CO2 Stress-Driven Room Temperature Ferromagnetism of Ultrathin 2D Gallium Oxide.

Spintronic devices work by manipulating the spin of electrons other than charge transfer, which is of revolutionary significance and can largely reduce energy consumption in the future. Herein, ultrathin two-dimensional (2D) non-van der Waals (non-vdW) γ-Ga2O3 with room temperature ferromagnetism is successfully obtained by using supercritical CO2 (SC CO2). The stress effect of SC CO2 under different pressures selectively modulates the orientation and strength of covalent bonds, leading to the change of atomic structure including lattice expansion, introduction of O vacancy, and transition of Ga-O coordination (GaO4 and GaO6). Magnetic measurements show that pristine γ-Ga2O3 is nonferromagnetic, whereas the SC CO2 treated γ-Ga2O3 exhibits obvious ferromagnetic behavior with an optimal magnetization of 0.025 emu g-1 and a Curie temperature of 300 K.

Evidence of deviant parasympathetic response to social exclusion in women with borderline personality disorder.

Stressful social situations like social exclusion are particularly challenging for patients with borderline personality disorder (BPD) and often lead to dysfunctional reactive behaviour of aggression and withdrawal. The autonomous signature of these core symptoms of BPD remains poorly understood. The present study investigated the parasympathetic response to social exclusion in women with BPD (n = 62) and healthy controls (HC; n = 87). In a between-subjects design, participants experienced objective social exclusion or overinclusion in the Cyberball task, a virtual ball-tossing game. Need threat scores served as individual measures of perceived exclusion and the resulting frustration of cognitive-emotional needs. Five-minute measurements of high-frequency heart rate variability (HF-HRV) at three time points (before, during, after Cyberball) indicated parasympathetic tone and regulation. We observed a trend towards lowered baseline HF-HRV in BPD vs. HC in line with previous findings. Interestingly, the parasympathetic response of patients with BPD to objective and perceived social exclusion fundamentally differed from HC: higher exclusion was associated with increased parasympathetic activation in HC, while this autonomic response was reversed and blunted in BPD. Our findings suggest that during social stress, the parasympathetic nervous system fails to display an adaptive regulation in patients with BPD, but not HC. Understanding the autonomous signature of the stress response in BPD allows the formulation of clinically relevant and biologically plausible interventions to counteract parasympathetic dysregulation in this clinical group.

Human embryonic stem cell-derived immunity-and-matrix regulatory cells promote intrahepatic cell renewal to rescue acute liver failure.

Acute liver failure (ALF) is a clinical syndrome characterized by the accelerated development of hepatocyte necrosis and significant mortality. Given that liver transplantation is now the only curative treatment available for ALF, there is an urgent need to explore innovative therapies. Mesenchymal stem cells (MSCs) have been applied in preclinical studies for ALF. It had been demonstrated that human embryonic stem cell-derived immunity-and-matrix regulatory cells (IMRCs) met the properties of MSCs and had been employed in a wide range of conditions. In this study, we conducted a preclinical evaluation of IMRCs in the treatment of ALF and investigated the mechanism involved. ALF was induced in C57BL/6 mice via intraperitoneal administration of 50% CCl4 (6 mL/kg) mixed with corn oil, followed by intravenous injection of IMRCs (3 × 106 cells/each). IMRCs improved histopathological changes in the liver and reduced alanine transaminase (ALT) or aspartate transaminase (AST) levels in serum. IMRCs also promoted cell renewal in the liver and protected it from CCl4 damage. Furthermore, our data indicated that IMRCs protected against CCl4-induced ALF by regulating the IGFBP2-mTOR-PTEN signaling pathway, which is associated with the repopulation of intrahepatic cells. Overall, IMRCs offered protection against CCl4-induced ALF and were capable of preventing apoptosis and necrosis in hepatocytes, which provided a new perspective for treating and improving the prognosis of ALF.

Impact of social exclusion on empathy in women with borderline personality disorder.

Unstable interpersonal relationships and fear of abandonment are core symptoms of borderline personality disorder (BPD) that often intensify during stress. Psychosocial stress, which includes components of social exclusion and increases cortisol secretion, enhances emotional empathy in healthy individuals. Women with BPD, on the contrary, react with reduced emotional empathy. The aim of the present study was to investigate the effects of perceived social exclusion without accompanying cortisol increase on empathy in women with BPD and healthy women. To induce social exclusion, we randomized 98 women with BPD and 98 healthy women to either an exclusion or an overinclusion (control) condition of Cyberball, a virtual ball game. Subsequently, participants underwent the Multifaceted Empathy Test (MET), which assesses cognitive and emotional empathy. There was no increase in cortisol release after Cyberball. Cognitive empathy did not differ between groups or conditions. Women with BPD reported lower emotional empathy for positive emotions (group by valence interaction), but not for negative emotions. Exploratory analyses suggested that this effect might be more pronounced after social exclusion. Our results confirm previous findings that cognitive empathy does not differ between women with BPD and healthy women and extend this evidence to social exclusion. Emotional empathy in women with BPD seems to be more sensitive to the effects of stress or ambiguous social situations. Specifically, emotional empathy seems to be reduced for positive emotions, and might further decline after social exclusion. Empathic reactions to emotional stimuli of different valences and to specific emotions should be further investigated.

