Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).

Comparison of 27-gauge beveled-tip and 25-gauge flat-tip microincision vitrectomy surgery in the treatment of proliferative diabetic retinopathy: a randomized controlled trial.

PURPOSE: To compare the effectiveness and safety of a 27-gauge (27G) beveled-tip microincision vitrectomy surgery (MIVS) with a 25-gauge (25G) flat-tip MIVS for the treatment of proliferative diabetic retinopathy (PDR). METHODS: A prospective, single-masked, randomized, controlled clinical trial included 52 eyes (52 patients) with PDR requiring proliferative membrane removal. They were randomly assigned in a 1:1 ratio to undergo the 27G beveled-tip and or 25G flat-tip MIVS (the 27G group and the 25G group, respectively). During surgery, the productivity of cutting the membrane, the number of vitrectomy probe (VP) exchanges to microforceps, total operation time, vitrectomy time and intraoperative complications were measured. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and postoperative complications were also assessed to month 6. RESULTS: Forty-seven eyes (47 patients) completed the follow-up, including 25 in the 27G group and 22 in the 25G group. During surgery in the 27G group, cutting the membrane was more efficient (P = 0.001), and the number of VP exchanges to microforceps was lower (P = 0.026). The occurrences of intraoperative hemorrhages and electrocoagulation also decreased significantly (P = 0.004 and P = 0.022). There were no statistical differences in the total operation time or vitrectomy time between the two groups (P = 0.275 and P = 0.372), but the former was slightly lower in the 27G group. Additionally, the 27G group required fewer wound sutures (P = 0.044). All the follow-up results revealed no significant difference between the two groups. CONCLUSIONS: Compared with the 25G flat-tip MIVS, the 27G beveled-tip MIVS could be more efficient in removing the proliferative membrane while reducing the occurrence of intraoperative hemorrhages and electrocoagulation using appropriate surgical techniques and instrument parameters. Its vitreous removal performance was not inferior to that of the 25G MIVS and might offer potential advantages in total operation time. In terms of patient outcomes, advanced MIVS demonstrates equal effectiveness and safety to 25G flat-tip MIVS. TRIAL REGISTRATION: The clinical trial has been registered at Clinicaltrials.gov (NCT0544694) on 07/07/2022. And all patients in the article were enrolled after registration.

Rational design of a ratiometric fluorescent aptasensor for patulin in traditional Chinese medicine through the studies of the interaction mechanism between its DNA aptamer and the target molecule.

Patulin (PAT) is a kind of mycotoxin which must be monitored for the sake of quality and safety in traditional Chinese medicine (TCM) owing to its harm to human health. On this account, a rationally designed ratiometric fluorescent aptasensor was developed based on the studies of the interaction mechanism between PAT and its aptamer (PAT-APT). First, CD spectroscopy, molecular docking, and molecular dynamic simulation were applied to investigate the details on how PAT-APT binds with its target molecule. The results indicated that the structure of PAT-APT changed to a certain extent and was stabilized after binding with PAT. C-11, C-37 and C-38 were the key sites for the recognition and interaction between PAT-APT and its target. Second, based on these results, a ratiometric aptasensor was designed using fluorescence resonance energy transfer (FRET) and synchronous fluorescence spectroscopy. A complementary sequence (cDNA) to the aptamer with an appropriate length and hybridization position was obtained through rational design and optimization. Both PAT-APT and cDNA were labeled using a pair of fluorophores, which could generate FRET when the two single-stranded oligonucleotides hybridized. The accurate detection of PAT could be realized according to the change ratio of the fluorescence intensity at the corresponding wavelengths of the two fluorophores before and after the assay. The aptasensor achieved an ultralow limit of detection of 0.16 nM, perfect selectivity, and satisfactory practicability in complex TCM samples. To our knowledge, this is the first aptasensor for PAT designed through the interaction mechanism between its aptamer and the target molecule. Moreover, the assay for PAT is cost-effective, does not need complicated pretreatment and only takes less than an hour. In summary, this study makes a contribution to the safety control of TCM and provides a thinking mode from mechanism to rational design to conquer the problem of sensitive aptasensing of one component in a complex system.

