Transcriptional and hormonal control of adipose Treg heterogeneity and function.

Adipose tissue stores excess energy and produces a broad range of factors that regulate multiple physiological processes including systemic energy homeostasis. Visceral adipose tissue (VAT) plays a particularly important role in glucose metabolism as its endocrine function underpins food uptake and energy expenditure. Caloric excess triggers VAT inflammation which can impair insulin sensitivity and cause metabolic deregulation. Regulatory T cells (Tregs) that reside in the VAT suppress inflammation and protect from metabolic disease. The cellular components of VAT and its secretory products play a vital role in fostering the differentiation and maintenance of VAT Tregs. Critically, the physiology and inflammatory tone of VAT exhibit sex-specific disparities, resulting in substantial VAT Treg heterogeneity. Indeed, cytokines and sex hormones promote the differentiation of distinct populations of mature VAT Tregs, each characterized by unique phenotypes, homeostatic requirements, and functions. This review focuses on key findings that have significantly advanced our understanding of VAT Treg biology and the current state of the field, while also discussing open questions that require further exploration.

High-resolution stereolithography: Negative spaces enabled by control of fluid mechanics.

Stereolithography enables the fabrication of three-dimensional (3D) freeform structures via light-induced polymerization. However, the accumulation of ultraviolet dose within resin trapped in negative spaces, such as microfluidic channels or voids, can result in the unintended closing, referred to as overcuring, of these negative spaces. We report the use of injection continuous liquid interface production to continuously displace resin at risk of overcuring in negative spaces created in previous layers with fresh resin to mitigate the loss of Z-axis resolution. We demonstrate the ability to resolve 50-µm microchannels, breaking the historical relationship between resin properties and negative space resolution. With this approach, we fabricated proof-of-concept 3D free-form microfluidic devices with improved design freedom over device material selection and resulting properties.

Identification and Characterization of Synaptic Vesicle Membrane Protein VAT-1 Homolog as a New Catechin-Binding Protein.

(-)-Epigallocatechin-3-gallate (EGCg), a major constituent of green tea extract, is well-known to exhibit many beneficial actions for human health by interacting with numerous proteins. In this study we identified synaptic vesicle membrane protein VAT-1 homolog (VAT1) as a novel EGCg-binding protein in human neuroglioma cell extracts using a magnetic pull-down assay and LC-tandem mass spectrometry. We prepared recombinant human VAT1 and analyzed its direct binding to EGCg and its alkylated derivatives using surface plasmon resonance. For EGCg and the derivative NUP-15, we measured an association constant of 0.02-0.85 ×103 M-1s-1 and a dissociation constant of nearly 8 × 10-4 s-1. The affinity Km(affinity) of their binding to VAT1 was in the 10-20 µM range and comparable with that of other EGCg-binding proteins reported previously. Based on the common structure of the compounds, VAT1 appeared to recognize a catechol or pyrogallol moiety around the B-, C- and G-rings of EGCg. Next, we examined whether VAT1 mediates the effects of EGCg and NUP-15 on expression of neprilysin (NEP). Treatments of mock cells with these compounds upregulated NEP, as observed previously, whereas no effect was observed in the VAT1-overexpressing cells, indicating that VAT1 prevented the effects of EGCg or NUP-15 by binding to and inactivating them in the cells overexpressing VAT1. Further investigation is required to determine the biological significance of the VAT1-EGCg interaction.

Formulating biopharmaceuticals using three-dimensional printing.

Additive manufacturing, commonly referred to as three-dimensional (3D) printing, has the potential to initiate a paradigm shift in the field of medicine and drug delivery. Ever since the advent of the first-ever United States Food and Drug Administration (US FDA)-approved 3D printed tablet, there has been an increased interest in the application of this technology in drug delivery and biomedical applications. 3D printing brings us one step closer to personalized medicine, hence rendering the "one size fits all" concept in drug dosing obsolete. In this review article, we focus on the recent developments in the field of modified drug delivery systems in which various types of additive manufacturing technologies are applied.

