CCL17 and CCL19 are markers of disease progression in alveolar echinococcosis.

OBJECTIVES: Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality. METHODS: This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses. RESULTS: The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80. CONCLUSION: CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.

Insights into the assembly process and properties of regenerated cellulose beads prepared in alkali/urea aqueous solutions.

Taking the perspective of cellulose molecular chain assembly via the "bottom-top" route, we delve into the influence of both the cellulose solution and the coagulation bath on the assembly process and structure of regenerated cellulose beads (RCBs). The results show that cellulose molecular weight, mass fraction, and the presence of surfactant have an impact on RCBs. Contrary to traditional views where the structures of material are determined by solvent-nonsolvent exchange rate, ion-cellulose binding capacity also affects RCBs. Overall, the influence of ions follows the Hofmeister sequence. Kosmotropes promote the assembly of cellulose chains and elementary fibers, leading to "salting out" effects, reduced pore size of RCBs, increased crystallinity, and enhanced mechanical properties. In contrast, chaotropes induce "salting in" effects, resulting in opposite outcomes. The average pore size of RCBs coagulated in NaSCN solution was approximately 15-folds larger than those prepared in sodium citrate solution. Anions have a greater impact than cations, and both "salting out" and "salting in" effects strengthen with concentration. Temperature variations primarily affect solvent and nonsolvent exchange speed during cellulose regeneration. These findings provide new insights into regulating RCBs, enabling tailored performance for different applications.

Identification and exploration of a new M2 macrophage marker MTLN in alveolar echinococcosis.

The pathogen of alveolar echinococcosis (AE) is Echinococcus multilocularis (E. multilocularis), which has the characteristics of diffuse infiltration and growth and has a high mortality rate. At present, the role of macrophages in AE infection has attracted more and more attention, but the new biomarkers and polarization mechanisms of macrophages are rarely studied. In this study, CIBERSORT and WGCNA algorithms were used to establish a weighted gene co-expression network, and MTLN was identified as a biological marker of M2-type macrophages, which participated in energy metabolism of macrophages and mediated inflammatory response, but the role of MTLN in AE was not studied. In this study, liver tissue samples from AE patients were collected and immunofluorescence co-localization showed the relationship between MTLN and macrophage distribution. E. multilocularis infected mouse model was established to analyze the expression of MTLN, liver fibrosis, and inflammatory reaction after E. multilocularis infection. The cell experiment simulated the liver microenvironment of E. multilocularis infected human body and analyzed the expression of MTLN by QRT-PCR and western blot in vitro. The data showed that liver fibrosis occurred in AE patients, and MTLN was activated near the focus. After E. multilocularis infected mice, the expression of MTLN increased with time. In the cell experiment, after the antigen of E. multilocularis protoscolex stimulated normal liver cells, the expression of MTLN increased 48 h, at this time, M2 was up-regulated and M1 was down-regulated. Therefore, MTLN may be the key gene to regulate the polarization of M2 macrophages and cause fibrosis.

A Sustainable Dual Cross-Linked Cellulose Hydrogel Electrolyte for High-Performance Zinc-Metal Batteries.

Aqueous rechargeable Zn-metal batteries (ARZBs) are considered one of the most promising candidates for grid-scale energy storage. However, their widespread commercial application is largely plagued by three major challenges: The uncontrollable Zn dendrites, notorious parasitic side reactions, and sluggish Zn2+ ion transfer. To address these issues, we design a sustainable dual cross-linked cellulose hydrogel electrolyte, which has excellent mechanical strength to inhibit dendrite formation, high Zn2+ ions binding capacity to suppress side reaction, and abundant porous structure to facilitate Zn2+ ions migration. Consequently, the Zn||Zn cell with the hydrogel electrolyte can cycle stably for more than 400 h under a high current density of 10 mA cm-2. Moreover, the hydrogel electrolyte also enables the Zn||polyaniline cell to achieve high-rate and long-term cycling performance (> 2000 cycles at 2000 mA g-1). Remarkably, the hydrogel electrolyte is easily accessible and biodegradable, making the ARZBs attractive in terms of scalability and sustainability.

Vancomycin relieves tacrolimus-induced hyperglycemia by eliminating gut bacterial beta-glucuronidase enzyme activity.

