Single-cell RNA-seq dissecting heterogeneity of tumor cells and comprehensive dynamics in tumor microenvironment during lymph nodes metastasis in gastric cancer.

Lymph node metastasis is the common metastasis route of gastric cancer. However, until now, heterogeneities of tumor cells and tumor microenvironment in primary tumors (PT) and metastatic lymph nodes (MLN) of gastric cancer (GC) remains uncharacterized. In our study, single cell RNA sequencing was performed on tissues from PT and MLN of gastric cancer. Trajectory analysis and function enrichment analyses were conducted to decode the underlying mechanisms contributing to LN metastasis of gastric cancer. Heterogeneous composition of immune cells and distinct intercellular interactions in PT and MLN were analyzed. Based on the generated single cell transcriptome profiles, dynamics of gene expressions in cancer cells between PT and MLN were characterized. Moreover, we reconstructed the developmental trajectory of GC cells' metastasis to LN and identified two subtypes of GC cells with distinct potentials of having malignant biological behaviors. We characterized the repression of neutrophil polarization associated genes, like LCN2, which would contribute to LN metastasis, and histochemistry experiments validated our findings. Additionally, heterogeneity in neutrophils, rather than macrophages, was characterized. Immune checkpoint associated interaction of SPP1 was found active in MLN. In conclusion, we decode the dynamics of tumor cells during LN metastasis in GC and to identify a subtype of GC cells with potentials of LN metastasis. Our data indicated that the disordering the neutrophils polarization and maturation and the activation of immune checkpoint SPP1 might contribute to LN metastasis in GC, providing a novel insight on the mechanism and potential therapeutic targets of LN metastasis in GC.

A study on the use of mental state terms in natural contexts of Chinese children aged 3 to 6 years.

Chinese children's mental state terms were studied in a sample of 79 Chinese mother-child pairs (with children aged 3-6 years). Children's mental state term categories were calculated according to age, gender, and context as well as socioeconomic status (SES) variations. The study found that there were no significant age or gender differences in the Chinese children's mental state terms use during the 3- to 6-year stage and that the Chinese children's perception, disposition, and cognition terms were highly dependent on the use of particular words: "see" "like" and "know". After removing the highly dependent word "know," children's cognition terms showed significant age differences. Further research on disposition terms showed that with age negative terms displayed an increasing trend. In addition, the use of Chinese children's mental state terms was closely related to specific contexts. For example, references to volition occurred most often in the context of drawing, whereas references to cognition occurred when playing with blocks. Meanwhile, disposition terms were maintained at a minimum frequency in all contexts, although the picture book used in the reading context was embedded with many disposition cues. Moreover, there was no significant difference in the mental state terms of children aged 3 to 6 years with high and low SES. Furthermore, in addition to perception terms, mothers' mental state terms were significantly and positively related to children's mental state terms of the same type. These findings provide evidence for the developmental pattern of mentalization development and appropriate education for Chinese children aged 3 to 6 years.

