Showing papers by "Li Yang published in 2023"
TL;DR: In this article , smart-responsive multifunctional hydrogels were developed to improve chronic diabetic wound healing, which could quickly respond to the acidic environment of the diabetic wound site and mediate multistage sequential delivery of silver and curcumin-loaded polydopamine nanoparticles.
2 citations
TL;DR: In this paper , the authors explored the pathophysiological mechanism of heart failure and summarized injectable hydrogels as a potential solution for current clinical trials and applications, and the mechanism of action of these hydrogel-based therapies was emphasized.
Abstract: Heart failure (HF) affects 60 million people worldwide and has developed into a global public health problem surpassing cancer and urgently needs to be solved. According to the etiological spectrum, HF due to myocardial infarction (MI) has become the dominant cause of morbidity and mortality. Possible treatments include pharmacology, medical device implantation, and cardiac transplantation, which are limited in their ability to promote long-term functional stabilization of the heart. Injectable hydrogel therapy has emerged as a minimally invasive tissue engineering treatment approach. Hydrogels can provide the necessary mechanical support for the infarcted myocardium and serve as carriers of various drugs, bioactive factors and cells to improve the cellular microenvironment in the infarcted region and induce myocardial tissue regeneration. Herein, we explored the pathophysiological mechanism of HF and summarized injectable hydrogels as a potential solution for current clinical trials and applications. Specifically, mechanical support hydrogels, decellularized ECM hydrogels, a variety of biotherapeutic agent-loaded hydrogels and conductive hydrogels for cardiac repair were discussed, and the mechanism of action of these hydrogel-based therapies was emphasized. Finally, the limitations and future prospects of injectable hydrogel therapy for HF post MI were proposed to inspire novel therapeutic strategies. This article is protected by copyright. All rights reserved.
2 citations
TL;DR: In this paper , atomically dispersed Ir atoms were incorporated into a spinel Co3O4 lattice as an acidic OER catalyst, which exhibits excellent activity and stability for water oxidation.
Abstract: Iridium oxide is considered the only practical catalyst for oxygen evolution reaction (OER) in commercial proton exchange membrane (PEM) electrolyzers. However, its low activity and high cost greatly hinder the large-scale development of PEM electrolyzers for hydrogen production. Herein, we report atomically dispersed Ir atoms incorporated into a spinel Co3O4 lattice as an acidic OER catalyst, which exhibits excellent activity and stability for water oxidation. The catalyst significantly lowers the overpotential down to 226 mV at 10 mA cm–2 with an ultrahigh turnover frequency value of 3.15 s–1 (η = 300 mV), 3 orders of magnitude higher than that of commercial IrO2. Meanwhile, the catalyst shows superior corrosion resistance in an acidic OER condition, reaching a lifespan of up to 500 h at 10 mA cm–2. First-principles calculations reveal that the key *OOH intermediate can be stabilized by the lattice oxygen coordinated to the Ir active site via hydrogen bond formation, which substantially regulates the rate-limiting step and lowers the activation free energy of the OER process. This work demonstrates a strategy for improving the OER activity of Ir-based catalysts and provides insights into the regulation of the reaction mechanism.
2 citations
TL;DR: In this article , the authors investigated the efficacy and safety of myeloid-derived supprfessor cells (MDSCs) in protecting against AIH, and explored the underlying mechanism.
1 citations
TL;DR: The use of microneedles to deliver bioactive molecules, mesenchymal stem cells, and growth factors in situ allows for targeted tissue and better spatial distribution as mentioned in this paper .
Abstract: Tissue injury is a common clinical problem, which may cause great burden on patients' life. It is important to develop functional scaffolds to promote tissue repair and regeneration. Due to their unique composition and structure, microneedles have attracted extensive attention in various tissues regeneration, including skin wound, corneal injury, myocardial infarction, endometrial injury, and spinal cord injury et al. Microneedles with micro-needle structure can effectively penetrate the barriers of necrotic tissue or biofilm, therefore improving the bioavailability of drugs. The use of microneedles to deliver bioactive molecules, mesenchymal stem cells, and growth factors in situ allows for targeted tissue and better spatial distribution. At the same time, microneedles can also provide mechanical support or directional traction for tissue, thus accelerating tissue repair. This review summarized the research progress of microneedles for in situ tissue regeneration over the past decade. At the same time, the shortcomings of existing researches, future research direction and clinical application prospect were also discussed.
TL;DR: In this paper , a dual-functional surface engineering strategy for CVCs by organic integration of endothelium-mimicking and fibrinolytic functions is presented, which provides a promising solution for long-term blood-contacting devices to combat thrombosis and infection.
