Prussian blue nanoparticle-based pH-responsive self-assembly for enhanced photothermal and chemotherapy of tumors.

In recent years, there has been growing interest in size-transformable nanoplatforms that exhibit active responses to acidic microenvironments, presenting promising prospects in the field of nanomedicine for tumor therapy. However, the design and fabrication of such size-adjustable nanotherapeutics pose significant challenges compared to size-fixed nanocomposites, primarily due to their distinct pH-responsive requirements. In this study, we developed pH-activated-aggregating nanosystems to integrate chemotherapy and photothermal therapy by creating size-transformable nanoparticles based on Prussian blue nanoparticles (PB NPs) anchored with acid-responsive polyoxometalates (POMs) quantum dots via electrostatic interactions (PPP NPs). Subsequently, we utilized doxorubicin (DOX) as a representative drug to formulate PPPD NPs. Notably, PPPD NPs exhibited a significant response to acidic conditions, resulting in changes in surface charge and rapid aggregation of PPP NPs. Furthermore, the aggregated PPP NPs demonstrated excellent photothermal properties under near-infrared laser irradiation. Importantly, PPPD NPs prolonged their retention time in tumor cells via a size-transformation approach. In vitro cellular assays revealed that the anticancer efficacy of PPPD NPs was significantly enhanced. The IC50 values for the PPPD NPs groupand the PPPD NPs + NIR group were 50.11 µg/mL and 30.9 µg/mL. Overall, this study introduces a novel strategy for cancer therapy by developing size-aggregating nano-drugs with stimuli-responsive properties, holding promise for improved therapeutic outcomes in future combination approaches involving photothermal therapy and chemotherapy.

The Relationship Between Gene Mutations and the Clinicopathological Features and Prognosis of Gastric Cancer.

Current treatments for gastric cancer (GC) are suboptimal. Potential therapeutic targets for GC were screened using next-generation sequencing. We examined many mutation genes linked to GC, including TP53 (60%), PIK3CA (19%), LRP1B (13%), and ERBB2 (12%), ARID1A (9%), KMT2C (9%), and KRAS (7%). The KMT2C, KRAS, CDK6, and ARID1A wild-type genes were dominant in diffuse-type GC (P < .05), but mutations did not influence prognosis. Patients with APC (6%) and CDH1 (8%) wild-type GC presented with vascular invasion (P < .05). Patients with ATR (2%) wild-type GC were prone to lymph node metastasis (P < .05). Patients with ARID1A (9%) wild-type GC had reduced programmed death ligand 1 expression (<1, P < .05). We found that patients who received chemotherapy had a better prognosis than those who did not (although there was no statistical difference), with platinum-based group having better prognosis and uracil combined with paclitaxel group having worse prognosis.

Biomedical applications of magnetosomes: State of the art and perspectives.

Magnetosomes, synthesized by magnetotactic bacteria (MTB), have been used in nano- and biotechnological applications, owing to their unique properties such as superparamagnetism, uniform size distribution, excellent bioavailability, and easily modifiable functional groups. In this review, we first discuss the mechanisms of magnetosome formation and describe various modification methods. Subsequently, we focus on presenting the biomedical advancements of bacterial magnetosomes in biomedical imaging, drug delivery, anticancer therapy, biosensor. Finally, we discuss future applications and challenges. This review summarizes the application of magnetosomes in the biomedical field, highlighting the latest advancements and exploring the future development of magnetosomes.

Online Monitoring Technology of Metal Powder Bed Fusion Processes: A Review.

