The Effectiveness of Four Nicotinamide Adenine Dinucleotide (NAD+) Precursors in Alleviating the High-Glucose-Induced Damage to Hepatocytes in Megalobrama amblycephala: Evidence in NAD+ Homeostasis, Sirt1/3 Activation, Redox Defense, Inflammatory Response, Apoptosis, and Glucose Metabolism.

The administration of NAD+ precursors is a potential approach to protect against liver damage and metabolic dysfunction. However, the effectiveness of different NAD+ precursors in alleviating metabolic disorders is still poorly elucidated. The current study was performed to compare the effectiveness of four different NAD+ precursors, including nicotinic acid (NA), niacinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN) in alleviating high-glucose-induced injury to hepatocytes in a fish model, Megalobrama amblycephala. An in vitro high-glucose model was successfully established to mimic hyperglycemia-induced damage to the liver, which was evidenced by the reduced cell viability, the increased transaminase activity, and the depletion of cellular NAD+ concentration. The NAD+ precursors all improved cell viability, with the maximal effect observed in NR, which also had the most potent NAD+ boosting capacity and a significant Sirt1/3 activation effect. Meanwhile, NR presented distinct and superior effects in terms of anti-oxidative stress, inflammation inhibition, and anti-apoptosis compared with NA, NAM, and NMN. Furthermore, NR could effectively benefit glucose metabolism by activating glucose transportation, glycolysis, glycogen synthesis and the pentose phosphate pathway, as well as inhibiting gluconeogenesis. Moreover, an oral gavage test confirmed that NR presented the most potent effect in increasing hepatic NAD+ content and the NAD+/NADH ratio among four NAD+ precursors. Together, the present study results demonstrated that NR is most effective in attenuating the high-glucose-induced injury to hepatocytes in fish compared to other NAD+ precursors.

Uncoordinated 51-like kinase 1a/b and 2 in fish Megalobrama amblycephala: Molecular cloning, functional characterization, and their potential roles in glucose metabolism.

Uncoordinated (Unc) 51-like kinase (ulk1) and ulk2 are closely involved in autophagy activation, but little is known about their roles in regulating glucose homeostasis. In this study, the genes of ulk1a, ulk1b and ulk2 were cloned and characterized in fish Megalobrama amblycephala. All the three genes shared the approximate N-terminal kinase domain and the C-terminal Atg1-like_tMIT domain structure, while the amino acid sequence identity of them are different between M. amblycephala and other vertebrates. Their transcripts were widely observed in various tissues (brain, muscle, gill, heart, spleen, eye, liver, intestine, abdominal adipose and kidney), but differed in tissue expression patterns. During the glucose tolerance test and the insulin tolerance test, the up-regulated transcriptions of ulk1a, ulk1b and ulk2 were all found despite some differences in the temporal patterns. At the same time, the activities of glycolytic enzymes like hexokinase and phosphofructokinase both showed parallel increases. Furthermore, the feeding of a high-carbohydrate diet decreased the transcriptions of ulk1a, ulk1b and ulk2. Collectively, this study demonstrated that ulk1a, ulk1b and ulk2 in M. amblycephala had similar molecular characterizations, but with different conservation and tissue expression patterns. In addition, ulk1/2 might play important roles in maintaining the glucose homeostasis in fish through regulating the glycolytic pathway.

Research on the village layout optimization in China's developed areas based on daily life circles.

Public service facilities are the basic material carrier of social services. It is of great significance for the operation of social justice and the improvement of residents' wellbeing. In the process of rapid urbanization, the demand for traffic convenience and diversity of public service facilities in rural areas has been further improved. Since the sudden outbreak of the COVID-19 epidemic, it is more necessary to meet the public service needs of human daily life within a certain space. The huge gap between urban and rural infrastructures, human living conditions, and supporting public services such as education, health, and culture has become a key bottleneck constraining the integration of urban and rural areas. It is appropriate to focus on the requirements for the construction of daily life circles and prioritize the satisfaction of villagers' increasing demand for public services in regions characterized by high levels of urban-rural integration. The behavior preference of public service facilities significantly affects the choice of residential areas. The existing research on village layout optimization focused on the spatial pattern, landscape morphology, influencing factors, and other contents. To some extent, the preference for equalization of public services in the context of urban-rural integration has been ignored. Uneven distribution and low utilization of public service facilities in villages resulted in an inability to adapt spatially and functionally in response to the renewal of urban-rural relations. Taking a highly developed urban and rural integration area named Wuxi City of Jiangsu Province in China as an example, this paper combines the current situation of public service facility allocation and the transport situation of residents in rural areas to build a life-circle system of different levels. On this basis, combined with the optimization goal of public service facilities and the constraints of agglomeration coverage, we try to determine the village layout optimization scheme under the construction of both the daily life circle and location-allocation model. The study can effectively adjust the allocation of public resources in rural areas and solve the problems of irrational village layout leading to long travel distances. It can also serve as a reference for improving the situation of lagging rural public service functions and promoting urban-rural equalization.