Dopamine 1 receptor activation protects mouse diabetic podocytes injury via regulating the PKA/NOX-5/p38 MAPK axis.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes that can lead to end-stage renal disease. Podocytes constitute the last barrier of glomerular filtration, whose damage are the direct cause of proteinuria. Dopamine receptors are involved in the regulation of diabetes-induced glomerular hyperfiltration, and only dopamine 1 receptor (D1R) can be amplified in cultured mouse podocytes. However, the exact effect of D1R on diabetic podocytes remains unclear. This study aims to investigate the protective role of D1R activation on diabetic podocytes injury in vivo and vitro as well as its potential mechanism. We observed D1R protective effect respectively in streptozotocin (STZ)-induced type 1 diabetes (T1D) mice as well as mouse podocytes (MPC5) cultured in high glucose (HG, 40 mM) medium. It showed that D1R and podocyte-associated proteins (Podocin, CD2AP and Nephrin) expression were significantly decreased both in the T1D mice (fed for 8 and 12 weeks) and HG-cultured MPC5 cells, while the NOX-5 expression increased. In T1D mice, the levels of 24-h urine protein, serum creatinine and urinary 8-OHdG were increased in a time-dependent manner, at the same time, hematoxylin-eosin (HE) staining and electron microscope observed the kidney lesion and podocytes injury. In vitro, HG induced podocytes oxidative stress and apoptosis, which could be inhibited by SKF38393 (a D1R agonist) and N-acetyl-l-cysteine (NAC, a reactive oxygen species scavenger). Furthermore, there was a decreasing Podocin expression and a significant increasing NOX-5 expression in podocytes transfected with D1R-small interfering RNA (siRNA). More importantly, the expression of phospho-CREB (the PKA downstream transcription factor) was decreased and phospho-p38 MAPK was increased in HG-induced podocytes, which can respectively be activated or blocked by SKF38393, 8-Bromo-CAMP (a PKA activator), NAC, and SB20380 (a p38 MAPK inhibitor). In conclusion, D1R activation can protect diabetic podocytes from apoptosis and oxidative damage, in part through the PKA/NOX-5/p38 MAPK pathway.

Dopamine receptor D2 inhibition alleviates diabetic hepatic stellate cells fibrosis by regulating the TGF-ß1/Smads and NFκB pathways.

Diabetic hepatic fibrosis (DHF) is a progressive liver disease and a chronic complication of diabetes mellitus. The main cause of DHF is the activation of quiescent hepatic stellate cells (HSCs) by high glucose stimulation. Dopamine receptor D2 (DRD2)-mediated dopamine signalling can be involved in the regulation of diabetic liver disease, but the exact role of DRD2 in DHF is still poorly understood. This study aimed to investigate the protective effect of DRD2 inhibition on diabetic liver fibrosis and the potential mechanism. We established both streptozotocin (STZ)-induced type 1 diabetes (T1D, fed for 20 weeks) rat model and high glucose (HG, 40 mmol/L)-stimulated HSCs model. The results from both the rats with STZ and the HSCs treated with HG showed increased expression of DRD2, NOX-5, inflammation-related proteins (IL-6 and TNFα) and fibrosis-related proteins (TGF-ß1, CO-Ⅰ/Ⅲ/ IV, MMP-2/9 and fibronectin). In vivo, the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (T-AOC) levels were significantly increased, and hematoxylin-eosin (HE) staining, Masson staining, and electron microscopy revealed liver lesions and hepatocyte injury. In addition, HG-treated HSCs exhibited altered oxidative stress - related indexes, including superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS), changed and abnormally proliferated in vitro. TGF-ß1, the phosphorylated Smad2, nuclear NFκB-p65, phosphorylated NFκB-p65 and phosphorylated IκBα were also increased. Interestingly, haloperidol (DRD2 inhibitor) and n-acetyl-L-cysteine (NAC, an active oxygen scavenger) reduced the above-mentioned changes. In conclusion, DRD2 inhibition can reduce diabetic HSCs oxidative damage and fibrotic proliferation partly via the TGF-ß1/Smads and NFκB pathways.

Study of collagen remodeling in structural disorders of the temporomandibular joint using second-harmonic generation microscopy.

Structural disorder of the temporomandibular joint (TMJ) is a progressive disease with poor prognosis due to its physiological three-dimensional anatomical position and the complicated relationship among muscles, ligaments, and cartilage. The lack of detection methods for changes in the collagen structure of the TMJ disc makes the diagnosis untimely and unclear. This work aimed to explore the feasibility of using a promising detection technique, second-harmonic generation (SHG), to characterize collagen fibers in a TMJ disc with structural disorders. The TMJ discs with structural disorder were observed using SHG microscopy, and assessment of collagen orientation was conducted by analyzing digitized images. The SHG images were also compared with the scanning electron microscopy images and microscopic images acquired after hematoxylin and eosin and Masson's trichrome staining. The SHG imaging showed that the collagen fibers in diseased TMJ were distributed in a disorderly manner, and pixel intensities in diseased TMJ discs were significantly different from those acquired in healthy TMJs. Moreover, the three dimensions of collagen fibers and dynamic images acquired by SHG nonlinear optical microscopy showed the structural disorder of the collagen fibers in a diseased TMJ. In summary, SHG imaging could provide three-dimensional and quantitative data, with dynamic and critical pathological information for clinical diagnosis, showing its potential value in the diagnosis and evaluation of structural disorders of the TMJ disc.

