Regulation of Protein Conformation Enables Cell-Selective Targeting of Virus-Mimicking Nanoparticles for siRNA Therapy of Glioblastoma.

Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood-brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.

Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage.

BACKGROUND: Dry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients' quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier. This calls for investigations to overcome these challenges associated with ocular drug administration. RESULTS: A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study. In terms of delivery, PHP-DPS@INS nanoparticles (NPs) overcame the ocular surface transport barrier by adopting the strategy of "ocular surface electrostatic adhesion-lysosomal site-directed escape". In terms of therapy, PHP-DPS@INS achieved mitochondrial targeting and antioxidant effects through SS-31 peptide, and exerted an anti-inflammatory effect by loading insulin to reduce mitochondrial inflammatory metabolites. Ultimately, the synergistic action of "anti-inflammation-antioxidation-mitochondrial function restoration" breaks the vicious cycle associated with DED. The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro. Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1ß, IL-6, and TNF-α). Additionally, PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production and facilitated mitochondrial structural repair. In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability. It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice. Moreover, it demonstrated favorable safety profiles both in vitro and in vivo. CONCLUSION: In summary, this study successfully developed a comprehensive DED management nanosystem that overcame the ocular surface transmission barrier and disrupted the vicious cycle that lead to dry eye pathogenesis. Additionally, it pioneered the regulation of mitochondrial metabolites as an anti-inflammatory treatment for ocular conditions, presenting a safe, efficient, and innovative therapeutic strategy for DED and other inflammatory diseases.

Bioinspired Robust Gas-Permeable On-Skin Electronics: Armor-Designed Nanoporous Flash Graphene Assembly Enhancing Mechanical Resilience.

Soft on-skin electrodes play an important role in wearable technologies, requiring attributes such as wearing comfort, high conductivity, and gas permeability. However, conventional fabrication methods often compromise simplicity, cost-effectiveness, or mechanical resilience. In this study, a mechanically robust and gas-permeable on-skin electrode is presented that incorporates Flash Graphene (FG) integrated with a bioinspired armor design. FG, synthesized through Flash Joule Heating process, offers a small-sized and turbostratic arrangement that is ideal for the assembly of a conductive network with nanopore structures. Screen-printing is used to embed the FG assembly into the framework of polypropylene melt-blown nonwoven fabrics (PPMF), forming a soft on-skin electrode with low sheet resistance (125.2 ± 4.7 Ω/□) and high gas permeability (≈10.08 mg cm⁻2 h⁻¹). The "armor" framework ensures enduring mechanical stability through adhesion, washability, and 10,000 cycles of mechanical contact friction tests. Demonstrating capabilities in electrocardiogram (ECG) and electromyogram (EMG) monitoring, along with serving as a self-powered triboelectric sensor, the FG/PPMF electrode holds promise for scalable, high-performance flexible sensing applications, thereby enriching the landscape of integrated wearable technologies.

Compressive Mechanical Behavior and Corresponding Failure Mechanism of Polymethacrylimide Foam Induced by Thermo-Mechanical Coupling.

Thermal-mechanical coupling during the molding process can cause compressive yield in the polymer foam core and then affect the molding quality of the sandwich structure. This work investigates the compressive mechanical properties and failure mechanism of polymethacrylimide (PMI) foam in the molding temperature range of 20-120 °C. First, the DMA result indicates that PMI foam has minimal mechanical loss in the 20~120 °C range and can be regarded as an elastoplastic material, and the TGA curve further proves that the PMI foam is thermally stable within 120 °C. Then, the compression results show that compared with 20 °C, the yield stress and elastic modulus of PMI foam decrease by 22.0% and 17.5% at 80 °C and 35.2% and 31.4% at 120 °C, respectively. Meanwhile, the failure mode changes from brittle fracture to plastic yield at about 80 °C. Moreover, a real representative volume element (rRVE) of PMI foam is established by using Micro-CT and Avizo 3D reconstruction methods, and the simulation results indicate that PMI foam mainly shows brittle fractures at 20 °C, while both brittle fractures and plastic yield occur at 80 °C, and most foam cells undergo plastic yield at 120 °C. Finally, the simulation based on a single-cell RVE reveals that the air pressure inside the foam has an obvious influence of about 6.7% on the yield stress of PMI foam at 80 °C (brittle-plastic transition zone).

