Search Results (153)

Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and their receptor (receptor for AGEs [RAGE]) as contributing factors to skin dullness. AGEs themselves have a yellowish hue, contributing to “yellow dullness.” Additionally, AGE–RAGE signaling promotes melanin production in melanocytes and impairs keratinocyte differentiation as a result of inflammation. Therefore, regulating the AGE–RAGE interaction may help reduce skin dullness. Through screening various natural ingredients, we found that peony root extract (PRE) inhibits AGE formation and blocks AGE–RAGE binding. Furthermore, the presence of PRE leads to the suppression of AGE-induced melanin production in melanocytes and the restoration of impaired keratinocyte differentiation in glycated basement membrane components. In a human clinical study, topical application of a 1% PRE-containing lotion for 2 weeks significantly reduced melanin content, with a trend toward decreased AGE accumulation and visible spots on the cheeks. These findings support the potential of PRE as a multifunctional cosmetic ingredient that comprehensively addresses skin dullness by modulating the AGE–RAGE interaction. Full article

Tumor immunotherapy has revolutionized cancer treatment by harnessing the immune system to recognize and eliminate malignant cells, with immune checkpoint inhibitors targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) demonstrating remarkable clinical success. However, challenges such as treatment resistance, immune-related adverse effects, and high costs highlight the need for novel therapeutic approaches. Aptamers, short, single-stranded oligonucleotides with high specificity and affinity for target molecules, have emerged as promising alternatives to conventional antibody-based therapies. This review provides a comprehensive analysis of aptamer-based strategies targeting immune checkpoints, with a particular focus on PD-1/PD-L1 and CTLA-4. We summarize recent advances in aptamer design, including bispecific and multifunctional aptamers, and explore their potential in overcoming immune resistance and improving therapeutic efficacy. Additionally, we discuss strategies to enhance aptamer stability, bioavailability, and tumor penetration through chemical modifications and nanoparticle conjugation. Preclinical and early clinical studies have demonstrated that aptamers can effectively block immune checkpoint pathways, restore T-cell activity, and synergize with other immunotherapeutic agents to achieve superior anti-tumor responses. By systematically reviewing the current research landscape and identifying key challenges, this review aims to provide valuable insights into the future directions of aptamer-based cancer immunotherapy, paving the way for more effective and personalized treatment strategies. Full article

The increasing frequency of extreme weather events, combined with the historic degradation of urban water systems, has prompted cities worldwide to reconsider the role of water in urban planning. This study examines the restoration and integration of historical watercourses into contemporary urban environments through blue and green infrastructure (BGI). Focusing on three case study cities—Poznań (Poland), Milan (Italy), and Beijing (China)—this research explores both spatial and regulatory conditions for reintroducing surface water into cityscapes. Utilizing historical maps, contemporary land use data, and spatial planning documents, this study applies a GIS-based multi-criteria decision analysis (GIS-MCDA) to assess restoration potential. The selected case studies, including the redesign of Park Rataje in Poznań, canal daylighting projects in Milan, and the multifunctional design of Beijing’s Olympic Forest Park, illustrate diverse approaches to ecological revitalization. The findings emphasize that restoring or recreating urban water systems can enhance urban resilience, ecological connectivity, and the quality of public space. Full article

Nitrogen-doped carbon dots (NCDs) exhibiting superior fluorescence characteristics were synthesized employing o-phenylenediamine and 2-methylimidazole as precursors. The synthesized NCDs exhibited yellow photoluminescence with an excitation/emission maxima of 410/554 nm with a quantum yield of 28.41%. The presence of pyridinic N, pyrrolic N, graphitic N, and amino N functionalities on the NCDs’ surface provided strong evidence for the successful nitrogen doping of the carbon dots. Upon exposure to hydrogen peroxide (H₂O₂), the NCDs exhibited a significant reduction in fluorescence intensity, which could be restored by the addition of ascorbic acid (AA), demonstrating a quantitative relationship between ascorbic acid and fluorescence efficiency. A novel fluorescence “off–on” system utilizing these NCDs was developed for the quantification of AA. The sensing mechanism relies on H₂O₂-induced fluorescence quenching via the selective oxidation of the NCDs’ surface, followed by fluorescence restoration upon AA addition due to the reduction in surface defects. Meanwhile, further experiments confirmed that the quenching mechanism was static quenching. The NCDs demonstrated a limit of detection (LOD) of 0.605 μM for AA detection. The use of NCDs for AA sensing was validated through the analysis of commercially available beverages. This study aimed to establish a simplified method for ascorbic acid detection. The experimental findings indicated that the developed technique exhibited high accuracy in quantifying ascorbic acid. These findings suggest that the developed NCDs possess considerable potential as a multifunctional sensing tool for various analytical applications. Full article

