment and accumulation of shale gas. This study aims to establish a scientific basis for understanding the enrichment mechanism of shale gas in Doushantuo dolomitic shale and other inorganic pore-dominated shales in southern China.

Mesenchymal Stem Cell-Laden In Situ-Forming Hydrogel for Preventing Corneal Stromal Opacity.

PURPOSE: The aims of this study were to construct a mesenchymal stem cell (MSC)-laden in situ-forming hydrogel and study its effects on preventing corneal stromal opacity. METHODS: The native gellan gum was modified by high temperature and pressure, and the rabbit bone marrow MSCs were encapsulated before adding Ca 2+ to initiate cross-linking. The effects of the hydrogel on 3D culture and gene expression of the rabbit bone marrow MSCs were observed in vitro. Then, the MSC-hydrogel was used to repair corneal stromal injury in New Zealand white rabbits within 28 days postoperation. RESULTS: The short-chain gellan gum solution has a very low viscosity (<0.1 Pa·s) that is ideal for encapsulating cells. Moreover, mRNA expressions of 3D-cultured MSCs coding for corneal stromal components (decorin, lumican, and keratocan) were upregulated (by 127.8, 165.5, and 25.4 times, respectively) ( P < 0.05) on day 21 in vitro and were verified by Western blotting results. For the in vivo study, the corneal densitometry of the experimental group was (20.73 ± 1.85) grayscale units which was lower than the other groups ( P < 0.05). The MSC-hydrogel downregulated mRNA expression coding for fibrosis markers (α-smooth muscle actin, vimentin, collagen type 5-α1, and collagen type 1-α1) in the rabbit corneal stroma. Furthermore, some of the 5-ethynyl-2'-deoxyuridine (EdU)-labeled MSCs integrated into the upper corneal stroma and expressed keratocyte-specific antigens on day 28 postoperation. CONCLUSIONS: The short-chain gellan gum allows MSCs to slowly release to the corneal stromal defect and prevent corneal stromal opacity. Some of the implanted MSCs can integrate into the corneal stroma and differentiate into keratocytes.

Formyl phloroglucinol meroterpenoids from the leaves of Eucalyptus globulus subsp. maidenii and their ATP-citrate lyase inhibitory activities.

Three new formyl phloroglucinol meroterpenoids, eumaidials A-C (1-3), were isolated from the leaves of Eucalyptus globulus subsp. maidenii, along with ten known analogues (4-13). Their chemical structures were determined by various spectral data and electronic circular dichroism calculations. Eumaidial A (1) is the first ß-caryophyllene-based formyl phloroglucinol meroterpenoids from the genus Eucalyptus. Compounds 1-4 and 10 exhibited ATP-citrate lyase inhibitory activities, and compounds 2 and 3 suppressed the hepatocyte lipogenesis.

Involvement of TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation.

T-2 toxin, a highly toxic type A monotrichothecene mycotoxin, has been found in many different types of cereals and is considered to be one of the most dangerous naturally occurring forms of food contamination. Globally, consuming grain-based food tainted with T-2 toxin poses significant risks to animal and human health. Prior research has indicated that the presence of T-2 toxin may lead to the demise of chondrocytes and the deterioration of the extracellular matrix of cartilage in degenerative bone and joint conditions, such as Kashin-Beck disease. However, the mechanisms by which T-2 toxin exerts its biological toxicity on the degradation of the extracellular matrix in cartilage are not well understood. In the current study, we found original results that demonstrate an upregulation of Toll-Like Receptors (TLR-2, TLR-4) and ESE-1 expression levels in the articular cartilage of a rat model subjected to T-2 toxin exposure. Furthermore, it was revealed that the exposure to T-2 toxin resulted in an increase in the expression of TLR-2, TLR-4, and ESE-1 in human C28/I2 chondrocytes. The findings of this study indicate that the increased expression of TLR-2, TLR-4, and ESE-1 may contribute to the development of degenerative osteoarthritic disease caused by T-2 toxin. Consistent with our hypotheses, we discovered that T-2 toxin increased the expression of MMP-1 and MMP-13 in human C28/I2 chondrocytes. We used a luciferase reporter gene assay to measure the activity of the ESE-1 promoter and transfected cells with plasmids encoding TLR-2 and TLR-4 to investigate their effects on this activity. TLR-2 and TLR-4 can activate ESE-1 transcriptional gene expression, and this expression is mediated through the NF-κB pathway, additional evidence is provided for the participation of the TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation. Together, the findings indicated that the TLRs/NF-κB/ESE-1 signaling pathway played an essential part in T-2 toxin-induced cartilage matrix degradation.