Amplifying STING Activation and Alleviating Immunosuppression through a Mn2+-Based Metal-Organic Framework Nanosystem for Synergistic Cancer Therapy.

The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganese-based nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn2+ accomplishes multiple objectives. It generates toxic hydroxyl radicals (•OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O2) from hydrogen peroxide (H2O2), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS-STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.

In Situ Quantitative Imaging of Plasma Membrane Stiffness in Live Cells Using a Genetically Encoded FRET Sensor.

Cell membrane stiffness is critical for cellular function, with cholesterol and sphingomyelin as pivot contributors. Current methods for measuring membrane stiffness are often invasive, ex situ, and slow in process, prompting the need for innovative techniques. Here, we present a fluorescence resonance energy transfer (FRET)-based protein sensor designed to address these challenges. The sensor consists of two fluorescent units targeting sphingomyelin and cholesterol, connected by a linker that responds to the proximity of these lipids. In rigid membranes, cholesterol and sphingomyelin are in close proximity, leading to an increased FRET signal. We utilized this sensor in combination with confocal microscopy to explore changes in plasma membrane stiffness under various conditions, including differences in osmotic pressure, the presence of reactive oxygen species (ROS) and variations in substrate stiffness. Furthermore, we explored the impact of SARS-CoV-2 on membrane stiffness and the distribution of ACE2 after attachment to the cell membrane. This tool offers substantial potential for future investigations in the field of mechanobiology.

Administration of flurbiprofen axetil and dezocine for the postoperative analgesia in patients with non­small cell lung cancer: A randomized, controlled study.

Flurbiprofen axetil or dezocine monotherapy has been applied for analgesia of postoperative non-small cell lung cancer (NSCLC); however, their combination is rarely investigated. Consequently, the present study aimed to explore the effect of flurbiprofen axetil plus dezocine on postoperative pain, surgical outcomes and its safety profile in patients with NSCLC. A total of 150 patients with resectable NSCLC were enrolled and randomized into three groups: i) The flurbiprofen axetil plus dezocine group (n=50), ii) the flurbiprofen axetil group (n=51) and iii) the dezocine group (n=49). A total of 50 mg flurbiprofen axetil, 5 mg of dezocine or their combination were administered intravenously 3 h prior to surgery and subsequently every 12 h until day 3 (D3) following surgery. The postoperative pain was lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil group at 6 h (P=0.008), 12 h (P=0.003), day 1 (D1) (P=0.013), day 2 (D2) (P=0.036) and D3 (P=0.010); in addition, it was lower in the flurbiprofen axetil plus dezocine group compared with that of the dezocine group at 6 h (P=0.010), 12 h (P=0.012) and D1 (P=0.020). Patient-controlled analgesia consumption was also lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil (P=0.010) and dezocine (P=0.002) groups. Furthermore, the length of hospital stay was lower in the flurbiprofen axetil plus dezocine group compared with that of the flurbiprofen axetil (P=0.008) and dezocine (P=0.048) groups, while other surgical outcomes and adverse events were similar among these three groups. Moreover, the expression of tumor necrosis factor-α was lower in the flurbiprofen axetil plus dezocine group compared with that of the dezocine group at 12 h (P<0.001), D1 (P<0.001) and D3 (P=0.033). The data indicated that flurbiprofen axetil and dezocine combination was superior to monotherapy for postoperative analgesia in patients with resectable NSCLC.

Morphological Reconstruction for Variable Wing Leading Edge Based on the Node Curvature Vectors.

