Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.

Lung cancer is closely associated with chronic inflammation, but the causes of inflammation and the specific immune mediators have not been fully elucidated. The lung is a mucosal tissue colonized by a diverse bacterial community, and pulmonary infections commonly present in lung cancer patients are linked to clinical outcomes. Here, we provide evidence that local microbiota provoke inflammation associated with lung adenocarcinoma by activating lung-resident γδ T cells. Germ-free or antibiotic-treated mice were significantly protected from lung cancer development induced by Kras mutation and p53 loss. Mechanistically, commensal bacteria stimulated Myd88-dependent IL-1ß and IL-23 production from myeloid cells, inducing proliferation and activation of Vγ6+Vδ1+ γδ T cells that produced IL-17 and other effector molecules to promote inflammation and tumor cell proliferation. Our findings clearly link local microbiota-immune crosstalk to lung tumor development and thereby define key cellular and molecular mediators that may serve as effective targets in lung cancer intervention.

γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis.

The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation1,2. The molecular basis of this bi-directional communication remains to be fully determined. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically γδ T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGFß1 in parenchymal cells via the IL-17 receptor C (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGFß1 in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes that are consistent with defective thermogenesis; innervation can be fully rescued by restoring TGFß1 expression. Ablating γδ Τ cells and the IL-17RC signalling pathway also impairs sympathetic innervation in other tissues such as salivary glands. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.

Immobilized horseradish peroxidase on boric acid modified polyoxometalate molecularly imprinted polymer for biocatalytic degradation of phenol in wastewater: Optimized immobilization, degradation and toxicity assessment.

The degradation of phenol from wastewater is crucial for environmental protection. Biological enzymes, such as horseradish peroxidase (HRP), have shown great potential in the degradation of phenol. In this research, we prepared a hollow CuO/Cu2O octahedron adsorbent with a carambola matrix shape through the hydrothermal method. The surface of the adsorbent was modified by silane emulsion self-assembly, where 3-aminophenyl boric acid (APBA) and polyoxometalate (PW9) were combined with silanization reagents and grafted onto the surface. The adsorbent was then molecularly imprinted with dopamine to obtain boric acid modified polyoxometalate molecularly imprinted polymer (Cu@B@PW9@MIPs). This adsorbent was used to immobilize HRP, which served as a biological enzyme catalyst from horseradish. The adsorbent was characterized, and its synthetic conditions, experimental conditions, selectivity, reproducibility, and reusability were evaluated. The maximum adsorption amount of HRP under optimized conditions was 159.1 mg g-1, as determined using high-performance liquid chromatography (HPLC). At pH 7.0, the immobilized enzyme showed a high efficiency of up to 90.0% in removing phenol, after 20 min of reaction with 25 mmol L-1 H2O2 and 0.20 mg mL-1 Cu@B@PW9@HRP. Growth tests of aquatic plants confirmed that the adsorbent reduced harm. Gas chromatography-mass spectrometry (GC-MS) tests revealed that the degraded phenol solution contained about fifteen phenol derivatives intermediates. This adsorbent has the potential to become a promising biological enzyme catalyst for dephenolization.

QuEChERS-Based Approach to the Extraction of Five Calcium Channel Blockers from Plasma Determined by UPLC-MS/MS.

Here, a QuEChERS (quick, easy, cheap, effective, rugged, and safe) pretreatment method was combined with UPLC-MS/MS to facilitate the rapid and reliable simultaneous detection of five calcium channel blockers (CCBs) in human plasma. For this approach, samples were treated with 1 mL of acetonitrile, 350 mg of magnesium sulfate, and 70 mg of PSA adsorbent prior to centrifugation. Supernatants then underwent gradient elution for 8 min with an Agilent C18 column using an acetonitrile-water solution supplemented with 5 mmol⋅L-1 of ammonium acetate. This technique exhibited a good linear response in the 1-800 ng⋅mL-1 range for the analyzed drugs, with an R2≥ 0.9921, an accuracy of 87.54-113.05%, a matrix effect (ME) of 91.21-116.39%, a precision of 0.19-11.64%, and stability of no more than 10.05%. This time-saving QuEChERS reagent-based pretreatment technique thus allowed for the simultaneous and accurate detection of five CCBs in human plasma samples, providing a promising new basis for therapeutic drug monitoring in patients with hypertension.