Effects of multimodal analgesia of flurbiprofen axetil, nalbuphine and patient controlled intravenous analgesia on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery.

To evaluate the efficacy of multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and patient controlled intravenous analgesia (PCIA) on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery. The data of 100 patients admitted to our hospital from May 2019 to May 2020 for laparoscopic radical gynecological malignancy surgery were retrospectively analyzed and they were assigned (1:1) to either an experimental group or a control group according to the alphabetical order of their initials. The experimental group was given preemptive analgesia with flurbiprofen axetil, postoperative analgesia with nalbuphine hydrochloride, and PCIA and the control group was given conventional analgesic measures. The pain scores at 1h, 6h, 12h, 24h and 48h postoperatively in the experimental group were remarkably lower than those in the control group (P<0.001). The experimental group showed significantly lower inflammatory factor levels, pain mediator levels and stress response indexes in the morning before surgery, 1d, and 2d after surgery than the control group (P<0.001). The multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and PCIA can effectively alleviate the stress response and inflammatory response in patients after radical gynecologic malignancy surgery and the patients' pain perception is reduced with a high safety profile.

Precise Capture and Direct Quantification of Tumor Exosomes via a Highly Efficient Dual-Aptamer Recognition-Assisted Ratiometric Immobilization-Free Electrochemical Strategy.

Tumor exosomes are promising biomarkers for early cancer diagnosis in a noninvasive manner. However, precise capture and direct analysis of tumor-specific exosomes in complex biological samples are still challenging. Herein, we present a highly efficient dual-aptamer recognition system for precisely isolating and quantifying tumor exosomes from the complex biological environment based on hyperbranched DNA superstructure-facilitated signal amplification and ratiometric dual-signal strategies. When tumor exosomes were captured by the dual-aptamer recognition system, the cholesterol-modified DNA probe was anchored on the surface of the exosomes, activating DNA tetrahedron-based hyperbranched hybridization chain reaction to generate a sandwich complex. Then, the sandwich complex could bind a large number of Ru(NH3)63+ (Ru(III)), leading to a small amount of unbound Ru(III) left in the supernatant after magnetic separation. Hence, the redox reaction between Ru(II) and [Fe(CN)6]3- (Fe(III)) was significantly prevented, causing an obviously enhanced IFe(III)/IRu(III) value. Consequently, highly sensitive detection of tumor exosomes was achieved. The developed approach successfully realized direct isolation and analysis of tumor exosomes in complex sample media and human serum samples as well. More significantly, this ratiometric dual-signal mode and immobilization-free strategy effectively circumvented the systematic errors caused by external factors and the tedious probe immobilization processes, thus displaying the excellent performances of high reliability, improved accuracy, and easy manipulation. Overall, this approach is expected to offer novel ways for nondestructive early cancer diagnosis.

Improvement for Testing the Gravitational Inverse-Square Law at the Submillimeter Range.

We improve the test of the gravitational inverse-square law at the submillimeter range by suppressing the vibration of the electrostatic shielding membrane to reduce the disturbance coupled from the residual surface potential. The result shows that, at a 95% confidence level, the gravitational inverse-square law holds (|α|≤1) down to a length scale λ=48 µm. This work establishes the strongest bound on the magnitude α of the Yukawa violation in the range of 40-350 µm, and improves the previous bounds by up to a factor of 3 at the length scale λ≈70 µm. Furthermore, the constraints on the power-law potentials are improved by about a factor of 2 for k=4 and 5.

Dual-pulse laser ignition of ethylene-air mixtures in a supersonic combustor.