Abstract: Long-term blood-contacting devices (e.g., central venous catheters, CVCs) still face the highest incidence of blood stream infection and thrombosis in clinical application. To effectively address these complications, this work reports a dual-functional surface engineering strategy for CVCs by organic integration of endothelium-mimicking and fibrinolytic functions. In this proposal, a lysine (Lys)/Cu2+ -incorporated zwitterionic polymer coating (defined as PDA/Lys/Cu-SB) w as designed and robustly fabricated onto commercial CVCs using a facile two-step process. Initially, adhesive ene-functionalized dopamine w as covalently reacted with Lys and simultaneously coordinated with bactericidal Cu2+ ions, leading to the deposition of a PDA/Lys/Cu coating on CVCs through mussel foot protein inspired surface chemistry. Next, zwitterionic poly(sulfobetaine methacrylate) (pSB) brushes w ere grafted onto the PDA/Lys/Cu coating to endow lubricant and antifouling properties. In the final PDA/Lys/Cu-SB coating, endothelium-mimicking function w as achieved by combining the catalytic generation of nitric oxide from the chelated Cu2+ with antifouling pSB brushes, which led to significant prevention of thrombosis, and bacterial infection in vivo. Furthermore, the immobilized Lys with fibrinolytic activity showed remarkably enhanced long-term anti-thrombogenic properties as evidenced in vivo by demonstrating the capability to lyse nascent clots. Therefore, this developed strategy provides a promising solution for long-term blood-contacting devices to combat thrombosis and infection. This article is protected by copyright. All rights reserved.
TL;DR: In this paper , the authors reviewed the development and therapeutic results of interventional devices for chordal implantation and discuss the possible clinical factors responsible for the rupture of the artificial chordal material.
Abstract: Mitral regurgitation (MR) was the most common heart valve disease. Surgical repair with artificial chordal replacement had become one of the standard treatments for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) was currently the most commonly used artificial chordae material due to its unique physicochemical and biocompatible properties. Interventional artificial chordal implantation techniques had emerged as an alternative treatment option for physicians and patients in treating mitral regurgitation. Using either a transapical or a transcatheter approach with interventional devices, a chordal replacement could be performed transcatheter in the beating heart without cardiopulmonary bypass, and the acute effect on the resolution of mitral regurgitation could be monitored in real-time by transesophageal echo imaging during the procedure. Despite the in vitro durability of the expanded polytetrafluoroethylene material, artificial chordal rupture occasionally occurred. In this article, we reviewed the development and therapeutic results of interventional devices for chordal implantation and discuss the possible clinical factors responsible for the rupture of the artificial chordal material.
TL;DR: In this paper , a double-blind, parallel-group study aimed to evaluate the pharmacokinetics, safety, and tolerability of bismuth-containing vonoprazan- or esomeprazole-based quadruple therapy in H. pylori-positive healthy subjects at a single site in China.
Abstract: Quadruple therapy comprising 2 antibiotics, a proton pump inhibitor, and bismuth, is recommended for Helicobacter pylori eradication in China. This Phase 1, double-blind, parallel-group study aimed to evaluate the pharmacokinetics, safety, and tolerability of bismuth-containing vonoprazan- or esomeprazole-based quadruple therapy in H. pylori-positive healthy subjects at a single site in China. Quadruple therapy comprising vonoprazan 20 mg or esomeprazole 20 mg with bismuth potassium citrate 600 mg (equivalent to bismuth 220 mg), clarithromycin 500 mg, and amoxicillin 1000 mg was administered twice daily for 2 weeks. Forty-four subjects were enrolled, 22 each in the vonoprazan (mean age, 34.5 years; men, 63.6%) and esomeprazole (mean age, 31.6 years; men, 59.1%) groups. Day 14 bismuth plasma pharmacokinetic parameters area under the plasma concentration-time curve during a dosing interval (geometric mean ratio, 1.07 [90% confidence interval, 0.82-1.40]) and maximum observed plasma concentration (geometric mean ratio, 1.30 [90% confidence interval, 0.94-1.81]) were similar between the treatment groups. At Day 42 follow-up, 100% and 94.4% of subjects were H. pylori negative in the vonoprazan and esomeprazole groups, respectively. The incidence of treatment-emergent adverse events was similar between the groups, with no serious adverse events. No new safety concerns were identified. In conclusion, vonoprazan had no significant effect on plasma bismuth exposure compared with esomeprazole.
