Bioinspired Adhesive Antibacterial Hydrogel with Self-Healing and On-Demand Removability for Enhanced Full-Thickness Skin Wound Repair.

Adhesive-caused injury is a great threat for extensive full-thickness skin trauma because extra-strong adhesion can incur unbearable pain and exacerbate trauma upon removal. Herein, inspired by the mussel, we designed and fabricated an adhesive antibacterial hydrogel dressing based on dynamic host-guest interaction that enabled on-demand stimuli-triggered removal to effectively care for wounds. In contrast with most hard-to-removable dressing, this adhesive antibacterial hydrogel exhibited strong adhesion property (85 kPa), which could achieve painless and noninvasive on-demand separation within 2 s through a host-guest competition mechanism (amantadine). At the same time, the hydrogel exhibited rapid self-healing properties, and the broken hydrogel could be completely repaired within 5 min. The hydrogel also had excellent protein adsorption properties, mechanical properties, antibacterial properties, and biocompatibility. This on-demand removal was facilitated by the introduction of amantadine as a competitive guest, without any significant adverse effects on cell activity (>90%) or wound healing (98.5%) in vitro. The full-thickness rat-skin defect model and histomorphological evaluation showed that the hydrogel could significantly promote wound healing and reduce scar formation by regulating inflammation, accelerating skin re-epithelialization, and promoting granulation tissue formation. These results indicate that the developed adhesive antibacterial hydrogel offers a promising therapeutic strategy for the healing of extensive full-layer skin injuries.

Oscillator strengths and integral cross sections of the valence-shell excitations of HCl studied by fast electron scattering.

The oscillator strengths and integral cross sections of the valence-shell excitations of HCl have significant applications in the studies of planetary atmospheres and interstellar gases. In the present work, the generalized oscillator strengths of the valence-shell excitations of HCl have been measured at an incident electron energy of 1500 eV and an energy resolution of 70 meV, and their momentum transfer dependence behaviors have been elucidated. It is observed that the generalized oscillator strength ratios of the b3Π1(ν' = 0) state to the C1Π(ν' = 0) state are a constant and independent of the squared momentum transfer, and this typical behavior in the momentum space is explained by the intraconfiguration mixing of the b3Π1 and C1Π states due to the spin-orbital interaction. The optical oscillator strengths of the valence-shell excitations have been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The present optical oscillator strengths give an independent cross-check to the previous experimental and theoretical results, and it is found that most of the photoabsorption measurements are limited by the line saturation effect. The integral cross sections of the valence-shell excitations of HCl have been obtained systematically from the threshold to 5000 eV with the aid of the BE-scaling method.

Investigations of the valence-shell excitations of molecular ethane by high-energy electron scattering.

The differential cross sections and generalized oscillator strengths for the low-lying excitations of the valence-shell 1eg orbital electron in ethane have been measured for the first time at a high incident electron energy of 1500 eV and a scattering angular range of 1.5°-10°. A weak feature, termed X here, with a band center of about 7.5 eV has been observed, which was also announced by the previous experimental and theoretical studies. The dynamic behaviors of the generalized oscillator strengths for the 3s (8.7 eV), 3s+3p (9.31 eV, 9.41 eV), and X (∼7.5 eV) transitions on the momentum transfer squared have been obtained. The integral cross sections of these transitions from their thresholds to 5000 eV have been obtained with the aid of the BE-scaling (B is the binding energy and E is the excitation energy) method. The optical oscillator strengths of the above transitions determined by extrapolating their generalized oscillator strengths to the limit of the squared momentum transfer K2 → 0 are in good agreement with the ones from the photoabsorption spectrum [J. W. Au et al., Chem. Phys. 173, 209 (1993)], which indicates that the present differential cross sections, generalized oscillator strengths, and integral cross sections can serve as benchmark data.

Oscillator strengths and integral cross sections for the valence-shell excitations of nitric oxide studied by fast electron impact.

