Search Results (58,418)

Cosmetic dermatology has largely focused on topical applications targeting the stratum corneum. However, emerging evidence suggests that visible aging is a systemic readout of internal “organ clocks” and molecular dysregulation across the epidermis and dermis. This review proposes an “inside–out strategy” that seeks to re-conceptualize aesthetic vitality as a measurable indicator of systemic physiological resilience. The author describes theoretically proposed organ–skin axes, including the role of molecular signaling of kidney-derived klotho (KL1 fragment) via FGFR1-α–klotho complexes and muscle-derived irisin through the AMPK/PGC-1-α pathway in modulating skin homeostasis. Drawing on recent breakthroughs in non-human primate models (2023–2025), this synthesis explores the potential of systemic interventions—including nicotinamide adenine dinucleotide (NAD+) precursors (sirtuin 1 SIRT1 activators), senolytics (targeting BCL-2/p16), and glucagon-like peptide-1 (GLP-1) receptor agonists—as candidates to potentially synchronize these internal clocks. Furthermore, the review identifies direct regenerative interventions, such as retinoids (RAR/RXR signaling), chemical peels (HIF-1-α induction), exosomes (miR-21/29 delivery), and poly-L-lactic acid PLLA (mechanotransduction via YAP/TAZ), positioning them as potential physical and chemical epigenetic modulators that may support the restoration of cellular transcriptional fidelity. This article proposes a new paradigm for regenerative aesthetics that focuses on restoring the youthful phenotype by optimizing systemic molecular crosstalk and epigenetic transcriptional fidelity. Full article

Spent brewer’s yeast, a major by-product of the brewing industry, is a valuable source of bioactive compounds. The main technological limitation for their recovery is the rigid yeast cell wall, while the high nucleic acid content may restrict the direct use of yeast-derived extracts for human nutrition. In this study, pulsed electric field (PEF) treatment, applied alone or in combination with enzymatic hydrolysis, was investigated for the production of yeast-derived extracts with different compositions. PEF treatment performed in continuous-flow mode resulted in more than 98% of cells with irreversibly permeabilized membranes and enabled the rapid and selective release of low-molecular-weight intracellular compounds during subsequent incubation of the cells in water. Within 4 h, approximately 61% of total antioxidant activity, 65% of glutathione, and around 80% of free α-amino nitrogen and B-group vitamins were recovered at different rates, while the aqueous extracts were characterized by low purine nucleotide content. Electropermeabilized cells exhibited high sensitivity to enzymatic hydrolysis. After 6 h of incubation with 0.2% (v/v) Alcalase, the obtained hydrolysates contained 254 ± 17 mg/g DCW of protein, mostly in the form of peptides, 148.2 ± 17.3 mg/g DCW of free α-amino nitrogen, and a total phenolic content of 16.7 ± 1.9 mg GAE/g DCW. The maximal antioxidant activity (62.7 ± 9.3 mg TE/g DCW) was reached after 4 h of incubation, corresponding to a 2.7-fold increase compared with cell lysates. Overall, PEF treatment, applied alone or in combination with enzymatic hydrolysis, provides an efficient and mild approach for the production of yeast-derived extracts with tailored compositions and potential applications in the food, pharmaceutical, and cosmetic industries. Full article

Marine red algae have been reported to contain a variety of bioactive compounds that are effective in promoting wound-healing processes. In the present study, the wound-healing potential of Grateloupia angusta, which has been rarely explored, was examined using in vitro and in vivo models. A 70% ethanol extract of G. angusta (GAE) was prepared and profiled by liquid chromatography–mass spectrometry (LC-MS). Its effects on the wound-healing process were examined using three different types of cells that participate in this process, namely, Raw264.7, human umbilical vein endothelial cells (HUVECs), and human dermal fibroblasts (HDFs). Various assays including migration/scratch, tube formation, procollagen type I C-peptide production, and Western blotting were used to investigate the therapeutic potential of GAE. In vivo efficacy was tested in a mouse full-thickness skin incision wound model. In HUVECs, GAE increased viability, migration, tube formation, and vascular endothelial growth factor (VEGF) expression. Raw264.7 cells also showed increased VEGF production following GAE treatment. In HDFs, GAE did not affect proliferation and migration, but did increase collagen production. In mice, GAE accelerated wound closure from day 3 to day 5 and increased granulation/matrix with higher proliferating cell nuclear antigen (PCNA) and cluster of differentiation 31 (CD31) expression after a single topical application. In addition, keratin 14 (K14) expression was restored in GAE-treated wound tissues, suggesting improved epidermal re-epithelialization. Taken together, GAE promotes matrix production and pro-angiogenic activity in vitro and improves early wound repair in vivo, suggesting that G. angusta is a promising marine-derived candidate for wound-healing adjuvants. The results of the present study support further bioassay-guided fractionation and mechanistic validation in future studies. Full article