CD44s and CD44v8-10 isoforms confer acquired resistance to osimertinib by activating the ErbB3/STAT3 signaling pathway.

AIMS: Although epidermal growth factor receptor (EGFR)-mutant lung cancers respond well to osimertinib, acquired resistance to osimertinib eventually develops through EGFR-dependent and EGFR-independent resistance mechanisms. CD44 splicing variants are widely expressed in lung cancer tissues. However, it remains unclear whether specific splicing variants are involved in acquired resistance to osimertinib. MAIN METHODS: The real-time PCR was performed to measure the expression levels of total CD44 and specific CD44 splicing variants (CD44s or CD44v). Gene knockdown and restoration were performed to investigate the effects of CD44 splicing variants on osimertinib sensitivity. Activation of the signaling pathway was evaluated using receptor-tyrosine-kinase phosphorylation membrane arrays, co-immunoprecipitation, and western blotting. KEY FINDINGS: Clinical analysis demonstrated that the expression level of total CD44 increased in primary cancer cells from lung adenocarcinomas patients after the development of acquired resistance to osimertinib. Furthermore, osimertinib-resistant cells showed elevated levels of either the CD44s variant or CD44v variants. Manipulations of CD44s or CD44v8-10 were performed to investigate their effects on treatment sensitivity to osimertinib. Knockdown of CD44 increased osimertinib-induced cell death in osimertinib-resistant cells. However, restoration of CD44s or CD44v8-10 in CD44-knockdown H1975/AZD-sgCD44 cells induced osimertinib resistance. Mechanically, we showed that ErbB3 interacted with CD44 and was transactivated by CD44, that consequently triggered activation of the ErbB3/STAT3 signaling pathway and led to CD44s- or CD44v8-10-mediated osimertinib resistance. SIGNIFICANCE: CD44 is a co-receptor for ErbB3 and triggers activation of the ErbB3 signaling axis, leading to acquired resistance to osimertinib. CD44/ErbB3 signaling may represent a therapeutic target for overcoming osimertinib resistance.

Establishment of plastic-associated microbial community from superworm gut microbiome.

Gut microbial communities of plastic-munching worms provide novel insights for the development of plastic-processing biotechnologies. Considering the complexity of worm maintenance and the gut microbial communities, it is challenging to apply the worms directly in plastic processing. Harnessing the power of microbial communities derived from the worm gut microbiomes in vitro may enable a promising bioprocess for plastic degradation. Here, we established stable and reproducible plastic-associated biofilm communities derived from the gut microbiome of a superworm, Zophobas atratus, through a two-stage enrichment process: feeding with plastics (HDPE, PP, and PS) and in vitro incubation of gut microbiomes obtained from the plastic-fed worms. Plastic feeding exhibited marginal influence on bacterial diversity but substantially changed the relative abundance of different bacterial groups, and intriguingly, enriched potential plastic degraders. More prominent shifts of microbial communities were observed during the in vitro incubation of the gut microbiomes. Taxa containing plastic-degrading strains were further enriched, while other taxa represented by lactic acid bacteria were depleted. Additionally, the plastic characterization confirmed the degradation of the incubated plastics by the plastic-associated microbial communities. Community functional inference for both gene abundance and community phenotype suggested that the in vitro incubation enhanced plastic-degrading potential. Deterministic ecological effects, in particular, selection processes, were identified as the main driving force of the observed community shifts. Our findings provide novel insights into plastic-munching-worm-inspired bioprocessing of plastic wastes.