Up to 40% of transplant recipients treated long-term with tacrolimus (TAC) develop post-transplant diabetes mellitus (PTDM). TAC is an important risk factor for PTDM, but is also essential for immunosuppression after transplantation. Long-term TAC treatment alters the gut microbiome, but the mechanisms of TAC-induced gut microbiota in the pathogenesis of PTDM are poorly characterized. Here, we showed that vancomycin, an inhibitor of bacterial beta-glucuronidase (GUS), prevents TAC-induced glucose disorder and insulin resistance in mice. Metagenomics shows that GUS-producing bacteria are predominant and flourish in the TAC-induced hyperglycemia mouse model, with upregulation of intestinal GUS activity. Targeted metabolomics analysis revealed that in the presence of high GUS activity, the hydrolysis of bile acid (BAs)-glucuronic conjugates is increased and most BAs are overproduced in the serum and liver, which, in turn, activates the ileal farnesoid X receptor (FXR) and suppresses GLP-1 secretion by L-cells. The GUS inhibitor vancomycin significantly eliminated GUS-producing bacteria and inhibited bacterial GUS activity and BAs levels, thereby enhancing L-cell GLP-1 secretion and preventing hyperglycemia. Our results propose a novel clinical strategy for inhibiting the bacterial GUS enzyme to prevent hyperglycemia without requiring withdrawal of TAC treatment. This strategy exerted its effect through the ileal bile acid-FXR-GLP-1 pathway.

Nurses' engagement in antimicrobial stewardship and its influencing factors: A cross-sectional study.

Objective: This study aimed to investigate the level and influencing factors of nurses' antimicrobial stewardship (AMS) engagement in China based on the capability, opportunity, motivation, and behavior (COM-B) theory, providing valuable insights for developing effective strategies to improve nursing quality in AMS. Methods: This cross-sectional study was conducted in 17 tertiary hospitals in Hunan, China, from November 2021 to January 2022. A total of 4,514 nurses were selected. The Nurse AMS Engagement Questionnaire (NAEQ), developed using the COM-B theory, was used for evaluation. The questionnaire included capability (14 items), opportunity (7 items), motivation (6 items), and behavior (12 items) four dimensions, 39 items. Results: The total NAEQ score was 155.08 ± 27.12, indicating a moderate level. The score of the capability, opportunity, motivation, and behavior dimensions were 52.33 ± 13.48, 28.64 ± 5.76, 24.57 ± 4.57 and 49.53 ± 8.83, respectively. Significant differences in nurses' AMS engagement were based on professional titles, whether working as a part-time infection control nurse, whether knowing the AMS teams and the defined daily doses of antibiotics, department type, the deployment of clinical pharmacists, and frequency of antimicrobial training and physician-nurse joint rounds (P < 0.05). Nurses with junior titles had higher scores on the NAEQ than nurses with intermediate titles (P < 0.05). Nurses who worked as part-time infection control nurses, knew the AMS team, and the defined daily doses of antibiotics had higher NAEQ scores than those who didn't (P < 0.01). Nurses working in the ICU and infectious disease department had lower NAEQ scores than those in other departments, such as the ear, nose, and throat (ENT) department (P < 0.01). Nurses who had clinical pharmacists deployed in their department had higher NAEQ scores than those without or unclear deployment (P < 0.01). Furthermore, nurses who received more frequent antimicrobial training and participated in physician-nurse joint rounds had higher NAEQ scores (P < 0.01). Conclusion: Multiple strategies, including enhanced education and training and improved multidisciplinary communication and collaboration, are expected to improve nurse AMS engagement. It is important to give more attention to nurses with intermediate professional titles, less experience, and those working in specific departments.

Intracellular tacrolimus concentration correlates with impaired renal function through regulation of the IS-AHR-ABC transporter in peripheral blood mononuclear cells.