Does the association between adiposity measures and pre-frailty among older adults vary by social position? Findings from the Tromsø study 2015/2016.

INTRODUCTION: Pre-frailty provides an ideal opportunity to prevent physical frailty and promote healthy ageing. Excess adiposity has been associated with an increased risk of pre-frailty, but limited studies have explored whether the association between adiposity measures and pre-frailty varies by social position. METHODS: We used data from the seventh survey of the Tromsø Study (Tromsø7) conducted in 2015-2016. Our primary sample consisted of 2,945 women and 2,794 men aged ≥ 65 years. Pre-frailty was defined as the presence of one or two of the five frailty components: low grip strength, slow walking speed, exhaustion, unintentional weight loss and low physical activity. Adiposity was defined by body mass index (BMI), waist circumference (WC), fat mass index (FMI) and visceral adipose tissue (VAT) mass. Education and subjective social position were used as measures of social position. Poisson regression with robust variance was used to assess the association between adiposity measures and pre-frailty, and the interaction term between adiposity measures and social position measures were utilised to explore whether the association varied by social position. RESULTS: In our sample, 28.7% of women and 25.5% of men were pre-frail. We found sub-multiplicative interaction of BMI-defined obesity with education in women and subjective social position in men with respect to development of pre-frailty. No other adiposity measures showed significant variation by education or subjective social position. Regardless of the levels of education or subjective social position, participants with excess adiposity (high BMI, high WC, high FMI and high VAT mass) had a higher risk of pre-frailty compared to those with low adiposity. CONCLUSION: We consistently observed that women and men with excess adiposity had a greater risk of pre-frailty than those with low adiposity, with only slight variation by social position. These results emphasize the importance of preventing excess adiposity to promote healthy ageing and prevent frailty among all older adults across social strata.

Population dynamics and bidirectional transfer of Listeria monocytogenes and Shiga toxin-producing Escherichia coli during cheese production in wooden vats.

Wooden vats are used in the production of some traditional cheeses as the biofilms on wooden vat surfaces are known to transfer large quantities of microbes to cheese. However, the safety of using wooden vats for cheese production remains controversial as the porous structure of wood provides an irregular surface that may protect any attached pathogen cells from cleaning and sanitation processes. On the other hand, the absence of pathogens in wooden vats has been reported in multiple studies and wooden materials have not been associated with foodborne illness outbreaks. The present study determined the survival of Listeria monocytogenes and Shiga toxin-producing Escherichia coli (STEC) during the production of an uncooked pressed cheese in wooden vats as well as their ability to transfer to the wood and then to milk used in subsequent batches of cheese production in the absence of formal cleaning. Results from the study indicate that pathogens inoculated in milk grew during production of the uncooked cheese, but showed limited ability to colonize the wooden vats and contaminate subsequent batches. These results suggest that the risks of using wooden vats to produce cheese is low if the milk is of high microbiological quality.

Additive Manufacturing: A Comprehensive Review.

Additive manufacturing has revolutionized manufacturing across a spectrum of industries by enabling the production of complex geometries with unparalleled customization and reduced waste. Beginning as a rapid prototyping tool, additive manufacturing has matured into a comprehensive manufacturing solution, embracing a wide range of materials, such as polymers, metals, ceramics, and composites. This paper delves into the workflow of additive manufacturing, encompassing design, modeling, slicing, printing, and post-processing. Various additive manufacturing technologies are explored, including material extrusion, VAT polymerization, material jetting, binder jetting, selective laser sintering, selective laser melting, direct metal laser sintering, electron beam melting, multi-jet fusion, direct energy deposition, carbon fiber reinforced, laminated object manufacturing, and more, discussing their principles, advantages, disadvantages, material compatibilities, applications, and developing trends. Additionally, the future of additive manufacturing is projected, highlighting potential advancements in 3D bioprinting, 3D food printing, large-scale 3D printing, 4D printing, and AI-based additive manufacturing. This comprehensive survey aims to underscore the transformative impact of additive manufacturing on global manufacturing, emphasizing ongoing challenges and the promising horizon of innovations that could further elevate its role in the manufacturing revolution.

