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The discovery of room-temperature ferromagnetism in van der Waals (vdW) materials opens new avenues for exploring low-dimensional magnetism and its applications in spintronics. Recently, the observation of the room-temperature topological Hall effect in the vdW ferromagnet Fe3GaTe2 suggests the possible existence of room-temperature skyrmions, yet skyrmions have not been directly observed. In this study, real-space imaging was employed to investigate the domain evolution of the labyrinth and skyrmion structure. First, Néel-type skyrmions can be created at room temperature. In addition, the influence of flake thickness and external magnetic field (during field cooling) on both labyrinth domains and the skyrmion lattice is unveiled. Due to the competition between magnetic anisotropy and dipole interactions, the specimen thickness significantly influences the density of skyrmions. These findings demonstrate that Fe3GaTe2 can host room-temperature skyrmions of various sizes, opening up avenues for further study of magnetic topological textures at room temperature.
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MOTIVATION: The associations between biomarkers and human diseases play a key role in understanding complex pathology and developing targeted therapies. Wet lab experiments for biomarker discovery are costly, laborious and time-consuming. Computational prediction methods can be used to greatly expedite the identification of candidate biomarkers. RESULTS: Here, we present a novel computational model named GTGenie for predicting the biomarker-disease associations based on graph and text features. In GTGenie, a graph attention network is utilized to characterize diverse similarities of biomarkers and diseases from heterogeneous information resources. Meanwhile, a pretrained BERT-based model is applied to learn the text-based representation of biomarker-disease relation from biomedical literature. The captured graph and text features are then integrated in a bimodal fusion network to model the hybrid entity representation. Finally, inductive matrix completion is adopted to infer the missing entries for reconstructing relation matrix, with which the unknown biomarker-disease associations are predicted. Experimental results on HMDD, HMDAD and LncRNADisease data sets showed that GTGenie can obtain competitive prediction performance with other state-of-the-art methods. AVAILABILITY: The source code of GTGenie and the test data are available at: https://github.com/Wolverinerine/GTGenie.
Subject(s)
Computational Biology , Software , Computational Biology/methods , HumansABSTRACT
There is a lack of robust generalizable predictive biomarkers of response to immune checkpoint blockade in multiple types of cancer. We develop hDirect-MAP, an algorithm that maps T cells into a shared high-dimensional (HD) expression space of diverse T cell functional signatures in which cells group by the common T cell phenotypes rather than dimensional reduced features or a distorted view of these features. Using projection-free single-cell modeling, hDirect-MAP first removed a large group of cells that did not contribute to response and then clearly distinguished T cells into response-specific subpopulations that were defined by critical T cell functional markers of strong differential expression patterns. We found that these grouped cells cannot be distinguished by dimensional-reduction algorithms but are blended by diluted expression patterns. Moreover, these identified response-specific T cell subpopulations enabled a generalizable prediction by their HD metrics. Tested using five single-cell RNA-seq or mass cytometry datasets from basal cell carcinoma, squamous cell carcinoma and melanoma, hDirect-MAP demonstrated common response-specific T cell phenotypes that defined a generalizable and accurate predictive biomarker.
Subject(s)
Immunotherapy , Melanoma , Biomarkers , Humans , Melanoma/drug therapy , Melanoma/genetics , T-LymphocytesABSTRACT
As the most abundant form of methylation modification in messenger RNA (mRNA), the distribution of N6-methyladenosine (m6A) has been preliminarily revealed in herbaceous plants under salt stress, but its function and mechanism in woody plants were still unknown. Here, we showed that global m6A levels increased during poplar response to salt stress. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that m6A significantly enriched in the coding sequence region and 3'-untranslated regions in poplar, by recognising the conserved motifs, AGACU, GGACA and UGUAG. A large number of differential m6A transcripts have been identified, and some have been proved involving in salt response and plant growth and development. Further combined analysis of MeRIP-seq and RNA-seq revealed that the m6A hypermethylated and enrich in the CDS region preferred to positively regulate expression abundance. Writer inhibitor, 3-deazaneplanocin A treatment increased the sensitivity of poplar to salt stress by reducing mRNA stability to regulate the expression of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Furthermore, we verified that the methyltransferase PagFIP37 plays a positively role in the response of poplar to salt stress, overexpressed lines have stronger salt tolerance, while RNAi lines were more sensitive to salt, which relied on regulating mRNA stability in an m6A manner of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Collectively, these results revealed the regulatory role of m6A methylation in poplar response to salt stress, and revealed the importance and mechanism of m6A methylation in the response of woody plants to salt stress for the first time.
