Lysosome-targeted ruthenium(II) complex encapsulated with pluronic® F-127 induces oncosis in A549 cells.

Transition metal complexes with characteristics of unique packaging in nanoparticles and remarkable cancer cell cytotoxicity have emerged as potential alternatives to platinum-based antitumor drugs. Here we report the synthesis, characterization, and antitumor activities of three new Ruthenium complexes that introduce 5-fluorouracil-derived ligands. Notably, encapsulation of one such metal complex, Ru3, within pluronic® F-127 micelles (Ru3-M) significantly enhanced Ru3 cytotoxicity toward A549 cells by a factor of four. To determine the mechanisms underlying Ru3-M cytotoxicity, additional in vitro experiments were conducted that revealed A549 cell treatment with lysosome-targeting Ru3-M triggered oxidative stress, induced mitochondrial membrane potential depolarization, and drastically reduced intracellular ATP levels. Taken together, these results demonstrated that Ru3-M killed cells mainly via a non-apoptotic pathway known as oncosis, as evidenced by observed Ru3-M-induced cellular morphological changes including cytosolic flushing, cell swelling, and cytoplasmic vacuolation. In turn, these changes together caused cytoskeletal collapse and activation of porimin and calpain1 proteins with known oncotic functions that distinguished this oncotic process from other cell death processes. In summary, Ru3-M is a potential anticancer agent that kills A549 cells via a novel mechanism involving Ru(II) complex triggering of cell death via oncosis.

Dual Stromal Targeting Sensitizes Pancreatic Adenocarcinoma for Anti-Programmed Cell Death Protein 1 Therapy.

BACKGROUND & AIMS: The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms. METHODS: A murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-programmed cell death protein 1 (PD-1) antibody, and stromal hyaluronan (HA) degradation by PEGylated recombinant human hyaluronidase (PEGPH20) to assess immune and stromal modulating effects of these agents and their combinations. RESULTS: The results showed that HA degradation by PEGPH20 and reduction in phosphorylated FAK expression by FAKi leads to improved survival in PDAC-bearing mice treated with anti-PD-1 antibody. HA degradation in combination with FAKi and anti-PD-1 antibody increases T-cell infiltration and alters T-cell phenotype toward effector memory T cells. FAKi alters the expression of T-cell modulating cytokines and leads to changes in T-cell metabolism and increases in effector T-cell signatures. HA degradation in combination with anti-PD-1 antibody and FAKi treatments reduces granulocytes, including granulocytic- myeloid-derived suppressor cells and decreases C-X-C chemokine receptor type 4 (CXCR4)-expressing myeloid cells, particularly the CXCR4-expressing granulocytes. Anti-CXCR4 antibody combined with FAKi and anti-PD-1 antibody significantly decreases metastatic rates in the PDAC liver metastasis model. CONCLUSIONS: This represents the first preclinical study to identify synergistic effects of targeting both intracellular and extracellular components within the PDAC stroma and supports testing anti-CXCR4 antibody in combination with FAKi as a PDAC treatment strategy.

Effects of polyvinylchloride microplastics on the toxicity of nanoparticles and antibiotics to aerobic granular sludge: Nitrogen removal, microbial community and resistance genes.

Copper oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) have ecological risk to humans and ecosystems. Polyvinylchloride microplastics (PVC MPs), as a representative of microplastics, may often coexist with CuO NPs and CIP in wastewater treatment systems due to their widespread application. However, the co-impact of PVC MPs in wastewater systems contained with CuO NPs and CIP on nitrogen removal and ecological risk is not clear. In this work, PVC MPs co-impacts on the toxicity of CuO NPs and CIP to aerobic granular sludge (AGS) systems and potential mechanisms were investigated. 10 mg/L PVC MPs co-addition did not significantly affect the nitrogen removal, but it definitely changed the microbial community structure and enhanced the propagation and horizontal transfer of antibiotics resistance genes (ARGs). 100 mg/L PVC MPs co-addition resulted in a raise of CuO NP toxicity to the AGS system, but reduced the co-toxicity of CuO NPs and CIP and ARGs expression. The co-impacts with different PVC MPs concentration influenced Cu2+ concentrations, cell membrane integrity, extracellular polymeric substances (EPS) contents and microbial communities in AGS systems, and lead to a change of nitrogen removal.

