pH-Responsive Inorganic/Organic Nanohybrids System for Controlled Nicotinic Acid Drug Release.

Although nicotinic acid (NA) has several clinical benefits, its potency cannot be fully utilized due to several undesirable side effects, including cutaneous flushing, GIT-associated symptoms, etc. To overcome such issues and improve the NA efficacy, a new inorganic-organic nanohybrids system was rationally designed. For making such a hybrid system, NA was intercalated into LDH through a coprecipitation technique and then coated with Eudragit® S100 to make the final drug delivery system called Eudragit® S100-coated NA-LDH. The as-made drug delivery system not only improved the NA release profile but also exhibited good bio-compatibility as tested on L929 cells. Such an inorganic-organic nanohybrid drug delivery agent is expected to reduce the undesirable side effects associated with NA and hopefully improve the pharmacological effects without inducing any undesirable toxicity.

Artificial cell factory design for shikimate production in Escherichia coli.

Shikimate is a key intermediate in high demand for synthesizing valuable antiviral drugs, such as the anti-influenza drug and oseltamivir (Tamiflu®). Microbial-based shikimate production strategies have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. Although shikimate biosynthesis has been reported in several engineered bacterial species, the shikimate production yield is still unsatisfactory. This study designed an Escherichia coli cell factory and optimized the fed-batch culture process to achieve a high titer of shikimate production. Using the previously constructed dehydroshikimate (DHS)-overproducing E. coli strain, two genes (aroK and aroL) responsible for converting shikimate to the next step were disrupted to facilitate shikimate accumulation. The genes with negative effects on shikimate biosynthesis, including tyrR, ptsG, and pykA, were disrupted. In contrast, several shikimate biosynthetic pathway genes, including aroB, aroD, aroF, aroG, and aroE, were overexpressed to maximize the glucose uptake and intermediate flux. The shiA involved in shikimate transport was disrupted, and the tktA involved in the accumulation of both PEP and E4P was overexpressed. The rationally designed shikimate-overproducing E. coli strain grown in an optimized medium produced approximately 101 g/l of shikimate in 7-l fed-batch fermentation, which is the highest level of shikimate production reported thus far. Overall, rational cell factory design and culture process optimization for microbial-based shikimate production will play a key role in complementing traditional plant-derived shikimate production processes.

A 3D Printable Electroconductive Biocomposite Bioink Based on Silk Fibroin-Conjugated Graphene Oxide.

Reduced graphene oxide (rGO) has wide application as a nanofiller in the fabrication of electroconductive biocomposites due to its exceptional properties. However, the hydrophobicity and chemical stability of rGO limit its ability to be incorporated into precursor polymers for physical mixing during biocomposite fabrication. Moreover, until now, no suitable rGO-combining biomaterials that are stable, soluble, biocompatible, and 3D printable have been developed. In this study, we fabricated digital light processing (DLP) printable bioink (SGOB1), through covalent reduction of graphene oxide (GO) by glycidyl methacrylated silk fibroin (SB). Compositional analyses showed that SGOB1 contains approximately 8.42% GO in its reduced state. Our results also showed that the rGO content of SGOB1 became more thermally stable and highly soluble. SGOB1 hydrogels demonstrated superior mechanical, electroconductive, and neurogenic properties than (SB). Furthermore, the photocurable bioink supported Neuro2a cell proliferation and viability. Therefore, SGOB1 could be a suitable biocomposite for neural tissue engineering.

Reliability of implant stability measuring devices depending on various clinical conditions: an in vitro study.

PURPOSE: The aim of this study was to evaluate the reliability of implant stability measuring devices depending on the location of the implant and the position of the patient. MATERIALS AND METHODS: Six implants were installed in different dentate sextants of six artificial bone models. Implant stability was measured in three conditions of the bone model (without mounting on a phantom head, mounted on a phantom head in supine position, and mounted on a phantom head in upright position). A resonance frequency analysis device (Osstell) and two damping capacity analysis devices (Periotest and Anycheck) were used to measure implant stability. The values measured outside the phantom head were treated as controls, and the values inside the phantom head were compared using an independent t-test. RESULTS: Osstell showed different results in two of the six divisions in both the supine and upright positions compared to outside of the mouth (P < .05). Periotest showed different results in all six parts in the supine position and in five parts in the upright position compared to outside of the mouth (P < .05). While Anycheck showed different results in five areas in the supine position compared to outside of the mouth, it showed different results in only one area in the upright position (P < .05). CONCLUSION: In the difficult implant position for the operator to access, the implant stability measuring devices show less reliability. The accessibility of implant is greatly affected in the order of Osstell, Anycheck, and Periotest.

