The Convergence of Sonodynamic Therapy and Cuproptosis in the Dual-Responsive Biomimetic CytoNano for Precision Mitochondrial Intervention in Cancer Treatment.

The integration of sonodynamic therapy (SDT) with cuproptosis for targeted cancer treatment epitomizes a significant advancement in oncology. Herein, we present a dual-responsive therapeutic system, "CytoNano", which combines a cationic liposome infused with copper-nitride nanoparticles and oxygen-rich perfluorocarbon (Lip@Cu3N/PFC-O2), all enveloped in a biomimetic coating of neutrophil membrane and acid-responsive carboxymethylcellulose. CytoNano leverages the cellular mimicry of neutrophils and acid-responsive materials, enabling precise targeting of tumors and their acidic microenvironment. This strategic design facilitates the targeted release of Lip@Cu3N/PFC-O2 within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu3N-driven SDT and cuproptosis while preserving healthy tissues. Additionally, CytoNano's ultrasound responsiveness enhances intratumoral oxygenation, overcoming physiological barriers and initiating a combined sonodynamic-cuproptotic effect that induces multiple cell death pathways. Thus, we pioneer a biomimetic approach in precise sonodynamic cuproptosis, revolutionizing cancer therapy.

A type I and II compatible vinyl-pyridine modified BODIPY dimer photosensitizer for photodynamic therapy in A-549 cells.

In this paper, the vinyl-pyridine group was used to modify the BODIPY dimer photosensitizer (T-BDP2) to obtain a VP-BDP2 photosensitizer. Compared with the T-BDP2 photosensitizer, the VP-BDP2 photosensitizer could work under pure water conditions, the singlet oxygen yield was increased from 9.38% to 22.2%, the charge transfer rate was increased from about 30 ps to about 10 ps, and the red emission was enhanced in fluorescence imaging. In addition, the VP-BDP2 photosensitizer could also generate the superoxide radical (O2˙-) under pure water conditions. The ROS generation mechanism of the VP-BDP2 photosensitizer was considered to be the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) mechanism, which was verified by fs-transient absorption spectra and theoretical calculation. In the photodynamic therapy of A-549 cells, the VP-BDP2 photosensitizers could generate singlet oxygen and superoxide radicals (O2˙-) under biological conditions, and showed high phototoxicity with the IC50 value at 12.1 µM under light at 525 nm. Additionally, the multiple dipolar configuration meant that the VP-BDP2 photosensitizer could be used in two-photon fluorescence zebrafish imaging under 800 nm excitation, which sets the stage for future two-photon photodynamic therapy.

Magnesium-based bioabsorbable screw fixation for hallux valgus surgery - A suitable alternative to metallic implants.

BACKGROUND: The primary aim of this pilot study was to prospectively evaluate outcomes of the MgYREZr bioabsorbable screw in the setting of hallux valgus corrective surgery. The secondary aim was to compare the outcomes against a control group treated with conventional titanium screws. METHODS: A consecutive series of patients with hallux valgus deformity (n=24) underwent forefoot reconstruction surgery with a scarf osteotomy to the first metatarsal using MgYREZr screws. Functional scores, radiological outcomes, and complication profile were recorded over 12 months. Results were compared against a control group of patients (n=69) using titanium alloy screws. RESULTS: At 1-year post-operative, both functional and radiological outcomes showed significant improvements. Compared to the control group, there was no significant difference in functional outcomes, yet radiological improvements were significantly better in the control group. CONCLUSIONS: The MgYREZr bioabsorbable screw is a suitable alternative to titanium alloy screws for hallux valgus corrective surgery.

Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide.

Neuromedin U (NMU) is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes. A key liability of NMU as a therapeutic is its very short half-life in vivo. We show here that conjugation of NMU to human serum albumin (HSA) yields a compound with long circulatory half-life, which maintains full potency at both the peripheral and central NMU receptors. Initial attempts to conjugate NMU via the prevalent strategy of reacting a maleimide derivative of the peptide with the free thiol of Cys34 of HSA met with limited success, because the resulting conjugate was unstable in vivo. Use of a haloacetyl derivative of the peptide led instead to the formation of a metabolically stable conjugate. HSA-NMU displayed long-lasting, potent anorectic, and glucose-normalizing activity. When compared side by side with a previously described PEG conjugate, HSA-NMU proved superior on a molar basis. Collectively, our results reinforce the notion that NMU-based therapeutics are promising candidates for the treatment of obesity and diabetes.