A Novel Mechanically Robust and Biodegradable Egg White Hydrogel Membrane by Combined Unidirectional Nanopore Dehydration and Annealing.

A homogeneous egg white obtained by high-speed shearing and centrifugation was dehydrated into a fragile and water-soluble egg white glass (EWG) by unidirectional nanopore dehydration (UND). After EWG annealing, it can become an egg white hydrogel membrane (EWHM) that is water-insoluble, flexible, biocompatible, and mechanically robust. Its tensile strength, elongation at break, and the swelling ratio are about 5.84 MPa, 50-110%, and 60-130%, respectively. Protein structure analysis showed that UND caused the rearrangement of the protein molecules to form EWG with random coil and α-helix structures. The thermal decomposition temperature of the EWG was 309.25 °C. After EWG annealing at over 100 or 110 °C for 1.0 h or 45 min, the porous network EWHM was mainly composed of ß-sheet structures, and the thermal decomposition temperature increased to 317.25-318.43 °C. Their 12-day residues in five proteases ranged from 1% to 99%, and the order was pepsin > neutral protease > papain > trypsin > alkaline protease. Mouse fibroblast L929 cells can adhere, grow, and proliferate well on these EWHMs. Therefore, the combined technology of UND and annealing for green and novel processing of EWHM has potential applications in the field of biomimetic and biomedical materials.

Association of oral care with periodontitis and glycemic control among US adults with diabetes.

BACKGROUND: Studies indicate that treating periodontitis may benefit glycemic control among people with diabetes. It is unclear whether oral self-care such as flossing may reduce risk for periodontitis and improve glycemic control among people with diabetes. The purpose of this study was to examine associations between oral care, specifically, flossing and preventive dental care, with periodontitis and glycemic control, among US dentate adults with diabetes. METHODS: We analyzed data from the National Health and Nutrition Examination Survey 2011-2014 for 892 participants aged 30 years and older with diabetes who completed the periodontal examination and lab test for hemoglobin A1c (HbA1c). Sampling weights were applied. Multivariable logistic regression and multivariable linear modeling were performed to examine the associations of flossing and preventive dental services on periodontal health and HbA1c levels, respectively, controlling for sociodemographic characteristics, health behaviors, and other risk factors. RESULTS: Among U.S. dentate adults with diabetes, 52.1% of flossers and 72.1% of non-flossers had periodontitis (p < 0.001). Flossers were 39% less likely to have periodontitis (Adj. OR 0.61, 95% CI 0.43-0.88) compared to non-flossers. Flossers had an average HbA1c reading 0.30% (95% CI 0.02%-0.58%) lower than non-flossers, adjusted for covariates (p = 0.037). Preventive dental visits were associated with reduced risk for periodontitis (Adj. OR 0.54, 95%CI, 0.38-0.75) but not glycemic control. CONCLUSION: Flossing was associated with periodontal health and glycemic control among US adults with diabetes. Although further research is needed, the findings support that oral self-care may be particularly beneficial for adults with diabetes.

Green immobilization and efficient proliferation of Escherichia coli cells in polyvinyl alcohol hydrogel membranes by unidirectional nanopore dehydration.

