Evaluation of Rhododendri Mollis Flos and its representative component as a potential analgesic.

Rhododendri Mollis Flos (R. mole Flos), the dried flowers of Rhododendron mole G. Don, have the ability to relieve pain, dispel wind and dampness, and dissolve blood stasis, but they are highly poisonous. The significance of this study is to explore the analgesic application potential of R. mole Flos and its representative component. According to the selected processing methods recorded in ancient literature, the analgesic activities of wine- and vinegar-processed R. mole Flos, as well as the raw product, were evaluated in a writhing test with acetic acid and a formalin-induced pain test. Subsequently, the HPLC-TOP-MS technique was utilized to investigate the changes in active components before and after processing once the variations in activities were confirmed. Based on the results, rhodojaponin VI (RJ-Vl) was chosen for further study. After processing, especially in vinegar, R. mole Flos did not only maintain the anti-nociception but also showed reduced toxicity, and the chemical composition corresponding to these effects also changed significantly. Further investigation of its representative components revealed that RJ-VI has considerable anti-nociceptive activity, particularly in inflammatory pain (0.3 mg/kg) and peripheral neuropathic pain (0.6 mg/kg). Its toxicity was about three times lower than that of rhodojaponin III, which is another representative component of R. mole Flos. Additionally, RJ-VI mildly inhibits several subtypes of voltage-gated sodium channels (IC50 > 200 µM) that are associated with pain or cardiotoxicity. In conclusion, the chemical substances and biological effects of R. mole Flos changed significantly before and after processing, and the representative component RJ-VI has the potential to be developed into an effective analgesic.

A derivative of trihydroxynaphthalenone and a pyrone metabolite from the endophytic fungus Talaromyces purpurpgenus.

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).

High-fat diet consumption promotes adolescent neurobehavioral abnormalities and hippocampal structural alterations via microglial overactivation accompanied by an elevated serum free fatty acid concentration.

Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.

Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue.

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.

Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.

PURPOSE: The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). EXPERIMENTAL DESIGN: A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. RESULTS: Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. CONCLUSION AND CLINICAL RELEVANCE: BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.

Aboveground Biomass Mapping and Analysis of Spatial Drivers in the Qinghai-Xizang Plateau Permafrost Zone: A Case Study of the Beilu River Basin.

Aboveground biomass (AGB) serves as a crucial measure of ecosystem productivity and carbon storage in alpine grasslands, playing a pivotal role in understanding the dynamics of the carbon cycle and the impacts of climate change on the Qinghai-Xizang Plateau. This study utilized Google Earth Engine to amalgamate Landsat 8 and Sentinel-2 satellite imagery and applied the Random Forest algorithm to estimate the spatial distribution of AGB in the alpine grasslands of the Beiliu River Basin in the Qinghai-Xizang Plateau permafrost zone during the 2022 growing season. Additionally, the geodetector technique was employed to identify the primary drivers of AGB distribution. The results indicated that the random forest model, which incorporated the normalized vegetation index (NDVI), the enhanced vegetation index (EVI), the soil-adjusted vegetation index (SAVI), and the normalized burn ratio index (NBR2), demonstrated robust performance in regards to AGB estimation, achieving an average coefficient of determination (R2) of 0.76 and a root mean square error (RMSE) of 70 g/m2. The average AGB for alpine meadows was determined to be 285 g/m2, while for alpine steppes, it was 204 g/m2, both surpassing the regional averages in the Qinghai-Xizang Plateau. The spatial pattern of AGB was primarily driven by grassland type and soil moisture, with q-values of 0.63 and 0.52, and the active layer thickness (ALT) also played a important role in AGB change, with a q-value of 0.38, demonstrating that the influences of ALT should not be neglected in regards to grassland change.

Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

Functional Characterization of the Niemann-Pick C2 Protein BdioNPC2b in the Parasitic Wasp Baryscapus dioryctriae (Chalcidodea: Eulophidae).