The efficient generation of functional human hepatocytes from chemically induced pluripotent stem cells.

Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs). Single-cell RNA sequencing (scRNA-seq) indicates the similarity between hepatoblasts differentiated in vitro and in vivo. Moreover, hCiPSC-derived hepatic progenitor cells can further differentiate into hepatocytes that are similar to primary human hepatocytes with respect to gene expression and key hepatic functions. Our results demonstrate the feasibility of generating hepatic progenitor cells and hepatocytes from hCiPSCs with high efficiency and set the foundation for broad translational applications of hCiPSC-derived hepatocytes.

miR-204 suppresses cancer stemness and enhances osimertinib sensitivity in non-small cell lung cancer by targeting CD44.

Osimertinib is an effective treatment option for patients with advanced non-small cell lung cancer (NSCLC) with EGFR activation or T790M resistance mutations; however, acquired resistance to osimertinib can still develop. This study explored novel miRNA-mRNA regulatory mechanisms that contribute to osimertinib resistance in lung cancer. We found that miR-204 expression in osimertinib-resistant lung cancer cells was markedly reduced compared to that in osimertinib-sensitive parental cells. miR-204 expression levels in cancer cells isolated from treatment-naive pleural effusions were significantly higher than those in cells with acquired resistance to osimertinib. miR-204 enhanced the sensitivity of lung cancer cells to osimertinib and suppressed spheroid formation, migration, and invasion of lung cancer cells. Increased miR-204 expression in osimertinib-resistant cells reversed resistance to osimertinib and enhanced osimertinib-induced apoptosis by upregulating BIM expression levels and activating caspases. Restoration of CD44 (the direct downstream target gene of miR-204) expression reversed the effects of miR-204 on osimertinib sensitivity, recovered cancer stem cell and mesenchymal markers, and suppressed E-cadherin expression. The study demonstrates that miR-204 reduced cancer stemness and epithelial-to-mesenchymal transition, thus overcoming osimertinib resistance in lung cancer by inhibiting the CD44 signaling pathway.

Comparisons of the clinical outcomes of Centurion® active fluidics system with a low IOP setting and gravity fluidics system with a normal IOP setting for cataract patients with low corneal endothelial cell density.

Background: During cataract phacoemulsification surgery, the Alcon Centurion with Active Sentry can achieve a more stable anterior chamber, which allows a lower intraocular pressure (IOP) setting than the gravity fluidics system. In this randomized controlled trial, we compared these two systems' damage to the cornea under different IOP settings. Methods: Seventy-eight eyes of 53 patients with corneal endothelial cell density (ECD) of 500∼1500/mm2 were enrolled and randomly divided into the active fluidics system (AFS) group using an Active Sentry handpiece with 30 mmHg IOP setting (40 eyes) and the gravity fluidics system (GFS) group using an Ozil handpiece with 80 cmH2O IOP setting (38 eyes). Intraoperative parameters, visual acuity, corneal edema ratio, central corneal thickness (CCT) changes as well as loss rate of ECD were analyzed. Results: We observed no significant differences in best corrected visual acuity (BCVA), cumulative dissipated energy (CDE), total case time, estimated fluidics usage (EFU) and ophthalmic viscoelastic devices (OVDs) usage between the two groups. The enrolled eyes were further divided into soft nucleus (27 eyes) and hard nucleus (51 eyes) subgroups. And we found less pain complaint during surgeries, lower corneal edema ratio at 1-day and 1-week visit, smaller CCT changes at 1-day visit and lower ECD loss rate at 1-month visit (p < 0.05) in both subgroups of the AFS group than in the GFS group, implying higher intraoperative comfort levels and less corneal damage of the AFS group with a low IOP setting. Conclusion: Owing to a lower IOP setting, Centurion® Vision System with Active Sentry handpiece causes less corneal damage and pain perception during phacoemulsification for patients with low pre-operative ECD. Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR2300077865.