The generalized oscillator strengths for the valence-shell excitations of A2Σ+, C2Π, and D2Σ+ electronic-states of nitric oxide have been determined at an incident electron energy of 1500 eV with an energy resolution of 70 meV. The optical oscillator strengths for these transitions have been obtained by extrapolating the generalized oscillator strengths to the limit that the squared momentum transfer approaches to zero, which give an independent cross-check to the previous experimental and theoretical results. The integral cross sections for the valence-shell excitations of nitric oxide have been determined systematically from the threshold to 2500 eV with the aid of the newly developed BE-scaling method for the first time. The present optical oscillator strengths and integral cross sections of the valence-shell excitations of nitric oxide play an important role in understanding many physics and chemistry of the Earth's upper atmosphere such as the radiative cooling, ozone destruction, day glow, aurora, and so on.

Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.

We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction.

Conversion of Ginsenoside Rb1 into Six Types of Highly Bioactive Ginsenoside Rg3 and Its Derivatives by FeCl3 Catalysis.

Ginsenoside Rb1 is an important saponin of ginseng(s); however, Rb1, with 3-O- and 20-O-sugar moieties, has low bioavailability. Here, we report the derivatization of ginsenoside Rb1 to completely generate six types of highly bioactive minor ginsenoside Rg3 and its derivatives by FeCl3 catalysis, the reaction conditions are similar to enzymatic reaction conditions. In FeCl3 catalysis, the only 20-O-sugar-moiety of ginsenoside Rb1 was decomposed into the minor ginsenosides Rk1 and Rg5 with newly produced C-20 ethylene bands; but also hydrolyzed into 20(S)-Rg3 and 20(R)-Rg3; subsequently the C-24(25) ethylene bands of 20(S)-Rg3 and 20(R)-Rg3 were hydrated to 20(S)-25-OH-Rg3 and 20(R)-25-OH-Rg3. After separation of reaction mixture from 34 g ginsenoside-Rb1 by silica-gel-column, the 3.3 g sample I of TLC top-band consisting of Rg5 and Rk1, 8.7 g sample II of TLC middle-band consisting of 20(S)-Rg3 and 20(R)-Rg3, 3.5 g sample III of TLC bottom-band consisting of unknown product-I and -II including 20(S)-25-OH-Rg3, were obtained. The sample III consisting of unknown product-I and -II was purified by crystallization, and identified to 20(S)-25-OH-Rg3 and 20(R)-25-OH-Rg3 by HPLC-Evaporative Light Scattering Detector (ELSD) and NMR. Therefore, six types of minor-ginsenosides Rk1, Rg5, 20(S)-Rg3, 20(R)-Rg3, 20(S)-25-OH-Rg3 and 20(R)-25-OH-Rg3 were successfully prepared from ginsenoside Rb1 by FeCl3 catalysis. FeCl3 has low toxicity and is inexpensive, and the reaction conditions are similar to enzymatic reaction conditions; thus, this method is applicable to the development of ginseng-based drugs.

Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress.

BACKGROUND: S-nitrosylation of mitochondrial enzymes involved in energy transfer under nitrosative stress may result in ATP deficiency. We investigated whether α-lipoic acid, a powerful antioxidant, could alleviate nitrosative stress by regulating S-nitrosylation, which could result in retaining the mitochondrial enzyme activity. METHODS: In this study, we have identified the S-nitrosylated forms of subunit 1 of dihydrolipoyllysine succinyltransferase (complex III), and subunit 2 of the α-ketoglutarate dehydrogenase complex by implementing a fluorescence-based differential quantitative proteomics method. RESULTS: We found that the activities of these two mitochondrial enzymes were partially but reversibly inhibited by S-nitrosylation in cultured endothelial cells, and that their activities were partially restored by supplementation of α-lipoic acid. We show that protein S-nitrosylation affects the activity of mitochondrial enzymes that are central to energy supply, and that α-lipoic acid protects mitochondrial enzymes by altering S-nitrosylation levels. CONCLUSIONS: Inhibiting protein S-nitrosylation with α-lipoic acid seems to be a protective mechanism against nitrosative stress. GENERAL SIGNIFICANCE: Identification and characterization of these new protein targets should contribute to expanding the therapeutic power of α-lipoic acid and to a better understanding of the underlying antioxidant mechanisms.