Human–robot interaction (HRI) takes place in dynamic environments where both humans and robots act as active agents, making the system inherently unpredictable. Abrupt movements can originate from either side and include human reflexes, fatigue, or unexpected reactions, as well as robot malfunctions, control errors, or task changes. These unpredictable events generate significant risks for both interaction fluency and safety, affecting not only the physical domain (e.g., collisions, excessive forces) but also cognitive aspects such as trust and predictability. Although different application areas present domain-specific challenges, a comprehensive overview of abrupt movements in HRI is still lacking, especially in the industrial scenario. This review aims to consolidate current knowledge regarding how abrupt phenomena are analyzed, prevented, and mitigated across various contexts and to offer new insights for researchers. In detail, after describing the literature search and the screening process, the review categorizes abrupt events, highlights key methodological approaches, and identifies gaps and future directions. By providing a structured synthesis of existing strategies, this work guides researchers in developing safer and more adaptive HRI frameworks capable of handling unpredictability. Full article

Measuring the service levels and spatial equity of urban parks constitutes a core research topic within the field of environmental justice. Against the backdrop of low-carbon urban transformation and sustainable development, this study constructs an ecological supply indicator calculation model for parks based on landscape ecology theory. Leveraging spatio-temporal big data such as Points of Interest (POI) and second-hand property transactions, it establishes a demand evaluation indicator system centered on human activity intensity. The study employs the Gini coefficient and location entropy to gauge the spatial equity of park supply–demand balance, utilizing the Z-score method to classify supply–demand matching types. An empirical case study is conducted in Shenzhen. Findings indicate that despite Shenzhen possessing abundant global-scale park resources, a Gini coefficient of 0.489 reveals significant deficiencies in the equitable provision of park services, with spatial distribution exhibiting pronounced social stratification. Specifically: (1) location entropy values exhibit an east-high, west-low spatial pattern; (2) areas with high location entropy are predominantly concentrated in Dapeng New District, rich in green space resources, where supply exceeds demand, creating an imbalance; and (3) areas with low locational entropy values are predominantly distributed in industrial clusters such as western Bao’an and western Longgang, exhibiting contradictory characteristics of low supply and high demand. Overall, the distribution of park and green space resources exhibits a polarized pattern. Full article

Hydra vulgaris, an ancient cnidarian, exhibits remarkable regenerative and neurogenic abilities, mediated by morphogenetic peptides, particularly the head activator peptide. This neuropeptide appears to regulate cell proliferation, differentiation, and nerve net maintenance in hydra and, surprisingly, exerts similar mitogenic and neurogenic effects in mammalian systems. Despite early enthusiasm, research on head activator has declined, due to controversies about its genetic origin, receptor identity, and artefacts generated during isolation. Nonetheless, a synthetic variant of head activator corresponding to the described sequence has consistently exhibited strong biological activity in a variety of mammalian cells. Experimental evidence implicates the sortilin-related receptor (SorLA) as a primary receptor in mammals, with potential modulatory roles for the G-protein-coupled receptor GPR37. This review consolidates current knowledge on the evolutionary context, molecular characteristics, and functional activities of head activator. Insights from mammalian systems highlight its pleiotropic effects across species. Given its neuroprotective, regenerative, and immunomodulatory properties, head activator may merit reconsideration as a therapeutic candidate for neurodegenerative disorders and regenerative medicine. Full article

Corneal fibrosis, clinically referred to as corneal scarring, disrupts the normal architecture and transparency of the cornea and remains a major cause of visual impairment worldwide. Although corneal transplantation can restore vision, its effectiveness is constrained by limited accessibility, donor tissue shortages, and the risk of allograft rejection. Treatments with human corneal stromal stem cells (hCSSCs) have demonstrated scarless healing in preclinical models of acute corneal injury. Here, we report that hCSSCs also modulated pre-existing corneal opacities. We established a reproducible in vivo model of chronic corneal opacity. Given that scar severity varies among corneas even after identical injuries, we developed a non-invasive, image-based method to quantify opacity volume longitudinally in individual corneas. Using this approach, we evaluated the scar-reducing potential of three hCSSC batches previously shown to inhibit acute scarring. Following cell treatment, the pre-existing opacity volumes gradually decreased. In vitro, hCSSCs exposed to pro-inflammatory stimulus exhibited increased metalloproteinase (MMP) activity relative to tissue inhibitor of metalloproteinase (TIMP), as indicated by an elevated MMP2/TIMP2 ratio. This shift may promote matrix remodeling and scar resolution. Overall, our findings provide proof-of-concept for hCSSC-based therapy as a strategy to reduce established corneal scarring and restore corneal transparency. Full article

