Thermosensitive Polyhedral Oligomeric Silsesquioxane Hybrid Hydrogel Enhances the Antibacterial Efficiency of Erythromycin in Bacterial Keratitis.

Bacterial keratitis is a serious ocular infection that can impair vision or even cause blindness. The clinical use of antibiotics is limited due to their low bioavailability and drug resistance. Hence, there is a need to develop a novel drug delivery system for this infectious disease. In this study, erythromycin (EM) was encapsulated into a bifunctional polyhedral oligomeric silsesquioxane (BPOSS) with the backbone of the poly-PEG/PPG urethane (BPEP) hydrogel with the aim of improving the drug efficiency in treating bacterial keratitis. A comprehensive characterization of the BPEP hydrogel was performed, and its biocompatibility was assessed. Furthermore, we carried out the evaluation of the antimicrobial effect of the BPEP-EM hydrogel in S. aureus keratitis using in vivo mouse model. The BPEP hydrogel exhibited self-assembling and thermogelling properties, which assisted the drug loading of drug EM and improved its water solubility. Furthermore, the BPEP hydrogel could effectively bind with mucin on the ocular surface, thereby markedly prolonging the ocular residence time of EM. In vivo testing confirmed that the BPEP-EM hydrogel exerted a potent therapeutic action in the mouse model of bacterial keratitis. In addition, the hydrogel also exhibited an excellent biocompatibility. Our findings demonstrate that the BPEP-EM hydrogel showed a superior therapeutic effect in bacterial keratitis and demonstrated its potential as an ophthalmic formulation.

Morphologic, cytometric, quantitative transcriptomic and functional characterisation provide insights into the haemocyte immune responses of Pacific abalone (Haliotis discus hannai).

In recent years, the abalone aquaculture industry has been threatened by the bacterial pathogens. The immune responses mechanisms underlying the phagocytosis of haemocytes remain unclear in Haliotis discus hannai. It is necessary to investigate the immune mechanism in response to these bacterial pathogens challenges. In this study, the phagocytic activities of haemocytes in H. discus hannai were examined by flow cytometry combined with electron microscopy and transcriptomic analyses. The results of Vibrio parahaemolyticus, Vibrio alginolyticus and Staphylococcus aureu challenge using electron microscopy showed a process during phagosome formation in haemocytes. The phagocytic rate (PP) of S. aureus was higher than the other five foreign particles, which was about 63%. The PP of Vibrio harveyi was about 43%, the PP peak of V. alginolyticus in haemocyte was 63.7% at 1.5 h. After V. parahaemolyticus and V. alginolyticus challenge, acid phosphatase, alkaline phosphatase, total superoxide dismutase, lysozyme, total antioxidant capacity, catalase, nitric oxide synthase and glutathione peroxidase activities in haemocytes were measured at different times, differentially expressed genes (DEGs) were identified by quantitative transcriptomic analysis. The identified DEGs after V. parahaemolyticus challenge included haemagglutinin/amebocyte aggregation factor-like, supervillin-like isoform X4, calmodulin-like and kyphoscoliosis peptidase-like; the identified DEGs after V. alginolyticus challenge included interleukin-6 receptor subunit beta-like, protein turtle homolog B-like, rho GTPase-activating protein 6-like isoform X2, leukocyte surface antigen CD53-like, calponin-1-like, calmodulin-like, troponin C, troponin I-like isoform X4, troponin T-like isoform X18, tumor necrosis factor ligand superfamily member 10-like, rho-related protein racA-like and haemagglutinin/amebocyte aggregation factor-like. Some immune-related KEGG pathways were significantly up-regulated or down-regulated after challenge, including thyroid hormone synthesis, Th17 cell differentiation signalling pathway, focal adhesion, melanogenesis, leukocyte transendothelial migration, inflammatory mediator regulation of TRP channels, ras signalling pathway, rap1 signalling pathway. This study is the first step towards understanding the H. discus hannai immune system by adapting several tools to gastropods and providing a first detailed morpho-functional study of their haemocytes.

Recommendations for nutritional supplements for dry eye disease: current advances.

Dry eye disease (DED) represents a prevalent ocular surface disease. The development of effective nutritional management strategies for DED is crucial due to its association with various factors such as inflammation, oxidative stress, deficiencies in polyunsaturated fatty acids (PUFAs), imbalanced PUFA ratios, and vitamin insufficiencies. Extensive research has explored the impact of oral nutritional supplements, varying in composition and dosage, on the symptoms of DED. The main components of these supplements include fish oils (Omega-3 fatty acids), vitamins, trace elements, and phytochemical extracts. Beyond these well-known nutrients, it is necessary to explore whether novel nutrients might contribute to more effective DED management. This review provides a comprehensive update on the therapeutic potential of nutrients and presents new perspectives for combination supplements in DED treatment.

