Enhanced mechanical and surface chemical stability in cobalt-free, high-nickel cathode materials for lithium-ion batteries.

Cobalt-free, high-nickel cathode materials are essential for the sustainable evolution of energy storage technologies, reducing the dependence on resources with significant environmental and social implications and simultaneously improving the efficiency and cost effectiveness of batteries. This paper introduces a cobalt-free, high-nickel cathode material called 0.01B-LiNi0.98Mg0.01Zr0.01O2 (NMZB) developed using a novel blend of elements to enhance mechanical and surface chemical stability. Detailed evaluations confirmed the successful integration of Mg, Zr, and B into the particles, with Mg and Zr primarily located within the particle interior and B predominantly on the surface. This unique elemental configuration significantly improves the stability of the bulk phase and surface structure of the material. In addition, the refinement of primary particles within NMZB further enhances its mechanical stability. As a result, NMZB exhibits exceptional electrochemical stability, achieving 90.5 % capacity retention after 200 cycles at a 1C rate. This compositional strategy incorporates a high nickel content into layered materials while eliminating cobalt, which is crucial for advancing the development of cost effective and high-performance lithium-ion battery technology.

Microglial forkhead box O3a deficiency attenuates LPS-induced neuro-inflammation and depressive-like behaviour through regulating the expression of peroxisome proliferator-activated receptor-γ.

BACKGROUND AND PURPOSE: Depression is closely linked with microglial activation and neuro-inflammation. Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in M2 activation of microglia. Forkhead box (FOX) O3a has been implicated in the regulation of mood-relevant behaviour. However, little is known about the inflammatory mechanisms of in the microglia of the brain. Here, we have investigated the role of microglial FOXO3a/PPAR-γ in the development of depression. EXPERIMENTAL APPROACH: The effect of FOXO3a on microglia inflammation was analysed in vitro and in lipopolysaccharide (LPS)-induced depression-like behaviours in vivo. ChIP-seq and Dual-luciferase reporter assays were used to confirm the interaction between FOXO3a and PPAR-γ. Behavioural changes were measured, while inflammatory cytokines, microglial phenotype and morphological properties were determined by ELISA, qRT-PCR, western blotting and immunostaining. KEY RESULTS: Overexpression of FOXO3a significantly attenuated expression of PPAR-γ and enhanced the microglial polarization towards the M1 phenotype, while knockdown of FOXO3a had the opposite effect. FOXO3a binds to the promoters of PPAR-γ and decreases its transcription activity. Importantly, deacetylation and activation of FOXO3a regulate LPS-induced neuro-inflammation by inhibiting the expression of PPAR-γ in microglia cells, supporting the antidepressant potential of histone deacetylase inhibitors. Microglial FOXO3a deficiency in mice alleviated LPS-induced neuro-inflammation and depression-like behaviours but failed to reduce anxiety behaviour, whereas pharmacological inhibition of PPAR-γ by GW9662 restored LPS-induced microglial activation and depressive-like behaviours in microglial FOXO3a-deficient mice. CONCLUSION AND IMPLICATIONS: FOXO3a/PPAR-γ axis plays an important role in microglial activation and depression, identifying a new therapeutic avenue for the treatment of major depression.

Impact of sarcopenia on outcomes following lumbar spine surgery for degenerative disease: an updated systematic review and meta-analysis.

PURPOSE: This study aimed to consolidate the evidence regarding the prognostic influence of sarcopenia in degenerative lumbar spine surgeries. METHODS: A literature search of public databases was conducted up to Nov 15, 2023 using combinations of the key words "sarcopenia" and "lumbar spine surgery". Eligible studies were those that focused on adults undergoing decompression or fusion surgery for degenerative lumbar spine diseases, and compared the outcomes between patients with and without preoperative sarcopenia. Primary outcomes were change in ODI and back and leg pain VAS pain scores. Secondary outcomes were changes in Eq. 5D, JOA, SFHS-p scores, and LOS. RESULTS: Ultimately, nine retrospective studies with a total of 993 patients were included. Sarcopenic patients exhibited significantly worse functional improvement as assessed by ODI compared to non-sarcopenic patients (pooled standardized mean difference [pSMD] = 0.53, 95% confidence interval [CI]: 0.17-0.90). Back pain (pSMD = 0.31, 95% CI:0.15-0.47) and leg pain (pSMD = 0.21, 95% CI:0.02 - 0.39) improvement were also less in sarcopenic patients. Non-sarcopenic patients had greater improvements in Eq. 5D (pSMD = 0.25) and SFHS-p (pSMD = 0.39), and shorter LOS (pSMD = 0.62). CONCLUSIONS: As compared to patients without sarcopenia, those with sarcopenia undergoing lumbar spine surgery for degenerative diseases have lower improvements in functional ability, quality of life, physical health, pain relief and extended hospitalization compared to those without sarcopenia.