Cellular Senescence and Extracellular Vesicles in the Pathogenesis and Treatment of Obesity-A Narrative Review.

This narrative review explores the pathophysiology of obesity, cellular senescence, and exosome release. When exposed to excessive nutrients, adipocytes develop mitochondrial dysfunction and generate reactive oxygen species with DNA damage. This triggers adipocyte hypertrophy and hypoxia, inhibition of adiponectin secretion and adipogenesis, increased endoplasmic reticulum stress and maladaptive unfolded protein response, metaflammation, and polarization of macrophages. Such feed-forward cycles are not resolved by antioxidant systems, heat shock response pathways, or DNA repair mechanisms, resulting in transmissible cellular senescence via autocrine, paracrine, and endocrine signaling. Senescence can thus affect preadipocytes, mature adipocytes, tissue macrophages and lymphocytes, hepatocytes, vascular endothelium, pancreatic ß cells, myocytes, hypothalamic nuclei, and renal podocytes. The senescence-associated secretory phenotype is closely related to visceral adipose tissue expansion and metaflammation; inhibition of SIRT-1, adiponectin, and autophagy; and increased release of exosomes, exosomal micro-RNAs, pro-inflammatory adipokines, and saturated free fatty acids. The resulting hypernefemia, insulin resistance, and diminished fatty acid ß-oxidation lead to lipotoxicity and progressive obesity, metabolic syndrome, and physical and cognitive functional decline. Weight cycling is related to continuing immunosenescence and exposure to palmitate. Cellular senescence, exosome release, and the transmissible senescence-associated secretory phenotype contribute to obesity and metabolic syndrome. Targeted therapies have interrelated and synergistic effects on cellular senescence, obesity, and premature aging.

Comprehensive analysis of body composition features in melanoma patients treated with tyrosine kinase inhibitors.

BACKGROUND: The introduction of tyrosine kinase inhibitors (TKI) has greatly improved the management of metastatic melanoma. Recent studies have uncovered a relationship between the body mass index (BMI) and outcome of patients with metastatic melanoma. However, conflicting results have challenged the relevance of this finding. In the current work, we aim to dissect body composition features of melanoma patients treated with TKI to evaluate their value as biomarkers. PATIENTS AND METHODS: We analyze body composition features via CT scans in a retrospective cohort of 57 patients with non-resectable stage III/IV melanoma receiving first-line treatment with TKI in our department, focusing on the impact of body composition on treatment efficacy and occurrence of adverse events. RESULTS: In uni- and multivariate analyses, we identify an association between the visceral adipose tissue gauge index (VATGI) and survival. We furthermore profile additional body composition features including sarcopenia, which was also associated with a shorter overall survival. Finally, we detected an enrichment of cases with fatigue in patients with low VATGI. CONCLUSIONS: Our study represents the first exploratory study evaluating the suitability of body composition measurements as biomarkers for melanoma patients treated with TKI. Our data suggest a putative use of VATGI as a biomarker predicting patient outcome.

Zirconia specimens printed by vat photopolymerization: Mechanical properties, fatigue properties, and fractography analysis.

