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PURPOSE: This study aimed to automatically and quantitatively analyse the characteristics of the optic disc by applying artificial intelligence (AI) to fundus images. METHODS: A total of 1084 undergraduates were recruited in this cross-sectional study. The optic disc area, cup-to-disc ratio (C/D), optic disc tilt, and the area, width, and height of peripapillary atrophy (PPA) were automatically and quantitatively detected using AI. Based on axial length (AL), participants were divided into five groups: Group 1 (AL ≤ 23 mm); Group 2 (23 mm < AL≤ 24 mm); Group 3 (24 mm < AL≤ 25 mm); Group 4 (25 mm < AL< 26 mm) and Group 5 (AL ≥ 26 mm). Relationships between ocular parameters and optic disc characteristics were analysed. RESULT: A total of 999 undergraduates were included in the analysis. The prevalence of optic disc tilting and PPA were 47.1% and 92.5%, respectively, and increased with the severity of myopia. The mean optic disc area, PPA area, C/D, and optic disc tilt ratio were 1.97 ± 0.46 mm2, 0.84 ± 0.59 mm2, 0.18 ± 0.07, and 0.81 ± 0.08, respectively. In Group 5, the average optic disc area (1.84 ± 0.41 mm2) and optic disc tilt ratio (0.79 ± 0.08) were significantly smaller and the PPA area (1.12 ± 0.61 mm2) was significantly larger than those in the other groups. AL was negatively correlated with optic disc area and optic disc tilt ratio (r=-0.271, -0.219; both p < 0.001) and positively correlated with PPA area, width, and height (r = 0.421, 0.426, 0.345; all p < 0.01). A greater AL (ß = 0.284, p < 0.01) and a smaller optic disc tilt ratio (ß=-0.516, p < 0.01) were related to a larger PPA area. CONCLUSION: The characteristics of the optic disc can be feasibly and efficiently extracted using AI. The quantization of the optic disc might provide new indicators for clinicians to evaluate the degree of myopia.

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BACKGROUND: We present the management and follow-up of a case of uveal effusion syndrome (UES). CASE PRESENTATION: We study the relevant recent literature reports and review the aetiology, clinical classification, pathogenesis, diagnostic characteristics, treatment methods, and prognosis of this disease. When we encounter UES patients clinically, we can classify them according to their clinical characteristics and adopt different treatment plans for different types. The retina of this patient reattached 5 months after receiving eight periocular injections of triamcinolone acetonide (TA). CONCLUSIONS: For type III UES patients, local hormone therapy can be applied, and follow-up should be done to optimize the clinical outcome.

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Myopia has become the major cause of visual impairment worldwide. Although the pathogenesis of myopia remains controversial, proteomic studies suggest that dysregulation of retinal metabolism is potentially involved in the pathology of myopia. Lysine acetylation of proteins plays a key role in regulating cellular metabolism, but little is known about its role in the form-deprived myopic retina. Hence, a comprehensive analysis of proteomic and acetylomic changes in the retinas of guinea pigs with form-deprivation myopia was performed. In total, 85 significantly differential proteins and 314 significantly differentially acetylated proteins were identified. Notably, the differentially acetylated proteins were markedly enriched in metabolic pathways such as glycolysis/gluconeogenesis, the pentose phosphate pathway, retinol metabolism, and the HIF-1 signaling pathway. HK2, HKDC1, PKM, LDH, GAPDH, and ENO1 were the key enzymes in these metabolic pathways with decreased acetylation levels in the form-deprivation myopia group. Altered lysine acetylation of key enzymes in the form-deprived myopic retina might affect the dynamic balance of metabolism in the retinal microenvironment by altering their activity. In conclusion, as the first report on the myopic retinal acetylome, this study provides a reliable basis for further studies on myopic retinal acetylation.