Genetic model of selective COX2 inhibition improve learning and memory ability and brain pathological changes in 5xFAD mouse.

Alzheimer's disease (AD) is the most common neurodegenerative disease that leads to dementia. Its pathogenesis is very complex, and inflammation is one of the main pathophysiological mechanisms of AD. Non-steroidal anti-inflammatory drugs (NSAIDs), which mainly target cyclooxygenase (COX) activity, are used to reduce the risk of AD, but several side effects limit their application. Here we assess the effect of Cyclooxygenase-2 (COX2) catalytic activity on learning ability and AD pathology using 5x Familial Alzheimer's Disease (FAD) mice with COX2 inhibition (5xFAD/COX2 KO), 5xFAD mice with cyclooxygenase inactivation of COX2 (5xFAD/COX2 Y385F), and 5xFAD mice with peroxidase (POX) inactivation of COX2 (5xFAD/COX2) H374Y), respectively. Our results indicate that learning ability of COX2 KO and mutants is improved compared to 5xFAD mice, further investigations show that Aß depositions are reduced, microglia and astrocytes homeostasis are changed in COX2 KO and mutants. Especially, there is more responsive microglia in the brain of 5xFAD/COX2 Y385F mice, and Aß depositions are more effectively cleaned at old age. Taken together, these results identify a role of COX2 Y385F in regulating microglia function and may have important implications for future treatment of AD.

Diagnosis of covert coarctation of the aorta in adolescents.

Objectives: By reviewing the diagnostic process for adolescents with coarctation of the aorta (CoA) in our institution, we analyzed the reasons for delayed diagnosis of CoA. We also proposed a diagnostic protocol to improve the detection rate of CoA. Methods: In this retrospective study, we included 48 patients aged 12-18 years who were diagnosed with CoA in our hospital from January 2000 to November 2022. Clinical data from involved cases in local hospitals and our institution were collected. Results: All patients had blood pressure (BP) measurements in upper and lower extremities in our institution. They all had hypertension, 29 (60.4%) of whom had known histories of the same. BP in the upper limbs of 47 (97.9%) patients was ≥20 mmHg higher than that in the lower limbs, and BP in the upper limb of 1 (2.1%) patient was greater than 0 and less than 20 mmHg than that in the lower limb. Echocardiography (ECHO) was performed in all patients, computed tomography (CT) or magnetic resonance imaging (MRI) was performed in 44 patients (91.7%). There were 38 (79.2%) patients who visited local hospitals. Among them, a total of 20 (52.6%) patients had their right upper extremity BP measured, 18 (47.4%) only had their left upper extremity BP measured, and 16 (42.1%) had their lower extremity BP measured. ECHO was performed in 27 (56.2%) patients and CT/MRI was performed in 18 (37.5%) patients. The detection rate for CT/MRI was 100%, and those of ECHO were 72.9% and 18.5% at our institution and a local hospital, respectively. Forty-eight (100%) and 23 (60.5%) patients were detected in our institution and local hospitals (P < 0.0001). Conclusion: We recommend measuring BP in the bilateral upper extremities. Measurement of BP in the lower extremities is recommended if hypertension is diagnosed. MRI/CT is recommended when BP in the upper extremity is greater than that in the lower extremity.