BACKGROUND: The immobilized technology for microbial or cells has the advantages of high microbial activity, high microbial density per unit space, good tolerance, strong shock, load resistance, high processing efficiency, and high reuse rate. It is now widely used in environmental remediation, water quality treatment, biodegradation, food industry, chemical analysis, energy development, medicine and pharmaceuticals, and other fields. RESULTS: A novel Escherichia coli cell-immobilizing polyvinyl alcohol hydrogel membrane (ECI-PVAHM) was prepared by unidirectional nanopore dehydration (UND) from a 10% polyvinyl alcohol (PVA) aqueous solution containing enhanced green fluorescent protein-labeled E. coli. This bacteria-loaded film has high water stability, flexibility, transparency, and mechanical robustness. Its tensile strength, elongation rate, and swelling rate are in the ranges 0.66-0.90 MPa, 300-390%, and 330-800%, respectively. The effective bacterial load of ECI-PVAHM is 2.375 × 109-1010 CFU/g (dry weight), which does not affect the original crystal structure of the PVAHM. This biofilm has a porous network structure with pore sizes between 0.2 and 1.0 µm, and these cells are embedded in the PVAHM network. When the immobilized cells were continuously cultured for 20 days, and the medium was renewed twice daily, their relative proliferation efficiency after 40 cycles could still be maintained at ~ 91%. CONCLUSION: The above results show that the cell division, proliferation ability, and metabolic activity of immobilized E. coli were not affected by the physical barrier of the porous network structure of the hydrogel. This UND-based ECI-PVAHM has potential applications in molecular biology, biopharmaceutical expression and production, bioreactors, and fuel cells.

Silk Protein Composite Bioinks and Their 3D Scaffolds and In Vitro Characterization.

This paper describes the use of silk protein, including fibroin and sericin, from an alkaline solution of Ca(OH)2 for the clean degumming of silk, which is neutralized by sulfuric acid to create calcium salt precipitation. The whole sericin (WS) can not only be recycled, but completely degummed silk fibroin (SF) is also obtained in this process. The inner layers of sericin (ILS) were also prepared from the degummed silk in boiling water by 120 °C water treatment. When the three silk proteins (SPs) were individually grafted with glycidyl methacrylate (GMA), three grafted silk proteins (G-SF, G-WS, G-ILS) were obtained. After adding I2959 (a photoinitiator), the SP bioinks were prepared with phosphate buffer (PBS) and subsequently bioprinted into various SP scaffolds with a 3D network structure. The compressive strength of the SF/ILS (20%) scaffold added to G-ILS was 45% higher than that of the SF scaffold alone. The thermal decomposition temperatures of the SF/WS (10%) and SF/ILS (20%) scaffolds, mainly composed of a ß-sheet structures, were 3 °C and 2 °C higher than that of the SF scaffold alone, respectively. The swelling properties and resistance to protease hydrolysis of the SP scaffolds containing sericin were improved. The bovine insulin release rates reached 61% and 56% after 5 days. The L929 cells adhered, stretched, and proliferated well on the SP composite scaffold. Thus, the SP bioinks obtained could be used to print different types of SP composite scaffolds adapted to a variety of applications, including cells, drugs, tissues, etc. The techniques described here provide potential new applications for the recycling and utilization of sericin, which is a waste product of silk processing.

Dissolution and processing of silk fibroin for materials science.

In recent decades, silk fibroin (SF) from silkworm Bombyx mori has been extensively researched and applied in several fields, including: cosmetics, biomedicine and biomaterials. The dissolution and regeneration of SF fibers is the key and prerequisite step for the application of silk protein-based materials. Various solvents and dissolving systems have been reported to dissolve SF fibers. However, the dissolution process directly affects the characteristics of SF and particularly impacts the mechanical properties of the resulting silk biomaterials in subsequent processing. The purpose of this review is to summarize the common solvents, the dissolution methods for silk protein, the properties of the resulting SF protein. The suitable use of SF dissolved in the corresponding solvent was also briefly introduced. Recent applications of SF in various biomaterials are also discussed.

Disparities in Preventive Oral Health Care and Periodontal Health Among Adults With Diabetes.