Potential mechanisms of aortic medial degeneration promoted by co-exposure to microplastics and lead.

Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta.

NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis.

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

Iron deficiency affects oxygen transport and activates HIF1 signaling pathway to regulate phenotypic transformation of VSMC in aortic dissection.

BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.

Visfatin Facilitates VEGF-D-Induced Lymphangiogenesis through Activating HIF-1α and Suppressing miR-2277-3p in Human Chondrosarcoma.

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Lymphangiogenesis plays an essential role in cancer metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with VEGF-D generation and lymphangiogenesis in chondrosarcoma remains undetermined. Our results from clinical samples reveal that VEGF-D levels are markedly higher in chondrosarcoma patients than in normal individuals. Visfatin stimulation promotes VEGF-D-dependent lymphatic endothelial cell lymphangiogenesis. We also found that visfatin induces VEGF-D production by activating HIF-1α and reducing miR-2277-3p generation through the Raf/MEK/ERK signaling cascade. Importantly, visfatin controls chondrosarcoma-related lymphangiogenesis in vivo. Therefore, visfatin is a promising target in the treatment of chondrosarcoma lymphangiogenesis.

Development of a Triphenylmethyl Alkylation Pre-Column Derivatization Method for HPLC Quantitative Analysis of Chemically Unstable Halogenated Compounds.

The primary limitations of the quantitative analysis of thermally labile halogenated compounds by traditional gas chromatography (GC) are the inadequacy of identifying the insufficiently volatile impurity (often with a high boiling point) and the difficulty in obtaining a standard substance with a reliable standardized assay. Taking the 4-(Chloromethyl)-5-methyl-1,3-dioxol-2-one (DMDO-Cl, 1) as an example, we reported a triphenylmethanamino-derivatization method to overcome the challenges of the assay determination of such species. During the quantification of 1, the presence of GC-undetectable polymeric impurity 10 poses a critical challenge in assessing the material quality. Moreover, the standard substance of 1 is not available on the market due to its inherent instability during storage and handling, further complicating the quantitative analysis. In this work, a precolumn HPLC-UV derivatization method based on triphenylmethanamino-alkylation was developed to quantitatively analyze 1. The resulting derivative 2 exhibits excellent crystallinity and superior physical and chemical stability and possesses effective chromophores for UV detection. The conversion from analyte 1 to derivative 2 demonstrates desirable reactivity and purity, facilitating quantitative analysis using the external standard method. The chemical derivatization-chromatographic detection method was optimized and validated, demonstrating its high specificity, good linearity, precision, accuracy, and stability. This method offers a valuable alternative to the general quantitative NMR (qNMR) detection technique, which exhibits reduced specificity in the presence of increased levels of impurities in compound 1.

Deployment Protection for Interference of 5G Base Stations with Aeronautical Radio Altimeters.

In this manuscript, we present a novel deployment protection method aimed at safeguarding aeronautical radio altimeters (RAs) from interference caused by fifth-generation (5G) telecommunication base stations (BSs). Our methodology involves an integrated interference model for defining prohibited zones and utilizes power control and angle shutoff methods to mitigate interference. First, to ensure reliable protection, we define both horizontal and vertical prohibited zones and investigate their variations to immunize RA against 5G interference. Second, we validate the effectiveness of the model in various operational scenarios, analyzing the influence of factors such as base station types, antenna parameters, flight altitude, and aircraft attitudes to cover a wide range of real-world scenarios. Third, to mitigate interference, we propose and analyze the power control and angle shutoff methods through simulation for the RMa prohibited zone. Our results demonstrate the efficacy of the deployment protection method in safeguarding RAs from 5G interference, providing guidance for interference protection during civil aviation operations and base station deployment near airports.

MCP-1 controls IL-17-promoted monocyte migration and M1 polarization in osteoarthritis.