Allylic Amination of Alkenes with Iminothianthrenes to Afford Alkyl Allylamines.

Allylic C-H amination is currently accomplished with (sulfon)amides or carbamates. Here we show the first allylic amination that can directly afford alkyl allylamines, enabled by the reactivity of thianthrene-based nitrogen sources that can be prepared from primary amines in a single step.

Exogenous spermine attenuates myocardial fibrosis in diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress and the canonical Wnt signaling pathway.

Myocardial fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Spermine (SPM), a product of polyamine metabolism, plays an important role in many cardiac diseases including hypertrophy, ischemia, and infarction, but its role in diabetic myocardial fibrosis has not been clarified. This study aimed to investigate the role of polyamine metabolism, specifically SPM, in diabetic myocardial fibrosis and to explore the related mechanisms. We used intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in Wistar rats and high glucose (HG, 40 mM) stimulated cardiac fibroblasts (CFs) to established a type 1 diabetes (T1D) model in vivo and in vitro, which were pretreated with exogenous SPM (5 mg/kg per day and 5 µM). The results showed that hyperglycemia induced the expression of the key polyamine synthesis enzyme ornithine decarboxylase (ODC) decreased and the key catabolic enzyme spermidine/spermine N1 -acetyltransferase (SSAT) increased compared with those in the control group. The body weight, blood insulin level, and cardiac ejection function were decreased, while blood glucose, heart weight, the ratio of heart weight to body weight, myocardial interstitial collagen deposition, and endoplasmic reticulum stress (ERS)-related protein (glucose-regulated protein-78, glucose-regulated protein-94, activating transcription factor-4, and C/EBP homology protein) expression in the T1D group were all significantly increased. HG also caused an increased expression of Wnt3, ß-catenin (in cytoplasm and nucleus), while Axin2 and phosphorylated ß-catenin decreased. Exogenous SPM improved the above changes caused by polyamine metabolic disorders. In conclusion, polyamine metabolism disorder occurs in the myocardial tissue of diabetic rats, causing myocardial fibrosis and ERS. Exogenous SPM plays a myocardial protective role via inhibiting of ERS and the canonical Wnt/ß-catenin signaling pathway.

Regio- and Stereoselective Thianthrenation of Olefins To Access Versatile Alkenyl Electrophiles.

Herein, we report a regioselective alkenyl electrophile synthesis from unactivated olefins that is based on a direct and regioselective C-H thianthrenation reaction. The selectivity is proposed to arise from an unusual inverse-electron-demand hetero-Diels-Alder reaction. The alkenyl sulfonium salts can serve as electrophiles in palladium- and ruthenium-catalyzed cross-coupling reactions to make alkenyl C-C, C-Cl, C-Br, and C-SCF3 bonds with stereoretention.

DR1 activation reduces the proliferation of vascular smooth muscle cells by JNK/c-Jun dependent increasing of Prx3.

Vascular smooth muscle cells (VSMCs) proliferation is a key process in atherosclerosis. However, little is known about the underlying mechanisms, leading to a lack of effective therapy. This study was to investigate whether dopamine receptor 1 (DR1) is involved in the VSMCs proliferation and related mechanisms. A7r5 cells were treated with oxidized low-density lipoprotein (ox-LDL, 10, 20, 50, 100, 200 µg/mL) in the presence or absence of the SKF38393 (DR1agonist), SCH23390 (DR1antiagonist), SP600125 (JNK inhibitor), PD98059(ERK1/2 inhibitor) or NAC (ROS inhibitor). Cell proliferation and related signaling pathway were evaluated. The expression of DR1 was negatively correlated with increasing of cell proliferation caused by ox-LDL. Cell proliferation and ROS generation in response to ox-LDL were prevented by DR1 agonist or over-expression. The peroxiredoxins protein (Prx1, 2, 3, 5, 6) were increased in A7r5 cells treated with ox-LDL; however, only Prx3 dramatically increased after activation of DR1 compared with ox-LDL group, which is related to activation of JNK/c-Jun pathway. In addition, ERK is associated with the restraining effects of DR1 activation. DR1 activation inhibits VSMCs proliferation primarily by JNK/c-Jun dependent increasing of Prx3, suggesting DR1 a potential target for the prevention of vascular proliferation disease.

