Enhanced Preoperative Planning for Intracranial Aneurysms Through Multimodal Image Fusion of Silent/Time-of-Magnetic Resonance Angiography and Computed Tomography Using 3DSlicer: A Comparative Efficacy Analysis With Computed Tomography Angiography.

OBJECTIVE: This study evaluates the effectiveness of multimodal image fusion (MIF) using silent and time-of-flight (TOF) magnetic resonance angiography (MRA) and computed tomography (CT) for preoperative planning in patients with intracranial aneurysms who have contraindications to contrast media. MATERIALS AND METHODS: A retrospective study included 40 patients with intracranial aneurysms, diagnosed using three-dimensional computed tomography angiography (CTA). These patients underwent both Silent and TOF MRA scans, followed by a CTA scan. The multi-image fusion (MIF) technique, applied using 3DSlicer software, integrated the silent/TOF-MRA with CT images for preoperative assessment. This study compared the image quality, aneurysm detection sensitivity, and anatomic accuracy of the MIF images with those of three-dimensional CTA. RESULTS: Silent-MRA-CT fusion images demonstrated higher sensitivity (95.5%) and lower false negative rates (4.5%) compared with TOF-MRA-CT. Furthermore, silent-MRA-CT fusion images outperformed TOF-MRA-CT in terms of signal homogeneity, venous signal interference suppression, and aneurysm visibility (all P < 0.05). The interclass correlation coefficient and kappa values for aneurysm morphology and shape indicated superior measurement consistency and shape concordance of silent-MRA-CT with CTA compared with TOF-MRA-CT (all P < 0.01). CONCLUSION: This study supports the use of silent/TOF-MRA-CT fusion imaging as a reliable alternative to CTA, noting that silent-MRA-CT closely mirrors CTA. Contrast-free MRA-CT fusion images have the potential to be used for preoperative planning in patients with intracranial aneurysms who have contraindications to contrast.

Comparative study of CTA/CTV and MRTA for preoperative simulation of microvascular decompression in neurovascular compression syndromes.

Neurovascular compression syndrome (NVCS), characterized by cranial nerve compression due to adjacent blood vessels at the root entry zone, frequently presents as trigeminal neuralgia (TN), hemifacial spasm (HFS), or glossopharyngeal neuralgia (GN). Despite its prevalence in NVCS assessment, Magnetic Resonance Tomographic Angiography (MRTA)'s limited sensitivity to small vessels and veins poses challenges. This study aims to refine vessel localization and surgical planning for NVCS patients using a novel 3D multimodal fusion imaging (MFI) technique incorporating computed tomography angiography and venography (CTA/CTV). A retrospective analysis was conducted on 76 patients who underwent MVD surgery and were diagnosed with single-site primary TN, HFS, or GN. Imaging was obtained from MRTA and CTA/CTV sequences, followed by image processing and 3D-MFI using FastSurfer and 3DSlicer. The CTA/CTV-3D-MFI showed higher sensitivity than MRTA-3D-MFI in predicting responsible vessels (98.6% vs. 94.6%) and NVC severity (98.6% vs. 90.8%). Kappa coefficients revealed strong agreement with MRTA-3D-MFI (0.855 for vessels, 0.835 for NVC severity) and excellent agreement with CTA/CTV-3D-MFI (0.951 for vessels, 0.952 for NVC). Resident neurosurgeons significantly preferred CTA/CTV-3D-MFI due to its better correlation with surgical reality, clearer depiction of surgical anatomy, and optimized visualization of approaches (p < 0.001). Implementing CTA/CTV-3D-MFI significantly enhanced diagnostic accuracy and surgical planning for NVCS, outperforming MRTA-3D-MFI in identifying responsible vessels and assessing NVC severity. This innovative imaging modality can potentially improve outcomes by guiding safer and more targeted surgeries, particularly in cases where MRTA may not adequately visualize crucial neurovascular structures.

Nicotinamide mononucleotide mitigates neuroinflammation by enhancing GPX4-mediated ferroptosis defense in microglia.

