Naked-Eye 3-Dimensional Vision Training for Myopia Control: A Randomized Clinical Trial.

Importance: Early onset of myopia increases the risk of high myopia, which can lead to irreversible retinal damage and even loss of central vision. Objective: To investigate the efficacy and safety of naked-eye 3-dimensional vision training (NVT) in preventing the progression of myopia in children. Design, Setting, and Participants: This randomized clinical trial was conducted in 3 hospitals from May 25, 2022, to February 24, 2023. Participants were children (aged 6-18 years) who had a diagnosis of myopia with a spherical equivalent refraction of -0.75 to -6.00 diopters (D). Intervention: Children in the intervention group received 20 minutes of NVT treatment every day, whereas children in the control group lived as usual without vision training. Main Outcome and Measure: The primary outcome was the change in axial length at 6 months. Spherical equivalent refraction (SER) was included as a secondary outcome. Results: Among 263 participants, 125 (47.5%) were male and 138 (52.5%) were female; the mean (SD) age was 10.3 (1.9) years (range, 6.1-15.6 years). A total of 227 patients (86.3%) completed the 6-month follow-up, including 102 in the intervention group and 125 in the control group. In the intervention group, the changes in axial length and SER at 6 months were 0.18 mm (95% CI, 0.16 to 0.20 mm) and -0.25 D (95% CI, -0.31 to -0.19 D), respectively. In the control group, the changes in axial length and SER at 6 months were 0.23 mm (95% CI, 0.21 to 0.25 mm) and -0.35 D (95% CI, -0.41 to -0.30 D), respectively. The differences in AL and SER between the 2 groups were significant (AL difference: -0.06 mm; 95% CI, -0.09 to -0.03; P < .001; SER difference: 0.10 D; 95% CI, 0.02 to 0.19; P = .02). No study-related adverse reactions were reported during follow-up. Conclusions and Relevance: NVT is a safe and promising means to control myopia progression in children with good adherence. Trial Registration: ClinicalTrials.gov Identifier: NCT05468775.

Recent advances in functional nucleic acid decorated nanomaterials for cancer imaging and therapy.

Nanomaterials possess unusual physicochemical properties including unique optical, magnetic, electronic properties, and large surface-to-volume ratio. However, nanomaterials face some challenges when they were applied in the field of biomedicine. For example, some nanomaterials suffer from the limitations such as poor selectivity and biocompatibility, low stability, and solubility. To address the above-mentioned obstacles, functional nucleic acid has been widely served as a powerful and versatile ligand for modifying nanomaterials because of their unique characteristics, such as ease of modification, excellent biocompatibility, high stability, predictable intermolecular interaction and recognition ability. The functionally integrating functional nucleic acid with nanomaterials has produced various kinds of nanocomposites and recent advances in applications of functional nucleic acid decorated nanomaterials for cancer imaging and therapy were summarized in this review. Further, we offer an insight into the future challenges and perspectives of functional nucleic acid decorated nanomaterials.

A Lesion-Fusion Neural Network for Multi-View Diabetic Retinopathy Grading.

As the most common complication of diabetes, diabetic retinopathy (DR) is one of the main causes of irreversible blindness. Automatic DR grading plays a crucial role in early diagnosis and intervention, reducing the risk of vision loss in people with diabetes. In these years, various deep-learning approaches for DR grading have been proposed. Most previous DR grading models are trained using the dataset of single-field fundus images, but the entire retina cannot be fully visualized in a single field of view. There are also problems of scattered location and great differences in the appearance of lesions in fundus images. To address the limitations caused by incomplete fundus features, and the difficulty in obtaining lesion information. This work introduces a novel multi-view DR grading framework, which solves the problem of incomplete fundus features by jointly learning fundus images from multiple fields of view. Furthermore, the proposed model combines multi-view inputs such as fundus images and lesion snapshots. It utilizes heterogeneous convolution blocks (HCB) and scalable self-attention classes (SSAC), which enhance the ability of the model to obtain lesion information. The experimental results show that our proposed method performs better than the benchmark methods on the large-scale dataset.

