The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens\' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

UNASSIGNED: In regular dental practice, dentinal hypersensitivity is a common oral condition affecting the adult population. Although a variety of treatment procedures are available, there is no single method that proved to be potent in eliminating dentine hypersensitivity and providing patients with complete relief. Hence the present study performed to estimate the occlusion of dentinal tubules using a diode laser alone and in combination with various desensitizing toothpaste, using the scanning electron microscope.
UNASSIGNED: This in-vitro study consisted of five groups wherein cervical cavities were prepared on the extracted teeth followed by the application of 17% EDTA. The cavities were then treated with Novamin toothpaste, pro-arginine toothpaste, diode laser, and in combinations respectively. Then SEM analysis was done and the results obtained were statistically analyzed using tukey\'s multiple post hoc analysis for intra and inter group comparisons.
UNASSIGNED: The groups which were treated with a combination of diode laser and the desensitizing agent showed statistically significant (P < 0.05) better dentinal tubule occlusion than other groups.
UNASSIGNED: The use of a diode laser has an added benefit in treating dentinal tubule occlusion when compared to desensitizing kinds of toothpaste.

Purple non-sulphur bacteria (PNSB) are of interest for biorefinery applications to create biomolecules, but their production cost is expensive due to substrate and biomass separation costs. This research has utilized fuel synthesis wastewater (FSW) as a low-cost carbon-rich substrate to produce single-cell protein (SCP) and examines PNSB biofilm formation using this substrate to achieve a more efficient biomass-liquid separation. In this study, PNSB were grown in Ca, Mg, S, P, and N-deficient media using green shade as biofilm support material. Among these nutrient conditions, only N-deficient and control (nutrient-sufficient) conditions showed biofilm formation. Although total biomass growth of the control was 1.5 times that of the N-deficient condition and highest overall, the total biofilm-biomass in the N-deficient condition was 2.5 times greater than the control, comprising 49% of total biomass produced. Total protein content was similar between these four biomass samples, ranging from 35.0 ± 0.2% to 37.2 ± 0.0%. The highest protein content of 44.7 ± 1.3% occurred in the Mg-deficient condition (suspended biomass only) but suffered from a low growth rate. Overall, nutrient sufficient conditions are optimal for overall protein productivity and dominated by suspended growth, but where fixed growth systems are desired for cost-effective harvesting, N-deficient conditions provide an effective means to maximize biofilm production without sacrificing protein content.

This study evaluated the viability of encapsulated Lactobacillus delbrueckii subsp. bulgaricus in chocolate during storage and in-vitro gastrointestinal transit. Flavonoid contents and short chain fatty acids (SCFAs) production during gastrointestinal transit were also assessed. Encapsulated L. delbrueckii subsp. bulgaricus survived well in chocolates >7 logs both after 120 days of storage at 4 °C and 25 °C, and during in-vitro gastrointestinal transit. The release of SCFAs through in-vitro gastrointestinal digestion and colonic fermentation revealed that probiotic-chocolates could be an excellent source of nutrients for the gut microbiota. Encapsulated probiotic in chocolates with 70% cocoa produced significantly (P < 0.05) more acetic, propionic, isobutyric, butyric and isovaleric acids than that with 45% cocoa. The bioconversion results of a specific polyphenol by L. delbrueckii subsp. bulgaricus exhibited that chocolate polyphenols could be utilized by probiotics for their metabolism. These findings confirmed that chocolate could be successfully fortified with L. delbrueckii subsp. bulgaricus encapsulation to improve health promoting properties of chocolates.