TL;DR: In this article , the authors present that Cos induces the differentiation of bone marrow mesenchymal stem cells into glia-like cells (C-bMSCs) capable of secreting neurotrophic factors and homing to injured brain tissues.
09 Jan 2023
TL;DR: In this paper , the authors showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and programmed cell death-1 (PD-1) blockade dramatically abrogated tumor growth, inhibited microvessel density, and promoted tumor apoptosis, compared to treatment with the single agents.
Abstract: Treatment with immune checkpoint inhibitors (ICIs) has recently achieved unprecedented clinical benefits, becoming a critical treatment for patients with cancer. However, a set of patients are resistant to immune checkpoint inhibitor therapy, likely due to the limited presence or lack of tumor-infiltrating lymphocytes in their tumors. Increasing data indicate that antiangiogenic therapy substantially reduces cancer-induced immunosuppression and is an effective way to enhance the efficacy of cancer immunotherapies by combination with ICIs. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and programmed cell death-1 (PD-1) blockade dramatically abrogated tumor growth, inhibited microvessel density, and promoted tumor apoptosis, compared to treatment with the single agents. Further investigation using flow cytometry showed that combined therapy significantly increased CD8+ T-cell infiltration into tumors and promoted the level of CD8+ IFN-γ+ T cells. Moreover, combined therapy effectively reduced the frequencies of CD11b+ F4/80+ tumor-associated macrophages (TAMs) and slightly increased M1/M2 ratio in the tumors. RNA-seq analysis of tumor tissue following combined therapy also demonstrated upregulated expression of genes associated with the antitumor immune response. These data support the rationale for combining antiangiogenic and ICIs for cancer therapy.
TL;DR: In this paper , a peptide-decorated hyaluronic acid was synthesized, and the grafted Fmoc-phenylalanine,phenylaline-phenylonine-COOH (FmocFF) peptide self-assembled with β-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution.
Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes endless pain and poor quality of life in patients. Usage of a lubricant combined with anti-inflammatory therapy is considered a reasonable and effective approach for the treatment of RA. Herein, inspired by glycopeptides, a peptide-decorated hyaluronic acid was synthesized, and the grafted Fmoc-phenylalanine-phenylalanine-COOH (FmocFF) peptide self-assembled with β-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution. The hydrophobic anti-inflammatory drug curcumin (Cur) could be embedded in the vesicle walls through π-π interactions with the FmocFF peptide. Furthermore, the inflammation suppression function of the Cur-loaded vesicles both in vitro and in vivo was demonstrated to be an effective treatment for RA therapy. This work proposes new insights into the folding and hierarchical assembly of glycopeptide mimics, providing an efficient approach for constructing intelligent platforms for drug delivery, disease therapy, and diagnostic applications.
01 Apr 2023
TL;DR: Trovato et al. as mentioned in this paper found that reduced lysophosphatidylcholines (LPC) levels are prognostic markers of poor outcome in acute liver failure.
TL;DR: In this paper , a dendritic cell-based neoantigen vaccine combined with ICI was used to treat advanced SqCC in a PD-1 blockade-resistant patient.
Abstract: Background: Although significant progress has been made in immune checkpoint inhibitor (ICI) treatment of advanced squamous cell carcinoma (SqCC), most patients still experience acquired drug resistance. Methods: We used a dendritic cell-based neoantigen vaccine combined with ICIs to treat advanced SqCC in a PD-1 blockade-resistant patient. Results: The follow-up of this patient after 12 months revealed significant tumor regression. We also identified a new JAK1 ICI-resistant mutation that could become a potential universal neoantigen target for tumor vaccines. Conclusion: Individualized management of advanced SqCC through a combined neoantigen vaccine and ICI administration could yield beneficial clinical outcomes. Vaccines targeting anti-PD-1-resistant JAK1 mutations might be of particular benefit to a specific group of solid tumor patients.
TL;DR: In this article , a simple electrostatic self-assembly approach was employed to prepare a film composed of PB nanocubes on the MXene substrates, which can realize the real-time monitoring of H2O2 secretion from living CTCs.
TL;DR: In this article , the role of neutrophils as the predominant phagocyte responsible for the clearance of apoptotic hepatic cells in the steady state was investigated, and it was shown that neutrophil burrowed directly into apoptotic hepatocytes, a process termed perforocytosis, and ingested the effete cells from the inside.