Comprehensive economic evaluation of enhanced recovery after surgery in hepatectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is attracting extensive attention and being widely applied to reduce postoperative stress and accelerate recovery. However, the economic benefits of ERAS are less clarified at the social level. We aimed to assess the economic impact of ERAS in hepatectomy from the perspectives of patients, hospitals and society, as well as identify the approach to create the economic benefits of ERAS. METHODS: By combining the literature and national statistical data, the cost-effectiveness framework was clarified, and parameter values were determined. Cost-effectiveness analysis, cost-benefit analysis and cost-minimisation analysis were used to compare ERAS and conventional treatment from the perspectives of patients, hospitals and society. The capital flow diagram was used to analyse the change between them. RESULTS: ERAS significantly reduced the economic burden of disease on patients ($8935.02 vs $10,470.02). The hospital received an incremental benefit in ERAS (the incremental benefit cost ratio value is 1.09), and the total social cost was reduced ($5958.67 vs $6725.80). Capital flow diagram analysis demonstrated that the average daily cost per capita in the ERAS group increased ($669.51 vs $589.98), whereas the benefits depended on the reduction of hospital stay and productivity loss. CONCLUSION: The mechanism by which ERAS works is to reduce the average length of stay, thereby reducing the economic burden and productivity loss on patients and promoting the hospital bed turnover rate. Therefore, ERAS should further focus on accelerating the rehabilitation process, and more economic support (such as subsidies) should be given to hospitals to carry out ERAS.

A prospective study of serum metabolomic and lipidomic changes in myopic children and adolescents.

BACKGROUND: Myopia is a prevalent eye disorder, especially among children and adolescents in eastern Asian countries. Multiple measures have already been taken to prevent and treat myopia, including atropine and dopamine. However, the serum metabolic picture of myopia has not yet been studied as a whole and remains largely unclear. In this paper, a prospective and panoramic study was carried out to find out the whole serum metabolomic and lipidomic picture of myopia. METHODS: With untargeted mass spectrometry (MS), myopia among 211 children and adolescents was studied. The MS features were first grouped across the samples. Then, compound annotation was carried out based on these features. Finally, the metabolite features were mapped to pathways, whose biological functions in myopia were studied and discussed. RESULTS: A total of 275 metabolite features were derived from 92 aligned MS peak groups with significant fold changes, and then mapped to 33 pathways. By a comprehensive consideration of significance, fold change, importance score and appearance in different omics, 9 pathways were selected, and their biological functions were further analyzed. Among these selected pathways, 5 pathways were related with oxidative stress, a validated phenomenon during myopia development, while 5 pathways were related with dopamine receptor D2, whose molecular function in myopia treatment is not fully understood. A total of 177 metabolite features from 45 peak groups were related with the studied pathways. CONCLUSION: This prospective study shed light on the whole picture of metabolomic mechanism underlying myopia and provided guidance to further elucidation of compounds and pathways in this whole picture.

Age distribution and associated factors of cornea biomechanical parameter stress-strain index in Chinese healthy population.

BACKGROUND: To investigate the new cornea biomechanical parameter stress-strain index (SSI) in Chinese healthy people and the factors associated with SSI. METHODS: A total of 175 eyes from 175 participants were included in this study. Axial length was measured with the Lenstar LS-900. Pentacam measured curvature of the cornea and anterior chamber volume (ACV). Cornea biomechanical properties assessments were performed by corneal visualization Scheimpflug technology (Corvis ST). Student's t-test, one-way ANOVA, partial least square linear regression (PLSLR) and linear mixed effects (LME) model were used in the statistical analysis. RESULTS: The mean (±SD) SSI was 1.14 ± 0.22 (range, 0.66-1.78) in all subjects and affected by age significantly after age of 35 (P < 0.05). In LME models, SSI was significantly associated with age (ß = 0.526, P < 0.001), axial length (AL) (ß = - 0.541, P < 0.001), intraocular pressure (IOP) (ß = 0.326, P < 0.001) and steepest radius of anterior corneal curvature (RsF) (ß = 0.229, P < 0.001) but not with ACV, biomechanical corrected intraocular pressure (bIOP), flattest radius of anterior corneal curvature (RfF) or central corneal thickness (CCT) (P > 0.05 for each). CONCLUSIONS: SSI increased with age after the age of 35. In addition to age, SSI was positively correlated with RsF and IOP, while negatively correlated with AL.

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.

Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer.

The microbiota is pivotal in the pathogenesis of inflammatory bowel disease (IBD)-associated inflammation-induced colorectal cancer (CRC), yet mechanisms for these effects remain poorly characterized. Here, we demonstrate that aberrant inflammasome-induced microbiota plays a critical role in CRC development, where mice deficient in the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome feature enhanced inflammation-induced CRC formation. Intriguingly, WT mice cohoused either with inflammasome-deficient mice or with mice lacking IL-18 feature exacerbated inflammation-induced CRC compared with singly housed WT mice. Enhanced tumorigenesis is dependent on microbiota-induced chemokine (C-C motif) ligand 5 (CCL5)-driven inflammation, which in turn promotes epithelial cell proliferation through local activation of the IL-6 pathway, leading to cancer formation. Altogether, our results mechanistically link the altered microbiota with the pathogenesis of inflammation-induced CRC and suggest that in some conditions, microbiota components may transfer CRC susceptibility between individuals.