UNASSIGNED: Large bone defect repair is a challenging clinical problem due to limited self-repair ability. A well-designed bone filling product should possess the ability to induce tissue in-growth and facilitate neovascularization and new bone formation. Puerarin has been used in clinics for a long time, and recently it was found to be able to promote osteogenesis. This study aimed to investigate a puerarin-based drug/delivery combination implant for promoting large bone defect repair.
UNASSIGNED: Puerarin was incorporated into the poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP, PT) to form a porous PLGA/TCP/Puerarin (PTP) composite scaffold by low-temperature rapid prototyping technology. Its structural and degradation were analyzed in vitro. Then we employed a rat calvarial critical size defect model to assess the potency of the PTP scaffold. MC3T3-E1 cells and EA. hy 926 ​cells were used to investigate the underlying mechanism.
UNASSIGNED: PTP scaffold inherited all advantages of PT scaffold in structural, mechanical, and biodegradation, meanwhile puerarin stably and continuously released from PTP scaffold and lasted for 5 months in vitro. At 8 weeks after implantation, the PTP scaffold triggered new bone formation in the macro-pores of the scaffold and inside the scaffold accompanied by the degrading materials. The underlying mechanism revealed that the PTP scaffold induced vascular infiltration and recruit repair cells through stimulating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) expressions to promote angiogenesis and osteogenesis.
UNASSIGNED: Puerarin-enriched porous PTP scaffold was a promising local delivery system with sustained release of puerarin for facilitating defect repair through getting synergistic angiogenic and osteogenic effects.
UNASSIGNED: The PTP scaffold presents a potential drug/device combination medical implant for large bone defect repair, which also provides a new and innovative application for the \"old drug\" puerarin.

Croton stellatopilosus (Plaunoi) leaves accumulate several diterpenes and possess various pharmacological activities. The present study aimed to prepare, characterize and assess the antibacterial activity of inclusion complexes prepared by mixing plaunotol (PL) or plaunoi extract (PE) with cyclodextrins (CD), including α-CD, β-CD, γ-CD, and hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes were characterized using SEM, XRD, DSC, and FT-IR and evaluated for aqueous solubility and thermal stability. The PL and PE lyophilized complexes with HP-β-CD were further evaluated for their antibacterial activity against acne-causing bacteria. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of PL, PE, and the inclusion complexes evaluated using the agar dilution method revealed that the MIC and MBC values of the inclusion complexes were lower than those of PL or PE alone. Interestingly, the complexes had a synergistic activity with clindamycin after testing with checkerboard assay. The hydrogel containing the inclusion complex and clindamycin were assessed for antibacterial activity using the agar well diffusion method. The results indicated that the hydrogels showed significant inhibition of bacterial growth. In conclusion, the prepared solid dispersion of PL or PE with HP-β-CD could enhance antibacterial activity by increasing the drug solubility. The hydrogels containing PL or PE complex and clindamycin could be considered as a candidate for the treatment of acne vulgaris.

Nanoscale positioning has numerous applications in both academia and industry. A growing number of applications require devices with long working distances and nanoscale resolutions. Friction-inertia piezoelectric positioners, which are based on the stick-slip mechanism, achieve both nanometer resolution and centimeter-scale travel. However, the requirements of complex preload mechanism, precision machining, and precise assembly increase the cost of conventional friction-inertia nanopositioners. Herein we present the design of an open-source XYZ-axis nanopositioning system. Utilizing a magnet-based stick-slip driving mechanism, the proposed XYZ nanopositioner provides several advantages, including sub-nanometer resolution, a payload capacity of up to 12 kg (horizontal), compact size, low cost, and easy assembly; furthermore, the system is adjustment-free. The performance tests validate the precision of the system in both scanning and stepping operation modes. Moreover, the resonant spectra affirm the rigidity and dynamic response of the mechanism. In addition, we demonstrate the practical applications of this nanopositioner in various measurement techniques, including scanning electron microscopy, vibrometry, and atomic force microscopy. Furthermore, we present 11 variations of the nanopositioner designs that are either compatible with ultra-high-vacuum systems and other existing systems, 3D printable, or hacking commercial linear slides.