PURPOSE: The mechanical and fatigue properties of zirconia specimens printed by vat photopolymerization (VPP) were evaluated and compared with those of zirconia specimens milled by computer numerical control (CNC). MATERIALS AND METHODS: Bar-shaped specimens were printed by stereolithography (SL) and digital light processing (DLP). CNC-milled specimens were used as control samples. The fracture toughness, hardness, and flexural strength properties of the zirconia specimens were evaluated via single edge V-notch beam tests, Vickers hardness tests, and 3-point bending tests. Dynamic fatigue tests were carried out in distilled water using a step-stress test. After static bending and dynamic step-stress testing, fractography analysis was performed. Statistical analysis was carried out to compare the fracture toughness, hardness, flexural strength, and fatigue cycle results of each group (α = 0.05). RESULTS: The fracture toughness values did not significantly differ among the groups (p > 0.05). The flexural strength was 894.10 MPa for SL, 831.46 MPa for DLP, and 1140.39 MPa for CNC. The flexural strength of CNC was greater than that of SL and DLP (p < 0.01). The mean fatigue cycles were 23498.07 for SL, 19858.60 for DLP, and 31566.80 for CNC. The mean fatigue failure strength was 643.13 MPa for SL, 530.63 MPa for DLP, and 903.75 MPa for CNC. The fatigue failure strength of CNC was greater than that of SL and DLP (p < 0.05). Fractography analysis revealed material defects at the fracture origin for each group. A partially fused structure of the incompletely debonded resin could be observed in SL, and a porous region of incompletely sintered zirconia grains could be observed in CNC. CONCLUSIONS: The fracture toughness and hardness of zirconia printed by VPP are comparable to those of zirconia milled by CNC. However, zirconia milled by CNC has superior static flexural strength and dynamic fatigue resistance. Further studies are needed to explore the clinical applications of VPP-printed zirconia.

Aphid adaptation to cucurbits: sugars, cucurbitacin and phloem structure in resistant and susceptible melons.

BACKGROUND: Aphis gossypii, a strictly phloemophagaous aphid, colonize hundreds of plant families, and a group of clones formed a cucurbit-specialised host-race. Cucurbits are unique in having evolved a specific extra-fascicular phloem (EFP), which carries defence-related metabolites such as cucurbitacin, whereas the fascicular phloem (FP) is common to all higher plants and carries primary metabolites, such as raffinose-family oligosaccharides (RFOs). Both cucurbitacins (in the EFP) and galactinol (in the FP) have been suggested to be toxic to aphids. We investigated these hypotheses in cucurbit-specialized A. gossypii fed on melon plants with or without aphid-resistance conferred by the NLR gene Vat. We selected a plant-aphid system with (i) Vat-mediated resistance not triggered, (ii) Vat-mediated resistance triggered by an aphid clone adapted to the presence of Vat resistant alleles and (iii) Vat-mediated resistance triggered by a non-adapted aphid clone. RESULTS: We quantified cucurbitacin B, its glycosylated derivative, and sugars, in melon plants and aphids that fed on. The level of cucurbitacin in plants was unrelated to both aphid infestation and aphid resistance. Galactinol was present at higher quantities in plants when Vat-mediated resistance was triggered, but its presence did not correlate with aphid performance. Finally, we showed that cucurbit-specialized A. gossypii fed from the FP but could also occasionally access the EFP without sustainably feeding from it. However, the clone not adapted to Vat-mediated resistance were less able to access the FP when the Vat resistance was triggered. CONCLUSION: We concluded that galactinol accumulation in resistant plants does not affect aphids, but may play a role in aphid adaptation to fasting and that Cucurbitacin in planta is not a real threat to Aphis gossypii. Moreover, the specific phloem of Cucurbits is involved neither in A. gossypii cucurbit specialisation nor in adaptation to Vat-dependent resistance.

Hopping Light Vat Photopolymerization for Multiscale Fabrication.

3D objects with features spanning from microscale to macroscale have various applications. However, the fabrication of such objects presents challenges to additive manufacturing (AM) due to the tradeoffs among manufacturable feature resolution, maximum build area, and printing speed. This paper presents a projection-based AM process called hopping light vat photopolymerization (HL-VPP) to address this critical barrier. The key idea of HL-VPP is to synchronize linear scanning projection with a galvo mirror's rotation. The projector moves continuously at a constant speed while periodically rotating a one-axis galvo mirror to compensate for the projector's linear movement so synchronized hopping motion can be achieved. By this means, HL-VPP can simultaneously achieve large-area (over 200 mm), fast-speed (scanning speed of 13.5 mm s-1 ), and high-resolution (10 µm pixel size) fabrication. The distinguishing characteristic of HL-VPP is that it allows for hundreds of times lower refresh rates without motion blur. Thus, HL-VPP decouples the fabrication efficiency limit imposed by the refresh rate and will enable super-fast curing in the future. This work will significantly advance VPP's use in applications that require macroscale part size with microscale features. The process has been verified by fabricating multiple multiscale objects, including microgrids and biomimetic structures.

