Chlorogenic acid/carboxymethyl chitosan nanoparticle-assisted biomultifunctional hyaluronic acid-based hydrogel scaffolds for burn skin repair.

Burns are a prevalent type of injury worldwide, affecting tens of millions of people each year and significantly impacting the physical and psychological well-being of patients. Consequently, prompt treatment of burn wounds is imperative, with oxidative stress and excessive inflammation identified as primary factors contributing to delayed healing. In recent years, there has been growing interest in in situ crosslinked multifunctional hydrogels as a minimally invasive approach for personalized treatment delivery. To address these, a photocrosslinkable methacryloyl hyaluronic acid hydrogel scaffold embedded with chlorogenic acid/carboxymethyl chitosan nanoparticles (CGA/CMCS-HAMA, CCH), was developed for the treatment of burn wounds. The hydrogel prepared degraded by over 50 % by day 20, demonstrating stability and meeting the therapeutic requirements for burn wounds. Leveraging the extracellular matrix-like properties of HAMA and the antioxidant capabilities of CGA/CMCS NPs, this hydrogel demonstrates the ability to locally and continuously scavenge ROS and inhibit lipid peroxidation, inhibiting ferroptosis. Moreover, hydrogels well modulate the expression of macrophage- and fibroblast-associated inflammatory factors. Additionally, the hydrogel promotes cell adhesion and migration, further supporting the healing process. Overall, this innovative approach offers a safe and promising solution for burn wound treatment, addressing drug breakthrough and safety concerns while being adaptable to various irregular wound types.

A Phase 1/2 Multicenter Randomized Trial of Local Ablation plus Toripalimab versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma.

PURPOSE: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240 mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3), or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. RESULTS: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate (ORR) than Schedule D14 for non-ablation lesions (37.5% vs. 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher ORR than with toripalimab alone (33.8% vs. 16.9%; P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 vs. 3.8 months; P < 0.001) and median overall survival (18.4 vs. 13.2 months; P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, eight (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. CONCLUSIONS: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone, with an acceptable safety profile.

Preparation and identification of novel antioxidant peptides from camel bone protein.

Collagen hydrolysates are a vital source of bioactive peptides. The objective of this study was to prepare camel bone collagen hydrolysates with antioxidant activity, and to identify the peptides responsible for the antioxidant activity. To this end, single-factor and orthogonal tests were performed to explore the optimum preparation conditions. A hydrolysis time of 5 h, enzyme:substrate ratio of 1200 U/g, pH of 7.0, and a material:water ratio of 1:3.0 were adopted. Subsequently, the hydrolysates were purified using a series of chromatography procedures, and three novel peptides, GPPGPPGPPGPPGPPSGGFDF (hydroxylation), PATGDLTDFLK, and GSPGPQGPPGSIGPQ, possessing antioxidant abilities, were identified from the fraction using liquid chromatography-tandem mass spectrometry. The peptide PATGDLTDFLK showed excellent DPPH scavenging activity (39%) and a good cytoprotective effect on H2O2-induced oxidative stress damage in HepG2 cells with a 21.1% increase observed.

Identification and Characterization of Peptides from Bovine Collagen Hydrolysates that Promote Myogenic Cell Proliferation.

In this study, bovine collagen hydrolysate was purified via a series of chromatograms, and the peptides with the highest activity for promoting myoblast proliferation were identified by LC-MS-MS. It was demonstrated that the peptide GDAGPPGPAGPAGPPGPIG (hydroxylation) could promote C2C12 proliferation (+18.5% ± 0.04, P < 0.05). The certain peptide was capable of regulating the myogenic cell cycle and inhibiting myogenic cell apoptosis. By combining molecular docking, quantitative real-time PCR, and metabonomics, we suggested that the peptide GDAGPPGPAGPAGPPGPIG (hydroxylation) might bind to FGFR1 and affect the expression of genes downstream of FGFR1 and influence protein synthesis to promote myoblast proliferation. The above results showed that the peptides isolated in this study have the potential to alleviate sarcopenia in the elderly.

Clinical characteristics and outcomes of MPO-ANCA-associated glomerulonephritis with bronchiectasis: A retrospective case-control study.