Analysis of postoperative ocular surface changes and intervention effect after pars plana vitrectomy in meibomian gland dysfunction dry eye patients.

AIM: To observe ocular surface changes after phacovitrectomy in patients with mild to moderate meibomian gland dysfunction (MGD)-type dry eye and track clinical treatment response using a Keratograph 5M and a LipiView interferometer. METHODS: Forty cases were randomized into control group A and treatment group B; the latter received meibomian gland treatment 3d before phacovitrectomy and sodium hyaluronate before and after surgery. The average non-invasive tear film break-up time (NITBUTav), first non-invasive tear film break-up time (NITBUTf), non-invasive measured tear meniscus height (NTMH), meibomian gland loss (MGL), lipid layer thickness (LLT) and partial blink rate (PBR) were measured preoperatively and 1wk, 1 and 3mo postoperatively. RESULTS: The NITBUTav values of group A at 1wk (4.38±0.47), 1mo (6.76±0.70), and 3mo (7.25±0.68) were significantly lower than those of group B (7.45±0.78, 10.46±0.97, and 11.31±0.89; P=0.002, 0.004, and 0.001, respectively). The NTMH values of group B at 1wk (0.20±0.01) and 1mo (0.22±0.01) were markedly higher than those of group A (0.15±0.01 and 0.15±0.01; P=0.008 and P<0.001, respectively); however, there was no difference at 3mo. The LLT of group B at 3mo [91.5 (76.25-100.00)] significantly exceeded that of group A [65.00 (54.50-91.25), P=0.017]. No obvious intergroup difference was found in MGL or PBR (P>0.05). CONCLUSION: Mild to moderate MGD dry eye worsens in the short term after phacovitrectomy. Preoperative cleaning, hot compresses, and meibomian gland massage as well as preoperative and postoperative sodium hyaluronate promote the rapid recovery of tear film stability.

Fluorescence-based aptasensors for small molecular food contaminants: From energy transfer to optical polarization.

Small molecular food contaminants, such as mycotoxins, pesticide residues and antibiotics, are highly probable to be passively introduced in food at all stages of its processing, including planting, harvest, production, transportation and storage. Owing to the high risks caused by the unknowing intake and accumulation in human, there is an urgent need to develop rapid, sensitive and efficient methods to monitor them. Fluorescence-based aptasensors provide a promising platform for this area owing to its simple operation, high sensitivity, wide application range and economical practicability. In this paper, the common sorts of small molecular contaminants in foods, namely mycotoxins, pesticides, antibiotics, etc, are briefly introduced. Then, we make a comprehensive review, from fluorescence resonance energy transfer (in turn-on, turn-off, and ratiometric mode, as well as energy upconversion) to fluorescence polarization, of the fluorescence-based aptasensors for the determination of these food contaminants reported in the last five years. The principle of signal generation, the advances of each sort of fluorescent aptasensors, as well as their applications are introduced in detail. Additionally, we also discussed the challenges and perspectives of the fluorescent aptasensors for small molecular food contaminants. This work will offer systematic overview and inspiration for amateurs, researchers and developers of fluorescence-based aptasensors for the detection of small molecules.

Negative effects of enlarging internal limiting membrane peeling for idiopathic macular hole surgery.