Continuous Vat Photopolymerization for Optical Lens Fabrication.

Optical lenses require feature resolution and surface roughness that are beyond most (3D) printing methods. A new continuous projection-based vat photopolymerization process is reported that can directly shape polymer materials into optical lenses with microscale dimensional accuracy (< 14.7 µm) and nanoscale surface roughness (< 20 nm) without post-processing. The main idea is to utilize frustum layer stacking, instead of the conventional 2.5D layer stacking, to eliminate staircase aliasing. A continuous change of mask images is achieved using a zooming-focused projection system to generate the desired frustum layer stacking with controlled slant angles. The dynamic control of image size, objective and imaging distances, and light intensity involved in the zooming-focused continuous vat photopolymerization are systematically investigated. The experimental results reveal the effectiveness of the proposed process. The 3D-printed optical lenses with various designs, including parabolic lenses, fisheye lenses, and a laser beam expander, are fabricated with a surface roughness of 3.4 nm without post-processing. The dimensional accuracy and optical performance of the 3D-printed compound parabolic concentrators and fisheye lenses within a few millimeters are investiagted. These results highlight the rapid and precise nature of this novel manufacturing process, demonstrating a promising avenue for future optical component and device fabrication.

Temporally Stable Supramolecular Polymeric Salts Enabling High-Performance 3D All-Aromatic Polyimide Lattices.

Vat photopolymerization (VP) Additive Manufacturing (AM), in which UV light is selectively applied to cure photo-active polymers into complex geometries with micron-scale resolution, has a limited selection of aliphatic thermoset materials that exhibit relatively poor thermal performance. Ring-opening dianhydrides with acrylate-containing nucleophiles yielded diacrylate ester-dicarboxylic acids that enabled photo-active polyimide (PI) precursors, termed polysalts, upon neutralization with an aromatic diamine in solution. In situ FTIR spectroscopy coupled with a solution and photo-rheological measurements revealed a previously unknown time-dependent instability of 4,4'-oxydianiline (ODA) polysalts due to an aza-Michael addition. Replacement of the electron-donating ether-containing diamine with an electron withdrawing sulfone-containing monomer, e.g., 4,4'-diaminodiphenyl sulfone (DDS), prohibited the aza-Michael addition of the aromatic amine to the activated acrylate double bond. Novel DDS polysalt photocurable solutions are similarly analyzed and validated long-term stability, which enabled reproducible printing of polyimide organogel intermediates. Subsequent VP AM afforded 3-dimensional (3D) structures of intricate complexity and excellent surface finish, as demonstrated with scanning electron microscopy. In addition, the novel PMDA-HEA/DDS solution enabled the production of the first beam latticed architecture comprised of all-aromatic polyimide. The versatility of a polysalt platform for multi-material printing is further demonstrated by printing parts with alternating polysalt compositions.

A Data-Driven Approach to Complex Voxel Predictions in Grayscale Digital Light Processing Additive Manufacturing Using U-Nets and Generative Adversarial Networks.

Data-driven U-net machine learning (ML) models, including the pix2pix conditional generative adversarial network (cGAN), are shown to predict 3D printed voxel geometry in digital light processing (DLP) additive manufacturing. A confocal microscopy-based workflow allows for the high-throughput acquisition of data on thousands of voxel interactions arising from randomly gray-scaled digital photomasks. Validation between prints and predictions shows accurate predictions with sub-pixel scale resolution. The trained cGAN performs virtual DLP experiments such as feature size-dependent cure depth, anti-aliasing, and sub-pixel geometry control. The pix2pix model is also applicable to larger masks than it is trained on. To this end, the model can qualitatively inform layer-scale and voxel-scale print failures in real 3D-printed parts. Overall, machine learning models and the data-driven methodology, exemplified by U-nets and cGANs, show considerable promise for predicting and correcting photomasks to achieve increased precision in DLP additive manufacturing.

