Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in ...chiral magnet Co
Zn
Mn
raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction.
Neurologic Wilson disease is an inherited disease characterized by a copper metabolic disorder that causes damage to many organs, especially the brain. Few studies report the relationships between ...these neurologic symptoms and MR imaging of the brain. Therefore, we investigated the correlation of brain abnormalities in patients with neurologic Wilson disease with their clinical symptoms, age of onset, and lag time to diagnosis.
A cohort of 364 patients was recruited in China between January 2003 and December 2017. Age of onset, lag time until diagnosis, and neurologic symptoms were recorded, and cranial MR imaging was performed. Patients were divided into groups within each of these factors for correlation analysis with the MR imaging brain scans.
Abnormal signals in the MR imaging brain scans were seen in all 364 cases. Affected regions included the putamen, pons, midbrain, and thalamus, while the medulla and occipital lobe were unaffected. The putamen was the most frequently damaged brain region in this study. With the age of onset younger than 10 years, cranial MR imaging scans showed only impairment in the putamen. Patients with a longer lag time before diagnosis were more likely to have impairment in the pons, midbrain, and cortex. Among neurologic symptoms of Wilson disease, torsion spasm is associated with the midbrain and cortex, and choreoathetosis is related to the caudate nucleus.
Abnormalities in the putamen, pons, midbrain, and thalamus are part of the neuroimaging spectrum of Wilson disease. There is a significant correlation between the site of brain injury and diagnosis lag time.
Behavioral variant frontotemporal dementia is characterized by heterogeneous frontal, insular, and anterior temporal atrophy patterns that vary along left-right and dorso-ventral axes. Little is ...known about how these structural imbalances impact clinical symptomatology. The goal of this study was to assess the frequency of frontotemporal asymmetry (right- or left-lateralization) and dorsality (ventral or dorsal predominance of atrophy) and to investigate their clinical correlates. Neuropsychiatric symptoms and structural images were analyzed for 250 patients with behavioral variant frontotemporal dementia. Frontotemporal atrophy was most often symmetric while left-lateralized (9%) and right-lateralized (17%) atrophy were present in a minority of patients. Atrophy was more often ventral (32%) than dorsal (3%) predominant. Patients with right-lateralized atrophy were characterized by higher severity of abnormal eating behavior and hallucinations compared to those with left-lateralized atrophy. Subsequent analyses clarified that eating behavior was associated with right atrophy to a greater extent than a lack of left atrophy, and hallucinations were driven mainly by right atrophy. Dorsality analyses showed that anxiety, euphoria, and disinhibition correlated with ventral-predominant atrophy. Agitation, irritability, and depression showed greater severity with a lack of regional atrophy, including in dorsal regions. Aberrant motor behavior and apathy were not explained by asymmetry or dorsality. This study provides additional insight into how anatomical heterogeneity influences the clinical presentation of patients with behavioral variant frontotemporal dementia. Behavioral symptoms can be associated not only with the presence or absence of focal atrophy, but also with right/left or dorsal/ventral imbalance of gray matter volume.
Purpose
To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments.
Materials and methods
Ninety-three ...patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM).
Results
Patients treated with GH had a significantly (
P
< 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (
P
< 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells.
Conclusion
GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.
The clinical success of immunotherapy that inhibits the negative immune regulatory pathway programmed cell death protein 1/PD-1 ligand (PD-1/PD-L1) has initiated a new era in the treatment of ...metastatic cancer. PD-L1 expression is upregulated in many solid tumors including lung cancer and functions predominantly in lactate-enriched tumor microenvironments. Here, we provided evidence for PD-L1 induction in response to lactate stimulation in lung cancer cells. Lactate-induced PD-L1 induction was mediated by its receptor GPR81. The silencing of GPR81 signaling in lung cancer cells resulted in a decrease in PD-L1 protein levels and functional inactivation of PD-L1 promoter activity. In addition, GPR81-mediated upregulation of PD-L1 in glucose-stimulated lung cancer cells that recapitulates the enhanced glycolysis in vivo was dependent on lactate dehydrogenase A (LDHA). We also demonstrated that activation of GPR81 decreases intracellular cAMP levels and inhibits protein kinase A (PKA) activity, leading to activation of the transcriptional coactivator TAZ. Interaction of TAZ with the transcription factor TEAD was essential for TAZ activation of PD-L1 and induction of its expression. Furthermore, we found that lactate-induced activation of PD-L1 in tumor cells led to reduced production of interferon-γ and induction of apoptosis of cocultured Jurkat T-cell leukemia cells. Our findings reveal an unexpected role of lactate in contributing to tumor cell protection from cytotoxic T-cell targeting and establishes a direct connection between tumor cell metabolic reprograming and tumor evasion from the immune response.
We report a design strategy to combine the benefits from both gradient structure and transformation-induced plasticity (TRIP). The resultant TRIP-gradient steel takes advantage of both mechanisms, ...allowing strain hardening to last to a larger plastic strain. 304 stainless steel sheets were treated by surface mechanical attrition to synthesize gradient structure with a central coarse-grained layer sandwiched between two grain-size gradient layers. The gradient layer is composed of submicron-sized parallelepiped austenite domains separated by intersecting ε-martensite plates, with increasing domain size along the depth. Significant microhardness heterogeneity exists not only macroscopically between the soft coarse-grained core and the hard gradient layers, but also microscopically between the austenite domain and ε-martensite walls. During tensile testing, the gradient structure causes strain partitioning, which evolves with applied strain, and lasts to large strains. The γ → α′ martensitic transformation is triggered successively with an increase of the applied strain and flow stress. Importantly, the gradient structure prolongs the TRIP effect to large plastic strains. As a result, the gradient structure in the 304 stainless steel provides a new route towards a good combination of high strength and ductility, via the co-operation of both the dynamic strain partitioning and TRIP effect.
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Accurate diagnosis and prognosis are essential in lung cancer treatment selection and planning. With the rapid advance of medical imaging technology, whole slide imaging (WSI) in pathology is ...becoming a routine clinical procedure. An interplay of needs and challenges exists for computer-aided diagnosis based on accurate and efficient analysis of pathology images. Recently, artificial intelligence, especially deep learning, has shown great potential in pathology image analysis tasks such as tumor region identification, prognosis prediction, tumor microenvironment characterization, and metastasis detection.
In this review, we aim to provide an overview of current and potential applications for AI methods in pathology image analysis, with an emphasis on lung cancer.
We outlined the current challenges and opportunities in lung cancer pathology image analysis, discussed the recent deep learning developments that could potentially impact digital pathology in lung cancer, and summarized the existing applications of deep learning algorithms in lung cancer diagnosis and prognosis.
With the advance of technology, digital pathology could have great potential impacts in lung cancer patient care. We point out some promising future directions for lung cancer pathology image analysis, including multi-task learning, transfer learning, and model interpretation.
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