Phenotypes and Lung Microbiota Signatures of Immunocompromised Patients with Pneumonia-Related Acute Respiratory Distress Syndrome.

Objective: We aim to identify the clinical phenotypes of immunocompromised patients with pneumonia-related ARDS, to investigate the lung microbiota signatures and the outcomes of different phenotypes, and finally, to develop a machine learning classifier for a specified phenotype. Methods: This prospective study included immunocompromised patients with pneumonia-related ARDS. We identified phenotypes using hierarchical clustering to analyze clinical variables and serum cytokine levels. We then compared outcomes and lung microbiota signatures between phenotypes. Based on lung microbiota markers, we developed a random forest classifier for a specified phenotype with worse outcomes. Results: This study included 92 patients, who were divided into three phenotypes, namely "type α" (N = 33), "type ß" (N = 12), and "type γ" (N = 47). Compared to type α or type ß, patients with type γ had no obvious inflammatory presentation and had significantly lower IL-6 levels and more severe oxygenation failure. Type γ was also related to higher 30-day mortality and lower ventilator free days. The microbiota signatures of type γ were characterized by lower alpha diversity and distinct compositions than those of other patients. We developed a lung microbiota-derived random forest model to differentiate patients with type γ from other phenotypes. Conclusion: Immunocompromised patients with pneumonia-related ARDS can be clustered into three clinical phenotypes, namely type α, type ß, and type γ. Phenotypes were distinguished from each other with different outcomes and lung microbiota signatures. Type γ, which was characterized by insufficient inflammation response and worse outcomes, can be detected with a random forest model based on lung microbiota markers.

CaCO3 nanoplatform for cancer treatment: drug delivery and combination therapy.

The use of nanocarriers for drug delivery has opened up exciting new possibilities in cancer treatment. Among them, calcium carbonate (CaCO3) nanocarriers have emerged as a promising platform due to their exceptional biocompatibility, biosafety, cost-effectiveness, wide availability, and pH-responsiveness. These nanocarriers can efficiently encapsulate a variety of small-molecule drugs, proteins, and nucleic acids, as well as co-encapsulate multiple drugs, providing targeted and sustained drug release with minimal side effects. However, the effectiveness of single-drug therapy using CaCO3 nanocarriers is limited by factors such as multidrug resistance, tumor metastasis, and recurrence. Combination therapy, which integrates multiple treatment modalities, offers a promising approach for tackling these challenges by enhancing efficacy, leveraging synergistic effects, optimizing therapy utilization, tailoring treatment approaches, reducing drug resistance, and minimizing side effects. CaCO3 nanocarriers can be employed for combination therapy by integrating drug therapy with photodynamic therapy, photothermal therapy, sonodynamic therapy, immunotherapy, radiation therapy, radiofrequency ablation therapy, and imaging. This review provides an overview of recent advancements in CaCO3 nanocarriers for drug delivery and combination therapy in cancer treatment over the past five years. Furthermore, insightful perspectives on future research directions and development of CaCO3 nanoparticles as nanocarriers in cancer treatment are discussed.

Secretory IgA reduced the ergosterol contents of Candida albicans to repress its hyphal growth and virulence.

Candida albicans, one of the most prevalent conditional pathogenic fungi, can cause local superficial infections and lethal systemic infections, especially in the immunocompromised population. Secretory immunoglobulin A (sIgA) is an important immune protein regulating the pathogenicity of C. albicans. However, the actions and mechanisms that sIgA exerts directly against C. albicans are still unclear. Here, we investigated that sIgA directs against C. albicans hyphal growth and virulence to oral epithelial cells. Our results indicated that sIgA significantly inhibited C. albicans hyphal growth, adhesion, and damage to oral epithelial cells compared with IgG. According to the transcriptome and RT-PCR analysis, sIgA significantly affected the ergosterol biosynthesis pathway. Furthermore, sIgA significantly reduced the ergosterol levels, while the addition of exogenous ergosterol restored C. albicans hyphal growth and adhesion to oral epithelial cells, indicating that sIgA suppressed the growth of hyphae and the pathogenicity of C. albicans by reducing its ergosterol levels. By employing the key genes mutants (erg11Δ/Δ, erg3Δ/Δ, and erg3Δ/Δ erg11Δ/Δ) from the ergosterol pathway, sIgA lost the hyphal inhibition on these mutants, while sIgA also reduced the inhibitory effects of erg11Δ/Δ and erg3Δ/Δ and lost the inhibition of erg3Δ/Δ erg11Δ/Δ on the adhesion to oral epithelial cells, further proving the hyphal repression of sIgA through the ergosterol pathway. We demonstrated for the first time that sIgA inhibited C. albicans hyphal development and virulence by affecting ergosterol biosynthesis and suggest that ergosterol is a crucial regulator of C. albicans-host cell interactions. KEY POINTS: • sIgA repressed C. albicans hyphal growth • sIgA inhibited C. albicans virulence to host cells • sIgA affected C. albicans hyphae and virulence by reducing its ergosterol levels.

