Analysis of health related event detection in big data for physical education training movement detection.

BACKGROUND: Physical education and training are essential ways to improve the physical quality of the nation, and China has incorporated "building a healthy China" and "fitness for all" into its national development strategy, integrating a strong sports nation into the Chinese dream. OBJECTIVE: The study of digital recording and automated training in sports is of profound value. Motion capture technology can digitally record the training process in a digital physical education training system. At the same time, accurate modeling and calculation can analyze the training effects and give appropriate guidance and feedback. This study develops a new and improved hierarchical K-means algorithm by combining the known classification algorithm K-means with a hierarchical algorithm. METHODS: The performance of the old and new algorithms are compared and then applied to physical education training data to produce clustering results and analysis to reduce the model, which is used to reduce the number of parameters in the model and improve the recognition speed. RESULTS: The experimental results demonstrate that the relevant models proposed in this study achieve an average accuracy of 91.27% and 92.26%, respectively, which is better than a single network model and can effectively use big data for health event detection. CONCLUSION: The empirical results show that the improved model algorithm outperforms the single network model and can detect health events using big data.

Suppression of lysosome metabolism-meditated GARP/TGF-ß1 complexes specifically depletes regulatory T cells to inhibit breast cancer metastasis.

Regulatory T cells (Tregs) prevent autoimmunity and contribute to cancer progression. They exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-ß1 (TGF-ß1). However, the absence of a specific surface marker makes inhibiting the production of active TGF-ß1 to specifically deplete human Tregs but not other cell types a challenge. TGF-ß1 in an inactive form binds to Tregs membrane protein Glycoprotein A Repetitions Predominant (GARP) and then activates it via an unknown mechanism. Here, we demonstrated that tumour necrosis factor receptor-associated factor 3 interacting protein 3 (TRAF3IP3) in the Treg lysosome is involved in this activation mechanism. Using a novel naphthalenelactam-platinum-based anticancer drug (NPt), we developed a new synergistic effect by suppressing ATP-binding cassette subfamily B member 9 (ABCB9) and TRAF3IP3-mediated divergent lysosomal metabolic programs in tumors and human Tregs to block the production of active GARP/TGF-ß1 for remodeling the tumor microenvironment. Mechanistically, NPt is stored in Treg lysosome to inhibit TRAF3IP3-meditated GARP/TGF-ß1 complex activation to specifically deplete Tregs. In addition, by promoting the expression of ABCB9 in lysosome membrane, NPt inhibits SARA/p-SMAD2/3 through CHRD-induced TGF-ß1 signaling pathway. In addition to expose a previously undefined divergent lysosomal metabolic program-meditated GARP/TGF-ß1 complex blockade by exploring the inherent metabolic plasticity, NPt may serve as a therapeutic tool to boost unrecognized Treg-based immune responses to infection or cancer via a mechanism distinct from traditional platinum drugs and currently available immune-modulatory antibodies.

Hyperosmotic Stress Induces Inflammation and Excessive Th17 Response to Blunt T-Cell Immunity in Tilapia.

Despite the advances in study on osmotic physiology in bony fish, the mechanism by which the immune system, especially T-cell immunity, adapts and responds to osmotic stress remains unknown. In the current study, we investigated the response of T cells to hyperosmotic stress in the bony fish Nile tilapia (Oreochromis niloticus). As a euryhaline fish, tilapia was able to adapt to a wide range of salinities; however, hypertonic stress caused inflammation and excessive T-cell activation. Furthermore, hypertonic stress increased the expression of IL-17A in T cells, upregulated the transcription factor RORα, and activated STAT3 signaling, along with IL-6- and TGF-ß1-mediated pathways, revealing an enhanced Th17 response in this early vertebrate. These hypertonic stress-induced events collectively resulted in an impaired antibacterial immune response in tilapia. Hypertonic stress elevated the intracellular ROS level, which in turn activated the p38-MK2 signaling pathway to promote IL-17A production by T cells. Both ROS elimination and the p38-MK2 axis blockade diminished the increased IL-17A production in T cells under hypertonic conditions. Moreover, the produced proinflammatory cytokines further amplified the hypertonic stress signaling via the MKK6-p38-MK2 axis-mediated positive feedback loop. To our knowledge, these findings represent the first description of the mechanism by which T-cell immunity responds to hypertonic stress in early vertebrates, thus providing a novel perspective for understanding the adaptive evolution of T cells under environmental stress.

Effect of salinity on the physiological response and transcriptome of spotted seabass (Lateolabrax maculatus).