Rh-Catalyzed Anti-Markovnikov Hydrocyanation of Terminal Alkynes.

We report the first highly stereo- and regioselective hydrocyanation of terminal alkynes to furnish E-configured alkenyl nitriles. Acrylonitriles can be accessed on gram scale with broad substrate scope and functional group tolerance. The hydrocyanation reaction employs acetone cyanohydrin as a practical alternative to HCN gas.

Analysis of precision in tumor tracking based on optical positioning system during radiotherapy.

Tumor tracking is performed during patient set-up and monitoring of respiratory motion in radiotherapy. In the clinical setting, there are several types of equipment for this set-up such as the Electronic Portal imaging Device (EPID) and Cone Beam CT (CBCT). Technically, an optical positioning system tracks the difference between the infra ball reflected from body and machine isocenter. Our objective is to compare the clinical positioning error of patient setup between Cone Beam CT (CBCT) with the Optical Positioning System (OPS), and to evaluate the traditional positioning systems and OPS based on our proposed approach of patient positioning. In our experiments, a phantom was used, and we measured its setup errors in three directions. Specifically, the deviations in the left-to-right (LR), anterior-to-posterior (AP) and inferior-to-superior (IS) directions were measured by vernier caliper on a graph paper using the Varian Linear accelerator. Then, we verified the accuracy of OPS based on this experimental study. In order to verify the accuracy of phantom experiment, 40 patients were selected in our radiotherapy experiment. To illustrate the precise of optical positioning system, we designed clinical trials using EPID. From our radiotherapy procedure, we can conclude that OPS has higher precise than conventional positioning methods, and is a comparatively fast and efficient positioning method with respect to the CBCT guidance system.

CoOOH Nanosheets with High Mass Activity for Water Oxidation.

Endowing transition-metal oxide electrocatalysts with high water oxidation activity is greatly desired for production of clean and sustainable chemical fuels. Here, we present an atomically thin cobalt oxyhydroxide (γ-CoOOH) nanosheet as an efficient electrocatalyst for water oxidation. The 1.4 nm thick γ-CoOOH nanosheet electrocatalyst can effectively oxidize water with extraordinarily large mass activities of 66.6 A g(-1), 20 times higher than that of γ-CoOOH bulk and 2.4 times higher than that of the benchmarking IrO2 electrocatalyst. Experimental characterizations and first-principles calculations provide solid evidence to the half-metallic nature of the as-prepared nanosheets with local structure distortion of the surface CoO(6-x) octahedron. This greatly enhances the electrophilicity of H2O and facilitates the interfacial electron transfer between Co ions and adsorbed -OOH species to form O2, resulting in the high electrocatalytic activity of layered CoOOH for water oxidation.

The clinical significance of endoplasmic reticulum stress related genes in non-small cell lung cancer and analysis of single nucleotide polymorphism for CAV1.