The potential role of omentin-1 in obesity-related metabolic dysfunction-associated steatotic liver disease: evidence from translational studies.

BACKGROUND: Obesity, characterized by visceral adipose tissue (VAT) expansion, is closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Recent research has highlighted the crucial role of the adipose tissue-liver axis in the development of MASLD. In this study, we investigated the potential role of omentin-1, a novel adipokine expressed by VAT, in obesity-related MASLD pathogenesis. METHODS: Through in silico analysis of differentially expressed genes in VAT from obese patients with and without MASH, we identified omentin-1 as a significant candidate. To validate our findings, we measured omentin-1 levels in VAT and plasma of lean controls and obese patients with biopsy-proven MASLD. Additionally, we assessed omentin-1 expression in the VAT of diet-induced mice MASLD model. In vitro and ex vivo studies were conducted to investigate the effects of omentin-1 on MASLD-related mechanisms, including steatosis, inflammation, endoplasmic reticulum (ER) stress, and oxidative stress. We also analyzed the impact of D-glucose and insulin on VAT omentin-1 levels ex vivo. RESULTS: Compared to the lean group, the obese groups exhibited significantly lower VAT and plasma levels of omentin-1. Interestingly, within the obese groups, omentin-1 is further decreased in MASH groups, independent of fibrosis. Likewise, VAT of mice fed with high-fat diet, showing histological signs of MASH showed decreased omentin-1 levels as compared to their control diet counterpart. In vitro experiments on fat-laden human hepatocytes revealed that omentin-1 did not affect steatosis but significantly reduced TNF-α levels, ER stress, and oxidative stress. Similar results were obtained using ex vivo VAT explants from obese patients upon omentin-1 supplementation. Furthermore, omentin-1 decreased the mRNA expression of NF-κB and mitogen-activated protein kinases (ERK and JNK). Ex vivo VAT explants showed that D-glucose and insulin significantly reduced omentin-1 mRNA expression and protein levels. CONCLUSIONS: Collectively, our findings suggest that reduced omentin-1 levels contribute to the development of MASLD. Omentin-1 supplementation likely exerts its beneficial effects through the inhibition of the NF-κB and MAPK signaling pathways, and it may additionally play a role in the regulation of glucose and insulin metabolism. Further research is warranted to explore omentin-1 as a potential therapeutic target and/or biomarker for MASLD.

Genome wide identification and evolutionary analysis of vat like NBS-LRR genes potentially associated with resistance to aphids in cotton.

Nucleotide Binding Site - Leucine Rich Repeat (NBS-LRR) genes play a significant role in plant defense against biotic stresses and are an integral part of signal transduction pathways. Vat gene has been well reported for their role in resistance to Aphis gossypii and viruses transmitted by them. Despite their importance, Vat like NBS-LRR resistance genes have not yet been identified and studied in cotton species. This study report hundreds of orthologous Vat like NBS-LRR genes from the genomes of 18 cotton species through homology searches and the distribution of those identified genes were tend to be clustered on different chromosome. Especially, in a majority of the cases, Vat like genes were located on chromosome number 13 and they all shared two conserved NBS-LRR domains, one disease resistant domain and several repeats of LRR on the investigated cotton Vat like proteins. Gene ontology study on Vat like NBS-LRR genes revealed the molecular functions viz., ADP and protein binding. Phylogenetic analysis also revealed that Vat like sequences of two diploid species, viz., G. arboreum and G. anomalum, were closely related to the sequences of the tetraploids than all other diploids. The Vat like genes of G. aridum and G. schwendimanii were distantly related among diploids and tetraploids species. Various hormones and defense related cis-acting regulatory elements were identified from the 2 kb upstream sequences of the Vat like genes implying their defensive response towards the biotic stresses. Interestingly, G. arboreum and G. trilobum were found to have more regulatory elements than larger genomes of tetraploid cotton species. Thus, the present study provides the evidence for the evolution of Vat like genes in defense mechanisms against aphids infestation in cotton genomes and allows further characterization of candidate genes for developing aphid and aphid transmitted viruses resistant crops through cotton breeding.