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BACKGROUND: In January 2021, we found one case of Axenfeld-Rieger syndrome combined with pigment dispersion syndrome (PDS), and this patient additionally manifested a symptom of ectropion uveae. The co-existence of both 2 syndromes is very rare and has not been reported in any literature yet. CASE PRESENTATION: A 34-year-old female truck driver presented to our institution with a dimness of vision in her right eye. The patient had obvious posterior embryotoxons at bitamporal, and peripheral anterior synechia could be visualized by the slit lamp. The dispersion of pigment granules was observed behind the cornea. The pupil was slightly shifted upwards the nose, with 360° ectropion uveae. Gonioscopy revealed pigment accumulation on the trabecular meshwork. The patient underwent cataract surgery on her right eye, during which, flaky pigmentation around the posterior capsule was observed. These signs were consistent with Axenfeld-Rieger syndrome and PDS. CONCLUSIONS: We report a rare case of Axenfeld-Rieger syndrome with PDS and uveal eversion. Although the patient did not present with glaucoma, follow-up should be noted. Besides, the correlation between these 2 syndromes needs to be demonstrated by more cases or further evidence.

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INTRODUCTION: The aim of this study was to quantitatively assess fundus tessellated density (FTD) and associated factors by artificial intelligence (AI) in young adults. METHODS: A total of 1,084 undergraduates (age, 17-23 years old) were enrolled in November 2021. The students were divided into three groups according to axial length (AL): group 1 (AL <24.0 mm, n = 155), group 2 (24 mm ≤ AL <26 mm, n = 578), and group 3 (AL ≥26 mm, n = 269). FTD was calculated by extracting the fundus tessellations as the regions of interest (circle 1, diameter of 3.0 mm; circle 2, diameter of 6.0 mm) and then calculating the average exposed choroid area per unit area of fundus. RESULTS: Among 1,084 students, 1,002 (92.5%) students' FTDs were extracted. The mean FTD was 0.06 ± 0.06 (range, 0-0.40). In multivariate analysis, FTD was significantly associated with male sex, longer AL, thinner subfoveal choroid thickness (SFCT), increased choriocapillaris vessel density (VD), and decreased deeper choroidal VD (all p < 0.05). In circle 1 (diameter of 3.0 mm) and circle 2 (diameter of 6.0 mm), analysis of variance showed that the FTD of the nasal region (p < 0.05) was significantly larger than that of the superior, inferior, and temporal regions. CONCLUSION: AI-based imaging processing could improve the accuracy of fundus tessellation diagnosis. FTD was significantly associated with a longer AL, thinner SFCT, increased choriocapillaris VD, and decreased deeper choroidal VD.

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Introduction: The purpose of this paper was to study the effect of electroacupuncture (EA) on choroidal blood flow (ChBF) in a guinea pig model of lens-induced myopia (LIM). Methods: Guinea pigs were randomly divided into 4 groups: normal control (NC) group, LIM group, LIM + electroacupuncture (LIM + EA) group, and LIM + sham acupoint (LIM + sham) group. Right eyes were covered with a -6D lens to induce myopia. Meanwhile, LIM + EA group and LIM + sham group were treated with EA at acupoints Hegu (LI4) and Taiyang (EX-HN5) and sham points. Refraction, axial length (AL), choroidal thickness (ChT), vessel density of choriocapillaris (CC) and choroidal layer, and scleral collagen fiber were measured. Besides, hypoxia-inducible factor-1α (HIF-1α), matrix metalloprotein-2 (MMP-2), and tissue inhibitor metalloprotease-2 (TIMP-2) expression in sclera were detected. Results: Refraction and AL were significantly decreased and ChT and vessel density of CC were significantly increased in LIM + EA group at 2 weeks and 4 weeks (all P < 0.05) compared with LIM group. However, no significant difference of vessel density of choroidal layer was observed between LIM and LIM + EA group at 2 weeks and 4 weeks. Scleral collagen fibrils diameters were significantly increased in LIM + EA group at 4 weeks (P < 0.001) compared with LIM group. At the end of experiment, the mRNA and protein expression of HIF-1α and MMP-2 were significantly decreased (all P < 0.05) and those of TIMP-2 were increased in LIM + EA, compared with LIM. However, there were no significant differences between LIM and LIM + sham group. Conclusions: EA can improve the vessel density of choroid and then possibly improve scleral hypoxia, which may inhibit the growth of the AL in myopia guinea pig.