Salinity fluctuations significantly impact the reproduction, growth, development, as well as physiological and metabolic activities of fish. To explore the osmoregulation mechanism of aquatic organisms acclimating to salinity stress, the physiological and transcriptomic characteristics of spotted seabass (Lateolabrax maculatus) in response to varying salinity gradients were investigated. In this study, different salinity stress exerted inhibitory effects on lipase activity, while the impact on amylase activity was not statistically significant. Notably, a moderate increase in salinity (24 psu) demonstrated the potential to enhance the efficient utilization of proteins by spotted seabass. Both Na+/K+-ATPase and malondialdehyde showed a fluctuating trend of increasing and then decreasing, peaking at 72 h. Transcriptomic analysis revealed that most differentially expressed genes were involved in energy metabolism, signal transduction, the immune response, and osmoregulation. These results will provide insights into the molecular mechanisms of salinity adaptation and contribute to sustainable development of the global aquaculture industry.

The Association between Dietary Protein Intake and Sources and the Rate of Longitudinal Changes in Brain Structure.

Few studies have examined dietary protein intake and sources, in combination with longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein, with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were separately included in the analysis. The relative and absolute amounts of dietary protein intake were calculated using a 24 h dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. The average interval between the assessments was three years. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake was associated with a slower reduction in the total hippocampus volume (THV, ß: 0.02524, p < 0.05), left hippocampus volume (LHV, ß: 0.02435, p < 0.01) and right hippocampus volume (RHV, ß: 0.02544, p < 0.05). A higher intake of animal protein relative to plant protein was linked to a lower atrophy rate in the THV (ß: 0.01249, p < 0.05) and LHV (ß: 0.01173, p < 0.05) and RHV (ß: 0.01193, p < 0.05). Individuals with a higher intake of seafood exhibited a higher longitudinal rate of change in the HV compared to those that did not consume seafood (THV, ß: 0.004514; p < 0.05; RHV, ß: 0.005527, p < 0.05). In the subgroup and sensitivity analyses, there were no significant alterations. A moderate increase in an individual's intake and the proportion of animal protein in their diet, especially from seafood, is associated with a lower atrophy rate in the hippocampus volume.

Uncovering the crystallography and formation mechanism of nanoscale clusters in Sb-rich SPPs of a p-type (Bi, Sb)2Te3 alloy.

Considering that the crystallographic characteristics of the Sb-rich secondary phase particles (SPPs) greatly affect the thermoelectric properties of Bi2Te3 based materials, it is of great significance to explore the mechanism behind the Sb-rich SPPs in the p-type (Bi, Sb)2Te3 material. Here a conventional TEM technique was used to characterize the composition, size and distribution of Sb-rich SPPs in a spark plasma sintered p-type (Bi, Sb)2Te3 alloy. The results indicated that two different morphologies of Sb-rich SPPs including elongated and circular Sb-rich SPPs were frequently observed. Combined with high-resolution transmission electron microscopy, this work provides atomic-scale evidence for the formation mechanism behind the Sb-rich SPPs in the (Bi, Sb)2Te3 material.

Comparative efficacy and safety of the treatment by Omalizumab for chronic idiopathic urticaria in the general population: A systematic review and network meta-analysis.

BACKGROUND: Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients. MATERIALS AND METHODS: Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta-analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk-of-bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs). RESULTS: In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta-regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo. CONCLUSION: 300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.

Naturally biocompatible melanin based iron-complex nanoparticles for pH-responsive magnetic resonance imaging.

The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on ther1of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM-1s-1at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effectin vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.

Determination of Azole Fungicide Residues in Fresh Juice by Magnetic Solid Phase Extraction Based on Fe3O4@ZnAl-LDH@MIL-53(Al) Sorbent in Combination with High-Performance Liquid Chromatograph.

In this work, a magnetic adsorption material based on metal-organic framework (Fe3O4@ZnAl-LDH@MIL-53(Al)) was synthesized and used as an adsorbent in the process of magnetic solid phase extraction. Then, a high-performance liquid chromatograph was used to quantitatively detect triazole fungicides in samples. In order to verify the successful preparation of the material, a series of characterization analyses were carried out. Besides, the key parameters that may affect the extraction efficiency have been optimized, and under optimal conditions the three triazole fungicides showed good linearity in the range of 10-1000 µg/L (R2 ≥ 0.9796); Limit of detections were ranged from 0.013 to 0.030 µg/mL. Finally, the established method was applied to the detection of triazole fungicides in four fresh juice samples. The results showed that the target analyte was not detected in all the test samples. By detecting the recoveries (73.3-104.3%) and coefficient variation (RSD ≤ 6.8%) of triazole fungicides in fortified samples, it proved that this established method meets the requirements of pesticide residue analysis and showed excellent application potential.

