Oral health self-management barriers among rural older adults in Guangxi, China: A qualitative study.

BACKGROUND: Objective: To understand the barriers associated with self-management of oral health among rural older adults in Guangxi, and to explore the high incidence of oral problems. This information will assist in the formulation of relevant strategies to solve the oral health problems in this population. METHODS: Taking a phenomenological approach, the current status of, and barriers to, oral health self-management in rural older adults from different regions of Guangxi were explored. Participants were purposively selected and interviewed face-to-face. RESULTS: The interviews yielded four overarching themes and six corresponding sub-themes pertaining to barriers in oral health self-management. These included: (1) Older adults' understanding of oral health and disease, perceptions of oral health and their oral health behaviours; (2) Problems in accessing oral health information; (3) Role of family support; and (4) Barriers to healthcare that included access to dental services, oral treatment experience and financial burden of access to dental care. CONCLUSION: Rural older adults in Guangxi face oral health self-management barriers. Improving access to oral healthcare services and changing existing oral health perceptions and habits may assist them in overcoming self-management challenges.

Tracheal microbiome and metabolome profiling in iatrogenic subglottic tracheal stenosis.

BACKGROUND: To study the role of microecology and metabolism in iatrogenic tracheal injury and cicatricial stenosis, we investigated the tracheal microbiome and metabolome in patients with tracheal stenosis after endotracheal intubation. METHODS: We collected 16 protected specimen brush (PSB) and 8 broncho-alveolar lavage (BAL) samples from 8 iatrogenic subglottic tracheal stenosis patients, including 8 PSB samples from tracheal scar sites, 8 PSB samples from scar-free sites and 8 BAL samples, by lavaging the subsegmental bronchi of the right-middle lobe. Metagenomic sequencing was performed to characterize the microbiome profiling of 16 PSB and 8 BAL samples. Untargeted metabolomics was performed in 6 PSB samples (3 from tracheal scar PSB and 3 from tracheal scar-free PSB) using high-performance liquid chromatography‒mass spectrometry (LC‒MS). RESULTS: At the species level, the top four bacterial species were Neisseria subflava, Streptococcus oralis, Capnocytophaga gingivals, and Haemophilus aegyptius. The alpha and beta diversity among tracheal scar PSB, scar-free PSB and BAL samples were compared, and no significant differences were found. Untargeted metabolomics was performed in 6 PSB samples using LC‒MS, and only one statistically significant metabolite, carnitine, was identified. Pathway enrichment analysis of carnitine revealed significant enrichment in fatty acid oxidation. CONCLUSION: Our study found that carnitine levels in tracheal scar tissue were significantly lower than those in scar-free tissue, which might be a new target for the prevention and treatment of iatrogenic tracheal stenosis in the future.

Coincidently oral lesions in Crohn's disease.

A 21-year-old patient with Crohn's disease, who was undergoing Infliximab treatment, presented at the hospital due to a painful oral mass. After confirming the absence of malignant cells through frozen sections, a complete excision of the infiltrated bone surrounding the lesion was performed. The postoperative pathology confirmed the presence of Central type giant cell granuloma in the mandible, which is distinct from non-caseating granulomas in oral CD and Infliximab-induced Sarcoidosis. As far as we are aware, this is the first to report an association between CGCG and both CD and anti-tumor necrosis factor therapy treatment.

[Advances in the Application of Hydroxyapatite Composite Materials in Bone Tissue Engineering].

Hydroxyapatite (HAp) is the main inorganic component of the bones and teeth, and it possesses bioactivity and biocompatibility. However, due to its poor mechanical performance, slow degradation speed, and lack of diversity in its function, it is difficult to apply HAp alone as a scaffold material for bone tissue engineering. By combining HAp with other types of materials, composite materials with specific properties can be prepared, and the scopes of HAp applications can be expanded. Firstly, we elaborated on the importance, and strengths and weaknesses of HAp for bone tissue engineering biomaterials and then reviewed the research status of HAp composite materials used in bone regeneration. Secondly, about hot research topics in the field of applying HAp composite materials in bone repair, we summarized the representative findings in the field, and discussions and analysis were made accordingly. Finally, we also examined the future development prospects of HAp composite bone repair materials.