Reverse chemical ecology has been widely applied for the functional characterization of olfactory proteins in various arthropods, but few related studies have focused on parasitic wasps. Here, the odorant carrier Niemann-Pick C2 protein of Baryscapus dioryctriae (BdioNPC2b) was studied in vitro and in vivo. Ligand binding analysis revealed that BdioNPC2b most strongly bound to 2-butyl-2-octenal and which compound could elicit an EAG response and attracted B. dioryctriae adults. Moreover, this odorant attractant significantly improved the reproductive efficiency of B. dioryctriae compared to that of the control. Then, the relationship between BdioNPC2b and 2-butyl-2-octenal was validated by RNAi, and site-directed mutagenesis revealed the involvement of three key residues of BdioNPC2b in binding to 2-butyl-2-octenal through hydrogen bonding. Our findings provide not only a deeper understanding of the olfactory function of NPC2 in wasps but also useful information for improving the performance of the parasitoid B. dioryctriae as a biological control agent.

Novel solid self-emulsifying drug delivery system to enhance oral bioavailability of cabazitaxel.

In this study, a novel cabazitaxel solid self-emulsifying drug delivery system (CTX S-SEDDS) was developed by solvent evaporation and liquid-solid compression technology, which overcame the limitations of the traditional SEDDS and improved the oral bioavailability. From the results of solubility, pseudo-ternary phase diagram, and single-factor analysis, Tween 80 (surfactant), Tricaprylin (oil), and Glyceryl monooleate (oil) with the ratio of 30:55:15 showed optimized particle size (140.87 nm), short emulsification and high cabazitaxel (CTX) loading capacity (50 mg·g-1). Based on the liquid-solid compression mathematical model, Syloid XDP3050 was determined as carrier material and Syloid 244FP as coating material. The prepared CTX S-SEDDS showed excellent flowability, tabletability, and reconstitution property. In vivo pharmacokinetics in rats demonstrated the absolute bioavailability of CTX S-SEDDS (17.27 %) was significantly enhanced compared with CTX solution (1.69 %), which was close to that of CTX-SEDSS (20.48 %). Lymphatic absorption was verified by in vitro imaging to be an important absorption route for self-emulsifying preparations. These results suggested that CTX S-SEDDS could enhance oral bioavailability of poorly water-soluble drug cabazitaxel while avoiding SEDDS limitations and harnessing the dual advantages of solid and liquid preparations.

Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.

G protein-coupled receptors (GPCRs) are the largest family of druggable proteins encoded in the human genome, but progress in understanding and targeting them is hindered by the lack of tools to reliably measure their nuanced behavior in physiologically relevant contexts. Here, we developed a collection of compact ONE vector G-protein Optical (ONE-GO) biosensor constructs as a scalable platform that can be conveniently deployed to measure G-protein activation by virtually any GPCR with high fidelity even when expressed endogenously in primary cells. By characterizing dozens of GPCRs across many cell types like primary cardiovascular cells or neurons, we revealed insights into the molecular basis for G-protein coupling selectivity of GPCRs, pharmacogenomic profiles of anti-psychotics on naturally occurring GPCR variants, and G-protein subtype signaling bias by endogenous GPCRs depending on cell type or upon inducing disease-like states. In summary, this open-source platform makes the direct interrogation of context-dependent GPCR activity broadly accessible.

Semantic Segmentation of Remote Sensing Data Based on Channel Attention and Feature Information Entropy.

The common channel attention mechanism maps feature statistics to feature weights. However, the effectiveness of this mechanism may not be assured in remotely sensing images due to statistical differences across multiple bands. This paper proposes a novel channel attention mechanism based on feature information called the feature information entropy attention mechanism (FEM). The FEM constructs a relationship between features based on feature information entropy and then maps this relationship to their importance. The Vaihingen dataset and OpenEarthMap dataset are selected for experiments. The proposed method was compared with the squeeze-and-excitation mechanism (SEM), the convolutional block attention mechanism (CBAM), and the frequency channel attention mechanism (FCA). Compared with these three channel attention mechanisms, the mIoU of the FEM in the Vaihingen dataset is improved by 0.90%, 1.10%, and 0.40%, and in the OpenEarthMap dataset, it is improved by 2.30%, 2.20%, and 2.10%, respectively. The proposed channel attention mechanism in this paper shows better performance in remote sensing land use classification.