Epidermal stem cells manipulated by pDNA-VEGF165/CYD-PEI nanoparticles loaded gelatin/ß-TCP matrix as a therapeutic agent and gene delivery vehicle for wound healing.

The success of gene therapy largely relies on a safe and effective gene delivery system. The objective of this study is to design a highly efficient system for the transfection of epidermal stem cells (ESCs) and investigate the transfected ESCs (TESCs) as a therapeutic agent and gene delivery reservoir for wound treatment. As a nonviral vector, ß-cyclodextrin-linked polyethylenimines (CYD-PEI) was synthesized by linking ß-cyclodextrin with polyethylenimines (600 Da). Gelatin scaffold incorporating ß-tricalcium phosphate (ß-TCP) was utilized as a substrate for the culture and transfection of ESCs. With the CYD-PEI/pDNA-VEGF165 polyplexes incorporated gelatin/ß-TCP scaffold based 3D transfection system, prolonged VEGF expression with a higher level was obtained at day 7 in ESCs than those in two-dimensional plates. Topical application of the TESCs significantly accelerated the skin re-epithelization, dermal collagen synthesis, and hair follicle regeneration. It also exhibited a potential in scar inhibition by regulating the distribution of different types of collagen. In contrast to ESCs, an additive capacity in stimulating angiogenesis at the wound site was observed in the TESCs. The present study provides a basis for the TESCs as a promising therapeutic agent and gene delivery reservoir for wound therapy.

DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord.

Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.

PEGylation of Neuromedin U yields a promising candidate for the treatment of obesity and diabetes.

Neuromedin U (NMU) is an endogenous peptide, whose role in the regulation of feeding and energy homeostasis is well documented. Two NMU receptors have been identified: NMUR1, expressed primarily in the periphery, and NMUR2, expressed predominantly in the brain. We recently demonstrated that acute peripheral administration of NMU exerts potent but acute anorectic activity and can improve glucose homeostasis, with both actions mediated by NMUR1. Here, we describe the development of a metabolically stable analog of NMU, based on derivatization of the native peptide with high molecular weight poly(ethylene) glycol (PEG) ('PEGylation'). PEG size, site of attachment, and conjugation chemistry were optimized, to yield an analog which displays robust and long-lasting anorectic activity and significant glucose-lowering activity in vivo. Studies in NMU receptor-deficient mice showed that PEG-NMU displays an expanded pharmacological profile, with the ability to engage NMUR2 in addition to NMUR1. In light of these data, PEGylated derivatives of NMU represent promising candidates for the treatment of obesity and diabetes.

Digital light processing (DLP) in tissue engineering: from promise to reality, and perspectives.

Tissue engineering technology provides a revolutionary strategy to completely restore the structure and function of damaged tissues or organs. Digital light processing (DLP), as a kind of three-dimensional (3D) printing technology, has great advantages in printing resolution and efficiency, with low requirements for bioinks. This review introduces DLP-based printing and its development, as well as the manufacturing processes and printable materials. We also focus on tissue engineering products such as bone, tooth, cartilage, nerve, blood vessel, and so on. This review expounds on the difficulties and shortcomings of DLP printing technology in tissue engineering today. Perspectives are given on the current outlook on DLP-based 3D printing tissue engineering.

Transparent Conductive Silk Film with a PEDOT-OH Nano Layer as an Electroactive Cell Interface.