A novel self-assembling peptide with UV-responsive properties.

A novel heptapeptide comprising Ile-Gln-Ser-Pro-His-Phe-Phe (IQSPHFF) identified and found to undergo self-assembly into microparticles in solution. To understand the effects of ultraviolet (UV) irradiation on the self-assembly process, IQSPHFF solutions were exposed to the UV light of 365 nm at room temperature. This exposure was found to have a profound effect on the morphology of the self-assembled aggregates, converting the microparticles to nanorod shapes. Circular dichroism and FTIR studies indicated distinct structural differences in the arrangements of the peptide moieties before and after UV irradiation. However, Mass spectrum analysis and high performance liquid chromatography of the peptide molecules before and after UV irradiation demonstrated that the chemical structure of IQSPHFF was not changed. UV-visible spectroscopy and fluorescence spectroscopy studies showed that the absorption peak both increased after UV irradiation. Overall, our data show that the heptapeptide with UV-responsive properties.

A study of allosteric binding behaviour of a 1,3-alternate thiacalix[4]arene-based receptor using fluorescence signal.

A novel heteroditopic thiacalix[4]arene receptor L possessing 1,3-alternate conformation, which contains two pyrene moieties attached to the lower rim via urea linkages together with a crown ether moiety appended at the opposite side of the thiacalix[4]arene cavity, has been synthesized. The complexation behaviour of receptor L was studied by means of fluorescence spectra and (1)H NMR titration experiments in the presence of K(+) ions and a variety of other anions. The results suggested that receptor L can complex efficiently via the urea cavity or the crown ether moiety, and a positive/negative allosteric effect operating in receptor L was observed.

NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy.

The proinflammatory and catabolic cytokine IL-1ß has been implicated in the pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and cartilage degeneration. Although synovial macrophages are suggested to be the source of IL-1ß, the mechanism remains unclear. Ectopic deposition of hydroxyapatite (HA) crystals in joints is closely associated with OA and other arthropathies, but the precise role of HA in arthritis pathogenesis has not been clearly demonstrated. Here we show that HA crystals of a particular size and shape can stimulate robust secretion of proinflammatory cytokines IL-1ß and IL-18 from murine macrophages in a NLRP3 inflammasome-dependent manner. HA-induced inflammasome activation is dependent on potassium efflux, generation of reactive oxygen species (ROS), and lysosomal damage, but independent of cell death. Mice lacking the inflammasome components are protected against HA-induced neutrophilic inflammation in the air-pouch model of synovitis, and they show decreased joint pathology accompanying spontaneous HA deposition in the ank-deficient mouse model of arthritis. Moreover, calcium crystal positive synovial fluids from some OA patients exhibited inflammasome-stimulatory activity in vitro. These results demonstrate that the NLRP3 inflammasome mediates the pathological effect of HA crystals in vitro and in vivo and suggest a critical role for the inflammasome in the pathogenesis of OA.

Innate sensors of pathogen and stress: linking inflammation to obesity.

Pathogen and nutrient response pathways are evolutionarily conserved and highly integrated to regulate metabolic and immune homeostasis. Excessive nutrients can be sensed by innate pattern recognition receptors as danger signals either directly or through production of endogenous ligands or modulation of intestinal microbiota. This triggers the activation of downstream inflammatory cascades involving nuclear factor κB and mitogen-activated protein kinase and ultimately induces the production of inflammatory cytokines and immune cell infiltration in various metabolic tissues. The chronic low-grade inflammation in the brain, islet, liver, muscle, and adipose tissue further promotes insulin resistance, energy imbalance, and impaired glucose/lipid metabolism, contributing to the metabolic complications of obesity, such as diabetes and atherosclerosis. In addition, innate pathogen receptors have now emerged as a critical link between the intestinal microbiota and host metabolism. In this review we summarize recent studies demonstrating the important roles of innate pathogen receptors, including Toll-like receptors, nucleotide oligomerization domain containing proteins, and inflammasomes in mediating the inflammatory response to metabolic stress in different tissues and highlight the interaction of innate pattern recognition receptors, gut microbiota, and nutrients during the development of obesity and related metabolic disorders.

Molecularly imprinted electrochemical sensor based on CoNi-MOF/RGO nanocomposites for sensitive detection of the hippuric acid.