To reduce the energy of an individual laser pulse, dual-pulse laser ignitions (LIs) at various pulse intervals were investigated in a Mach 2.92 scramjet engine fueled with ethylene. For comparison, experiments on a single-pulse LI were also performed. Schlieren visualization and high-speed photography were employed to observe the ignition processes simultaneously. The results indicate that the energy of an individual laser pulse can be reduced by half via a dual-pulse LI method as compared with a single-pulse LI with the same total energy. The reduction of the individual laser pulse energy degrades the requirements on the laser source and the beam delivery system, which facilitates the practical application of LI in hypersonic vehicles. A pulse interval shorter than 40 µs is suggested for dual-pulse LI in the present study. Because of the intense heat loss and radical dissipation in high-speed flows, the pulse interval for dual-pulse LI should be short enough to narrow the spatial distribution of the initial flame kernel.

Stage of cancer diagnoses among migrants from the former Soviet Union in comparison to the German population - are diagnoses among migrants delayed?

BACKGROUND: In this study, we compared stage at diagnosis, standardized incidence ratio (SIR) and standardized mortality ratio (SMR) of most frequent cancer diagnoses between re-settlers (Aussiedler) from the former Soviet Union and the general population in the Saarland in Germany to assess possible delays in diagnosis of cancer among this migrant group. METHODS: Lung cancer, colorectal cancer, breast cancer, prostate cancer, malignant melanoma of the skin and stomach cancer diagnoses among a cohort of 18,619 re-settlers living in the Saarland between 1990 and 2009 were identified by the federal state's cancer registry. Vital status was available for the respective time-period and used to calculate SIR and SMR in comparison to the autochthonous population. Tumor stages were condensed into local and advanced stages. Odds ratios (OR) for an advanced tumor stage were modeled in dependence of re-settler-status and relevant covariates by logistic regression. Missing values were addressed in a sensitivity analysis. The influence of duration of stay in Germany on advanced stage diagnosis was analyzed among re-settlers. RESULTS: SIR and SMR of lung and breast cancer were lower among female re-settlers, while SIR and SMR of colorectal and prostate cancer were lower among male re-settlers. SIR and SMR of stomach cancer were elevated among both sexes. Female re-settlers showed an elevated OR for being diagnosed with advanced stage breast cancer. Both male and female re-settlers showed an elevated OR when observing all six sites combined (OR among males 1.47, p = 0.04; OR among females 1.37, p = 0.05). The result of elevated ORs was supported in the sensitivity analysis. Finally, male re-settlers showed a weak association between duration of stay in Germany and reduced risk for advanced stage diagnosis. CONCLUSION: Re-settlers were more likely to be diagnosed at an advanced tumor stage. These findings are in line with previous research having shown unfavorable health care utilization of re-settlers. Overall, low mortality rates despite an increased risk of advanced stage at diagnosis argue for a sufficient follow-up care, comparable to the autochthonous population.

A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus.

In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.

New Test of the Gravitational Inverse-Square Law at the Submillimeter Range with Dual Modulation and Compensation.

By using a torsion pendulum and a rotating eightfold symmetric attractor with dual modulation of both the interested signal and the gravitational calibration signal, a new test of the gravitational inverse-square law at separations down to 295 µm is presented. A dual-compensation design by adding masses on both the pendulum and the attractor was adopted to realize a null experiment. The experimental result shows that, at a 95% confidence level, the gravitational inverse-square law holds (|α|≤1) down to a length scale λ=59 µm. This work establishes the strongest bound on the magnitude α of Yukawa-type deviations from Newtonian gravity in the range of 70-300 µm, and improves the previous bounds by up to a factor of 2 at the length scale λ≈160 µm.

Antiapoptotic gene BAG-1 vector structure of RNA interference and endogenous targeted screening in colon cancer cell lines.

The purposes of the present work were to construct the shRNA plasmids for BAG-1 gene of human and test the expression of mRNA and protein of BAG-1. Recombinant plasmids containing green fluorescent protein reporter genes are constructed using gene cloning methods. The shRNA plasmids for the BAG-1 gene are constructed by RNA interference technology. We applied fluorescent plasmid-transfected target cells in the cell transfection experiments and monitored the transfection rate of plasmids by observing the fluorescence amount. We transfected three synthesized shRNA in target screening cell and adopted RT-PCR and Western test to identify the difference of target gene transfection and translation level in cells. The specific shRNA plasmid for the BAG-1 gene was successfully recombined, and stably transfected colon cancer Lo Vo cell lines were obtained. The results present that the constructed shRNA plasmids significantly inhibited the expression of mRNA and protein of Lo Vo cell BAG-1, and can maintain the effect for a long term. pGPH1/GFP/Neo-BAG-1-homo-825 was screened as the optimum sequence of interference so as to lay a solid foundation to explore into the research on the BAG-1 gene and the biological behavior of colon cancer cells. It showed the remarkable advantage of RNAi in the generation of posttranscriptional gene silencing.

Radiofrequency-assisted versus clamp-crush liver resection: a systematic review and meta-analysis.