Dynamic repulsive interaction enables an asymmetric electron-phonon coupling for improving Raman scattering.

Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). For ReS2, the Raman enhancement effect can be highly improved through the dipole-dipole interactions and synergistic resonance effects in the phase-engineering ReS2 films. However, the performance of the substrate can be improved further through regulating the electronic interaction between the ReS2 and probe molecules. Herein, a dynamic coulomb repulsion strategy is proposed to trigger an electronic state redistribution by asymmetric electrostatic interactions. With the phase-engineering ReS2/graphene heterostructure as a prototype, under laser excitation, the generated hot electrons in graphene and ReS2 can repel each other due to Coulomb interaction, which breaks the symmetrical distribution of hot electrons in ReS2, and increases the electronic concentration at the interface between ReS2 and the probe molecule. With R6G as the probe molecule, the asymmetric electron distribution and synergistic resonance effects on their interface improve the limit of detection to 10-12 M with an EF of 2.15 × 108. Meanwhile, the heterostructure also shows good uniformity, stability as well as unique anisotropy. This strategy can be generalized to other 2D heterostructures to obtain the ultrasensitive SERS substrates.

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems.

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.

Corrigendum: The Photorhabdus virulence cassettes RRSP-like effector interacts with cyclin-dependent kinase 1 and causes mitotic defects in mammalian cells.

[This corrects the article DOI: 10.3389/fmicb.2020.00366.].

[Role of coagulation dysfunction in thrombocytopenia-related death in patients with septic shock].

OBJECTIVE: To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death. METHODS: A retrospective case-control study was conducted. Patients with septic shock admitted to emergency intensive care unit (EICU) and intensive care unit (ICU) in Peking University People's Hospital from April 1, 2015 to January 31, 2023 were enrolled. Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group, according to whether the minimum platelet count was less than 100×109/L within 24 hours after admission to ICU. The outcome index was the mortality during ICU stay. The baseline data, hospitalization information and laboratory test results of the two groups were compared, and the risk factors of in-hospital death were analyzed by Logistic regression, and the mediation effect was performed by Bootstrap method. RESULTS: A total of 301 patients with septic shock were enrolled, of which 172 (57.1%) had thrombocytopenia and 129 (42.9%) did not. There were significant differences between the two groups in age, mortality, disseminated intravascular coagulation (DIC), continuous renal replacement therapy, and level of creatinine, urea nitrogen, total bilirubin, white blood cell count, lymphocyte count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Univariate Logistic regression analysis showed thrombocytopenia [odds ratio (OR) = 4.478], continuous renal replacement therapy (OR = 4.601), DIC (OR = 6.248), serum creatinine (OR = 1.005), urea nitrogen (OR = 1.126), total bilirubin (OR = 1.006) and PT (OR = 1.126) were risk factors of death during hospitalization in patients with septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that thrombocytopenia [OR = 3.338, 95% confidence interval (95%CI) was 1.910-5.834, P = 0.000], continuous renal replacement therapy (OR = 3.175, 95%CI was 1.576-6.395, P = 0.001) and PT (OR = 1.077, 95%CI was 1.011-1.147, P = 0.021) were independent risk factors for in-hospital mortality in patients with septic shock. Mediation analysis showed that 51% of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy. CONCLUSIONS: Thrombocytopenia is a powerful predictor of death in septic shock patients, and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.

Theoretical study of protein adsorption on graphene/h-BN heterostructures.