Non-Invasive Self-Adaptive Information States' Acquisition inside Dynamic Scattering Spaces.

Pushing the information states' acquisition efficiency has been a long-held goal to reach the measurement precision limit inside scattering spaces. Recent studies have indicated that maximal information states can be attained through engineered modes; however, partial intrusion is generally required. While non-invasive designs have been substantially explored across diverse physical scenarios, the non-invasive acquisition of information states inside dynamic scattering spaces remains challenging due to the intractable non-unique mapping problem, particularly in the context of multi-target scenarios. Here, we establish the feasibility of non-invasive information states' acquisition experimentally for the first time by introducing a tandem-generated adversarial network framework inside dynamic scattering spaces. To illustrate the framework's efficacy, we demonstrate that efficient information states' acquisition for multi-target scenarios can achieve the Fisher information limit solely through the utilization of the external scattering matrix of the system. Our work provides insightful perspectives for precise measurements inside dynamic complex systems.

Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression.

Rationale: Pharmacological targeting of mitochondrial ion channels is developing as a new direction in cancer therapy. The opening or closing of these channels can impact mitochondrial function and structure by interfering with intracellular ion homeostasis, thereby regulating cell fate. Nevertheless, their abnormal expression or regulation poses challenges in eliminating cancer cells, and further contributes to metastasis, recurrence, and drug resistance. Methods: We developed an engineered mitochondrial targeted delivery system with self-reinforcing potassium ion (K+) influx via amphiphilic mitochondrial targeting polymer (TMP) as carriers to co-deliver natural K+ channel agonists (Dinitrogen oxide, DZX) and artificial K+ channel molecules (5F8). Results: Using this method, DZX specifically activated natural K+ channels, whereas 5F8 assembled artificial K+ channels on the mitochondrial membrane, leading to mitochondrial K+ influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway. Conclusion: The synergistic effect of 5F8 and DZX presents greater effectiveness in killing cancer cells than DZX alone, and effectively inhibited tumor recurrence and lung metastasis following surgical resection of breast cancer tumors in animal models. This strategy innovatively integrates antihypertensive drugs with artificial ion channel molecules for the first time to effectively inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis, which will provide a novel perspective for postoperative tumor therapy.

Functional Oxidized Hyaluronic Acid Cross-Linked Decellularized Heart Valves for Improved Immunomodulation, Anti-Calcification, and Recellularization.

Tissue engineering heart valves (TEHVs) are expected to address the limitations of mechanical and bioprosthetic valves used in clinical practice. Decellularized heart valve (DHV) is an important scaffold of TEHVs due to its natural three-dimensional structure and bioactive extracellular matrix, but its mechanical properties and hemocompatibility are impaired. In this study, DHV is cross-linked with three different molecular weights of oxidized hyaluronic acid (OHA) by a Schiff base reaction and presented enhanced stability and hemocompatibility, which could be mediated by the molecular weight of OHA. Notably, DHV cross-linked with middle- and high-molecular-weight OHA could drive the macrophage polarization toward the M2 phenotype in vitro. Moreover, DHV cross-linked with middle-molecular-weight OHA scaffolds are further modified with RGD-PHSRN peptide (RPF-OHA/DHV) to block the residual aldehyde groups of the unreacted OHA. The results show that RPF-OHA/DHV not only exhibits anti-calcification properties, but also facilitates endothelial cell adhesion and proliferation in vitro. Furthermore, RPF-OHA/DHV shows excellent performance under an in vivo hemodynamic environment with favorable recellularization and immune regulation without calcification. The optimistic results demonstrate that OHA with different molecular weights has different cross-linking effects on DHV and that RPF-OHA/DHV scaffold with enhanced immune regulation, anti-calcification, and recellularization properties for clinical transformation.

A smartphone-based diagnostic analyzer for point-of-care milk somatic cell counting.