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OBJECTIVE: To analyse the morphological characteristics of the ciliary muscle (CM) and to explore its relationship with different ocular biometric parameters in myopic young Chinese adults. METHODS: This observational, cross-sectional study included 50 right eyes from 50 myopic adults. The CM area (CMA), CM thickness (CMT) and CM length (CML) were measured using the ArcScan Insight® 100. CMT was determined at three points: 1.0 mm (CMT-1), 2.0 mm (CMT-2) and 3.0 mm (CMT-3) posterior to the scleral spur. CML was measured on the scleral (CMLs) and vitreous (CMLv) aspects. The spherical equivalent refraction (SER), axial length (AL) and subfoveal choroidal thickness (SFCT) were examined to determine their associations with CM parameters (CMA, CML and CMT). RESULTS: The mean SER and AL were -4.39 ± 2.29 D and 25.61 ± 1.15 mm, respectively. Compared with the nasal CMA, CML and CMT (CMT-1, CMT-2 and CMT-3) findings, the temporal CM parameters (CMA, CMLs, CMLv, CMT-1, CMT-2 and CMT-3) were found to be significantly thicker (all p < 0.001, except CMLv and CMT-1; p < 0.01). The nasal CMA was associated with the average corneal curvature (r = 0.30, p = 0.03) and SER (r = -0.30, p = 0.04). Nasal and temporal CMT-2 were negatively correlated with SER (r = -0.33 and -0.32, respectively, both p < 0.05). There was no correlation between CM parameters (except nasal CMLs, r = 0.31, p = 0.03) and SFCT, or between CM parameters and either the AL or anterior chamber depth (all p > 0.05). CONCLUSION: These results suggest that there is temporal versus nasal asymmetry of the CM. CMA, CMT or CML did not vary with axial growth of the eye. The CM is not simply stretched as the eye elongates in myopic young adults.

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In the past decade, multifunctional peptides have attracted increasing attention in the biomedical field. Peptides possess many impressive advantages, such as high penetration ability, low cost, and etc. However, the short half-life and instability of peptides limit their application. In this study, a poly-peptide drug loading system (called HKMA composite) was designed based on the different functionalities of four peptides. The peptide compositions of HKMA composite from N-terminal to C-terminal were HCBP1, KLA, matrix metalloproteinase-2 (MMP-2)-cleavable peptide and albumin-binding domain. The targeting and lethality of HKMA to NSCLC cell line H460 sphere cells and the half-life of the system were measuredin vivo. The results showed that the HKMA composite had a long half-life and specific killing effect on H460 sphere cellsin vitroandin vivo. Our result proposed smart peptide drug loading system and provided a potential methodology for effective cancer treatment.

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In November 2021, a 19-year-old medical student was diagnosed with a rabbit-derived Thelazia callipaeda infection in her left eye. She visited her doctor because she removed the white object by herself with a cotton swab 2 days earlier. She explained to the doctor that she rubbed her eyes without washing her hands when rabbit hair got into her eyes during the animal experiment class at school 2 weeks earlier. The other 2 worms were then taken out with ophthalmic forceps and were placed into physiological saline. The worms were sent to the Shandong Academy of Eye Disease Prevention and Therapy for examination. After identification, the worms were regarded as the female T. callipaeda. Ofloxacin eye drops and peranapulin eye drops were administered to control inflammation. No abnormality was found in the follow-up 2 weeks and 1 month later. This report highlights that it is very important to strengthen the health and safety education of medical students during animal experiment classes.

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PURPOSE: To explore the effect of chronic unpredictable mild stress (CUMS) on the immune response involved in rats with experimental autoimmune uveitis (EAU). METHODS: Lewis rats were randomly divided into control, EAU, CUMS, and EAU+CUMS groups and received relevant treatments. On days 7, 11, 14, 21 and 28, frequencies of Th17 and Treg cells and the related cytokines were analyzed. RESULTS: The intraocular inflammation of EAU rats peaked between days 11 and 13, while the severity of inflammation of the rats in EAU+CUMS group fluctuated between 11 and 15 days. Both frequencies of Th17, Treg cells and the related cytokines exhibited a significant difference between the two groups on days 11 and 14. CONCLUSION: CUMS may protect against the possible harmful effects of immune disorder in rats with EAU through suppressing the immune disorder of T lymphocyte and the related cytokine responses.