Osteoarthritis (OA) is a low-grade inflammatory joint illness in which monocytes migrate and infiltrate synovial tissue, differentiating into the pro-inflammatory M1 macrophage phenotype. IL-17 is a proinflammatory mediator principally generated by Th17 cells, which is elevated in OA patients; nevertheless, investigators have yet to elucidate the function of IL-17 in M1 polarization during OA development. Our analysis of clinical tissues and results from the open online dataset discovered that the level of M1 macrophage markers is elevated in human OA tissue samples than in normal tissue. High-throughput screening demonstrated that MCP-1 is a potential candidate factor after IL-17 treatment in OA synovial fibroblasts (OASFs). Immunohistochemistry data revealed that the level of MCP-1 is higher in humans and mice with OA than in normal tissues. IL-17 stimulation facilitates MCP-1-dependent macrophage polarization to the M1 phenotype. It also appears that IL-17 enhances MCP-1 synthesis in human OASFs, enhancing monocyte migration via the JAK and STAT3 signaling cascades. Our findings indicate the IL-17/MCP-1 axis as a novel strategy for the remedy of OA.

Navigation-Assisted One-Staged Posterior Spinal Fusion Using Pedicle Screw Instrumentation in Adolescent Idiopathic Scoliosis-A Case Series.

Background and Objectives: Adolescent idiopathic scoliosis (AIS) is a prevalent three-dimensional spinal disorder, with a multifactorial pathogenesis, including genetics and environmental aspects. Treatment options include non-surgical and surgical treatment. Surgical interventions demonstrate positive outcomes in terms of deformity correction, pain relief, and improvements of the cardiac and pulmonary function. Surgical complications, including excessive blood loss and neurologic deficits, are reported in 2.27-12% of cases. Navigation-assisted techniques, such as the O-arm system, have been a recent focus with enhanced precision. This study aims to evaluate the results and complications of one-stage posterior instrumentation fusion in AIS patients assisted by O-arm navigation. Materials and Methods: This retrospective study assesses 55 patients with AIS (12-28 years) who underwent one-stage posterior instrumentation correction supported by O-arm navigation from June 2016 to August 2023. We examined radiological surgical outcomes (initial correction rate, loss of correction rate, last follow-up correction rate) and complications as major outcomes. The characteristics of the patients, intraoperative blood loss, operation time, number of fusion levels, and screw density were documented. Results: Of 73 patients, 55 met the inclusion criteria. The average age was 16.67 years, with a predominance of females (78.2%). The surgical outcomes demonstrated substantial initial correction (58.88%) and sustained positive radiological impact at the last follow-up (56.56%). Perioperative complications, including major and minor, occurred in 18.18% of the cases. Two patients experienced a major complication. Blood loss (509.46 mL) and operation time (402.13 min) were comparable to the literature ranges. Trend analysis indicated improvements in operation time and blood loss over the study period. Conclusions: O-arm navigation-assisted one-stage posterior instrumentation proves reliable for AIS corrective surgery, achieving significant and sustained positive radiological outcomes, lower correction loss, reduced intraoperative blood loss, and absence of implant-related complications. Despite the challenges, our study demonstrates the efficacy and maturation of this surgical approach.

Assessing Neurological Complications in Thoracic Three-Column Osteotomy: A Clinical Application of a Novel MRI-Based Classification Approach.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To investigate the occurrence of neurological complications in patients undergoing thoracic three-column osteotomy (3CO) utilizing an magnetic resonance imaging (MRI)-based classification that assesses spinal cord shape and the presence of cerebrospinal fluid at the curve apex and evaluate its prognostic capacity for postoperative neurological deficits. SUMMARY OF BACKGROUND DATA: Recent advancements in correction techniques have improved outcomes for severe spinal deformity patients undergoing 3CO. A novel MRI-based spinal cord classification system was introduced, but its validation and association with postoperative complications remain unexplored. MATERIALS AND METHODS: Between September 2012 and September 2018, a retrospective analysis was conducted on 158 adult patients with spinal deformities undergoing 3CO. Radiographic parameters were measured. T2-weighted axial MRI was used to describe spinal cord morphology at the apex. Intraoperative neurophysiological monitoring alerts were recorded, and preoperative and postoperative neurological functions were assessed using the Frankel score. Categorical data were compared using the χ 2 or the Fisher exact test. The paired t test was utilized to assess the mean difference between preoperative and postoperative measurements, while the one-way analysis of variance and independent t test were used for comparative analyses among the different spinal cord types. RESULTS: Patients were categorized into three groups: type 1, type 2, and type 3, consisting of 12, 85, and 61 patients. Patients with type 3 morphology exhibited larger Cobb angles of the main curve ( P <0.001). This disparity persisted both postoperatively and during follow-up ( P <0.05). Intraoperative neurophysiological monitoring alerts were triggered in 32 patients (20.3%), with a distribution of one case in type 1, six cases in type 2, and 22 cases in type 3 morphologies ( P <0.001). New neurological deficits were observed in 15 patients (9.5%), with 1, 3, and 11 cases in type 1, 2, and 3 morphologies, respectively. CONCLUSIONS: Patients with type 3 morphology exhibited greater spinal deformity severity, a higher likelihood of preoperative neurological deficits, and an elevated risk of postoperative neurological complications. This underscores the utility of the classification as a tool for predicting postoperative neurological complications in patients undergoing thoracic 3CO. LEVEL OF EVIDENCE: 4.