Precise morphology acquisition for the variable wing leading edge is essential for its bio-inspired adaptive control. Therefore, this study proposes a morphological reconstruction method for the variable wing leading edge, utilizing the node curvature vectors-based curvature propagation method (NCV-CPM). By establishing a strain-arc curvature function, the method fundamentally mitigates the impact of surface curvature angle on curvature computation accuracy at sensing points. We introduce a technique that uses high-order curvature fitting functions to determine the curvature vectors of arc segment nodes. This method reduces cumulative errors in curvature computation linked to the linear interpolation-based curvature propagation method (LI-CPM) at unattached sensor positions. Integrating curvature-strain functions aids in wing leading-edge strain field reconstruction, supporting structural health monitoring. Additionally, a particle swarm algorithm optimizes the sensing point distribution, reducing network complexity. This study demonstrates significantly enhanced morphological reconstruction accuracy compared to those obtained with conventional LI-CPM.

High Trunk Truncation as a Potential Sustainable Management Option for Asian Longhorned Beetle on Salix babylonica.

The Asian longhorned beetle (ALB) causes substantial economic and ecological losses, thus, an environmentally friendly management strategy is needed. Here, we propose high trunk truncation (HTT), the removal of the above 200 cm portion of trees, as a sustainable management strategy to control ALB. To examine the hypothesis, an initial step involved the assessment of various biological characteristics of ALB. Subsequently, a controlled field experiment was carried out utilizing HTT. Finally, HTT was applied in two additional ALB infestation regions. The results of the study of the biological characteristics of ALB showed that 76.31-78.88% of frass holes and 85.08-87.93% of emergence holes were located on branches above 200 cm. Adults preferred to feed on branches 2-3 cm in diameter, ALB eggs were predominantly laid on 5 cm branches, and both were primarily located above 200 cm. These results revealed a correlation between the number of ALBs and the tree crown height. The controlled field experiment showed that the number of ALBs was significantly decreased when the HTT strategy was implemented: approximately 90% of frass holes and 95% of adults were eradicated by HTT compared with the control. Different field surveys involving HTT have shown similar results. These findings provide valuable insights into a sustainable and efficient management strategy for reducing the number of ALBs.

Electrochemiluminescence-Based Single-Particle Tracking of the Biomolecules Moving along Intercellular Membrane Nanotubes between Live Cells.

Electrochemiluminescence (ECL) imaging, a rapidly evolving technology, has attracted significant attention in the field of cellular imaging. However, its primary limitation lies in its inability to analyze the motion behaviors of individual particles in live cellular environments. In this study, we leveraged the exceptional ECL properties of quantum dots (QDs) and the excellent electrochemical properties of carbon dots (CDs) to develop a high-brightness ECL nanoprobe (CDs-QDs) for real-time ECL imaging between living cells. This nanoprobe has excellent signal-to-noise ratio imaging capabilities for the single-particle tracking (SPT) of biomolecules. Our finding elucidated the enhanced ECL mechanism of CDs-QDs in the presence of reactive oxygen species through photoluminescence, electrochemistry, and ECL techniques. We further tracked the movement of single particles on membrane nanotubes between live cells and confirmed that the ECL-based SPT technique using CD-QD nanoparticles is an effective approach for monitoring the transport behaviors of biomolecules on membrane nanotubes between live cells. This opens a promising avenue for the advancement of ECL-based single-particle detection and the dynamic quantitative imaging of biomolecules.

Confinement effects of mandrel degradation in ICF target fabrication.

Understanding and further regulating the degradation of mandrel materials is a key aspect of target fabrication in inertial confinement fusion (ICF). Here, a quasi-one-dimensional confinement model is developed using a series of single-walled carbon nanotubes with varying diameters (Dm), and the degradation of poly-α-methylstyrene (PAMS) as a typical mandrel material is investigated under such confined conditions by using the combined method of quantum mechanics and molecular mechanics. In comparison to the isolated system, the calculations show that confinement can decrease or increase the energy barriers of PAMS degradation, which directly depends on Dm. Following which a clear exponential relationship between the degradation rate of PAMS and its own density is derived, indicating that the density of PAMS can be used to regulate mandrel degradation. This work highlights the important effects of confinement on degradation and provides a valuable reference for further development of polymer degradation technologies in ICF target fabrication and other fields.