Subject(s)
Adenosine/analogs & derivatives , Populus , RNA Methylation , Salt Stress/genetics , Methyltransferases/genetics , Populus/genetics , RNA, Messenger/geneticsABSTRACT
AIMS: To analyse spatial and temporal changes in the global burden of diabetes mellitus (DM) attributable to dietary factors from 1990 to 2019. MATERIALS AND METHODS: The burden of DM was analysed in terms of age-standardized disability-adjusted life-year (DALY) rates and age-standardized death rates (ASDRs), which were obtained from the Global Burden of Disease Study 2019, and their corresponding estimated annual percentage changes (EAPCs). RESULTS: The ASDR exhibited a decreasing trend (EAPC = -0.02), while the age-standardized DALY rate exhibited an increasing trend (EAPC = 0.65). Forty-four percent of the burden of DM was attributable to dietary factors, with the three largest contributors being high intake of red meat, high intake of processed meat, and low intake of fruit. Residence in a region with a high sociodemographic index (SDI) was associated with a diet low in whole grains and high in red meat and processed meat, while residence in a low-SDI region was associated with a diet low in whole grains and fruits, and high in red meat. CONCLUSIONS: The age-standardized DALYs of DM attributable to dietary factors increased between 1990 and 2019 but differed among areas. The three largest dietary contributors to the burden of DM were high intake of red meat, high intake of processed meat, and low intake of fruit.
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Diabetes Mellitus , Global Burden of Disease , Humans , Diabetes Mellitus/epidemiology , Meat/adverse effects , Fruit , Quality-Adjusted Life YearsABSTRACT
The advancement of anode materials for achieving high energy storage is a crucial topic for high-performance Li-ion batteries (LIBs). Here, first-principles calculations were used to conduct a thorough and systematic investigation into lithium storage properties of MXenes with new S functional groups as LIB anode materials. Density of states, diffusion energy barriers, open circuit voltages and storage capacities were calculated to comprehensively evaluate the lithium storage properties of S-functionalized MXenes. Based on the computational results, Ti2CS2 and V2CS2 were selected as excellent candidates from ten M2CS2 MXenes. The diffusion energy barriers of M2CS2 within the range of 0.26-0.32 eV are lower than those of M2CO2 and M2CF2, indicating that M2CS2 anodes exhibit faster charge/discharge rates. By examining the stable crystal structures and comparing atomic positions before and after Li adsorptions, structural phase transitions during Li-ion adsorptions could happen for nearly all M2CS2 MXenes. The phase transitions predicted were directly observed using ab initio molecular dynamic simulations. The cycle stability, storage capacity and other lithium storage properties were enhanced by the reversible structural phase transition.
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Piglet birth weight is associated with preweaning survival, and its related traits have been included in the breeding program. Thus, understanding its genetic basis is essential. This study identified four birth weight-associated genomic regions on chromosomes 2, 4, 5, and 7 through genome-wide association study analysis in 7286 pigs from three different pure breeds using the FarmCPU model. The genetic and phenotypic variance explained by the four candidate regions is 8.42% and 1.85%, respectively. Twenty-eight candidate genes were detected, of which APPL2, TGFBI, MACROH2A1, and SEC22B have been reported to affect body growth or development. In addition, 21 H3K4me3-enriched peaks overlapped with the birth weight-associated genomic regions were identified by integrating the genome-wide association study results with our previous ChIP-seq and RNA-seq data generated in the pig placenta, a fetal organ relevant to birth weight, and three of the regulatory regions influence TGFBI, MACROH2A1, and SEC22B expression. This study provides new insights into understanding the mechanisms for birth weight. Further investigating the variants in the regulatory regions would help identify the functional variants for birth weight in pigs.