BACKGROUND: Numerous neurological diseases involving neuroinflammation, particularly microglia, contribute to neuronal death. Ferroptosis is implicated in various diseases characterized by neuronal injury. Studies showed that nicotinamide mononucleotide (NMN) inhibits both neuroinflammation and ferroptosis. However, the mechanisms of NMN in both ferroptosis and neuroinflammation remain unclear. We aimed to explore the effects of NMN on neuroinflammation and the susceptibility of microglia to ferroptosis. METHODS: Ferroptosis markers in macroglia exposed to lipopolysaccharides (LPS) were analyzed using CCK8, flow cytometry, ELISA, and quantitative RT-PCR. The effects of NMN on LPS-induced ferroptosis in microglia were evaluated through flow cytometry, western blot, and immunofluorescence staining. RT-PCR analysis assessed the inflammatory cytokine production of microglia subjected to Ferrostatin-1-regulated ferroptosis. RNA sequencing elucidated the underlying mechanism of NMN-involved microglia ferroptosis under LPS induction. In BV2 microglia, an inhibitor of GPX4, RSL3, was employed to suppress GPX4 expression. Intracerebroventricular injection of LPS was performed to evaluate neuroinflammation and microglia activation in vivo. RESULTS: NMN effectively rescued LPS-induced ferroptosis and improved cell viability in microglia. Co-administration of NMN and ferrostatin-1 significantly reduced proinflammatory cytokine production in microglia following the introduction of LPS stimuli. Mechanistically, NMN facilitated glutathione (GSH) production, and enhanced resistance to lipid peroxidation occurred in a manner dependent on GPX4, repressing cytokine transcription and protecting cells from ferroptosis. RNA sequencing elucidated the underlying mechanism of NMN-associated microglia ferroptosis under LPS induction. Furthermore, simultaneous injection of NMN ameliorated LPS-induced ferroptosis and neuroinflammation in mouse brains. The data from the present study indicated that NMN enhances GPX4-mediated ferroptosis defense against LPS-induced ferroptosis in microglia by recruiting GSH, thereby inhibiting neuroinflammation. CONCLUSION: Therapeutic approaches to effectively target ferroptosis in diseases using NMN, consideration should be given to both its anti-ferroptosis and anti-inflammatory effects to attain optimal outcomes, presenting promising strategies for treating neuroinflammation-related diseases or disorders.

MRI in the prenatal genetic diagnosis and intrauterine treatment of fetal congenital cystic adenoma of the lung.

OBJECTIVE: To investigate the value of magnetic resonance examination technique for prenatal genetic diagnosis and clinical intrauterine treatment of fetal congenital cystic adenoma (CCAM) of the lung. METHODS: A retrospective analysis was conducted on 108 pregnant women admitted to a certain hospital from January 2016 to January 2022 for pre natal examination and consultation on eugenics. The selected pregnant women were aged 20-40 and had a gestational age of 17-36 weeks. Ultrasound and MRI examinations were performed on 108 pregnant women who met the inclusion criteria. Follow-up and investigation were conducted on the fetus after being diagnosed with CCAM. To analyze the results of prenatal genetic diagnosis, chromosome microarray analysis (CMA) was used to analyze samples with pathogenic Copy Number Variants (CNV) and identify pathogenic genes. Finally, the imaging diagnosis results obtained through statistical software were analyzed, and the correlation between pathogenic genes and CCAM, as well as the clinical application value of MRI in fetal intrauterine treatment was explored. RESULTS: Among all cases, 68 fetuses were diagnosed with CCAM through ultrasound examination; 71 fetuses were diagnosed with CCAM through MRI examination. A total of 74 samples were confirmed as CCAM by autopsy and neonatal CT. The sensitivity, specificity, and accuracy of MRI in diagnosing fetal congenital CCAM were higher than those of ultrasound examination. The expression of CCAM was positively correlated with DUSP22, PRSS1, and SHOX, with all R values greater than 0.8. The clinical decision curve showed that when the probability of fetal CCAM was less than 0.03, the prenatal genetic diagnostic model of MRI was not applicable; But when the probability of fetal CCAM was higher than 0.05, the auxiliary intrauterine treatment effect that MRI diagnostic methods achieved was significantly better than conventional diagnosis. CONCLUSION: MRI is significantly better than ultrasound in the diagnosis of CCAM, which can effectively improve the sensitivity of diagnosis and provide accurate information for the eugenics of pregnant women, and has high clinical application value.

Anthropocene 129I Record in the Yellow Sea Sediments and Its Indication for River-Delivered Radioactive Pollution to Marginal Seas.