Study of Mechanics and Durability of Non-Spontaneous Combustion Coal Gangue Coarse-Aggregate High-Performance Concrete.

The coal gangue coarse-aggregate content in ordinary concrete should not be too large. In order to further improve the utilization rate of coal gangue coarse aggregate, this study used the principle of "strong wrapped weak" to prepare high-performance concrete. This study considered four factors, namely, water-binder (W/B) ratios, non-spontaneous combustion coal gangue (NCCG) coarse-aggregate contents, fly ash-slag mass ratios, and silica fume coating to prepare high-performance concrete. The workability, mechanical, and durability properties were studied, and the changes in the interfacial transition zone (ITZ) of concrete before and after sulfate attack and freeze-thaw cycles were analyzed based on the SEM test. The life prediction of NCCG coarse-aggregate high-performance concrete was carried out based on the grey system GM(1,1) prediction model. The results show that the NCCG coarse-aggregate contents have the greatest effect on compressive strength, sulfate resistance, and frost resistance. The W/B ratio has the greatest effect on the anti-carbonization properties. Fly ash-slag mixing can obtain better durability. Considering the effect on the design service life of high-performance concrete, NCCG coarse aggregate is used to prepare high-performance concrete in North China, and the recommended content is 60%; in the Northwest and Northeast regions, the recommended content is 45%. This study provides a basis for the preparation of high-performance concrete with NCCG coarse aggregate.

Effects of the seedling tray overlapping for seed emergence mode on emergence characteristics and growth of rice seedlings.

Seedling mode plays a crucial role in the rice production process, as it significantly affects the growth and development of seedlings. Among the various seedling modes, the seedling tray overlapping for seed emergence mode (STOSE mode) has been demonstrated to be effective in enhancing seedling quality. However, the impact of this mode on the germination and growth of seeds with varying plumpness remains uncertain. To investigate the effect of the STOSE mode on seedling emergence characteristics, growth uniformity, and nutrient uptake of seeds with varying plumpness levels, we conducted a study using super early rice Zhongzao 39 (ZZ39) as the test material. The seeds were categorized into three groups: plumped, mixed, and unplumped. The results indicated that the STOSE mode significantly improved the seedling rate for all types of seeds in comparison to the seedling tray nonoverlapping for seed emergence mode (TSR mode). Notably, the unplumped seeds exhibited the most pronounced enhancement effect. The soluble sugar content of the seeds increased significantly after 2 days of sowing under the STOSE mode, whereas the starch content exhibited a significant decrease. Furthermore, the STOSE mode outperformed the TSR mode in several aspects including seedling growth uniformity, aboveground dry matter mass, root traits, and nutrient uptake. Overall, the STOSE mode not only promoted the germination and growth of plumped and mixed seeds but also had a more pronounced impact on unplumped seeds.

The mitochondria-targeted Kaempferol nanoparticle ameliorates severe acute pancreatitis.

Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy.

Protective Effects of Lycium ruthenicum Murray against Acute Alcoholic Liver Disease in Mice via the Nrf2/HO-1/NF-κB Signaling Pathway.

