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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38678587

ABSTRACT

Deep learning-based multi-omics data integration methods have the capability to reveal the mechanisms of cancer development, discover cancer biomarkers and identify pathogenic targets. However, current methods ignore the potential correlations between samples in integrating multi-omics data. In addition, providing accurate biological explanations still poses significant challenges due to the complexity of deep learning models. Therefore, there is an urgent need for a deep learning-based multi-omics integration method to explore the potential correlations between samples and provide model interpretability. Herein, we propose a novel interpretable multi-omics data integration method (DeepKEGG) for cancer recurrence prediction and biomarker discovery. In DeepKEGG, a biological hierarchical module is designed for local connections of neuron nodes and model interpretability based on the biological relationship between genes/miRNAs and pathways. In addition, a pathway self-attention module is constructed to explore the correlation between different samples and generate the potential pathway feature representation for enhancing the prediction performance of the model. Lastly, an attribution-based feature importance calculation method is utilized to discover biomarkers related to cancer recurrence and provide a biological interpretation of the model. Experimental results demonstrate that DeepKEGG outperforms other state-of-the-art methods in 5-fold cross validation. Furthermore, case studies also indicate that DeepKEGG serves as an effective tool for biomarker discovery. The code is available at https://github.com/lanbiolab/DeepKEGG.


Subject(s)
Biomarkers, Tumor , Deep Learning , Neoplasm Recurrence, Local , Humans , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/genetics , Computational Biology/methods , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Genomics/methods , Multiomics
2.
Brief Bioinform ; 25(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38446740

ABSTRACT

Protein annotation has long been a challenging task in computational biology. Gene Ontology (GO) has become one of the most popular frameworks to describe protein functions and their relationships. Prediction of a protein annotation with proper GO terms demands high-quality GO term representation learning, which aims to learn a low-dimensional dense vector representation with accompanying semantic meaning for each functional label, also known as embedding. However, existing GO term embedding methods, which mainly take into account ancestral co-occurrence information, have yet to capture the full topological information in the GO-directed acyclic graph (DAG). In this study, we propose a novel GO term representation learning method, PO2Vec, to utilize the partial order relationships to improve the GO term representations. Extensive evaluations show that PO2Vec achieves better outcomes than existing embedding methods in a variety of downstream biological tasks. Based on PO2Vec, we further developed a new protein function prediction method PO2GO, which demonstrates superior performance measured in multiple metrics and annotation specificity as well as few-shot prediction capability in the benchmarks. These results suggest that the high-quality representation of GO structure is critical for diverse biological tasks including computational protein annotation.


Subject(s)
Benchmarking , Computational Biology , Gene Ontology , Learning , Molecular Sequence Annotation
3.
J Neurosci ; 44(7)2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38124211

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and stereotyped behaviors. Although major advances in basic research on autism have been achieved in the past decade, and behavioral interventions can mitigate the difficulties that individuals with autism experience, little is known about the many fundamental issues of the interventions, and no specific medication has demonstrated efficiency for the core symptoms of ASD. Intermittent hypobaric hypoxia (IHH) is characterized by repeated exposure to lowered atmospheric pressure and oxygen levels, which triggers multiple physiological adaptations in the body. Here, using two mouse models of ASD, male Shank3B -/- and Fmr1 -/y mice, we found that IHH training at an altitude of 5,000 m for 4 h per day, for 14 consecutive days, ameliorated autistic-like behaviors. Moreover, IHH training enhanced hypoxia inducible factor (HIF) 1α in the dorsal raphe nucleus (DRN) and activated the DRN serotonergic neurons. Infusion of cobalt chloride into the DRN, to mimic IHH in increasing HIF1α expression or genetically knockdown PHD2 to upregulate HIF1α expression in the DRN serotonergic neurons, alleviated autistic-like behaviors in Shank3B -/- mice. In contrast, downregulation of HIF1α in DRN serotonergic neurons induced compulsive behaviors. Furthermore, upregulating HIF1α in DRN serotonergic neurons increased the firing rates of these neurons, whereas downregulation of HIF1α in DRN serotonergic neurons decreased their firing rates. These findings suggest that IHH activated DRN serotonergic neurons via upregulation of HIF1α, and thus ameliorated autistic-like phenotypes, providing a novel therapeutic option for ASD.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Mice , Male , Animals , Autistic Disorder/genetics , Autistic Disorder/therapy , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/therapy , Dorsal Raphe Nucleus , Serotonergic Neurons/physiology , Hypoxia , Phenotype , Fragile X Mental Retardation Protein
4.
J Infect Dis ; 229(6): 1791-1795, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38134382