Toluene, a volatile organic compound, may have adverse effects on the nervous and digestive system when inhaled over an extended period. The assessment of environmental toluene exposure can be effectively conducted by detecting hippuric acid (HA), a toluene metabolite. In this investigation, a molecularly imprinted electrochemical sensor was developed for HA detection, utilizing the synergistic effects of reduced graphene oxide (RGO) and a bimetallic organic skeleton known as CoNi-MOF. Initially, graphene oxide (GO) was synthesized using a modified Hummers' method, and RGO with better conductivity was achieved through reduction with ascorbic acid (AA). Subsequently, CoNi-MOF was introduced to enhance the material's electron transport capabilities further. The molecularly imprinted membrane was then prepared via electropolymerization to enable selective HA recognition. Under optimal conditions, the synthesized sensor exhibited accurate HA detection within a concentration range of 2-800 nM, with a detection limit of 0.97 nM. The sensor's selectivity was assessed using a selectivity coefficient, yielding an imprinting factor of 6.53. The method was successfully applied to the quantification of HA in urine, demonstrating a favorable recovery rate of 93.4%-103.9%. In conclusion, this study presents a practical platform for the detection of human metabolite detection.

Change in three-dimensional choroidal vessel network after AR device assisted 1-hour visual task in 2D/3D mode in young healthy subjects.

PURPOSE: The purpose of the study was to investigate the changes of choroidal blood perfusion in different layers and quadrants and its possible related factors after 1 h visual task by augmented reality (AR) device in two-dimensional (2D) and three-dimensional (3D) mode, respectively. METHODS: Thirty healthy subjects aged 22-37 years watched the same video source in 2D and 3D mode separately using AR glasses for 1 h with a one-week interval. Swept-source optical coherence tomography angiography (SS-OCTA) was performed before and immediately after watching to acquire choroidal thickness (ChT), three-dimensional choroidal vascularity index (CVI) of large- and middle-sized choroidal vessels and choriocapillaris flow voids (FV%) at macular and peripapillary area. Near point of accommodation (NPA) and accommodative facility (AF) were examined to evaluate the accommodative ability. Pupil diameters by infrared-automated pupillometer under scotopic, mesopic and photopic condition were also obtained. RESULTS: Compared with pre-visual task, the subfoveal CVI decreased from 0.406 ± 0.097 to 0.360 ± 0.102 after 2D watching (p < 0.001) and to 0.368 ± 0.102 after 3D watching (p = 0.002). Pupil sizes under different illuminance conditions became smaller after both 2D and 3D watching (all p < 0.001). AF increased after both 2D and 3D watching (both p < 0.05). NPA receded in post-3D watching (p = 0.017) while a not significant tendency was observed in post-2D. CONCLUSION: A reduction in subfoveal choroidal blood flow accompanied with pupil constriction was observed immediately after 1 h visual task using AR glasses in 2D and 3D mode. Accommodative facility improved after 2D and 3D watching with AR glasses, whereas decrease in the maximum accommodation power was only found in 3D mode.

Tri-substituted hexahomotrioxacalix[3]arene derivatives bearing imidazole units: synthesis and extraction properties for cations and chromate anions.

The article describes the synthesis and extraction properties of the new hexahomotrioxacalix[3]arenebased derivatives cone- and partial-cone-2 bearing 1-methyl-1H-imidazole moieties at the lower rim. It has been demonstrated that O-alkylation of the flexible macrocycle 1 with 2-(chloromethyl)-1-methyl-1Himidazole hydrochloride affords tri-O-alkylated products with a cone or partial-cone conformation. Alkali metal salts such as NaH and Cs2CO3 can play an important role in the conformer distribution via a template effect. The conformation of receptors 2 has been confirmed by X-ray crystallographic analysis. Furthermore, the complexation properties of receptors 2 toward selected alkali/transition metal cations and alkylammonium ions are reported. The new 1-methyl-1H-imidazole-substituted hexahomotrioxacalix[3] arene frameworks are also efficient extractors of HCr2O7(-)/Cr2O7(2-) anions at low pH.

Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4.

Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association is currently unknown. The inflammasome, a multiprotein complex formed by NOD-like receptor (NLR) family members, has recently been shown to orchestrate multiple innate and adaptive immune responses, yet its potential role in inflammation-induced cancer has been little studied. Using the azoxymethane and dextran sodium sulfate colitis-associated colorectal cancer model, we show that caspase-1-deficient (Casp1(-/-)) mice have enhanced tumor formation. Surprisingly, the role of caspase-1 in tumorigenesis was not through regulation of colonic inflammation, but rather through regulation of colonic epithelial cell proliferation and apoptosis. Consequently, caspase-1-deficient mice demonstrate increased colonic epithelial cell proliferation in early stages of injury-induced tumor formation and reduced apoptosis in advanced tumors. We suggest a model in which the NLRC4 inflammasome is central to colonic inflammation-induced tumor formation through regulation of epithelial cell response to injury.