BACKGROUND: Mastitis, a pervasive and detrimental disease in dairy farming, poses a significant challenge to the global dairy industry. Monitoring the milk somatic cell count (SCC) is vital for assessing the incidence of mastitis and the quality of raw cow's milk. However, existing SCC detection methods typically require large-scale instruments and specialized operators, limiting their application in resource-constrained settings such as dairy farms and small-scale labs. To address these limitations, this study introduces a novel, smartphone-based, on-site SCC testing method that leverages smartphone capabilities for milk somatic cell identification and enumeration, offering a portable and user-friendly testing platform. RESULTS: The central findings of our study demonstrate the effectiveness of the proposed method for counting milk somatic cells. Its on-site applicability, facilitated by the microfluidic chip, optical system, and smartphone integration, heralds a paradigm shift in point-of-care testing (POCT) for dairy farms and smaller laboratories. This approach bypasses complex processing and presents a user-friendly solution for real-time SCC monitoring in resource-limited settings. This device boasts several unique features: small size, low cost (<$1,000 total manufacturing cost and <$1 per test), and high accuracy. Remarkably, it delivers test results within just 2 min. Actual-sample testing confirmed its consistency with results from the commercial Bentley FTS/FCM cytometer, affirming the reliability of the proposed method. Overall, these results underscore the potential for transformative change in dairy farm management and laboratory testing practices. SIGNIFICANCE: In summary, this study concludes that the proposed smartphone-based method significantly contributes to the accessibility and ease of SCC testing in resource-limited environments. By fostering the use of POCT technology in food safety control, particularly in the dairy industry, this innovative approach has the potential to revolutionize the monitoring and management of mastitis, ultimately benefiting the global dairy sector.

Mechanism study of aging oil demulsification and dehydration under ultrasonic irradiation.

With the tertiary oil recovery in the oilfield, the content of aging oil emulsion with high water content and complex components has become more prevalent, so it is crucial for aging oil to break the emulsification. In this paper, the experimental laws of water content are explored under the conditions of different transducer input powers through the ultrasonic reforming of aging oil, and the microscopic topography, particle size, components, etc. of oil samples before and after the irradiation of ultrasound are characterized through the microscopic analysis, particle size analysis and component analysis and other ways. The results show that the oil samples achieve the effect of demulsification and dehydration in the presence of ultrasonic cavitation effect, with a maximum dehydration rate of 98.24 %, and that the dehydration rate follows an "M-type" trend with the increase of power. The results of microscopic and particle size analyses demonstrate that ultrasonic irradiation destabilizes the oil-water interfacial membrane, and causes droplets of different sizes to collide, agglomerate, and settle. It was also observed that the droplets of the emulsion system are more evenly distributed and the intervals are increased. Furthermore, we hypothesize that ultrasound may be less irreversible in demulsification and dehydration of aging oil.

Recent advances in biomaterial designs for assisting CAR-T cell therapy towards potential solid tumor treatment.

Chimeric antigen receptor T (CAR-T) cells have shown promising outcomes in the treatment of hematologic malignancies. However, CAR-T cell therapy in solid tumor treatment has been significantly hindered, due to the complex manufacturing process, difficulties in proliferation and infiltration, lack of precision, or poor visualization ability. Fortunately, recent reports have shown that functional biomaterial designs such as nanoparticles, polymers, hydrogels, or implantable scaffolds might have potential to address the above challenges. In this review, we aim to summarize the recent advances in the designs of functional biomaterials for assisting CAR-T cell therapy for potential solid tumor treatments. Firstly, by enabling efficient CAR gene delivery in vivo and in vitro, functional biomaterials can streamline the difficult process of CAR-T cell therapy manufacturing. Secondly, they might also serve as carriers for drugs and bioactive molecules, promoting the proliferation and infiltration of CAR-T cells. Furthermore, a number of functional biomaterial designs with immunomodulatory properties might modulate the tumor microenvironment, which could provide a platform for combination therapies or improve the efficacy of CAR-T cell therapy through synergistic therapeutic effects. Last but not least, the current challenges with biomaterials-based CAR-T therapies will also be discussed, which might be helpful for the future design of CAR-T therapy in solid tumor treatment.

Mitochondrial Artificial K+ Channel Construction Using MPTPP@5F8 Nanoparticles for Overcoming Cancer Drug Resistance via Disrupting Cellular Ion Homeostasis.

Mitochondrial potassium ion channels have become a promising target for cancer therapy. However, in malignant tumors, their low expression or inhibitory regulation typically leads to undesired cancer therapy, or even induces drug resistance. Herein, this work develops an in situ mitochondria-targeted artificial K+ channel construction strategy, with the purpose to trigger cancer cell apoptosis by impairing mitochondrial ion homeostasis. Considering the fact that cancer cells have a lower membrane potential than that of normal cells, this strategy can selectively deliver artificial K+ channel molecule 5F8 to the mitochondria of cancer cells, by using a mitochondria-targeting triphenylphosphine (TPP) modified block polymer (MPTPP) as a carrier. More importantly, 5F8 can further specifically form a K+ -selective ion channel through the directional assembly of crown ethers on the mitochondrial membrane, thereby inducing mitochondrial K+ influx and disrupting ions homeostasis. Thanks to this design, mitochondrial dysfunction, including decreased mitochondrial membrane potential, reduced adenosine triphosphate (ATP) synthesis, downregulated antiapoptotic BCL-2 and MCL-1 protein levels, and increased reactive oxygen species (ROS) levels, can further effectively induce the programmed apoptosis of multidrug-resistant cancer cells, no matter in case of pump or nonpump dependent drug resistance. In short, this mitochondria-targeted artificial K+ -selective ion channel construction strategy may be beneficial for potential drug resistance cancer therapy.