In recent years, protein homeostasis imbalance caused by endoplasmic reticulum stress has become a major hallmark of cancer. Studies have shown that endoplasmic reticulum stress is closely related to the occurrence, development, and drug resistance of non-small cell lung cancer, however, the role of various endoplasmic reticulum stress-related genes in non-small cell lung cancer is still unclear. In this study, we established an endoplasmic reticulum stress scores based on the Cancer Genome Atlas for non-small cell lung cancer to reflect patient features and predict prognosis. Survival analysis showed significant differences in overall survival among non-small cell lung cancer patients with different endoplasmic reticulum stress scores. In addition, endoplasmic reticulum stress scores was significantly correlated with the clinical features of non-small cell lung cancer patients, and can be served as an independent prognostic indicator. A nomogram based on endoplasmic reticulum stress scores indicated a certain clinical net benefit, while ssGSEA analysis demonstrated that there was a certain immunosuppressive microenvironment in high endoplasmic reticulum stress scores. Gene Set Enrichment Analysis showed that scores was associated with cancer pathways and metabolism. Finally, weighted gene co-expression network analysis displayed that CAV1 was closely related to the occurrence of non-small cell lung cancer. Therefore, in order to further analyze the role of this gene, Chinese non-smoking females were selected as the research subjects to investigate the relationship between CAV1 rs3779514 and susceptibility and prognosis of non-small cell lung cancer. The results showed that the mutation of rs3779514 significantly reduced the risk of non-small cell lung cancer in Chinese non-smoking females, but no prognostic effect was found. In summary, we proposed an endoplasmic reticulum stress scores, which was an independent prognostic factor and indicated immune characteristics in the microenvironment of non-small cell lung cancer. We also validated the relationship between single nucleotide polymorphism locus of core genes and susceptibility to non-small cell lung cancer.

Symptom progression in neuromyelitis optica spectrum disorder from ataxia through syncope to neuropathic pain: A case report.

RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) involves autoimmune and inflammatory responses in the central nervous system, primarily affecting the optic nerves and spinal cord. Atypical presentations such as ataxia and syncope complicate the diagnosis, and lesions in the medulla are easily mistaken for cerebral infarction. This case report emphasizes the need to recognize such manifestations to avoid misdiagnosis and ensure timely treatment. PATIENT CONCERNS: This case report presents an NMOSD female patient who experienced ataxia, syncope, and neuropathic pain during her illness. DIAGNOSIS: NMOSD. INTERVENTIONS: The patient managed her blood sugar with insulin, controlled neuropathic pain with pregabalin, and underwent 5 plasma exchanges. OUTCOMES: Significant improvement was noted 1 week post-plasma exchange, with complete resolution of neuropathic pain and no symptom recurrence reported at 6-month follow-up. LESSONS: Atypical manifestations of NMOSD, such as ataxia, syncope, and trigeminal neuralgia, increase diagnostic difficulty. Recognizing these symptoms is crucial to avoid misdiagnosis and ensure timely and appropriate treatment for patients.

One-step regeneration and upgrading of spent LiFePO4 cathodes with phytic acid.

The regeneration and upgrading of spent LiFePO4 cathodes (S-LFP) were achieved via a one-step hydrothermal treatment. The reducing effect of phytic acid could restore the degraded structure associated with an aqueous Li source. Meanwhile, Li ions are easily chelated by phytic acid groups, and a Li3PO4 coating layer could be formed to reconstruct the surface of the LFP. The regenerated LFP exhibits faster reaction kinetics, larger high-rate charge/discharge capacity, and better cycling performance than commercial LFPs, suggesting that our proposed strategy is a promising technology for the recovery of spent cathode materials.

Heme Oxygenase-1 Gene (GT)n Polymorphism Linked to Deep White Matter Hyperintensities, Not Periventricular Hyperintensities.