Determination of five mTOR inhibitors in human plasma for hepatocellular carcinoma treatment using QuEChERS-UHPLC-MS/MS.

A fast and reliable QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method for pre-processing combined with Ultra - high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS) was established for the analysis of five mammalian rapamycin target protein (mTOR) inhibitors (vistusertib, AZD8055, pictilisib, everolimus, temsirolimus)in human plasma. Extraction was achieved by addition of acetonitrile to the sample followed by anhydrous magnesium sulfate and 30 mg C18 for salting out and purification, respectively. MTOR inhibitors were detected using selective response monitoring (SRM) under positive ion electrospray mode. Vistusertib, AZD8055 and pictilisib showed good linearity with a range of 1-80 ng/ml, Additionally, the concentration of everolimus and temsirolimus was 2.5-200 ng/ml and10-800 ng/ml, respectively. The linear correlation coefficient (R2) of each analysis was ≥ 0.9950. The limit of detection (LOD) and Limit of Quantitation (LOQ) were 0.015-0.75 ng/ml and 1-10 ng/ml, respectively. This method showed a high accuracy with high recovery rate and excellent stability. This method is fast, accurate and reliable, suitable for quantitative detection of mTOR inhibitors in human plasma.

Determination of nine cardiovascular drugs in human plasma by QuEChERS-UPLC-MS/MS.

To determine the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma through QuEChERS pre-treatment combined with ultra-performance liquid chromatography-tandem mass spectrometry. Plasma samples were extracted with 3 mL of acetonitrile, 400 mg of anhydrous magnesium sulfate as a salting agent, and 20 mg of C18 as a sorbent. An Agilent Poroshell 120 EC-C18 column (4.6 × 100 mm, 2.7 µm) was selected and methanol-0.1 % water was used as the mobile phase, and ESI positive ion detection mode was selected. Results: The plasma concentrations of nisoldipine, metoprolol, and prazosin exhibited good linearity within the range of 0.05-4.0 ng/mL (r > 0.99), while atenolol, bisoprolol, propranolol, rosuvastatin, and atorvastatin showed linearity within the range of 0.5-40 ng/mL (r > 0.99). Fluvastatin showed good linearity within the range of 5.0-400 ng/mL. The accuracy of the method ranged from 94.15 to 110.62 %, while the recovery levels were in the range of 85.23 %-115.13 %. The matrix effects were observed between-6.54 % and 12.43 %. The intra-day and inter-day RSD was <15 % for the three concentrations of low, medium, and high. Conclusion The proposed method is rapid, accurate, specific, simple, reproducible, and suitable for the simultaneous measurement of the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma.

The Impact of Corneal Epithelial Thickening and Inhomogeneity on Corneal Aberrations After Small Incision Lenticule Extraction.

PURPOSE: To investigate the corneal epithelial remodeling profile after small incision lenticule extraction (SMILE), the correlated explanatory variables, and its potential impact on corneal higher order aberrations (HOAs). METHODS: This single-center study prospectively evaluated 75 right eyes of 75 patients scheduled for SMILE. An anterior segment optical coherence tomography device was used to automatically obtain central 6-mm corneal epithelial thickness (ET), total corneal HOAs, and individual Zernike components before and after surgery. The ET inhomogeneity over the central 3- and 6-mm cornea was quantified with coefficient of variance (CV). RESULTS: Both ET and CV significantly increased 1 month postoperatively (all P < .05). The stepwise multiple regression analysis showed that ET and CV were significantly correlated with preoperative ET and CV, respectively (all P < .01). The corrected spherical equivalent also significantly influenced ET and CV (all P < .01). Over the central 6-mm zone, the alterations of total corneal HOAs and individual Zernike components such as vertical coma (Z7) and spherical aberration (Z12, Z24) were significantly correlated with ET and CV (all P < .05). CONCLUSIONS: The SMILE-induced epithelial remodeling involved both ET and ET inhomogeneity. The modulation was associated with preoperative and treatment parameters, and exerted a significant impact on corneal HOA alterations especially over the central 6-mm cornea. Together with the amount of correction and corneal curvature gradient change, preoperative assessment of ET and ET inhomogeneity might help predict postoperative epithelial remodeling. [J Refract Surg. 2023;39(1):23-32.].