BACKGROUND: Conflicting results were found between radiofrequency-assisted liver resection (RF-LR) and clamp-crush liver resection (CC-LR) during liver surgery. We conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and non-RCTs to compare the effectiveness and safety of RF-LR versus CC-LR during liver surgery. METHODS: Articles comparing RF-LR and CC-LR that were published before December 2012 were retrieved and subjected to a systematic review and meta-analysis. Data synthesis and statistical analysis were carried out by Review Manager Version 5.2 software. RESULTS: In all, four RCTs and five nonrandomized studies evaluating 728 patients were included. Compared with CC-LR, the RF-LR group had significantly reduced total intraoperative blood loss (weighted mean difference [WMD] = -187 mL; 95% confidence interval [CI] = -312, -62; data on 628 patients), and blood loss during liver transection (WMD = -143.7 mL; 95% CI = -200, -87; data on 190 patients). However, RF-LR is associated with a higher rate of intra-abdominal abscess than the clamp-crushing method (odds ratio = 3.61; 95% CI = 1.26, 10.32; data on 366 patients). No significant difference was observed between both the groups for the incidence of both blood transfusion and bile leak. CONCLUSIONS: There is currently not sufficient evidence to support or refute the use of RF-LR in liver surgery. RF-LR has advantages in terms of reducing blood loss. However, RF-LR may increase the rates of both bile leak and abdominal abscess. So, the safety of RF-LR has not been established. Future well-designed RCTs are awaited to further investigate the efficacy and safety of RF devices in liver resection.

Liver transplantation using organs from deceased organ donors: a single organ transplant center experience.

BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program. METHODS: From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively. RESULTS: Among the 29 donors, 24 were China Category II donors (organ donation after cardiac death), and five were China Category III donors (organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422 (2-696) days. Among the five mortalities during the follow-up, three died of tumor recurrence. In terms of post-transplant complications, 9 recipients (34.6%) experienced early allograft dysfunction, 1 (3.8%) had non-anastomotic biliary stricture, and 1 (3.8%) was complicated with hepatic arterial thrombosis. None of these complications resulted in patient death. Notably, primary non-function was not observed in any of the grafts. CONCLUSION: With careful donor selection, liver transplant from deceased donors can be performed safely and plays a critical role in overcoming the extreme organ shortage in China.

[94 km Brillouin distributed optical fiber sensors based on ultra-long fiber ring laser pumping].

A novel optical amplification configuration based on ultra-long fiber laser with a ring cavity was proposed and applied to Brillouin optical time-domain analysis (BOTDA) sensing system, in order to extend the measurement distance significantly. The parameters used in the experiment were optimized, considering the main limitations of the setup, such as depletion, self-phase modulation (SPM) and pump-signal relative intensity noise (RIN) transfer. Through analyzing Brillouin gain spectrum, we demonstrated distributed sensing over 94 km of standard single-mode fiber with 3 meter spatial resolution and strain/temperature accuracy of 28 /1. 4 degree C.

Research Progress on Bonding Wire for Microelectronic Packaging.

Wire bonding is still the most popular chip interconnect technology in microelectronic packaging and will not be replaced by other interconnect methods for a long time in the future. Au bonding wire has been a mainstream semiconductor packaging material for many decades due to its unique chemical stability, reliable manufacturing, and operation properties. However, the drastic increasing price of Au bonding wire has motivated the industry to search for alternate bonding materials for use in microelectronic packaging such as Cu and Ag bonding wires. The main benefits of using Cu bonding wire over Au bonding wire are lower material cost, higher electrical and thermal conductivity that enables smaller diameter Cu bonding wire to carry identical current as an Au bonding wire without overheating, and lower reaction rates between Cu and Al that serve to improve the reliability performance in long periods of high temperature storage conditions. However, the high hardness, easy oxidation, and complex bonding process of Cu bonding wire make it not the best alternative for Au bonding wire. Therefore, Ag bonding wire as a new alternative with potential application comes to the packaging market; it has higher thermal conductivity and lower electric resistivity in comparison with Cu bonding wire, which makes it a good candidate for power electronics, and higher elastic modulus and hardness than Au bonding wire, but lower than Cu bonding wire, which makes it easier to bond. This paper begins with a brief introduction about the developing history of bonding wires. Next, manufacturability and reliability of Au, Cu, and Ag bonding wires are introduced. Furthermore, general comparisons on basic performance and applications between the three types of bonding wires are discussed. In the end, developing trends of bonding wire are provided. Hopefully, this review can be regarded as a useful complement to other reviews on wire bonding technology and applications.