AIM: To observe the effects of the different extents of internal limiting membrane (ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole (IMH). METHODS: In this retrospective cohort study, 36 patients were reviewed and divided into two groups according to the extent of ILM peeling: group A (18 patients), with the peeling area within one-half of the optic disc macular distance as the radius; group B (18 patients), with the peeling area larger than that of group A but did not exceed the optic disc macular distance as the radius. The main outcomes included the best corrected visual acuity (BCVA), light-adaptive electroretinography, macular hole (MH) closure rate, central macular thickness (CMT), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness [nine regions based on the Early Treatment of Diabetic Retinopathy Study (ETDRS) ring] before and 1, 3, and 6mo after surgery. RESULTS: The closure rate was 94.4% (17/18) both in groups A and B. The BCVA in both groups improved significantly compared with the preoperative values, but there was no difference between the two groups. The b-wave amplitude of the electroretinogram analysis was significantly improved in both groups compared to that of the preoperative period, with a greater increase in group A than in group B at 6mo (P=0.017). The CMT in both groups gradually decreased after surgery, and there was no difference between the two groups. The RNFL thickness of the temporal outer ring region in group B was significantly lower than that in group A at 3 and 6mo after surgery (P=0.010, 0.032). The GCC thickness of the temporal outer ring region in group B was significantly lower than that in group A at 6mo after surgery (P=0.038). CONCLUSION: Enlarging the extent of ILM peeling doesn't affect the IMH closure rate and visual acuity recovery, but the greater the extent of peeling, the greater the damage to the inner retinal structures.

Downregulation of fatty acid binding protein 4 alleviates lipid peroxidation and oxidative stress in diabetic retinopathy by regulating peroxisome proliferator-activated receptor γ-mediated ferroptosis.

This study aims to explore the role of fatty acid binding protein 4 (FABP4) in diabetic retinopathy (DR), and to elucidate the potential regulatory mechanism. We firstly developed a mouse model of DR by injection with streptozocin (STZ) into C57BL/6 male mice and a cell model of DR by induction of high glucose (HG) to ARPE-19 cells. BMS309403, an inhibitor of FABP4, was employed for treatment. The blood glucose in vivo was monitored and the histological changes of retinal tissues were observed by hematoxylin and eosin staining and Evans blue assay. The expression level of FABP4 was detected by western blot and Immunohistochemical staining. The critical factors related to lipid peroxidation and oxidative stress were detected using their commercial kits, respectively. Prussian blue staining, iron content assay and thiobarbituric acid-reactive substances (TBARS) assay were conducted to evaluate ferroptosis. As a result, FABP4 was elevated in retina and serum of STZ-induced mice and in HG-induced ARPE-19 cells. BMS309403 treatment notably alleviated reduced blood glucose, reduced histological damage, and vascular permeability. In addition, BMS309403 treatment inhibited lipid peroxidation, oxidative stress, and ferroptosis both in vivo and in vitro. Furthermore, BMS309403 promoted the activation of peroxisome proliferator-activated receptor γ (PPARγ). GW9662 (an inhibitor of PPARγ) or Erastin (an inducer of ferroptosis) partially weakened the suppressive effects of BMS309403 on HG-induced lipid peroxidation, oxidative stress and ferroptosis. Taken together, FABP4 inhibition alleviates lipid peroxidation and oxidative stress in DR by regulating PPARγ-mediated ferroptosis.

Feasibility of developing hospital preparation by semisolid extrusion 3D printing: personalized amlodipine besylate chewable tablets.

Semisolid extrusion (SSE) 3D printing is an emerging technology in personalized medicine. To address clinical multi-dose requirements, SSE has been explored to manufacture new preparations. In this study, amlodipine besylate (AMB) was the model drug, and SSE was the pharmaceutical strategy. We developed semisolids suitable for SSE and AMB chewable tablets with six strengths (1.5-5 mg) to meet the needs of 2-16-year-old patients. First, the semisolid extrudability was evaluated by texture analyzer, and then the amounts of carboxymethyl cellulose sodium, sodium starch glycolate, and glycerin were optimized by full factorial design. Then, rheological tests were performed to evaluate the properties of the semisolid and the effect of starch sodium glycolate on printability. Finally, the amount of corrigents was optimized using the electronic tongue. Laboratory amplified semisolids and 3D printed tablets can be stored for a few months, and the whole SSE process had no effect on crystal type. This study validated the feasibility of SSE 3D printing, and tablets with appropriate taste and cartoon appearance can meet or even exceed the traditional preparations. Our study provides a new strategy for multi-dose solid preparations and effectively meet the need for personalized amlodipine medicine.