Metal powder bed fusion (PBF) is an advanced metal additive manufacturing (AM) technology. Compared with traditional manufacturing techniques, PBF has a higher degree of design freedom. Currently, although PBF has received extensive attention in fields with high-quality standards such as aerospace and automotive, there are some disadvantages, namely poor process quality and insufficient stability, which make it difficult to apply the technology to the manufacture of critical components. In order to surmount these limitations, it is necessary to monitor the process. Online monitoring technology can detect defects in time and provide certain feedback control, so it can greatly enhance the stability of the process, thereby ensuring its quality of the process. This paper presents the current status of online monitoring technology of the metal PBF process from the aspects of powder recoating monitoring, powder bed inspection, building process monitoring, and melt layer detection. Some of the current limitations and future trends are then highlighted. The combination of these four-part monitoring methods can make the quality of PBF parts highly assured. We unanimously believe that this article can be helpful for future research on PBF process monitoring.

Enhancing the Efficiency of Mild-Temperature Photothermal Therapy for Cancer Assisting with Various Strategies.

Conventional photothermal therapy (PTT) irradiates the tumor tissues by elevating the temperature above 48 °C to exert thermal ablation, killing tumor cells. However, thermal ablation during PTT harmfully damages the surrounding normal tissues, post-treatment inflammatory responses, rapid metastasis due to the short-term mass release of tumor-cellular contents, or other side effects. To circumvent this limitation, mild-temperature photothermal therapy (MTPTT) was introduced to replace PTT as it exerts its activity at a therapeutic temperature of 42-45 °C. However, the significantly low therapeutic effect comes due to the thermoresistance of cancer cells as MTPTT figures out some of the side-effects issues. Herein, our current review suggested the mechanism and various strategies for improving the efficacy of MTPTT. Especially, heat shock proteins (HSPs) are molecular chaperones overexpressed in tumor cells and implicated in several cellular heat shock responses. Therefore, we introduced some methods to inhibit activity, reduce expression levels, and hinder the function of HSPs during MTPTT treatment. Moreover, other strategies also were emphasized, including nucleus damage, energy inhibition, and autophagy mediation. In addition, some therapies, like radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, exhibited a significant synergistic effect to assist MTPTT. Our current review provides a basis for further studies and a new approach for the clinical application of MTPTT.

Fucoidan-Mediated Anisotropic Calcium Carbonate Nanorods of pH-Responsive Drug Release for Antitumor Therapy.

The shape of nanoparticles can determine their physical properties and then greatly impact the physiological reactions on cells or tissues during treatment. Traditionally spherical nanoparticles are more widely applied in biomedicine but are not necessarily the best. The superiority of anisotropic nanoparticles has been realized in recent years. The synthesis of the distinct-shaped metal/metal oxide nanoparticles is easily controlled. However, their biotoxicity is still up for debate. Hence, we designed CaCO3 nanorods for drug delivery prepared at mild condition by polysaccharide-regulated biomineralization in the presence of fucoidan with sulfate groups. The CaCO3 nanorods with a pH sensitivity-loaded antitumor drug mitoxantrone hydrochloride (MTO) showed excellent antitumor efficacy for the HeLa cells and MCF-7 cells in vitro. We believe that anisotropic nanoparticles will bring forth an emblematic shift in nanotechnology for application in biomedicine.

Combination of Mussel Inspired Method and "Thiol-Michael" Click Reaction for Biocompatible Alginate-Modified Carbon Nanotubes.

Carbon nanotubes (CNTs) have attracted great interest in biomedical fields. However, the potential toxicity and poor dispersion of CNTs have greatly limited its application. In this work, a mussel-inspired method combined with the "thiol-Michael" click reaction was used to modify the surface of CNT and improve its properties. Firstly, a CNT was treated with dopamine, and then alginate grafted with L-cysteine was anchored onto the surface of CNT via click reaction, which realized the long-time dispersion of CNT in water. Furthermore, the in vitro test also demonstrated that the alginate may improve the biocompatibility of CNT, and thus may broaden the application of CNT in the biomedical field.

Cancer Cytomembrane-Cloaked Prussian Blue Nanoparticles Enhance the Efficacy of Mild-Temperature Photothermal Therapy by Disrupting Mitochondrial Functions of Cancer Cells.

Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications.

A New Method for Automatic Detection of Defects in Selective Laser Melting Based on Machine Vision.