Analysis of primary oral and oropharyngeal squamous cell carcinoma in inhabitants of Beijing, China-a 10-year continuous single-center study.

BACKGROUND: This study aimed to describe some of the characteristics of the inhabitants of Beijing with oral and oropharyngeal squamous cell carcinoma (OSCC) who had received treatment at the Stomatology Hospital of Peking University and to analyze the survival rate and the prognostic factors of patients following surgical treatment. METHODS: Data for 603 consecutive cases with primary OSCC between 2004 and 2013 were obtained from the Stomatology Hospital of Peking University. Clinical data including age, sex, living district, primary tumor site, TNM stage, history of drinking and smoking, pathological differentiation, treatment, and survival were retrospectively analyzed. RESULTS: The male:female ratio was 1.1:1. The frequency of site involvement in descending order was tongue (34.3%), gingiva (25.0%), buccal mucosa (13.8%), oral floor (9.0%), oropharynx (8.5%), lip (6.3%) and palate (3.2%). Female OSCC patients tended to be significantly older than men with OSCC (P < 0.05). The percentage of patients with TNM stage III-IV OSCC was 52.4%. The results revealed that 65.3% of male patients and only 6.3% of female patients smoked or drank. The overall 5-year survival rate was 64%. Female patients had a worse prognosis than male patients. Among the patients who received surgery, tumor size and lymph node involvement were independent prognostic factors. Smoking and drinking were not prognostic factors. CONCLUSION: Among the Beijing inhabitants who were diagnosed with OSCC and treated in our hospital in the past 10 years, more than half were in the advanced stage, and the cancer stage was the main prognostic factor of oral cancer. Therefore, the recognition of oral cancer should be strengthened, and early detection and treatment of OSCC should be achieved to improve the survival rate.

Flexible Zinc-Ion Hybrid Fiber Capacitors with Ultrahigh Energy Density and Long Cycling Life for Wearable Electronics.

Emerging wearable electronics require flexible energy storage devices with high volumetric energy and power densities. Fiber-shaped capacitors (FCs) offer high power densities and excellent flexibility but low energy densities. Zn-ion capacitors have high energy density and other advantages, such as low cost, nontoxicity, reversible Faradaic reaction, and broad operating voltage windows. However, Zn-ion capacitors have not been applied in wearable electronics due to the use of liquid electrolytes. Here, the first quasisolid-state Zn-ion hybrid FC (ZnFC) based on three rationally designed components is demonstrated. First, hydrothermally assembled high surface area and conductive reduced graphene oxide/carbon nanotube composite fibers serve as capacitor-type positive electrodes. Second, graphite fibers coated with a uniform Zn layer work as battery-type negative electrodes. Third, a new neutral ZnSO4 -filled polyacrylic acid hydrogel act as the quasisolid-state electrolyte, which offers high ionic conductivity and excellent stretchability. The assembled ZnFC delivers a high energy density of 48.5 mWh cm-3 at a power density of 179.9 mW cm-3 . Further, Zn dendrite formation that commonly happens under high current density is efficiently suppressed on the fiber electrode, leading to superior cycling stability. Multiple ZnFCs are integrated as flexible energy storage units to power wearable devices under different deformation conditions.

Technical feasibility and tissue reaction after silicone-covered biodegradable magnesium stent insertion in the oesophagus: a primary study in vitro and in vivo.