Immunosuppression dramatically increases tissue and organ susceptibility to infection, injury, and even cancer. This poses a serious threat to human and animal health. In a previous study, we established a platform for high-throughput design and screening of multifunctional peptides. Using this platform, we successfully identified a novel hybrid peptide, VLP-Aβ (VA), which exhibits both immunomodulatory and antioxidant properties. This study aimed to evaluate the immunomodulatory activity of VA and investigate the underlying molecular mechanisms. In the cyclophosphamide (CTX)-induced immunodeficient mouse model, VA significantly alleviated CTX-induced weight loss. It also restored thymus and spleen indices, and increased serum immunoglobulins (IgA, IgM, IgG) and cytokines (TNF-α, IL-6, IL-1β) levels. VA also improved splenic lymphocyte proliferation, CD4⁺/CD8⁺ T cell ratios, and NK cell cytotoxicity. At the cellular level, western blot analysis showed that VA activated the TLR4-NF-κB pathway in RAW264.7 macrophages. Mechanistically, inhibition of the MD2 protein by L6H21 abolished VA’s immunomodulatory effects. This confirms MD2 as a critical mediator. Molecular docking and dynamics simulations revealed that VA binds stably to the hydrophobic pocket of MD2. These findings suggest that VA exerts immunomodulatory effects by stimulating MD2 and activating the TLR4-NF-κB pathway, which provides new ideas, techniques, and approaches for the development of novel peptide immunomodulators. Full article

Calcium (Ca²⁺) signaling is a fundamental regulatory mechanism controlling essential processes in the endothelium, vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM), including maintaining the endothelial barrier, modulation of vascular tone, and vascular remodeling. Cytosolic free Ca²⁺ concentration is tightly regulated by a balance between Ca²⁺ mobilization mechanisms, including Ca²⁺ release from the intracellular stores in the sarcoplasmic/endoplasmic reticulum and Ca²⁺ entry via voltage-dependent, transient-receptor potential, and store-operated Ca²⁺ channels, and Ca²⁺ elimination pathways including Ca²⁺ extrusion by the plasma membrane Ca²⁺-ATPase and Na⁺/Ca²⁺ exchanger and Ca²⁺ re-uptake by the sarco(endo)plasmic reticulum Ca²⁺-ATPase and the mitochondria. Some cell membranes/organelles are multifunctional and have both Ca²⁺ mobilization and Ca²⁺ removal pathways. Also, the individual Ca²⁺ handling pathways could be integrated to function in a regenerative, capacitative, cooperative, bidirectional, or reciprocal feed-forward or feed-back manner. Disruption of these pathways causes dysregulation of the Ca²⁺ signaling dynamics and leads to pathological cardiovascular conditions such as hypertension, coronary artery disease, atherosclerosis, and vascular calcification. In the endothelium, dysregulated Ca²⁺ signaling impairs nitric oxide production, reduces vasodilatory capacity, and increases vascular permeability. In VSMCs, Ca²⁺-dependent phosphorylation of the myosin light chain and Ca²⁺ sensitization by protein kinase-C (PKC) and Rho-kinase (ROCK) increase vascular tone and could lead to increased blood pressure and hypertension. Ca²⁺ activation of matrix metalloproteinases causes collagen/elastin imbalance and promotes vascular remodeling. Ca²⁺-dependent immune cell activation, leukocyte infiltration, and cholesterol accumulation by macrophages promote foam cell formation and atherosclerotic plaque progression. Chronic increases in VSMCs Ca²⁺ promote phenotypic switching to mesenchymal cells and osteogenic transformation and thereby accelerate vascular calcification and plaque instability. Emerging therapeutic strategies targeting these Ca²⁺-dependent mechanisms, including Ca²⁺ channel blockers and PKC and ROCK inhibitors, hold promise for restoring Ca²⁺ homeostasis and mitigating vascular disease progression. Full article