Recent advances in enone chemistry have enabled the development of structurally optimized derivatives with improved anticancer selectivity. In this study, the cytotoxic activity and underlying mechanisms of sodium salts of four α,β-unsaturated enones (ES1–ES4), synthesized from vanillin-based scaffolds, were evaluated in human colorectal carcinoma (HCT-116), cervical adenocarcinoma (HeLa), and normal lung fibroblast (MRC-5) cell lines. All compounds exhibited concentration- and time-dependent cytotoxicity, with ES2 showing the highest potency (IC₅₀ = 14.25 μM in HCT-116 and 18.12 μM in HeLa at 72 h) and minimal toxicity toward MRC-5 cells (IC₅₀ > 90 μM). Although cisplatin demonstrated greater overall cytotoxicity, the enone salts displayed significantly higher selectivity indices, indicating a more favorable therapeutic window. Phase-contrast microscopy revealed characteristic morphological features of apoptosis, including cell rounding and membrane blebbing. Mechanistic investigations confirmed mitochondrial-mediated apoptosis, evidenced by increased early and late apoptotic populations, Bax upregulation, Bcl-2 downregulation, and caspase-3 activation. JC-10 staining demonstrated mitochondrial membrane depolarization accompanied by cytochrome c release. In addition, cell cycle analysis revealed pronounced G2/M phase arrest, particularly in HCT-116 cells. Collectively, these findings indicate that vanillin-derived enone sodium salts exert selective anticancer effects through mitochondrial apoptosis and cell cycle disruption, supporting their potential as low-toxicity anticancer candidates. Full article

This study quantifies the sustainable development thresholds of marine ecosystems under high-intensity human development by establishing a composite evaluation framework based on the Pressure–State–Response (PSR) model. Taking the Nantong sea area as a typical study region, this research indicates that prior to large-scale development (2006–2010), the comprehensive carrying capacity was higher in the northern region than in the south. The lowest capacity was observed near the Yangtze River Estuary, while the Subei Radial Sand Ridges in the north exhibited the highest capacity. Following the period of intensive coastal development (2016–2020), a significant decline in composite marine carrying capacity occurred in the northern radial sand ridge area, whereas the central waters remained stable. The nearshore areas in the south exhibited the poorest capacity. Despite a substantial increase in anthropogenic pressure, the overall decline of the sea area’s composite marine carrying capacity remains within an acceptable range, with all levels categorized as “Near Carrying Capacity” or above. Quantitative assessment of marine environmental carrying capacity and marine ecological carrying capacity provides an effective pathway for monitoring the specific status of the marine environment and determining whether critical thresholds have been reached under high-intensity human development scenarios. Full article

Current efforts to improve photodynamic therapy focus on nanomaterials that integrate deep tissue imaging with efficient reactive oxygen species generation. Gold nanoclusters (Au NCs) are promising alternatives to conventional photosensitizers due to their effective ROS production and enhanced biocompatibility when stabilized by a protein corona. However, both photosensitizers and Au NCs are typically activated by ultraviolet or visible light, which cannot penetrate deeper into tissues and is limited to superficial applications. Here, we report a near-infrared (NIR)-activated photodynamic nanoplatform based on core–shell upconverting nanoparticles (UCNPs; NaGdF₄:Yb³⁺,Er³⁺@NaGdF₄:Yb³⁺,Nd³⁺), functionalized with a protein corona containing bovine serum albumin-stabilized Au NCs (BSA–Au NCs) and photosensitizer chlorin e6 (Ce6). Spectroscopic data confirmed the formation of the UCNP-BSA–Au-Ce6 nanoplatform and demonstrated 32% energy transfer efficiency from UCNPs to Ce6, resulting in efficient reactive oxygen species generation under 808 nm irradiation. Cellular experiments confirmed the effective internalization and optimal biocompatibility of the nanoplatform in human breast cancer and healthy cells. Upon irradiation at 808 nm, the nanoplatform significantly reduced the viability of MDA-MB-231 cancer cells. These findings indicate that the UCNP-BSA–Au-Ce6 nanoplatform couples NIR activation with enhanced singlet oxygen production, providing a multifunctional platform for deep tissue imaging and NIR-activated photodynamic therapy. Full article