Selective laser melting (SLM) is a forming technology in the field of metal additive manufacturing. In order to improve the quality of formed parts, it is necessary to monitor the selective laser melting forming process. At present, most of the research on the monitoring of the selective laser melting forming process focuses on the monitoring of the melting pool, but the quality of forming parts cannot be controlled in real-time. As an indispensable link in the SLM forming process, the quality of powder spreading directly affects the quality of the formed parts. Therefore, this paper proposes a detection method for SLM powder spreading defects, mainly using industrial cameras to collect SLM powder spreading surfaces, designing corresponding image processing algorithms to extract three common powder spreading defects, and establishing appropriate classifiers to distinguish different types of powder spreading defects. It is determined that the multilayer perceptron (MLP) is the most accurate classifier. This detection method has high recognition rate and fast detection speed, which cannot only meet the SLM forming efficiency, but also improve the quality of the formed parts through feedback control.

A carboxymethyl lentinan layer by layer self-assembly system as a promising drug chemotherapeutic platform.

Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient strategy for enhancing the biocompatibility and efficiency of an MSN-based carrier platform. Herein, natural polyelectrolyte multilayers composed of poly-l-ornithine (PLO) and carboxymethyl lentinan (LC) were coated on the surface of MSNs through a layer-by-layer (LbL) self-assembly technique, and were characterized by ζ-potential, FTIR, 13C NMR, SEM, TEM, XRD, and TG. The prepared carrier presented alternating positive and negative potentials when coated with the polyelectrolytes, and the surface of MSN-PLO/LC was rougher compared to the naked MSNs. The biocompatibility tests, including cytocompatibility, hemocompatibility, and histocompatibility, showed that MSNs biocompatibility could be improved by modifying LC. A high loading and sustained release drug delivery system was constructed after loading doxorubicin (DOX) into the prepared MSN-PLO/LC, which exhibited significant anti-proliferative efficiency in human cervical cancer cell lines (Hela). Therefore, the PLO/LC LbL NPs (layer-by-layer self-assembled nanoparticles coated with PLO/LC layers) based on MSNs, which is easily prepared by electrostatic interactions, can be considered a promising drug chemotherapeutic platform and delivery technique for future human cervical cancer therapy.

A dissolving and glucose-responsive insulin-releasing microneedle patch for type 1 diabetes therapy.

Diabetes and its complications have become crucial public health challenges worldwide. In this study, we aim to develop a dissolving and glucose-responsive insulin-releasing microneedle (MN) patch system, for minimally invasive and glucose-responsive insulin delivery for type 1 diabetes therapy. The MNs were composed of dissolving and biodegradable gelatin and starch materials, which encapsulated glucose-responsive insulin-releasing gold nanocluster (AuNC) nanocarriers. The fabricated MNs had a complete and uniform structure, consisting of an array of 11 × 11 conical needles, with a needle height of 756 µm, a bottom diameter of 356 µm, a tip diameter of 10 µm, and a tip-to-tip distance of 591 µm. The encapsulated AuNC nanocarriers as additives in the MNs enhanced the mechanical strength of the MNs, and facilitated the penetration of the MNs into the skins of mice. Moreover, the AuNC nanocarrier drugs in the MNs enabled MN patches with a glucose-responsive insulin releasing behavior. With one transdermal application of MN patches on the dorsal skin of mice, the MN patches effectively regulated the BG levels of mice in normoglycemic ranges for 1 to 2 days, and effectively alleviated the diabetic symptoms in type 1 diabetic mice. This dissolving and glucose-responsive insulin-releasing MN patch system realized a closed-loop administration of insulin with minimal invasion, providing great potential applications for type 1 diabetes therapy.

Synergistic induction of IL-23 by TNFα, IL-17A, and EGF in keratinocytes.