INTRODUCTION: People with diabetes are more vulnerable to periodontal disease than those without; thus, practicing preventive oral health care is an important part of diabetes self-care. Our objective was to examine disparities in preventive oral health care among US adults with diabetes. METHODS: We performed a secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016. Periodontal examinations were conducted in adults aged 30 and older. We compared the weighted prevalence of periodontal disease and the practice of preventive oral health care, including practicing dental interproximal cleaning (flossing or using other interproximal cleaning devices) and use of preventive dental services, among people with and without diabetes. Multivariable logistic regressions were performed to examine the relationship between the presence of diabetes, periodontal disease, and preventive oral health care practices. RESULTS: Weighted prevalence of periodontal disease in the US population was higher among adults with diabetes than those without (58.0% vs 37.6%). This difference persisted after controlling for sociodemographic characteristics and smoking status. People with diabetes were more likely to have periodontal disease (adjusted odds ratio [aOR] 1.39; 95% CI, 1.17-1.65), less likely to practice daily interproximal cleaning (aOR 0.85; 95% CI, 0.75-0.95), and less likely to visit a dentist for preventive care in the past year (aOR 0.86; 95% CI, 0.76-0.96) than people without diabetes. CONCLUSION: Adults with diabetes reported suboptimal preventive oral health care behaviors in use of preventive dental services and interproximal dental cleaning than people without diabetes, despite their health disparity related to periodontal disease. Educating people to improve their preventive oral health care is essential for good oral health and diabetes self-management.

Murine liver damage caused by exposure to nano-titanium dioxide.

Due to its unique physiochemical properties, nano-titanium dioxide (nano-TiO2) is widely used in all aspects of people's daily lives, bringing it into increasing contact with humans. Thus, this material's security issues for humans have become a heavily researched subject. Nano-TiO2 can enter the body through the mouth, skin, respiratory tract or in other ways, after which it enters the blood circulation and is deposited in the liver, changing biochemical indicators and causing liver inflammation. Meanwhile, the light sensitivity of these nanoparticles allows them to become media-generating reactive oxygen species (ROS), causing an imbalance between oxidation and anti-oxidation that leads to oxidative stress and liver damage. Nano-TiO2 can be transported into cells via phagocytosis, where the nanoparticles bind to the mitochondrial membrane, resulting in the disintegration of the membrane and the electron transport chain within the mitochondria. Thus, more ROS are produced. Nano-TiO2 can also enter the nucleus, where it can directly embed into or indirectly affect DNA, thereby causing DNA breakage or affecting gene expression. These effects include increased mRNA and protein expression levels of inflammation-related factors and decreased mRNA and protein expression levels of IκB and IL-2, resulting in inflammation. Long-term inflammation of the liver causes HSC cell activation, and extracellular matrix (ECM) deposition is promoted by multiple signalling pathways, resulting in liver fibrosis. In this paper, the latest progress on murine liver injury induced by environmental TiO2 is systematically described. The toxicity of nano-TiO2 also depends on size, exposure time, surface properties, dosage, administration route, and its surface modification. Therefore, its toxic effects in humans should be studied in greater depth. This paper also provides useful reference information regarding the safe use of nano-TiO2 in the future.

Integrated versus non-integrated orbital implants for treating anophthalmic sockets.

