SNX10-mediated LPS sensing causes intestinal barrier dysfunction via a caspase-5-dependent signaling cascade.

Altered intestinal microbial composition promotes intestinal barrier dysfunction and triggers the initiation and recurrence of inflammatory bowel disease (IBD). Current treatments for IBD are focused on control of inflammation rather than on maintaining intestinal epithelial barrier function. Here, we show that the internalization of Gram-negative bacterial outer membrane vesicles (OMVs) in human intestinal epithelial cells promotes recruitment of caspase-5 and PIKfyve to early endosomal membranes via sorting nexin 10 (SNX10), resulting in LPS release from OMVs into the cytosol. Caspase-5 activated by cytosolic LPS leads to Lyn phosphorylation, which in turn promotes nuclear translocalization of Snail/Slug, downregulation of E-cadherin expression, and intestinal barrier dysfunction. SNX10 deletion or treatment with DC-SX029, a novel SNX10 inhibitor, rescues OMV-induced intestinal barrier dysfunction and ameliorates colitis in mice by blocking cytosolic LPS release, caspase-5 activation, and downstream signaling. Our results show that targeting SNX10 may be a new therapeutic approach for restoring intestinal epithelial barrier function and promising strategy for IBD treatment.

Rapid pulmonary 129Xe ventilation MRI of discharged COVID-19 patients with zigzag sampling.

PURPOSE: To demonstrate the feasibility of zigzag sampling for 3D rapid hyperpolarized 129Xe ventilation MRI in human. METHODS: Zigzag sampling in one direction was combined with gradient-recalled echo sequence (GRE-zigzag-Y) to acquire hyperpolarized 129Xe ventilation images. Image quality was compared with a balanced SSFP (bSSFP) sequence with the same spatial resolution for 12 healthy volunteers (HVs). For another 8 HVs and 9 discharged coronavirus disease 2019 subjects, isotropic resolution 129Xe ventilation images were acquired using zigzag sampling in two directions through GRE-zigzag-YZ. 129Xe ventilation defect percent (VDP) was quantified for GRE-zigzag-YZ and bSSFP acquisitions. Relationships and agreement between these VDP measurements were evaluated using Pearson correlation coefficient (r) and Bland-Altman analysis. RESULTS: For 12 HVs, GRE-zigzag-Y and bSSFP required 2.2 s and 10.5 s, respectively, to acquire 129Xe images with a spatial resolution of 3.96 × 3.96 × 10.5 mm3. Structural similarity index, mean absolute error, and Dice similarity coefficient between the two sets of images and ventilated lung regions were 0.85 ± 0.03, 0.0015 ± 0.0001, and 0.91 ± 0.02, respectively. For another 8 HVs and 9 coronavirus disease 2019 subjects, 129Xe images with a nominal spatial resolution of 2.5 × 2.5 × 2.5 mm3 were acquired within 5.5 s per subject using GRE-zigzag-YZ. VDP provided by GRE-zigzag-YZ was strongly correlated (R2 = 0.93, p < 0.0001) with that generated by bSSFP with minimal biases (bias = -0.005%, 95% limit-of-agreement = [-0.414%, 0.424%]). CONCLUSION: Zigzag sampling combined with GRE sequence provides a way for rapid 129Xe ventilation imaging.

Dynamic evaluation of acute lung injury using hyperpolarized 129 Xe magnetic resonance.

Prognosticating acute lung injury (ALI) is challenging, in part because of a lack of sensitive biomarkers. Hyperpolarized gas magnetic resonance (MR) has unique advantages in pulmonary function measurement and can provide promising biomarkers for the assessment of lung injuries. Herein, we employ hyperpolarized 129 Xe MRI and generate a number of imaging biomarkers to detect the pulmonary physiological and morphological changes during the progression of ALI in an animal model. We find the measured ratio of 129 Xe in red blood cells to interstitial tissue/plasma (RBC/TP) is significantly lower in the ALI group on the second (0.32 ± 0.03, p = 0.004), seventh (0.23 ± 0.03, p < 0.001), and 14th (0.29 ± 0.04, p = 0.001) day after lipopolysaccharide treatment compared with that in the control group (0.41 ± 0.04). In addition, significant differences are also observed for RBC/TP measurements between the second and seventh day (p = 0.001) and between the seventh and 14th day (p = 0.018) in the ALI group after treatment. Besides RBC/TP, significant differences are also observed in the measured exchange time constant (T) on the second (p = 0.038) and seventh day (p = 0.009) and in the measured apparent diffusion coefficient (ADC) and alveolar surface-to-volume ratio (SVR) on the 14th day (ADC: p = 0.009 and SVR: p = 0.019) after treatment in the ALI group compared with that in the control group. These findings indicate that the parameters measured with 129 Xe MR can detect the dynamic changes in pulmonary structure and function in an ALI animal model.