Background: Diabetic wounds represent a major clinical challenge due to persistent inflammation, oxidative stress, and impaired angiogenesis. Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential, and their therapeutic effects and optimization strategies for diabetic wounds warrant further exploration. Objective: This study aimed to improve the therapeutic efficacy of BMSCs in diabetic wound healing via chrysin pretreatment, as well as to evaluate the healing capacity and molecular mechanisms of the derived chrysin-pretreated BMSC-conditioned medium (Chrysin-CM). Methods: BMSCs were pretreated with 1 μM chrysin for 48 h to generate Chrysin-CM. The therapeutic effects were evaluated in vitro by analyzing the proliferation, migration, and matrix synthesis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs) under high-glucose (HG) conditions. In vivo, a diabetic mouse model with full-thickness excisional wounds was established and treated topically with Chrysin-CM. Transcriptomic sequencing and immune infiltration analysis of wound tissues were performed on day 14 in order to investigate the underlying mechanisms. Results: Chrysin pretreatment significantly enhanced the functional activity of BMSCs, accompanied by increased proliferative capacity and accelerated cell cycle progression. In vitro, Chrysin-CM demonstrated superior efficacy, robustly protecting HUVECs and HSFs from HG-induced dysfunction. In vivo, Chrysin-CM significantly accelerated wound closure, re-epithelialization, and neovascularization compared to the control. Mechanistically, RNA sequencing (RNA-seq) revealed that Chrysin-CM induced multi-level remodeling, characterized by reduced inflammatory gene expression and immune cell infiltration, along with the upregulation of regenerative genes and alternative splicing events. Conclusions: Chrysin successfully improved the therapeutic efficacy of the BMSC secretome in wound healing. Chrysin-CM effectively accelerated diabetic wound healing by actively resolving chronic inflammation and promoting angiogenesis and structural remodeling, thus providing a potential strategy for stem cell-based cell-free treatment for chronic diabetic wounds. Full article

Vascular endothelial growth factor (VEGF)-driven pathological angiogenesis constitutes a primary driver of neovascular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). Although anti-VEGF agents demonstrate clinical efficacy, their limited intraocular half-life mandates repeated intravitreal injections, thereby highlighting the imperative for long-term therapeutic strategies. In the present study, we assessed the anti-angiogenic potential of retinal organoid-derived microRNAs (miRNA) delivered via an engineered adeno-associated virus vector. Human umbilical vein endothelial cells (HUVEC) were transduced with AAV2.7m8 vectors to overexpress three candidate miRNA (miR-26a, miR-122, and let-7a), followed by VEGF stimulation to evaluate downstream signaling pathways and angiogenic responses. AAV2.7m8-mediated transduction of HUVEC demonstrated high efficiency without inducing detectable cytotoxicity. Overexpression of these miRNA markedly attenuated VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Functional assays demonstrated suppression of endothelial cell proliferation and cell cycle progression, with miR-122-5p additionally inhibiting migration. All three miRNA substantially inhibited capillary-like tube formation. In aggregate, these results affirm that AAV2.7m8-mediated delivery of retinal organoid-derived miRNA —namely miR-26a-5p, miR-122-5p, and let-7a-5p—markedly suppresses VEGF-induced angiogenic signaling cascades and endothelial cell activation in vitro, thereby establishing their viability as a sustained therapeutic approach for pathological retinal neovascularization. Full article