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a grave hazard to human health. Circular RNA (circRNAs) and micro RNA (miRNAs), which are competitive endogenous RNA, have been shown to play a critical role inHCM pathogenicity. However, to a great extent, the biological activities of ceRNA in HCM pathophysiology and prognosis remain to be investigated. MATERIALS AND METHODS: By analyzing the expression files in the Gene Expression Comprehensive (GEO) database, differentially expressed (DE) circRNAs, miRNAs, and mRNAs in HCM were identified, and the target molecules of circRNAs and miRNAs were predicted. The intersection of the differentially expressed RNA molecules and the expected target was then calculated, and a ceRNA network was subsequently constructed using RNA molecules. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the potential etiology was elucidated. qPCR was used to validate a portion of the hub gene using Angiotensin II to generate a cell hypertrophy model. RESULTS: Three large-scale HCM sample datasets were extracted from the GEO database. After crossing these molecules with their expected targets, the circRNA-miRNA-mRNA network had two DEcircRNAs, two DEmiRNAs, and thirty DEmRNAs, compared to normal tissues. Functional enrichment analysis of GO and KEGG demonstrated that many of the HCM pathways and mechanisms were associated with calcium channel release, which is also the primary focus of future research. The qPCR results revealed that circRNA, miRNA, and mRNA expression levels were different. They may include novel noninvasive indicators for the early screening and prognostic prediction of HCM. CONCLUSION: In this study, we hypothesized a circRNA-miRNA-mRNA regulation network that is closely related to the progression and clinical outcomes of HCM and may contain promising biomarkers and treatment targets for HCM.

Recent Advances in the Enzyme-Activatable Organic Fluorescent Probes for Tumor Imaging and Therapy.

The exploration of advanced probes for cancer diagnosis and treatment is of high importance in fundamental research and clinical practice. In comparison with the traditional "always-on" probes, the emerging activatable probes enjoy advantages in promoted accuracy for tumor theranostics by specifically releasing or activating fluorophores at the targeting sites. The main designing principle for these probes is to incorporate responsive groups that can specifically react with the biomarkers (e. g., enzymes) involved in tumorigenesis and progression, realizing the controlled activation in tumors. In this review, we summarize the latest advances in the molecular design and biomedical application of enzyme-responsive organic fluorescent probes. Particularly, the fluorophores can be endowed with ability of generating reactive oxygen species (ROS) to afford the photosensitizers, highlighting the potential of these probes in simultaneous tumor imaging and therapy with rational design. We hope that this review could inspire more research interests in the development of tumor-targeting theranostic probes for advanced biological studies.

Deletion of 11q24.2-qter in a male child with cleft lip and palate: an atypical feature of Jacobsen syndrome.

Jacobsen syndrome (JS) is caused by the terminal deletion at the long arm of chromosome 11. It is characterized by growth retardation, intellectual disability, facial dysmorphism, and other congenital abnormalities. The subband 11q24.1 has been confirmed to be the critical region for the typical features of JS. The patient in the current study is a 2-year-old male child with prominent craniofacial abnormalities and congenital heart disease. High-resolution single-nucleotide polymorphism arrays revealed breakage in chromosome 11q beginning at 11q24.2, with complete deletion of the distal portion. We collected all available reports describing patients with breakages at 11q24.1 or 11q24.2, and compared it with the typical features of JS. We found that the phenotype of cleft lip and palate (CLP) was present in both groups of patients with no overlap region in the deletion region (between 11q21-q23 and 11q24.2-qter), which indicated that other genes may be related to CLP in JS.

PACT promotes the metastasis of basal-like breast cancer through Rac1 SUMOylation and activation.

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which is associated with high malignancy, high rate of recurrence and distant metastasis, and poor prognosis among all types of breast cancer. However, there are currently no effective therapies for BLBC. Furthermore, chemoresistance limits the therapeutic options for BLBC treatment. In this study, we screen out protein activator of the interferon-induced protein kinase (PACT) as an essential gene in BLBC metastasis. We find that high PACT expression level was associated with poor prognosis among BLBC patients. In vivo and in vitro investigations indicated that PACT could regulate BLBC metastasis by interacting with SUMO-conjugating enzyme Ubc9 to stimulate the SUMOylation and thus consequently the activation of Rac1. BLBC patients receiving chemotherapy presents poorer prognosis with PACT high expression, and PACT disruption sensitizes experimental mammary tumor metastases to chemotherapy, thus providing insights to consider PACT as a potential therapeutic target to overcome acquired chemoresistance in BLBC.

Exploring the trend in religious diversity: Based on the geographical perspective.