Silk Fibroin-Based Biomaterials for Hemostatic Applications.

Hemostasis plays an essential role in all surgical procedures. Uncontrolled hemorrhage is the primary cause of death during surgeries, and effective blood loss control can significantly reduce mortality. For modern surgeons to select the right agent at the right time, they must understand the mechanisms of action, the effectiveness, and the possible adverse effects of each agent. Over the past decade, various hemostatic agents have grown intensely. These agents vary from absorbable topical hemostats, including collagen, gelatins, microfibrillar, and regenerated oxidized cellulose, to biologically active topical hemostats such as thrombin, biological adhesives, and other combined agents. Commercially available products have since expanded to include topical hemostats, surgical sealants, and adhesives. Silk is a natural protein consisting of fibroin and sericin. Silk fibroin (SF), derived from silkworm Bombyx mori, is a fibrous protein that has been used mostly in fashion textiles and surgical sutures. Additionally, SF has been widely applied as a potential biomaterial in several biomedical and biotechnological fields. Furthermore, SF has been employed as a hemostatic agent in several studies. In this review, we summarize the several morphologic forms of SF and the latest technological advances on the use of SF-based hemostatic agents.

Effect of phosphorus concentration on phosphorus removal and biomass.

Membrane bioreactor (MBR) process was employed to study the effect of biological phosphorus removal (bio-P removal) and P-content in treated sludge with increased phosphorus concentration present in the wastewater. Further, the following four test fractions of raw wastewaters was obtained having different P-concentrations viz., run 1: P-20 mg/L, run 2: P-40 mg/L, run 3: P-60 mg/L, run 4: P-80 mg/L. The effective P-removal obtained for these four test fractions were found to be 23.07 mg/L (98.17%), 41.35 mg/L (88.16%), 45.75 mg/L (72.04%) and 55.80 mg/L (66.82%) respectively for run 1, 2, 3 and 4 fractions. Moreover, the similar increase in phosphorous concentration i.e., from 20 to 80 mg/L caused an apparent increase in total solid (TS) values from 7 to 8.3 g TS/L, whereas the total volatile solid (TVS) content remained constant (i.e. 4.5 g TVS/L). These results inferred that the proportion of TVS in the TS decreased from 70 to 55%. Moreover, by increasing the initial P-concentration from 20 to 80 mg/L, the corresponding P-proportion of excess sludge was increased from 2 to 6.2%.

Cytocompatibility of Modified Silk Fibroin with Glycidyl Methacrylate for Tissue Engineering and Biomedical Applications.

Hydrogel with chemical modification has been used for 3D printing in the biomedical field of cell and tissue-based regeneration because it provides a good cellular microenvironment and mechanical supportive ability. As a scaffold and a matrix, hydrogel itself has to be modified chemically and physically to form a ß-sheet crosslinking structure for the strength of the biomaterials. These chemical modifications could affect the biological damage done to encapsulated cells or surrounding tissues due to unreacted chemical residues. Biological assessment, including assessment of the cytocompatibility of hydrogel in clinical trials, must involve testing with cytotoxicity, irritation, and sensitization. Here, we modified silk fibroin and glycidyl methacrylate (Silk-GMA) and evaluated the physical characterizations, residual chemical detection, and the biological effect of residual GMA depending on dialysis periods. Silk-GMA depending on each dialysis period had a typical ß-sheet structure in the characterization analysis and residual GMA decreased from dialysis day 1. Moreover, cell proliferation and viability rate gradually increased; additionally, necrotic and apoptotic cells decreased from dialysis day 2. These results indicate that the dialysis periods during chemical modification of natural polymer are important for removing unreacted chemical residues and for the potential application of the manufacturing standardization for chemically modified hydrogel for the clinical transplantation for tissue engineering and biomedical applications.

Brimonidine-montmorillonite hybrid formulation for topical drug delivery to the eye.

Brimonidine (BMD) is often prescribed as an eye drop to reduce the intraocular pressure (IOP) for glaucoma treatment. However, eye drops are limited by rapid clearance from the preocular surface, and hence a low ocular drug bioavailability. Therefore, in this study, we propose montmorillonite (MMT), as a delivery carrier, hybridized with BMD (BMD-MMT) for topical drug delivery to the eye. The BMD-MMT hybrid was prepared by intercalating the BMD molecules in the interlayer space of the MMT lattice via ion-exchange reaction; it was then formulated with polyvinyl alcohol (PVA) to produce a dry tablet (i.e., BMD-MMT@PVA). The BMD-MMT@PVA hybrid drug released BMD in a sustained manner for more than 5 h under in vitro conditions. When the hybrid drug was administered to rabbit eyes in vivo, 43% and 18.5% BMD-MMT still remained on the preocular surface for 10 and 60 min after administration, respectively. Thus, the BMD-MMT@PVA hybrid drug exhibited a prolonged decrease in IOP, that is, for 12 h, which was approximately two times longer than that observed with the commercially available BMD eye drop, Alphagan® P.