Choriocapillaris flow features in children with myopic anisometropia.

AIMS: To examine differences between the eyes in choriocapillaris perfusion and choroidal thickness in children with myopic anisometropia. METHODS: In this observational and prospective study, 46 children with myopic anisometropia were enrolled. Choriocapillaris perfusion parameters, including the percentage of flow voids, the total number of flow voids and the average flow void area were obtained by optical coherence tomography angiography (OCTA). The OCTA image was divided into a 1 mm-diameter central circle (C1) and a 2.5 mm-diameter annulus (without the inner central 1 mm circle, C1-2.5). Both C1 and C1-2.5 are centred on the foveola. The C1-2.5 was divided into nasal (N1-2.5), temporal (T1-2.5), inferior (I1-2.5) and superior (S1-2.5) areas. Differences in these parameters in different regions between eyes were analysed. RESULTS: There were no significant differences in the percentage of flow voids and the average flow void area between the fellow eyes. The total number of signal voids was significantly higher in the less myopic eyes in C1-2.5 (p=0.032), S1-2.5 (p=0.008) and N1-2.5 (p=0.019). Changes in spherical equivalent refraction and axial length were both correlated with the changes in the total number of flow voids in N1-2.5 (R=-0.431, p=0.03; R=-0.297, p=0.047). CONCLUSIONS: The choroid in the macular region becomes thinner and the total number of flow voids in the nasal macular region decreased with the amplitude of myopia. This suggests that a decrease in total number of flow voids may indicate an early change in myopia.

A universal ANN-to-SNN framework for achieving high accuracy and low latency deep Spiking Neural Networks.

Spiking Neural Networks (SNNs) have become one of the most prominent next-generation computational models owing to their biological plausibility, low power consumption, and the potential for neuromorphic hardware implementation. Among the various methods for obtaining available SNNs, converting Artificial Neural Networks (ANNs) into SNNs is the most cost-effective approach. The early challenges in ANN-to-SNN conversion work revolved around the susceptibility of converted SNNs to conversion errors. Some recent endeavors have attempted to mitigate these conversion errors by altering the original ANNs. Despite their ability to enhance the accuracy of SNNs, these methods lack generality and cannot be directly applied to convert the majority of existing ANNs. In this paper, we present a framework named DNISNM for converting ANN to SNN, with the aim of addressing conversion errors arising from differences in the discreteness and asynchrony of network transmission between ANN and SNN. The DNISNM consists of two mechanisms, Data-based Neuronal Initialization (DNI) and Signed Neuron with Memory (SNM), designed to respectively address errors stemming from discreteness and asynchrony disparities. This framework requires no additional modifications to the original ANN and can result in SNNs with improved accuracy performance, simultaneously ensuring universality, high precision, and low inference latency. We verify it experimentally on challenging object recognition datasets, including CIFAR10, CIFAR100, and ImageNet-1k. Experimental results show that the SNN converted by our framework has very high accuracy even at extremely low latency.

Regulation of Electronic Structures of the Urchin-Like NiCoP/CoP Nanocatalysts for Fast Hydrogen Evolution.

The exploration of stable, efficient, and low-cost catalysts toward ammonia borane hydrolysis is of vital significance for the practical implementation of this hydrogen production technology. Integrating interface engineering and nano-architecture engineering is a favorable strategy to elevate catalytic performance, as it can modify the electronic structure and provide sufficient active sites simultaneously. In this work, urchin-like NiCoP/CoP heterostructures are prepared via a three-step hydrothermal-oxidation-phosphorization synthesis route. It is demonstrated that the original Ni/Co molar ratio and the amount of phosphorus are crucial for adjusting the morphology, enhancing the exposed surface area, facilitating charge transfer, and modulating the adsorption and activation of H2O molecules. Consequently, the optimal Ni1Co2P heterostructure displays remarkable catalytic properties in the hydrolysis of ammonia borane with a turnover frequency (TOF) value of 30.3 molH2 ⋅ min-1 ⋅ molmetal -1, a low apparent activation energy of 25.89 kJ ⋅ mol-1, and good stability. Furthermore, by combining infrared spectroscopy and isotope kinetics experiments, a possible mechanism for the hydrolysis of ammonia borane was proposed.