OBJECTIVES: Determine the feasibility of and tissue response to biodegradable magnesium-silicone stent insertion into the oesophagus of rabbits. METHODS: Mechanical compression-recovery and degradation behaviours of the stents were investigated in vitro. Thirty rabbits were randomly divided into a magnesium-silicone stent group (n = 15) that received stent insertion into the lower 1/3 of the oesophagus under fluoroscopic guidance and a control group (n = 15). Oesophagography was performed at 1, 2 and 4 weeks. Five rabbits in each group were euthanized at each time point for histological examination. RESULTS: Magnesium-silicone stents showed good flexibility and elasticity, and degraded more slowly than bare stents at pH 4.0 and 7.4. All stent insertions were well tolerated. The oesophageal diameters at 1, 2 and 4 weeks were 9.7 ± 0.7, 9.6 ± 0.8 and 9.6 ± 0.5 mm, respectively (vs. 9.2 ± 0.8 mm before intervention; P > 0.05). Stent migration occurred in six rabbits (one at 1 week, one at 2 and four at 4). Microscopy demonstrated dilation of the oesophageal wall within 1 week of insertion. Oesophageal injury and collagen deposition following stent insertion were similar to control (P > 0.05). CONCLUSIONS: Oesophageal magnesium-silicone stent insertion was feasible and provided reliable support for 2 weeks without causing oesophageal injury or collagen deposition. KEY POINTS: • Mg stent provided apparently adequate radial force and silicone membrane reduced magnesium biodegradation • Stent insertion provided good support for at least 2 weeks before biodegradation • Stenting effectively resulted in oesophageal wall remodelling, without demonstrable injury.

Evolution of Membrane Fouling Revealed by Label-Free Vibrational Spectroscopic Imaging.

Membrane fouling is the bottleneck that restricts the sustainability of membrane technology for environmental applications. Therefore, the development of novel analytical tools for characterizing membrane fouling processes is essential. In this work, we demonstrate a capability of probing the chemical structure of foulants and detecting their 3-dimentional spatial distribution on membranes based on stimulated Raman scattering (SRS) microscopy as a vibrational spectroscopic imaging approach. The adsorption process of foulants onto membrane surfaces and their aggregation process within membrane pores during the microfiltration of protein and polysaccharide solutions were clearly monitored. Pore constriction and cake layer formation were found to be the coupled membrane fouling mechanisms. This work establishes an ultrafast, highly sensitive, nondestructive and label-free imaging platform for the characterization of membrane fouling evolution. Furthermore, this work provides new insights into membrane fouling and offers a powerful tool for membrane-based process exploration.

Effects of bisphosphonates on mandibular condyle of ovariectomized osteoporotic rats using micro-ct and histomorphometric analysis.

OBJECTIVE: To evaluate microarchitectural changes in condylar cartilage and associated subchondral bone after bisphosphonates treatment using an ovariectomized (OVX) osteoporosis rat model. METHODS: Thirty six-month-old female Sprague-Dawley rats were randomly divided into sham, OVX, and risedronate (RIS)-treated groups. Both OVX and RIS groups received bilateral ovariectomy. OVX group was treated subcutaneously with saline, whereas RIS group received risedronate treatment (2.4 µg/kg) subcutaneously for 3 months. At the end of 3 months, animals were sacrificed and the entire condyles were harvested for micro-CT and histological analyses. Immunohistochemistry (IHC) was performed to assess the expression of type I/II collagen protein by semiquantitative imaging analysis. RESULTS: Micro-CT analysis showed OVX group had significant condylar subchondral bone loss compared to sham as shown by significant decrease in bone volume fraction (P = 0.028), trabecular thickness (P = 0.041), and significant increase in trabecular spacing (P = 0.003). In RIS group, partial inhibition of OVX-induced bone loss was detected. HE staining showed proliferative layer of condylar cartilage reduced, while hypertrophic chondrocyte layer increased significantly in RIS group compared to sham and OVX groups. IHC showed reduced expression of Col I in both the OVX and RIS groups, whereas expression of Col II was reduced in the OVX group but increased in the RIS group. CONCLUSION: Our findings suggest that systemic bisphosphonate treatment influences the structure and ossification of condylar cartilage and it has a dual action on condyle in a postmenopausal osteoporosis rat model which raises the concerns for the potential side effects of BPs on condyle to elder patients.

Anti-inflammation performance of curcumin-loaded mesoporous calcium silicate cement.