A facile "turn-on" fluorescent aptasensor for simultaneous detection of dual mycotoxins in traditional Chinese medicine based on graphene oxide and FRET.

Mycotoxin is a common sort of harmful contaminant in traditional Chinese medicine (TCM), which is in a great demand of controlling. On this account, a facile "turn-on" fluorescent aptasensor based on fluorescence resonance energy transfer (FRET) for simultaneous detection of patulin (PAT) and zearalenone (ZEN) was developed. In this study, the aptamers of PAT and ZEN were labeled by FAM and Cy3, respectively, serving as fluorescence probes. Both aptamers could adsorb on the surface of graphene oxide (GO) via π-π stacking, which will consequently result in the occurrence of FRET between the fluorophores and GO. In the absence of the targets, the fluorescence would be quenched "off". In the presence of any of the dual mycotoxins, the corresponding aptamers would interact with the targets and release from GO due to the conformational variation, leading to a fluorescence "turn-on" effect. The limit of detection of this difunctional aptasensor was 2.29 nM for PAT and 0.037 nM for ZEN, respectively. This aptasensing platform exhibited satisfactory selectivity against interferents and reliability in real TCM sample detection. To our knowledge, it is the first aptasensor based on GO and FRET that realizes simultaneous detection of dual mycotoxin in TCM. Moreover, the measurement takes merely ∼60 min, does not need complicated pretreatment, and uses only inexpensive aptamer and GO as consuming materials. To sum up, this aptasensor exhibits great potential in fast, cost-effective and reliable simultaneous detection of multiple targets, and is expected to contribute to the quality and safety control of TCM.

Targeted drug delivery vehicles mediated by nanocarriers and aptamers for posterior eye disease therapeutics: barriers, recent advances and potential opportunities.

Nanomedicine and aptamer have excellent potential in giving play to passive and active targeting respectively, which are considered to be effective strategies in the retro-ocular drug delivery system. The presence of closely adjoined tissue structures in the eye makes it difficult to administer the drug in the posterior segment of the eye. The application of nanomedicine could represent a new avenue for the treatment, since it could improve penetration, achieve targeted release, and improve bioavailability. Additionally, a novel type of targeted molecule aptamer with identical objective was proposed. As an emerging molecule, aptamer shows the advantages of penetration, non-toxicity, and high biocompatibility, which make it suitable for ocular drug administration. The purpose of this paper is to summarize the recent studies on the effectiveness of nanoparticles as a drug delivery to the posterior segment of the eye. This paper also creatively looks forward to the possibility of the combined application of nanocarriers and aptamers as a new method of targeted drug delivery system in the field of post-ophthalmic therapy.

Signal enhancing strategies in aptasensors for the detection of small molecular contaminants by nanomaterials and nucleic acid amplification.

Small molecular contaminants (such as mycotoxins, antibiotics, pesticide residues, etc.) in food and environment have given rise to many biological and ecological toxicities, which has attracted worldwide attention in recent years. Meanwhile, due to the advantages of aptamers such as high specificity and stability, easy synthesis and modification, as well as low cost and immunogenicity, various aptasensors for the detection of small molecular contaminants have been flourishing. An aptasensor as a whole is composed of an aptamer-based target recognizer and a signal transducer, which are fields of concentrated research. In the practical detection applications, in order to achieve the quantitative detection of small molecular contaminants at low abundance in real samples, a large number of signal enhancing strategies have been utilized in the development of aptasensors. Recent years is a vintage period for efficient signal enhancing strategies of aptasensors by the aid of nanomaterials and nucleic acid amplification that are applied in the elements for target recognition and signal conversion. Therefore, this paper meticulously reviews the signal enhancing strategies based on nanomaterials (including the (quasi-)zero-dimensional, one-dimensional, two-dimensional and three-dimensional nanomaterials) and nucleic acid amplification (including enzyme-assisted nucleic acid amplification and enzyme-free nucleic acid amplification). Furthermore, the challenges and future trends of the abovementioned signal enhancing strategies for application are also discussed in order to inspire the practitioners in the research and development of aptasensors for small molecular contaminants.