BACKGROUNDS: Tacrolimus (TAC) concentration in peripheral blood mononuclear cells (PBMCs) is regarded as a better predictor of its immunosuppressive effect than the TAC concentration in whole blood. However, whether the exposure of TAC in PBMCs or WB was altered in post-transplant recipients with renal impairment remains unclear. METHODS: We investigated the relationship of trough TAC concentration in WB and PBMCs with renal functions in post-transplant recipients. The pharmacokinetic profiles of TAC in PBMCs and WB in the two chronic kidney disease (CKD) rat models were examined using UPLC-MS/MS. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to analyze the expression of proteins and mRNAs related to TAC metabolism and transport, respectively. In addition, the effects of uremic toxins on human PBMCs were investigated using whole-transcriptome sequencing (RNA sequencing [RNA-seq]). RESULTS: We observed a decrease in the trough TAC concentration in PBMCs in the recipients with estimated glomerular filtration rate (eGFR) < 90 mL/min, compared with those of recipients with eGFR > 90 mL/min, but there was no difference in blood based on TAC concentrations (C0Blood). In a 150-patient post-transplant cohort, no significant relationship was observed between PBMCs and WB concentrations of TAC, and the eGFR value was correlated with TAC C0PBMCs but not with TAC C0Blood. In two CKD rat models, the TAC pharmacokinetic profile in the PBMCs was significantly lower than that in the control group; however, the blood TAC pharmacokinetic profiles in the two groups were similar. Transcriptome results showed that co-incubation of human PBMCs with uremic toxins upregulated the expression of AHR, ABCB1, and ABCC2. Compared to control rats, plasma IS increased by 1.93- and 2.26-fold and the expression of AHR, P-gp, and MRP2 in PBMCs was higher in AD and 5/6 nephrectomy (NX) rats, without modifying the expression of other proteins related to TAC exposure. CONCLUSION: The pharmacokinetics of TAC in PBMCs changed with a decline in renal function. Uremic toxins accumulate during renal insufficiency, which activates AHR, upregulates the expression of P-gp and MRP2, and affects their intracellular concentrations. Our findings suggest that monitoring TAC concentrations in PBMCs is more important than monitoring WB concentrations in post-transplant recipients with renal impairment.

Scalable synthesis of N, O co-doped hierarchical porous carbon for high energy density supercapacitors.

Rational design of hierarchical porous architecture with abundant pseudocapacitive sites is highly desirable for carbon electrode materials. However, the lengthy production process and high economic input limit its broader application. Herein, we successfully prepared N, O co-doped hierarchical porous carbon (NOHC) through hydrothermal carbonization (HTC) of chitin biomass with the assist of NH4Cl and subsequent carbonization with NaNH2. The optimal NOHC600 exhibits a remarkable hierarchical porous structure and an ultrahigh specific surface area (SSA) of 2555 m2 g-1. Furthermore, it showcases a significant content of N, O co-doping, thereby providing abundant defects and additional active sites for ion adsorption. The aforementioned characteristics ensure outstanding capacitance performance of NOHC600. In the three-electrode system, NOHC600 exhibits a remarkable specific capacitance of up to 455 F g-1 at a current density of 0.5 A g-1. The symmetric supercapacitors (SCs) based on NOHC600 achieve an impressive energy density of 30.4 Wh kg-1 at a power density of 180 W kg-1. Moreover, the all-solid-state NOHC600 microsupercapacitors (MSCs) demonstrate an exceptional areal capacitance of 78.2 mF cm-2 and an areal energy density of up to 10.8 µWh cm-2. Accordingly, this facile and scalable strategy shows a great potential for producing high-heteroatom-doped porous carbon materials from chitin biomass, which can be applied in practical energy-related applications.

Effect of hemicellulose content on the solution properties of cellulose carbamates in NaOH/ZnO aqueous system.