ABSTRACT

Vaginal inserts that can be used on demand before or after sex may be a desirable human immunodeficiency virus (HIV) prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF, 20 mg) and elvitegravir (EVG, 16 mg) were highly protective against repeated simian/human immunodeficiency virus (SHIV) vaginal exposures when administered to macaques 4 hours before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8 hours or 24 hours after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women.


Subject(s)
Adenine , Alanine , Anti-HIV Agents , Quinolones , Simian Acquired Immunodeficiency Syndrome , Tenofovir , Animals , Tenofovir/administration & dosage , Tenofovir/analogs & derivatives , Female , Quinolones/administration & dosage , Quinolones/pharmacology , Alanine/administration & dosage , Simian Acquired Immunodeficiency Syndrome/prevention & control , Simian Acquired Immunodeficiency Syndrome/virology , Anti-HIV Agents/administration & dosage , Adenine/analogs & derivatives , Adenine/administration & dosage , Adenine/pharmacology , Adenine/therapeutic use , Vagina/virology , Vagina/drug effects , Simian Immunodeficiency Virus/drug effects , HIV Infections/prevention & control , HIV Infections/virology , Administration, Intravaginal , Macaca mulatta , Disease Models, Animal
5.
Small ; : e2401834, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623962

ABSTRACT

Different facets in perovskite crystals exhibit distinct atomic arrangements, influencing their electronic, physical, and chemical properties. Perovskite films incorporating tin oxide (SnO2) as the electron transport layer face challenges in facet regulation. This study reveals that tea saponin (TS), a natural compound serves as a SnO2 modifier, facilitates optimal growth of perovskite crystals on the (111) facet. The modification promotes preferential crystal orientation through hydrogen bond and Lewis coordination. TS forms a chelate with SnO2, resulting in a smoother film and n-type doping, leading to improved carrier extraction and reduced defects. The TS-modified perovskite solar cells achieve a champion efficiency of 24.2%, leveraging from an obvious enhancement of open-circuit voltage (Voc) of 1.18 V and fill factor (FF) of 82.8%. The devices also demonstrate enhanced humidity tolerance and storage stability, ensuring improved stability without encapsulation.

6.
BMC Microbiol ; 24(1): 156, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724913

ABSTRACT

BACKGROUND: To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion. RESULTS: Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes. CONCLUSIONS: Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.


Subject(s)
Anti-Bacterial Agents , Campylobacter Infections , Campylobacter jejuni , Cefoperazone , Feces , Gastrointestinal Microbiome , Mice, Inbred C57BL , RNA, Ribosomal, 16S , Sulbactam , Animals , Campylobacter jejuni/drug effects , Campylobacter jejuni/growth & development , Female , Anti-Bacterial Agents/pharmacology , Cefoperazone/pharmacology , Feces/microbiology , Campylobacter Infections/microbiology , Mice , Gastrointestinal Microbiome/drug effects , Sulbactam/pharmacology , RNA, Ribosomal, 16S/genetics , Intestines/microbiology , Colon/microbiology , Colon/pathology , Disease Models, Animal , Intestinal Mucosa/microbiology , Intestinal Mucosa/drug effects , DNA, Bacterial/genetics , DNA, Ribosomal/genetics
7.
J Exp Bot ; 75(10): 3153-3170, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38394357