Artificial intelligence can assist with diagnosing retinal vein occlusion.

AIM: To assist with retinal vein occlusion (RVO) screening, artificial intelligence (AI) methods based on deep learning (DL) have been developed to alleviate the pressure experienced by ophthalmologists and discover and treat RVO as early as possible. METHODS: A total of 8600 color fundus photographs (CFPs) were included for training, validation, and testing of disease recognition models and lesion segmentation models. Four disease recognition and four lesion segmentation models were established and compared. Finally, one disease recognition model and one lesion segmentation model were selected as superior. Additionally, 224 CFPs from 130 patients were included as an external test set to determine the abilities of the two selected models. RESULTS: Using the Inception-v3 model for disease identification, the mean sensitivity, specificity, and F1 for the three disease types and normal CFPs were 0.93, 0.99, and 0.95, respectively, and the mean area under the curve (AUC) was 0.99. Using the DeepLab-v3 model for lesion segmentation, the mean sensitivity, specificity, and F1 for four lesion types (abnormally dilated and tortuous blood vessels, cotton-wool spots, flame-shaped hemorrhages, and hard exudates) were 0.74, 0.97, and 0.83, respectively. CONCLUSION: DL models show good performance when recognizing RVO and identifying lesions using CFPs. Because of the increasing number of RVO patients and increasing demand for trained ophthalmologists, DL models will be helpful for diagnosing RVO early in life and reducing vision impairment.

A disposable gold foil paper-based aptasensor for detection of enteropathogenic Escherichia coli with SERS analysis and magnetic separation technology.

Rapid and sensitive detection of enteropathogenic Escherichia coli (EPEC) in fluids with complex background is an important task for safety quality control in the field of medicine, environment, and food. In this study, a gold foil paper-based aptasensor was developed for the detection of enteropathogenic EPEC O26:K60 with surface-enhanced Raman spectroscopy (SERS) and magnetic separation technology mediated by Fe3O4@Au composite. The gold foil paper was firstly modified with thiolated capture probe and SERS tag. The thiolated aptamer probe for EPEC was immobilized onto a Fe3O4@Au composite. In the presence of EPEC, highly specific recognition between the aptamer probe and EPEC made the Fe3O4@Au composite partially dissociated from the gold foil paper. This led to a decreased Raman intensity response, which showed an obvious negative linear correlation with increasing concentration of EPEC over a wide concentration range from 10 to 107 CFU/mL under an excitation wavelength of 633 nm. The detection limit was about 2.86 CFU/mL in a buffer solution and a licorice extractum and the detection time was only 2.5 h. The results demonstrate that the gold foil paper-based aptasensor can be an excellent biosensing platform that offers a reliable, rapid, and sensitive alternative for EPEC detection.

Taste Masking Study Based on an Electronic Tongue: the Formulation Design of 3D Printed Levetiracetam Instant-Dissolving Tablets.

PURPOSE: Proper taste-masking formulation design is a critical issue for instant-dissolving tablets (IDTs). The purpose of this study is to use the electronic tongue to design the additives of the 3D printed IDTs to improve palatability. METHODS: A binder jet 3D printer was used to prepare IDTs of levetiracetam. A texture analyzer and dissolution apparatus were used to predict the oral dispersion time and in vitro drug release of IDTs, respectively. The palatability of different formulations was investigated using the ASTREE electronic tongue in combination with the design of experiment and a model for masking bitter taste. Human gustatory sensation tests were conducted to further evaluate the credibility of the results. RESULTS: The 3D printed tablets exhibited rapid dispersion (<30 s) and drug release (2.5 min > 90%). The electronic tongue had an excellent ability of taste discrimination, and levetiracetam had a good linear sensing performance based on a partial least square regression analysis. The principal component analysis was used to analyze the signal intensities of different formulations and showed that 2% sucralose and 0.5% spearmint flavoring masked the bitterness well and resembled the taste of corresponding placebo. The results of human gustatory sensation test were consistent with the trend of the electronic tongue evaluation. CONCLUSIONS: Owing to its objectivity and reproducibility, this technique is suitable for the design and evaluation of palatability in 3D printed IDT development.