The formation and development of religious diversity is a manifestation of the free expression of human thought, belief, and practice, as well as a historical premise and ideological condition for the gradual recognition and integration of modern religions into modern political values. This study examines the spatial characteristics of the development of the global religious diversity index (RDI) and the evolution trend through a geographical perspective by the LISA space-time transition and convergence test. The results show that: (1) At the temporal level, RDI showed a fast and then slow increase after WWII, with an increase of 61.11%. (2) At the spatial level, Latin America has seen the most significant increase in RDI, followed by Europe, North America and the Caribbean, while Asia has a slight decrease. (3) At the country level, most countries with the highest levels of RDI are located in North America and the Caribbean, Sub-Saharan Africa, and most of these countries have a history of being colonized. RDI was mainly influenced by factors such as the missionary effect in the colonial period, precipitation, GDP per capita, and genetic diversity. (4) The evolution of the spatial structure of global RDI has a certain path-dependent, but this trend is gradually weakening. In addition to countries' own development, RDI is also influenced by spillover effects from the neighboring countries. (5) There is a significant σ convergence and absolute ß convergence in the global RDI, and most of the continental units have club convergence, i.e., the internal differences in RDI levels at the global and regional levels are gradually narrowing, and there is a spillover effect of higher RDI levels to the surrounding lower regions, and this diffusion or influence allows the lower regions to catch up in the gap of RDI.

Altered pain sensitivity in 5×familial Alzheimer disease mice is associated with dendritic spine loss in anterior cingulate cortex pyramidal neurons.

ABSTRACT: Chronic pain is highly prevalent. Individuals with cognitive disorders such as Alzheimer disease are a susceptible population in which pain is frequently difficult to diagnosis. It is still unclear whether the pathological changes in patients with Alzheimer disease will affect pain processing. Here, we leverage animal behavior, neural activity recording, optogenetics, chemogenetics, and Alzheimer disease modeling to examine the contribution of the anterior cingulate cortex (ACC) neurons to pain response. The 5× familial Alzheimer disease mice show alleviated mechanical allodynia which can be regained by the genetic activation of ACC excitatory neurons. Furthermore, the lower peak neuronal excitation, delayed response initiation, as well as the dendritic spine reduction of ACC pyramidal neurons in 5×familial Alzheimer disease mice can be mimicked by Rac1 or actin polymerization inhibitor in wild-type (WT) mice. These findings indicate that abnormal of pain sensitivity in Alzheimer disease modeling mice is closely related to the variation of neuronal activity and dendritic spine loss in ACC pyramidal neurons, suggesting the crucial role of dendritic spine density in pain processing.

Case Report: Three-Dimensional Printing-Assisted Surgical Treatment of Complex Body Vein Ectopic Drainage.

INTRODUCTION: Complex ectopic drainage of body veins is a rare congenital disease. Its preoperative diagnosis and surgical choice can be considerable challenges. CASE SUMMARY: A 5-year-old patient was diagnosed precisely by preoperative transthoracic echocardiography, computed tomography (CT), three-dimensional (3D) reconstruction, and three-dimensional (3D) printing of the heart and great blood vessels. The operation was performed successfully using flexible intraoperative intubation strategies. CONCLUSION: 3D printing technology can assist in the formulation of surgical protocols for complex body vein ectopic drainage. Flexible intubation strategies can increase the success of the operation.