Assessment of Global and Regional Lung Compliance in Pulmonary Fibrosis With Hyperpolarized Gas MRI.

BACKGROUND: Lung compliance, a biomarker of pulmonary fibrosis, is generally measured globally. Hyperpolarized 129Xe gas MRI offers the potential to evaluate lung compliance regionally, allowing for visualization of changes in lung compliance associated with fibrosis. PURPOSE: To assess global and regional lung compliance in a rat model of pulmonary fibrosis using hyperpolarized 129Xe gas MRI. STUDY TYPE: Prospective. ANIMAL MODEL: Twenty Sprague-Dawley male rats with bleomycin-induced fibrosis model (N = 10) and saline-treated controls (N = 10). FIELD STRENGTH/SEQUENCE: 7-T, fast low-angle shot (FLASH) sequence. ASSESSMENT: Lung compliance was determined by fitting lung volumes derived from segmented 129Xe MRI with an iterative selection method, to corresponding airway pressures. Similarly, lung compliance was obtained with computed tomography for cross-validation. Direction-dependencies of lung compliance were characterized by regional lung compliance ratios (R) in different directions. Pulmonary function tests (PFTs) and histological analysis were used to validate the pulmonary fibrosis model and assess its correlation with 129Xe lung compliance. STATISTICAL TESTS: Shapiro-Wilk tests, unpaired and paired t-tests, Mann-Whitney U and Wilcoxon signed-rank tests, and Pearson correlation coefficients. P < 0.05 was considered statistically significant. RESULTS: For the entire lung, the global and regional lung compliance measured with 129Xe gas MRI showed significant differences between the groups, and correlated with the global lung compliance measured using PFTs (global: r = 0.891; regional: r = 0.873). Additionally, for the control group, significant difference was found in mean regional compliance between areas, eg, 0.37 (0.32, 0.39) × 10-4 mL/cm H2O and 0.47 (0.41, 0.56) × 10-4 mL/cm H2O for apical and basal lung, respectively. The apical-basal direction R was 1.12 ± 0.09 and 1.35 ± 0.13 for fibrosis and control groups, respectively, indicating a significant difference. DATA CONCLUSION: Our findings demonstrate the feasibility of using hyperpolarized gas MRI to assess regional lung compliance. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Wireless Multimodal Light-Emitting Arrays Operating on the Principles of LEDs and ECL.

Electrochemistry-based light-emitting devices have gained considerable attention in different applications such as sensing and optical imaging. In particular, such systems are an interesting alternative for the development of multimodal light-emitting platforms. Herein we designed a multicolor light-emitting array, based on the electrochemical switch-on of light-emitting diodes (LEDs) with a different intrinsic threshold voltage. Thermodynamically and kinetically favored coupled redox reactions, i. e. the oxidation of Mg and the reduction of protons on Pt, act as driving force to power the diodes. Moreover, this system enables to trigger an additional light emission based on the interfacial reductive-oxidation electrochemiluminescence (ECL) mechanism of the Ru(bpy)3 2+/S2O8 2- system. The synergy between these light-emission pathways offers a multimodal platform for the straightforward optical readout of physico-chemical information based on composition changes of the solution.

Assessment of pulmonary physiological changes caused by aging, cigarette smoking, and COPD with hyperpolarized 129Xe magnetic resonance.