BACKGROUND/PURPOSE: Calcium silicate (CS) cements have excellent bioactivity and can induce the bone-like apatite formation. They are good biomaterials for bone tissue engineering and bone regenerative medicine. However, they have degradability and the dissolved CS can cause the inflammatory response at the early post-implantation stage. The purpose of this study was to design and prepare the curcumin-loaded mesoporous CS (MesoCS/curcumin) cements as a strategy to reduce the inflammatory reaction after implantation. METHODS: The MesoCS/curcumin cements were designed and prepared. The characteristics of MesoCS/curcumin specimens were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their physical properties, biocompatibility, and anti-inflammatory ability were also evaluated. RESULTS: The MesoCS/curcumin cements displayed excellent biocompatibility and physical properties. Their crystalline characterizations were very similar with MesoCS cements. After soaking in simulated body fluid, the bone-like apatite layer of the MesoCS/curcumin cements could be formed. In addition, it could inhibit the expression of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) after inflammation reaction induced by lipopolysaccharides and had good anti-inflammatory ability. CONCLUSION: Adding curcumin in MesoCS cements can reduce the inflammatory reaction, but does not affect the original biological activity and properties of MesoCS cements. It can provide a good strategy to inhibit the inflammatory reaction after implantation for bone tissue engineering and bone regenerative medicine.

Synergism of Water Shock and a Biocompatible Block Copolymer Potentiates the Antibacterial Activity of Graphene Oxide.

Graphene oxide (GO) is promising in the fight against pathogenic bacteria. However, the antibacterial activity of pristine GO is relatively low and concern over human cytotoxicity further limits its potential. This study demonstrates a general approach to address both issues. The developed approach synergistically combines the water shock treatment (i.e., a sudden decrease in environmental salinity) and the use of a biocompatible block copolymer (Pluronic F-127) as a synergist co-agent. Hypoosmotic stress induced by water shock makes gram-negative pathogens more susceptible to GO. Pluronic forms highly stable nanoassemblies with GO (Pluronic-GO) that can populate around bacterial envelopes favoring the interactions between GO and bacteria. The antibacterial activity of GO at a low concentration (50 µg mL(-1) ) increases from <30% to virtually complete killing (>99%) when complemented with water shock and Pluronic (5 mg mL(-1) ) at ≈2-2.5 h of exposure. Results suggest that the enhanced dispersion of GO and the osmotic pressure generated on bacterial envelopes by polymers together potentiate GO. Pluronic also significantly suppresses the toxicity of GO toward human fibroblast cells. Fundamentally, the results highlight the crucial role of physicochemical milieu in the antibacterial activity of GO. The demonstrated strategy has potentials for daily-life bacterial disinfection applications, as hypotonic Pluronic-GO mixture is both safe and effective.

Three-dimensional poly-(ε-caprolactone) nanofibrous scaffolds directly promote the cardiomyocyte differentiation of murine-induced pluripotent stem cells through Wnt/ß-catenin signaling.

BACKGROUND: Environmental factors are important for stem cell lineage specification, and increasing evidence indicates that the nanoscale geometry/topography of the extracellular matrix (ECM) directs stem cell fate. Recently, many three-dimensional (3D) biomimetic nanofibrous scaffolds resembling many characteristics of the native ECM have been used in stem cell-based myocardial tissue engineering. However, the biophysical role and underlying mechanism of 3D nanofibrous scaffolds in cardiomyocyte differentiation of induced pluripotent stem cells (iPSCs) remain unclear. RESULTS: Here, we fabricated a 3D poly-(ε-caprolactone) (PCL) nanofibrous scaffold using the electrospinning method and verified its nanotopography and porous structure by scanning electron microscopy. We seeded murine iPSCs (miPSCs) directly on the 3D PCL nanofibrous scaffold and initiated non-directed, spontaneous differentiation using the monolayer method. After the 3D PCL nanofibrous scaffold was gelatin coated, it was suitable for monolayer miPSC cultivation and cardiomyocyte differentiation. At day 15 of differentiation, miPSCs differentiated into functional cardiomyocytes on the 3D PCL nanofibrous scaffold as evidenced by positive immunostaining of cardiac-specific proteins including cardiac troponin T (cTnT) and myosin light chain 2a (MLC2a). In addition, flow cytometric analysis of cTnT-positive cells and cardiac-specific gene and protein expression of cTnT and sarcomeric alpha actinin (α-actinin) demonstrated that the cardiomyocyte differentiation of miPSCs was more efficient on the 3D PCL nanofibrous scaffold than on normal tissue culture plates (TCPs). Furthermore, early inhibition of Wnt/ß-catenin signaling by the selective antagonist Dickkopf-1 significantly reduced the activity of Wnt/ß-catenin signaling and decreased the cardiomyocyte differentiation of miPSCs cultured on the 3D PCL nanofibrous scaffold, while the early activation of Wnt/ß-catenin signaling by CHIR99021 further increased the cardiomyocyte differentiation of miPSCs. CONCLUSION: These results indicated that the electrospun 3D PCL nanofibrous scaffolds directly promoted the cardiomyocyte differentiation of miPSCs, which was mediated by the activation of the Wnt/ß-catenin signaling during the early period of differentiation. These findings highlighted the biophysical role of 3D nanofibrous scaffolds during the cardiomyocyte differentiation of miPSCs and revealed its underlying mechanism involving Wnt/ß-catenin signaling, which will be helpful in guiding future stem cell- and scaffold-based myocardium bioengineering.