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BACKGROUND: In August 2020, we found one case of thelazia callipaeda infection during phacoemulsification cataract surgery. This maybe the first report for thelazia callipaeda discovered during phacoemulsification cataract surgery in China. CASE PRESENTATION: An 85 years old farmer was found thelazia callipaeda infection during phacoemulsification cataract surgery. The patient admitted whose foreign body sensation was often found in the right eye in recent 2 months. The worm was then taken out with ophthalmic forceps and put into sterile normal saline. The worm was sent to the Eye Institute of Shandong University of Traditional Chinese Medicine for identification. After identification, the worm was regarded as the male thelazia callipaeda. The head is blunt and round, the tail end curls to the abdomen, and the long copulation spines protrudes from the cloaca. The conjunctival sac was washed carefully with a large amount of Sodium Lactate Ringer 's Solution. After operation, antibiotics, pranoprofen eye drops, and tobramycin dexamethasone eye drops were further applied. After continuous examination of conjunctival sac for 2 weeks, the patient's visual acuity maintained 20/20, confirming that there was no residual thelazia. CONCLUSIONS: This report highlights the physician should ask the patient's history carefully before operation and it is necessary to strengthen health publicity and education, maintaining clean environment and keeping personal eye hygiene.

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To examine the refractive lens power (RLP) and lens thickness and their associated factors in children from North-Western China. Children from two schools (primary school and junior high school) in the North-Western Chinese province of Qinghai underwent a comprehensive ophthalmic examination including biometry and cycloplegic refractometry. The RLP was calculated using Bennett's equation. The study included 596 (77.9%) individuals (mean age: 11.0 ± 2.8 years; range: 6-16 years) with a mean axial length of 23.65 ± 1.24 mm (range: 20.02-27.96 mm). Mean lens thickness was 3.30 ± 0.16 mm (range: 2.85-3.99 mm) and mean RLP was 24.85 ± 1.98D (range: 19.40-32.97). In univariate analysis, girls as compared to boys had a significantly thicker lens and greater RLP, shorter axial length, smaller corneal curvature radius and shorter corneal curvature radius (all P < 0.001). Both sexes did not differ significantly in refractive error (P = 0.11) and corneal thickness (P = 0.16). RLP was positively associated with refractive error (correlation coefficient r = 0.33; P < 0.001) and lens thickness (r = 0.62; P < 0.001) and negatively with axial length (r = - 0.70; P < 0.001). In univariate analysis, RLP decreased significantly with older age in the age group from age 6-13, while it plateaued thereafter, with no significant difference between boys and girls. In multivariate regression analysis, a higher RLP was associated with younger age (P < 0.001; standard regression coefficient ß = - 0.07), female sex (P < 0.001; ß = - 0.08), shorter axial length (P < 0.001; ß = - 0.48) and higher lens thickness (P < 0.001; ß = 0.42). In Chinese children, RLP with a mean of 24.85 ± 1.98D decreases with older age, male sex, longer axial length, and thinner lens thickness. Changes in RLP and axial length elongation are important players in the emmetropization and myopization.

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PURPOSE: This study aimed to investigate the prevalence of refractive error and visual acuity among school children in the plateau region of Qinghai, China. METHODS: The school-based, cross-sectional study was performed in Menyuan, Qinghai, China. Three kindergartens and three primary schools were randomly enrolled from both rural areas and county towns. The participants had undergone ophthalmic examinations of the intraocular pressure (IOP), uncorrected visual acuity (UCVA), presenting visual acuity (PVA) and best corrected visual acuity (BCVA), cycloplegic refraction, and axial length (AL). Regression analysis was applied to investigate the potential risk factors affecting the prevalence of various refractive errors. RESULTS: A total of 3770 children were invited to participate, and 3524 (93.5%) had undergone examination. Among the 3524 children (51.8% boys) with a mean age of 8.3±2.3 years, 1049 (29.8%) had myopia, 30 (0.9%) had high myopia, 1692 (48.0%) had mild hyperopia, 152 (4.3%) had medium to marked hyperopia and 925 (26.2%) had astigmatism. The mean SER was -0.16±1.86 D and decreased with age. The AL increased with age from 21.80±0.59 mm at 4-years to 23.53±1.05 mm at 12-years. The myopia prevalence increased with age from 2.0% at 4 years to 62.8% at 12-years. Myopia was associated with increasing age, county town habitation and girls. Among the 723 participants with PVA 20/40 or worse in one eye, 564 (78.0%) were due to uncorrected refractive error, and 83 (22.0%) were due to undercorrected refractive error. Among the 1049 children with myopia, only 254 wore glasses, and 151 children with PVA had a worse BCVA and did not have accurate spectacles. CONCLUSION: The prevalence of myopia is very high among school children in Menyuan. Only 24.2% of myopic children wore glasses, and 59.4% of children did not have accurate spectacles. Strategies to improve access to eye care and affordable glasses are needed.