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Birth Weight , Genome-Wide Association Study , Sus scrofa , Animals , Birth Weight/genetics , Genome-Wide Association Study/veterinary , Sus scrofa/genetics , Polymorphism, Single Nucleotide , Female , Regulatory Sequences, Nucleic Acid , Phenotype , BreedingABSTRACT
Sepsis-induced myopathy is one of the serious complications of sepsis, which severely affects the respiratory and peripheral motor systems of patients, reduces their quality of life, and jeopardizes their lives, as evidenced by muscle atrophy, loss of strength, and impaired regeneration after injury. The pathogenesis of sepsis-induced myopathy is complex, mainly including cytokine action, enhances free radical production in muscle, increases muscle protein hydrolysis, and decreases skeletal muscle protein synthesis, etc. The above mechanisms have been demonstrated in existing studies. However, it is still unclear how the overall pattern of gene co-expression affects the pathological process of sepsis-induced myopathy. Therefore, we intend to identify hub genes and signaling pathways. Weighted gene co-expression network analysis was our main approach to study gene expression profiles: skeletal muscle transcriptome in ICU patients with sepsis-induced multi-organ failure (GSE13205). After data pre-processing, about 15,181 genes were used to identify 13 co-expression modules. Then, 16 genes (FEM1B, KLHDC3, GPX3, NIFK, GNL2, EBNA1BP2, PES1, FBP2, PFKP, BYSL, HEATR1, WDR75, TBL3, and WDR43) were selected as the hub genes including 3 up-regulated genes and 13 down-regulated genes. Then, Gene Set Enrichment Analysis was performed to show that the hub genes were closely associated with skeletal muscle dysfunction, necrotic and apoptotic skeletal myoblasts, and apoptosis in sepsis-induced myopathy. Overall, 16 candidate biomarkers were certified as reliable features for more in-depth exploration of sepsis-induced myopathy in basic and clinical studies.
Subject(s)
Gene Regulatory Networks , Muscular Diseases , Protein Interaction Maps , Sepsis , Humans , Sepsis/genetics , Sepsis/metabolism , Sepsis/complications , Muscular Diseases/genetics , Muscular Diseases/etiology , Muscular Diseases/diagnosis , Gene Expression Profiling , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Transcriptome , Signal Transduction/geneticsABSTRACT
Infantile hemangiomas (IHs) are the most common benign soft tissue tumors of infancy. Oral propranolol has become a first-line treatment option since the unexpected discovery of its surprising efficacy in the treatment of IHs in 2008. However, oral propranolol causes systemic complications, including hypotension, bradycardia, and hypoglycemia. To minimize systemic adverse effects of oral propranolol, timolol maleate, a nonselective ß-blocker similar to propranolol, has been used as a topical agent to treat superficial IHs. The authors evaluated the efficacy and safety of oral propranolol or topical timolol in 60 patients with IHs. Of the 60 patients recruited, 30 patients were treated using orally administrated propranolol and an additional 30 patients received topical timolol. The efficacy rate of the oral propranolol and topical timolol was 96.7% and 93.3%, respectively. There were no significant differences between the two treatment patterns for the efficacy rate. The incidence of systemic adverse effects for patients treated with oral propranolol was significantly higher than that for cases received topically timolol treatment. Topical timolol maleate is effective and well-tolerated in the treatment of IHs. It could be considered as the first-line treatment choice, especially for superficial IHs.
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Background: Supine percutaneous nephrolithotomy (s-PCNL) offers great benefits from urological and anaesthetic points of view. We present the first evaluation of the outcomes of s-PCNL in Malaysia. Our aim was to explore the safety and efficacy of s-PCNL. Methods: Institutional review board approval was obtained from the National Medical Research Register (NMRR ID-21002225-WLP). We retrospectively reviewed 115 patients with renal pelvis stones who underwent single renal access during s-PCNL between November 2020 and May 2023. Patients who underwent simultaneous ipsilateral or contralateral endourological procedures were included. The data were analysed to determine stone-free rates (SFR), major complication rates, blood transfusion rates, operative times and lengths of hospital stay (LOS). Results: The SFR was higher for the single middle calyceal renal access (MCA) group than for the lower calyceal renal access (LCA) or upper calyceal renal access (UCA) groups (OR: 1.76; 95% confidence interval [CI]: 0.63, 4.92). In total, 0, 1 and 2 patients had major complications in the UCA, MCA and LCA groups, respectively (P = 0.453). One of the 115 patients (0.9%) needed blood transfusion. Subgroup analysis revealed mean operative times of 76.3 min and 78.6 min for patients who underwent sole s-PCNL (PCNL-only group) and those who had simultaneous ipsilateral and contralateral endourological procedures (PCNL-plus group), respectively (P = 0.786). The overall mean LOS was 2.9 days. Conclusion: s-PCNL is a safe and effective alternative treatment for renal stones. We would recommend s-PCNL for patients who require an ipsilateral/contralateral endourological procedure (URS/RIRS) because it is time-efficient. All renal accesses are safe. Single MCA is recommended for complete stone clearance.