BACKGROUND: Anophthalmia is the absence of one or both eyes, and it can be congenital (i.e. a birth defect) or acquired later in life. There are two main types of orbital implant: integrated, whereby the implant receives a blood supply from the body that allows for the integration of the prosthesis within the tissue; and non-integrated, where the implant remains separate. Despite the remarkable progress in anophthalmic socket reconstruction and in the development of various types of implants, there are still uncertainties about the real roles of integrated (hydroxyapatite (HA), porous polyethylene (PP), composites) and non-integrated (polymethylmethacrylate (PMMA)/acrylic and silicone) orbital implants in anophthalmic socket treatment. OBJECTIVES: To assess the effects of integrated versus non-integrated orbital implants for treating anophthalmic sockets. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 8 August 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of integrated and non-integrated orbital implants for treating anophthalmic sockets. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant trials, assessed methodological quality and extracted data. MAIN RESULTS: We included three studies with a total of 284 participants (250 included in analysis). The studies were conducted in India, Iran and the Netherlands. The three studies were clinically heterogenous, comparing different materials and using different surgical techniques. None of the included studies used a peg (i.e. a fixing pin used to connect the implant to the prosthesis). In general the trials were poorly reported, and we judged them to be at unclear risk of bias.One trial compared HA using traditional enucleation versus alloplastic implantation using evisceration (N = 100). This trial was probably not masked. The second trial compared PP with scleral cap enucleation versus PMMA with either myoconjunctival or traditional enucleation (N = 150). Although participants were not masked, outcome assessors were. The last trial compared HA and acrylic using the enucleation technique (N = 34) but did not report comparative effectiveness data.In the trial comparing HA versus alloplastic implantation, there was no evidence of any difference between the two groups with respect to the proportion of successful procedures at one year (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.95 to 1.09, N = 100, low-certainty evidence). People receiving HA had slightly worse horizontal implant mobility compared to the alloplastic group (mean difference (MD) -3.35 mm, 95% CI -4.08 to -2.62, very low-certainty evidence) and slightly worse vertical implant motility (MD -2.76 mm, 95% CI -3.45 to -2.07, very low-certainty evidence). As different techniques were used - enucleation versus evisceration - it is not clear whether these differences in implant motility can be attributed solely to the type of material. Investigators did not report adverse events.In the trial comparing PP versus PMMA, there was no evidence of any difference between the two groups with respect to the proportion of successful procedures at one year (RR 0.92, 95% CI 0.84 to 1.01, N = 150, low-certainty evidence). There was very low-certainty evidence of a difference in horizontal implant motility depending on whether PP was compared to PMMA with traditional enucleation (MD 1.96 mm, 95% CI 1.01 to 2.91) or PMMA with myoconjunctival enucleation (-0.57 mm, 95% CI -1.63 to 0.49). Similarly, for vertical implant motility, there was very low-certainty evidence of a difference in the comparison of PP to PMMA traditional (MD 3.12 mm 95% CI 2.36 to 3.88) but no evidence of a difference when comparing PP to PMMA myoconjunctival (MD -0.20 mm 95% CI -1.28 to 0.88). Four people in the PP group (total N = 50) experienced adverse events (i.e. exposures) compared to 6/100 in the PMMA groups (RR 17.82, 95% CI 0.98 to 324.67, N = 150, very low-certainty evidence).None of the studies reported socket sphere size, cosmetic effect or quality of life measures. AUTHORS' CONCLUSIONS: Current very low-certainty evidence from three small published randomised controlled trials did not provide sufficient evidence to assess the effect of integrated and non-integrated material orbital implants for treating anophthalmic sockets. This review underlines the need to conduct further well-designed trials in this field.

Functional modification of silk fibroin from silkworms and its application to medical biomaterials: A review.

Silk fibroin (SF) from the silkworm Bombyx mori is a fibrous protein identified as a widely suitable biomaterial due to its biocompatibility, tunable degradation, and mechanical strength. Various modifications of SF protein can give SF fibers new properties and functions, broadening their applications in textile and biomedical industries. A diverse array of functional modifications on various forms of SF has been reported. In order to provide researchers with a more systematic understanding of the types of functional modifications of SF protein, as well as the corresponding applications, we comprehensively review the different types of functional modifications, including transgenic modification, modifications with chemical groups or biologically active substance, cross-linking and copolymerization without chemical reactions, their specific modification methods and applications. Furthermore, recent applications of SF in various medical biomaterials are briefly discussed.

The role of glycosylation in non-productive adsorption of cellulase to lignin isolated from pretreated corn stover.