The biological characteristics of planar heterojunction nanomaterials and their interactions with biomolecules are crucial for the potential application of these materials in the biomedical field. This study employed molecular dynamics (MD) simulations to investigate the interactions between proteins with distinct secondary structures (a single α-helix representing the minimal oligomeric domain protein, a single ß-sheet representing the WW structural domain of the Yap65 protein, and a mixed α/ß structure representing the BBA protein) and a planar two-dimensional heterojunction (a GRA/h-BN heterojunction consisting of a graphene nanoplate (GRA) and a hexagonal boron nitride nanoplate (h-BN)). The results indicate that all three kinds of protein can be quickly and stably adsorbed on the GRA/h-BN heterojunction due to the strong van der Waals interaction, regardless of their respective types, structures and initial orientations. Moreover, the proteins exhibit a pronounced binding preference for the hBN region of the GRA/h-BN heterojunction. Upon adsorption, the α-helix structure of the minimal oligomeric domain protein experiences partial or complete denaturation. Conversely, while the secondary structure of the single ß-sheet and mixed α/ß structure (BBA protein) undergoes slight changes (focus on the coil and turn regions), the main α-helix and ß-sheet structures remain intact. The initial orientation significantly impacts the degree of protein adsorption and its position on the GRA/h-BN heterojunction. However, regardless of the initial orientation, proteins can ultimately be adsorbed onto the GRA/h-BN heterojunction. Furthermore, the initial orientation has a minor influence on the structural changes of proteins. Significantly, the combination of different secondary structures helps mitigate the denaturation of a single α-helix structure to some extent. Overall, the adsorption of proteins on GRA/h-BN is primarily driven by van der Waals and hydrophobic interactions. Proteins with ß-sheet or mixed structures exhibit stronger biocompatibility on the GRA/h-BN heterojunction. Our research elucidated the biological characteristics of GRA/h-BN heterojunction nanomaterials and their interactions with proteins possessing diverse secondary structures. It offers a theoretical foundation for considering heterojunction nanomaterials as promising candidates for biomedical applications.

Corrigendum: The Photorhabdus virulence cassettes RRSP-like effector interacts with cyclin-dependent kinase 1 and causes mitotic defects in mammalian cells.

[This corrects the article DOI: 10.3389/fmicb.2020.00366.].

The quantitative analysis of low-concentration (2%) ALA-PDT assisted with Q-switch 1064-nm Nd:YAG laser for acne vulgaris treatment.

Conventional 5-aminolevulinic acid-photodynamic (ALA-PDT) therapy (10-20%) has been widely applied for moderate-to-severe acne. The aim of this study is to investigate the effects of non-ablative Q-switched 1064-nm Nd:YAG laser-assisted ALA-PDT with low concentration (2%) on the treatment of acne vulgaris. Enrolled patients were randomly assigned to 2 groups. One group received combined therapy of 2% ALA-PDT and non-ablative Q-switched 1064-nm Nd:YAG laser, and the other received only 2% ALA-PDT. Patients in each group had received 3-session treatments with 4-week intervals (week 0, 4, and 8). Sebum secretion, melanin index, erythema index, and transepidermal water loss (TEWL) were assessed at week 2, 8, 12, and 24. VISIA® skin image system score and global esthetic improvement scale (GAIS) were also evaluated. Twenty-four participants were enrolled and evenly randomized to two groups. Significant improvement in sebum secretion was noted in combined therapy group compared to the monotherapy group at week 12 (37.5% versus 16.3%), and the improvement would still be noted until week 24 (18.3% versus 17.4%). Combined group also showed more severe melanin index and erythema index after treatment. For VISIA® skin analysis, patients in combined group had better percentile ranking in porphyrins and red-light images. There were no significant differences in GAIS at the end of the follow-up between each group, whereas higher proportion of satisfaction was noted in combined group at week 2. With the assistance of laser, low concentrations (2%) of 5-ALA can provide effective phototoxic reactions in treating acne vulgaris. The satisfaction of patients is high with acceptable adverse effects.

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development.

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging.