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Successful attachment of conceptus to the uterine luminal epithelium (LE) is crucial for establishing a functional placenta in pigs. However, the underlying mechanisms are yet to be elucidated. The uterine LE-conceptus interface is enriched in various glycoconjugates essential to implantation. Using MALDI-MS profiling, we identified for the first time the O-glycan repertoire of pig endometrium during the conceptus attachment stage. The expression pattern of blood group A, O(H), Lewis x, y, a, b (Lex, Ley, Lea, and Leb), the sialylated and sulfated Lex antigens in the uterine LE-conceptus interface was assessed using immunofluorescence assays. Notably, the Lex-carrying O-glycans exhibited a temporal-spatial expression pattern. They were absent in the endometrium on estrous cycle days but strongly and spatially presented in the conceptus and uterine LE to which the conceptus apposes during the early conceptus attachment stage. In addition, Lex-carrying O-glycans were co-localized with secreted phosphoprotein 1 (SPP1), a well-characterized factor that plays a role in promoting conceptus attachment through interacting with integrin αVß3 and integrin αVß6. Meanwhile, the immunoprecipitation assays revealed an interaction between the Lex-carrying O-glycans and SPP1, integrin αV, and integrin ß6. Furthermore, we provided evidence that the ß1,4-galactosyltransferase 1 (B4GALT1) gene is a potential regulator for Lex antigen expression in the uterine LE-conceptus interface during the early conceptus attachment stage. In conclusion, our findings show that Lex-carrying O-glycans, presumably dependent on B4GALT1 gene expression, might modulate conceptus attachment by interacting with the SPP1-integrin receptor complex in pigs.
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Embryo Implantation , Uterus , Pregnancy , Female , Swine , Animals , Uterus/metabolism , Placenta/metabolism , Endometrium/metabolism , Polysaccharides/metabolismABSTRACT
SUMMARY: Mutation is the key for a variant of concern (VOC) to overcome selective pressures, but this process is still unclear. Understanding the association of the mutational process with VOCs is an unmet need. Motivation: Here, we developed VOC-alarm, a method to predict VOCs and their caused COVID surges, using mutations of about 5.7 million SARS-CoV-2 complete sequences. We found that VOCs rely on lineage-level entropy value of mutation numbers to compete with other variants, suggestive of the importance of population-level mutations in the virus evolution. Thus, we hypothesized that VOCs are a result of a mutational process across the globe. Results: Analyzing the mutations from January 2020 to December 2021, we simulated the mutational process by estimating the pace of evolution, and thus divided the time period, January 2020-March 2022, into eight stages. We predicted Alpha, Delta, Delta Plus (AY.4.2) and Omicron (B.1.1.529) by their mutational entropy values in the Stages I, III, V and VII with accelerated paces, respectively. In late November 2021, VOC-alarm alerted that Omicron strongly competed with Delta and Delta plus to become a highly transmissible variant. Using simulated data, VOC-alarm also predicted that Omicron could lead to another COVID surge from January 2022 to March 2022. AVAILABILITY AND IMPLEMENTATION: Our software implementation is available at https://github.com/guangxujin/VOC-alarm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Mutation , SoftwareABSTRACT
Brucellosis is a zoonotic infectious disease caused by Brucella spp, which could cause serious economic losses to animal husbandry and threaten human public health. Ingestion of contaminated animal products is a common way to acquire Brucella infection in humans, while research on effect of oral Brucella infection on host gut microbiota and the gene expression in intestinal tissues is limited. In the present study, 16S rRNA sequencing and RNA sequencing were conducted to explore gut microbiota and expression profiles of mRNAs in the colon of BALB/c mice, which were infected by Brucella abortus 2308. The fecal samples were collected at 7 and 28 days post infection to observe changes in the gut microbiota during Brucella infection. In the alpha diversity analysis, significantly increased Chao 1 index was observed at 28 days after Brucella infection. The Bray-Curtis distancebased principal coordinate analysis indicated that the WT group showed a separation from the Brucella infection groups. In addition, analysis of composition of microbes revealed that Prevotellaceae_NK3B31_group were more abundant in 1 week and 4 week infection groups, while Turicibacter was only more abundant in 4 week infection group. Based on the RNA-seq assay, a total of 45 differentially expressed genes were detected between Brucella abortus infection group and control group. Furthermore, KEGG pathway enrichment analysis showed that protein processing in endoplasmic reticulum, Legionellosis, Spliceosome, Hippo signaling pathway and Influenza A were significantly enriched in response to Brucella abortus infection. Our finding will help to improve the knowledge of the mechanisms underlying Brucella infection and may provide novel targets for future treatment of this pathogen infection.