Microstructure and Friction Properties of AlCrTiVNbx High-Entropy Alloys via Annealing Manufactured by Vacuum Arc Melting.

To enhance the friction and wear properties of alloys, AlCrTiVNbx high-entropy alloys (HEAs) with various Nb contents were prepared using the arc melting technique and then annealed at 1000 °C for 2 h. The microstructure and hardness changes in the AlCrTiVNbx (x = 0.3, 0.4, and 0.5) HEAs after casting and annealing were studied via scanning electron microscopy, X-ray diffractometry, optical microscopy and the Vickers hardness test. The MFT-EC400 ball disc reciprocating friction and wear tester was used to investigate the wear resistance of the HEAs before and after annealing. The results show that the annealed AlCrTiVNbx HEAs changed from a single-phase structure to a multi-phase structure, and the content of the face-center cubic (FCC) phase and hexagonal close-packed (HCP) phase further increases with the increase in Nb content. The hardness value of the annealed HEAs is greatly enhanced compared with the casting state, and the hardness of the Nb0.5 HEA is increased from 543 HV to 725 HV after annealing. The wear resistance of the alloys after the annealing treatment is also greatly improved, among which Nb0.5 has the best wear resistance. The average friction coefficient of Nb0.5 is 0.154 and the wear rate is 2.117 × 10-5 mm3/(N·m). We believe that the precipitation strengthening after the annealing treatment and the lubrication effect of the FCC phase are the reasons for the significant improvement in wear resistance. The morphology of the samples indicates that the wear mechanism of the alloy includes adhesive wear, abrasive wear and a certain degree of oxidation wear.

AMHGCN: Adaptive multi-level hypergraph convolution network for human motion prediction.

Human motion prediction is the key technology for many real-life applications, e.g., self-driving and human-robot interaction. The recent approaches adopt the unrestricted full-connection graph representation to capture the relationships inside the human skeleton. However, there are two issues to be solved: (i) these unrestricted full-connection graph representation methods neglect the inherent dependencies across the joints of the human body; (ii) these methods represent human motions using the features extracted from a single level and thus can neither fully exploit the various connection relationships among the human body nor guarantee the human motion prediction results to be reasonable. To tackle the above issues, we propose an adaptive multi-level hypergraph convolution network (AMHGCN), which uses the adaptive multi-level hypergraph representation to capture various dependencies among the human body. Our method has four different levels of hypergraph representations, including (i) the joint-level hypergraph representation to capture inherent kinetic dependencies in the human body, (ii) the part-level hypergraph representation to exploit the kinetic characteristics at a higher level (in comparison to the joint-level) by viewing some part of the human body as an entirety, (iii) the component-level hypergraph representation to model the semantic information, and (iv) the global-level hypergraph representation to extract long-distance dependencies in the human body. In addition, to take full advantage of the knowledge carried in the training data, we propose a reverse loss (i.e., adopting the future human poses to predict the historical poses reversely) to realize data augmentation. Extensive experiments show that our proposed AMHGCN can achieve state-of-the-art performance on three benchmarks, i.e., Human3.6M, CMU-Mocap, and 3DPW.

Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway.