Understanding the Mechanochemistry of Mechano-Radicals in Self-Growth Materials by Single-Molecule Force Spectroscopy.

Recent research on mechano-radicals has provided valuable insights into self-growth and adaptive responsive materials. Typically, mechanophores must remain inert in the absence of force but respond quickly to external tension before other linkages within the polymer network. Azo compounds exhibit promising combinations of mechanical stability and force-triggered reactivity, making them widely used as mechano-radicals in force-responsive materials. However, the activation conditions and behavior of azo compounds have yet to be quantitatively explored. In this study, we investigated the mechanical strength of three azo compounds using single-molecule force spectroscopy. Our results revealed that these compounds exhibit rupture forces ranging from ~500 to 1000 pN, at a loading rate of 3×104 pN s-1. Importantly, these mechanophores demonstrate distinct kinetic properties. Their unique mechanical attributes enable azo bond scission and free radical generation before causing major polymer backbone damage of entire material during polymer network deformation. This fundamental understanding of mechanophores holds significant promise for the development of self-growth materials and their related applications.

Effect of artificial natural light on the development of myopia among primary school-age children in China: a three-year longitudinal study.

AIM: To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children. METHODS: This is a prospective, randomized control, intervention study. A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study. The whole randomization method was adopted to include classes as a group according to 1:1 randomized control. Classrooms in the control group were illuminated by usual light, and classrooms in the intervention group were illuminated by artificial natural light. All students received uncorrected visual acuity and best-corrected visual acuity measurement, non-cycloplegic autorefraction, ocular biometric examination, slit lamp and strabismus examination. Three-year follow-up, the students underwent same procedures. Myopia was defined as spherical equivalent refraction ≤ -0.50 D and uncorrected visual acuity <20/20. RESULTS: There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y. The three-year cumulative incidence rate of myopia was 26.4% (207 incident cases among 784 eligible participants at baseline) in the control group and 21.2% (164 incident cases among 774 eligible participants at baseline) in the intervention group [difference of 5.2% (95%CI, 3.7% to 10.1%); P=0.035]. There was also a significant difference in the three-year change in spherical equivalent refraction for the control group (-0.81 D) compared with the intervention group [-0.63 D; difference of 0.18 D (95%CI, 0.08 to 0.28 D); P<0.001]. Elongation of axial length was significantly different between in the control group (0.77 mm) and the intervention group [0.72 mm; difference of 0.05 mm (95%CI, 0.01 to 0.09 mm); P=0.003]. CONCLUSION: Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

CNT@SrTiO3 Nanocomposites Synthesized by In Situ Reaction for a High-Performance Flexible Supercapacitor.

This study presents the in situ synthesis of CNT@SrTiO3 nanocomposite films for the development of high-performance flexible supercapacitors. The synthesis process involved the use of organic-inorganic hybrid polymers containing metal elements as precursors for thermal decomposition reaction under a reducing atmosphere. Due to the formation of chemical bonding between Ti elements and the CNTs, the interface between STO and CNT surface could provide additional active sites for ion transport and storage. Thereby, the incorporation of SrTiO3 nanoparticles into CNTs enhanced the electrochemical performance of the resulting nanocomposite membranes. To further investigate the influence of STO content and synthesis temperature, we conducted a detailed analysis. The findings indicated that the CNT@STO film with 25% STO content, synthesized at 700 °C, and possessed optimal performance with an areal capacitance of 6682 mF·cm-2 at 5 mV·s-1. Furthermore, a symmetrical flexible supercapacitor assembled by two CNT@STO-25 electrodes demonstrated strong application potential in wearable devices, owing to its long cycle life, excellent flexibility, and high energy density of 430.2 µWh·cm-2 (corresponding power density of 4.5 mW·cm-2). Based on these results, we believe that this study provides a fresh idea for the development of novel flexible energy storage materials.

Efficacy and safety of CO2 fractional laser versus Er:YAG fractional laser in the treatment of atrophic acne scar: A meta-analysis and systematic review.