OBJECTIVE: To comprehensively assess the impact of aging, cigarette smoking, and chronic obstructive pulmonary disease (COPD) on pulmonary physiology using 129Xe MR. METHODS: A total of 90 subjects were categorized into four groups, including healthy young (HY, n = 20), age-matched control (AMC, n = 20), asymptomatic smokers (AS, n = 28), and COPD patients (n = 22). 129Xe MR was utilized to obtain pulmonary physiological parameters, including ventilation defect percent (VDP), alveolar sleeve depth (h), apparent diffusion coefficient (ADC), total septal wall thickness (d), and ratio of xenon signal from red blood cells and interstitial tissue/plasma (RBC/TP). RESULTS: Significant differences were found in the measured VDP (p = 0.035), h (p = 0.003), and RBC/TP (p = 0.003) between the HY and AMC groups. Compared with the AMC group, higher VDP (p = 0.020) and d (p = 0.048) were found in the AS group; higher VDP (p < 0.001), d (p < 0.001) and ADC (p < 0.001), and lower h (p < 0.001) and RBC/TP (p < 0.001) were found in the COPD group. Moreover, significant differences were also found in the measured VDP (p < 0.001), h (p < 0.001), ADC (p < 0.001), d (p = 0.008), and RBC/TP (p = 0.032) between the AS and COPD groups. CONCLUSION: Our findings indicate that pulmonary structure and functional changes caused by aging, cigarette smoking, and COPD are various, and show a progressive deterioration with the accumulation of these risk factors, including cigarette smoking and COPD. CLINICAL RELEVANCE STATEMENT: Pathophysiological changes can be difficult to comprehensively understand due to limitations in common techniques and multifactorial etiologies. 129Xe MRI can demonstrate structural and functional changes caused by several common factors and can be used to better understand patients' underlying pathology. KEY POINTS: Standard techniques for assessing pathophysiological lung function changes, spirometry, and chest CT come with limitations. 129Xe MR demonstrated progressive deterioration with accumulation of the investigated risk factors, without these limitations. 129Xe MR can assess lung changes related to these risk factors to stage and evaluate the etiology of the disease.

Enhancing Inverted Internal Limiting Membrane Flap Stability in Macular Hole Retinal Detachment by the "Viscoelastic Agent Pool" Technique.

PURPOSE: To evaluate the surgical, anatomical, and functional results of "viscoelastic agent pool" technique-assisted stability of inverted internal limiting membrane flap in macular hole retinal detachment. METHODS: The innovative surgical technique was performed on 10 patients with macular hole retinal detachment. The primary outcomes included best-corrected visual acuity after surgery, rate of closure of macular hole, retinal reattachment, and occurrence of complications. RESULTS: The mean age of the individuals was 67.70 ± 8.75 (range, 55-84) years; mean axial length, 29.34 ± 1.53 (range, 27.10-30.93) mm; mean corrected MH diameter, 685.30± 345.65 (range, 172-1,325) µ m; and average follow-up period, 6.01 ± 1.71 (range, 3.10-8.4) months. In 6 eyes (60%), the postoperative best-corrected visual acuity showed improvement. All patients had macular hole closure, and the retinal reattachment rate was 100%. No postoperative complications were noted. CONCLUSION: The "viscoelastic agent pool" technique, an innovative surgical approach designed to enhance the stability of the internal limiting membrane flap, serves as an effective adjunctive procedure for the inverted internal limiting membrane flap technique. It presents a viable option for patients with macular hole retinal detachment.

The role of neutrophil extracellular traps in ß-methylamino L-alanine-induced liver injury in mice.

The non-protein amino acid ß-N-methylamino-L-alanine (BMAA), produced by cyanobacteria, has been recognized as a neurotoxin. L-serine as an antagonist of BMAA can effectively alleviate BMAA-induced neurotoxicity. Although BMAA has long been emphasized as a neurotoxin, with the emergence of BMAA detected in a variety of algae in freshwater around the world and its clear biological enrichment effect, it is particularly important to study the non-neurotoxic adverse effects of BMAA. However, there is only limited evidence to support the ability of BMAA to cause oxidative damage in the liver. The exact molecular mechanism of BMAA-induced liver injury is still unclear. The formation of neutrophil extracellular traps (NETs) is a 'double-edged sword' for the organism, excessive formation of NETs is associated with inflammatory diseases of the liver. Our results innovatively confirmed that BMAA was able to cause the formation of NETs in the liver during the liver injury. The possible mechanism may associated with the regulation of ERK/p38 and cGAS/STING signaling pathways. The massive formation of NETs was able to exacerbate the BMAA-induced oxidative stress and release of inflammatory factors in the mice liver. And the removal of NETs could alleviate this injury. This article will bring a new laboratory evidence for BMAA-induced non-neurotoxicity and immunotoxicity.

Simultaneous detection of SO2 and viscosity in drug-induced inflammation in live cells and zebrafish.