Hemicellulose removal from bleached bamboo pulp is key to produce qualified dissolving pulps. In this work, alkali/urea aqueous solution was firstly applied to remove hemicellulose in bleached bamboo pulp (BP). The effect of urea usage, time and temperature on the hemicellulose content of BP was studied. The reduction of hemicellulose content from 15.9 to 5.7 % was achieved in 6 wt% NaOH/1 wt% urea aqueous solution at 40 °C for 30 min. Cellulose carbamates (CCs) were obtained from the esterification of BP with urea. The dissolution behavior of CCs in NaOH/ZnO aqueous solutions with different degree of polymerization (DP), hemicellulose and nitrogen contents were studied by using optical microscope and rheology. The highest solubility was up to 97.7 % when the hemicellulose was 5.7 % and Mη was 6.5 × 104 (g/mol). With the decrease of hemicellulose content from 15.9 % to 8.60 % and 5.70 %, the gel temperature increased from 59.0, 69.0 to 73.4 °C. The apparent gelation time increased from 5640 to 12,120 s with the hemicellulose content increased from 8.60 % to 15.9 %. CC solution with 5.70 % hemicellulose always keeps a liquid-state (G" > G') until the test time reached 17,000 s. The results showed that the removal of hemicellulose, the decrease of DP and the increase of esterification endowed CC with higher solubility and solution stability.

Ink Based on the Tunable Swollen Microsphere for a 3D Printing Hydrogel with Broad-Range Mechanical Properties.

The development of the effective 3D printing strategy for diverse functional monomers is still challenging. Moreover, the conventional 3D printing hydrogels are usually soft and fragile due to the lack of an energy dissipation mechanism. Herein, a microsphere mediating ink preparation strategy is developed to provide tailored rheological behavior for various monomer direct ink writings. The chitosan microspheres are used as an exemplary material due to their tunable swelling ratio under the acid-drived electrostatic repulsion of the protonated amino groups. The rheological behaviors of the swollen chitosan microsphere (SCM) are independent on the monomer types, and various functional secondary polymers could be carried at a wide loading ratio by the acid driving. The SCM reinforces the hydrogel as the sacrificial bonds. With the adjustable composition, the 3D printing hydrogel mechanical properties are tunable in wide windows: strength (0.4-1.01 MPa), dissipated energy (0.11-3.25 MJ m-3), and elongation at break (47-626%). With the excellent printing and mechanical properties, the SCM inks enable multi-functional integration for soft device production, such as 4D printing robots and wearable strain sensors. We anticipate that this microsphere mediating 3D printing strategy can inspire new possibilities for the design of the robust hydrogels with a broad range of functionalities and mechanical performances.

Effect of Matrix Metalloproteinase 23 Accelerating Wound Healing Induced by Hydroxybutyl Chitosan.

Skin wounds may cause severe financial and social burden due to the difficulties in wound healing. Original inert dressings cannot meet multiple needs in the process of wound healing. Therefore, the development of materials to accelerate healing progress is essential and urgent. In the previous study, we found that the homogeneously synthesized hydroxybutyl chitosan (HBCS) had an effective performance in promoting wound healing. Proteomic analysis of the same specimen suggested that matrix metalloproteinase 23 (MMP23) may play a key role in HBCS expediting the progress of wound healing. In this work, we aim to reveal the underlying mechanism of MMP23 in the dynamic process of cutaneous proliferation and repair period. In order to regulate the expression level of MMP23 in the local wound area, we leaded in adeno-associated virus (AAV) to specifically decreased expression quantity of MMP23 in rat skin. In contrast to the negative control groups, we found that the wound closed faster and the collagen fibers and neovascularization were significantly increased in AAV groups. These findings highlighted that MMP23 was involved in wound healing after traumatic injury, and managing the expression of MMP23 could be a potential intervention target to accelerate wound healing.

Fabrication of an exosome-loaded thermosensitive chitin-based hydrogel for dental pulp regeneration.

Injective thermosensitive hydrogels are considered promising scaffolds to trigger dental pulp regeneration in devitalized human teeth. In this study, we developed a hydroxypropyl chitin (HPCH)/chitin whisker (CW) thermosensitive hydrogel with enhanced mechanical properties and biological activities. Exosomes can serve as biomimetic tools for tissue engineering, but the rapid clearance of unconjugated exosomes in vivo limits their therapeutic effects. To address this challenge, exosomes were isolated from human pulp stem cells (hDPSCs) and directly embedded into the HPCH/CW pre-gel to form an exosome-loaded hydrogel (HPCH/CW/Exo). The exosome-loaded thermosensitive hydrogel can be easily injected into an irregular endodontic space and gelated in situ. In vitro cell experiments proved that the delivery of exosomes significantly improved the ability of hydrogels to promote odontogenesis and angiogenesis. Meanwhile, in vivo animal experiments revealed the formation of new dental pulp-like tissues in an implanted tooth root model. Therefore, the proposed hydrogel provides a great potential alternative to traditional root canal therapy in dental clinics.

