Liposomal delivery of self-peptide and calcitriol as tolerogenic immunotherapy in rheumatoid arthritis: an exploration using sensory science.

Immunology research holds significant potential for enhanced inclusivity at the beginning of the science literacy journey, but persistent challenges stem from limited awareness that improvement is needed in this field. At the 2023 Monash Sensory Science Exhibition, we had the opportunity to present several tactile posters, using simple materials, for visually impaired participants to showcase our research on the pathogenesis of rheumatoid arthritis as a result of immune tolerance breakdown and liposome-based tolerogenic immunotherapy. The posters stimulated lively discussions about autoimmune arthritic diseases and our research. With consideration of the diversity of the participants, the efforts of scientists in promoting science literacy for the community can promote a more inclusive environment and engage and inspire a broader audience.

Elevated neutrophil extracellular trap levels in periodontitis: Implications for keratinization and barrier function in gingival epithelium.

AIM: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms. MATERIALS AND METHODS: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation. RESULTS: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent. CONCLUSIONS: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization.

Flexible Recyclable Cellulose Paper Templated Cu-Doped Polydopamine Membranes with Dual Enzyme-Like Activity.

The development of high-efficiency enzyme mimics is of great significance in the field of biocatalysis. However, it remains challenging to design novel enzyme mimics with multiple enzyme-like activities, excellent stability, and good reusability. Herein, a facile molecular assembly strategy to construct dialdehyde cellulose (DAC) templated Cu-doped polydopamine (DAC@PDA/Cu) membrane with dual enzyme-like activities is presented. The Schiff base bonds formed between polydopamine (PDA) and DAC can not only accelerate the adhesion of PDA thin layer but also contribute to Cu-loading and high stability of DAC@PDA/Cu membrane. Importantly, the assembled DAC@PDA/Cu membrane exhibits a remarkable catalytic activity that is superior to the natural laccase along with high stability and excellent reusability. Moreover, the DAC@PDA/Cu membrane also demonstrates peroxidase-like activity, and it is successfully applied in the sensitive detection of ascorbic acid (AA). This work will provide a new paradigm methodology for rational design and practical applications of enzyme mimics based on bioinspired molecular assemblies.

Reorganization of Hydrogen Bonding in Biobased Polyamide 5,13 under the Thermo-Mechanical Field: Hierarchical Microstructure Evolution and Achieving Excellent Mechanical Performance.

The hierarchical microstructure evolution of an emerging biobased odd-odd polyamide 5,13 (PA5,13) films under the thermo-mechanical field, stepping from hydrogen bond (H-bond) arrangement to the crystalline morphology, has been investigated systematically. It is found that the reorganization of H-bonds under the thermo-mechanical field plays a crucial role in the crystallization of PA5,13. Especially, it is revealed that the crystallization process under the thermo-mechanical field develops along the chain axis direction, while lamellar fragmentation occurs perpendicular to the chain axis. Consequently, a stable and well-organized H-bond arrangement and lengthened lamellae with significant orientation have been constructed. Laudably, an impressive tensile strength of about 500 MPa and modulus of about 4.7 GPa are thus achieved. The present study could provide important guidance for the industrial-scale manufacture of high-performance biobased odd-odd PAs with long polymethylene segment in the dicarboxylic unit combined with a large difference between the polymethylene segments in the dicarboxylic and diamine units.

Tumor microenvironment and redox dual stimuli-responsive polymeric nanoparticles for the effective cisplatin-based cancer chemotherapy.

The serious side effects of cisplatin hindered its clinical application and the nanotechnology might be the potential strategy to address the limitation. However, rapid clearance in the blood circulation and ineffective controlled drug release from nanocarriers hamper the therapeutic efficacy of the nano-delivery system. We constructed a tumor microenvironment and redox dual stimuli-responsive nano-delivery system PEG-c-(BPEI-SS-Pt) by cross-linking the disulfide-containing polymeric conjugate BPEI-SS-Pt with the dialdehyde group-modified PEG2000via Schiff base. After optimized the cross-linking time, 72 h was selected to get the nano-delivery system.1H NMR and drug release assays showed that under the acidic tumor microenvironment (pH 6.5-6.8), the Schiff base can be broken and detached the PEG cross-linked outer shells, displaying the capability to release the drugs with a sequential pH- and redox-responsive manner. Moreover, PEG-c-(BPEI-SS-Pt) showed more effective anti-tumor therapeutic efficacyin vivowith no significant side effects when compared with the drug of cisplatin used in the clinic. This strategy highlights a promising platform with the dual stimuli-responsive profile to achieve better therapeutic efficacy and minor side effects for platinum-based chemotherapy.