Abstract: Billions of apoptotic cells are removed daily in a human adult by professional phagocytes (e.g. macrophages) and neighboring nonprofessional phagocytes (e.g. stromal cells). Despite being a type of professional phagocyte, neutrophils are thought to be excluded from apoptotic sites to avoid tissue inflammation. Here we report a fundamental and unexpected role of neutrophils as the predominant phagocyte responsible for the clearance of apoptotic hepatic cells in the steady state. In contrast to the engulfment of dead cells by macrophages, neutrophils burrowed directly into apoptotic hepatocytes, a process we term perforocytosis, and ingested the effete cells from the inside. The depletion of neutrophils caused defective removal of apoptotic bodies, induced tissue injury in the mouse liver and led to the generation of autoantibodies. Human autoimmune liver disease showed similar defects in the neutrophil-mediated clearance of apoptotic hepatic cells. Hence, neutrophils possess a specialized immunologically silent mechanism for the clearance of apoptotic hepatocytes through perforocytosis, and defects in this key housekeeping function of neutrophils contribute to the genesis of autoimmune liver disease.
TL;DR: In this article , the authors conducted a systematic search for studies in which survival analysis among high-risk T1 colorectal cancer patients undergoing local resection and surgical resection was performed.
TL;DR: Neo-DCVac-02 as mentioned in this paper is a personalized neoantigen pulsed autologous dendritic cell vaccine for hepatocellular carcinoma (HCC) patients.
Abstract: e14658 Background: The primary means of treating hepatocellular carcinoma (HCC) is radical surgery. However, HCC has a high propensity to recur post-operatively, and no standard adjuvant therapies have been approved. Tumor neoantigens, which are epitopes derived from tumor-specific mutations, may be utilized in personalized vaccines to activate T cell responses. This trial aims to assess the safety and efficacy of personalized neoantigen pulsed autologous dendritic cell vaccine (Neo-DCVac-02) in patients with HCC. Methods: Eligible patients had histologically confirmed high-risk HCC after radical surgery. Upon obtaining the baseline biopsy specimens and PBMCs of appropriate quality for DNA and RNA sequencing, neoantigen prediction, screening, and synthesis were performed. Subsequently, autologous dendritic cells (DCs) were generated and pulsed with neoantigen peptides to produce Neo-DCVac-02.On day 0, patients were treated with cyclophosphamide at a dose of 250 mg/m2. The prepared Neo-DCVac-02 vaccine was administered subcutaneously on day 1, followed by GM-CSF administered daily for 5 days. The primary objectives of this study were to evaluate the feasibility and safety/tolerability. Secondary objectives included assessment of immune responses (via vaccine response: IFNγ ELISpot), recurrence-free survival (RFS), and overall survival (OS). Results: A total of 32 patients provided informed consent to initiate the process of personalized neoantigen discovery, of which 26 (81%) met the requirements for successful product selection for clinical manufacturing. And feasibility was shown with 13 patients receiving Neo-DCVac-02. Thirteen patients did not receive neoantigen vaccines (7 for progressive disease,6 for withdrawal of informed consent because of COVID-19). Treatment was well-tolerated with no grade 2+ treatment-related adverse events (TRAEs). The common grade 1TRAEs were neutropenia (8.3%), injection site reactions (75%), rash (16.7%), fatigue (8.3%), and headache (8.3%). The median follow-up to date is 19.30 (14.4-31.9) months, with median RFS and OS not yet reached and a 1-year RFS of 83%. Five of 13 evaluable patients showed elevated antigen-specific T-cell activity by IFNγ ELISpot for more than 50% of neoantigen peptides in Neo-DCVac-02, and persistent cellular responses were noted out to 1 year. Increases in activation/co-stimulatory of T cells seen after treatment with Neo-DCVac-02 revealed by Flow-cytometric analyses, suggest immune priming. Conclusions: These data demonstrate that Neo-DCVac-02 is safe, well tolerated, and able to generate durable antigen-specific lymphocyte immune responses. Early signs of clinical efficacy were observed in HCC patients. Clinical trial information: NCT04147078 .
TL;DR: In this paper , the 5-HT2A receptor plays a key role in cell injury, which leads to the activation of the 5 -HT degradation system (5DS) axis, leading to the phosphorylation of JNK, p38 MAPK, STAT3, and NF-κB.
TL;DR: In this article , a strawberry petiole derived carbon fiber (SCF) /magnetic CoFe composites were synthesized via solvothermal reaction and calcination treatment, which achieved a minimum reflection loss of −40.4 dB and a wide effective absorption bandwidth of 3.5 GHz.
TL;DR: In this article , the authors proposed a transfer learning method based on an iterative neural operator to assimilate numerical data with experimental data for effusion cooling, which significantly reduced the requirements for the number of training samples and training epochs to reach the same accuracy.