Monocyte mediated brain targeting delivery of macromolecular drug for the therapy of depression.

Leukocytes can cross intact blood-brain barrier under healthy conditions and in many neurological diseases, including psychiatric diseases. In present study, a cyclic RGD (cRGD) peptide with high affinity for integrin receptors of leukocytes was used to modify liposomes. The cRGD-modified liposomes (cRGDL) showed high affinity for monocytes in vitro and in vivo and co-migrated across in vitro BBB model with THP-1. The trefoil factor 3 (TFF3), a macromolecular drug, was rapidly and persistently delivered to brain for at least 12 h when loaded into cRGDL while 2.8-fold increase in drug concentration in basolateral amygdala regions related to depression was observed. A systemic administration of cRGDL-TFF3 mimicked antidepressant-like effect of direct intra-basolateral amygdala administration of TFF3 solution in rats subjected to chronic mild stress. The effective dual-brain targeting delivery resulting from the combination and co-migration of cRGDL with leukocyte cross BBB may be a promising strategy for targeted brain delivery. FROM THE CLINICAL EDITOR: In an effort to treat depression, brain targeted delivery via monocyte-cRGD liposome complexes capable of crossing the intact BBB was performed in this study in a murine model. Similar approaches may be helpful in the treatment of other neuropsychiatric conditions.

EFFECTS OF MEDICAL DISPUTES ON INTERNET COMMUNICATIONS OF NEGATIVE EMOTIONS AND NEGATIVE ONLINE WORD-OF-MOUTH.

Emotions play an important role in human behavior. Negative emotions resulting from medical disputes are problems for medical personnel to solve but also have a significant impact on a hospital's reputation and people's trust in the hospital. One medical dispute case was chosen from an Internet news source to assess the correlation between people's negative emotions and negative online word-of-mouth. Convenience sampling was used in school faculties and university students who had shared their medical treatment experiences online were the research participants. A total of 221 Taiwanese participants volunteered (158 women, 63 men; ages: 26.7% under 19, 22.6% 20-29, 30.8% 30-39,19.9% over 40). Four negative emotions were measured using rating scales: uncertainty, anger, disappointment, and sadness. Four negative online word-of-mouth measures were: venting, advice search, helping receiver, and revenge. A modeled relationship was assessed by partial least square method (PLS). Then, people's positive emotions were further analyzed to assess changes after spreading negative word-of-mouth. The results showed that uncertainty had a positive effect on venting and advice search. People who felt anger or regret spread word-of-mouth in order to help the receiver. Disappointment may trigger the revenge behavior of negative word-of-mouth. Negative emotions could be relieved after engaging in the behavior of helping the receiver.

[Preparation of curcumin-EC sustained-release composite particles by supercritical CO2 anti-solvent technology].

Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes, on the basis of single factor tests, orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading, yield, particle size distribution, electron microscope analysis (SEM) , infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 45 degrees C, crystallization pressure 10 MPa, curcumin concentration 8 g x L(-1), solvent flow rate 0.9 mL x min(-1), and CO2 velocity 4 L x min(-1). Under the optimal conditions, the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%, and the average particle size of the particles was 20.632 µm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles.