UNASSIGNED: Efficient induction of the otic placode, the developmental origin of the inner ear from human pluripotent stem cells (hPSCs), provides a robust platform for otic development and sensorineural hearing loss modelling. Nevertheless, there remains a limited capacity of otic lineage specification from hPSCs by stepwise differentiation methods, since the critical factors for successful otic cell differentiation have not been thoroughly investigated. In this study, we developed a novel differentiation system involving the use of a three-dimensional (3D) floating culture with signalling factors for generating otic cell lineages via stepwise differentiation of hPSCs.
UNASSIGNED: We differentiated hPSCs into preplacodal cells under a two-dimensional (2D) monolayer culture. Then, we transferred the induced preplacodal cells into a 3D floating culture under the control of the fibroblast growth factor (FGF), bone morphogenetic protein (BMP), retinoic acid (RA) and WNT signalling pathways. We evaluated the characteristics of the induced cells using immunocytochemistry, quantitative PCR (qPCR), population averaging, and single-cell RNA-seq (RNA-seq) analysis. We further investigated the methods for differentiating otic progenitors towards hair cells by overexpression of defined transcription factors.
UNASSIGNED: We demonstrated that hPSC-derived preplacodal cells acquired the potential to differentiate into posterior placodal cells in 3D floating culture with FGF2 and RA. Subsequent activation of WNT signalling induced otic placodal cell formation. By single-cell RNA-seq (scRNA-seq) analysis, we identified multiple clusters of otic placode- and otocyst marker-positive cells in the induced spheres. Moreover, the induced otic cells showed the potential to generate hair cell-like cells by overexpression of the transcription factors ATOH1, POU4F3 and GFI1.
UNASSIGNED: We demonstrated the critical role of FGF2, RA and WNT signalling in a 3D environment for the in vitro differentiation of otic lineage cells from hPSCs. The induced otic cells had the capacity to differentiate into inner ear hair cells with stereociliary bundles and tip link-like structures. The protocol will be useful for in vitro disease modelling of sensorineural hearing loss and human inner ear development and thus contribute to drug screening and stem cell-based regenerative medicine.

UNASSIGNED: Coating-thickness-dependent physical properties can induce different cutting temperatures with physical vapor deposition (PVD) titanium aluminum nitride (TiAlN) ceramic-coated tools. The determination of the optimal TiAlN coating thickness is important to obtain superior coating physical properties and decrease the cutting temperature of Inconel 718 alloy.
UNASSIGNED: The present study investigates the effects of coating thickness on the physical properties of TiAlN coatings and the cutting temperature during the machining of Inconel 718 alloy. The optimal coating thickness is also determined.
UNASSIGNED: First, the direct-current-arc method was utilized to deposit PVD Ti0.55Al0.45N coatings with thickness of 1.6 µm, 2 µm, 2.5 µm, and 3 µm, onto a cemented carbide substrate. Second, the coating-thickness-dependent physical properties were characterized and estimated with a radar chart. Third, the effects of coating thickness on coating antifriction were analyzed with the tool-chip friction coefficient when cutting Inconel 718 with PVD TiAlN coated tools. Both the maximum cutting temperature generated in the chip and the cutting temperature of the tool bodies were measured for analyzation of the thermal barrier effect of coating. Finally, the topographies of the deformed chip and tool-chip contact area were obtained and investigated to determine the effects of coating thickness on the cutting temperature.
UNASSIGNED: The tool-chip friction coefficient and coating thermal barrier effect were affected by the coating thickness. Ti0.55Al0.45N coated tools with moderate coating thickness had fine antifriction effect with Inconel 718. The thermal barrier effect of Ti0.55Al0.45N coating was positively related to the coating thickness.
UNASSIGNED: The optimal TiAlN coating thickness was determined as 2 μm, which resulted in superior physical properties and reduced the cutting temperature of Inconel 718.

Uropathogens develop biofilms on urinary catheters, resulting in persistent and chronic infections that are associated with resistance to antimicrobial therapy. Therefore, the current study was performed to control biofilm-associated urinary tract infections through assaying the anti-biofilm ability of lactic acid bacteria (LAB) against multidrug-resistant (MDR) uropathogens. Twenty LAB were obtained from pickles and fermented dairy products, and screened for their anti-biofilm and antimicrobial effects against MDR Escherichia coli U12 (ECU12). Lactobacillus plantarum Y3 (LPY3) (MT498405), showed the highest inhibitory effect and biofilm production. Pre-coating of a microtitre plate with LPY3 culture was more potent than co-incubation. Pre-coating with LPY3 culture generated a higher anti-biofilm effect with an adherence of 14.5% than cell free supernatant (CFS) (31.2%). Anti-biofilm effect of CFS was heat stable up to 100 °C with higher effect at pH 4-6. Pre-coating urinary catheter with LPY3 culture reduced the CFU/cm2 of ECU12 attached to the catheter for up to seven days. Meanwhile, CFS reduced the ECU12 CFU/cm2 for up to four days. Scanning electron microscope confirmed the reduction of ECU12 adherence to catheters after treatment with CFS. Therefore, Lactobacillus plantarum can be applied in medical devices as prophylactic agent and as a natural biointervention to treat urinary tract infections.