Efficacy of local hemostatic agents after endoscopic submucosal dissection: a meta-analysis.

INTRODUCTION: Topical hemostatic agents have been used to reduce bleeding rates after endoscopic submucosal dissection (ESD) for gastric cancer. However, to date, no review has summarized evidence on their efficacy. MATERIAL AND METHODS: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar were searched for studies comparing bleeding rates after ESD with and without local hemostatic agents. RESULTS: Eleven studies were included. The studies used polyglycolic acid (PGA) sheets and fibrin glue, fibrin glue, oxidized regenerated cellulose, polysaccharide hemostatic powder, or polyethylene oxide adhesive. Meta-analysis revealed a statistically significant reduction in the risk of delayed bleeding with the use of PGA sheets & fibrin glue (six studies; RR: 0.35 95% CI: 0.20, 0.63 p = 0.0005). However, meta-analysis of two studies showed no difference in the risk of bleeding based on the use of fibrin glue (RR: 0.44 95% CI: 0.03, 7.17 p = 0.56). Scarce data were available for the remaining hemostatic agents. CONCLUSION: A large number of different hemostatic agents have been used to reduce the risk of bleeding after ESD for gastric cancer. Observational studies indicate that the use of PGA with fibrin glue could reduce the risk of bleeding after ESD. However, evidence for other agents was too scarce to derive conclusions.

[Cognition and Ability of Emergency Physicians for Palliative Care in Tertiary Hospitals].

Objective To understand the cognition and related abilities of emergency physicians for palliative care in China. Methods A total of 115 emergency physicians were selected by convenient sampling to conduct a questionnaire survey.The questionnaire included the physicians' basic information,feelings and attitudes towards end-stage patients and their families,cognition of palliative care,and personal ability for palliative care. Results 25.2%,59.1%,and 15.7% of the emergency physicians considered they had "no understanding","partial understanding",and "full understanding" of palliative care,respectively.32(27.8%)physicians participated in palliative care-related lectures and they showed higher self-rated cognition levels(P=0.002).Wechat(39.1%),media(36.5%),and word of mouth(33.0%)were the main ways for emergency physicians to acquire the knowledge of palliative care.Among the emergency physicians,68.7% felt "powerless" in the face of end-stage patients,and 60.9% and 59.1% felt tangled and worried about death causing disputes,respectively.The emergency physicians had low self-rated ability in relieving dyspnea after removal of ventilator[3(2,4)]and eliminating the fear of death[3(3,4)].The self-rated cognition level of emergency physicians to palliative care was positively correlated with most of the self-rated ability indexes. Conclusions Lectures have a significant impact on emergency physicians' cognition level of palliative care.Most of the self-rated indexes of palliative care ability are positively correlated with the cognition level of palliative care.In the face of end-stage patients,most of the emergency physicians are powerless,tangled,and worried about disputes,and their self-rated indexes in relieving dyspnea after removal of ventilator and eliminating the fear of death are low,which necessitates relevant training.

Molecular Assembly of Rotary and Linear Motor Proteins.

