What Are the Reliable Plasma Biomarkers for Mild Cognitive Impairment? A Clinical 4D Proteomics Study and Validation.

Objective: At present, Alzheimer's disease (AD) lacks effective treatment means, and early diagnosis and intervention are the keys to treatment. Therefore, for mild cognitive impairment (MCI) and AD patients, blood sample analysis using the 4D nonstandard (label-free) proteomic in-depth quantitative analysis, looking for specific protein marker expression differences, is important. These marker levels change as AD progresses, and the analysis of these biomarkers changes with this method, which has the potential to show the degree of disease progression and can be used for the diagnosis and preventive treatment of MCI and AD. Materials and Methods: Patients were recruited according to the inclusion and exclusion criteria and divided into three groups according to scale scores. Elderly patients diagnosed with AD were selected as the AD group (n = 9). Patients diagnosed with MCI were classified into the MCI group (n = 10). Cognitively healthy elderly patients were included in the normal cognition control group (n = 10). Patients' blood samples were used for 4D label-free proteomic in-depth quantitative analysis to identify potential blood biomarkers. The sample size of each group was expanded (n = 30), and the selected biomarkers were verified by enzyme-linked immunosorbent assay (ELISA) to verify the accuracy of the proteomic prediction. Results: Six specific blood markers, namely, APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8, were detected by 4D label-free proteomic quantitative analysis. These markers showed a statistically significant upregulation trend in the MCI and AD groups compared with the normal cognition control group (P < 0.05). ELISA results showed that the levels of these six proteins in the MCI group were significantly higher than those in the normal cognition control group, and the levels of these six proteins in the AD group were significantly higher than those in the MCI group (P < 0.05). Conclusion: The plasma levels of APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8 in cognitively healthy elderly patients and patients with MCI and AD were significantly different and, more importantly, showed a trend of increasing expression. These results indicate that these six human plasma markers have important diagnostic and therapeutic potential in the identification of cognitive impairment and have value for in-depth research and clinical application.

A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing.

Hyaluronic acid (HA)-based biopolymer hydrogels are promising therapeutic dressings for various wounds but still underperform in treating diabetic wounds. These wounds are extremely difficult to heal and undergo a prolonged and severe inflammatory process due to bacterial infection, overexpression of reactive oxygen species (ROS), and insufficient synthesis of NO. In this study, a dynamic crosslinked hyaluronic acid (HA) hydrogel dressing (Gel-HAB) loaded with allomelanin (AMNP)-N, N'-dis-sec-butyl-N, N'-dinitroso-1, 4-phenylenediamine (BNN6) nanoparticles (AMNP-BNN6) was developed for healing diabetic wounds. The dynamic acylhydrazone bond formed between hydrazide-modified HA (HA-ADH) and oxidized HA (OHA) makes the hydrogel injectable, self-healing, and biocompatible. The hydrogel, loaded with AMNP-BNN6 nanoparticles, exhibits promising ROS scavenging ability and on-demand release of nitric oxide (NO) under near-infrared (NIR) laser irradiation to achieve mild photothermal antibacterial therapy (PTAT) (∼ 48 °C). Notably, the Gel-HAB hydrogel effectively reduced the oxidative stress level, controlled infections, accelerated vascular regeneration, and promoted angiogenesis, thereby achieving rapid healing of diabetic wounds. The injectable self-healing nanocomposite hydrogel could serve as a mild photothermal-enhanced antibacterial, antioxidant, and nitric oxide release platform for the treatment of diabetic wounds.

Cation-π Interaction-Enhanced Self-Healing Injectable Hydrogels for Gastric Perforation Repair.

Surgical operations are the preferred treatment for gastric perforation (GP) but incur postoperative complications such as gastrointestinal adhesions and bacterial infections, leading to inefficient wound healing and serious complications that may even threaten the life of the patient. Developing hydrogel dressings capable of adapting to the gastric environment (acid) and decreasing visceral adhesions and bacterial infections after GP treatment is crucial. In this article, we developed an injectable, self-healing hydrogel using cation-π interactions between protonated amines and aromatic rings under acidic conditions and explored it for GP repair. The hydrogels demonstrate exceptional self-healing capabilities under acidic conditions and can be effectively tailored for the gastric environment. In addition, the hydrogel demonstrated significant efficacy in preventing gastrointestinal adhesion, reducing inflammation, promoting angiogenesis, and effectively facilitating wound healing in a rat GP model. This novel hydrogel demonstrates adaptability to the gastric environment, rendering it highly promising for potential applications in gastric trauma healing.

Modified Chitosan-Based Coating/Packaging Composites with Enhanced Antibacterial, Antioxidant, and UV-Resistant Properties for Fresh Food Preservation.

