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160 result(s) for "Zhang, Yaowu"
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Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2 + TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44 + TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy. The intratumoural heterogeneity of spinal ependymomas and the role of microglia in tumour progression remain underexplored. Here, the authors perform single-cell RNA- and ATAC-sequencing data analysis of three subtypes and reveal tumour-associated macrophage subsets with distinct functional phenotypes.
Intramedullary spinal cavernous malformations with high ossification: a case report and review of the literature
Background Cavernous malformations of the spinal cord are a rare type of vascular malformation, comprising approximately 5 to 16% of all vascular lesions in the spinal cord. Depending on their origin position, these malformations can be distributed in different locations within the spinal canal. Although intramedullary cavernous malformations have been reported in the literature, they are exceedingly rare. Furthermore, highly calcified or ossified intramedullary cavernous spinal malformations are even rarer. Case presentation Here, we present a case report of a 28-year-old woman diagnosed with a thoracic intramedullary cavernous malformation. The patient had been experiencing progressive numbness in her distal limbs for a period of 2 months. During routine lung computed tomography screening for COVID-19, a hyperdense mass was noted in the patient’s spinal canal. Magnetic resonance imaging revealed a mulberry-shaped intramedullary mass at the T1-2 level. The patient underwent surgical treatment, during which the entire lesion was successfully removed, resulting in a gradual improvement of her symptoms. Histological examination confirmed the presence of cavernous malformations with calcification. Conclusions Intramedullary cavernous malformations with calcification are rare and special type that should be treated surgically in the early stage without significant neurological impairment before rebleeding or enlargement of the lesion can occur.
The Mechanism of Acetal Formation in Acid-Free Rh-Catalyzed Tandem Hydroformylation–Acetalization of Olefins in MeOH
The acetal formation mechanism under acid-free Rh-catalyzed hydroformylation–acetalization condition has been studied using different rhodium catalyst precursors in MeOH. In the absence of added acidic co-catalyst, the acetalization is catalyzed by the H + formed in situ under hydroformylation condition, and Rh active site on Rh-phosphine catalyst did not exhibit catalytic activity for acetalization. Whether H + can be generated in situ is related with the structure of rhodium catalyst precursor. Under hydroformylation condition, added Brønsted acids as co-catalysts can improve acetalization efficiency, but the H + concentration in the system should not be excessively high to avoid the acid-induced inhibition for hydroformylation. Graphical Abstract
MEASURING AND TESTING FOR INTERVAL QUANTILE DEPENDENCE
In this article, we introduce the notion of interval quantile independence which generalizes the notions of statistical independence and quantile independence. We suggest an index to measure and test departure from interval quantile independence. The proposed index is invariant to monotone transformations, nonnegative and equals zero if and only if the interval quantile independence holds true. We suggest a moment estimate to implement the test. The resultant estimator is root-n-consistent if the index is positive and n-consistent otherwise, leading to a consistent test of interval quantile independence. The asymptotic distribution of the moment estimator is free of parent distribution, which facilitates to decide the critical values for tests of interval quantile independence. When our proposed index is used to perform feature screening for ultrahigh dimensional data, it has the desirable sure screening property.
A LACK-OF-FIT TEST WITH SCREENING IN SUFFICIENT DIMENSION REDUCTION
Researchers often need to infer how the conditional mean of a response varies with the predictors. Sufficient dimension-reduction techniques reduce the dimension by identifying a minimal set of linear combinations of the original predictors, without loss of information. This study tests whether a given small number of linear combinations of the original ultrahigh-dimensional covariates is suficient to characterize the conditional mean of the response. We first introduce a novel consistent lack-of-fit test statistic for the case when the dimensionality of the covariates is moderate. The proposed test is shown to be n-consistent under the null hypothesis, and root-n-consistent under the alternative hypothesis. A bootstrap procedure is developed to approximate the p-values, and the consistency of the test is studied theoretically. To deal with the ultrahigh dimensionality, we introduce a two-stage lack-of-fit test with screening (LOFTS) procedure, based on a datasplitting strategy. The data are randomly partitioned into two equal halves. In the first stage, we apply the martingale di erence correlation-based screening to one half of the data, and select a moderate set of covariates. In the second stage, we perform the proposed test, based on the selected covariates, using the second half of the data. The data-splitting strategy is crucial to eliminate the effect of spurious correlations and to prevent an increase in the type-I error rates. We also demonstrate the effectiveness of our two-stage test procedure by means of comprehensive simulations and a real-data application.