Nanoplastics (NPs) may pass through the blood-brain barrier, giving rise to serious concerns about their potential toxicity to the brain. In this study, the effects of NPs exposure on learning and memory, the primary cognitive functions of the brain, are assessed in zebrafish with classic T-maze exploration tasks. Additionally, to reveal potential affecting mechanisms, the impacts of NPs exposure on brain aging, oxidative damage, energy provision, and the cell cycle are evaluated. The results demonstrate that NP-exposed zebrafish takes significantly longer for their first entry and spends markedly less time in the reward zone in the T-maze task, indicating the occurrence of learning and memory deficits. Moreover, higher levels of aging markers (ß-galactosidase and lipofuscin) are detected in the brains of NP-exposed fish. Along with the accumulation of reactive free radicals, NP-exposed zebrafish suffer significant levels of brain oxidative damage. Furthermore, lower levels of Adenosine triphosphate (ATP) and cyclin-dependent kinase 2 and higher levels of p53 are observed in the brains of NP-exposed zebrafish, suggesting that NPs exposure also results in a shortage of energy supply and an arrestment of the cell cycle. These findings suggest that NPs exposure may pose a severe threat to brain health, which deserves closer attention.

Adaptability of melanocytes post ultraviolet stimulation in patients with melasma.

BACKGROUND: Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described. OBJECTIVES: To determine whether melasma lesions and nearby perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face. METHODS: We collected sequential images from real-time cellular resolution full-field optical coherence tomography (CRFF-OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer-aided detection (CADe) system that utilizes spatial compounding-based denoising convolutional neural networks. RESULTS: The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome-rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers. CONCLUSIONS: Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were "fixed" on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV-responsive perilesions rather than lesions.

Characterization of a Novel Gja8 (Cx50) Mutation in a New Cataract Rat Model.

Purpose: To describe a novel spontaneous cataract inbred strain isolated from large-scale breeding SD rats, identify the responsible gene mutation, and understand how this mutation affects lens function. Methods: Exome sequencing of 12 cataract-associated genes was performed in the affected and healthy relatives. Sequences of rat wild-type or mutant gap junction protein alpha 8 gene (Gja8) were transfected into cells. The expression level of protein was assayed by Western blot analysis. Subcellular localization of connexin 50 (Cx50) was analyzed in confocal fluorescent images. Wound-healing, 5-ethynyl-2'-deoxyuridine incorporation, and attachment assay were performed to characterize the cell migration, proliferation and adhesion. Results: The abnormality was found to be inheritable in an autosomal semi-dominant pattern through different mating patterns. We found a G to T transversion at codon 655 in Gja8, leading to a substitution of valine by phenylalanine (p.V219F). Gja8V219F/+ heterozygotes expressed nuclear cataract while Gja8V219F/V219F homozygotes manifested microphthalmia in addition to cataract. Histology revealed fiber disorders and loss of organelle-free zone in the mutant lens. Cx50V219F altered its location in HeLa cells and inhibited the proliferation, migration and adhesion abilities of HLEB3 cells. The mutation also reduced the expression of focal adhesion kinase and its phosphorylation. Conclusions: The c.655G>T mutation (p.V219F) is a novel mutation in Gja8, inducing semi-dominant nuclear cataracts in a new spontaneous cataract rat model. The p.V219F mutation altered Cx50 distribution, inhibited lens epithelial cell proliferation, migration, and adhesion, and disrupted fiber cell differentiation. As a consequence, the nuclear cataract and small lens formed.

Risk factors and predictive model for pulmonary complications in patients transferred to ICU after hepatectomy.

OBJECTIVE: Postoperative pulmonary complications (PPCs) seriously harm the recovery and prognosis of patients undergoing surgery. However, its related risk factors in critical patients after hepatectomy have been rarely reported. This study aimed at analyzing the factors related to PPCs in critical adult patients after hepatectomy and create a nomogram for prediction of the PPCs. METHODS: 503 patients' data were collected form the Peking University People's Hospital. Multivariate logistic regression analysis was used to identify independent risk factors to derive the nomogram. Nomogram's discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC), and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and calibration curve. RESULTS: The independent risk factor for PPCs are advanced age (odds ratio [OR] = 1.026; P = 0.008), higher body mass index (OR = 1.139; P < 0.001), lower preoperative serum albumin level (OR = 0.961; P = 0.037), and intensive care unit first day infusion volume (OR = 1.152; P = 0.040). And based on this, we created a nomogram to predict the occurrence of PPCs. Upon assessing the nomogram's predictive ability, the AUC for the model was 0.713( 95% CI: 0.668-0.758, P<0.001). The Hosmer-Lemeshow test (P = 0.590) and calibration curve showed good calibration for the prediction of PPCs. CONCLUSIONS: The prevalence and mortality of postoperative pulmonary complications in critical adult patients after hepatectomy are high. Advanced age, higher body mass index, lower preoperative serum albumin and intensive care unit first day infusion volume were found to be significantly associated with PPCs. And we created a nomogram model which can be used to predict the occurrence of PPCs.