Bioelectronics based on biomaterial substrates are advancing toward biomedical applications. As excellent conductors, poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives have been widely developed in this field. However, it is still a big challenge to obtain a functional layer with a good electroconductive property, transparency, and strong adhesion on the biosubstrate. In this work, poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-OH) was chemically polymerized and deposited on the surface of a regenerated silk fibroin (RSF) film in an aqueous system. Sodium dodecyl sulfate (SDS) was used as the surfactant to form micelles which are beneficial to the polymer structure. To overcome the trade-off between transparency and the electroconductive property of the PEDOT-OH coating, a composite oxidant recipe of FeCl3 and ammonium persulfate (APS) was developed. Through electrostatic interaction of oppositely charged doping ions, a well-organized conductive nanoscale coating formed and a transparent conductive RSF/PEDOT-OH film was produced, which can hardly be achieved in a traditional single oxidant system. The produced film had a sheet resistance (Rs) of 5.12 × 104 Ω/square corresponding to a conductivity of 8.9 × 10-2 S/cm and a maximum transmittance above 73% in the visible range. In addition, strong adhesion between PEDOT-OH and RSF and favorable electrochemical stability of the film were demonstrated. Desirable transparency of the film allowed real-time observation of live cells. Furthermore, the PEDOT-OH layer provided an improved environment for adhesion and differentiation of PC12 cells compared to the RSF surface alone. Finally, the feasibility of using the RSF/PEDOT-OH film to electrically stimulate PC12 cells was demonstrated.

Toxicity of Microplastics and Nanoplastics in Mammalian Systems.

Fragmented or otherwise miniaturized plastic materials in the form of micro- or nanoplastics have been of nagging environmental concern. Perturbation of organismal physiology and behavior by micro- and nanoplastics have been widely documented for marine invertebrates. Some of these effects are also manifested by larger marine vertebrates such as fishes. More recently, possible effects of micro- and nanoplastics on mammalian gut microbiota as well as host cellular and metabolic toxicity have been reported in mouse models. Human exposure to micro- and nanoplastics occurs largely through ingestion, as these are found in food or derived from food packaging, but also in a less well-defined manner though inhalation. The pathophysiological consequences of acute and chronic micro- and nanoplastics exposure in the mammalian system, particularly humans, are yet unclear. In this review, we focus on the recent findings related to the potential toxicity and detrimental effects of micro- and nanoplastics as demonstrated in mouse models as well as human cell lines. The prevailing data suggest that micro- and nanoplastics accumulation in mammalian and human tissues would likely have negative, yet unclear long-term consequences. There is a need for cellular and systemic toxicity due to micro- and nanoplastics to be better illuminated, and the underlying mechanisms defined by further work.

[The remove of intraocular foreign body by the assistance of the injection of silicone oil].

OBJECTIVE: To evaluate the effect of the injection of silicone oil in helping the remove of intraocular foreign body throughout pars plana vitrectomy (PPV). METHODS: It was a series case study. This study included 17 eyes with intraocular foreign body from June 2007 to April 2008. Intraocular foreign bodies in these eyes were hardly removed, and all of the eyes had complicated and severe retinal injuries. The intraocular foreign bodies were taken out followed intravitreal injection of silicon oil. The retinal protective effects of silicon oil were studied. RESULTS: All the intraocular foreign bodies were removed successfully without any damage to the retina due to the viscosity of silicon oil and its gasket function. CONCLUSIONS: Intravitreal injection of silicon oil was able to help the removement of hardly-hold intraocular foreign body with PPV and avoid secondary retinal injury in this process.

Surface Modification by Divalent Main-Group-Elemental Ions for Improved Bone Remodeling To Instruct Implant Biofabrication.

Divalent main-group-elemental ions are widely used to improve osteogenic capacity of implants biofabricated from Ti and its alloys. However, the conclusions regarding their osseointegration and immunogenicity are always inconsistent because of the multiple bone remodeling processes as well as the distinct material surface features arising from processing. Here we successfully manufactured the porous micro/nanostructured surface topography with divalent main-group-elemental ions (Mg2+, Ca2+, Sr2+, Ba2+) on substrates through hydrothermal treatment and comprehensively evaluated the complex bone remodeling processes, including osseointegration, immunogenicity, and fibrosis of substrates and implants. We found that Sr-modified implants not only upregulated the adhesion and proliferation of mesenchymal stem cells but also the differentiation of osteogenic markers compared with those modified by other divalent main-group-elemental ions (Mg2+, Ca2+, Ba2+). More importantly, the osteoclastogenesis, immunogenicity, and fibrosis of Sr-modified implants were also significantly downregulated. In vivo, evaluations of new bone formation and histological morphology at the interface of implant and host as well as the removal torque similarly indicated the improved osseointegration of Sr-modified implants as well as the absence of immunogenicity, fibrosis, or necrosis. Our results suggested that among various divalent main-group-elemental ions, Sr2+ might be a promising one for enhancing bone remodeling, which can be used to instruct functionalization of the surfaces of biofabricated Ti-based orthopedic and dental implants in the future.