Glycosylation, a general post-translational modification for fungal cellulase, has been shown to affect cellulase binding to its substrate. However, the exact impact of glycosylation on cellulase-lignin interaction remain unclear. Here, we demonstrated that the lignin isolated from tetrahydrofuran-pretreated corn stover exhibits strong adsorption capability to cellulase due to its negatively charged and porous structure. For the cellulases with varying glycosylation levels, the less-glycosylated protein showed high adsorption capability to lignin, and that trend was observed for the main cellulase components secreted by Penicillium oxilicum, including endoglucanase PoCel5B, cellobiohydrolase PoCel7A-2, and ß-glucosidase PoBgl1. Additionally, N-glycan sites and motifs were examined using mass spectrometry, and protein structures with N-glycans were constructed, where PoBgl1 and PoCel7A-2 contained 13 and 1 glycosylated sites respectively. The results of molecular dynamics simulations indicated that the N-glycans impacted on the solvent-accessible surface area and secondary structure of protein, and the binding conformation of lignin fragment on cellulase, resulting in a decrease in binding energy (14 kcal/mol for PoBgl1 and 13 kcal/mol for PoCel7A-2), particularly for van der Waals and electrostatic interaction. Those findings suggested that glycosylation negatively impacted the lignin-cellulase interaction, providing a theoretical basis for the rational engineering of enzymes to reduce lignin-enzyme interaction.

Polymerization strategy for cellulose nanocrystals-based photonic crystal films with water resisting property.

Cellulose nanocrystals (CNCs) can form a liquid crystal film with a chiral nematic structure by evaporative-induced self-assembly (EISA). It has attracted much attention as a new class of photonic liquid crystal material because of its intrinsic, unique structural characteristics, and excellent optical properties. However, the CNCs-based photonic crystal films are generally prepared via the physical crosslinking strategy, which present water sensitivity. Here, we developed CNCs-g-PAM photonic crystal film by combining free radical polymerization and EISA. FT-IR, SEM, POM, XRD, TG-DTG, and UV-Vis techniques were employed to characterize the physicochemical properties and microstructure of the as-prepared films. The CNCs-g-PAM films showed a better thermo-stability than CNCs-based film. Also, the mechanical properties were significantly improved, viz., the elongation at break was 9.4 %, and tensile strength reached 18.5 Mpa, which was a much better enhancement than CNCs-based film. More importantly, the CNCs-g-PAM films can resist water dissolution for more than 24 h, which was impossible for the CNCs-based film. The present study provided a promising strategy to prepare CNCs-based photonic crystal film with high flexibility, water resistance, and optical properties for applications such as decoration, light management, and anti-counterfeiting.

Validation of a double-semicircular notched configuration for mechanical testing of orthodontic thermoplastic aligner materials.

The potential of using specimens with a double-semicircular-notched configuration for performing tensile tests of orthodontic thermoplastic aligner materials was explored. Unnotched and double-semicircular-notched specimens were loaded in tension using a universal testing machine to determine their tensile strength, while finite element analysis (FEA) and digital image correlation (DIC) were used to estimate stress and strain, respectively. The shape did affect the tensile strength, demonstrating the importance of unifying the form of the specimen. During the elastic phase under tension, double-semicircular-notched specimens showed similar behavior to unnotched specimens. However, great variance was observed in the strain patterns of the unnotched specimens, which exhibited greater chance of end-failure, while the strain patterns of the double-semicircular-notched specimens showed uniformity. Considerable agreement between the theoretical (FEA) and practical models (DIC) further confirmed the validity of the double-semicircular-notched models.

Jinlida granules combined with metformin improved the standard-reaching rate of blood glucose and clinical symptoms of patients with type 2 diabetes: secondary analysis of a randomized controlled trial.