This study investigated the potential cosmetic properties of the ethyl acetate (EtOAc) fraction obtained from the roots of Astilboides tabularis (Hemsl.) Engl., focusing on skin-whitening, antiwrinkle, and moisturizing effects using cell-based assays and three-dimensional (3D) artificial skin models (Neoderm-ED and Neoderm-ME). The EtOAc fraction showed significant dose-dependent inhibitory activity against tyrosinase (TYR) (72.0% inhibition at 50 µg/mL), comparable to that of kojic acid. In α-melanocyte-stimulating hormone (α-MSH)-stimulated Neoderm-ME artificial skin containing melanocytes, the EtOAc fraction reduced melanin synthesis at concentrations of 50 and 75 µg/mL and decreased melanogenesis-related gene expression, including TYR, microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and TRP-2. In the antiwrinkle assays, the EtOAc fraction effectively inhibited elastase activity (41.5% inhibition at 10 µg/mL), exceeding the efficacy of ursolic acid. In the Neoderm-ED artificial skin model, the EtOAc fraction reversed structural damage induced by particulate matter (PM10), restoring epidermal thickness and dermal density. This improvement was supported by the increased expression of skin barrier and antiwrinkle genes, including filaggrin, hyaluronic acid synthase-1 (HAS-1), HAS-2, aquaporin-3 (AQP-3), collagen type I alpha 1 chain (COL1A1), elastin, tissue inhibitor of metalloproteinases-1 (TIMP-1), and TIMP-2, as well as decreased expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9). Our results indicate that the EtOAc fraction from A. tabularis root has considerable potential as a multifunctional cosmetic. Full article

In this study, we developed a multifunctional graphene oxide (GO)-based nanoprobe co-loaded with antisense peptide nucleic acid (PNA) and the chemotherapeutic agent doxorubicin (DOX). The nanoplatform was strategically functionalized with folic acid ligands to enable folate receptor-mediated tumor targeting. Upon cellular internalization, the antisense PNA component selectively hybridized with human telomerase reverse transcriptase (hTERT) mRNA through sequence-specific recognition, inducing structural detachment from the GO surface. This displacement restored the fluorescence signal of previously quenched fluorophores conjugated to the PNA strand, thereby enabling the real-time in situ detection and quantitative fluorescence imaging of intracellular hTERT mRNA dynamics. The antisense PNA component effectively reduced the hTERT mRNA level and downregulated telomerase activity via an antisense gene regulation pathway, while the pH-responsive release of DOX induced potent cancer cell apoptosis through chemotherapeutic action. This combinatorial therapeutic strategy demonstrated enhanced anticancer efficacy compared to single-modality treatments, achieving a 60% apoptosis induction in HeLa cells through coordinated gene silencing and chemotherapy. This study establishes GO as a promising dual-drug nanocarrier platform for developing next-generation theranostic systems that integrate molecular diagnostics with multimodal cancer therapy. Full article

TSGA10, a multifunctional protein critical for mitochondrial coupling and metabolic regulation, plays a paradoxical role in cancer progression and carcinogenesis. Here, we outline a potential mechanism by which TSGA10 mediates metabolism in oncogenesis and thermal modulation. Initially identified in spermatogenesis, TSGA10 interacts with mitochondrial Complex III: it directly binds cytochrome c1 (CytC1). In our model, TSGA10 optimizes electron transport to minimize reactive oxygen species (ROS) and heat production while enhancing Adenosine Triphosphate (ATP) synthesis. In cancer, TSGA10’s expression is context-dependent: Its downregulation in tumors like glioblastoma might disrupt mitochondrial coupling, promoting electron leakage, ROS accumulation, and genomic instability. This dysfunction would be predicted to contribute to a glycolytic shift, facilitating tumor survival under hypoxia. Conversely, TSGA10 overexpression in certain cancers suppresses HIF-1$\alpha$, inhibiting glycolysis and metastasis. TSGA10 and HIF-1$\alpha$ engage in mutual counter-regulation—TSGA10 represses HIF-1$\alpha$ to sustain oxidative phosphorylation (OXPHOS), while HIF-1$\alpha$ suppression of TSGA10 under hypoxia or thermal stress amplifies glycolytic dependency. This interplay is pivotal in tumors adapting to microenvironmental stressors, such as cold-induced mitochondrial uncoupling, which mimics brown adipose tissue thermogenesis to reduce ROS and sustain proliferation. Tissue-specific TSGA10 expression further modulates cancer susceptibility: high levels in the testes and brain may protect against thermal and oxidative damage, whereas low expression in the liver permits HIF-1$\alpha$-driven metabolic plasticity. Altogether, our model suggests that TSGA10 plays a central role in mitochondrial fidelity. We suggest that its crosstalk with oncogenic pathways position it as a metabolic rheostat, whose dysregulation fosters tumorigenesis through ROS-mediated mutagenesis, metabolic reprogramming, and microenvironmental remodeling. Targeting the hypothesized TSGA10-mediated mitochondrial coupling may offer therapeutic potential to disrupt cancer’s adaptive energetics and restore metabolic homeostasis. Full article