Comparative study of riboflavin-UVA cross-linking and "flash-linking" using surface wave elastometry.

PURPOSE: To investigate comparative stiffness values in porcine corneas after standard cross-linking and a new, rapid method of cross-linking (flash-linking) using surface wave elastometry. METHODS: Ten porcine eyes were treated using an ultraviolet A (UVA) double diode light source with a wavelength of 370 nm and delivering an irradiance of 4.2 mW/cm2 at a distance of 1.2 cm while applying 0.1% riboflavin-5-phosphate drops to the central cornea every 5 minutes as a photosensitizer for 30 minutes (riboflavin-UVA group). The next 10 porcine corneas were treated with a single application of a customized photoactive crosslinking agent and 30 seconds of UVA light at the same power and wavelength (flash-linking group). Following treatment, the Sonic Eye system (PriaVision Inc) was used to measure ultrasound surface wave propagation time between two fixed-distance transducers applied to the cornea along central horizontal and vertical positions. Intraocular pressure was continuously monitored. RESULTS: Mean surface wave velocity was determined from the last 5 of 10 sequential measurements for each eye, and was 90.87 +/- 15.26 m/s for all eyes with a mean standard deviation (SD) of 2.34 m/s among each eye in the riboflavin-UVA group versus 83.66 +/- 12.30 m/s with a mean SD of 2.69 m/s among each eye in the flash-linking group before treatment and 109.2 +/- 21.76 m/s with a mean SD of 2.15 m/s among each eye (riboflavin-UVA group) versus 109.2 +/- 18.42 m/s with a mean SD of 2.26 m/s among each eye (flash-linking group) after cross-linking. The mean surface wave velocity increased by 18.3 units from 90.87 to 109.2 m/s (P = .003) after cross-linking with riboflavin-UVA, and by 25.5 m/s from 83.66 to 109.2 m/s (P = .0001) after flash-linking. Surface wave velocity was noted to increase after both cross-linking techniques, but the differences observed did not reach statistical significance (P = .74). CONCLUSIONS: A new, rapid method of cross-linking (flash-linking) is introduced by the use of a customized photoactive cross-linking agent. The method demonstrates similar efficacy in stiffening the cornea (when measured with surface wave elastometry) in comparison to standard cross-linking, but requires only 30 seconds of UVA exposure.

Psychosocial impact of dental aesthetics and desire for orthodontic treatment among Chinese undergraduate students.

OBJECTIVE: The objective of this study is to evaluate the psychosocial impact of dental aesthetics in undergraduate students in the People's Republic of China and to investigate the association between normal orthodontic treatment needs, psychosocial impact of dental aesthetics, and desire for orthodontic treatment. MATERIALS AND METHODS: A cross-sectional study was carried out in two universities in a city of the People's Republic of China with 374 young adults aged between 19 years and 24 years. The students answered a Chinese version of the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) and addressed their desire for orthodontic treatment. Objective malocclusion severity was assessed with the Index of Orthodontic Treatment Need (IOTN). Statistical analysis was performed by the SPSS software (Version 15.0). RESULTS: There was no statistical sex difference in relation to the dental health component of IOTN (P=0.893) and PIDAQ scores (P=0.06), but it was found that the desire for orthodontic treatment was significantly stronger among females. The total and subscale PIDAQ scores and malocclusion severity differed significantly among the five grades of desire (P<0.01). Significant positive correlation was found among desire for orthodontic treatment, IOTN-dental health component grades, and total or subscale PIDAQ scores (P<0.01). High correlation was found between desire and PIDAQ score (r=0.93). CONCLUSION: The desire for orthodontic treatment is higher among female young adults who have the same orthodontic treatment needs compared to males. The desire for orthodontic treatment has high positive correlation with PIDAQ scores and increases with the increase in self-perceived psychosocial impacts of malocclusion and the needs for orthodontic treatment.