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D on allergic sensitization.Polymalate (PMA) produced by the whole genome duplicated strain Aureobasidium melanogenum OUC had a high molecular weight (Mw) of 3.9 × 105 Da while the Mw of PMA produced by A. melanogenum ATCC62921 was 3.8 × 104 Da. Therefore, the purified PMA produced by A. melanogenum OUC could form hydrogel and film and the precipitated Ca2+-PMA looked like noodle whereas the purified PMA produced by A. melanogenum ATCC62921 could not form such a hydrogel and a film and the precipitated PMA was powder-like. The high Mw PMA biosynthesis in A. melanogenum OUC was also controlled by the PMA synthetase. However, it was still unclear why the PMA synthetase in A. melanogenum OUC could catalyze the high Mw PMA biosynthesis. Both removal of two copies of the PKS genes and overexpression of the PYC1 gene, the VGB gene and the CRZ2 gene rendered the new transformant Crz46 to produce 34.6 ± 0.3 g/L of extracellular Ca2+-PMA with Mw of 4.9 × 105 Da while its native A. melanogenum OUC only produced 17.2 ± 0.3 g/L of Ca2+-PMA. During the 10-Liter fermentation, 35.6 ± 1.2 g/L of Ca2+-PMA and 13.9 g/Lof cell mass were produced within 168 h, leading to the yield of 0.36 g/g of glucose and the productivity of 0.21 g/L/h. This was the first time to report that the whole genome duplicated strain A. melanogenum OUC and its engineered mutants could produce the high Mw PMA.Thermo-gels based on chitosan crosslinked poly(N-isopropylacrylamide) were developed as alternatives to conventional eye drops for the sustained release of ketotifen fumarate in the treatment of allergic conjunctivitis. The thermo-gelling properties of the base polymer were altered prior to crosslinking with chitosan by incorporation of the hydrophilic and hydrophobic comonomers acrylic acid and methyl methacrylate respectively. Varying amounts of chitosan were incorporated by ionic interaction to produce polyelectrolyte complexes or by carbodiimide chemistry to produce covalently crosslinked networks. The lower critical solution temperature of all the chitosan crosslinked thermo-gels produced was below the surface temperature of the eye. All the chitosan crosslinked thermo-gels were found to have greater than 80% equilibrium water contents following gelation. The method and amount of chitosan incorporation allowed for tailor-ability of material rheologic properties, with full degradation occurring over a one of degradation and drug release over several days. This work also focuses on studying the rheological properties of the chitosan crosslinked thermo-gels which has not been investigated previously.Most dry eye syndromes (DES) are caused by oxidative stress and an overactive inflammatory response, leading to tear deficiency and excessive tear evaporation. Conventional eye drops for DES treatment require high doses and frequent administration due to their insufficient precorneal residence time. To overcome these problems, in this study, we have developed carbonized nanogels (CNGs) via the straightforward pyrolysis of lysine hydrochloride (Lys) to provide a long-lasting eye drop formulation for topical DES therapy. This methodology thermally converts Lys-into nitrogen-doped crosslinked polymers with embedded nanographitic structures, which enable efficient free radical scavenging. The cationic and crosslinked polymeric features of the Lys-CNGs also prolong the precorneal retention time and improve ocular bioavailability. These Lys-CNGs exhibit high biocompatibility with corneal epithelial cells both in vitro and in vivo, indicating their safety as eye drops. In a DES rabbit model, a single dose of Lys-CNG alleviating dry eye syndrome (DES). We present evidence that the thermal transformation of lysine hydrochloride into carbonized nanogels (Lys-CNGs) endows superior antioxidant, anti-inflammatory, and bioadhesive properties. While a single dose of Lys-CNGs (50 µg mL-1) is sufficient to relieve the symptoms of DES for 4 days, multiple treatments of 10-fold higher concentration of commercially available cyclosporine eye drops are needed to achieve similar therapeutic outcomes (one dose every 12 h; 500 µg mL-1), suggesting an effective and long-lasting ocular carbonized nanomedicine.Peripheral nerve injury causes severe loss of motor and sensory functions, consequently increasing morbidity in affected patients. An autogenous nerve graft is considered the current gold standard for reconstructing nerve defects and recovering lost neurological functions; however, there are certain limitations to this method, such as limited donor nerve supply. With advances in regenerative medicine, recent research has focused on the fabrication of tissue-engineered nerve grafts as promising alternatives to the autogenous nerve grafts. In this study, we designed a nerve guidance conduit using an electrospun poly(lactide-co-ε-caprolactone) (PLCL) membrane with a visible light-crosslinked gelatin hydrogel. The PLCL nanoporous membrane with permeability served as a flexible and non-collapsible epineurium for the nerve conduit; the inner-aligned gelatin hydrogel paths were fabricated via 3D printing and a photocrosslinking system. The resultant gelatin hydrogel with microgrooved surface pattern was established r structure of the peripheral nerve. In particular, in vitro cell tests clearly showed that gelatin hydrogel could guide the cells and function as a reservoir that incorporate and release nerve growth factor. From in vivo performance tests, our regenerative conduit successfully led to axonal regeneration with effective functional recovery.The extracellular matrix (ECM) of the tumor microenvironment undergoes constant remodeling that alters its biochemical and mechano-physical properties. Non-enzymatic glycation can induce the formation of advanced glycation end-products (AGEs), which may cause abnormal ECM turnover with excessively cross-linked collagen fibers. However, the subsequent effects of AGE-mediated matrix remodeling on the characteristics of