Key Factor Study for Generic Long-Acting PLGA Microspheres Based on a Reverse Engineering of Vivitrol®.

The FDA (U.S. Food and Drug Administration) has approved only a negligible number of poly(lactide-co-glycolide) (PLGA)-based microsphere formulations, indicating the difficulty in developing a PLGA microsphere. A thorough understanding of microsphere formulations is essential to meet the challenge of developing innovative or generic microspheres. In this study, the key factors, especially the key process factors of the marketed PLGA microspheres, were revealed for the first time via a reverse engineering study on Vivitrol® and verified by the development of a generic naltrexone-loaded microsphere (GNM). Qualitative and quantitative similarity with Vivitrol®, in terms of inactive ingredients, was accomplished by the determination of PLGA. Physicochemical characterization of Vivitrol® helped to identify the critical process parameters in each manufacturing step. After being prepared according to the process parameters revealed by reverse engineering, the GNM demonstrated similarity to Vivitrol® in terms of quality attributes and in vitro release (f2 = 65.3). The research on the development of bioequivalent microspheres based on the similar technology of Vivitrol® will benefit the development of other generic or innovative microspheres.

PSF functions as a repressor of hypoxia-induced angiogenesis by promoting mitochondrial function.

BACKGROUND: Abnormal neovascularization is the most common cause of blindness, and hypoxia alters tissue metabolism, function, and morphology. HIF-1α, the transcriptional activator of VEGF, has intricate mechanisms of nuclear translocation and activation, but its signal termination mechanisms remain unclear. METHODS: We investigated the role of polypyrimidine tract-binding protein-associated splicing factor (PSF) in cellular energy production, migration, and proliferation by targeting HIF-1α in vivo and in vitro PSF plasmids were transfected with liposome 2000 transfection reagent. Young C57/BL6J mice were kept in a hyperoxia environment, followed by indoor air, resulting in oxygen-induced retinopathy. Oxygen-induced retinopathy (OIR) animals were randomly divided into three groups: OIR group, OIR + vector group (OIR cubs treated with rAAV vector) and OIR + PSF group (OIR cubs treated with rAAV-PSF). Age-matched C57/BL6J mice were used as controls and exposed to constant normoxic conditions. The animals were executed and their pupils were subjected to subsequent experiments. The metabolic spectrum was analyzed by Seahorse XFe96 flux analyzer, and OCR and extracellular acidification rate were quantified at the same time. RESULTS: PSF ameliorated retinal neovascularization and corrected abnormal VEGF expression in mice with oxygen-induced retinopathy and reduced intra-retinal neovascularization in Vldlr - / - mice. PSF reprogrammed mitochondrial bioenergetics and inhibited the transition of endothelial cells after hypoxia, suggesting its involvement in pathological angiogenesis.Ectopic PSF expression inhibited hypoxia-induced HIF-1α activation in the nucleus by recruiting Hakai to the PSF/HIF-1α complex, causing HIF-1α inhibition. PSF knockdown increased hypoxia-stimulated HIF-1α reactions. These hypoxia-dependent processes may play a vital role in cell metabolism, migration, and proliferation. Thus, PSF is a potential treatment target in neovascularization-associated ophthalmopathy. CONCLUSION: This is the first study showing that PSF inhibits HIF-1α via recruitment of Hakai, modulates mitochondrial oxidation and glycolysis, and downregulates VEGF expression under hypoxia. We propose a new HIF-1 α/Hakai regulatory mechanism that may play a vital role in the pathogenesis of neovascularization in ophthalmopathy. PSF-Hakai-HIF-1α signaling pathway under hypoxia condition. Schematic diagram showing that the PSF-Hakai-HIF-1α signaling pathway. Under hypoxia condition, PSF-Hakai complex regulate HIF-1α signaling, thus inhibiting downstream target gene VEGF, cell metabolism and angiogenesis eventually. Video Abstract: Detailed information of Materials and Methods.