Pharmacokinetics and bioequivalence evaluation of omeprazole and sodium bicarbonate dry suspensions in healthy Chinese volunteers.

Omeprazole and sodium bicarbonate dry suspension are effective treatments for acid-related disorders. This study compared the bioequivalence and safety of the two formulations of omeprazole and sodium bicarbonate powder and assessed how CYP2C19 gene polymorphisms affect pharmacokinetics (PK). A single-center, randomized, single-dose, 2-sequence and 2-period crossover method was performed in forty healthy Chinese subjects. Blood samples were collected after a single dose for PK (AUC0-∞, AUC0-t, and Cmax) analysis. The concentrations of Omeprazole in human plasma were determined by HPLC-MS/MS. Besides, the gene polymorphisms of CYP2C19 were assessed by Sanger sequencing. The geometric mean ratios (90% confidence interval) [GMR (95% CI)] of Test/Reference preparation for Cmax: 95.2% (88.48%, 102.43%), AUC0-t: 97.47% (94.4%, 101.02%), AUC0-∞: 97.68% (94.27%, 101.21%) were within the range of 80.00-125.00%. The non-parametric test showed no statistical difference in Tmax between the two groups (p > 0.05). All drugs were well tolerated, no severe adverse reactions occurred, and no significant differences in adverse events between the two drugs. For CYP2C19 gene polymorphisms, the results showed that of 40 subjects, 12 subjects were extensive metabolizers, 24 were intermediate metabolizers, and 4 were poor metabolizers, the frequency of metabolic genotypes were 30%, 60%, and 10%. And the allele distributions for CYP2C19 were *1, *2, and *3 at 60%, 38.75%, and 1.25%. Both the CYP2C19 alleles and metabolic genotypes were consistent with other studies in Chinese. The results of PK parameters showed that different genotypes of CYP2C19 lead to significant differences in t1/2, AUC0-t, AUC0-∞ and Cmax, but no significant differences in Tmax in each group. At the same time, we confirmed that the PK parameters of the test and reference had no differences between the males and females. This study has shown that the pharmacokinetic parameters of the two formulations are not significantly different, which showed bioequivalence and exemplary safety. CYP2C19 gene polymorphism significantly differed in the PK parameters of omeprazole sodium bicarbonate powder.

Amphoteric Cellulose-Based Double-Network Hydrogel Electrolyte Toward Ultra-Stable Zn Anode.

Zinc (Zn) metal anode suffers from uncontrollable Zn dendrites and parasitic side reactions at the interface, which restrict the practical application of aqueous rechargeable zinc batteries (ARZBs). Herein, an amphoteric cellulose-based double-network is introduced as hydrogel electrolyte to overcome these obstacles. On one hand, the amphoteric groups build anion/cation transport channels to regulate electro-deposition behavior on Zn (002) crystal plane enabled by homogenizing Zn2+ ions flux. On the other hand, the strong bonding between negatively charged carboxyl groups and Zn2+ ions promote the desolvation process of [Zn(H2 O)6 ]2+ to eliminate side reactions. Based on the above two functions, the hydrogel electrolyte enables an ultra-stable cycling with a cumulative capacity of 7 Ah cm-2 at 20 mA cm-2 /20 mAh cm-2 for Zn||Zn cell. This work provides significant concepts for developing hydrogel electrolytes to realize stable anode for high-performance ARZBs.

A Pharmacokinetic Drug-Drug Interactions Study between Entecavir and Hydronidone, a Potential Novel Antifibrotic Small Molecule, in Healthy Male Volunteers.