In the treatment of unresectable advanced hepatocellular carcinoma (HCC), cisplatin is administered transhepatic arterially for local treatment, but the clinical application of cisplatin drugs is frequently hindered by the emergence of drug resistance. Kinesin family member 2C( KIF2C ) has been shown as oncogene in a variety of tumors. Nevertheless, its effect on cisplatin sensitivity has yet to be ascertained. Herein, we aim to investigate the impact of the KIF2C gene on cisplatin sensitivity within HCC and the plausible underlying molecular mechanism. We examined the expression level of the KIF2C gene in HCC cells by real-time quantitative reverse transcription PCR and Western blot analysis, and analyzed bioinformatically by The Gene Expression Omnibus database and The Cancer Genome Atlas database. The KIF2C gene was silenced using the small interfering RNA technology, and its effect on cisplatin drug sensitivity in HCC cells was evaluated by flow cytometry, cell proliferation, cell migration, and invasion assays. Our results indicated that KIF2C was highly expressed in HCC cells. KIF2C silencing inhibits HCC cell proliferation, migration and invasion, promotes apoptosis, and keeps the cell cycle in G2 phase. In addition, KIF2C silencing enhanced the sensitivity of HCC cells to cisplatin. KIF2C silencing down-regulates the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mitogen-activated protein kinase 3 (MAPK3) proteins. In conclusion, KIF2C silencing amplifies the sensitivity of HCC cells to cisplatin by regulating the PI3K/AKT/MAPK signaling pathway. Consequently, targeting KIF2C shows great application potential as a strategy for enhancing the effectiveness of HCC treatment.

Biomass carbon and Ti2C3MXene quantum dots as ratiometric fluorescent probes for sensitive detecting malachite green in fish sample.

A visual detection method for malachite green (MG) in food was established based on 'double-response-OFF' ratiometric fluorescent paper-based sensor. Biomass carbon quantum dots (BCQDs) using broad bean shell, and Ti3C2MXene quantum (MQDs) dots modified by ethylenediamine were synthesized by solvothermal method. The MG and two kinds of quantum dots could undergo static quenching, and the fluorescence color of two kinds of quantum dots gradually changed from red to blue, eventually the fluorescence was quenched, and the pattern had a two-stage linear relationship using fluorescent spectrofluorometer in the range of 0.1-140.0µM and the detection limit of 0.07µM. On this basis, a BCQDs/MQDs ratiometric fluorescence paper-based sensor was constructed and applied to fish sample. Through mobile phone software-Color recognizer, RGB values of fluorescent paper-based sensor at various concentrations of MG were extracted. The results showed that MG concentration was linearly correlated withR' value of RGB in the range of 20.0-140.0µM with 16.5µM detection limit. The method had been applied to the determination of canned fish and fresh basa fish samples, and the recovery rates were 97.33%-108.93% and 96.04%-117.97%, respectively. It proved that the ratiometric fluorescent paper-based sensor could be used for the rapid visual quantitative detecting MG in real samples.

Experiences of Non-Family Paid Helpers Providing Palliative Care to Stroke Patients: The Toll of Professional Informal Caregiving in a Job Lacking Recognition.

Background: Employing non-family paid helpers has become a prevalent practice across North America, Europe, and Asia, which families adopt to alleviate the stroke care burden, allowing family to take a break from their obligations and perform other social activities. However, paid helpers' experiences of providing palliative care to stroke patients are under-explored. This study aimed to explore the caregiving experiences of non-family paid helpers providing palliative care to stroke patients. Method: A qualitative descriptive study was undertaken using purposive sampling and semi-structured individual in-depth interviews. Thematic analysis was used for data analysis. Results: Seventeen participants (mean age: 51.23 years) were included, predominantly being female (88%), and their caregiving experiences with patients ranged from four to 26 years. Participants shared that monetary compensation offset the exhaustion, familial and health sacrifices of palliative caregiving. They emphasized emotional self-management through accepting and coping or avoiding and distancing, and appreciated rewarding appraisals from stroke patients and family members. They also expressed a lack of recognition from the public, being invisible to the healthcare system/professionals, and insecurity in employment rights. Conclusions: Findings support the need for governmental initiatives to subsidize families in employing helpers to provide palliative care. Helpers perceived monetary compensation and a reciprocal caregiving relationship as the primary motives for providing care. Public recognition of this role as a helper in caregiving, contractual employment rights, and being recognized by the healthcare system and healthcare professionals are considerations in promoting quality care and alleviating a health care burden. The findings may contribute to further understanding of the experiences of non-family paid helpers in a job lacking recognition when delivering palliative care in a hospital for stroke patients. Evidence-based interventions that enhance reciprocity and recognition should be considered as part of the global initiatives to support paid helpers in palliative care.