Effects of Process Parameters on Bond Properties of Ag-2.35Au-0.7Pd-0.2Pt-0.1Cu Alloy Wire.

Bond properties were performed on Ag-2.35Au-0.7Pd-0.2Pt-0.1Cu alloy wire with a diameter of 25 µm under different process parameters. The effects of electrical flaming off (EFO) current and EFO time on the deformability of the free air ball (FAB) were investigated using scanning electron microscopy (SEM), as well as the effects of ultrasonic power and bonding force on the bond characteristic. The experimental results show that FAB grows from a preheated tip to a small ball, a regular ball, and finally to a golf ball with increasing either the EFO current or the EFO time, and the FAB presents an optimal shape at 25 mA and 650 µs. Moreover, a nonlinear relationship between FAB diameter and EFO time is obtained at an EFO current of 25 mA, which could be expressed by a cubic equation. Further, at a constant bonding force, as the ultrasonic power increased, the mashed ball diameter grew larger and larger, the capillary hole imprint became more and more obvious, and the tail width also increased, and vice versa. The optimal ultrasonic power and bonding force are 70 mW and 45 gf for ball bonding and 90 mW and 75 gf for wedge bonding, respectively. Finally, for all the bonded wire samples prepared under optimal process parameters, no ball and wedge bond lifts happened after the destructive pull test, and full intermetallic compound coverage with perfect morphology occurred on the bond pad after the ball shear test, which meant that the bonded wire samples had high bond strength and hence improved the reliability of microelectronic products. It provided technical support for the reliability research of Pt-containing Ag-based bonding alloy wires.

A Review of Silver Wire Bonding Techniques.

The replacement of gold bonding wire with silver bonding wire can significantly reduce the cost of wire bonding. This paper provides a comprehensive overview of silver wire bonding technology. Firstly, it introduces various types of silver-based bonding wire currently being studied by researchers, including pure silver wire, alloy silver wire, and coated silver wire, and describes their respective characteristics and development statuses. Secondly, the development of silver-based bonding wire in manufacturing and bonding processes is analyzed, including common silver wire manufacturing processes and their impact on silver wire performance, as well as the impact of bonding parameters on silver wire bonding quality and reliability. Subsequently, the reliability of silver wire bonding is discussed, with a focus on analyzing the effects of corrosion, electromigration, and intermetallic compounds on bonding reliability, including the causes and forms of chlorination and sulfurization, the mechanism and path of electromigration, the formation and evolution of intermetallic compounds, and evaluating their impact on bonding strength and reliability. Finally, the development status of silver wire bonding technology is summarized and future research directions for silver wire are proposed.

Copper Wire Bonding: A Review.

This paper provides a comprehensive review on copper (Cu) wire bonding. Firstly, it introduces the common types of Cu wire available in the market, including bare Cu wire, coated Cu wire, insulated Cu wire, and alloyed Cu wire. For each type, their characteristics and application areas are discussed. Additionally, we provide detailed insights into the impact of Free Air Ball (FAB) morphology on bonding reliability, including its effect on bond strength and formation mechanisms. Next, the reliability of Cu wire bonding is analyzed, with a focus on the impact of intermetallic compounds and corrosion on bonding reliability. Specifically, the formation, growth, and stability of intermetallic compounds at bonding interfaces are discussed, and their effects on bonding strength and reliability are evaluated. The detrimental mechanisms of corrosion on Cu wire bonding and corrosion inhibition methods are also analyzed. Subsequently, the applications of simulation in Cu wire bonding are presented, including finite element analysis and molecular dynamics simulations, which provide important tools for a deeper understanding of the bonding process and failure mechanisms. Finally, the current development status of Cu wire bonding is summarized, and future research directions are discussed.

Safety and efficacy of human ESC-derived corneal endothelial cells for corneal endothelial dysfunction.

BACKGROUND: Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge. RESULTS: Here we defined an adapted differentiation protocol to generate induced corneal endothelial cells (iCECs) consistently and efficiently from clinical-grade human embryonic stem cells (hESCs) with xeno-free medium and manufactured cryopreserved iCECs. Cells express high levels of typical CECs markers and exhibit transendothelial potential properties in vitro typical of iCECs. After rigorous quality control measures, cells meeting all release criteria were available for in vivo studies. We found that there was no overgrowth or tumorigenicity of grafts in immunodeficient mice. After grafting into rabbit models, the surviving iCECs ameliorated edema and recovered corneal opacity. CONCLUSIONS: Our work provides an efficient approach for generating iCECs and demonstrates the safety and efficacy of iCECs in disease modeling. Therefore, clinical-grade iCECs are a reliable source for future clinical treatment of corneal endothelial dysfunction.