As the number of coastal nuclear facilities rapidly increases and the wastewater from the Fukushima Nuclear Plant has been discharged into the Pacific Ocean, the nuclear environmental safety of China's marginal seas is gaining increased attention along with the heightened potential risk of nuclear accidents. However, insufficient work limits our understanding of the impact of human nuclear activities on the Yellow Sea (YS) and the assessment of their environmental process. This study first reports the 129I and 127I records of posthuman nuclear activities in the two YS sediments. Source identification of anthropogenic 129I reveals that, in addition to the gaseous 129I release and re-emission of oceanic 129I discharged from the European Nuclear Fuel Reprocessing Plants (NFRPs), the Chinese nuclear weapons testing fallout along with the global fallout is an additional 129I input for the continental shelf of the YS. The 129I/127I atomic ratios in the North YS (NYS) sediment are significantly higher than those in the other adjacent coastal areas, attributed to the significant riverine input of particulate 129I by the Yellow River. Furthermore, we found a remarkable 129I latitudinal disparity in the sediments than those in the seawaters in the various China seas, revealing that sediments in China's marginal seas already received a huge anthropogenic 129I from terrigenous sources via rivers and thus became a significant sink of anthropogenic 129I. This study broadens an insight into the potential impacts of terrigenous anthropogenic pollution on the Chinese coastal marine radioactive ecosystem.

A dicoumarol-graphene oxide quantum dot polymer inhibits porcine reproductive and respiratory syndrome virus through the JAK-STAT signaling pathway.

Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses in the global swine industry. The current vaccine options offer limited protection against PRRSV transmission, and there are no effective commercial antivirals available. Therefore, there is an urgent need to develop new antiviral strategies that slow global PRRSV transmission. Methods: In this study, we synthesized a dicoumarol-graphene oxide quantum dot (DIC-GQD) polymer with excellent biocompatibility. This polymer was synthesized via an electrostatic adsorption method using the natural drug DIC and GQDs as raw materials. Results: Our findings demonstrated that DIC exhibits high anti-PRRSV activity by inhibiting the PRRSV replication stage. The transcriptome sequencing analysis revealed that DIC treatment stimulates genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway. In porcine alveolar macrophages (PAMs), DIC-GQDs induce TYK2, JAK1, STAT1, and STAT2 phosphorylation, leading to the upregulation of JAK1, STAT1, STAT2, interferon-ß (IFN-ß) and interferon-stimulated genes (ISGs). Animal challenge experiments further confirmed that DIC-GQDs effectively alleviated clinical symptoms and pathological reactions in the lungs, spleen, and lymph nodes of PRRSV-infected pigs. Discussion: These findings suggest that DIC-GQDs significantly inhibits PRRSV proliferation by activating the JAK/STAT signalling pathway. Therefore, DIC-GQDs hold promise as an alternative treatment for PRRSV infection.

Application of Synthetic Time-Of-Flight Magnetic Resonance Angiography-Computed Tomography Fusion Imaging in Preoperative Planning for Aneurysm Clipping Surgery: A Comparative Study with Three-Dimensional Computed Tomography Angiography.

OBJECTIVE: Some patients with intracranial aneurysms (IAs) cannot undergo three-dimensional computed tomography angiography (3D-CTA) or digital subtraction angiography due to contraindications to contrast agents or radiation. Time-of-flight magnetic resonance angiography (TOF-MRA) offers a contrast-free alternative but lacks cranial bone detail critical for surgical planning. This study evaluates the feasibility of using 3D Slicer to fuse TOF-MRA with thin-section CT images to generate synthetic images resembling CTA for surgical clipping planning. METHODS: This prospective study included 22 patients with unruptured IAs and 8 with ruptured IAs undergoing aneurysm clipping surgery (≥3 mm). TOF-MRA and CT/3D-CTA scans were fused using 3D Slicer. Neuroradiologists and neurosurgeons independently assessed 3D-CTA and synthetic TOF-MRA-CT images for aneurysm detection rates, morphology, and dimensions. Evaluation metrics included dice similarity coefficient and 95% Hausdorff distance. RESULTS: Evaluation of aneurysm detection rates, morphology, and dimensions showed no significant differences between synthetic TOF-MRA-CT fusion images and 3D-CTA (all P > 0.05). Neuroradiologist assessments revealed strong concordance in aneurysm morphology between synthetic TOF-MRA-CT fusion images and 3D-CTA (κ = 0.867, P < 0.001). The dice similarity coefficient (0.937 ± 0.012) and Hausdorff distance (4.54 ± 0.26) indicated a high degree of image overlap between synthetic TOF-MRA-CT fusion images and 3D-CTA. Surgeons rated the consistency of aneurysm morphology between synthetic TOF-MRA-CT fusion images and intraoperative findings as strongly concordant (κ = 0.873, P < 0.001). CONCLUSIONS: Synthetic TOF-MRA-CT fusion images closely match 3D-CTA for ≥3 mm aneurysms, demonstrating comparable diagnostic and surgical clipping planning effectiveness. They represent a promising alternative for personalized preoperative planning, particularly when contrast agents are contraindicated.