BACKGROUND: To date, a consensus on the relative efficacy and safety of CO2 fractional laser versus erbium-doped yttrium aluminum garnet (Er:YAG) fractional laser treatments for atrophic acne scars has not been reached. This meta-analysis aims to systematically assess and compare their effectiveness and safety in clinical practice. METHODS: For this meta-analysis, we conducted comprehensive searches in Pubmed, Embase, and Cochrane databases, covering publications from their inception up to August 2023. Our focus was on studies comparing fractional CO2 laser with Er:YAG fractional laser treatments for atrophic acne scars. We excluded duplicate publications, research lacking full-text access, incomplete data, or cases where data extraction was not feasible. Additionally, animal experiments, reviews, and systematic reviews were not considered. Data analysis was performed using STATA 15.1. RESULTS: Eight studies (seven randomized controlled trials (RCTs) and a retrospective study) were included in this meta-analysis. The sample size ranged from 28 to 106 with a total of 418 patients, including 210 in the CO2 fractional group and 208 in Er:YAG fractional group. The pooled results showed that the effective rate of CO2 fractional laser in treating atrophic acne scar was significantly higher than that of Er:YAG fractional laser (OR = 1.81, 95% CI: 1.08-3.01) and the downtime of CO2 fractional laser in treating atrophic acne scar was significantly shorter than that of Er:YAG fractional laser (Weighted Mean Difference (WMD) = -2.11, 95% CI: -3.11 to -1.10). In addition, VAS of CO2 fractional laser in treating atrophic acne scar was significantly higher than that of Er:YAG fractional laser (WMD = 1.77, 95% CI: 1.32-2.21) and the duration of erythema of CO2 fractional laser in treating atrophic acne scar was significantly longer than that of Er:YAG fractional laser (WMD = 1.85, 95% CI: 1.63-2.07). However, there was no significant difference in the duration of pain and incidence of PIHbetween CO2 fractional laser and of Er:YAG fractional laser. CONCLUSION: When it comes to treating atrophic acne scars, CO2 fractional laser demonstrates superior efficacy and leads to shorter downtime. However, it is important to note that CO2 fractional laser treatments tend to result in higher pain intensity and may carry a higher risk of post-treatment pigmentation compared to Er:YAG fractional laser procedures.

Polar Bloch points in strained ferroelectric films.

Topological domain structures have drawn great attention as they have potential applications in future electronic devices. As an important concept linking the quantum and classical magnetism, a magnetic Bloch point, predicted in 1960s but not observed directly so far, is a singular point around which magnetization vectors orient to nearly all directions. Here we show polar Bloch points in tensile-strained ultrathin ferroelectric PbTiO3 films, which are alternatively visualized by phase-field simulations and aberration-corrected scanning transmission electron microscopic imaging. The phase-field simulations indicate local steady-state negative capacitance around the Bloch points. The observation of polar Bloch points and their emergent properties consequently implies novel applications in future integrated circuits and low power electronic devices.

Metabolic dysfunction associated steatotic liver disease in patients with plaque psoriasis: a case-control study and serological comparison.

Background: The relationship between plaque psoriasis and both MASLD and lean MASLD has not been sufficiently explored in the current literature. Method: This retrospective and observational study was carried out from January 2021 to January 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University. Patients diagnosed with plaque psoriasis and a control group consisting of individuals undergoing routine physical examinations were enrolled. The incidence of MASLD and lean MASLD among these groups was compared. Additionally, patients with plaque psoriasis were divided into those with MASLD, those with lean MASLD, and a control group with only psoriasis for a serological comparative analysis. Results: The incidence of MASLD in the observation group and the control group was 43.67% (69/158) and 22.15% (35/158), respectively (p < 0.01). Furthermore, the incidence of lean MASLD within the observation group and the control group was 10.76% (17/158) and 4.43% (7/158), respectively (p < 0.01). After controlling for potential confounding variables, plaque psoriasis was identified as an independent risk factor for MASLD with an odds ratio of 1.88 (95% cl: 1.10-3.21). In terms of serological comparison, compared to the simple psoriasis group, we observed a significant elevation in the tumor marker CYFRA21-1 levels in both groups compared to the control group with simple psoriasis (p < 0.01). Moreover, the MASLD group exhibited elevated levels of inflammatory markers and psoriasis score, whereas these effects were mitigated in the lean MASLD group. Conclusion: The prevalence of MASLD and lean MASLD is higher among patients with psoriasis. Those suffering from psoriasis along with MASLD show increased psoriasis scores and inflammatory markers compared to those without metabolic disorders. MASLD likely worsens psoriasis conditions, indicating the necessity of targeted health education for affected individuals to reduce the risk of MASLD, this education should include guidelines on exercise and diet. In serological assessments, elevated levels of cytokeratin 19 fragment (CYFRA21-1) were noted in both MASLD and lean MASLD groups, implying a potential synergistic role between psoriasis and MASLD.