Exploring the Correlation between Changes in Gut Microbial Community Diversity and Depression in Human Populations
Depression, also known as depressive disorder, is a group of psychosomatic affective disorders characterized by persistent and significantly depressed mood, delayed thinking, and cognitive impairment. The aim of this study was to explore the correlation between changes in gut microbial community diversity and depression to provide data on new strategies for the prevention and treatment of depression. In this study, we separated participants into a group of depressed patients and a healthy comparison group. We analyzed the gut microbial community structure of depressed patients and healthy comparisons using second-generation sequencing of the bacterial 16S RNA gene. There were significant differences in the gut microflora structure between patients with depression and healthy individuals. The gut flora alpha diversity index was significantly reduced in patients with depression compared to that in the healthy population. At the species level, the relative abundance of Coprococcus catus and Bacteroides barnesiae was significantly lower in the depressed group than that in the control group. The development of depression may be associated with a decrease in beneficial gut bacteria.
JNK pathway mediates curcumin-induced apoptosis and autophagy in osteosarcoma MG63 cells
Human osteosarcoma is a common primary malignancy of the bone in children and adolescents. It has been reported that curcumin is able to induce apoptosis in osteosarcoma MG63 cells through the mitochondrial pathway. However, whether curcumin is able to induce autophagy and the interaction between apoptosis and autophagy in osteosarcoma cells has yet to be fully elucidated. In the current study, it was determined that curcumin was able to significantly induce apoptosis, and lead to autophagy in MG63 cells. Notably, inhibition of apoptosis enhanced curcumin-induced autophagy due to upregulation of the c-Jun N-terminal kinase (JNK) signaling pathway. This finding was confirmed by the use of JNK-specific inhibitor, SP600125. Furthermore, our data showed that curcumin-induced apoptosis was increased when autophagy was completely inhibited by 3-methyladenine in MG63 cells. These results suggest that autophagy may have an important role in resistance to apoptosis when MG63 cells are incubated with curcumin. Thus, these results provide important insights into the interaction between apoptosis and autophagy in osteosarcoma cells and clinical treatment strategies using curcumin.
A mouse model of classical trigeminal neuralgia via intradural compression of the trigeminal nerve
Introduction Trigeminal neuralgia (TN) is a debilitating orofacial pain condition that adversely affects quality of life. Although heterogeneous, the most common form of TN is classical TN, characterized by paroxysmal bouts of pain in response to otherwise innocuous stimuli. It is believed that classical TN results from neurovascular compression of the trigeminal nerve. However, the underlying pathophysiology of TN is not well understood, thus limiting the development of targeted therapies. Current animal models lack translational relevance, particularly in their inability to replicate intradural nerve root compression, a core anatomic component of TN. Methods We developed a TN mouse model that achieves intradural nerve root compression via a retro-orbital approach confirmed by anatomic dissection and magnetic resonance imaging. To assess behavioral outcomes, we measured orofacial pain through facial wiping and interaction with a reward stimulus. Pharmacological responsiveness was tested using carbamazepine administration. Mechanistic studies included calcium imaging of trigeminal ganglia (TG), electrophysiologic recordings to measure resting membrane potential and rheobase, and immunohistochemical analysis of the TG. Results The model elicited orofacial neuropathic pain, substantiated by increased facial wiping and reduced interaction with a reward stimulus, behaviors that suggest both spontaneous and evoked pain. Carbamazepine attenuated these behaviors, suggesting pharmacologic relevance to current TN treatment. Calcium imaging showed heightened spontaneous activity in the TG, and electrophysiologic recordings revealed an increased resting membrane potential and a reduced rheobase. Finally, immunohistochemical studies showed infiltration of CD45 + cells, demyelination and an increase in CGRP expression in the TG, supporting the presence of neuroinflammation after nerve root compression. Conclusion These findings show that our approach replicates the anatomy and clinical presentation of classical TN in humans. This model may represent a new and robust platform for future mechanistic studies of TN and subsequent preclinical evaluation of therapies in mice.