Significantly enhanced enzymatic hydrolysis of waste rice hull through a novel surfactant-based deep eutectic solvent pretreatment.

The potential of green solvents, specifically deep eutectic solvents (DESs), has piqued the interest of researchers in the field of lignocellulose pretreatment. To enhance the enzymatic digestion efficiency of waste rice hull (RCH), an effective pretreatment approach was developed using the DES [AA][CATB], which was made with acetic acid (AA) and cetyltrimethylammonium bromide (CTAB). The results showed that [AA][CATB] improved enzymatic saccharification by 3.7 times compared to raw RCH and efficiently eliminated lignin and removed xylan. The improvement in enzymatic hydrolysis efficiency was then interpreted by a series of characterizations that showed a great morphological changed RCH with an obvious accessibility increase and a lignin surface area and hydrophobicity reduction. This work demonstrates that functional, and easily recoverable DESs have potential for improving the efficiency of lignocellulose pretreatment in biorefineries, providing a promising approach for developing green solvents and achieving more sustainable and efficient biorefinery processes.

Impacts of ammonia stress on different Pacific whiteleg shrimp Litopenaeus vannamei families and the underlying adaptive mechanisms.

Ammonia stress in aquaculture systems poses a great threat to the growth and survival of the Pacific whiteleg shrimp Litopenaeus vannamei. Although the ammonia stress tolerance capacity of L. vannamei has been found to vary significantly among different breeding families, the underneath mechanisms are still largely unknown. In this study, the ammonia tolerance capacity of different L. vannamei breeding families was compared. Results confirmed the significant differences in the ammonia adaptability among different families. To ascertain the underlying adaptive strategies, ATP status, ATP synthase activity, expression and activities of ammonia excretion and metabolism-related enzymes, and apoptosis in shrimp gills were analyzed. Furthermore, transcriptomic analyses were also performed to elucidate the molecular mechanisms. Our results indicated that ammonia-tolerant L. vannamei may possess (1) enhanced ability to excrete ammonia, (2) better capacity to convert ammonia into less toxic products, and (3) sufficient energy reserves for ammonia-compensating processes.

Clinical observation of tear film breakup time with a novel smartphone-attachable technology.

PURPOSE: To demonstrate the practicability of a portable instrument in assessing tear film breakup time (TFBUT): a lens attachment for smartphones (LAS). METHODS: By applying LAS in combination with the iPhone 12 pro, and a recordable slit-lamp microscope, we obtained TFBUT videos from 58 volunteers. The comparison between the conventional slit-lamp microscope and LAS by an experienced ophthalmologist. Moreover, we also invited an ophthalmic postgraduate student and an undergraduate student with no clinical experience to assess TFBUT in those videos. The inter-observer reliability was assessed using intraclass correlation coefficients (ICC). RESULTS: The TFBUT of 116 eyes in total was recorded. Reliability indexes were adequate. The Spearman's correlation analysis and the intraclass correlation coefficient suggested a strong correlation between the 2 modalities (Right eye: Spearman's r = 0.929, 95% confidence interval (CI) = 0.847-0.963, ICC = 0.978, p < 0.001; Left eye: Spearman's r = 0.931, 95% CI = 0.866-0.964, ICC = 0.985, p < 0.001;). Between instruments, the majority of TFBUT measurements showed good agreement on Bland Altman plot. A high concordance was observed in TFBUT, when assessed by an ophthalmologist and an ophthalmic postgraduate student (Left eye: LAS ICC = 0.951, p < 0.001; Left eye: slit-lamp microscope ICC = 0.944, p < 0.001). CONCLUSIONS: Compared with the conventional slit-lamp microscope, the LAS has sufficient validity for evaluating TFBUT in clinics or at home.