INTRODUCTION: Hepatic fibrosis is an inevitable process of hepatic sclerosis, malignancy, and insufficiency, and hydronidone is an innovative antifibrosis drug. This study focus on the pharmacokinetic interaction of hydronidone and entecavir in healthy Chinese male subjects. METHODS: An open-label, three-period, multiple-dosage, self-controlled clinical trial was executed in 12 healthy male subjects. In period 1, the subjects took hydronidone 60 mg, q8h, for 7 days. In period 2, they were given entecavir 0.5 mg once daily for 9 days. Then, hydronidone and entecavir were given in combination for 6 days (days 20-26). Blood samples were taken up to 24 h post-dosing, while pre-dose blood samples were drawn on days 7, 19, and 26. RESULTS: The area under the curve (AUC)0-t_ss of entecavir slightly increased from 15.56 ± 2.67 to 16.17 ± 2.77 ng h/ml with coadministration with hydronidone, while the other pharmacokinetic parameters of hydronidone and entecavir were comparable between monotherapy and combination therapy. The geometric mean ratios (GMRs) [90% confidence intervals (CIs)] of Cmax_ss, AUC0-t_ss, and AUC0-∞_ss of entecavir after coadministration compared with entecavir alone were 107.21% (97.04-118.45%), 103.85% (100.94-106.83%), and 110.81% (97.19-126.33%), respectively. And the GMRs and 90% CIs of Cmax,ss, AUC0-t_ss, and AUC0-∞_ss for combination therapy compared with the hydronidone monotherapy group were 102.72% (84.21-125.29%), 106.52% (97.06-116.90%), and 108.86% (96.42-122.89%), respectively. CONCLUSIONS: There was no drug-drug interaction between hydronidone and entecavir in healthy male volunteers. However, multiple doses of hydronidone have a risk with increasing exposure to entecavir in vivo, which needs to be further clarified. REGISTRATION NUMBER: ChiCTR2200059683 (retrospectively registered).

Effects of intestinal microbiota on pharmacokinetics of cyclosporine a in rats.

Background: Intestinal microbiota has been confirmed to influencing the pharmacokinetic processes of a variety of oral drugs. However, the pharmacokinetic effects of the gut microbiota on cyclosporine A, a drug with a narrow therapeutic window, remain to be studied. Method: Twenty-one rats were randomly divided into three groups: (a) control group (CON), (b) antibiotic treatment group (ABT) and (c) fecal microbe transplantation group (FMT). The ABT group was administrated with water containing multiple antibiotics to deplete microorganisms. FMT was with the same treatment, followed by oral administration of conventional rat fecal microorganisms for normalization. Result: The bioavailability of CSA increased by 155.6% after intestinal microbes were consumed by antibiotics. After intestinal microbiota reconstruction by fecal transplantation, the increased bioavailability was significantly reduced and basically returned to the control group level. Changes in gut microbiota alter the protein expression of CYP3A1, UGT1A1 and P-gp in liver. The expressions of these three proteins in ABT group were significantly lower than those in CON and FMT groups. The relative abundance of Alloprevolleta and Oscillospiraceae UCG 005 was negatively correlated with CSA bioavailability while the relative abundance of Parasutterella and Eubacterium xylanophilum group was negatively correlated with CSA bioavailability. Conclusion: Intestinal microbiota affects the pharmacokinetics of CSA by regulating the expression of CYP3A1, UGT1A1 and P-GP.

Transparent, Ultra-Stretching, Tough, Adhesive Carboxyethyl Chitin/Polyacrylamide Hydrogel Toward High-Performance Soft Electronics.

To date, hydrogels have gained increasing attentions as a flexible conductive material in fabricating soft electronics. However, it remains a big challenge to integrate multiple functions into one gel that can be used widely under various conditions. Herein, a kind of multifunctional hydrogel with a combination of desirable characteristics, including remarkable transparency, high conductivity, ultra-stretchability, toughness, good fatigue resistance, and strong adhesive ability is presented, which was facilely fabricated through multiple noncovalent crosslinking strategy. The resultant versatile sensors are able to detect both weak and large deformations, which owns a low detection limit of 0.1% strain, high stretchability up to 1586%, ultrahigh sensitivity with a gauge factor up to 18.54, as well as wide pressure sensing range (0-600 kPa). Meanwhile, the fabrication of conductive hydrogel-based sensors is demonstrated for various soft electronic devices, including a flexible human-machine interactive system, the soft tactile switch, an integrated electronic skin for unprecedented nonplanar visualized pressure sensing, and the stretchable triboelectric nanogenerators with excellent biomechanical energy harvesting ability. This work opens up a simple route for multifunctional hydrogel and promises the practical application of soft and self-powered wearable electronics in various complex scenes.