Standard ophthalmology residency training in China: an evaluation of resident satisfaction on training program in Guangdong Province.

BACKGROUND: National standardized training for resident doctors (STRD) in mainland China has been formally established since 2014 as a kind of postgraduate education. The purpose of this survey was to assess the satisfaction of the training residents in Guangdong Province on the ophthalmology STRD program after a duration of 5 years. METHOD: A 48-item survey was sent to all postgraduate ophthalmology residents from bases in Guangdong Province to inquire about their attitude towards the program. The survey contained questions about demographic and work-related information, job satisfaction, psychological resilience, and job performance. All responses were verified, and invalid questionnaires were excluded. Statistical analyses were performed using SPSS software version 22.0 (SPSS, Inc., Chicago, IL). Multiple logistic regression analysis was used to evaluate the factors (demographic information, working environment, clinical exposure, supervision and hands-on training opportunities, and involvement in academic activities) impacting the overall satisfaction. P < 0.05 was considered statistically significant. RESULTS: A total of 471/635 (74.17%) valid questionnaires were returned from all the STRD bases of Guangdong Province, which included 38 hospitals. 60.3% of the respondents reported overall satisfaction with their training. The satisfaction with operative teaching (60.7%) was slightly lower than the other settings of teaching experience (above 65%). Meanwhile, the satisfaction on different secessions of operative experience was all below 70%, of which in the areas of cornea and orbit were 55.42% and 57.53%, respectively. Some potential factors were found to affect general satisfaction, including the training grade, marriage, working time, income level, the doctor-patient relationship, family members working as doctors, the time proportion spent on writing medical documents during clinical work, and the frequency of attending academic meetings. Improvement was observed in both performing and reporting clinical examinations in the last year of training in comparison to the first year. Finally, 82.8% of the residents acknowledged this training was helpful for future clinical work. The first five career preferences for residents were cataract (67.1%), refractive surgery (42.3%), vitreo-retina (36.5%), optometry (28.7%), and oculoplastic (27.2%). CONCLUSION: Ophthalmology residents in Guangdong Province expressed comparable satisfaction with the STRD program. To further improve satisfaction, factors such as resident subsidy, harmonious marriage, the patient-doctor relationship, and chances of attending academic conferences should be emphasized.

A biologically inspired auto-associative network with sparse temporal population coding.

Associative system has attracted increasing attention for it can store basic information and then infer details to match perception with an efficient self-organization algorithm. However, the implementation of the associative system with the application of real-world data is relatively difficult. To address this issue, we propose a novel biologically inspired auto-associative (BIAA) network to explore the structure, encoding and formation of associative memory as well as to extend the ability to real-world application. Our network is constructed by imitating the organization of the cortical minicolumns where each minicolumn contains plenty of parallel biological spiking neurons. To allow the network to learn and predict one symbol per theta cycle, we incorporate synaptic delay and theta oscillation into the neuron dynamic process. Subsequently, we design a sparse temporal population (STP) coding scheme that allows each input symbol to be represented as stable, unique, and easily recallable sparsely distributed representations. By combining associative learning dynamics with the STP coding, our network realizes efficient storage and inference in an ordered manner. Experimental results indicate that the proposed network successfully performs sequence retrieval from partial text and sequence recovery from distorted information. BIAA network provides new insight into introducing biologically inspired mechanisms into associative system and has enormous potential for hardware and software applications.

hESC-Derived Epicardial Cells Promote Repair of Infarcted Hearts in Mouse and Swine.