Primary aldosteronism and impaired natriuresis in mice underexpressing TGFß1.

To uncover the potential cardiovascular effects of human polymorphisms influencing transforming growth factor ß1 (TGFß1) expression, we generated mice with Tgfb1 mRNA expression graded in five steps from 10% to 300% normal. Adrenal expression of the genes for mineralocorticoid-producing enzymes ranged from 50% normal in the hypermorphs at age 12 wk to 400% normal in the hypomorphs accompanied with proportionate changes in plasma aldosterone levels, whereas plasma volumes ranged from 50% to 150% normal accompanied by marked compensatory changes in plasma angiotensin II and renin levels. The aldosterone/renin ratio ranged from 0.3 times normal in the 300% hypermorphs to six times in the 10% hypomorphs, which have elevated blood pressure. Urinary output of water and electrolytes are markedly decreased in the 10% hypomorphs without significant change in the glomerular filtration rate. Renal activities for the Na(+), K(+)-ATPase, and epithelial sodium channel are markedly increased in the 10% hypomorphs. The hypertension in the 10% hypomorphs is corrected by spironolactone or amiloride at doses that do not change blood pressure in wild-type mice. Thus, changes in Tgfb1 expression cause marked progressive changes in multiple systems that regulate blood pressure and fluid homeostasis, with the major effects being mediated by changes in adrenocortical function.

Investigation of Compton profiles of molecular methane and ethane.

The Compton profiles of methane and ethane molecules have been determined at an incident photon energy of 20 keV based on the third generation synchrotron radiation, and the statistical accuracy of 0.2% is achieved near pz = 0. The density functional theory with aug-cc-pVTZ basis set was used to calculate the Compton profiles of methane and ethane. The present experimental Compton profiles are in better agreement with the theoretical calculations in the whole pz region than the previous experimental results, which indicates that the present experimental Compton profiles are accurate enough to serve as the benchmark data for methane and ethane molecules.

Preparation of przewalskinic acid A from salvianolic acid B using a crude enzyme from an Aspergillus oryzae strain.

Przewalskinic acid A is a rare, water-soluble, and highly biologically active ingredient found, thus far, only in the Salvia przewalskii Maxim herb; however, the content in S. przewalskii herb is very low. In order to obtain useful quantities of przewalskinic acid A, the biotransformatin of salvianolic acid B from Salvia miltiorrhiza root (danshen in Chinese) into przewalskinic acid A was studied using a crude enzyme produced from Aspergillus oryzae D30s strain. The crude enzyme from the A. oryzae strain hydrolyzed salvianolic acid B into przewalskinic acid A and danshensu. The preparation afforded 31.3 g przewalskinic acid A (91.0 % purity) and 13.1 g danshensu (95 % purity) from 75 g salvianolic acid B. The preparation of przewalskinic acid A was therefore very successful with a yield of over 86 %, but the yield of danshensu was only 33 %. The product przewalskinic acid A was identified using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and NMR.

Reduced expression of lipoic acid synthase accelerates diabetic nephropathy.

Oxidative stress contributes to the pathogenesis of diabetic nephropathy. In mitochondria, lipoic acid synthase produces α-lipoic acid, an antioxidant and an essential cofactor in α-ketoacid dehydrogenase complexes, which participate in glucose oxidation and ATP generation. Administration of lipoic acid abrogates diabetic nephropathy in animal models, but whether lower production of endogenous lipoic acid promotes diabetic nephropathy is unknown. Here, we crossed mice heterozygous for lipoic acid synthase deficiency (Lias(+/-)) with Ins2(Akita/+) mice, a well characterized model of type 1 diabetes. Double mutant mice had more overt diabetic nephropathy, including microalbuminuria, glomerular basement thickening, mesangial matrix expansion, and hypertension, compared with Lias(+/+)Ins2(Akita/+) controls. We also identified proximal tubules as a major site for generation of superoxide anions during diabetic nephropathy. Mitochondria in proximal tubular cells were particularly sensitive to damage in diabetic mice with reduced lipoic acid production. These results suggest that lipoic acid synthase deficiency increases oxidative stress and accelerates the development of diabetic nephropathy.