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The co-pyrolysis of sewage sludge and biomass is considered a promising technique for reducing the volume of sewage sludge, adding value, and decreasing the risk associated with this waste. In this study, sewage sludge and cotton stalks were pyrolyzed together with different amounts of K2CO3 to evaluate the potential of chemical activation using K2CO3 for improving the porosity of the biochar formed and immobilizing the heavy metals present in it. It was found that K2CO3 activation effectively improved the pore structure and increased the aromaticity of the biochar. Moreover, K2CO3 activation transformed the heavy metals (Cu, Zn, Pb, Ni, Cr, and Cd) into more stable forms (oxidizable and residual fractions). The activation effect became more pronounced with increasing amount of added K2CO3, eventually resulting in a significant reduction in the mobility and bioavailability of the heavy metals in the biochar. Further analysis revealed that, during the co-pyrolysis process, K2CO3 activation resulted in a reductive atmosphere, increased the alkalinity of the biochar, and led to the formation CaO, CaCO3, and aluminosilicates, which aided the immobilization of the heavy metals. K2CO3 activation also effectively reduced the leachability, and thus, the environmental risks of the heavy metals. Thus, K2CO3 activation can improve the porosity of the biochar derived from sewage sludge/cotton stalks and aid the immobilization of the heavy metals in it.

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INTRODUCTION: This study aimed to investigate the therapeutic effects of overnight orthokeratology (OK) lenses on anisometropes. METHODS: We enrolled 178 anisometropes from August 2015 to August 2017. We then divided these patients into 2 parts depending on them wearing either monocular or binocular OK lenses. In part one, 47 monocular myopic subjects (25 males and 22 females) were treated with OK lenses in the myopic eyes only. We also labeled the myopic eyes as the OK group and the contralateral nonmyopic eyes as the control group. The initial average wearing age of the subjects was 12.35 ± 2.37 years (8-16 years). The mean follow-up duration was 15.43 ± 4.88 months (7-25 months). The average spherical equivalent refraction (SER) was -2.31 ± 1.16 diopter (D) in the OK group and 0.15 ± 0.49 D in the control group (p < 0.001). In part 2, 131 binocular myopic anisometropes (56 males and 75 females) were involved in the study. The eyes with more severe myopia were assigned to the G group and the contralateral eyes to the L group. The initial average wearing age of the subjects was 12.92 ± 2.60 years ( 8-16 years). The mean follow-up duration was 17.83 ± 5.02 months (7-26 months). The average SER was -4.79 ± 1.90 D in the G group and -3.14 ± 1.88 D in the L group (p < 0.001). We calculated the axial length (AL) difference and AL elongation as our primary outcome measures. RESULTS: In part one, the AL elongation in the OK group (0.21 ± 0.09 mm) was significantly lower than that in the control group (0.70 ± 0.17 mm) at 24 months (p < 0.001). Meanwhile, the AL difference exhibited a decrease of 0.50 ± 0.29 mm from a baseline of 1.08 ± 0.35 to 0.58 ± 0.25 mm at 24 months (F = 24.539, p < 0.001). In part 2, the AL had increased by 0.17 ± 0.13 mm in the G group and 0.24 ± 0.18 mm in the L group after 24-month follow-up, respectively (p < 0.001). While the AL difference decreased from 0.55 ± 0.11 mm at the baseline, to 0.48 ± 0.08 mm at 24 months, eliciting a decrement in AL difference of 0.07 ± 0.09 mm (F = 3.884, p = 0.030). CONCLUSIONS: OK lenses can slow down AL growth in anisometropes and has a greater effect on reducing AL elongation in the more severely affected myopic eyes of anisometropic patients.