Myocardial infarction (MI) causes excessive damage to the myocardium, including the epicardium. However, whether pluripotent stem cell-derived epicardial cells (EPs) can be a therapeutic approach for infarcted hearts remains unclear. Here, the authors report that intramyocardial injection of human embryonic stem cell-derived EPs (hEPs) at the acute phase of MI ameliorates functional worsening and scar formation in mouse hearts, concomitantly with enhanced cardiomyocyte survival, angiogenesis, and lymphangiogenesis. Mechanistically, hEPs suppress MI-induced infiltration and cytokine-release of inflammatory cells and promote reparative macrophage polarization. These effects are blocked by a type I interferon (IFN-I) receptor agonist RO8191. Moreover, intelectin 1 (ITLN1), abundantly secreted by hEPs, interacts with IFN-ß and mimics the effects of hEP-conditioned medium in suppression of IFN-ß-stimulated responses in macrophages and promotion of reparative macrophage polarization, whereas ITLN1 downregulation in hEPs cancels beneficial effects of hEPs in anti-inflammation, IFN-I response inhibition, and cardiac repair. Further, similar beneficial effects of hEPs are observed in a clinically relevant porcine model of reperfused MI, with no increases in the risk of hepatic, renal, and cardiac toxicity. Collectively, this study reveals hEPs as an inflammatory modulator in promoting infarct healing via a paracrine mechanism and provides a new therapeutic approach for infarcted hearts.

Deep Reinforcement Learning for Joint Trajectory Planning, Transmission Scheduling, and Access Control in UAV-Assisted Wireless Sensor Networks.

Unmanned aerial vehicles (UAVs) can be used to relay sensing information and computational workloads from ground users (GUs) to a remote base station (RBS) for further processing. In this paper, we employ multiple UAVs to assist with the collection of sensing information in a terrestrial wireless sensor network. All of the information collected by the UAVs can be forwarded to the RBS. We aim to improve the energy efficiency for sensing-data collection and transmission by optimizing UAV trajectory, scheduling, and access-control strategies. Considering a time-slotted frame structure, UAV flight, sensing, and information-forwarding sub-slots are confined to each time slot. This motivates the trade-off study between UAV access-control and trajectory planning. More sensing data in one time slot will take up more UAV buffer space and require a longer transmission time for information forwarding. We solve this problem by a multi-agent deep reinforcement learning approach that takes into consideration a dynamic network environment with uncertain information about the GU spatial distribution and traffic demands. We further devise a hierarchical learning framework with reduced action and state spaces to improve the learning efficiency by exploiting the distributed structure of the UAV-assisted wireless sensor network. Simulation results show that UAV trajectory planning with access control can significantly improve UAV energy efficiency. The hierarchical learning method is more stable in learning and can also achieve higher sensing performance.

Supplementation of Lactobacillus plantarum ATCC14917 mitigates non-alcoholic fatty liver disease in high-fat-diet-fed rats.

Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) have been increasing at an alarming rate worldwide. Many clinical studies have underlined the link between NAFLD and atherosclerosis. Our previous experiments have discovered that Lactobacillus (L.) plantarum ATCC14917 supplementation could decrease the progression of atherosclerotic lesion formation. In this study, we aimed to investigate the role of supplementation of L. plantarum ATCC14917 mitigates liver injury in rats fed with a high-fat diet (HFD, 45% kcal from fat). A total of 32 rats were randomly divided into four groups, including two intervention groups, who fed with HFD and administering either 1 × 107 or 1 × 109 colony forming units (CFU) of L. plantarum ATCC14917, the normal control group, and the HFD control group. The results showed that supplementation with low-dose and high-dose of L. plantarum ATCC14917 for 8 weeks could alleviate the body weight gain (p < 0.05), hepatic steatosis, and serum lipid metabolism (p < 0.05) in HFD-fed rats. Moreover, supplementation of L. plantarum ATCC 14917 decreased total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels (p < 0.05) in serum, and improved HFD-associated inflammation (p < 0.05). Furthermore, cecal contents were analyzed by high-throughput 16S ribosomal RNA sequencing. The results indicated that supplementation of L. plantarum ATCC 14917 could ameliorate HFD-induced gut dysbiosis. In summary, our findings suggest that supplementation of L. plantarum ATCC 14917 could mitigate NAFLD in rats, suggesting it may be considered as a probiotic agent for preventing HFD-induced obesity.

Information Recovery-Driven Deep Incomplete Multiview Clustering Network.