Coupling and coordinated evolution characteristics of regional economy-energy-carbon emission multiple systems: A case study of main China's Basin.

Comprehensive analysis of the Economy-Energy-Carbon Emission (EECE) system is beneficial for promoting sustainable social development. This study analyzes the system development of major watersheds in China from 2010 to 2019. The research fully considers the system's internal and external inputs and outputs and proposes an evaluation index system for regional EECE coupling and coordinated development. Then, using the difference in system weight allocation to improve the coupling and coordination model, the study explores the dynamic system's coupling and coordination. The results show that (1) The development of the system structure is relatively stable, but the overall development status is not ideal; (2) The downstream of China's main river basins has obvious economic advantages, while the energy system fluctuates greatly. The efficiency of the carbon emission system will decrease in areas with rapid economic development. The coupling and coordination level of the EECE system is better in the Yangtze River Basin than in the Yellow River Basin; (3) From the perspective of dynamic coordinated development, the main river basins have been divided into two states since 2012, but it is relatively stable overall. Regional dynamic coordination is often at a disadvantage in regions with rapid economic and energy development; (4) The coupling coordination degree of the two river basins has significant positive spatial autocorrelation. Most provinces' significant spatial clustering characteristics of the coupling coordination degree are High-High type. Low-Low type provinces are mainly concentrated downstream. The research process has certain reference significance for the collaborative governance of complex regional systems.

Scenario analysis of the eco-efficiency for municipal solid waste management: A case study of 211 cities in western China.

Mitigating greenhouse gas (GHG) emissions is vital for creating sustainable municipal solid waste management systems (MSWMS). In this study, we constructed an MSWMS considering recycling and carried out GHG emission accounting for MSWMS in western China from 2012 to 2021 based on the IPCC mass balance (MB) method. Then, we modeled the emission reduction potentials and economic benefits under different scenarios for 211 prefectural and county-level cities. We formed an eco-efficiency analysis framework that can be used to explore the sustainable development mode. Results revealed that: (1) Emissions from the western region's municipal solid waste (MSW) disposal exhibit an inverted "U" pattern, increasing at an annual rate of about 1.3 % since 2012, peaking in 2019, and then decreasing at rates of 14.4 % and 10.6 %. (2) The GHG emissions show a spatial pattern of decreasing evolution from east to west and south to north, and the provincial-municipal level shows different trends. (3) The SB3 scenario (optimization of landfill gas power generation technology) was the most ecologically efficient in 43 % of the western cities, followed by SB4 (33 %) and SA3 (24 %). (4) The development of integrated urban domestic waste management strategies by the three-level scenarios derived from this study will help local governments achieve the goal of sustainable urban development. Clarifying the differences in GHG emissions and eco-efficiency among cities will help provide policy recommendations for regions with similar characteristics to explore technically applicable, economically affordable implementation paths for city management according to local conditions.

Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy-based virtual screening and machine learning evaluation.

PIM2, part of the PIM kinase family along with PIM1 and PIM3, is often overexpressed in hematologic cancers, fueling tumor growth. Despite its significance, there are no approved drugs targeting it. In response to this challenge, we devised a thorough virtual screening workflow for discovering novel PIM2 inhibitors. Our process includes molecular docking and diverse scoring methods like molecular mechanics generalized born surface area, XGBOOST, and DeepDock to rank potential inhibitors by binding affinities and interaction potential. Ten compounds were selected and subjected to an adequate evaluation of their biological activity. Compound 2 emerged as the most potent inhibitor with an IC50 of approximately 135.7 nM. It also displayed significant activity against various hematological cancers, including acute myeloid leukemia, mantle cell lymphoma, and anaplastic large cell lymphoma (ALCL). Molecular dynamics simulations elucidated the binding mode of compound 2 with PIM2, offering insights for drug development. These results highlight the reliability and efficacy of our virtual screening workflow, promising new drugs for hematologic cancers, notably ALCL.