Difference analysis of the structure and functional properties among coix seed prolamin fractions (α-, ß-, and γ-coixin).

The differences in proteins in structural characteristics are reported to affect their physicochemical and functional properties. In this study, three types of prolamins (γ-, α-, and ß-coixin) derived from coix seed separately distributed among fractions 1-3 extracts. They were studied respecting molecular weight, amino acid composition, secondary structure, microstructure, surface hydrophobicity, solubility, water holding capacity, and oil holding capacity. Results showed that the molecular weights of those three fractions were between 10 and 40 kDa. The secondary structure of those fractions was almost the same, mainly based on ß-sheet and irregular structure. The microstructure of α- and γ-coixin presented an irregular shape, whereas ß-coixin presented a regular spherical shape. Those three fractions exhibited species of abundant essential amino acids with the same amino acid composition but different contents. The ß-coixin fraction had the highest content of hydrophobic amino acids (238.39 mg/g) followed by the α-coixin fraction (235.05 mg/g), whereas the γ-coixin fraction had the lowest content (33.27 mg/g). The γ-coixin fraction has the maximum surface hydrophobicity, whereas the ß-coixin fraction has the highest solubility. In addition, the good amphiphilicity of ß-coixin fraction made it possible to be used as a surfactant. The excellent functional properties of the ß-coixin fraction presented in this research would widen the applications of coix seed prolamins. PRACTICAL APPLICATION: The molecular weights of those three fractions were between 10 and 40 kDa. The secondary structure was almost the same, mainly based on ß-sheet and irregular structure. Those three fractions exhibited species of abundant essential amino acids with the same amino acid composition but different contents. The WHC and OHC of ß-coixin were the best, indicating its potential as a surfactant and forming stable lotion.

Modulating the performance of lipase-hydrogel microspheres in a "micro water environment".

In our previous work, we successfully stimulated lipase activity in an anhydrous reaction system using porous polyacrylamide hydrogel microsphere (PPAHM) as a carrier of lipase and free water. However, the effect of the existence state and content of water in lipase-porous polyacrylamide hydrogel microsphere (L-PPAHM) on the interfacial activation remained unclear. In this work, L-PPAHM with different water contents were obtained by water mist rehydration and were used to catalyze the synthesis of conjugated linoleic acid ethyl ester (CLA-EE). The results revealed that there were three existence states of water in L-PPAHM: bound water, semi-bound water and free water, and free water provided the "micro water environment" for the interfacial activation of lipase. The reusability of L-PPAHM with different water contents showed that the activity and stability of L-PPAHM could be achieved by varying the water content of L-PPAHM. The proportion of free water in L-PPAHM increased, and the activity of L-PPAHM increased, but the strength of hydrogen bond interaction between PPAHM and lipase weakened, resulting in the decrease of stability. L-PPAHM with 2/3 of water absorption could ensure sufficient immobilized lipase activity and stability, and its water absorption property could reduce the free water generated during esterification, thus increasing the yield of CLA-EE.

A Janus supramolecular hydrogel prepared by one-pot method for wound dressing.