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INTRODUCTION: This study aimed to determine the role of the choroid in lens-induced myopia (LIM) in guinea pigs. METHODS: Guinea pigs were randomly divided into two groups: a normal control (NC) group and a LIM group. Refraction and axial length (AL) were measured by streak retinoscopy and A-scan ultrasonography. The choroidal thickness (ChT), vessel density of the choriocapillaris (VDCC) and vessel density of the choroidal layer (VDCL) were assessed by Spectral-domain Optical Coherence Tomography Angiography (SD-OCT). In addition, the choroidal expression of nitric oxide synthase (NOS) enzymes at the mRNA and protein levels was analyzed by real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: In the LIM group, refraction and AL were increased significantly compared with those in the NC group at 2 weeks (refraction: LIM vs. NC, -4.23 ± 0.43 D vs. 2.20 ± 0.48 D; AL: LIM vs. NC, 8.36 ± 0.05 mm vs. 8.22 ± 0.03 mm) and 4 weeks (refraction: LIM vs. NC, -5.88 ± 0.49 D vs. 1.63 ± 0.41 D; AL: 8.57 ± 0.06 mm vs. 8.40 ± 0.04 mm). The ChT and VDCC were decreased significantly compared with those in the NC group at 2 weeks (ChT: LIM vs. NC, 60.92 ± 8.15 µm vs. 79.11 ± 7.47 µm; VDCC: LIM vs. NC, 23.43 ± 3.85% vs. 28.74 ± 4.11%) and 4 weeks (ChT: LIM vs. NC, 48.43 ± 6.85 µm vs. 76.38 ± 7.84 µm; VDCC: LIM vs. NC, 21.29 ± 2.17% vs. 27.64 ± 2.91%). The VDCL was also decreased compared with that in the NC group at 2 weeks and 4 weeks (NC vs. LIM, 24.87 ± 5.16% vs. 22.45 ± 3.26%; 23.37 ± 5.85% vs. 21.39 ± 2.62%; all P > 0.05). Moreover, the ChT was positively correlated with the VDCC and VDCL. The mRNA and protein expression of NOS enzymes (eNOS and nNOS) was increased. CONCLUSIONS: During the development of myopia, the ChT, VDCC and VDCL were decreased, while NOS expression in the choroid was increased. The expression of NOS was negatively correlated with the ChT, VDCC and VDCL. NO may play an important role in regulating the choroid during myopia development.

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The development of an effective delivery system for peptides targeting the tumor microenvironment has always been a hot topic of research in the field of cancer diagnosis and therapy. In this study, superparamagnetic iron oxide nanoparticles (SPIO NPs) were encapsulated with H460 lung cancer cell membranes (SPIO NP@M), and two peptides, namely PD-L1 inhibitory peptide (TPP1) and MMP2 substrate peptide (PLGLLG), were conjugated to the H460 membrane (SPIO NP@M-P). Homologous targeting, cytotoxicity, and pharmacokinetics of SPIO NP@M-P were evaluated. The TPP1 peptide was delivered and released to the tumor microenvironment through the homotypic effect of tumor cell membrane and specific digestion by the tumor-specific enzyme MMP2. The newly developed delivery system (SPIO NP@M-P) for the PD-L1 inhibitory peptide could effectively extend the half-life of the peptides (60 times longer than that for peptides alone) and could maintain the ability to reactivate T cells and inhibit the tumor growth both in vitro and in vivo. Furthermore, SPIO NPs in the system could be used as a tumor imaging agent and thus show the effect of peptide treatment. The SPIO NP@M might serve as a promising theranostic platform for therapeutic application of peptides in cancer therapy. STATEMENT OF SIGNIFICANCE: A multifunctional delivery system (SPIO NP@M) was constructed for effectively delivering therapeutic peptides into the tumor microenvironment for cancer diagnosis and therapy. In this paper, the TPP-1 peptide inhibiting the binding of PD-L1 and PD-1 was delivered and released into the tumor microenvironment by the homotypic targeting of H460 cell membrane and specific digestion by the MMP2 enzyme. SPIO NPs in this system were aggregated effectively at the tumor sites and were used for magnetic resonance imaging of tumors. The SPIO NP@M-P delivery system could effectively extend the half-life of the TPP-1 peptide (60 times longer than that of the free peptide) and could maintain the ability to re-activate T cells and inhibit tumor growth in vitro and in vivo. In conclusion, the SPIO NP@M system coated with lung cancer cell membrane and loaded with the PD-L1-blocking TPP-1 peptide could be a promising integrated platform for tumor diagnosis and treatment.