Molecular machines are an important and emerging frontier in research encompassing interdisciplinary subjects of chemistry, physics, biology, and nanotechnology. Although there has been major interest in creating synthetic molecular machines, research on natural molecular machines is also crucial. Biomolecular motors are natural molecular machines existing in nearly every living systems. They play a vital role in almost every essential process ranging from intracellular transport to cell division, muscle contraction and the biosynthesis of ATP that fuels life processes. The construction of biomolecular motor-based biomimetic systems can help not only to deeply understand the mechanisms of motor proteins in the biological process but also to push forward the development of bionics and biomolecular motor-based devices or nanomachines. From combination of natural biomolecular motors with supramolecular chemistry, great opportunities could emerge toward the development of intelligent molecular machines and biodevices. In this Account, we describe our efforts to design and reconstitute biomolecular motor-based active biomimetic systems, in particular, the combination of motor proteins with layer-by-layer (LbL) assembled cellular structures. They are divided into two parts: (i) reconstitution of rotary molecular motor FOF1-ATPase, which is coated on the surface of LbL assembled microcapsules or multilayers and synthesizes adenosine triphosphate (ATP) through creating a proton gradient; (ii) molecular assembly of linear molecular motors, the kinesin-based active biomimetic systems, which are coated on a planar surface or LbL assembled tubular structure and drive the movement of microtubules. LbL assembled structures offer motor proteins with an environment that resembles the natural cell. This enables high activity and optimized function of the motor proteins. The assembled biomolecular motors can mimic their functionalities from the natural system. In addition, LbL assembly provides facile integration of functional components into motor protein-based active biomimetic systems and achieves the manipulation of FOF1-ATPase and kinesin. For FOF1-ATPase, the light-driven proton gradient and controlled ATP synthesis are highlighted. For kinesin, the strategies used for the direction and velocity control of kinesin-based molecular shuttles are discussed. We hope this research can inspire new ideas and propel the actual applications of biomolecular motor-based devices in the future.

Polyethylenimine-based nanovector grafted with mannitol moieties to achieve effective gene delivery and transfection.

Polyethylenimine (PEI), a kind of cationic non-viral gene delivery vector, is capable of stable and efficient transgene expression for gene delivery. However, low transfection efficiency in vivo along with high toxicity limited the further application of gene therapy in the clinic. To enhance gene transfection performance and reduce cytotoxicity of polyethylenimine, branched polyethylenimine-derived cationic polymers BPEI25 k-man-S/L/M/H with different grafting degree with mannitol moieties were prepared and the transfection efficiency was evaluated. Among them, BPEI25 k-man-L showed the best transfection efficiency, lower toxicity, and significantly enhanced long-term systemic transgene expression for 96 h in vivo even at a single-dose administration. The results of cellular uptake mechanism and western-blot experiments revealed that the mannitol modification of BPEI25 k induced and up-regulated the phosphorylation of caveolin-1 and thus enhanced the caveolae-mediated cellular uptake. This class of gene delivery system highlights a paradigmatic approach for the development of novel and safe non-viral vectors for gene therapy.

Morphologies Transformation of BODIPY-Based Main Chain Supramolecular Polymers Amphiphiles: From Helical Nanowires to Nanosheets.

The aggregate morphologies of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) main chain supramolecular polymer amphiphiles (SPA) are tunable by a fine balance of different non-covalent interactions. When the BODIPY segments and sodium cholate are mixed in aqueous solution, they form SPA by electrostatic attraction and hydrogen-bonds. This SPA displays helical nanowires' morphology. After the third component dimeric ß-cyclodextrin (ß-CD-C) is added, the hydrogen bonds between the cholate are substituted by the host-guest interaction between cholate and ß-CD-C. Therefore, these SPA transform their aggregate morphologies into nanosheets' architecture. Therefore, a simple and effective way to regulate self-assembly by non-covalent forces is developed. This supramolecular method may provide an effective way to prepare various nanostructures in aqueous solution and show promising application in the future.

Supramolecularly Assembled Nanocomposites as Biomimetic Chloroplasts for Enhancement of Photophosphorylation.

Prototypes of natural biosystems provide opportunities for artificial biomimetic systems to break the limits of natural reactions and achieve output control. However, mimicking unique natural structures and ingenious functions remains a challenge. Now, multiple biochemical reactions were integrated into artificially designed compartments via molecular assembly. First, multicompartmental silica nanoparticles with hierarchical structures that mimic the chloroplasts were obtained by a templated synthesis. Then, photoacid generators and ATPase-liposomes were assembled inside and outside of silica compartments, respectively. Upon light illumination, protons produced by a photoacid generator in the confined space can drive the liposome-embedded enzyme ATPase towards ATP synthesis, which mimics the photophosphorylation process in vitro. The method enables fabrication of bioinspired nanoreactors for photobiocatalysis and provides insight for understanding sophisticated biochemical reactions.

Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery.

The covalently cross-linked chitosan-poly(ethylene glycol)1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG1540-dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEG1540H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery.

Complex Assembly of Polymer Conjugated Mesoporous Silica Nanoparticles for Intracellular pH-Responsive Drug Delivery.

There is a great challenge in constructing pH-responsive drug delivery systems in biomedical application research. Many nanocomposites are intended to be pH-responsive as drug carriers because of a tumorous or intracellular mildly acidic environment. However, it is always difficult to find an appropriate system for quick response and release before the carrier is excreted from the living system. In this work, hyperbranched polymer, hyperbranched polyglycerol (hPG), and conjugated mesoporous silica nanoparticles (MSNs) were assembled as complexes to serve as drug carriers. Herein, the conjugated polymer-MSNs interacted through the Schiff base bond, which possessed a mildly acidic responsive property. Interestingly, the assembled system could rapidly respond and release guest molecules inside cancer cells. This would make the entrapped drug released before the carriers escape from the endosome counterpart. The results show that the assembled composite complexes can be considered to be a drug delivery system for cancer therapy.

Cholesterol derived cationic lipids as potential non-viral gene delivery vectors and their serum compatibility.

Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery.

Preparation, Physicochemical Properties, and Transfection Activities of Tartaric Acid-Based Cationic Lipids as Effective Nonviral Gene Delivery Vectors.

In this work two novel cationic lipids using natural tartaric acid as linking backbone were synthesized. These cationic lipids were simply constructed by tartaric acid backbone using head group 6-aminocaproic acid and saturated hydrocarbon chains dodecanol (T-C12-AH) or hexadecanol (T-C16-AH). The physicochemical properties, gel electrophoresis, transfection activities, and cytotoxicity of cationic liposomes were tested. The optimum formulation for T-C12-AH and T-C16-AH was at cationic lipid/dioleoylphosphatidylethanolamine (DOPE) molar ratio of 1 : 0.5 and 1 : 2, respectively, and N/P charge molar ratio of 1 : 1 and 1 : 1, respectively. Under optimized conditions, T-C12-AH and T-C16-AH showed effective gene transfection capabilities, superior or comparable to that of commercially available transfecting reagent 3ß-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol) and N-[2,3-dioleoyloxypropyl]-N,N,N-trimethylammonium chloride (DOTAP). The results demonstrated that the two novel tartaric acid-based cationic lipids exhibited low toxicity and efficient transfection performance, offering an excellent prospect as nonviral vectors for gene delivery.

Carrier-inside-carrier: polyelectrolyte microcapsules as reservoir for drug-loaded liposomes.

Conventional liposomes have a short life-time in blood, unless they are protected by a polymer envelope, most often polyethylene glycol. However, these stabilizing polymers frequently interfere with cellular uptake, impede liposome-membrane fusion and inhibit escape of liposome content from endosomes. To overcome such drawbacks, polymer-based systems as carriers for liposomes are currently developed. Conforming to this approach, we propose a new and convenient method for embedding small size liposomes, 30-100 nm, inside porous calcium carbonate microparticles. These microparticles served as templates for deposition of various polyelectrolytes to form a protective shell. The carbonate particles were then dissolved to yield hollow polyelectrolyte microcapsules. The main advantage of using this method for liposome encapsulation is that carbonate particles can serve as a sacrificial template for deposition of virtually any polyelectrolyte. By carefully choosing the shell composition, bioavailability of the liposomes and of the encapsulated drug can be modulated to respond to biological requirements and to improve drug delivery to the cytoplasm and avoid endosomal escape.

Cu-chelated polydopamine nanozymes with laccase-like activity for photothermal catalytic degradation of dyes.