The viscosity within cells is a crucial microenvironmental factor, and sulfur dioxide (SO2 ) has essential functions in regulating cellular apoptosis and inflammation. Some evidence has been confirmed that changes in viscosity and overexposure of SO2 within the cell may cause detrimental effects including, but not limited to, respiratory and cardiovascular illnesses, inflammation, fatty liver, and various types of cancer. Therefore, precise monitoring of SO2 and viscosity in biological entities holds immense practical importance. Therefore, in this research, we developed a versatile fluorescent TCF-Cou that enables the dual detection of SO2 and viscosity in the living system. Probe TCF-Cou possessed a response to viscosity and SO2 through red and green emissions. The alteration of SO2 and viscosity levels in live cells and zebrafish were also monitored using probe TCF-Cou. We hope that this fluorescent probe could be a potential tool for revealing the related pathological and physiological processes through monitoring the changes in SO2 and viscosity.

Fluorescent dyes based on rhodamine derivatives for bioimaging and therapeutics: recent progress, challenges, and prospects.

Since their inception, rhodamine dyes have been extensively applied in biotechnology as fluorescent markers or for the detection of biomolecules owing to their good optical physical properties. Accordingly, they have emerged as a powerful tool for the visualization of living systems. In addition to fluorescence bioimaging, the molecular design of rhodamine derivatives with disease therapeutic functions (e.g., cancer and bacterial infection) has recently attracted increased research attention, which is significantly important for the construction of molecular libraries for diagnostic and therapeutic integration. However, reviews focusing on integrated design strategies for rhodamine dye-based diagnosis and treatment and their wide application in disease treatment are extremely rare. In this review, first, a brief history of the development of rhodamine fluorescent dyes, the transformation of rhodamine fluorescent dyes from bioimaging to disease therapy, and the concept of optics-based diagnosis and treatment integration and its significance to human development are presented. Next, a systematic review of several excellent rhodamine-based derivatives for bioimaging, as well as for disease diagnosis and treatment, is presented. Finally, the challenges in practical integration of rhodamine-based diagnostic and treatment dyes and the future outlook of clinical translation are also discussed.

Identification of a Novel TP63 Variant in a Chinese Patient with Orofacial Clefts and Ectrodactyly: Case Report and Literature Review.

The TP63 gene is essential for epithelial proliferation, differentiation, and maintenance during embryogenesis. Despite considerable clinical variability, TP63-related symptoms are characterized by ectodermal dysplasia, distal limb malformations, and orofacial clefts. We identified a novel TP63 variant (c.619A > G, p.K207E) in a seven-month-old Chinese patient with orofacial clefts and ectrodactyly but no evident signs of ectodermal dysplasia. This phenotype was rarely reported before. We summarized the presence of the three main TP63-related manifestations in the literature and noted different distributions of CP- and CL/P-related variants regarding p63 structural domains.

Activatable Near-Infrared Versatile Fluorescent and Chemiluminescent Dyes Based on the Dicyanomethylene-4H-pyran Scaffold: From Design to Imaging and Theranostics.

Activatable fluorescent and chemiluminescent dyes with near-infrared emission have indispensable roles in the fields of bioimaging, molecular prodrugs, and phototheranostic agents. As one of the most popular fluorophore scaffolds, the dicyanomethylene-4H-pyran scaffold has been applied to fabricate a large number of versatile activatable optical dyes for analytes detection and diseases diagnosis and treatment by virtue of its high photostability, large Stokes shift, considerable two-photon absorption cross-section, and structural modifiability. This review discusses the molecular design strategies, recognition mechanisms, and both in vitro and in vivo bio-applications (especially for diagnosis and therapy of tumors) of activatable dicyanomethylene-4H-pyran dyes. The final section describes the current shortcomings and future development prospects of this topic.

An ER-targeted, Viscosity-sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway.

The concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend of modern medical advancement. Herein, we rationally designed the smart molecule ER-ZS for endoplasmic reticulum (ER)-targeted diagnosis and treatment in cell and animal models by combining hemicyanine dyes with ER-targeted functional groups (p-toluenesulfonamide). Owing to its ability to target the ER with a highly specific response to viscosity, ER-ZS demonstrated substantial fluorescence turn-on only after binding to the ER, independent of other physiological environments. In addition, ER-ZS, being a small molecule, allows for the diagnosis of nonalcoholic fatty liver disease (NAFLD) via liver imaging based on high ER stress. Importantly, ER-ZS is a type I photosensitizer, producing O2 ⋅- and ⋅OH under light irradiation. Thus, after irradiating for a certain period, the photodynamic therapy inflicted severe oxidative damage to the ER of tumor cells in hypoxic (2 % O2 ) conditions and activated the unique pyroptosis pathway, demonstrating excellent antitumor capacity in xenograft tumor models. Hence, the proposed strategy will likely shed new light on integrating molecular optics for NAFLD diagnosis and cancer therapy.