Tanshinone IIA alleviates NLRP3 inflammasome-mediated pyroptosis in Mycobacterium tuberculosis-(H37Ra-) infected macrophages by inhibiting endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Tanshinone IIA (Tan), extracted from Salvia miltiorrhiza Bunge, is a perennial herbal plant widely used as a folk remedy in Asian countries. Several studies have proved that Tanshinone IIA possesses many biological activities, such as anti-inflammatory, free-radical scavenging abilities, antioxidant properties, liver protection, and anti-cancer properties. AIM OF THE STUDY: The objective of the present study was to examine the anti-inflammatory effects of Tan. MATERIALS AND METHODS: The in vitro infection model of Mycobacterium tuberculosis-infected macrophages with the H37Ra strain was established. Murine macrophage Raw 264.7 and human monocyte THP-1 were used for the experiments. Cell viability was determined by the MTT assay. Western blot and lactate dehydrogenase (LDH) activity assays were used to detect the effects of Tan on cell pyroptosis and the level of NLRP3 inflammasome activation. Western blot, Co-immunoprecipitation and Immunofluorescence assays were used to observe the effect of Tan on the expression level of TXNIP. Immunofluorescence assays were applied to explore the effect of Tan on mtROS. Western blot and agarose gel electrophoresis were adopted to observe the effect of Tan on endoplasmic reticulum stress. The siRNA technique was applied to knockdown the expression levels of PERK/peIF2α, IRE1α and ATF6, and Western blot assay was employed to explore the NLRP3 inflammasome activation and possible molecular regulation mechanism of Tan. RESULTS: This study demonstrated that Tan decreased Mtb-induced cell pyroptosis by measuring GSDMD-N and LDH release provoked by NLRP3 inflammasome activation. Additionally, Tan inhibited endoplasmic reticulum stress (ERS), mitochondrial damage, and TXNIP protein expression, all of which acted as upstream signals of NLRP3 inflammasome activation in Mtb-infected macrophages. Significantly, NLRP3 inflammasome activation was suppressed by knocking down ERS pathway proteins, which further clarified that Tan partly targeted ERS to exert anti-inflammatory and immunoregulatory actions. CONCLUSION: This research confirms Tan's anti-inflammatory and immunoregulatory mechanisms in Mtb-infected macrophages by downregulating NLRP3 inflammasome activation-mediated pyroptosis provoked by ERS. Tan may function as an adjuvant drug to treat TB by adjusting host immune responses.

Case Report: Transcatheter Closure of Ruptured Sinus of Valsalva With Ventricular Septal Defect Occluder in a 3-Year-Old Child After Repair of Ventricular Septal Defect.

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that can undergo spontaneous rupture into other cardiac chambers or the pericardial space. A ruptured SVA has a very poor prognosis with high morbidity and mortality. These aneurysms often present as a rupture from the right coronary sinus into the right ventricle. Transcatheter closure has become an effective alternative to surgical treatment. However, it has been rarely reported in patients after ventricular defect repair in the past. We here describe a 3-year-and-3-month-old boy who was found to have a ruptured sinus of Valsalva. He underwent surgical closure of a ventricular septal defect at the age of 2 months, which occurred in the non-coronary sinus (NCS) and ruptured into the right atrium. We successfully occluded the ruptured sinus of Valsalva with a ventricular septal occluder.

A Rigid-Flexible Protecting Film with Surface Pits Structure for Dendrite-Free and High-Performance Lithium Metal Anode.

An artificial organic/inorganic composite protecting film for lithium metal anode with one-side surface pits structure was prepared by poly(vinylidene fluoride-co-hexafluoropropylene) and Al2O3+LiNO3 inorganic additives. Due to the unique surface structure, the composite film can not only serve as an artificial protective film, but also act as an additional lithium plating host, which synergistically enabled the lithium metal anode to adapt to high current densities meanwhile maintain dendrite-free during long-term cycling. As a result, the protected lithium metal anode can operate stably for 1000 h at a high current density of 10.0 mA cm-2. When paired with a LiFePO4 or sulfur cathode, the full cells with unflooded electrolyte showed significantly improved cycling performance, demonstrating great potential of this artificial protecting film in lithium metal batteries.

Study on the influencing factors of natural pectin's flocculation: Their sources, modification, and optimization.

Natural pectin, derived from fruit residue, presented a certain flocculation performance in previous studies. However, the process of extraction and treatment affected the flocculation performance considering the uncontrollable chemical composition and the molecule structure. In this study, degree of esterification (DE), degree of amidation (DA) were used as the internal factors affecting flocculation performance. The DE/DA values of pectin were obtained through FTIR, elemental analyses, H-NMR, and titration measurements. The kaolin suspension was employed for the coagulation jar tests, and the removal of NTU (Nephelometric Turbidity Unit) was used as the index of the flocculation performance. Results showed that the flocculation performance of pectin arising from different fruits was different, which was associated with the various preparation processes. By introducing polar groups into pectin, the flocculation was found to be related to bridging, adsorption, and charge neutralization. Based on the trends of three-dimensional response surfaces, the flocculation effect was improved with the decreased DE and the increased DA. The optimized amidated pectin was obtained by the amidation experiment, the turbidity reduction in wastewater was 99.63%. PRACTITIONER POINTS: The internal influencing factors of pectin as a flocculant were investigated. Different sources of pectin show different flocculation ability. Amidation modification can improve the flocculation performance of pectin. Response surface method to study the interaction of different influencing factors. Pectin may replace synthetic flocculants in water treatment.