BACKGROUND: Oxidative stress plays a principal role in the pathogenesis of white matter hyperintensities (WMHs). The induction of heme oxygenase-1 (HO-1) gene in the brain represents 1 of the pivotal mechanisms to counteract the noxious effects of reactive oxygen species, and the transcriptional modulation of HO-1 induction depends on the length of a GT-repeat (GT)n in the promoter region. We investigated whether the HO-1 gene (GT)n polymorphism is associated with the risk of WMHs. METHODS AND RESULTS: A total of 849 subjects from the memory clinic were consecutively enrolled, and the HO-1 (GT)n genotype was determined. WMHs were assessed with the Fazekas scale and further divided into periventricular WMHs and deep WMHs (DWMHs). Allelic HO-1 (GT)n polymorphisms were classified as short (≤24 (GT)n), median (25≤[GT]n<31), or long (31≤[GT]n). Multivariate logistic regression analysis was used to evaluate the effect of the HO-1 (GT)n variants on WMHs. The number of repetitions of the HO-1 gene (GT)n ranged from 15 to 39 with a bimodal distribution at lengths 23 and 30. The proportion of S/S genotypes was higher for moderate/severe DWMHs than none/mild DWMHs (22.22% versus 12.44%; P=0.001), but the association for periventricular WMHs was not statistically significant. Logistic regression suggested that the S/S genotype was significantly associated with moderate/severe DWMHs (S/S versus non-S/S: odds ratio, 2.001 [95% CI, 1.323-3.027]; P<0.001). The HO-1 gene (GT)n S/S genotype and aging synergistically contributed to the progression of DWMHs (relative excess risk attributable to interaction, 6.032 [95% CI, 0.149-11.915]). CONCLUSIONS: Short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from DWMHs, but not periventricular WMHs. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100045869.

Prominent Vessel Signs After Endovascular Thrombectomy Corelates with Unexplained Neurological Deterioration and is a More Reliable Imaging Predictor of Prognosis in Anterior Large Vessel Occlusion Stroke.

OBJECTIVE: Fifty percent of patients who undergo endovascular thrombectomy (EVT) for large-vessel occlusion exhibit unfavorable outcomes. The primary factor is attributed to persistent brain impairment even after successful EVT. The prominent vessel sign (PVS) on magnetic resonance susceptibility-weighted imaging reflects the territory of dysmetabolism and may facilitate an expeditious assessment for prognostication. We aimed to examine the relationship between PVS after EVT and the occurrence of early neurological deterioration (END) and 3-month outcomes. METHODS: Patients who underwent EVT and multimodal magnetic resonance imaging were included. END was defined as an increase of ≥2 in the National Institutes of Health Stroke Scale within 72 hours after EVT. Symptomatic intracranial hemorrhage, malignant edema, and surgical complications were defined as definite END, whereas the other symptoms were categorized as unexplained END (ux-END). The PVS-Alberta Stroke Program Early CT Score (ASPECTS) score was used to evaluate the asymmetric cerebral venous signal on the susceptibility-weighted imaging sequences semiquantitatively. RESULTS: A total of 116 eligible patients were included, 18 (15.5%) of whom presented with ux-END. The 72 hour National Institutes of Health Stroke Scale was strongly correlated with diffusion-weighted imaging infarct volume and PVS-ASPECTS and was significantly higher in the ux-END group (16 ± 6 vs. 5 ± 4, P = 0.001). The PVS-ASPECTS score was significantly associated with poor outcomes (odds ratio 2.551, 95% confidence interval (CI) 1.722-3.780, P＜0.001), and PVS-ASPECTS (area under the curve 0.884, 95% CI 0.815-0.953, P < 0.001) was superior to diffusion-weighted imaging infarct volume (area under the cure 0.720, 95% CI 0.620-0.820, P = 0.001) in predicting 3-month poor outcome. At the optimal cut-off of 2, the PVS-ASPECT predicted poor outcomes with a sensitivity of 89.7% and a specificity of 78.2%. CONCLUSIONS: PVS 72 hours after EVT correlated with ux-END. The PVS-ASPECTS is a more reliable predictor of stroke prognosis and provides valuable information regarding post-EVT management.

U-type π-conjugated phosphorescent ligand sensitized lanthanide metal-organic frameworks for efficient white-light-emitting diodes.