Disentangling spatiotemporal dynamics in metacommunities through a species-patch network approach.

Colonization and extinction at local and regional scales, and gains and losses of patches are important processes in the spatiotemporal dynamics of metacommunities. However, analytical challenges remain in quantifying such spatiotemporal dynamics when species extinction-colonization and patch gain and loss processes act simultaneously. Recent advances in network analysis show great potential in disentangling the roles of colonization, extinction, and patch dynamics in metacommunities. Here, we developed a species-patch network approach to quantify metacommunity dynamics including (i) temporal changes in network structure, and (ii) temporal beta diversity of species-patch links and its components that reflect species extinction-colonization and patch gain and loss. Application of the methods to simulated datasets demonstrated that the approach was informative about metacommunity assembly processes. Based on three empirical datasets, our species-patch network approach provided additional information about metacommunity dynamics through distinguishing the effects of species colonization and extinction at different scales from patch gains and losses and how specific environmental factors related to species-patch network structure. In conclusion, our species-patch network framework provides effective methods for monitoring and revealing long-term metacommunity dynamics by quantifying gains and losses of both species and patches under local and global environmental change.

Engineered and Durable Antimicrobial Polymer via Controllable Immobilization of Ionic Liquids onto the Poly(lactic acid) Chains.

Nowadays, the development of effective modification methods for PLA has gained significant interest because of the wide application of antimicrobial PLA materials in the medical progress. Herein, the ionic liquid (IL) 1-vinyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide, has been grafted onto the PLA chains successfully in the PLA/IL blending films via electron beam (EB) radiation for the miscibility between PLA and IL. It was found that the existence of IL in the PLA matrix can significantly improve the chemical stability under EB radiation. The Mn of PLA-g-IL copolymer did not change obviously but was just decreased from 6.80 × 104 g/mol to 5.20 × 104 g/mol after radiation with 10 kGy. The obtained PLA-g-IL copolymers showed excellent filament forming property during electrospinning process. The spindle structure on the nanofibers can be completely eliminated after feeding only 0.5 wt % ILs for the improvement of ionic conductivity. Specially, the prepared PLA-g-IL nonwovens exhibited outstanding and durable antimicrobial activity for the enrichment of immobilized ILs on the nanofiber surface. This work provides a feasible strategy to realize the modification of functional ILs onto PLA chains with low EB radiation doses, which may have huge potential application in the medical and packaging industry.

Two similar carbon monoxide poisoning cases with different outcomes: evidence from longitudinal fMRI.

Prognosis after carbon monoxide (CO) poisoning is difficult to assess using structural images. Functional connectivity provided by functional magnetic resonance imaging (fMRI) may explain the mechanism of differential prognosis. We report here two cases of carbon monoxide poisoning with simultaneous coma. They were nearly normal on days 7-8, but diagnosed with delayed neurological sequelae (DNS) with cognitive and motor impairments on days 22-29. Similar Methylprednisolone pulse therapy and hyperbaric oxygen therapy were given to them. The movement disorder of case 1 improved slightly during the recovery stage, while the movement disorder of case 2 worsened significantly. In case 1, the function of supplementary motor area decreased first and then increased, and the function of pallidum increased first and then decreased. Case 2 showed a reduction in the supplementary motor area and small changes in the pallidum after DNS, but both were reduced during recovery stage. The cognitive ability of case 1 remained poor, while that of case 2 improved during the recovery stage. FMRI showed damage to the right and bilateral hippocampus in case 1 and partial damage to the left hippocampus in case 2. Taken together, fMRI can be a useful method to study functional connectivity abnormalities corresponding to different prognoses.

PATHOLOGIC STUDY OF UNTREATED INTRARETINAL GLIOSIS SURGICALLY EXCISED VIA PARS PLANA VITRECTOMY.