ABSTRACT

Endophytic symbioses between plants and fungi are a dominant feature of many terrestrial ecosystems, yet little is known about the signaling that defines these symbiotic associations. Hydrogen peroxide (H2O2) is recognized as a key signal mediating the plant adaptive response to both biotic and abiotic stresses. However, the role of H2O2 in plant-fungal symbiosis remains elusive. Using a combination of physiological analysis, plant and fungal deletion mutants, and comparative transcriptomics, we reported that various environmental conditions differentially affect the interaction between Arabidopsis and the root endophyte Phomopsis liquidambaris, and link this process to alterations in H2O2 levels and H2O2 fluxes across root tips. We found that enhanced H2O2 efflux leading to a moderate increase in H2O2 levels at the plant-fungal interface is required for maintaining plant-fungal symbiosis. Disturbance of plant H2O2 homeostasis compromises the symbiotic ability of plant roots. Moreover, the fungus-regulated H2O2 dynamics modulate the rhizosphere microbiome by selectively enriching for the phylum Cyanobacteria, with strong antioxidant defenses. Our results demonstrated that the regulation of H2O2 dynamics at the plant-fungal interface affects the symbiotic outcome in response to external conditions and highlight the importance of the root endophyte in reshaping the rhizosphere microbiota.


Subject(s)
Arabidopsis , Endophytes , Homeostasis , Hydrogen Peroxide , Microbiota , Plant Roots , Rhizosphere , Symbiosis , Arabidopsis/microbiology , Arabidopsis/physiology , Endophytes/physiology , Hydrogen Peroxide/metabolism , Plant Roots/microbiology , Plant Roots/physiology , Ascomycota/physiology
8.
Chemistry ; : e202402231, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008402

ABSTRACT

Supramolecular polymers (SPs) are constructed through non-covalent interactions. The dynamic or reversible nature of SPs endows them unique physical and chemical properties, such as self-adaptive and stimuli-response abilities. The topological structures of SPs play an important role in determining the physicochemical properties and functionality. Hyperbranched polymers (HBPs) are highly branched 3D macromolecules with linear, dendritic, and terminal units, which makes them versatile candidates for the construction of SPs with fascinating architectures. The resultant HBP-based SPs perfectly integrated the dynamic/reversible nature of SPs and the 3D topological features and multifunctionality of HBP polymers. To date, various types of HBP-based SPs and their assemblies have been constructed, and their potential applications have been explored as well. This article overviews the current progress on self-assembly of HBP-based SPs. The strategies for construction of HBP-based SPs and their assemblies are discussed. Typical potential applications of the assemblies of HBP-based SPs are also introduced.

9.
Chemistry ; : e202402636, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39109460

ABSTRACT

In this work, we report the syntheses of three Pt(II) emitters, namely, Pt4N1, Pt4N2, and Pt4N3, to which their tetradentate chelates were assembled by linking two pyrazolate chelates with a single xylenylamino entity. Functionalization of Pt4N1 was achieved upon addition of electronegative CF3 substituent on pyridinyl groups and switching to more electron deficient pyrazinyl groups in giving Pt4N2 and Pt4N3, respectively. The vertical arranged xylenylamino entity has effectively suppressed the inter-molecular π-π stacking and Pt···Pt interaction, as shown by the single crystal X-ray structural analyses. Upon fabrication of OLED devices, Pt4N2 and Pt4N3 based devices delivered efficient cyan and green emission, with an EQEmax of 15.2% and 11.2%, respectively, affirming the successfulness of the tetradentate chelating strategy.