stromal cells in tumor microenvironments remain unclear. Here, we demonstrate that AGEs accumulated in the ECM alter the fibroblast phenotype within a three-dimensional collagen matrix. Both the AGE interaction with its receptor (RAGE) and integrin-mediated mechanotransduction signaling were up-regulated in glycated collagen matrix, leading to fibroblast activation to acquire a cancer-associated fibroblast (CAF)-like phenotype. These effects were blocked with neutralizing antibodies against RAGE or the inhibition of focal adhesion (FA) signaling. An AGE cross-link breaker, phenyl-4,5-dimethylthia both the AGE interaction with its receptor (RAGE) and integrin-mediated mechanotransduction were up-regulated in glycated collagen matrix, leading to fibroblast activation. We further demonstrated that an AGE cross-link breaker, ALT-711, reduced the CAF-like transformation because of its dual inhibitory role in the AGE-modified matrix. Our findings offer promising extracellular-reversion strategies targeting the non-enzymatic ECM glycation, to regulate fibroblast activation.The mechanical properties of connective tissues are tailored to their specific function, and changes can lead to dysfunction and pathology. In most mammalian tissues the mechanical environment is governed by the micro- and nano-scale structure of collagen and its interaction with other tissue components, however these hierarchical properties remain poorly understood. In this study we use the human cornea as a model system to characterise and quantify the dominant deformation mechanisms of connective tissue in response to cyclic loads of physiological magnitude. Synchronised biomechanical testing, x-ray scattering and 3D digital image correlation revealed the presence of two dominant mechanisms collagen fibril elongation due to a largely elastic, spring-like straightening of tropocollagen supramolecular twist, and a more viscous straightening of fibril crimp that gradually increased over successive loading cycles. The distinct mechanical properties of the two mechanisms suggest they have separate roles in vivo strain than fibril straightening, and was found to be elastic while fibril straightening was more viscous. The results suggest that the viscoelastic behaviour of a biomaterial is controlled, at least in part, by the relative amount of fibril-scale crimp and tropocollagen supramolecular twist.The objective was to test the effectiveness of a new strategy, i.e., adding artificial macrophytes (AMs) to surface-flow constructed wetlands (SFCWs) planted with emergent macrophytes (EMs), to improve COD and N removal efficiencies (REs) at the pilot scale. During EM-dominant periods, the SFCWs with only EMs had REs of 78.2%, 59.8%, 50.8% and -54.2% for NH4+-N, NO3--N, TN, and COD, respectively, while the SFCWs with both AMs and EMs increased the REs to 85.1%, 72.2%, 73.8%, and 2.0%. The addition of AMs to SFCWs had no significant effect on EM growth (biomass or root activity). Mutual benefit was found between EMs and AMs, i.e., AMs reduced the secondary pollution caused by withered EMs, while EMs improved AM-attached biofilm functions of chemoheterotrophy, nitrate_reduction, and nitrification. Therefore, AM addition is a useful strategy to improve COD and N REs during EM-dominant periods when pollutant removal is a challenge for SFCWs.The feasibility of stable nitritation of sludge alternately treated by free nitrous acid (FNA) and heat shock in a sequencing batch reactor (SBR) was investigated in this study. [https://www.selleckchem.com/products/vevorisertib-trihydrochloride.html Vevorisertib] The linear regression method was used to determine the optimal treatment conditions. Results revealed that an FNA concentration of 2.20 mg HNO2-N/L, exposure time of 24 h, and treatment ratio of 20% could inhibit nitrite oxidizing bacteria (NOB) activity to the greatest extent while maintaining the maximum ammonium oxidizing bacteria (AOB) activity; after heat shock at 60 °C for 20 min, NOB were inhibited while AOB still had certain activity. In the long-term continuous-flow experiment, the single FNA or heat shock treatments easily allowed adapt NOB to affect the stability of nitritation. The alternating FNA/heat shock treatment can achieve long-term stability of nitritation. Microbial community analysis revealed that the alternating FNA/heat shock treatment could inhibit NOB while maintaining high AOB abundance.This study investigates psychosocial factors that influence people's face-touching mitigation behaviors. A nationwide survey was conducted online, and the results showed that perceived risk severity of touching face, and barriers and self-efficacy of not touching face were stable predictors. COVID-19 was related to a higher likelihood of mitigation behavior in public spaces. This study provides important implications to health communication and promotion for COVID-19 and general infection control.<br />Portable medical equipment (PME) may contribute to transmission of multidrug-resistant organisms without proper disinfection. We studied whether a Disinfection Tracking System (DTS) with feedback prompt, attached to PME, can increase the frequency of PME disinfection.<br />DTS devices were placed on 10 workstations-on-wheels (WOWs) and 5 vitals machine (VM). After a 25 day "screen-off" period, the DTS device screens were turned on to display the number of hours since the last recorded disinfection event for a 42 day period. We used a Bayesian multilevel zero-inflated negative binomial model to compare the number of events in the display "screen-off" to the "screen-on" period.<br />During the "screen-off" period, there were 1.26 and 0.49 mean disinfection events and during the "screen-on" period, there were 1.76 and 0.50 mean disinfection events for WOWs and VM, respectively, per day. The model estimated mean events per device per day in the the "screen-on" period for WOW's were 1.32 (1.10 - 1.57) times greater than those in the"screen-off" period and the "screen-on" period for VM devices was 1.