Background: Previous studies found that Jinlida granules could significantly reduce blood glucose levels and enhance the low-glucose action of metformin. However, the role of Jinlida in the standard-reaching rate of blood glucose and improving clinical symptoms has yet to be studied. We aimed to elaborate on the efficacy of Jinlida in type 2 diabetes (T2D) patients who experience clinical symptoms based on secondary analysis of a randomized controlled trial. Methods: Data were analyzed from a 12-week, randomized, placebo-controlled study of Jinlida. The standard-reaching rate of blood glucose, the symptom disappearance rate, the symptom improvement rate, the efficacy of single symptoms, and the total symptom score were evaluated. The correlation between HbA1c and the improvement of clinical symptoms was analyzed. Results: For 12 weeks straight, 192 T2D patients were randomly assigned to receive either Jinlida or a placebo. The treatment group showed statistically significant differences in the standard-reaching rate of HbA1c < 6.5% (p = 0.046) and 2hPG (< 10 mmol/L, 11.1 mmol/L) (p < 0.001), compared with the control group. The standard-reaching rate of HbA1c < 7% (p = 0.06) and FBG < 7.0 mmol/L (p = 0.079) were not significantly different between the treatment and control groups. Five symptoms exhibited a statistical difference in symptom disappearance rate (p < 0.05). All the symptoms exhibited a significant difference in symptom improvement rate (p < 0.05). The mean change in total symptom score from baseline to week 12 was -5.45 ± 3.98 in the treatment group and -2.38 ± 3.11 in the control group, with statistically significant differences (p < 0.001). No significant correlations were noted between symptom improvement and HbA1c after 12 weeks of continuous intervention with Jinlida granules or placebo. Conclusion: Jinlida granules can effectively improve the standard-reaching rate of blood glucose and clinical symptoms of T2D patients, including thirst, fatigue, increased eating with rapid hungering, polyuria, dry mouth, spontaneous sweating, night sweat, vexing heat in the chest, palms, and soles, and constipation. Jinlida granules can be used as an effective adjuvant treatment for T2D patients who experience those symptoms.

Polymorphs of a 1:1 salt of sulfadiazine and piperazine-relative stability, dissolution studies, pharmacokinetics and anti-meningitis efficiency.

Two new salt forms of sulfadiazine (SDZ) and piperazine (PIP) were synthesized and characterized. Out of the two polymorphs (SDZ-PIP Ⅰ and SDZ-PIP II), SDZ-PIP Ⅱ is the more stable form at low temperature, room temperature and high temperature. The solution-mediated phase transformation result shows that SDZ-PIP II can transform into pure SDZ within 15 s in phosphate buffer at 37 °C, which leads to a loss in solubility advantage. The addition of 2 mg/mL PVP K30, a polymeric crystallization inhibitor, maintains the solubility advantage and permits supersaturation for a longer period of time. SDZ-PIP II showed 2.5 times the solubility of SDZ alone. The area under the curve (AUC) of SDZ-PIP II with 2 mg/mL PVP K30 was approximately 165% of that of SDZ alone. Moreover, SDZ-PIP II with PVP K30 was more effective than SDZ alone in treating meningitis. Therefore, the SDZ-PIP II salt improves the solubility, bioavailability, and anti-meningitis activity of SDZ.

Mucus-Permeable Sonodynamic Therapy Mediated Amphotericin B-Loaded PEGylated PLGA Nanoparticles Enable Eradication of Candida albicans Biofilm.