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Brucellosis, Bovine , Brucellosis , Gastrointestinal Microbiome , Animals , Mice , Cattle , Humans , Brucella abortus/genetics , Brucella abortus/metabolism , Transcriptome , Mice, Inbred BALB C , RNA, Ribosomal, 16S/geneticsABSTRACT
HDAC10 has been reported to be associated with poor prognosis in patients with non-small cell lung cancer (NSCLC), however, the regulatory role and mechanisms of HDAC10 in NSCLC have not been investigated. In this study, we found that HDAC10 was increased in NSCLC patients and cell lines. And high expression of HDAC10 is linked to poor survival in NSCLC patients. The results showed that knockdown of HDAC10 triggered DNA damage, S-phase arrest, and proliferation inhibition in A549 and H1299 cells. In addition, knockdown of HDAC10 promoted cell ferroptosis by enhancing ROS, MDA and Fe2+ levels. Mechanistically, HDAC10 knockdown reduced SP1 expression and elevated the acetylation level of SP1, which inhibited the binding of SP1 to the promoter of POLE2, resulting in reduced POLE2 expression. Overexpression of SP1 or POLE2 partially reversed the effects of HDAC10 deletion on NSCLC cell proliferation and ferroptosis. In conclusion, knockdown of HDAC10 inhibited the proliferation of NSCLC cells and promoted their ferroptosis by regulating the SP1/POLE2 axis. HDAC10 might be a promising target for the treatment of NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Acetylation , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation , DNA Damage , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/metabolismABSTRACT
The process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.
Subject(s)
Peptide Hydrolases , Animals , Mice , Brucella abortus/genetics , Endopeptidase Clp/genetics , Proteomics , Virulence , Disease Models, AnimalABSTRACT
Along with Li-ion extraction/intercalation during charge and discharge processes, structural phase transitions often occur in the electrode materials of Li-ion batteries (LIBs). By determining atomic positions before and after Li adsorptions, structural phase transitions of two-dimensional MXenes were investigated systematically using first-principles density functional calculations. The lithiation-induced phase transitions of ten M2C MXenes with oxygen groups can be divided into three types. No phase transitions occur for Ti-type MXenes including Ti2CO2, Zr2CO2 and Hf2CO2. The oxygens in Ta-type MXenes (Sc2CO2, Y2CO2, Nb2CO2 and Ta2CO2) move from one type of octahedral void to another type of octahedral void. However, for Mo-type MXenes including V2CO2, Cr2CO2 and Mo2CO2, the oxygens move from octahedral voids to tetrahedral voids. The mechanisms whether phase transitions happen or not are dependent on the sizes of M ions. Furthermore, all the predicted phase transitions were confirmed by ab initio molecular dynamics simulations. The calculated results of electron localization functions and Bader charge illustrate that there exist strong Coulomb interactions (ionic bonds) between Li and MXene surfaces. The band structure, diffusion energy barrier, open circuit voltage and storage capacity were calculated to evaluate the lithium storage properties of different MXenes, which reveals that V2CO2 and Cr2CO2 should be optimal candidates as electrode materials for LIBs.