Background/Objectives: Antibodies are a rapidly expanding field in drug discovery, but their monospecificity limits therapeutic applications, particularly in complex inflammatory diseases. Multispecific therapeutics, which combine variable regions targeting two or more antigens, offer potential advantages such as enhanced efficacy, broader target modulation, and reduced side effects. This study aimed to identify and characterize bispecific, VHH-based antibodies simultaneously targeting IL-6 and IL-17A—two key cytokines involved in autoimmune and chronic inflammatory conditions. Methods: A phage display screening was conducted using llama-derived VHH libraries to select binders against human IL-6 and IL-17A. Binding affinities of individual VHHs and assembled bispecific constructs were assessed using Bio-Layer Interferometry (BLI). Functional activity was evaluated using reporter cell lines responsive to IL-6 and IL-17A signaling. Biophysical and quality assessments of selected VHHs and bispecific antibodies were performed using the Uncle screening platform and LabChip capillary electrophoresis. Results: Several high-affinity VHH binders were identified for both IL-6 and IL-17A, and incorporated into bispecific antibody formats. The bispecific candidates exhibited simultaneous inhibition of both cytokine pathways in functional reporter assays. Biophysical characterization confirmed good stability and purity profiles for selected molecules. Conclusions: This study demonstrates the feasibility of generating stable, functional bispecific VHH-based antibodies targeting IL-6 and IL-17A. These constructs show potential as therapeutic agents for treating autoimmune and chronic inflammatory diseases by modulating multiple signaling pathways simultaneously. Full article

FAM3A, FAM3B, FAM3C and FAM3D are members of the “family with sequence similarity 3” (FAM3) gene family, an emerging class of cytokine-like proteins with a unique structural globular β-β-α fold and distinct biological functions. With widespread expression in tissue, organs and in many cell types, their specific roles in human diseases have been the focus of much research. FAM3A acts as a positive regulator of metabolic health, typically activating canonical pro-survival and metabolic pathways. FAM3B, also called PANDER (PANcreatic DERived Factor), exerts critical physiological functions in the regulation of glycemic levels via promotion of hepatic glucose production and pancreatic β-cell insulin secretion. FAM3C, also named ILEI (Interleukin-like EMT inducer), is involved as an inducer of epithelial–mesenchymal transition (EMT) and cancer metastasis, as well as osteoblast differentiation and bone mineralization. FAM3D is a gut-secreted protein and potential regulator of gastrointestinal homeostasis and microbiota-induced inflammation. Here we provide an overview of previous studies supporting that FAM3 proteins act through putative membrane receptors and co-partners, including fibroblast growth factor receptor (FGFR), leukemia inhibitory factor receptor (LIFR), formyl peptide receptor (FPR1/2), to activate diverse downstream signaling pathways on different cellular contexts. Basic and clinical studies suggest that the FAM3 family influences both obesity, diabetes, and other metabolic disorders; thus, its expression may have diagnostic potential. The differential and often cancer-specific expression patterns make members of the FAM3 family promising candidates for biomarkers and therapeutic targets of some types of neoplasia. Full article

Human activities and climate change are influencing the survival and distribution of species, threatening the current distribution pattern of biodiversity and potentially leading to the “sixth mass extinction.” The forest musk deer (Moschus berezovskii) is among the most numerous and widely distributed musk deer species in China. However, its habitat is severely threatened by human activities and climate change. Due to the lack of field surveys and research data, it is difficult to assess the threats posed by human activities and climate change effectively. In this study, we integrate the new records of forest musk deer with climate and human activity data, and apply the MaxEnt species distribution model to evaluate the impact of human activities and climate change on the forest musk deer under current conditions and future scenarios (SSP1-2.6 and SSP5-8.5 for the 2030s, 2050s, and 2070s). Our results showed that the forest musk deer prefer areas with high vegetation cover (NDVI > 0.7), low GDP, and low levels of human activity disturbance. The areas of high-suitability habitats are 90.10 × 10⁴ km², 72.85 × 10⁴ km², and 30.43 × 10⁴ km², respectively. The optimal climatic conditions are an annual precipitation (BIO12) of 750–1500 mm and a seasonal temperature variation (BIO4) of 500–600. Their occurrence probability is highest at elevations between 1500 and 3000 m. Under the current climate conditions, the area of high-suitability habitats is estimated at 5.54 × 10⁴ km², primarily distributed across central–northern Sichuan, northwestern Guangxi, and southern Gansu. Under the future climate scenarios, low and medium-suitability habitats are projected to shrink to varying degrees, whereas the high-suitability area is expected to expand, particularly under the SSP5-8.5-2030s scenario where it is projected to increase by 2.88 × 10⁴ km². The centroid of suitable habitat is projected to shift toward higher-elevation areas in northwestern China, with regional hotspots emerging in southwestern regions such as central–northern Sichuan and northwestern Guangxi. These elevational and distributional shifts highlight the vulnerability of current habitats and the importance of adaptive conservation strategies to strengthen species protection, including continuously advancing forest protection programs, mitigating the impact of human activities in high-altitude areas, and strengthening the protection of key areas in the southwestern region. Full article