Despite the adhesive hydrogels have gained progress and popularity, it is still an enormous challenge to develop a smart adhesion hydrogel for clinical medicine, which is an asymmetric adhesion hydrogel with on-demand detachment. Motivated by the thermal phase transition mechanism of gelatin, we have synthesized a Janus supramolecular hydrogel dressing with skin temperature-triggered adhesion by a simple one-pot process. This hydrogel has asymmetric and controllable adhesion, which not only can become the external objects barrier but also can achieve repeated adhesion and on-demand detachment triggered by temperature in tens of seconds. This hydrogel presents great mechanical performance (compressive strain of 65 %, 1.38 MPa) owing to the presence of supramolecular interactions in the hydrogel. Additionally, this hydrogel exhibits excellent antibacterial activity and biocompatibility. The synergistic effect of modified gelatin and ionic liquid greatly facilitates wound healing of full-thickness skin with high wound healing efficiency (98.45 %). Therefore, thanks to all these advantages, the Janus supramolecular hydrogel can be applied for wound management and treatment, which has huge potential in healing skin wounds.

A novel multi-scale pressure sensing hydrogel for monitoring the physiological signals of long-term bedridden patients.

For long-term bedridden patients who need to wear diapers, the timely replacement of diapers is very important to ensure their quality of life. Therefore, it is urgent to develop a pressure sensor that can monitor the physiological conditions of patients in real time. Inspired by the multi-scale network structure of the multi-fiber protein in the muscle, a multi-scale hydrogel as a pressure sensor was prepared by introducing micron-scale hydrogel microspheres as physical crosslinking agents. Compared with the traditional polyacrylamide hydrogel (0.17 MPa of compressive strength), the multi-scale hydrogel showed a higher compressive strength of up to 1.37 MPa. Meanwhile, the hydrogel exhibited better pressure sensitivity (0.59 kPa-1) than the existing hydrogels (0.27-0.40 kPa-1). The sensor prepared by this hydrogel could monitor the patient's physiological condition (urine outflow and urinary filling) in real time through the conductivity response to ion concentration and pressure, and then transmit the signal to the caregivers in time to avoid skin damage. This multi-scale hydrogel provided a great convenience for the physiological monitoring of long-term bedridden patients by acting as a pressure sensor.

Biomass-based hydrogels with high ductility, self-adhesion and conductivity inspired by starch paste for strain sensing.

Currently, hydrogel sensors for health monitoring require external tapes, bandages or adhesives to immobilize them on the surface of human skin. However, these external fixation methods easily lead to skin allergic reactions and the decline of monitoring accuracy. A simple strategy to solve this problem is to endow hydrogel sensors with good adhesion. Inspired by the starch paste adhesion mechanism, a biomass-based hydrogel with good conductivity and high repetitive adhesion strength was prepared by introducing modified starch into polyacrylic acid hydrogel system. The properties of biomass-based hydrogels could be controlled by changing the proportion of amylose and amylopectin. The biomass-based hydrogel exhibited a variety of excellent properties, including good stretchability (1290 %), high adhesion strength (pig skin: 46.51 kPa) and conductivity (2.3 S/m). Noticeably, the repeated adhesive strength of biomass-based hydrogel did not decrease with the increase of adhesion times. The strain sensor based on the biomass-based hydrogel could accurately monitor the large-scale and small movements of the human body, and had broad application prospects in the field of flexible wearable devices.

A ionic liquid enhanced conductive hydrogel for strain sensing applications.

Strain-sensitive and conductive hydrogels have attracted extensive research interest due to their potential applications in various fields, such as healthcare monitoring, human-machine interfaces and soft robots. However, low electrical signal transmission and poor tensile properties still limit the application of flexible sensing hydrogels in large amplitude and high frequency motion. In this study, a novel ionic liquid segmental polyelectrolyte hydrogel consisting of acrylic acid (AAc), 1-vinyl-3-butylimidazolium bromide (VBIMBr) and aluminum ion (Al3+) was prepared by molecular design and polymer synthesis. The cationic groups and amphiphilicity of ionic liquid chain segments effectively improve the tensile behavior of the polyelectrolyte hydrogel, with a maximum tensile strength of 0.16 MPa and a maximum breaking strain of 604%. The introduction of ionic liquid segments increased the current carrying concentration of polyelectrolyte hydrogel, and the conductivity reached the initial 4.8 times (12.5 S/m), which is a necessary condition for detecting various amplitude and high frequency limb movements. The flexible electronic sensor prepared by this polyelectrolyte hydrogel efficiently detects the movement of different parts of the human body stably and sensitively, even in extreme environment (-20 °C). These outstanding advantages demonstrate the great potential of this hydrogel in healthcare monitoring and wearable flexible strain sensors.