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Alcohol dependence (AD) is a risk factor for death and disability. Relapse prevention for AD has been exclusively dominated by psychotherapy intervention for many years. Our study aimed to investigate the efficacy of group motivational interviewing (MI) on the psychological craving for alcohol and depressive symptoms in AD patients in the rehabilitation phase, as well as the impact of age. The participants included 108 individuals with AD in the rehabilitation phase. All participants were assigned to the MI intervention group or the control group and were treated for 6 weeks. The severity of psychological craving for alcohol was assessed by the Penn Alcohol Craving Scale (PACS), and psychological status was evaluated by the Hamilton Depression Rating Scale (HAMD). We found that group MI significantly reduced the psychological craving for alcohol in patients with AD in the rehabilitation phase (p < 0.05). In addition, when patients were divided into two groups according to their ages, we found that group MI interventions tended to be effective only in younger patients with AD, but not in older patients. Our findings provide further evidence that the efficacy of group MI interventions was influenced by the age of patients with AD in the rehabilitation stage.
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As a biological characteristic, gait uses the posture characteristics of human walking for identification, which has the advantages of a long recognition distance and no requirement for the cooperation of subjects. This paper proposes a research method for recognising gait images at the frame level, even in cases of discontinuity, based on human keypoint extraction. In order to reduce the dependence of the network on the temporal characteristics of the image sequence during the training process, a discontinuous frame screening module is added to the front end of the gait feature extraction network, to restrict the image information input to the network. Gait feature extraction adds a cross-stage partial connection (CSP) structure to the spatial-temporal graph convolutional networks' bottleneck structure in the ResGCN network, to effectively filter interference information. It also inserts XBNBlock, on the basis of the CSP structure, to reduce estimation caused by network layer deepening and small-batch-size training. The experimental results of our model on the gait dataset CASIA-B achieve an average recognition accuracy of 79.5%. The proposed method can also achieve 78.1% accuracy on the CASIA-B sample, after training with a limited number of image frames, which means that the model is more robust.
Subject(s)
Gait , Research Design , Humans , Walking , Posture , SkeletonABSTRACT
Double-perovskite oxides have attracted recent attention due to their attractive functionalities and application potential. In this paper, we demonstrate the effect of dual controls, i.e., the deposition pressure of oxygen (PO2) and lattice mismatch (ε), on tuning magnetic properties in epitaxial double-perovskite Sr2FeReO6 films. In a nearly lattice matched Sr2FeReO6/SrTiO3 film, the ferrimagnetic-to-paramagnetic phase transition occurs when PO2 is reduced to 30 mTorr, probably due to the formation of Re4+ ions that replace the stoichiometric Re5+ to cause disorders of B-site ions. On the other hand, a large compressive strain or tensile strain shifts this critical PO2 to below 1 mTorr or above 40 mTorr, respectively. The observations can be attributed to the modulation of B-site ordering by epitaxial strain through affecting elemental valence. Our results provide a feasible way to expand the functional tunability of magnetic double-perovskite oxides that hold great promise for spintronic devices.
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Colorectal cancer is one of the most prevalent and lethal malignancies, affecting approximately 900,000 individuals each year worldwide. Patients with colorectal cancer are found with elevated serum interleukin-6 (IL-6), which is associated with advanced tumor grades and is related to their poor survival outcomes. Although IL-6 is recognized as a potent inducer of colorectal cancer progression, the detail mechanisms underlying IL-6-induced colorectal cancer epithelial-mesenchymal transition (EMT), one of the major process of tumor metastasis, remain unclear. In the present study, we investigated the regulatory role of IL-6 signaling in colorectal cancer EMT using HCT116 human colorectal cancer cells. We noted that the expression of epithelial marker E-cadherin was reduced in HCT116 cells exposed to IL-6, along with the increase in a set of mesenchymal cell markers including vimentin and α-smooth muscle actin (α-SMA), as well as EMT transcription regulators-twist, snail and slug. The changes of EMT phenotype were related to the activation of Src, FAK, ERK1/2, p38 mitogen-activated protein kinase (p38MAPK), as well as transcription factors STAT3, κB and C/EBPß. IL-6 treatment has promoted the recruitment of STAT3, κB and C/EBPß toward the Twist promoter region. Furthermore, the Src-FAK signaling blockade resulted in the decline of IL-6 induced activation of ERK1/2, p38MAPK, κB, C/EBPß and STAT3, as well as the decreasing mesenchymal state of HCT116 cells. These results suggested that IL-6 activates the Src-FAK-ERK/p38MAPK signaling cascade to cause the EMT of colorectal cancer cells. Pharmacological approaches targeting Src-FAK signaling may provide potential therapeutic strategies for rescuing colorectal cancer progression.