A responsive nanoplatform with molecular and structural imaging capacity for assisting accurate diagnosis of early rheumatoid arthritis.

Accurate early diagnosis of rheumatoid arthritis (RA) and prompt implementation of appropriate treatment approaches are crucial. In the clinic, magnetic resonance imaging (MRI) has been recommended for implementation to aid in the precise and early diagnosis of RA. However, they are still limited by issues regarding specificity and their ability to capture comprehensive information about the pathological features. Herein, a responsive multifunctional nanoplatform with targeting capabilities (hMnO2-IR@BSA-PEG-FA) is constructed through integrating a RA microenvironment-responsive MRI contrast agent with activatable near-infrared (NIR) fluorescence imaging, aiming to simultaneously acquire comprehensive pathological features of RA from both structural and molecular imaging perspectives. Moreover, taking advantage of its targeting function to synovial microphages, hMnO2-IR@BSA-PEG-FA demonstrated a remarkable capability to accumulate effectively at the synovial tissue. Additionally, hMnO2 responded to the mild acidity and reactive oxygen species (ROS) in the RA microenvironment, leading to the controlled release of Mn2+ ions and IR780, which separately caused special MRI contrast enhancement of synovial tissues and sensitively demonstrated the presence of ROS and weakly acid microenvironment by NIR imaging. Consequently, hMnO2-IR@BSA-PEG-FA is expected to serve as a promising nanoplatform, offering valuable assistance in the precise diagnosis of early-stage RA by specially providing comprehensive information about the pathological features.

Research on provincial water resources carrying capacity and coordinated development in China based on combined weighting TOPSIS model.

With the continuous development of the economy and society, along with the sustained population growth, the issue of water resources carrying capacity in China has attracted increasing attention. This paper constructs a model for evaluating the provincial water resources carrying capacity in China from four dimensions: water, economy, society, and ecology. Utilizing this model, we analyze the spatiotemporal variations in water resources carrying capacity among 31 provinces in China from 2005 to 2021. Additionally, we delve into the coupling coordination and influencing factors of water resources carrying capacity. The study reveals an overall increasing trend in China's water resources carrying capacity index, with the ecological indicator exhibiting the most significant growth while the water resources sub-indicator lags behind. There are notable regional differences, with higher water resources carrying capacity observed in the eastern coastal areas and relatively lower capacity in the western regions. The ecological criterion becomes a core factor constraining water resources carrying capacity from 2005 to 2015, gradually giving way to the prominence of the social criterion since 2015. The coordination degree is relatively higher in the eastern regions, more scattered in the western regions, and relatively stable in the central regions. Based on the research findings, a series of recommendations are proposed, including strengthening environmental protection policies, optimizing water resources management mechanisms, improving water use efficiency, and promoting economic structural diversification. These suggestions aim to facilitate the sustainable development of water resources carrying capacity in China.

An Engineered Nanoplatform with Tropism toward Irradiated Glioblastoma Augments Its Radioimmunotherapy Efficacy.

Combining radiotherapy with immune checkpoint blockade therapy offers a promising approach to treat glioblastoma multiforme (GBM), yet challenges such as limited effectiveness and immune-related adverse events (irAEs) persist. These issues are largely due to the failure in targeting immunomodulators directly to the tumor microenvironment. To address this, we developed a biomimetic nanoplatform that combines a genetically modified mesenchymal stem cell (MSC) membrane with a bioactive nanoparticle core for chemokine-directed radioimmunotherapy of GBM. The CCR2-overexpressing MSC membrane acts as a tactical tentacle to achieve radiation-induced tropism toward the abundant chemokine ligand CCL2 in irradiated gliomas. The nanoparticle core, comprising diselenide-bridged mesoporous silica nanoparticles (MSNs) and PD-L1 antibodies (αPD-L1), enables X-ray-responsive drug release and radiosensitization. In two murine models with orthotopic GBM tumors, this nanoplatform reinvigorated immunogenic cell death, and augmented the efficacy and specificity of GBM radioimmunotherapy, with reduced occurrence of irAEs. This study suggests a promising radiation-induced tropism strategy for targeted drug delivery, and presents a potent nanoplatform that enhances the efficacy and safety of radio-immunotherapy. This article is protected by copyright. All rights reserved.

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.