Lanthanide metal-organic framework (Ln-MOF) based phosphors for light-emitting diodes (LEDs) play an important role in the fields of solid-state lighting and display. The rational design of organic antennae to address the drawback of low extinction coefficients of the lanthanide ions is highly desired. In this work, we provide a new design strategy to achieve an energy transfer molecule with a through-space conjugated folded structure, which can strengthen the skeleton rigidity and facilitate triplet state energy transfer. Consequently, one U-type π-conjugated molecule 2,6-bis(3,5-dicarboxylphenoxy) pyridine (H4L) was selected as a light gatherer to sensitize lanthanide ions for the construction of Ln-MOFs [Ln(HL)(H2O)3]n (Eu-MOF and Tb-MOF), which exhibit a long-lived luminescence lifetime (0.88 ms for Eu-MOF and 1.31 ms for Tb-MOF) and high quantum yields (50.87% for Eu-MOF and 85.64% for Tb-MOF). Furthermore, a white LED device with a colour rendering index (89) was fabricated using the mixture of Ln-MOFs with a commercial blue phosphor.

Formation and Applications in Electronic Devices of Lattice-Aligned Gallium Oxynitride Nanolayer on Gallium Nitride.

Gallium nitride (GaN), a promising alternative semiconductor to Si, is widely used in photoelectronic and electronic technologies. However, the vulnerability of the GaN surface is a critical restriction that hinders the development of GaN-based devices, especially in terms of device stability and reliability. In this study, this challenge is overcome by converting the GaN surface into a gallium oxynitride (GaON) epitaxial nanolayer through an in situ two-step "oxidation-reconfiguration" process. The O plasma treatment overcomes the chemical inertness of the GaN surface, and sequential thermal annealing manipulates the kinetic-thermodynamic reaction pathways to create a metastable GaON nanolayer with a wurtzite lattice. The GaN-derived GaON nanolayer is a tailored structure for surface reinforcement and possesses several advantages, including a wide bandgap, high thermodynamic stability, and large valence band offset with a GaN substrate. These physical properties can be further leveraged to enhance the performance of GaN-based devices in various applications, such as power systems, complementary logic integrated circuits, photoelectrochemical water splitting, and ultraviolet photoelectric conversion.

A Non-Linear Role of Hyperlipidemia on Progression of Intracranial Atherosclerotic Plaques and Acute Downstream Ischemic Events.

AIM: Intracranial atherosclerotic stenosis (ICAS) is the leading cause of ischemic stroke worldwide. Hyperlipidemia is a major contributor to atherosclerosis. However, the effect of hyperlipidemia on the evolution of intracranial atherosclerotic plaques and downstream ischemic episodes remains unclear. In this study, we aimed to assess the radiological features of ICAS plaques and to explore the relationship between hyperlipidemia and plaque progression. METHODS: We included people with ICAS (≥50% stenosis) undergoing high-resolution magnetic resonance imaging. The culprit plaque was defined as the sole, or in case of multiple stenosis, the narrowest plaque on the intracranial artery responsible for acute ischemic stroke. Demographic, clinical data, plaque features on MRI, and lipid parameters were compared between culprit and non-culprit plaques. Plaque enhancement was graded as Grade 0, 1 and 2 by comparing to the adjacent normal vessel wall and pituitary funnel after contrast enhancement on T1-weighted sequences. RESULTS: 162 patients were included (mean age 57.7±12.1 years, male 61.6%), 110 of whom were identified as culprit plaque with an ipsilateral acute stroke. High-grade enhancement was the most prominent MRI feature of the culpable plaque (Grade-2: OR 6.539, 95%CI 1.706-23.707, p=0.006). LDL cholesterol was significantly associated with overall acute ischemic stroke caused by culprit plaque. After stratification by enhancement grading LDL was independently associated with ischemic events in Grade-1 enhancement plaques (OR 6.778, 95%CI 2.122-21.649, p=0.001). In patients with Grade-2 enhancement plaques, however, LDL was not associated with ischemic event; in contrast, Neutrophil/Lymphocyte ratio was independently associated with ischemic events caused by Grade-2 enhancement plaques (OR 2.188, 95%CI 1.209-3.961, p=0.010). CONCLUSIONS: LDL was related with ischemia events in intermediate stage of intracranial atherosclerotic plaque progression, an excellent period for intensive lipid-lowering treatment. In advanced stage, inflammatory agents maybe the main contributor to ischemic events.