Acute alcoholic liver disease (ALD) resulting from short-term heavy alcohol consumption has become a global health concern. Moreover, anthocyanins have attracted much attention for their ability to prevent oxidation and inflammation. The present work evaluates the protective effects of Lycium ruthenicum Murray (LRM) against ALD and explores the possible underlying mechanism involved. The total anthocyanin content in LRM was 43.64 ± 9.28 Pt g/100 g dry weight. Mice were orally administered 50, 125, or 375 mg LRM/kg body weight (BW) for 21 days. On days 18-21, mice were orally administered 15 mL of ethanol/kg BW. Markers of liver damage, oxidative stress, and inflammation were examined. Furthermore, the modulatory effect of LRM on Nrf2/HO-1/NF-κB pathway molecules was evaluated through quantitative reverse transcription polymerase chain reaction (RT‒qPCR) and immunohistochemistry analyses. The difference between the groups indicated that LRM improved liver histopathology and the liver index, decreased aspartate transaminase, alanine transaminase, malondialdehyde, reactive oxygen species, IL-6, TNF-α, and IL-1ß expression, but elevated superoxide dismutase, catalase, and glutathione-s-transferase levels. Moreover, LRM upregulated Nrf2 and Ho-1 but downregulated Nf-κb and Tnf-α genes at the transcript level. In summary, LRM alleviated ethanol-induced ALD in mice by reducing oxidative damage and associated inflammatory responses. LRM protects against ALD by reducing damage factors and enhancing defense factors, especially via the Nrf2/HO-1/NF-κB pathway. Thus, LRM has application potential in ALD prophylaxis and treatment.

Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

BACKGROUND: Infliximab, an anti-tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research. METHODS: The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement. RESULTS: Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record-integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration. CONCLUSIONS: Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory.

NIR-responsive copper nanoliposome composites for cascaded ferrotherapy via ferroptosis actived ICD and IFN-γ released.

Metallic biomaterials activate tumor ferroptosis by increasing oxidative stress, but their efficacy is severely limited in tumor microenvironment. Although interferon gamma (IFN-γ) can promote tumor ferroptosis sensitivity by inhibiting the antioxidant system and promoting lipid accumulation, this effect limited by the lack of IFN-γ accumulation in tumors. Herein, we report a near-infrared (NIR)-responsive HCuS nanocomposite (HCuS-PE@TSL-tlyp-1) that can stimulate immunogenic cell death (ICD)-mediated IFN-γ secretion through exogenous oxidative stress, thereby achieving cascaded ferrotherapy by mutually reinforcing ferroptosis and systemic immunity. Upon laser irradiation, the dissolution of the thermal coating, and the introduction of Cu ions and piperazine-erastin (PE) simultaneously induce oxidative stress by reactive oxygen species (ROS)/lipid peroxide (LPO) accumulation and deplete cystine-glutamate transporter (xCT)/GSH. The onset of oxidative stress-mediated ferroptosis is thus achieved, and ICD is triggered, significantly promoting cytotoxic T-cell (CTL) infiltration for IFN-γ secretion. Furthermore, IFN-γ induces immunogenic tumor ferroptosis by inhibiting xCT-antioxidant pathways and enhancing the ACSL4-fatty acid recruitment pathway, which further promotes sensitivity to ferroptosis in cells. These HCuS nanocomposites combined with aPD-L1 effectively in inhibiting tumor metastasis and recurrence. Importantly, these cascade ferrotherapy results broadens the application of HCuS biomaterials.

Thermal structure regulates the dynamics of carbon dioxide flux in alpine saline lake on the Qinghai-Tibet Plateau, China.

Thermal stratification and mixing play important roles in the physicochemical composition of lakes and affect the geochemical cycle. However, the regulation of lake carbon exchange at the water-air interface by seasonal thermal structures remains unclear, especially for alpine saline lake on the Qinghai-Tibet Plateau (QTP). Based on continuous field sampling, carbon dioxide flux (FCO2) at the water-air interface in Qinghai Lake during the ice-free period was quantitatively analyzed by thin boundary layer model, as well as the driving factors of the change in FCO2 at the water-air interface. The findings revealed that the FCO2 was -22.16 ± 11.73 mmol m-2d-1 during the stratification period, and - 45.32 ± 29.67 mmol m-2d-1 during the mixing period. We found that thermal stratification limits the matter-energy exchange between the upper and bottom water columns, and carbonate precipitation results in a higher FCO2 than during mixing stage. However, the mixing process reduces the limiting effect of thermal stratification. During the carbonate process, water with higher salinity and pH at the bottom of the water column enters the upper part of the water column, reducing the partial pressure of carbon dioxide (pCO2) in the water column and causing the absorption of CO2 by the lake. Thermal stratification affects the vertical material-energy exchange and atmospheric CO2 uptake of lake. The present study further explains the possible underlying regulation of CO2 uptake in saline lake on the QTP involving the varied thermal structure.