Incomplete multiview clustering (IMC) is a hot and emerging topic. It is well known that unavoidable data incompleteness greatly weakens the effective information of multiview data. To date, existing IMC methods usually bypass unavailable views according to prior missing information, which is considered a second-best scheme based on evasion. Other methods that attempt to recover missing information are mostly applicable to specific two-view datasets. To handle these problems, in this article, we propose an information-recovery-driven-deep IMC network, termed as RecFormer. Concretely, a two-stage autoencoder network with self-attention structure is built to synchronously extract high-level semantic representations of multiple views and recover the missing data. Besides, we develop a recurrent graph reconstruction mechanism that cleverly leverages the restored views to promote representation learning and further data reconstruction. Visualization of recovery results are given and sufficient experimental results confirm that our RecFormer has obvious advantages over other top methods.

Tumor Targeting with Apatinib-loaded Nanoparticles and Sonodynamic Combined Therapy

INTRODUCTION: This study implies the enhancement of apatinib killing effect in 4T1 tumor cells through constructing drug-loaded nanoparticles apatinib/Ce6@ZIF-8@Membranes (aCZM) to enhance tumor therapeutic targeting and reduce toxic side following sonodynamic therapy (SDT). METHODS: apatinib/Ce6@ZIF-8 (aCZ) were synthesized by in situ encapsulation, and aCZM were constructed by encapsulating the nanoparticles with extracted breast cancer 4T1 cell membranes. aCZM were characterized and tested for the stability by electron microscopy, and the membrane proteins on the nanoparticles' surface were assessed using SDS-PAGE gel electrophoresis. The cell viability of 4T1 cells following treatment with aCZM was tested using cell counting kit-8 (CCK-8). The uptake of nanoparticles was detected by laser confocal microscopy and flow cytometry, and the SDT-mediated production of reactive oxygen species (ROS) was verified by singlet oxygen sensor green (SOSG), electron spin resonance (ESR), and DCFH-DA fluorescent probes. The CCK-8 assay and flow cytometry using Calcein/PI were used to assess the antitumoral effect of aCZM nanoparticles under SDT. The biosafety of aCZM was further verified in vitro and in vivo using the hemolysis assay, routine blood test and H&E staining of vital organs in Balb/c mice. RESULTS: aCZM with an average particle size of about 210.26 nm were successfully synthesized. The results of the SDS-PAGE gel electrophoresis experiment showed that aCZM have a band similar to that of pure cell membrane proteins. The CCK-8 assay demonstrated the absence of effects on cell viability at a low concentration range, and the relative cell survival rate reached more than 95%. Laser confocal microscopy and flow cytometry analysis showed that aCZM treated group has the strongest fluorescence and the highest cellular uptake of nanoparticles. SOSG, ESR, and DCFH-DA fluorescent probes all indicated that the aCZM + SDT treated group has the highest ROS production. The CCK-8 assay also showed that when the ultrasound intensity was fixed at 0.5 W/cm2, the relative cell survival rates in the medium concentration group (10 µg/ml) (5.54 ± 1.26%) and the high concentration group (20 µg/ml) (2.14 ± 1.63%) were significantly lower than those in the low concentration group (5 µg/ml) (53.40 ± 4.25%). Moreover, there was a concentration and intensity dependence associated with the cell-killing effect. The mortality rate of the aCZM in the ultrasound group (44.95±3.03%) was significantly higher than that of the non-ultrasound (17.00±2.26%) group and aCZ + SDT group (24.85 ± 3.08%) (P<0.0001). The live and dead cells' staining (Calcein/PI) also supported this result. Finally, in vitro hemolysis test at 4 and 24 hours showed that the hemolysis rate of the highest concentration group was less than 1%. The blood routine, biochemistry, and H&E staining results of major organs in Balb/c mice undergoing nano-treatments showed no obvious functional abnormalities and tissue damage in 30 days. CONCLUSION: In this study, a multifunctional bionic drug delivery nanoparticles (aCZM) system with good biosafety and compatibility in response to acoustic dynamics was successfully constructed and characterized. This system enhanced apatinib killing effect on tumor cells and reduced toxic side effects under SDT.