Risk Genetic Variants
Background: Osteoporosis (OP) is a common metabolic bone disease characterized by loss of bone mass. IL-10 is considered to be a powerful immune and inflammatory suppressor. This study aimed to assess association between genetic loci in IL-10 and susceptibility to OP. Methods: Association analysis between IL-10 genetic loci and OP risk through SNPStats online software. FPRP analysis (false-positive report probability) verified whether the positive results were noteworthy findings. Linkage disequilibrium (LD) and haplotype analysis were completed by Haploview 4.2 and SNPStats. Multi-factor dimensionality reduction (MDR) was used to assess interaction of SNP--SNP in susceptibility to OP. Results: Allele \"G\" of IL-10-rs1554286 (OR = 1.21, p = 0.013), allele \"C\" of IL-10-rs1518111 (OR = 1.22, p = 0.011), allele \"C\" of IL-10-rs3024490 (OR = 1.20, p = 0.018), and allele \"G\" of IL-10-rs1800871 (OR = 1.21, p = 0.015) were risk factors for OP. In females, smoking, drinking, or aging [less than or equal to]60 years old participants, the above genetic loci are also significantly associated with the increased risk of OP. FPRP analysis showed that all positive results are noteworthy findings. There are significant differences in serum levels of uric acid, mean hemoglobin concentration, or mean hemoglobin among different genotypes of IL-10 gene loci. MDR showed that four loci model composed rs1554286, rs1518111, rs3021094, and rs1800871 is the best model for predicting OP risk. Conclusion: IL-10-rs1554286, -rs1518111, -rs3021094, and -rs1800871 are risk factors for susceptibility to OP. Keywords: osteoporosis, IL-10, genetic loci, Han population from northwest China
Risk Genetic Variants (IL-10) for Osteoporosis in Han Population from Northwest China
Osteoporosis (OP) is a common metabolic bone disease characterized by loss of bone mass. is considered to be a powerful immune and inflammatory suppressor. This study aimed to assess association between genetic loci in and susceptibility to OP. Association analysis between genetic loci and OP risk through SNPStats online software. FPRP analysis (false-positive report probability) verified whether the positive results were noteworthy findings. Linkage disequilibrium (LD) and haplotype analysis were completed by Haploview 4.2 and SNPStats. Multi-factor dimensionality reduction (MDR) was used to assess interaction of SNP-SNP in susceptibility to OP. Allele \"G\" of -rs1554286 (OR = 1.21, p = 0.013), allele \"C\" of -rs1518111 (OR = 1.22, = 0.011), allele \"C\" of -rs3024490 (OR = 1.20, = 0.018), and allele \"G\" of -rs1800871 (OR = 1.21, = 0.015) were risk factors for OP. In females, smoking, drinking, or aging ≤60 years old participants, the above genetic loci are also significantly associated with the increased risk of OP. FPRP analysis showed that all positive results are noteworthy findings. There are significant differences in serum levels of uric acid, mean hemoglobin concentration, or mean hemoglobin among different genotypes of gene loci. MDR showed that four loci model composed rs1554286, rs1518111, rs3021094, and rs1800871 is the best model for predicting OP risk. -rs1554286, -rs1518111, -rs3021094, and -rs1800871 are risk factors for susceptibility to OP.