Source, preservation and re-suspension of 239,240Pu in a well dated peat core collected from northwest China.

Owning to the high radiotoxicity in high concentrations, as well as the irreplaceability in quantifying soil erosion rates, demarcating the Anthropocene, and dating of sediment, anthropogenic 239,240Pu have drawn high attention. However, the source in specific areas, preservation characteristics in different environment media, and re-distribution process after the cessation of atmospheric nuclear weapons tests, have not been fully understood, which obscures the exact start year, temporal variation, and deposition flux of 239,240Pu in sedimentary records, and hinders the wide application of 239,240Pu in environment study. A sediment core from the Yiwu peat bog with dominance of atmospheric deposition in the source material, simple sedimentary environment, and high dust deposition flux, was collected to examine the 239,240Pu, and explore the source, preservation, and re-distribution process. The double peaks of 239,240Pu in 1952 CE and 1963 CE, as well as 240Pu/239Pu ratios of 0.163-0.190 with an average of 0.177 ± 0.010 confirmed that the 239,240Pu source originated predominantly from global fallout. The minimal vertical migration of plutonium in the Yiwu peat core was attributed to the near-neutral pH condition. The high inventory of 128 ± 7 Bq m-2, as well as the atypical negative correlation between 239,240Pu concentrations and organic matter content (r = - 0.79, P < 0.01), was attributed to the contribution of 239,240Pu re-suspended with dust from the neighboring Gobi Desert, particularly in the cold and dry years. The total re-suspended 239,240Pu was estimated to be 77 Bq m-2, exceeding the direct fallout level of 51 Bq m-2 during 1945-2016 CE. In this study, the specified deposition pattern of 239,240Pu after the cessation of atmospheric nuclear weapons was established, providing an important standard for multiple environmental studies, and the re-suspended amount of 239,240Pu in a typical arid area was quantified for the first time.

Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.

Engineering Phage Nanocarriers Integrated with Bio-Intelligent Plasmids for Personalized and Tunable Enzyme Delivery to Enhance Chemodynamic Therapy.

Customizable and number-tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4-Lox-DNA-Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron-based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO-Keap1 plasmid (DNA) with tumor hypoxia-activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio-intelligent plasmids, presenting a promising approach for tumor therapy.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Quantitative estimation of dust transport in the desert region of northwest China by plutonium isotopes.

Dust is an important source of atmospheric pollution, and quantitative estimation of desert dust transport is crucial for air pollution control. In this study, five typical sandy soil profiles in the Tengger Desert were collected and analyzed for 239,240Pu concentration and 240Pu/239Pu atomic ratios in order to identify the source of 239,240Pu in this area and explore the sedimentary characteristics of dust in different profiles. The results revealed that the concentrations of 239,240Pu in the soil profiles were between 0.002 and 0.443 mBq/g with an exception of the deep layer soil at one site. The measured atomic ratios of 240Pu/239Pu are at the global atmospheric fallout level with a mean of 0.184 ± 0.020, indicating that global fallout is the dominant source of plutonium in this region. The total inventories of 239,240Pu in the reference sites in this area were estimated to be 39.2-44.6 Bq/m2, this is in agreement with the value from the global fallout of atmospheric nuclear weapon tests at the similar latitude (30-40 °N: 42 Bq/m2). The estimated erosion rate in the erosion profile utilizing soil erosion intensity mode is 2491 t/km2/yr and the soil erosion depth is 9.86 cm, While, the stacking rate of the accumulation profile is 1383 t/km2/yr, and the depth of accumulation is estimated to be 5.48 cm. The difference between the erosion and accumulation profiles indicated that approximately 1107 t/km2/yr of dust was exported from the Gobi landform area of the Tengger Desert, which might be transported long distance in the downwind direction.