Magnesium Ion Storage Properties in a Layered (NH4)2V6O16·1.5H2O Nanobelt Cathode Material Activated by Lattice Water.

Magnesium ion batteries have attracted increasing attention as a promising energy storage device due to the high safety, high volumetric capacity, and low cost of Mg. However, the strong Coulombic interactions between Mg2+ ions and cathode materials seriously hinder the electrochemical performance of the batteries. To seek a promising cathode material for magnesium ion batteries, in this work, (NH4)2V6O16·1.5H2O and water-free (NH4)2V6O16 materials are synthesized by a one-step hydrothermal method. The effects of NH4+ and lattice water on the Mg2+ storage properties in these kinds of layered cathode materials are investigated by experiments and first-principles calculations. Lattice water is demonstrated to be of vital importance for Mg2+ storage, which not only stabilizes the layered structure of (NH4)2V6O16·1.5H2O but also promotes the transport kinetics of Mg2+. Electrochemical experiments of (NH4)2V6O16·1.5H2O show a specific capacity of 100 mA·h·g-1 with an average discharge voltage of 2.16 V vs Mg2+/Mg, highlighting the potential of (NH4)2V6O16·1.5H2O as a high-voltage cathode material for magnesium ion batteries.

Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.

Self-Assembly of Hollow Graphene Oxide Microcapsules Directed by Cavitation for Loading Hydrophobic Drugs.

Hollow graphene oxide microcapsules (GOMs) have been widely used in energy, electronics, catalysis, sensing, tissue engineering, and drug loading due to their unique properties. However, it is still a great challenge to prepare GOMs with high quality and in large quantity using a simple method. In this work, we obtained single-component GOMs using the liquid nitrogen cavitation effect, which directed the self-assembly of graphene oxide (GO) debris at the gas-liquid interface. This method avoids the introduction of additional components and removal of templates. The morphology of GOM with wrinkles on its surface was characterized by transmission electron microscopy and scanning electron microscopy. The abundant polar groups of GO microcapsules enabled them to easily disperse in water. Based on this, GOMs have good potential for loading hydrophobic drugs. Subsequently, we used GOMs as carriers to deliver a hydrophobic drug paclitaxel (PTX), which exhibited a good loading capacity. Moreover, PTX loaded GOMs showed excellent cytotoxicity to A549 and MDA-MB-231 cells. The GOMs also showed a pH-dependent drug release performance. Therefore, GOMs can be regarded as potential carriers for biomedical applications.

Suppressing NK Cells by Astragaloside IV Protects Against Acute Ischemic Stroke in Mice Via Inhibiting STAT3.

Natural killer (NK) cells, a key member of innate lymphocytes, are a promising immunotherapeutic target for ischemic stroke. Astragaloside IV (ASIV) is isolated from Astragalus mongholicus Bunge (Fabaceae), a herbal medicine possessing immunomodulatory ability. This study investigated the effect of ASIV on NK cells during the acute stage of brain ischemic injury in a mouse model of middle cerebral artery occlusion (MCAO). MCAO mice treated with ASIV had better functional outcomes, smaller brain infarction and less NK cell brain infiltration. NK cell depletion echoed the protective effect of ASIV. Notably, ASIV did not enhance the protective effect of NK cell depletion against brain ischemic injury. ASIV inhibited glial cell-derived CCL2-mediated chemotaxis to prevent post-ischemic NK cell brain recruitment. Meanwhile, ASIV also abrogated NK cell-mediated cytolytic killing of neurons subjected to oxygen-glucose deprivation and suppressed NK cell-derived IFN-γ and NKG2D expression in the ischemic brain. The inhibitory effect of ASIV on NK cell brain infiltration and activation was mimicked by cryptotanshinone, a STAT3 inhibitor. There was no additive effect when ASIV and cryptotanshinone were used together. In conclusion, ASIV inhibits post-ischemic brain infiltration and activation of NK cells through STAT3 suppression, and this inhibitory effect of ASIV on NK cells plays a key role in its protection against acute ischemic brain injury. Our findings suggest that ASIV is a promising therapeutic candidate in NK cell-based immunotherapy for the treatment of acute ischemic stroke and pave the way for potential clinical trials.