IL-23 is an inflammatory cytokine that plays an essential role in Th17 immunity by enhancing Th17 cell proliferation and survival, and Th17 cytokine production. IL-23 has pathogenic roles in the development of Th17-mediated inflammatory diseases including psoriasis. Despite successful treatment of psoriasis by blocking IL-23, the regulation of IL-23 expression in psoriasis patients is largely unknown. Dendritic cells are generally considered to be the primary source of IL-23 in psoriasis. While high levels of IL-23 are found in psoriatic epidermis, IL-23 expression in psoriatic keratinoctyes remains a controversial issue. In this study, we demonstrated that IL-23 production is induced by a combination of TNFα and IL-17A in human keratinocytes. Additionally, this IL-23 induction by TNFα and IL-17A is further increased in psoriatic keratinocytes and is enhanced by EGFR signaling. Although IL-23 is also robustly induced by toll-like receptor agonists in dendritic cells and macrophages, IL-23 expression in these cell types is not regulated by TNFα, IL-17A, and EGFR signaling. Given that IL-23 is essential for maintaining Th17 activation, IL-23 induction by TNFα, IL-17A, and EGF in keratinocytes could play an important pathological role in psoriasis pathogenesis as well as the cutaneous rash associated with EGFR inhibition therapy.

Inverse Correlation of TRIM32 and Protein Kinase C ζ in T Helper Type 2-Biased Inflammation.

Atopic dermatitis (AD) is a T helper (Th)2-biased disease with elevated expression of Th2 cytokines that responds to Th2 signaling blockade. TRIM32 is an E3 ubiquitin ligase with innate antiviral activity. In our previous studies, we showed that Trim32 null mice developed Th2-biased skin inflammation in response to imiquimod and associated a low level of TRIM32 with AD. In this study, we provide evidence that TRIM32 deficiency contributes to enhanced Th2 cell differentiation in vitro. Analysis of TRIM32-associated proteins from public databases identified protein kinase C (PKC)ζ as a TRIM32-associated protein that contributes to the regulation of Th2 signaling. We demonstrated that PKCζ was specifically ubiquitinated by TRIM32 and, further, that PKCζ stability tended to be increased in Th2 cells with a Trim32 null background. Furthermore, Prkcz null mice showed compromised AD-like phenotypes in the MC903 AD model. Consistently, a high PKCζ and low TRIM32 ratio was associated with CD4+ cells in AD human skin compared with those in healthy controls. Taken together, these findings suggest that TRIM32 functions as a regulator of PKCζ that controls the differentiation of Th2 cells important for AD pathogenesis.

Electrospinning With Lyophilized Platelet-Rich Fibrin Has the Potential to Enhance the Proliferation and Osteogenesis of MC3T3-E1 Cells.

Platelet-rich fibrin (PRF) as a reservoir of various growth factors plays an essential role in wound healing and tissue engineering at present. Electrospinning technology is an efficient approach to acquire artificial scaffold which has large specific surface area and high porosity. The goal of this study was to investigate the potential of electrospinning on the proliferation and osteogenesis of osteogenic precursor cells in vitro, with lyophilized PRF added as a component for electrospinning preparation. The surface structure of lyophilized PRF and nanofibers were investigated, and the proliferation, osteogenesis of MEC3T3-E1 cells with lyophilized PRF or nanofibers extract were studied. The results showed that the diameters of the lyophilized PRF pores were 1.51 ± 0.75 µm, and lyophilized PRF medium promoted the proliferation and osteocalcin (OCN) and osteopontin (OPN) genes expression of MEC3T3-E1 cells. Furthermore, the diameters of the polyvinyl alcohol/sodium alginate/lyophilized PRF (PVA/SA/PRF) fibers were 201.14 ± 40.14 nm. Compared to PVA/SA nanofibers extract and control medium, PVA/SA/PRF nanofibers extract also enhanced the proliferation and mineralization activity of MEC3T3-E1 cells. These results might be instructive to future therapeutics with PVA/SA/PRF electrospinning for bone tissue engineering or other applications.