Reconstructing atmospheric 129I deposition over 170 years with the varved sediment in the Sihailongwan Maar Lake, northeast China.

Long-term deposition of atmospheric radioactive iodine-129 (129I) is important for assessing the impact of human nuclear activities (HNAs), but still not well understood in East Asia. In this study, we quantitatively reconstructed the deposition history of airborne 129I using varved sediment from Sihailongwan Maar Lake (SHLW) in northeast China. Our results revealed significant increases in 129I concentrations and 129I/127I atomic ratios since the 1950s, indicating the influence of HNAs on the environment and marking the onset of the Anthropocene. The variation of 129I in the investigated site can be primarily attributed to the global fallout of ANWT as well as nuclear fuel reprocessing in Europe, Russia and the USA. Notably, neither the Chernobyl nor the Fukushima nuclear accidents have had any discernable impact on the SHLW Lake. Over the past 170 years (1846-2021), the reconstructed fluxes indicate a rapid increase in 129I deposition from the early 1950s until the 1970s followed by dramatic changes thereafter. The measured 129I fluxes range between (1.26-349) × 109 atoms m-2 yr-1 in the SHLW Lake, which are consistent with similar latitude zones across East Asia, but differ significantly from those observed in high-elevation glaciers within the Northern Hemisphere due to prevailing atmospheric circulation patterns. The total 129I inventory was calculated to be 11.9 × 1012 atoms m-2, with natural and anthropogenic 129I accounting for 2.86 % and 97.1 %, respectively, suggesting an overwhelming artificial contribution. The reconstructed fluxes and inventory of atmospheric 129I deposition quantitatively distinguish the natural and artificial contributions, and provide a novel insight into the historical environmental impact of HNAs in East Asia and the characteristics of the Anthropocene.

Sources of highly regional 129I in soils in northeast China.

The transport and deposition pathways of anthropogenic radionuclides at the global scale, particularly volatile 129I, remain somewhat elusive due to a dearth of comprehensive investigations. To gain a better understanding of the transport dynamics and deposition mechanism of anthropogenic 129I in the terrestrial environment, one hundred surface soil samples collected from northeast China were analyzed for 129I and 127I concentrations in this study. Our findings reveal that 129I/127I atomic ratios in the mid-eastern Inner Mongolia (MIM) were approximately an order of magnitude higher than the rest of the investigated area. This is, besides the global fallout and the long-range transport of 129I released from the European nuclear reprocessing plants via westerly winds, possibly attributed to the dust with high 129I levels from the East Asian arid regions. In addition to the significant dust-induced 129I input, the unique meteorological conditions and topographical features in the MIM synergistically contribute to the pronounced accumulation and deposition of 129I in this region. This study will provide novel insights into the transport and deposition mechanism of anthropogenic radionuclides, which is significant for the assessment of anthropogenic nuclear activities on the environment in the future.

Cortical Sulcal Abnormalities Revealed by Sulcal Morphometry in Patients with Chronic and Episodic Migraine.

Purpose: Previous studies have reported mixed results regarding the importance of cortical abnormalities in patients with migraines. However, cortical sulci, as a component of the cerebral cortex, have not been specifically investigated in migraine patients. Therefore, we aim to evaluate alterations in cortical sulcal morphology among patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs). Patients and Methods: In this cross-sectional study, structural magnetic resonance images were acquired from 35 patients with CM, 35 with EM, and 35 HCs. Cortical sulci were identified and reconstructed using the BrainVisa 5.0.4 software. We focused on regions involved in pain processing in which abnormal cortical structure were identified in previous neuroimaging studies. Morphometric analysis was performed to calculate sulcal parameters including mean depth, cortical thickness, and opening width. Partial correlation analyses of clinical characteristics and sulcal parameters were performed for CM, EM and the combined migraine (CM + EM) groups. Results: In comparison with HCs, both CM and EM groups showed increased opening width in bilateral insula. In comparison with HC and EM groups, CM patients showed increased cortical thickness in bilateral superior postcentral sulcus, bilateral median frontal sulcus and left superior parietal sulcus, as well as increased mean depth in the left anterior callosomarginal fissure and decreased mean depth in bilateral superior frontal sulcus and left median frontal sulcus. Migraine frequency and disease duration were both correlated with cortical thickness in bilateral superior postcentral sulcus. Conclusion: Abnormal sulcal morphometry primarily affected areas associated with pain processing in patients with migraine, with CM exhibiting more extensive abnormalities in areas related to sensory and affective processing. These changes may contribute to understanding the pathology of EM and CM.