Would hyaluronic acid-induced mental bone resorption be a concern? A prospective controlled cohort study and an updated retrospective cohort study.

BACKGROUND: Hyaluronic acid (HA) is a widely used filler for face contouring and is generally believed to be safe and effective. However, there have been reports of HA-related bone erosion in the chin area without clear scientific data regarding its existence, incidence, and severity. This exploratory study was to evaluate HA-related mental bone resorption through a prospective, controlled, observer-blind, nonrandomized clinical trial and a retrospective cohort study. METHODS: On the one hand, a prospective, controlled, nonrandomized, single-shot HA-injection clinical trial was conducted. Computed tomographic scans were collected at baseline and at 6-12 months of follow-up for both HA-injection and control groups. On the other hand, an updated retrospective cohort study compared the HA-injection with a blank control group. The primary outcomes composed of three quantitative parameters [bone resorption index (BRI M and BRI N ), bone resorption thickness ratio] and one subjective evaluation index (severity ranking). Information about demographics, complications, and injection volume were also recorded. RESULTS: From June 2021 to March 2023, 78 patients were prospectively recruited for the study. There was a significant association between HA-injection and bone resorption [BRI M : pre (84.24±8.10%) vs post (79.21±8.70%), P <0.001; BRI N : pre 92.50% (73, 144%) vs 87.99% (63, 132%), P <0.001; bone thickness ratio: HA 24.08% (0, 48%) vs control 0 (0, 17%), P <0.001]. However, there was no difference in large-volume (>1 ml) and small-volume (≦1 ml) injection subgroups [bone resorption thickness ratio: (21.50±10.91%) vs (24.51±11.92%), P =0.350]. The imaging manifestation revealed discernible bone resorption in 35.90% of the patients, with an median bone resorption thickness ratio of 24.08%. Between October of 2019 and March 2023, 95 HA-injection patients (190 semimandibular cases), 95 normal controls were enrolled. The BRI M was significantly lower in the HA-injection group compared to the controls ( P <0.001). CONCLUSIONS: HA may induce bone resorption in the mentum. Large-scale randomized controlled clinical trial is warranted for further confirmation. Patients should be informed of this potential complication.

Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.

G protein-coupled receptors (GPCRs) are the largest family of druggable proteins in the human genome, but progress in understanding and targeting them is hindered by the lack of tools to reliably measure their nuanced behavior in physiologically-relevant contexts. Here, we developed a collection of compact ONE vector G-protein Optical (ONE-GO) biosensor constructs as a scalable platform that can be conveniently deployed to measure G-protein activation by virtually any GPCR with high fidelity even when expressed endogenously in primary cells. By characterizing dozens of GPCRs across many cell types like primary cardiovascular cells or neurons, we revealed new insights into the molecular basis for G-protein coupling selectivity of GPCRs, pharmacogenomic profiles of anti-psychotics on naturally-occurring GPCR variants, and G-protein subtype signaling bias by endogenous GPCRs depending on cell type or upon inducing disease-like states. In summary, this open-source platform makes the direct interrogation of context-dependent GPCR activity broadly accessible.

Fire needle acupuncture at Neiyingxiang (EX-HN 9) in the treatment of moderate and severe refractory perennial allergic rhinitis: A case report.

RATIONALE: In recent decades, the incidence of perennial allergic rhinitis (PAR) has been increasing annually. However, some patients could not achieve adequate symptomatic relief with routine pharmacological treatment. Consequently, there exists an urgent clinical imperative for the development of safe and efficacious treatments with sustained therapeutic impact to ameliorate the symptomatic burden and enhance the quality of life. PATIENT CONCERNS: The patient was a 35-year-old woman. She had suffered moderate and severe refractory PAR for decades and failed to sustain symptom mitigation from regular treatment. DIAGNOSES: Perennial allergic rhinitis. INTERVENTIONS: The patient underwent a 4-week course of fire needle acupuncture at Neiyingxiang, administered weekly, during which all allopathic medication was discontinued. OUTCOMES: The total nasal symptoms score, total non nasal symptoms score, rhinoconjunctivitis quality of life questionnaire, and the total nasal resistance of the patient were decreased after treatment and achieved symptomatic relief. Follow-up conducted 3 months post-treatment revealed enduring symptom relief, with only sporadic nasal congestion elicited by cold stimulus. LESSONS: This case proves that, fire needle acupuncture at Neiyingxiang may be beneficial in treating moderate and severe refractory PAR patient and have a lasting effect.