Background/Objectives: Dry eye disease (DED), also known as “keratoconjunctivitis sicca”, is a common chronic ocular surface disease accompanied by inflammation and diminished tear production. Bovine Lactoferrin (BLF), a multi-functional iron-binding glycoprotein found in tears, decreased significantly in patients with DED, used for the treatment of dry eye, conjunctivitis, and ocular inflammation. BLF has limited therapeutic efficacy due to poor ocular bioavailability. Methods: This study developed and optimized a BLF-loaded nanosuspension (BLF-NS) using the Box–Behnken Design (BBD). Optimized BLF-NS was then incorporated with polyvinyl pyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) dissolving microneedles (MNs). The formulations were characterized by Scanning and transmission microscopy, DSC, FTIR, ex vivo studies in corneal tissue from sheep and tested for its antibacterial and antifungal efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Aspergillus niger, respectively. Moreover, they were tested for their Benzalkonium chloride (BCL) dry eye in a rabbit model. Results: The optimized nanosuspension showed a vesicle size of (215 ± 0.45) nm, a Z.P (zeta potential) of (−28 ± 0.34) mV, and an Entrapment Efficiency (EE%) of (90 ± 0.66) %. The MNs were fabricated using a ratio of biodegradable polymers, PVP/HPMC. The resulting BLF-NS-MNs exhibited sharp pyramidal geometry with high mechanical strength, ensuring ocular insertion. In vitro release showed 95% lactoferrin release over 24 h, while ex vivo permeation achieved 93% trans-corneal delivery. In vivo, BLF-NS-MNs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6, MMP-9, IL-1β, MCP-1) and upregulated antioxidant and anti-inflammatory genes (PPARA, SOD 1), restoring their levels to near-normal (p < 0.001). Conclusions: The nanosuspension combined with MNs has shown higher ocular tolerance against DED ensured by the Draize and Schirmer Tear Test. Full article

Soil heavy metal contamination poses critical challenges to ecological sustainability in mining regions, particularly in acidic soils from copper sulfide mines. This study developed a sustainable remediation strategy using a carbonyl iron powder–biochar composite (CIP@BC) derived from agricultural waste (rice husk) and industrial byproducts. The composite was synthesized through an energy-efficient mechanical grinding method at a 10:1 mass ratio of biochar to carbonyl iron powder, aligning with circular economy principles. Material characterization revealed CIP particles uniformly embedded within biochar’s porous structure, synergistically enhancing surface functionality and redox activity. CIP@BC demonstrated exceptional Cu²⁺ immobilization capacity (910.5 mg·g⁻¹), achieved through chemisorption and monolayer adsorption mechanisms. Notably, the remediation process concurrently improved key soil health parameters. Soil incubation trials demonstrated that 6% CIP@BC application elevated soil pH from 4.27 to 6.19, reduced total Cu content by 29.43%, and decreased DTPA-extractable Cu by 67.26%. This treatment effectively transformed Cu speciation from bioavailable to residual fractions. Concurrent improvements in electrical conductivity (EC), cation exchange capacity (CEC), soil organic matter (OM), and soil water content (SWC) collectively highlighted the composite’s multifunctional remediation potential. This study bridges environmental remediation with sustainable land management through an innovative waste-to-resource approach that remediates acidic mine soils. The dual functionality of CIP@BC in contaminant immobilization and soil quality restoration provides a scalable solution. Full article