Background: Candida albicans (C. albicans) forms pathogenic biofilms, and the dense mucus layer secreted by the epithelium is a major barrier to the traditional antibiotic treatment of mucosa-associated C. albicans infections. Herein, we report a novel anti-biofilm strategy of mucus-permeable sonodynamic therapy (mp-SDT) based on ultrasound (US)-mediated amphotericin B-loaded PEGylated PLGA nanoparticles (AmB-NPs) to overcome mucus barrier and enable the eradication of C. albicans biofilm. Methods: AmB-NPs were fabricated using ultrasonic double emulsion method, and their physicochemical and sonodynamic properties were determined. The mucus and biofilm permeability of US-mediated AmB-NPs were further investigated. Moreover, the anti-biofilm effect of US-mediated AmB-NPs treatment was thoroughly evaluated on mucus barrier abiotic biofilm, epithelium-associated biotic biofilm, and C. albicans-induced rabbit vaginal biofilms model. In addition, the ultrastructure and secreted cytokines of epithelial cells and the polarization of macrophages were analyzed to investigate the regulation of local cellular immune function by US-mediated AmB-NPs treatment. Results: Polymeric AmB-NPs display excellent sonodynamic performance with massive singlet oxygen (1O2) generation. US-mediated AmB-NPs could rapidly transport through mucus and promote permeability in biofilms, which exhibited excellent eradicating ability to C. albicans biofilms. Furthermore, in the vaginal epithelial cells (VECs)-associated C. albicans biofilm model, the mp-SDT scheme showed the strongest biofilm eradication effect, with up to 98% biofilm re-formation inhibition rate, improved the ultrastructural damage, promoted local immune defense enhancement of VECs, and regulated the polarization of macrophages to the M1 phenotype to enhance macrophage-associated antifungal immune responses. In addition, mp-SDT treatment exhibited excellent therapeutic efficacy against C. albicans-induced rabbit vaginitis, promoted the recovery of mucosal epithelial ultrastructure, and contributed to the reshaping of a healthier vaginal microbiome. Conclusion: The synergistic anti-biofilm strategies of mp-SDT effectively eradicated C. albicans biofilm and simultaneously regulated local antifungal immunity enhancement, which may provide a new approach to treat refractory drug-resistant biofilm-associated mucosal candidiasis.

Performance-enhanced regenerated cellulose film by adding grape seed extract.

Eco-friendly packaging material with intelligent colorimetric performance has been a requirement for food safety and quality. This work focused on a food packaging material from regenerated cellulose films that added the grape seed extract (GSE) and polyethylene glycol 200 (PEG). FTIR and SEM techniques were employed to prove the compatibility of GSE with cellulose matrix. The composite film showed an enhanced elongation at break (16.61 %) and tensile strength (33.09 MPa). The addition of PEG and GSE also improved the water contact angle of regenerated-cellulose film from 53.8° to 83.8°. Moreover, the composite films exhibited UV-blocking properties while maintaining adequate transparency. The GSE induced the regenerated films with a macroscopic change in color under different pH conditions. Furthermore, the loading of GSE slowed down the decomposition of strawberries and delayed the self-biodegradation compared with the control for more than 3 days and 18 days. The present study showed a regenerated cellulose film with acceptable mechanical and hydrophilia properties, pH-responsiveness, anti-decomposition, and delayed biodegradation performances, indicating a potential color sensor in food packaging.

Mangrove degradation retarded microplastics weathering and affected metabolic activities of microplastics-associated microbes.

Currently, information on microplastics (MPs) weathering characteristics and ecological functions driven by MPs-associated microbes in mangrove ecosystems remains unclear, especially in the degraded areas. Herein, we compared the weathering characteristics of MPs in both undegraded and degraded mangrove sediments, and then explored the potential interactions between their weathering characteristics and microbially-driven functions. After 70 days of incubation, different MPs (including polyethylene PE, polystyrene PS, and polylactic acid PLA) were strongly weathered in mangrove sediments, with significant erosion features. Interestingly, more obvious weathering characteristics were found for MPs in the undegraded mangrove sediments. O/C ratio value of MPs in the undegraded sediments was 2.3-3.0 times greater than that in the degraded ones. Besides, mangrove degradation reduced network complexity among MPs-associated microorganisms and affected their metabolic activities. Bacteria involved in carbon cycle process enriched on nondegradable MPs, whereas abundant bacteria responsible for sulphur cycle were observed on PLA-MPs. Moreover, these relevant bacteria were more abundant on MPs in the undegraded mangrove sediments. Mangrove degradation could directly and indirectly affect MPs weathering process and microbially-driven functions through regulating sediment properties and MPs-associated microbes. During weathering, contact angle and roughness of MPs were key factors influencing the colonisation of hydrocarbon degradation bacteria on MPs.