Simultaneous remediation of diesel-polluted soil and promoted ryegrass growth by non-thermal plasma pretreatment.

The remediation of petroleum-polluted soil has garnered significant global attention. In this study, a pot-culture experiment was conducted to assess the feasibility of using non-thermal plasma (NTP) as an efficient and economic-friendly pretreatment method in the phytoremediation of diesel-polluted soil. The remediation effectiveness was evaluated via both the removal of diesel and the ryegrass growth. Specifically, at the 50th d of ryegrass growth, the increase of diesel removal efficiency with NTP pretreatment ranged from 16 % to 30 %. Moreover, both clean and diesel-polluted soils pretreated by NTP promoted the growth of ryegrass in shoot lengths and biomass especially after the 35th d. It was found that nitrate nitrogen fixed by NTP not only stimulated the nitrate reductase activities in leaves and promoted plant growth, but also was transformed to more ammonia nitrogen for organism life activity. Subsequent investigation proved that the related nitrogen-metabolism activities of microbes were enriched in rhizosphere soils with NTP pretreatment. Furthermore, NTP treatment increased the abundance of beneficial microbial communities in diesel soil rhizosphere on the 42nd d of growth period. In addition, changes in the proportions of soil dissolved organic matter indicated enhanced nutrient cycling in soils with NTP pretreatment. These promotional effects underscored the contribution of NTP pretreatment in rapidly detoxifying diesel-contaminated soil within 10 min and accelerated the establishment of ryegrass ecosystem. This study provides valuable insights into the role of nitrogen fixation and offers an efficient and promising advanced approach for the phytoremediation of diesel-polluted soil with NTP pretreatment.

The Influence of Extracellular Vesicles Secreted by Dural Cells on Osteoblasts.

To explore the influence of extracellular vesicles secreted by dural cells (Dura-EVs) on osteoblasts. Our methodology involves assessing the effects of these EVs at concentrations of 50ug/ml, 100ug/ml, and 200ug/ml on osteoblasts proliferation, differentiation, migration, osteogenesis, and inhibition of apoptosis. We also treated a cranial defect model with injections of these Dura-EVs and monitored the healing rate of cranial defects. Tissue sections were analyzed using Hematoxylin and Eosin (H & E), Masson's trichrome, and immunofluorescence (IF) staining. Our results suggest that Dura-EVs can enhance osteoblasts proliferation, migration, differentiation, and osteogenesis in a dose-dependent manner in vitro. In vivo, Dura-EVs may promote the repair of skull defects. Dura-EVs have an important influence on osteoblasts, our findings shed light on a novel aspect of the dura mater's contribution to cranial osteogenesis.

Stimuli-Responsive Protein Hydrogels: Their Design, Properties, and Biomedical Applications.

Protein-based hydrogels are considered ideal biomaterials due to their high biocompatibility, diverse structure, and their improved bioactivity and biodegradability. However, it remains challenging to mimic the native extracellular matrices that can dynamically respond to environmental stimuli. The combination of stimuli-responsive functionalities with engineered protein hydrogels has facilitated the development of new smart hydrogels with tunable biomechanics and biological properties that are triggered by cyto-compatible stimuli. This review summarizes the recent advancements of responsive hydrogels prepared from engineered proteins and integrated with physical, chemical or biological responsive moieties. We underscore the design principles and fabrication approaches of responsive protein hydrogels, and their biomedical applications in disease treatment, drug delivery, and tissue engineering are briefly discussed. Finally, the current challenges and future perspectives in this field are highlighted.