Chitosan-based biomass packaging materials are a promising material for food preservation, but their limited solubility, antioxidant capacity, UV resistance, and mechanical properties severely restrict their application. In this study, we developed a novel chitosan-based coating/packaging composite (QCTO) using quaternary ammonium salt and tannic acid (TA)-modified chitosan (QCS-TA) and oxidized chitosan (OCS). The introduction of quaternary ammonium salt and TA effectively improves the water solubility and antibacterial, antioxidant, and UV-resistant properties of chitosan. The Schiff-base bond formed between OCS and QCS-TA, along with the TA-mediated multiple interactions, conferred the prepared composite film with good mechanical properties (69.9 MPa tensile strength) and gas barrier performance to water (14.3 g·h-1·m-2) and oxygen (3.5 g·mm·m-2·h-1). Meanwhile, the prepared QCTO composites demonstrate excellent biocompatibility and safety and are applied as coatings for strawberries and bananas as well as packaging films for mushrooms. These preservation experiments demonstrated that the prepared composites are able to effectively reduce weight loss, prevent microbial growth, maintain color, and significantly prolong the shelf life of fresh products (bananas, strawberries, and mushrooms extended shelf life by 6, 5, and 6 days, respectively). Therefore, the developed QCTO coating/packaging film shows great potential for applications in the field of food preservation and packaging.

Versatile conductive hydrogel orchestrating neuro-immune microenvironment for rapid diabetic wound healing through peripheral nerve regeneration.

Diabetic wound (DW), notorious for prolonged healing processes due to the unregulated immune response, neuropathy, and persistent infection, poses a significant challenge to clinical management. Current strategies for treating DW primarily focus on alleviating the inflammatory milieu or promoting angiogenesis, while limited attention has been given to modulating the neuro-immune microenvironment. Thus, we present an electrically conductive hydrogel dressing and identify its neurogenesis influence in a nerve injury animal model initially by encouraging the proliferation and migration of Schwann cells. Further, endowed with the synergizing effect of near-infrared responsive release of curcumin and nature-inspired artificial heterogeneous melanin nanoparticles, it can harmonize the immune microenvironment by restoring the macrophage phenotype and scavenging excessive reactive oxygen species. This in-situ formed hydrogel also exhibits mild photothermal therapy antibacterial efficacy. In the infected DW model, this hydrogel effectively supports nerve regeneration and mitigates the immune microenvironment, thereby expediting the healing progress. The versatile hydrogel exhibits significant therapeutic potential for application in DW healing through fine-tuning the neuro-immune microenvironment.

Thermoresponsive Self-Healing Zwitterionic Hydrogel as an In Situ Gelling Wound Dressing for Rapid Wound Healing.

It is highly desired yet challenging to fabricate biocompatible injectable self-healing hydrogels with anti-bacterial adhesion properties for complex wounds that can autonomously adapt to different shapes and depths and can promote angiogenesis and dermal collagen synthesis for rapid wound healing. Herein, an injectable zwitterionic hydrogel with excellent self-healing property, good cytocompatibility, and antibacterial adhesion was developed from a thermoresponsive ABA triblock copolymer poly[(N-isopropyl acrylamide)-co-(butyl acrylate)-co-(sulfobetaine methacrylate)]-b-poly(ethylene glycol)-b-poly[(N-isopropyl acrylamide)-co-(butyl acrylate)-co-(sulfobetaine methacrylate)] (PZOPZ). The prepared PZOPZ hydrogel exhibits a distinct thermal-induced sol-gel transition around physiological temperature and could be easily applied in a sol state and in situ gelled to adapt complex wounds of different shapes and depths for complete coverage. Meanwhile, the hydrogel possesses a rapid self-healing ability and can recover autonomously from damage to maintain structural and functional integrity. In addition, the CCK-8 and 2D/3D cell culture experiments revealed that the PZOPZ hydrogel dressing shows low cytotoxicity to L929 cells and can effectively prevent the adhesion of Staphylococcus aureus and Escherichia coli. In vivo investigations verified that the PZOPZ hydrogel could increase angiogenesis and dermal collagen synthesis and shorten the transition from the inflammatory to the proliferative stage, thereby providing more favorable conditions for faster wound healing. Overall, this work provides a promising strategy to develop injectable zwitterionic hydrogel dressings with multiple functions for clinic wound management.

Beneficial Effects of Sagacious Confucius' Pillow Elixir on Cognitive Function in Senescence-Accelerated P8 Mice (SAMP8) via the NLRP3/Caspase-1 Pathway.

Sagacious Confucius' Pillow Elixir (SCPE) is a traditional Chinese medicine that is mainly used for cognitive impairment in aging; however, the underlying mechanisms remain unclear. Aging is one of the most important pathogenic factors leading to inflammation and pyroptosis in the hippocampus, which may be a potential mechanism in elderly patients with cognitive impairment. Here, we examined whether SCPE could improve cognitive impairment in SAMP8 mice by reducing hippocampal inflammation and pyroptosis. Seven-month-old senescence-accelerated P8 mice (SAMP8) received SCPE (2.3 g/kg/day; 4.6 g/kg/day; 9.2 g/kg/day) for 28 days. Cognitive function and morphometric examinations were performed followed by water maze testing, hematoxylin-eosin staining, Congo red staining, toluidine blue staining, and TUNEL analysis of hippocampal CA1 and CA3 regions. Escape latency increased and times across platforms decreased in SAMP8 mice; however, both of them were normalized by SCPE after 28 days. Aging caused significant pyroptosis in hippocampal CA1 and CA3 regions, as evidenced by neuronal degeneration and necrosis, amyloid deposition, and decreased Nissl body amounts after cognitive impairment, which were greatly improved by SCPE. SCPE reduced serum IL-1ß, IL-6, IL-18, and TNF-α levels and reduced hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1ß, IL-6, IL-18, and Aß expression. Thus, SCPE exerts an antipyroptotic effect in aging, mainly by suppressing the NLRP3/caspase-1 signaling pathway.