Biodegradation of oxidized low density polyethylene by Pelosinus fermentans lipase.

Polyethylene (PE) exhibits high resistance to degradation, contributing to plastic pollution. PE discarded into the environment is photo-oxidized by sunlight and oxygen. In this study, a key enzyme capable of degrading oxidized PE is reported for the first time. Twenty different enzymes from various lipase families were evaluated for hydrolytic activity using substrates mimicking oxidized PE. Among them, Pelosinus fermentans lipase 1 (PFL1) specifically cleaved the ester bonds within the oxidized carbon-carbon backbone. Moreover, PFL1 (6 µM) degraded oxidized PE film, reducing the weight average and number average molecular weights by 44.6 and 11.3 %, respectively, within five days. Finally, structural analysis and molecular docking simulations were performed to elucidate the degradation mechanism of PFL1. The oxidized PE-degrading enzyme reported here will provide the groundwork for advancing PE waste treatment technology and for engineering microbes to repurpose PE waste into valuable chemicals.

Biotechnological Plastic Degradation and Valorization Using Systems Metabolic Engineering.

Various kinds of plastics have been developed over the past century, vastly improving the quality of life. However, the indiscriminate production and irresponsible management of plastics have led to the accumulation of plastic waste, emerging as a pressing environmental concern. To establish a clean and sustainable plastic economy, plastic recycling becomes imperative to mitigate resource depletion and replace non-eco-friendly processes, such as incineration. Although chemical and mechanical recycling technologies exist, the prevalence of composite plastics in product manufacturing complicates recycling efforts. In recent years, the biodegradation of plastics using enzymes and microorganisms has been reported, opening a new possibility for biotechnological plastic degradation and bio-upcycling. This review provides an overview of microbial strains capable of degrading various plastics, highlighting key enzymes and their role. In addition, recent advances in plastic waste valorization technology based on systems metabolic engineering are explored in detail. Finally, future perspectives on systems metabolic engineering strategies to develop a circular plastic bioeconomy are discussed.

A Versatile Strategy for Screening Custom-Designed Warhead-Armed Cyclic Peptide Inhibitors.

Demand for peptide-based pharmaceuticals has been steadily increasing, but only limited success has been achieved to date. To expedite peptide-based drug discovery, we developed a general scheme for cell-based screening of cyclic peptide inhibitors armed with a user-designed warhead. We combined unnatural amino acid incorporation and split intein-mediated peptide cyclization techniques and integrated a yeast-based colorimetric screening assay to generate a new scheme that we call the custom-designed warhead-armed cyclic peptide screening platform (CWCPS). This strategy successfully discovered a potent inhibitor, CY5-6Q, that targets human histone deacetylase 8 (HDAC8) with a KD value of 15 nM. This approach can be a versatile and general platform for discovering cyclic peptide inhibitors.

Prediction of breast cancer-related lymphedema risk after postoperative radiotherapy via multivariable logistic regression analysis.

Purpose: We identified novel clinical and dosimetric prognostic factors affecting breast cancer-related lymphedema after postoperative radiotherapy (RT) and developed a multivariable logistic regression model to predict lymphedema in these patients. Methods and materials: In total, 580 patients with unilateral breast cancer were retrospectively reviewed. All patients underwent breast surgery and postoperative RT with or without systemic treatment in 2015. Among the 580 patients, 532 with available RT plan data were randomly divided into training (n=372) and test (n=160) cohorts at a 7:3 ratio to generate and validate the lymphedema prediction models, respectively. An area under the curve (AUC) value was estimated to compare models. Results: The median follow-up duration was 5.4 years. In total, 104 (17.9%) patients experienced lymphedema with a cumulative incidence as follows: 1 year, 10.5%; 3 years, 16.4%; and 5 years, 17.6%. Multivariate analysis showed that body mass index ≥25 kg/m2 (hazard ratio [HR] 1.845), dissected lymph nodes ≥7 (HR 1.789), and taxane-base chemotherapy (HR 4.200) were significantly associated with increased lymphedema risk. Conversely, receipt of RT at least 1 month after surgery reduced the risk of lymphedema (HR 0.638). A multivariable logistic regression model using the above factors, as well as the minimum dose of axillary level I and supraclavicular lymph node, was created with an AUC of 0.761 and 0.794 in the training and test cohorts, respectively. Conclusions: Our study demonstrated that a shorter interval from surgery to RT and other established clinical factors were associated with increased lymphedema risk. By combining these factors with two dosimetric parameters, we propose a multivariable logistic regression model for breast cancer-related lymphedema prediction after RT.