BACKGROUND: The association of bronchiectasis with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV) has been widely described in recent studies. However, the clinical features and outcomes of MPO-ANCA-associated glomerulonephritis (MPO-ANCA GN) patients with bronchiectasis remain enigmatic. METHODS: MPO-ANCA GN patients with bronchiectasis were compared to MPO-ANCA GN patients alone. Clinical imaging, pathological tests, and follow-up examination data of patients were collected retrospectively. Progression to end-stage renal disease (ESRD) and death was treated as endpoint events. RESULTS: 153 cases (52 patients with bronchiectasis) were included in this study. Compared to MPO-ANCA GN patients alone, MPO-ANCA GN patients with bronchiectasis exhibited a lower level of proteinuria (p = 0.019) and relatively higher eGFR level. MPO-ANCA GN patients with bronchiectasis had less frequent incidences of interstitial lung disease (ILD) and emphysema (p<0.001, p = 0.016, respectively) but with higher rates of pulmonary infection (p<0.001). Bronchiectasis severity (the modified Reiff score) was positively correlated with MPO antibody titers (ρ=0.480, p<0.001), but not with shorter renal survival. A relatively higher remission rate was been seen in MPO-ANCA GN patients with bronchiectasis, who showed reduced susceptibility in progressing to ESRD in multivariate analysis (p = 0.043, HR=0.542, 95% CI 0.299-0.982). One-and three-year overall survival rates were 88.2% and 77.3% for MPO-ANCA GN with bronchiectasis cases versus 83.7% and 67.2% for MPO-ANCA GN patients alone (p = 0.431, p = 0.241, respectively). CONCLUSION: The severity of bronchiectasis was correlated with anti-MPO antibody titers in MPO-ANCA GN patients. For MPO-ANCA GN patients, bronchiectasis associated with good renal prognosis, but it did not improve overall survival.

A Dynamic Gain Approach to Consensus Control of Nonlinear Multiagent Systems With Time Delays.

This article proposes a dynamic gain approach for investigating the leader-follower consensus problem of nonlinear multiagent systems with both distributed delays and discrete delays. It is assumed that each agent is in the strict-feedback form and satisfies the Lipschitz condition with an unknown constant. A novel dynamic gain observer is first constructed for each follower by only utilizing the output information of the follower and its neighbors. By introducing an observer, a distributed output-feedback control protocol is designed for each follower agent under a directed communication topology. It is proved by the Lyapunov-Razumikhin theorem that the consensus of the multiagent system is achieved with the proposed consensus protocol. Different from the existing results, the dynamic gain is constructed for each follower to propose the consensus protocol, without resorting to the celebrated backstepping technique. Moreover, the time-varying gain is designed in a uniform framework. The effectiveness of the proposed approaches is illustrated by a simulation example.

Event-Triggered Output Feedback Control of Switched Nonlinear Systems With Input Saturation.

This article is concerned with the event-triggered output feedback control problem for a class of switched nonlinear strict-feedback systems subject to asymmetric input saturation. The nonlinear terms are assumed to be bounded by a continuous function of the output multiplied by unmeasured states. The hyperbolic tangent function is employed to process the error caused by the event-triggered scheme, and an indicator function of the saturation degree is used to analyze the influence generated by the asymmetric input saturation. By adopting the common Lyapunov function method and the dynamic gain control design approach, a new design procedure based on a reduced-order observer is proposed to construct an output feedback controller. It is proved by the Lyapunov analysis that the proposed event-triggered control scheme can ensure that all the signals of the closed-loop system are globally bounded. Furthermore, the output can be converged to a bounded region around the origin, and this region can be tuned to be small by adjusting the design parameters. Different from typical existing results on the switched nonlinear strict-feedback systems, the celebrated backstepping method is not employed in this article. The continuous stirred tank reactor is finally used to demonstrate the effectiveness of the proposed control scheme.

Design of output feedback controller for stochastic feedforward systems with unknown measurement sensitivity.

This paper investigates the problem of output feedback control for a class of stochastic feedforward systems with unknown measurement sensitivity. Unknown measurement sensitivity is only a bounded continuous function and its derivative is not guaranteed. To solve the considered problem, the low-gain linear K-filters are performed without using the information of the output, and a gain design method based on backstepping is proposed to construct an output feedback controller. By the stochastic stability theory, the asymptotically stable in probability of the closed-loop control system is analyzed. A nonlinear liquid level control resonant circuit system with unknown measurement sensitivity is given to demonstrate the effectiveness of the proposed control scheme.