Wavelength Selective Multi-Material 3D Printing of Soft Active Devices Using Orthogonal Photoreactions.

Orthogonal photoreactions provide a unique way to locally and independently control (thermo)mechanical properties and functionality of polymer networks simply by choice of the wavelength. Herein, a library of acrylate functional coumarin monomers is synthesized, which are cured by sequence-dependent wavelength orthogonality. In the presence of a long wavelength absorbing photoinitiator, the monomers undergo rapid curing by visible light induced radical chain growth polymerization. Subsequent irradiation with light in the UV-A region selectively initiates the [2+2] photocycloaddition of the coumarin chromophores, which is confirmed by FTIR and UV-vis experiments. Through a well-targeted design, acrylate-based and thiol-acrylate resin formulations are prepared, whose fast curing rate, low viscosity, and prolonged storage stability enable the one-step fabrication of multi-material structures by digital light processing (DLP) 3D printing. By using a dual-wavelength printer, which operates at two different wavelengths (405 and 365 nm), objects comprising soft (ε = 22%, σ = 7.5 MPa) and stiff (ε = 2%, σ = 8.3 MPa) domains are printed with a single resin vat. Along with tensile properties, the wavelength selective change in the network structure features a local control of the glass transition temperature (ΔTg  = 17 °C) in the 3D-printed objects. Soft active devices are fabricated by dual-wavelength DLP 3D printing, with distinct domains having a higher Tg and the local programming of multi shapes is demonstrated.

Fabrication of 3D-Printed Contact Lens Composed of Polyethylene Glycol Diacrylate for Controlled Release of Azithromycin.

Since three-dimensional (3D)-printed tablets were approved by the United States Food and Drug Administration (FDA), 3D printing technology has garnered increasing interest for the fabrication of medical and pharmaceutical devices. With various dosing devices being designed for manufacture by 3D printing, 3D-printed ophthalmic formulations to release drugs have been one such target of investigation. In the current study, 3D-printed contact lenses designed for the controlled release of the antibiotic azithromycin were produced by vat photopolymerization, and the effect of the printer ink composition and a second curing process was investigated. The azithromycin-loaded contact lenses were composed of the cross-linking reagent polyethylene glycol diacrylate (PEGDA), PEG 400 as a solvent, a photoinitiator, and azithromycin. The 3D-printed contact lenses were fabricated successfully, and formulations with lower PEGDA concentrations produced thicker lenses. The mechanical strength of the PEGDA-based contact lenses was dependent on the amount of PEGDA and was improved by a second curing process. Drug release from 3D-printed contact lenses was reduced in the samples with a second curing process. The azithromycin-loaded contact lenses exhibited antimicrobial effects in vitro for both Gram-positive and -negative bacteria. These results suggest that 3D-printed contact lenses containing antibiotics are an effective model for treating eye infections by controlling drug release.

Valbenazine isomers and enantiomer determination by chiral normal phase liquid chromatography.

A novel, simple, specific, rapid, enantioselective normal phase chiral high-performance liquid chromatographic method with amylose-based Chiral Pak IG-3(250 × 4.6 mM) 3.0 µM column was developed and validated for separation and quantification of isomers and enantiomer of Valbenazine. The mobile phase composed of n-Heptane, isopropyl alcohol, dichloromethane, ethanol, and diethylamine in the ratio of 70:10:15:5:0.1 (V/V/V/VV) with a gradient flow rate was applied. The injection volume was 10 µl, and detection was carried out using a photodiode array detector at 282 nM. The column compartment was set at 35°C. The resolution between the enantiomer and isomers was found to be more than 2.0. The method was linear over the concentration range of limit of quantitation to 250% for isomers and enantiomers. The method was found to be robust with column temperature. The proposed chiral method is applicable for the determination of isomers and enantiomer of Valibenazine and was successfully used in the quality control of bulk drug manufacturing and pharmaceuticals.