Contamination status, partitioning behavior, ecological risks assessment of legacy and emerging per- and polyfluoroalkyl substances in a typical heavily polluted semi-enclosed bay, China.

The contaminant status, spatial distribution, partitioning behavior, and ecological risks of 26 legacy and emerging perfluoroalkyl and polyfluoroalkyl substances (PFASs) in Laizhou Bay, China were investigated. The concentrations of ∑PFASs in surface and bottom seawater ranged from 37.2 to 222 ng/L and from 34.2 to 305 ng/L with an average of 116 ± 62.7 and 138 ± 93.8 ng/L, respectively. There were no significant differences in the average concentrations between the surface and bottom seawater (P > 0.05). Perfluorooctanoic acid (PFOA) and short-chain PFASs dominated the composition of PFASs in seawater. The concentrations of ∑PFASs in sediments ranged from 0.997 to 7.21 ng/g dry weight (dw), dominated by perfluorobutane sulfonate (PFBS), perfluorobutanoic acid (PFBA), and long-chain PFASs. The emerging alternatives of perfluoro-1-butane-sulfonamide (FBSA) and 6:2 fluorotelomer sulfonic acid (6:2 FTSA) were detected for the first time in Laizhou Bay. The ∑PFASs in seawater in the southwest of the bay were higher than those in the northeast of the bay. The ∑PFASs in sediments in the northeast sea area were higher than those in the inner area of the bay. Log Kd and log Koc values increased with increasing carbon chain length for PFASs compounds. Ecological risk assessments indicated a low ecological risk associated with HFPO-DA but a moderate risk associated with PFOA contamination in Laizhou Bay. Positive matrix factorization (PMF) analysis revealed that fluoropolymer manufacturing, metal plating plants, and textile treatments were identified as major sources contributing to PFASs contamination.

S-adenosylmethionine attenuates angiotensin II-induced aortic dissection formation by inhibiting vascular smooth muscle cell phenotypic switch and autophagy.

It is well known that aortic dissection (AD) is a very aggressive class of vascular diseases. S-adenosylmethionine (SAM) is an autophagy inhibitor with anti-inflammatory and anti-oxidative stress effects; however, the role of SAM in AD is unknown. In this study, we constructed an animal model of AD using subcutaneous minipump continuous infusion of AngII-induced ApoE-/-mice and a cytopathic model using AngII-induced primary vascular smooth muscle cells (VSMCs) to investigate the possible role of SAM in AD. The results showed that mice in the AngII + SAM group had significantly lower AD incidence, significantly prolonged survival, and reduced vascular elastic fiber disruption compared with mice in the AngII group. In addition, SAM significantly inhibited autophagy in vivo and in vitro. Meanwhile, SAM also inhibited the cellular phenotypic switch, mainly by up regulating the expression levels of contractile marker proteins [α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)] and down regulating the expression levels of synthetic marker proteins [osteoblast protein (OPN), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9)]. Molecularly, SAM inhibited AD formation mainly by activating the PI3K/AKT/mTOR signaling pathway. Using a PI3K inhibitor (LY294002) significantly reversed the protective effect of SAM in AngII-induced mice and VSMCs.Our study demonstrates the protective effect of SAM on mice under AngII-induced AD for the first time. SAM prevented AD formation mainly by inhibiting cellular phenotypic switch and autophagy, and activation of the PI3K/AKT/mTOR signaling pathway is a possible molecular mechanism. Thus, SAM may be a novel strategy for the treatment of AD.

Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1.

Microglial HO-1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co-located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG-mediated autophagy and HO-1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf-A1 or HO-1 inhibitor ZnPP protected against hemin-induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG-mediated autophagy and HO-1 signalling pathway. Knock-down of FoxO3a inhibited autophagy and prevented hemin-induced ferroptosis dependent of HO-1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO-1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro-inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis-induced striatum injury in the autologous blood-induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG-mediated autophagy and HO-1 play an important role in microglial activation and ferroptosis-induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.