Injectable Supramolecular Hydrogels for In Situ Programming of Car-T Cells toward Solid Tumor Immunotherapy.

Chimeric antigen receptor (CAR)-T cell immunotherapy is approved in the treatment of hematological malignancies, but remains far from satisfactory in solid tumor treatment due to inadequate intra-tumor CAR-T cell infiltration. Herein, an injectable supramolecular hydrogel system, based on self-assembly between cationic polymer mPEG-PCL-PEI (PPP) conjugated with T cell targeting anti-CD3e f(ab')2 fragment and α-cyclodextrin (α-CD), is designed to load plasmid CAR (pCAR) with a T cell specific CD2 promoter, which successfully achieves in situ fabrication and effective accumulation of CAR-T cells at the tumor site in humanized mice models. More importantly, due to this tumor microenvironment reprogramming, secretion of cellular inflammatory cytokines (interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)) or tumor killer protein granzyme B is significantly promoted, which reverses the immunosuppressive microenvironment and significantly enhances the intra-tumor CAR-T cells and cytotoxic T cells infiltration. To the best of the current knowledge, this is a pioneer report of using injectable supramolecular hydrogel for in situ reprogramming CAR-T cells, which might be beneficial for solid tumor CAR-T immunotherapy.

S14G-humanin alleviates acute lung injury by inhibiting the activation of NF-κB.

Acute lung injury (ALI) is characterized by severely damaged alveoli and blood vessels, seriously affecting the health of patients and causing a high mortality rate. The pathogenesis of ALI is complex, with inflammatory reactions and oxidative stress (OS) mainly involved. S14G humanin (HNG) is derived from humanin (HN), which is claimed with promising anti-inflammatory functions. Herein, the protective influence of HNG on ALI will be explored in a mouse model. The ALI model was established in mice via intratracheal instillation of 3 mg/kg LPS, followed by an intraperitoneal injection of 3 and 6 mg/kg HNG, respectively. Thicker alveolar walls, aggravated neutrophil infiltration, and increased wet weight/dry weight (W/D) ratio were observed in ALI mice, accompanied by an aggravated apoptotic state, all of which were notably alleviated by HNG. Furthermore, increased number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF), elevated secretion of inflammatory cytokines, enhanced reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, and declined superoxide dismutase-2 (SOD2) levels were observed in ALI mice, which were markedly ameliorated by HNG. Moreover, the upregulated levels of NOD-like receptor family pyrin domain containing 3 (NLRP3), caspase-1, and caspases cleave gasdermin D N/caspases cleave gasdermin D FL (GSDMD N/GSDMD FL) in ALI mice were signally repressed by HNG. Lastly, the upregulation of Toll-like receptor 4 (TLR4) and p-p65/p65, and downregulation of IκB-α observed in ALI mice were sharply reversed by HNG. Collectively, HNG alleviated the ALI in mice by inhibiting the activation of nuclear factor kappa B (NF-κB) signaling.

Experimental validation and mathematical simulation for laser protection performance of light field imaging.

Photoelectric imaging systems typically employ a focal plane detector structure, rendering them vulnerable to laser damage. Laser damage can severely impair or even completely deprive the information acquisition capability of photoelectric imaging systems. A laser damage protection method based on a microlens array light field imaging system is proposed to prevent photoelectric imaging systems from laser damage. The technique utilizes the light field modulation effect of the microlens array to homogenize the spot energy, thereby reducing the maximum single-pixel receiving power at the image sensor. The method's effectiveness has been verified through numerical simulations and experimental validation. First, the laser transmission theoretical model of light field imaging is proposed. Then an experimental setup is established, and measurements are conducted to capture the spot profiles and intensity distributions on the imaging plane across various defocus distances. Finally, the impact of the propagation distance on the maximum single-pixel receiving power and suppression ratio of the light field imaging system is experimentally measured. The simulation and experimental results indicate that, with the proposed method, the energy suppression ratio can easily reach two orders of magnitude, significantly reducing the probability of laser damage in photoelectric imaging systems.

Widely tunable and high resolution mid-infrared laser based on BaGa4Se7 optical parametric oscillator.