Influence of SGLT2i and RAASi and Their Combination on Risk of Hyperkalemia in DKD: A Network Meta-Analysis.

BACKGROUND: This network meta-analysis investigated the effect of various combined regimens of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and renin-angiotensin-aldosterone system inhibitors (RAASis) on the occurrence of hyperkalemia in diabetic kidney disease. METHODS: The risk of hyperkalemia was compared using the random-effects model of network meta-analysis, with results expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The comparative effects of all medications and their combinations with placebo were ranked using the surface under the cumulative ranking probabilities. RESULTS: In total, 27 eligible studies involving 43,589 participants with diabetic kidney disease were included. Major findings showed that the use of mineralocorticoid receptor antagonists (MRAs) on top of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) prominently increased hyperkalemia incidence when compared with placebo (OR, 6.08; 95% CI, 2.30 to 16.08), ACEI (OR, 3.07; 95% CI, 1.14 to 8.31), ARB (OR, 2.57; 95% CI, 1.10 to 6.02), SGLT2i (OR, 9.22; 95% CI, 2.99 to 28.46), renin inhibitors+ACEI/ARB (OR, 2.23; 95% CI, 1.14 to 4.36), or SGLT2i+ACEI/ARB (OR, 4.10; 95% CI, 2.32 to 7.26). Subgroup analysis among different generations of MRA found that spironolactone had the strongest effect in combination with ACEI/ARB, even higher than the combined use of ACEI and ARB (OR, 2.89; 95% CI, 1.26 to 6.63). In addition, SGLT2i had a significantly lower incidence of hyperkalemia compared with ACEI (OR, 0.33; 95% CI, 0.12 to 0.91), ARB (OR, 0.28; 95% CI, 0.13 to 0.61), dual RAASi (ACEI combined with ARB; OR, 0.17; 95% CI, 0.06 to 0.47), or MRA or renin inhibitors combined with ACEI/ARB (OR, 0.11; 95% CI, 0.04 to 0.33; OR, 0.24; 95% CI, 0.08 to 0.76, respectively). Moreover, adding SGLT2i to the combination of MRA and ACEI/ARB, as well as the combinations of different RAASis, markedly reduced the occurrence of hyperkalemia. CONCLUSIONS: Among the therapeutic drugs with the potential risk of increasing serum potassium in patients with diabetic kidney disease, MRA added an extra risk of hyperkalemia while SGLT2i had the opposite effect and could even reverse the elevation of serum potassium caused by the combined regimen, including MRAs.

Effect of naringenin on the anti-inflammatory, vascularization, and osteogenesis differentiation of human periodontal ligament stem cells via the stromal cell-derived factor 1/C-X-C motif chemokine receptor 4 signaling axis stimulated by lipopolysaccharide.

OBJECTIVES: This study aimed to investigate how naringenin (Nar) affected the anti-inflammatory, vascula-rization, and osteogenesis differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by lipopolysaccharide (LPS) and to preliminarily explore the underlying mechanism. METHODS: Cell-counting kit-8 (CCK8), cell scratch test, and Transwell assay were used to investigate the proliferation and migratory capabilities of hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red staining, lumen-formation assay, enzyme-linked immunosorbent assay, quantitative timed polymerase chain reaction, and Western blot were used to measure the expression of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), vascular endothlial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrand factor (vWF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. RESULTS: We observed that 10 µmol/L Nar could attenuate the inflammatory response of hPDLSCs stimulated by 10 µg/mL LPS and promoted their proliferation, migration, and vascularization differentiation. Furthermore, 0.1 µmol/L Nar could effectively restore the osteogenic differentiation of inflammatory hPDLSCs. The effects of Nar's anti-inflammatory and promotion of osteogenic differentiation significantly decreased and inflammatory vascularization differentiation increased after adding AMD3100 (a specific CXCR4 inhibitor). CONCLUSIONS: Nar demonstrated the ability to promote the anti-inflammatory, vascularization, and osteogenic effects of hPDLSCs stimulated by LPS, and the ability was associated with the stromal cell-derived factor/C-X-C motif chemokine receptor 4 signaling axis.