How sintering temperature affects the electrochemical performance of ultra-high nickel (Ni > 0.9) cathode material.

The burgeoning demand for electric vehicles with extended driving ranges has propelled ongoing development efforts for ultra-high nickel (Ni > 0.9) cathode materials. Despite significant ongoing research focused on Ni-rich cathode materials, a more comprehensive foundational understanding of ultra-high nickel cathode materials is essential. In our research, we employed LiNi0.94Co0.06O2 as a model ultra-high nickel cathode material to systematically delve into the interplay between sintering temperature, structural features, and electrochemical behavior. Within a sintering temperature spectrum of 660-720 °C, we discerned that specimens produced at diminished temperatures manifest a reduced initial discharge capacity yet excel in cycling endurance. In stark contrast, their counterparts produced at augmented temperatures behave inversely. Identifying a singular sintering temperature that achieves equilibrium between initial discharge capacity and cycling performance proves elusive. Through X-ray diffraction and high-resolution transmission electron microscopy, it became evident that samples synthesized at lower temperatures exhibit pronounced lithium-nickel mixing and develop a thicker NiO layer on the surface, leading to compromised initial discharge performance and capacity. Utilizing focused ion beam scanning electron microscopy, differential capacity analysis, and in-situ X-ray diffraction, we confirm that samples synthesized at lower temperatures possess smaller particle sizes, enabling them to withstand volumetric expansion stress during cycling, resulting in enhanced cycling performance. In the realm of ultra-high nickel cathode materials, elevating the sintering temperature is a conduit to superior initial discharge efficiency and capacity. Yet, the imperative of preserving diminutive particle dimensions, as a stratagem to bolster cycling performance, stands out as a pivotal research frontier.

Mitochondrion-targeted carboxymethyl chitosan hybrid nanoparticles loaded with Coenzyme Q10 protect cardiac grafts against cold ischaemia‒reperfusion injury in heart transplantation.

BACKGROUND: Heart transplantation (HT) has been approved as an optimal therapeutic regimen for patients with terminal-stage cardiac failure. However, cold ischaemia‒reperfusion (I/R) injury remains an unavoidable and outstanding challenge, which is a major factor in early graft dysfunction and an obstacle to long-term survival in HT. Cold I/R injury induces cardiac graft injury by promoting mitochondrial dysfunction and augmenting free radical production and inflammatory responses. We therefore designed a mitochondrion-targeted nanocarrier loaded with Coenzyme Q10 (CoQ10) (CoQ10@TNPs) for treatment of cold I/R injury after cardiac graft in a murine heterotopic cardiac transplantation model. METHODS: Hybrid nanoparticles composed of CaCO3/CaP/biotinylated-carboxymethylchitosan (CaCO3/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used for characterisation. In vitro, the hypoxia-reoxygenation model of H9c2 cells was employed to replicate in vivo cold I/R injury and treated with CoQ10@TNPs. The impact of CoQ10@TNPs on H9c2 cell injury was assessed by analysis of oxidative damage and apoptosis. In vivo, donor hearts (DHs) were perfused with preservation solution containing CoQ10@TNPs and stored in vitro at 4 °C for 12 h. The DHs were heterotopically transplanted and analysed for graft function, oxidative damage, apoptosis, and inflammatory markers 1 day post-transplantation. RESULTS: CoQ10@TNPs were successfully synthesized and delivered CoQ10 to the mitochondria of the cold ischaemic myocardium. In vitro experiments demonstrated that CoQ10@TNPs was taken up by H9c2 cells at 4 °C and localized within the mitochondria, thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury. In vivo experiments showed that CoQ10@TNPs accumulated in DH tissue at 4 °C, localized within the mitochondria during cold storage and improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation. CONCLUSIONS: CoQ10@TNPs can precisely deliver CoQ10 to the mitochondria of cold I/R-injured cardiomyocytes to effectively eliminate mitochondrial reactive oxygen species (mtROS), thus reducing oxidative injury and inflammatory reactions in cold I/R-injured graft tissues and finally improving heart graft function. Thus, CoQ10@TNPs offer an effective approach for safeguarding cardiac grafts against extended periods of cold ischaemia, emphasizing the therapeutic potential in mitigating cold I/R injury during HT. These findings present an opportunity to enhance existing results following HT and broaden the range of viable grafts for transplantation.