The widely tunable and high resolution mid-infrared laser based on a BaGa4Se7 (BGSe) optical parametric oscillator (OPO) was demonstrated. A wavelength tuning range of 2.76-4.64 µm and a wavelength tuning resolution of about 0.3 nm were obtained by a BGSe (56.3°, 0°) OPO, which was pumped by a 1064 nm laser. It is the narrowest reported wavelength tuning resolution for BGSe OPO, and was obtained by simultaneously controlling the angle and temperature of BGSe.

Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties.

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem. Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity, good drug-loading ability and sustained drug release properties. As a typical example, hyaluronic acid dressing (Healoderm) has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers. However, the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment. Due to the intricacy of diabetic wounds, antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice, although these medications are easily hindered by the hostile environment. In this case, scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds (such as high glucose and low pH) or combined with external stimuli (such as light or magnetic field) to achieve controllable drug release, gel degradation, and microenvironment improvements in order to overcome these clinical issues. These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings. Here, we review recent advances on responsive-hydrogel dressings towards diabetic wound healing, with focus on hydrogel structure design, the principle of responsiveness, and the behavior of degradation. Last but not least, the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed. We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

Advance in topical biomaterials and mechanisms for the intervention of pressure injury.

Pressure injuries (PIs) are localized tissue damage resulting from prolonged compression or shear forces on the skin or underlying tissue, or both. Different stages of PIs share common features include intense oxidative stress, abnormal inflammatory response, cell death, and subdued tissue remodeling. Despite various clinical interventions, stage 1 or stage 2 PIs are hard to monitor for the changes of skin or identify from other disease, whereas stage 3 or stage 4 PIs are challenging to heal, painful, expensive to manage, and have a negative impact on quality of life. Here, we review the underlying pathogenesis and the current advances of biochemicals in PIs. We first discuss the crucial events involved in the pathogenesis of PIs and key biochemical pathways lead to wound delay. Then, we examine the recent progress of biomaterials-assisted wound prevention and healing and their prospects.

Multi-functional nanogel with cascade catalytic performance for treatment of diabetic oral mucosa ulcer.

Introduction: Diabetic oral mucosa ulcers face challenges of hypoxia, hyperglycemia and high oxidative stress, which result in delayed healing process. Oxygen is regarded as an important substance in cell proliferation, differentiation and migration, which is beneficial to ulcer recovery. Methods: This study developed a multi-functional GOx-CAT nanogel (GCN) system for the treatment of diabetic oral mucosa ulcers. The catalytic activity, ROS scavenge and oxygen supply ability of GCN was validated. The therapeutic effect of GCN was verified in the diabetic gingival ulcer model. Results: The results showed that the nanoscale GCN was capable of significantly eliminating intracellular ROS, increasing intracellular oxygen concentration and accelerating cell migration of human gingival fibroblasts, which could promote diabetic oral gingival ulcer healing in vivo by alleviating inflammation and promoting angiogenesis. Discussion: This multifunctional GCN with ROS depletion, continuous oxygen supply and good biocompatibility, which might provide a novel therapeutic strategy for effective treatment of diabetic oral mucosa ulcers.

Recent advances in stimuli-responsive polymeric carriers for controllable CRISPR/Cas9 gene editing system delivery.

Non-viral polymeric vectors with good biocompatibility have been recently explored as delivery systems for clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) nucleases. In this review, based on current limitations and critical barriers, we summarize the advantages of stimulus-responsive polymeric delivery vectors (i.e., pH, redox, or enzymes) towards controllable CRISPR/Cas9 genome editing system delivery as well as the advances in using stimulus-responsive CRISPR/Cas9 polymeric carriers towards cancer treatment. Last but not least, the key challenges and promising development strategies of stimulus-responsive polymeric vector designs for CRISPR/Cas9 systems will also be discussed.

Recent Advances in Nanozyme-Based Materials for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a type of chronic inflammatory disorder that interferes with the patient's lifestyle and, in extreme situations, can be deadly. Fortunately, with the ever-deepening understanding of the pathological cause of IBD, recent studies using nanozyme-based materials have indicated the potential toward effective IBD treatment. In this review, the recent advancement of nanozymes for the treatment of enteritis is summarized from the perspectives of the structural design of nanozyme-based materials and therapeutic strategies, intending to serve as a reference to produce effective nanozymes for moderating inflammation in the future. Last but not least, the potential and current restrictions for using nanozymes in IBD will also be discussed. In short, this review may provide a guidance for the development of innovative enzyme-mimetic nanomaterials that offer a novel and efficient approach toward the effective treatment of IBD.