Micropatterned Hydrogels with Highly Ordered Cellulose Nanocrystals for Visually Monitoring Cardiomyocytes.

Cardiac microphysiological systems are accurate in vitro platforms that reveal the biological mechanisms underlying cardiopathy, accelerating pharmaceutical research in this field. Current cardiac microphysiological devices and organs-on-chips consist of several layers prepared with complex, multi-step processes. Incorporating inorganic photonic crystals may cause long-term biocompatibility issues. Herein, micropatterned hydrogels with anisotropic structural colors are prepared by locking shear-oriented tunicate cellulose nanocrystals (TCNCs) in hydrogel networks through in situ polymerization, allowing the visualization and monitoring of cardiomyocytes. The anisotropic hydrogels are composed of highly ordered TCNCs with bright interference color and micro-grooved methacrylated gelatin with excellent biocompatibility. The microgroove patterns induce cardiomyocyte alignment and the autonomous beating of cardiomyocytes causes the hydrogels to deform, dynamically shifting the interference color. These micropatterned hydrogels could noninvasively monitor real-time changes of cardiomyocytes under pharmaceutical treatment and electrical stimulation through wavelength shifts in the transmittance spectra. This system provides a new way to detect the beat rate of cardiac tissue and it may contribute to high throughput develop.

Dual-network polyacrylamide/carboxymethyl chitosan-grafted-polyaniline conductive hydrogels for wearable strain sensors.

Conductive, wearable, and flexible hydrogel-based sensors are considered as promising applications in human motion detection and physiological signal monitoring. However, it is still a problem to integrate multiple functions into one material for the next-generation smart devices. Herein, we fabricated an ionic/electronic dual conductive hydrogel by combining the chemically crosslinked polyacrylamide (PAM) and the physically crosslinked carboxymethyl chitosan-grafted-polyaniline (CMCS-g-PANI)/Ag+ network. The double-network hydrogel displays a high stretchability, repeatable adhesiveness, antibacterial activities, and biocompatibility. It also has high sensitivity and stable electrical performance for wearable strain sensors. Furthermore, we assembled a self-powered strain sensor based on the conversion of chemical energy to electrical energy. It can be used for human motion detection even without external power supply. This work provides an avenue for the development of multifunctional hydrogels with outstanding mechanical and electronic performances for application in wearable electronic devices.

A novel, simple and reliable method for the determination of hydronidone and its metabolites M3 and M4 in human plasma and urine by HPLC-MS/MS and its application to a pharmacokinetic study in health Chinese subjects.

In this study, a novel, simple and reliable high-performance liquid chromatography with tandem mass spetrometry method (HPLC-MS/MS) was developed for the determination of hydronidone and its metabolites M3 and M4 in human plasma and urine so as to study the clinical pharmacokinetics of hydronidone. By effectively inhibiting the proliferation of hepatic stellate cells (HSC), hydronidone can reduce collagen synthesis and curbs the process of liver fibrosis, and is currently in the stage of clinical research for anti-liver fibrosis. Hydronidone and its metabolites M3, M4 were extracted from human plasma by protein precipitation, and the urine samples were directly diluted with acetonitrile and analyzed by HPLC-MS/MS. The quantification ranges in plasma were 1.00-1000 ng/mL, 2.00-2000 ng/mL and 4.00-4000 ng/mL, respectively and in urine were 10.0-2000 ng/L, 100-25000 ng/L and 300-75000 ng/L, respectively. Coefficients of variation of less than 15% between intraday and interday accuracy and precision values were observed for hydronidone, M3 and M4. The S/N (signal-to-noise ratio) of the analyte in each Low limit of quantification sample in the analytical batch was greater than 5, indicating good sensitivity. The recovery rates were above 50% for all analytes. The parameters such as linearity, selectivity, lower precision, accuracy, recovery, stability and matrix effects were validated by the methodology and met the requirements specified by the FDA and the European Medicines Agency. The method has been successfully applied to the pharmacokinetics of hydronidone and its metabolites M3 and M4 in healthy Chinese volunteers.