Novel drug delivery strategies for antidepressant active ingredients from natural medicinal plants: the state of the art.

Depression is a severe mental disorder among public health issues. Researchers in the field of mental health and clinical psychiatrists have long been faced with difficulties in slow treatment cycles, high recurrence rates, and lagging efficacy. These obstacles have forced us to seek more advanced and effective treatments. Research has shown that novel drug delivery strategies for natural medicinal plants can effectively improve the utilization efficiency of the active molecules in these plants and therefore improve their efficacy. Currently, with the development of treatment technologies and the constant updating of novel drug delivery strategies, the addition of natural medicinal antidepressant therapy has given new significance to the study of depression treatment against the background of novel drug delivery systems. Based on this, this review comprehensively evaluates and analyses the research progress in novel drug delivery systems, including nanodrug delivery technology, in intervention research strategies for neurological diseases from the perspective of natural medicines for depression treatment. This provided a new theoretical foundation for the development and application of novel drug delivery strategies and drug delivery technologies in basic and clinical drug research fields.

Understanding the Plasmonic Effect of Enhanced Photodegradation with Au Nanoparticle Decorated ZnO Nanosheet Arrays under Visible Light Irradiation.

Plasmonic-enhanced photocatalysis using visible light is considered a promising strategy for pollution photodegradation. However, there is still a lack of comprehensive and quantitative understanding of the underlying mechanisms and interactions involved. In this study, we employed a two-step process to fabricate arrays of ZnO nanosheets decorated with Au nanoparticles (Au-ZnO NS). Various characterization techniques were used to examine the morphological, structural, and chemical properties of the fabricated Au-ZnO NS array. Furthermore, we systematically investigated the photocatalytic degradation of methyl orange under visible light irradiation using Au-ZnO NS arrays prepared with varying numbers of photochemical reduction cycles. The results indicated that as the number of photochemical reduction cycles increased, the photodegradation efficiency initially increased but subsequently decreased. Under visible light irradiation, the Au-ZnO NS array obtained via four cycles of photochemical reduction exhibits the highest photocatalytic degradation rate of methyl orange 0.00926 min-1, which is six times higher than that of the ZnO NS array. To gain a better understanding of the plasmonic effect on photodegradation performance, we utilized electromagnetic simulations to quantitatively investigate the enhancement of electric fields in the Au-ZnO NS array. The simulations clearly presented the nonlinear dependencies of electric field intensity on the distribution of Au nanoparticles and the wavelength of radiation light, leading to a nonlinear enhancement of hot electron injection and eventual plasmonic photodegradation. The simulated model, corresponding to four cycles of photochemical reduction, exhibits the highest electric field intensity at 550 nm, which can be attributed to its strong plasmonic effect. This work provides mechanistic insights into plasmonic photocatalysts for utilizing visible light and represents a promising strategy for the rational design of high-performance visible light photocatalysts.

Chitosan nanoparticles encapsulated with BEZ235 prevent acute rejection in mouse heart transplantation.

Acute rejection may manifest following heart transplantation, despite the implementation of relatively well-established immunosuppression protocols. The significance of the mTOR signaling pathway in rejection is widely acknowledged. BEZ235, a second-generation mTOR inhibitor with dual inhibitory effects on PI3K and mTOR, holds promise for clinical applications. This study developed a nanodelivery system, BEZ235@NP, to facilitate the intracellular delivery of BEZ235, which enhances efficacy and reduces adverse effects by improving the poor solubility of BEZ235. In the complete MHCII-mismatched model, BEZ235@NP significantly prolonged cardiac allografts survival compared to free BEZ235, which was attributed to more effective suppression of effector T cell activation and promotion of greater expansion of Tregs. These nanoparticles demonstrated excellent biosafety and exhibited no short-term biotoxicity upon investigation. To elucidate the mechanism, primary T cells were isolated from the spleen and it was observed that BEZ235@NP treatment resulted in the arrest of these cells in the G0/G1 phase. As indicated by Western blot analysis, BEZ235@NP substantially reduced mTOR phosphorylation. This, in turn, suppressed downstream pathways and ultimately exerted an anti-proliferative and anti-activating effect on cells. Furthermore, it was observed that inhibition of the mTOR pathway stimulated T-cell autophagy. In conclusion, the strategy of intracellular delivery of BEZ235 presents promising applications for the treatment of acute rejection.