Epoxidase inhibitor-aspirin resistance and the relationship with genetic polymorphisms: a review.

Strokes are the leading cause of death in most regions of the world. Epoxidase inhibitors include the drug aspirin (acetylsalicylic acid). Aspirin is widely used as first-line treatment for the prevention of cardiovascular and cerebrovascular diseases in at-risk patients. However, patients using conventional doses of aspirin can still develop ischaemic cardiovascular and cerebrovascular diseases, a phenomenon known as aspirin resistance. The occurrence of aspirin resistance hinders the prevention and treatment of ischaemic cardiovascular and cerebrovascular diseases. There are many factors affecting aspirin resistance, such as sex, drug dose, metabolic disease, genetic polymorphisms, drug interactions and pharmacokinetics. Genetic polymorphism refers to the simultaneous and frequent presence of two or more discontinuous variants or genotypes or alleles in a population of organisms. Platelets contain a large number of highly polymorphic transmembrane glycoprotein receptors encoded by two or more isomeric alleles. Changes in gene polymorphisms in various pathways during platelet aggregation can lead to aspirin resistance. This narrative review describes the gene polymorphisms that have been demonstrated to be significantly associated with aspirin resistance. Research on the mechanisms of aspirin resistance and increased knowledge should provide accurate drug guidance in individuals that require first-line antiplatelet therapy.

Synergistic treatment of androgenetic alopecia with follicular co-delivery of minoxidil and cedrol in metal-organic frameworks stabilized by covalently cross-linked cyclodextrins.

Androgenetic alopecia seriously affects the physical and mental health of patients. The main clinical therapeutic agent, minoxidil tincture, is challenged by solvent irritation and dose-dependent side effects. Our recent work has identified a biosafety natural product, cedrol, that is synergistic in combination with minoxidil, thereby improving medication safety by substantially reducing the clinical dose of minoxidil. In addition, ccross-linked CD-MOF were designed as carriers for hair follicle delivery, and γ-CD in the carriers was cross-linked by diphenyl carbonate with covalent bonds to protect the CD-MOF from rapid disintegration in an aqueous environment. This improved nanocarrier has a drug loading of 25%, whereas nanocarriers increased drug delivery to the hair follicles through ratchet effect, and increased human dermal papilla cells uptake of drugs via endocytosis pathways mainly mediated by lattice proteins, energy-dependent active transport, and lipid raft-dependent, thus improved cell viability, proliferation, and migration, followed by significantly enhancing the anti-androgenetic alopecia effect, with cedrol focusing on inhibiting 5α-reductase and activating Shh/Gli pathway, and minoxidil, which up-regulated VEGF, down-regulated TGF-ß, and activated ERK/AKT pathway. This drug combination provides a new therapeutic strategy for androgenetic alopecia, while the newly developed cross-linked CD-MOF has been shown to serve as a promising follicular delivery vehicle.

Level, distribution and sources of Np, Pu and Am isotopes in Peter the Great Bay of Japan sea.

Transuranium elements such as Np, Pu and Am, are considered to be the most important radioactive elements in view of their biological toxicity and environmental impact. Concentrations of 237Np, Pu isotopes and 241Am in two sediment cores collected from Peter the Great Bay of Japan Sea were determined using radiochemical separation combined with inductively coupled plasma mass spectrometry (ICP-MS) measurement. The 239,240Pu and 241Am concentrations in all sediment samples range from 0.01 Bq/kg to 2.02 Bq/kg and from 0.01 Bq/kg to 1.11 Bq/kg, respectively, which are comparable to reported values in the investigated area. The average atomic ratios of 240Pu/239Pu (0.20 ± 0.02 and 0.21 ± 0.01) and 241Am/239+240Pu activity ratios (3.32 ± 2.76 and 0.45 ± 0.17) in the two sediment cores indicated that the sources of Pu and Am in this area are global fallout and the Pacific Proving Grounds through the movement of prevailing ocean currents, and no measurable release of Np, Pu and Am from the local K-431 nuclear submarine incident was observed. The extremely low 237Np/239Pu atomic ratios ((2.0-2.5) × 10-4) in this area are mainly attributed to the discrepancy of their different chemical behaviors in the ocean due to the relatively higher solubility of 237Np compared to particle active plutonium isotopes. It was estimated using two end members model that 23% ± 6% of transuranium radionuclides originated from the Pacific Proving Grounds tests, and the rest (ca. 77%) from global fallout.