Scleral Fixation of a Hydrophobic Acrylic Intraocular Lens with Eyelets Using 8-0 Polypropylene Suture.

PURPOSE: To report clinical outcomes of a scleral fixation technique of a hydrophobic acrylic intraocular lens with eyelets using 8-0 polypropylene suture. METHODS: Nine eyes of nine patients who underwent combined pars plana vitrectomy and sclera fixation of an intraocular lens using this technique were analyzed. RESULTS: The mean follow-up period was 7.11 months (range, 6-12 months), and there was a significant visual improvement at 6 months after surgery. The mean logarithm of the minimum angle of the resolution changed from 0.54 at baseline to 0.29 at postoperative 6 months (p = 0.016). The mean postoperative spherical equivalent at 6 months was -0.90 ± 0.90 diopters, and the mean predictive error was -0.49 ± 0.62 diopters. CONCLUSIONS: Postoperative visual and refractive outcomes were favorable, and the positions of intraocular lenses were well centered in all cases. This technique could be a useful alternative for surgeons without easy access to Gore-Tex suture.

Spontaneous Rib Fractures After Breast Cancer Treatment Based on Bone Scans: Comparison Of Conventional Versus Hypofractionated Radiotherapy.

BACKGROUND: Spontaneous rib fractures (SRFs) are defined as fractures without apparent blunt force trauma. This study evaluated the incidence and risk factors of SRFs after treatment of patients with breast cancer based on bone scans. In addition, we analyzed radiation-associated SRFs and identified radiotherapy (RT) factors related to SRF. PATIENTS AND METHODS: We retrospectively reviewed 1265 patients with breast cancer who underwent surgery in 2015 at our institution, and were followed-up with at least 3 bone scans. Bone scans were conducted approximately every 12 months after breast cancer treatment. The endpoint was SRF detected by bone scan. In this study, 754 (60%) patients were treated with chemotherapy, 867 (69%) with RT, and 946 (75%) with anti-hormone therapy. RESULTS: The median follow-up duration was 37.5 months. A total of 209 (16.5%) patients experienced SRFs during follow-up. The incidence of SRFs increased sharply during the 3-year follow-up period after completion of treatment. In multivariate analyses, abnormal bone density, chemotherapy, and RT were significant risk factors for SRFs. In patients treated with RT (n = 867), 159 (18%) rib fractures occurred: 127 (80%) in the ipsilateral breast and 32 (20%) in the contralateral breast. Among the patients with ipsilateral SRFs who received tumor bed boost (n = 84), the SRF occurred inside the boost field in 80 (95%) cases. Multivariate analysis of RT subgroups showed that hypofractionated RT increased the rate of SRFs (P = .002). CONCLUSIONS: Most of the rib fractures that occurred after treatment were spontaneous. Hypofractionated RT increased the risk of ipsilateral rib fractures in RT-treated patients.

Cyclic Peptides: Promising Scaffolds for Biopharmaceuticals.

To date, small molecules and macromolecules, including antibodies, have been the most pursued substances in drug screening and development efforts. Despite numerous favorable features as a drug, these molecules still have limitations and are not complementary in many regards. Recently, peptide-based chemical structures that lie between these two categories in terms of both structural and functional properties have gained increasing attention as potential alternatives. In particular, peptides in a circular form provide a promising scaffold for the development of a novel drug class owing to their adjustable and expandable ability to bind a wide range of target molecules. In this review, we discuss recent progress in methodologies for peptide cyclization and screening and use of bioactive cyclic peptides in various applications.

Effect of Co-Implantation of a Capsular Tension Ring on Clinical Outcomes after Cataract Surgery with Monofocal Intraocular Lens Implantation.

PURPOSE: The objective was to evaluate the effect of co-implantation of a preloaded capsular tension ring (CTR) and aberration-free monofocal intraocular lens (IOL) on clinical outcomes and visual quality after cataract surgery. MATERIALS AND METHODS: Patients who underwent cataract surgery were randomized into two groups that were implanted with a CTR and IOL (group 1, 26 eyes) or an IOL only (group 2, 26 eyes). At 1 and 3 months after surgery, visual acuity, refractive errors, refractive prediction errors, ocular aberrations, and modulation transfer function (MTF) were analyzed. At 3 months postoperatively, anterior chamber depth (ACD) and contrast sensitivity were evaluated. RESULTS: Group 1 showed greater hyperopic shift, which caused the refractive prediction error at 3 months after surgery to be significantly different between the two groups (p=0.049). Differences in ACD between the preoperative and postoperative periods tended to be greater in group 1 than in group 2. At 3 months postoperatively, internal MTF values at 20, 25, and 30 cycles per degree were significantly better in group 1 than in group 2 (p=0.034, 0.017, and 0.017, respectively). Contrast sensitivity showed comparable results at almost all spatial frequencies between the groups. CONCLUSION: Regarding visual acuity and quality, both groups showed comparable results. Co-implantation of a CTR and aberration-free monofocal IOL was associated with hyperopic refractive outcomes. Surgeons should consider the position of the IOL when planning co-implantation of a CTR and IOL.