Refractive outcomes after vitrectomy combined with phacoemulsification of idiopathic macular holes.

AIM: To report the refractive outcomes after vitrectomy combined with phacoemulsification and intraocular lens (IOL) implantation (phaco-vitrectomy) in idiopathic macular holes (IMH). METHODS: A total of 56 eyes with IMH (IMH group) that underwent phaco-vitrectomy and 44 eyes with age-related cataract (ARC group) that underwent cataract surgery were retrospectively reviewed. The best corrective visual acuity (BCVA), predicted refractive error (PRE), actual refractive error (ARE), axial length (AL), were measured in both groups before and 6mo after operation. The power calculation of IOL and the predicted refractive error (PRE) were calculated according to the SRK/T formula. The difference of PRE and ARE between the two groups were compared and analyzed. RESULTS: In the IMH group, the diameters of macular holes were 271.73±75.85 µm, the closure rate was 100%. The pre- and post-operative BCVA were 0.80±0.35 and 0.40±0.35 logMAR. The PRE of A-ultrasound and IOL Master in the IMH group was -0.27±0.25 and 0.10±0.66 D. The postoperative mean absolute prediction error (MAE) was observed to be 0.58±0.65 and 0.53±0.37 D in the IOL Master and A-ultrasound (P=0.758). The PRE and ARE of the IMH group were 0.10±0.66 D and -0.19±0.64 D (P=0.102). The PRE and ARE of the ARC group was -0.43±0.95 and -0.31±0.93 D (P=0.383). The difference between PRE and ARE was -0.33±0.81 and 0.09±0.64 D in the IMH and ARC groups (P=0.021). The proportion of myopic shift was 67.9% in the IMH group and 27.3% in the ARC group (P=0.004). CONCLUSION: The myopic shift can be observed in patients with IMH after phaco-vitrectomy.

Target-triggered entropy-driven amplification system-templated silver nanoclusters for multiplexed microRNA analysis.

MicroRNAs (miRNAs) are important biomarkers for the diagnosis, prognosis, and treatment of human diseases. Sensitive and selective detection of multiple miRNAs simultaneously will greatly facilitate the early and accurate diagnosis of cancers. Herein, a novel entropy-driven amplification system-templated silver nanoclusters sensing platform was developed for the multiplexed analysis of tumor-associated miRNAs. The sensing platform was constructed by coupling target-triggered entropy-driven catalysis with luminescence adjustable DNA-templated silver nanoclusters (Ag NCs). In the presence of target miRNA, the sensing platform initiates the branch migration and strand displacement of the complex, which has a six-base cytosine loop for stabilizing the luminous Ag NCs. The target is cyclically generated for new catalysis while turning off the fluorescence of Ag NCs; this is accompanied by a significantly amplified optical readout. In this study, two different complex-stabilized Ag NCs systems were proposed, the yellow-emitting Ag NCs and red-emitting Ag NCs biosensors enabled the analysis of miRNA-141 and miRNA-155 with detection limits of 6.1 pM and 8.7 pM, respectively. Impressively, owing to the excellent selectivity, flexibility, and narrow-band excitation of the platform, the multiplexed synchronous detection of miRNA-141 and miRNA-155 were achieved in buffer, biological cell lysates and human serum samples with satisfactory results. The simple, flexible, and convenient strategy provides a powerful tool for multiple biomarkers analysis and related clinical applications.