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Our previous study reveals that gamma delta (γδ) T cells were activated and dendritic cells (DCs) underwent maturation during the inflammation phase in experimental autoimmune uveitis (EAU) mice, and the interaction between DCs and γδ T cells may significantly exacerbate the development of EAU. However, the interactions between DCs and γδ T cells that can affect DCs maturation to influence EAU development must be further addressed. In this study we showed that mature DC numbers in TCR-δ-/- (KO) EAU mice were lower than those in wild-type (WT) C57BL/6 (B6) mice. The γδ T cells harvested from WT EAU mice secreted more interferon-γ (IFN-γ), however, after blocking IFN-γ, the maturation of DCs was significantly downregulated. By contrast, the percentage of IFN-γ- and IL-17-producing CD4+ T cells in KO EAU mice decreased to a greater extent than that in WT EAU mice during the inflammatory phase. Additionally, the levels of IFN-γ/IL-17 in serum were in agreement with those of CD4+ T cells. Furthermore, after activated γδ T cells injection, the inflammatory symptoms of EAU mice were more aggravated. In vitro co-cultures of both cell types showed that activated γδ T cells may induce DCs to generate higher levels of intracellular cell adhesion molecule-1 (ICAM-1/CD54), CD80, CD83, and CD86. Moreover, co-culture of the two cells may induce the activation of CD4+ T cells. Taken together, our results demonstrated that activated γδ T cells may promote DCs maturation and further enhance the generation of Th1/Th17 cells in EAU mice, resulting in exacerbated EAU.

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Cancer stem cells (CSCs) are responsible for cancer initiating, recurrence, and drug resistance. Discovery of novel biomarkers for CSCs is helpful for early diagnosis and prognosis. Lung cancer stem cells (LCSCs) were closely related to the occurrence and development of lung cancer. In our study, the important role of miR-2861 in maintaining the stemness of LCSCs was investigated. The LCSC differentiation model was established through introducing serum into the medium of H460 spheres. miR-2861 expression was significantly higher in LCSCs no matter compared to the differentiation cells or normal cells. HDAC5 expression was positively correlated with miR-2861 in LCSCs, and knockdown of miR-2861 decreased the expression of HDAC5, which implied that HDAC5 may be involved in the differentiation of LCSCs mediated by miR-2861. The role of HDAC5 in the regulation of LCSC differentiation was further verified by the inhibitory effect of LMK-235 on the phosphorylation of ERK1/2, which was recognized as the regulator of CSC differentiation. Our study provided a better understanding of miR-2861 and HDAC5 axis in maintaining the stemness of LCSCs and laid a foundation for molecular targeted therapy.

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Thrombosis, a critical event in blood vessels, not only is associated with myocardial infarction and stroke, but also accounts for considerable morbidity and mortality. Thrombolytic drugs are usually applied to the treatment of acute myocardial infarction, acute cerebral infarction and pulmonary embolism. However, thrombolytic drugs show limited efficacy in clinical practice because of the short half-life in plasma and systemic side effects. In this study, the cyclic RGD (cRGD) functionalized liposomes were prepared to encapsulate urokinase, a cheap and widely used thrombolytic drug in clinic and better thrombolysis efficacy was achieved. The flow cytometry analysis showed that the cRGD liposomes could bind to the activated platelets while not to the resting platelets. In vitro release study revealed that the release percentage reached plateau in about 5 h with 60% urokinase being released from liposomes. Results from the in vitro thrombolysis experiments demonstrated a good thrombolysis potential of the cRGD urokinase liposomes. The in vivo thrombolysis study demonstrated that the cRGD liposomes could significantly reduce the dose of urokinase by 75% while achieving the equivalent thrombolysis effect as the free urokinase in mouse mesenteric thrombosis model. In conclusion, the cRGD liposomes encapsulating urokinase hold great promise in clinic for better thrombolytic efficacy. STATEMENT OF SIGNIFICANCE: In this paper, the cRGD liposomes were prepared to encapsulate urokinase for targeted thrombolysis therapy. The cRGD liposomes could specifically bind to the activated platelets and could stably and continuously release its loaded urokinase. The mouse mesenteric thrombosis model was established to evaluate the thrombolysis effect of the cRGD urokinase liposomes. The results demonstrated that the cRGD liposomes could improve the thrombolytic efficacy by almost 4-fold over free urokinase. In conclusion, the cRGD liposomes encapsulating urokinase had great potential for the clinical treatment of thrombosis.

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