Microneedle-mediated nose-to-brain drug delivery for improved Alzheimer's disease treatment.

Conventional transnasal brain-targeted drug delivery strategies are limited by nasal cilia clearance and the nasal mucosal barrier. To address this challenge, we designed dissolving microneedles combined with nanocarriers for enhanced nose-to-brain drug delivery. To facilitate transnasal administration, a toothbrush-like microneedle patch was fabricated with hyaluronic acid-formed microneedles and tannic acid-crosslinked gelatin as the base, which completely dissolved in the nasal mucosa within seconds leaving only the base, thereby releasing the loaded cyclodextrin-based metal-organic frameworks (CD-MOFs) without affecting the nasal cilia and nasal microbial communities. As nanocarriers for high loading of huperzine A, these potassium-structured CD-MOFs, reinforced with stigmasterol and functionalized with lactoferrin, possessed improved physical stability and excellent biocompatibility, enabling efficient brain-targeted drug delivery. This delivery system substantially attenuated H2O2- and scopolamine-induced neurocyte damage. The efficacy of huperzine A on scopolamine- and D-galactose & AlCl3-induced memory deficits in rats was significantly improved, as evidenced by inhibiting acetylcholinesterase activity, alleviating oxidative stress damage in the brain, and improving learning function, meanwhile activating extracellular regulated protein kinases-cyclic AMP responsive element binding protein-brain derived neurotrophic factor pathway. Moreover, postsynaptic density protein PSD-95, which interacts with two important therapeutic targets Tau and ß-amyloid in Alzheimer's disease, was upregulated. This fruitful treatment was further shown to significantly ameliorate Tau hyperphosphorylation and decrease ß-amyloid by ways including modulating beta-site amyloid precursor protein cleaving enzyme 1 and a disintegrin and metalloproteinase 10. Collectively, such a newly developed strategy breaks the impasse for efficient drug delivery to the brain, and the potential therapeutic role of huperzine A for Alzheimer's disease is further illustrated.

Simultaneous Determination of Transuranium Radionuclides in Urine by Tandem Quadrupole ICP-MS/MS with Mass-Shift Mode Combined with Chemical Separation.

The urine bioassay method for transuranium nuclides (237Np, 239,240,241Pu, 241Am, and 244Cm) is needed to quickly assess the potential internal contamination in emergency situations. However, in the case that the analysis of multiple radionuclides is required in the same sample, time-consuming/tedious sequential analytical procedures using multiple chromatographic separation resins would have to be employed for the separation of every single radionuclide. In this work, a rapid method for the simultaneous determination of transuranium nuclides in urine was developed by using triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS/MS) combined with a single DGA resin column. The chemical behaviors of Np/Pu and Am/Cm on the DGA resin were consistent in 8-10 mol/L HNO3 and 0.005-0.02 mol/L NaNO2 when 242Pu and 243Am were selected as tracers for Np/Pu and Am/Cm yield monitoring. Based on their different reaction rates with O2, 237Np, 239,240,241Pu, 241Am, and 244Cm in the same solution were simultaneously measured by ICP-MS/MS in the same run. The elimination efficiency of 238U+ tailing (7.43 × 10-9), 238U1H16O2+/238U16O2+ (8.11 × 10-8) and cross contamination of 241Pu and 241Am (<1%) were achieved using 10.0 mL/min He-0.3 mL/min O2 even if the eluate was directly measured without any evaporation. The detection limits of transuranium nuclides were at the femtogram level, demonstrating the feasibility of ICP-MS/MS for simultaneous transuranic radionuclides urinalysis. The developed method was validated by analyzing the spiked urine samples.