First-line cancer chemotherapy necessitates high parenteral dosage and repeated dosing of a combination of drugs over a prolonged period. Current commercially available chemotherapeutic agents, such as Doxil and Taxol, are only capable of delivering single drug in a bolus dose. The aim of this study is to develop dual-drug-loaded, multilayered microparticles and to investigate their antitumor efficacy compared with single-drug-loaded particles. Results show hydrophilic doxorubicin HCl (DOX) and hydrophobic paclitaxel (PTX) localized in the poly(dl-lactic-co-glycolic acid, 50:50) (PLGA) shell and in the poly(l-lactic acid) (PLLA) core, respectively. The introduction of poly[(1,6-bis-carboxyphenoxy) hexane] (PCPH) into PLGA/PLLA microparticles causes PTX to be localized in the PLLA and PCPH mid-layers, whereas DOX is found in both the PLGA shell and core. PLGA/PLLA/PCPH microparticles with denser shells allow better control of DOX release. A delayed release of PTX is observed with the addition of PCPH. Three-dimensional MCF-7 spheroid studies demonstrate that controlled co-delivery of DOX and PTX from multilayered microparticles produces a greater reduction in spheroid growth rate compared with single-drug-loaded particles. This study provides mechanistic insights into how distinctive structure of multilayered microparticles can be designed to modulate the release profiles of anticancer drugs, and how co-delivery can potentially provide better antitumor response.

Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis.

Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, the neurotoxicity and mechanism of oxidized polyethylene (Ox-PE) MPs to organisms remain unclear. Herein, we prepared oxidized low-density polyethylene (Ox-LDPE) and established a model of MPs exposure by continuously orally gavage of C57BL/6 J mice with LDPE-MPs/Ox-LDPE-MPs for 28 days with or without oral administration of Lactobacillus plantarum DP189 and galactooligosaccharides (DP189&GOS). The experimental results indicated that LDPE-MPs or Ox-LDPE-MPs caused several adverse effects in mice, mainly manifested by behavioral changes, disruption of the intestinal and blood-brain barrier (BBB), and simultaneous oxidative stress, inflammatory reactions, and pathological damage in the brain and intestines. Brain transcriptomic analysis revealed that the cholinergic synaptic signaling pathways, which affect cognitive function, were significantly disrupted after exposure to LDPE-MPs or Ox-LDPE-MPs. Real-time quantitative polymerase chain reaction and Western Blotting results further demonstrated that the critical genes (Slc5a7, Chat and Slc18a3) and proteins (Chat and Slc18a3) in the cholinergic synaptic signaling pathway were significantly down-regulated after exposure to LDPE-MPs or Ox-LDPE-MPs. These alterations lead to reduced acetylcholine concentration, which causes cognitive dysfunction in mice. Importantly, the DP189&GOS interventions effectively mitigated the MPs-induced cognitive dysfunction and intestinal microbiota alteration, improved intestinal and BBB integrity, attenuated the oxidative stress and inflammatory response, and also saw a rebound in the release of acetylcholine. These results indicated that LDPE-MPs and Ox-LDPE-MPs exert neurotoxic effects on mice by inducing oxidative stress, inflammatory responses, and dysregulation of cholinergic signaling pathways in the mouse brain. That probiotic supplementation is effective in attenuating MPs-induced neurotoxicity in mice. Overall, this study reveals the potential mechanisms of neurotoxicity of LDPE-MPs and Ox-LDPE-MPs on mice and their improvement measures, necessary to assess the potential risks of plastic contaminants to human health.

Size-tunable nanogels for cascaded release of metronidazole and chemotherapeutic agents to combat Fusobacterium nucleatum-infected colorectal cancer.