PURPOSE: To evaluate the pathologic process of intraretinal glioses by investigating mass tissues resected from untreated eyes with intraretinal glioses. METHODS: Five patients with intraretinal gliosis without previous conservative treatment were included. All patients underwent pars plana vitrectomy. The mass tissues were excised and processed for the pathologic study. RESULTS: During surgery, it was observed that the intraretinal gliosis mainly affected the neuroretina and the retinal pigment epithelium was not affected. Pathologic examination revealed that all intraretinal glioses consisted of different proportions of hyaline vessels and hyperplastic spindle-shaped glial cells. In one case, the intraretinal gliosis was mainly composed of hyaline vascular components. In another case, the intraretinal gliosis showed a predominance of glial cells. The intraretinal glioses in the other three cases had vascular and glial components. The proliferated vessels showed different amounts of collagen deposits against different backgrounds. Vascularized epiretinal membrane was found in some intraretinal glioses. CONCLUSION: Intraretinal glioses affected the inner retinal layer. Hyaline vessels were the most characteristic pathologic changes; the proportion of proliferative glial cells varied in different intraretinal glioses. The natural course of intraretinal gliosis may involve the proliferation of abnormal vessels in the early stage, which then gradually become scarred and are replaced by glial cells.

Establishment of a Three-Dimensional Finite Element Model and Mechanical Analysis of the Upper Lip Flap With Secondary Cleft Lip Deformity.

Cleft lip secondary deformity is a common oral and maxillofacial deformity, usually accompanied by the upper lip and nasal cleft. The main treatment method for cleft lip secondary deformity is surgical repair. Among them, upper lip flap repair is a common method; the principle is to transplant the healthy tissue to the lesion site to achieve the purpose of repair. However, during the surgical process, each key point's stress distribution and strain conditions are quite different. Therefore, special attention should be paid to the mechanical properties of each key point during the repair operation to ensure the surgical effect. This paper aims to establish a 3-dimensional finite element model and perform finite element analysis to simulate the mechanical properties and key point displacement of the upper lip flap repair operation for cleft lip secondary deformity to improve the operation's success rate and safety.

Autologous Costal Cartilage With Expanded Polytetrafluorethylene (ePTFE) Implants for the Treatment of Nasal Deformity After Unilateral Cleft Lip Repair.

OBJECTIVE: To repair and reconstruct the secondary nasal deformity after unilateral cleft lip repair, we used autologous costal cartilage and expanded polytetrafluorethylene (ePTFE) to get a better nasal shape. METHOD: Nineteen patients with nasal deformity after unilateral cleft lip repair were treated from July 2018 to July 2021. During the operation, autologous costal cartilage was carved and formed and then implanted into the nasal tip and nasal columella, while the back of the nose was raised with ePTFE. RESULT: Nineteen cases were followed up for 6 to 30 months. No transplanted cartilage and swelling were exposed or discharged. The appearance was good, and the patients were satisfied. CONCLUSION: Autologous costal cartilage combined with ePTFE is an ideal treatment for nasal deformity after cleft lip repair.

A Novel Neurovascular Protection Method In Nasolabial Muscle Biomechanical Bionic Surgery For Secondary Unilateral Cleft Lip Repair: A Three-Dimensional Evaluation Of Short And Long-Term Results.

BACKGROUND: Neurovascular protection within the upper lip muscles is essential in muscle tension reconstruction and functional recovery during surgery. This study aimed to investigate a novel neurovascular protection method based on the intramuscular neurovascular partitions of the upper lip applied to nasolabial muscle biomechanical bionic surgery for secondary unilateral cleft lip repair and to evaluate postoperative outcomes. METHODS: From November 30, 2019 to October 31, 2020, 50 consecutive patients with secondary unilateral cleft lips who underwent the modified biomechanical bionic surgery were reviewed retrospectively. Three-dimensional (3D) photographs of patients were collected preoperatively, 7-day postoperatively, and during long-term follow-up (at least 6 months). The Global Aesthetic Improvement Scale was used to evaluate surgical subjective outcomes, and statistical analysis of nasolabial measurements on 3D photographs was used to evaluate objective outcomes before and after surgery. RESULTS: The Global Aesthetic Improvement Scale showed that 94% of patients had improved upper lip morphology and 92% had improved nasal morphology 7-day postoperatively. In all, 84% maintained favorable nasolabial morphology during long-term follow-up. Statistical results showed that the postoperative alar width, philtral depth, columellar angle, and nasal base inclination angle were significantly improved compared with preoperatively (P<0.01). The differences between the above 4 indexes were not statistically significant (P >0.05) between 7-day postoperatively and long-term follow-up, indicating that the postoperative lasting outcomes were satisfactory. CONCLUSIONS: The novel method of neurovascular protection in nasolabial muscle biomechanical bionic surgery can achieve a long-term improvement of labial-nasal morphology and function in patients with secondary unilateral cleft lip.