Geniposide alleviates imiquimod-induced psoriasis-like skin lesions in mice via inhibition of angiogenesis.

In this study, we aimed to evaluate the protective effect of geniposide (GEN) on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Firstly, visual changes of psoriatic skin lesions were observed and the severity was recorded using psoriasis area and severity index (PASI) score. Histological changes were assessed by HE staining for epidermal thickness and Masson's staining for collagen fibers. Then, photographs of microvascular inside the skin were taken for macroscopic observation, and microscopic changes associated with angiogenesis were evaluated. Furthermore, expression of angiogenic factors were analyzed by ELISA, immunohistochemistry and immunofluorescence, separately. Lastly, the expression of VEGFR signaling-related proteins was detected by WB. Compared with control, IMQ drove a significant increment of epidermal thicknesses with higher PASI scores and more dermal collagen deposition. IMQ treatment led to abnormal keratinocyte proliferation, increased microvascular inside skin, growing production of angiogenesis-related factors, up-regulated expression of VEGFR1 and VEGFR2, and enhanced phosphorylation of p38. However, GEN significantly ameliorated the psoriatic skin lesions, the epidermal thickness, the formation of collagen fibers, and abnormal keratinocyte proliferation. Importantly, GEN inhibited angiogenesis, the production of angiogenic factors (VEGF-A, Ang-2, TNF-α, and IL-17A), and the proliferation of vascular endothelial cells. Simultaneously, GEN curbed the expression of VEGFR1, VEGFR2, p38, and P-p38 proteins involved in VEGFR signaling. Of note, the suppressive effect of GEN was reversed in the HUVECs with over-expressed VEGFR1 or VEGFR2 related to the cells without transfection. These findings suggest that VEGFR1 and VEGFR2 participate in the anti-angiogenesis of GEN in IMQ-induced psoriasis-like skin lesions in mice.

pH-Activatable Pre-Nanozyme Mediated H2S Delivery for Endo-Exogenous Regulation of Oxidative Stress in Acute Kidney Injury.

Oxidative stress induced by excess reactive oxygen species (ROS) is a primary pathogenic cause of acute kidney injury (AKI). Development of an effective antioxidation system to mitigate oxidative stress for alleviating AKI remains to be investigated. This study presents the synthesis of an ultra-small Platinum (Pt) sulfur cluster (Pt5.65S), which functions as a pH-activatable prefabricated nanozyme (pre-nanozyme). This pre-nanozyme releases hydrogen sulfide (H2S) and transforms into a nanozyme (Ptzyme) that mimics various antioxidant enzymes, including superoxide dismutase and catalase, within the inflammatory microenvironment. Notably, the Pt5.65S pre-nanozyme exhibits an endo-exogenous synergy-enhanced antioxidant therapeutic mechanism. The Ptzyme reduces oxidative damage and inflammation, while the released H2S gas promotes proneurogenesis by activating Nrf2 and upregulating the expression of antioxidant molecules and enzymes. Consequently, the Pt5.65S pre-nanozyme shows cytoprotective effects against ROS/reactive nitrogen species (RNS)-mediated damage at remarkably low doses, significantly improving treatment efficacy in mouse models of kidney ischemia-reperfusion injury and cisplatin-induced AKI. Based on these findings, the H2S-generating pre-nanozyme may represent a promising therapeutic strategy for mitigating inflammatory diseases such as AKI and others.