Bacteria play important roles in tumor formation, growth and metastasis through downregulating immune response and initiating drug resistance. Herein, size-tunable nanogels (NGs) have been developed to address the existing size paradox in tumor accumulation, intratumoral penetration and intracellular release of therapeutics for the treatment of Fusobacterium nucleatum (F. nucleatum)-infected colorectal cancer. Zinc-imidazolate frameworks with doxorubicin (DOX) loading and folate grafting (f-ZIFD) were mixed with metronidazole (MET) and encapsulated in NGs through thiol-ene click crosslinking of sulfhydryl hyaluronan, sulfhydryl alginate and 4-arm poly(ethylene glycol) acrylate. Hyaluronidase-initiated matrix degradation causes NG swelling to release sufficient MET and maintains a large size for an extended time period, and the gradually discharged f-ZIFD nanoparticles (NPs) from NGs exhibit acid-responsive intracellular release of DOX after folate-mediated internalization into tumor cells. The encapsulation into NGs significantly enhances the bioavailability and increases half-lives of MET and DOX by around 20 times. In the F. nucleatum-infected tumor model, the extended retention of swollen NGs and the efficient tumor infiltration and cellular uptake of the discharged f-ZIFD NPs cause 6 times higher DOX levels in tumors than that of free DOX administration. F. nucleatum promotes tumor cell proliferation and tumor growth, and the cascaded releases of MET and f-ZIFD NPs eliminate F. nucleatum to effectively inhibit tumor growth with a significant extension of animal survival. Thus, the hyaluronidase-mediated NG expansion and dual-responsive cascaded drug release have overcome challenges in the release regimen and size paradox of drug delivery carriers to combat bacteria-infected cancer.

Oxidation enhances the toxicity of polyethylene microplastics to mouse eye: Perspective from in vitro and in vivo.

Microplastics (MPs) are ubiquitously dispersed in the environment, and undergoing the process of oxidation that alters their physical and chemical properties. Eyes, which directly interface with the external milieu, inevitably encounter MPs. Nonetheless, the ophthalmic toxicity of MPs towards organisms remains unclear. In this study, primary mouse corneal epithelial cells (MCECs), C57BL/6 mice, and CX3CrlGFP/+ mice were utilized to evaluate the toxicity and differences between oxidized low-density polyethylene MPs (modified-MPs) and low-density polyethylene MPs (virgin-MPs) on eyes. The results manifested that virgin-MPs and modified-MPs could be endocytosed by primary MCECs, resulting in a range of cellular damage. Furthermore, they could diminish tear secretion, increase intraocular pressure, and could be internalized into cornea and retina in mice, instigating a series of detrimental reactions. Importantly, modified-MPs exhibited heightened toxicity towards mouse eyes, seemingly due to oxidation enhances the interaction between virgin-MPs/modified-MPs and tissues/cells, and leading to the release of toxic substances increased. In conclusion, our discoveries demonstrate that oxidation exacerbates the harm of virgin-MPs to eyes, and are of great significance for evaluating the risk of MPs to ocular health.

Herbal Products-Powered Thermosensitive Hydrogel with Phototherapy and Microenvironment Reconstruction for Accelerating Multidrug-Resistant Bacteria-Infected Wound Healing.

Wound healing and infection remain significant challenges due to the ineffectiveness against multidrug-resistant (MDR) bacteria and the complex oxidative wound microenvironments. To address these issues, thymoquinone-reinforced injectable and thermosensitive TQ@PEG-PAF-Cur hydrogels with dual functions of microenvironment reshaping and photodynamic therapy are developed. The hydrogel comprises natural compound thymoquinone (TQ) and poly (ethylene glycol)-block-poly (alanine-co-phenyl alanine) copolymers (PEG-PAF) conjugated with natural photosensitizer curcumin (Cur). The incorporation of TQ and Cur reduces the sol-to-gel transition temperature of TQ@PEG-PAF-Cur to 30°C, compared to PEG-PAF hydrogel (37°C), due to the formation of strong hydrogen bonding, matching the wound microenvironment temperature. Under blue light excitation, TQ@PEG-PAF-Cur generates significant amounts of reactive oxygen species such as H2O2, 1O2, and ·OH, exhibiting rapid and efficient bactericidal capacities against methicillin-resistant Staphylococcus aureus and broad spectrum ß-lactamases Escherichia coli via photodynamic therapy (PDT). Additionally, Cur effectively inhibits the expressions of proinflammatory cytokines in skin tissue-forming cells. As a result, the composite hydrogel can rapidly transform into a gel to cover the wound, reshape the wound microenvironment, and accelerate wound healing in vivo. This collaborative antibacterial strategy provides valuable insights to guide the development of multifunctional materials for efficient wound healing.