Aiming at the problem that conventional friction reducers used in fracturing cannot simultaneously possess properties such as temperature resistance, salt resistance, shear resistance, rapid dissolution, and low damage. Under the design concept of “medium-low molecular weight, salt-resistant functional monomer, supramolecular physical crosslinking aggregation, and enhanced chain mechanical strength”, acrylamide, sulfonic acid salt-resistant monomer 2-acrylamide-2-methylpropanesulfonic acid, hydrophobic association monomer, and rigid skeleton functional monomer acryloyl morpholine were introduced into the friction reducer molecular chain by free radical polymerization, and combined with the compound suspension technology to develop a new type of multi-functional viscous friction reducer suspension (SAMD), the comprehensive performance of SAMD was investigated. The results indicated that the critical micelle concentration of SAMD was 0.33 wt%, SAMD could be dissolved in 80,000 mg/L brine within 3.0 min, and the viscosity loss of 0.5 wt% SAMD solution was 24.1% after 10 min of dissolution in 80,000 mg/L brine compared with that in deionized water, the drag reduction rate of 0.1 wt% SAMD solution could exceed 70% at 120 °C and still maintained good drag reduction performance in brine with a salinity of 100,000 mg/L. After three cycles of 170 s⁻¹ and 1022 s⁻¹ variable shear, the SAMD solution restored viscosity quickly and exhibited good shear resistance. The Tan δ (a parameter characterizing the viscoelasticity of the system) of 1.0 wt% SAMD solution was 0.52, which showed a good sand-carrying capacity, and the proppant settling velocity in it could be as low as 0.147 mm/s at 120 °C, achieving the function of high drag reduction at low concentrations and strong sand transportation at high concentrations. The viscosity of 1.4 wt% SAMD was 95.5 mPa s after shearing for 120 min at 140 °C and at 170 s⁻¹. After breaking a gel, the SAMD solution system had a core permeability harm rate of less than 15%, while the SAMD solution also possessed the performance of enhancing oil recovery. Compared with common friction reducers, SAMD simultaneously possessed the properties of temperature resistance, salt resistance, shear resistance, rapid dissolution, low damage, and enhanced oil recovery. Therefore, the use of this multi-effect friction reducer is suitable for the development of unconventional oil reservoirs with a temperature lower than 140 °C and a salinity of less than 100,000 mg/L. Full article

Background/Objectives: Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. Methods: A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. Results: RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. Conclusions: The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease. Full article

Background: Spinal cord injury (SCI) is a devastating neurological condition with limited therapeutic options. Current clinical interventions predominantly rely on prolonged or high-dose pharmacological regimens, often causing systemic toxicity and adverse events. Although black phosphorus nanosheets (BPNSs) exhibit remarkable reactive oxygen species (ROS)-scavenging capacity to mitigate oxidative damage, their rapid degradation severely compromises their therapeutic efficacy. Methods: This study presents a thermosensitive hydrogel with rapid gelation properties by incorporating different proportions and concentrations of sodium alginate (SA) into a chitosan/β-glycerophosphate (CS/β-GP) hydrogel and loading it with BPNS for the treatment of SCI in rats. In vitro, the physical properties of the composite were characterized and the cytotoxicity and ROS scavenging abilities were assessed using PC12 cells; in vivo, behavioral tests, histopathological analysis, transcriptomics, immunohistochemistry, and Western blotting were performed to explore the therapeutic effects and mechanisms. Results: The results demonstrate that this hydrogel effectively slows BPNS degradation, exhibits a high ROS scavenging capacity, reduces lipid peroxidation, and thereby inhibits ferroptosis and apoptosis, offering neuroprotective effects and promoting motor function recovery. Conclusions: Our findings establish the CS/β-GP/SA-BPNS hydrogel as a multifunctional therapeutic platform for SCI, synergizing sustained drug release with ROS–ferroptosis–apoptosis axis modulation to achieve neuroprotection and functional restoration. This strategy provides a translatable paradigm for combining nanotechnology and biomaterial engineering in neural repair. Full article

This study explores the potential of ginseng-derived peptides (GPs) as multifunctional bioactive agents for skincare. Unlike previous research into ginseng saponins and polysaccharides, we identified that ginseng extracts containing water-soluble small molecules and polypeptides exhibit potent antioxidant, anti-inflammatory, and anti-aging properties. In vitro assays revealed that ginseng peptide extract (GPE) reduced reactive oxygen species (ROS) and inflammatory cytokines (IL-6, TNF-α, IL-1β) in RAW264.7 macrophages while enhancing collagen synthesis in human skin fibroblasts (HSFs). Validation using 3D epidermal and dermal models further confirmed GPE’s ability to mitigate UV-induced damage, restore skin barrier proteins (filaggrin, loricrin), and increase collagen content. In addition, we screened 19 candidate peptides from ginseng extract using machine learning and prioritized their interaction with skin aging and inflammation-related targets. Three peptides (QEGIYPNNDLYRPK, VDCPTDDATDDYRLK, and ADEVVHHPLDKSSEVE) demonstrated significant collagen-promoting, antioxidant, and anti-inflammatory effects in cellular models. These findings highlight the efficacy of computational approaches in identifying natural bioactive ingredients, positioning ginseng peptides as promising candidates for innovative cosmeceutical formulations targeting inflammaging and skin rejuvenation. Full article