INTRAVITREAL RANIBIZUMAB THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND THE RISK OF STROKE: A National Sample Cohort Study.

PURPOSE: To evaluate the risk of stroke after ranibizumab treatment for neovascular age-related macular degeneration. METHODS: National registry data for 1,025,340 random subjects in the year 2002 were used. The ranibizumab group comprised patients diagnosed with neovascular age-related macular degeneration and treated with ranibizumab between 2009 and 2013 (n = 467). The two types of comparison groups were defined as comorbidity-matched controls (n = 2,330) comprised of randomly selected patients (5 per age-related macular degeneration patient), who were matched to the ranibizumab group according to sociodemographic factors, hypertension, atrial fibrillation, and the Charlson comorbidities index, and sociodemographic-matched controls (n = 2,331) matched according to sociodemographic factors only. Each sampled patient was tracked until 2013. The Cox proportional hazard regression was used. RESULTS: Stroke occurred in 6.6% of the ranibizumab group versus 7.0% of the comorbidity-matched controls and 6.7% of the sociodemographic-matched controls; these differences were not statistically significant. The overall incidence of stroke was similar for the ranibizumab group versus the comorbidity-matched controls and sociodemographic-matched controls, based on the multivariable Cox regression (hazard ratio = 0.88; 95% confidence interval, 0.60-1.30; hazard ratio = 0.95, 95% confidence interval, 0.64-1.41, respectively). CONCLUSION: Ranibizumab treatment for neovascular age-related macular degeneration did not increase the overall risk of stroke, compared with comorbidity-matched controls or sociodemographic-matched controls.

Optic Atrophy in a Patient With Atypical Pantothenate Kinase-Associated Neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegeneration with brain iron accumulation and characterized by extrapyramidal signs, vision loss, and intellectual decline. PKAN is caused by mutations in the PANK2 gene, which codes for a mitochondrial enzyme that phosphorylates vitamin B5 in the first reaction of the coenzyme A biosynthetic pathway. Visual failure in this disorder is typically due to pigmentary retinopathy. Yet our patient, a 13-year-old girl with PKAN, developed bilateral optic atrophy and the appearance of the retina and electroretinography were normal. Optic atrophy is a rare finding in patients with PKAN. It is important for the clinician to consider PKAN in the differential diagnosis of patients presenting with signs of extrapyramidal dysfunction, cognitive decline, and vision loss because of optic atrophy.

Effect of trabeculectomy on the accuracy of intraocular lens calculations in patients with open-angle glaucoma.

BACKGROUND: The objective of the study is to examine the effect of trabeculectomy on intraocular lens power calculations in patients with open-angle glaucoma (OAG) undergoing cataract surgery. DESIGN: The design is retrospective data analysis. PARTICIPANTS: There are a total of 55 eyes of 55 patients with OAG who had a cataract surgery alone or in combination with trabeculectomy. METHODS: We classified OAG subjects into the following groups based on surgical history: only cataract surgery (OC group), cataract surgery after prior trabeculectomy (CAT group), and cataract surgery performed in combination with trabeculectomy (CCT group). MAIN OUTCOME MEASURES: Differences between actual and predicted postoperative refractive error. RESULTS: Mean error (ME, difference between postoperative and predicted SE) in the CCT group was significantly lower (towards myopia) than that of the OC group (P = 0.008). Additionally, mean absolute error (MAE, absolute value of ME) in the CAT group was significantly greater than in the OC group (P = 0.006). Using linear mixed models, the ME calculated with the SRK II formula was more accurate than the ME predicted by the SRK T formula in the CAT (P = 0.032) and CCT (P = 0.035) groups. CONCLUSIONS: The intraocular lens power prediction accuracy was lower in the CAT and CCT groups than in the OC group. The prediction error was greater in the CAT group than in the OC group, and the direction of the prediction error tended to be towards myopia in the CCT group. The SRK II formula may be more accurate in predicting residual refractive error in the CAT and CCT groups.