Polyionic liquids supramolecular hydrogel with anti-swelling properties for underwater sensing.

The preparation of hydrogel-based wearable sensors for underwater application with high mechanical properties and electrical conductivity is an urgent challenge. Here, a supramolecular hydrogel based on polyionic liquids was designed and prepared for underwater sensing. The introduction of functional ionic liquid structures effectively increased the supramolecular interaction in the hydrogel network, which made the hydrogel successfully resist the interference of external water molecules. Depending on the effect of charge and hydrophobic interactions, this supramolecular hydrogel sensor exhibited high tensile (759 %), high tensile strength (0.23 MPa), high sensitivity (GF = 10.76) and extensive antibacterial properties, even in seawater environment. The obtained hydrogel sensor successfully monitored the swimming posture, which was helpful to digitally reflect the limb movement of athletes during underwater sports. This work made progress in the field of underwater wearable sensors based on hydrogels, and this design of multifunctional hydrogel provided a new idea for the development of functional sensors.

A starch-regulated adhesive hydrogel dressing with controllable separation properties for painless dressing change.

The development of hydrogel dressings provides unprecedented opportunities for clinical medicine. However, the traditional hydrogel dressings cannot achieve controllable adhesion and separation, which often brings unbearable pain and secondary damage to patients during removal. In this work, a starch-regulated adhesive hydrogel dressing with controllable separation properties is reported. This hydrogel dressing can achieve rapid separation through the dissociation competition mechanism of polar small molecules, which will not cause any damage or discomfort to the skin or tissues, and greatly facilitate dressing replacement. The adhesive strength of the hydrogel reaches 0.06 MPa, and remains relatively stable after repeated utilization. Meanwhile, the inhibition rate of the hydrogel for E. coli, S. aureus and C. albicans is more than 99.9%. At the same time, the hydrogel also has good swelling properties, mechanical properties and biocompatibility, and exhibits a high healing efficiency (95.01 ± 3.76%) in a rat full-thickness skin defect model. This novel hydrogel dressing with controllable separation properties provides a facile and effective method for wound management and treatment, and has great promise for long-term application of wound dressings.

Pressure-sensitive antibacterial hydrogel dressing for wound monitoring in bed ridden patients.

Pressure ulcer is a common chronic injury in the bedridden population. The wound is easily subjected to secondary pressure injury due to the inconvenient mobility of patients, which greatly prolongs the hospital stay of patients and is highly prone to wound infection or other complications. It is urgent to develop a multifunctional wound dressing with pressure sensing, real-time monitoring, and wound therapy to overcome the secondary pressure injury during treatment. Here, a polyvinyl alcohol/acrylamide-ionic liquid hydrogel dressing is designed based on the antibacterial property and electrical conductivity of imidazolidine ionic liquids. Compared with existing pressure-sensing hydrogels, the hydrogel exhibits extremely high pressure sensitivity (9.19 kPa-1). Meanwhile, the good real-time responsiveness, stable signal output as well as excellent mechanical properties enable the hydrogel to monitor human movement on a large scale, and transmit the pressure status of patient wounds to nursing staff in a timely manner to avoid secondary pressure injuries. In addition, this hydrogel dressing exhibits a wide range of antibacterial activities against Gram-negative and Gram-positive bacteria as well as fungi, and has a significant therapeutic effect on full-thickness skin wounds by inhibiting wound infection, rapidly eradicating inflammation, promoting proliferation and tissue remodeling. This multifunctional hydrogel dressing opens a therapeutic and regulatory two-pronged strategy avenue through chronic wound management and pressure sensing monitoring.