Early exposure to UV radiation overshadowed by precipitation and litter quality as drivers of decomposition in the northern Chihuahuan Desert.

Dryland ecosystems cover nearly 45% of the Earth's land area and account for large proportions of terrestrial net primary production and carbon pools. However, predicting rates of plant litter decomposition in these vast ecosystems has proven challenging due to their distinctly dry and often hot climate regimes, and potentially unique physical drivers of decomposition. In this study, we elucidated the role of photopriming, i.e. exposure of standing dead leaf litter to solar radiation prior to litter drop that would chemically change litter and enhance biotic decay of fallen litter. We exposed litter substrates to three different UV radiation treatments simulating three-months of UV radiation exposure in southern New Mexico: no light, UVA+UVB+Visible, and UVA+Visible. There were three litter types: mesquite leaflets (Prosopis glandulosa, litter with high nitrogen (N) concentration), filter paper (pure cellulose), and basswood (Tilia spp, high lignin concentration). We deployed the photoprimed litter in the field within a large scale precipitation manipulation experiment: ∼50% precipitation reduction, ∼150% precipitation addition, and ambient control. Our results revealed the importance of litter substrate, particularly N content, for overall decomposition in drylands, as neither filter paper nor basswood exhibited measurable mass loss over the course of the year-long study, while high N-containing mesquite litter exhibited potential mass loss. We saw no effect of photopriming on subsequent microbial decay. We did observe a precipitation effect on mesquite where the rate of decay was more rapid in ambient and precipitation addition treatments than in the drought treatment. Overall, we found that precipitation and N played a critical role in litter mass loss. In contrast, photopriming had no detected effects on mass loss over the course of our year-long study. These results underpin the importance of biotic-driven decomposition, even in the presence of photopriming, for understanding litter decomposition and biogeochemical cycles in drylands.

Primary Sjogren syndrome diagnosed simultaneously with localized amyloidosis of the lacrimal gland: A case report.

INTRODUCTION: Amyloidosis accompanied by Sjögren's syndrome (SS) has been reported to occur primarily in the skin, lungs, tongue, and mammary gland. However, SS in association with secondary amyloidosis is rarely reported, and knowledge of its relevance is inadequate. Here we report a case of primary SS diagnosed simultaneously with localized amyloidosis of the lacrimal gland. CASE PRESENTATION: A 45-year-old woman complaining of a left eyelid mass was referred to the hospital and was diagnosed with localized amyloidosis after excisional biopsy. She was then referred to the rheumatology department for additional evaluation for amyloidosis. Subsequently, her diagnosis was primary SS based on the presented symptoms and results of the Schirmer test, serologic testing, and minor salivary gland biopsy. Pilocarpine (10 mg/d) and hydroxychloroquine (200 mg/d) were initiated for the treatment of SS. Six months after the initial diagnosis, the dry eyes and mouth did not worsen and no masses suggestive of localized amyloidosis were reported. CONCLUSION: This is a rare case of amyloidosis, localized to the lacrimal gland, with SS. Therefore, despite its rarity, physicians should be aware of the potential coexistence of secondary amyloidosis, even in the localized form, in patients with SS.

Fast in situ enzymatic gelation of PPO-PEO block copolymer for injectable intraocular lens in vivo.

Foldable intraocular lenses (IOLs) have been utilized to substitute natural lens of cataract patients. In this study, we developed a fast, in situ gelable hydrogel requiring no toxic agent as an injectable IOL material. A 4-armed PPO/PEO-phenol conjugate by a non-degradable linker was synthesized to form a hydrogel in situ by horseradish peroxidase. The gelation time and modulus could be controlled, ranging from 20 s to 2 min and from 1 to 43 kPa. The adhesion of human lens epithelial cells on the hydrogel was significantly reduced compared to that on commercial IOLs. The hydrogels were injected into the rabbit eyes to evaluate the in vivo biocompatibility for 8 weeks. Corneal endothelial cell loss and central corneal thickness were comparable with the common IOL implantation procedure. Histologically, the cornea and retina showed the intact structure. The change of refraction after application of pilocarpine was +0.42 D preoperatively and +0.83 D postoperatively, which may indicate the maintenance of accommodation amplitude.