The industrial applications of enzymes are usually hindered by the high production cost, intricate reusability, and low stability in terms of thermal, pH, salt, and storage. Therefore, the de novo design of nanozymes that possess the enzyme mimicking biocatalytic functions sheds new light on this field. Here, we propose a facile one-pot synthesis approach to construct Cu-chelated polydopamine nanozymes (PDA-Cu NPs) that can not only catalyze the chromogenic reaction of 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AP), but also present enhanced photothermal catalytic degradation for typical textile dyes. Compared with natural laccase, the designed mimic has higher affinity to the substrate of 2,4-DP with Km of 0.13 mM. Interestingly, PDA-Cu nanoparticles are stable under extreme conditions (temperature, ionic strength, storage), are reusable for 6 cycles with 97 % activity, and exhibit superior substrate universality. Furthermore, PDA-Cu nanozymes show a remarkable acceleration of the catalytic degradation of dyes, malachite green (MG) and methylene blue (MB), under near-infrared (NIR) laser irradiation. These findings offer a promising paradigm on developing novel nanozymes for biomedicine, catalysis, and environmental engineering.

Blood cellular membrane-coated Au/polydopamine nanoparticle-targeted NIR-II antibacterial therapy.

Bacterial infections are the primary causes of infectious diseases in humans. In recent years, the abuse of antibiotics has led to the widespread enhancement of bacterial resistance. Concerns have been raised about the identification of a common treatment platform for bacterial infections. In this study, a composite nanomaterial was used for near-infrared II (NIR-II) photothermal antibacterial treatment. Red blood cell membrane was peeled and coated onto the surface of the Au/polydopamine nanoparticle-containing aptamer. The composite nanomaterials based on Au/polydopamine exhibit highest photothermal conversion capability. Moreover, these assembled nanoparticles can quickly enter the body's circular system with a specific capability to recognise bacteria. In vivo experiments demonstrated that the composites could kill bacteria from infected blood while significantly reducing the level of bacteria in various organs. Such assemblies offer a paradigm for the treatment of bacterial infections caused by the side effects of antibiotics.

Self-organization of honeycomb-like porous TiO2 films by means of the breath-figure method for surface modification of titanium implants.

This study describes a facile breath-figure method for the preparation of honeycomb-like porous TiO2 films with an organometallic small-molecule precursor. Multiple characterization techniques have been used to investigate the porous films and a mechanism for the formation process of porous TiO2 films through the breath-figure method is proposed. The pore size of the TiO2 films could be modulated by varying the experimental parameters, such as the concentration of titanium n-butoxide (TBT) solution, the content of cosolvent, and the air flow rate. In vitro cell-culture experiments indicate that NIH 3T3 fibroblast cells seeded on the honeycomb-like porous TiO2 films show good adhesion, spreading, and proliferation behaviors, which suggests that honeycomb-like porous TiO2 films are an attractive biomaterial for surface modification of titanium and its alloys implants in tissue engineering to enhance their biocompatibility and bioactivity.

The preparation and characterization of highly aligned poly(epsilon-caprolactone)/poly ethylene oxide/chitosan ultrafine fiber for the application to tissue scaffold.

The purpose of this study was to fabricate poly(epsilon-caprolactone) (PCL)/poly ethylene oxid (PEO)/chitosan (CS) ultrafine fiber in both aligned and random structures using electrospinning technique and their process parameters were optimized. The aligned and random PCL/PEO/chitosan ultrafine fibers were also used as scaffold for tissue engineering and their cell affinity was investigated. In the first part, we inspected the effect of environment conditions, solution properties, process parameters on PCL/PEO/chitosan ultrafine fiber. In the second part, the apparatus of electrospinning to manufacture highly aligned PCL/PEO/chitosan ultrafine fiber was developed. The effects of process parameters such as flow rate, design of collector and rotation speed of collecting drum on the morphology of ultrafine fiber were discussed. In addition, the cross link of PCL/PEO/chitosan ultrafine fiber by cross-linking agent was examined, too. The physical properties, chemical properties, and cell affinities of the aligned PCL/PEO/chitosan ultrafine fiber with or without cross link were measured. The chemical analysis and tensile strength of the ultrafine fiber were characterized using Fourier Transfer Infared Spectrophotometer and Universal Tensile Machine, respectively. The results show that the aligned PCL/PEO/chitosan ultrafine fibrous mat had the capacity to induce cellular alignment and enhance cellular elongation.