10.
J Magn Reson Imaging ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609076

ABSTRACT

BACKGROUND: Lymph node metastasis (LNM) in patients with intrahepatic cholangiocarcinoma (iCCA) affects treatment strategies and prognosis. However, preoperative imaging is not reliable enough for identifying LNM. PURPOSE: To develop and validate a radiomics nomogram based on dynamic contrast enhanced (DCE)-MR images for identifying LNM and prognosis in iCCA. STUDY TYPE: Retrospective. SUBJECTS: Two hundred four patients with pathologically proven iCCA who underwent curative-intent resection and lymphadenectomy (training cohort: N = 107, internal test cohort: N = 46, and external test cohort: N = 51). FIELD STRENGTH/SEQUENCE: T1- and T2-weighted imaging, diffusion-weighted imaging and DCE imaging at 1.5 T or 3.0 T. ASSESSMENT: Radiomics features were extracted from intra- and peri-tumoral regions on preoperative DCE-MR images. Imaging features were evaluated by three radiologists, and significant variables in univariable and multivariable regression analysis were included in clinical model. The best-performing radiomics signature and clinical characteristics (intrahepatic duct dilatation, MRI-reported LNM) were combined to build a nomogram. Patients were divided into high-risk and low-risk groups based on their nomogram scores (cutoff = 0.341). Patients were followed up for 1-102 months (median 12) after surgery, the overall survival (OS) and recurrence-free survival (RFS) were calculated. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, calibration, decision curve, Delong test, Kaplan-Meier curves, log rank test. Two tailed P < 0.05 was considered statistically significant. RESULTS: The nomogram incorporating intra- and peri-tumoral radiomics features, intrahepatic duct dilatation and MRI-reported LNM obtained the best discrimination for LNM, with areas under the ROC curves of 0.946, 0.913, and 0.859 in the training, internal, and external test cohorts. In the entire cohort, high-risk patients had significantly lower RFS and OS than low-risk patients. High-risk of LNM was an independent factor of unfavorable OS and RFS. DATA CONCLUSION: The nomogram integrating intra- and peri-tumoral radiomics signatures has potential to identify LNM and prognosis in iCCA. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

11.
Nutr Cancer ; 76(6): 486-498, 2024.
Article in English | MEDLINE | ID: mdl-38680010

ABSTRACT

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1ß), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1ß, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1ß, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.


Subject(s)
Body Mass Index , Cytokines , Disease Progression , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Neoadjuvant Therapy , Weight Loss , Humans , Male , Female , Middle Aged , Cytokines/blood , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/blood , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Neoplasms/therapy , Esophageal Neoplasms/blood , Esophageal Neoplasms/pathology , Retrospective Studies , Aged , Neoadjuvant Therapy/methods , Malnutrition/blood , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/pathology , Neoplasm Staging , Chemoradiotherapy/methods , Tumor Necrosis Factor-alpha/blood
12.
J Org Chem ; 89(5): 3471-3480, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38350101

ABSTRACT

A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.

13.
J Med Primatol ; 53(4): e12723, 2024 08.
Article in English | MEDLINE | ID: mdl-38978165

ABSTRACT

BACKGROUND: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. METHODS: Eighteen female PTMs were evaluated. Blood was collected 1-24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. RESULTS: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. CONCLUSIONS: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.


Subject(s)
Algorithms , Macaca nemestrina , Animals , Female , Reference Values , Hematologic Tests/veterinary
14.
Fish Shellfish Immunol ; 150: 109649, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797336

ABSTRACT

In mammals, CD4 is found to be expressed on T cells and innate immune cells, however, teleost cells bearing CD4 have not been well identified and characterized. In this study, we identified two different CD4-1+ cell subsets in grass carp (Ctenopharyngodon idella): CD4-1+ lymphocytes (Lym) and CD4-1+ myeloid cells (Mye), both of which had the highest proportions in the head kidney. The mRNA expression analysis showed that CD4-1, CD4-2, TCRß, CD3γ/δ, and LCK1 are highly expressed in CD4-1+ Lym and also expressed in CD4-1+ Mye. Furthermore, we found that CD4-1+ Lym have a Lym morphology and highly express T-cell cytokines, suggesting that they are CD4+ T cells equivalent to mammalian Th cells. On the other hand, CD4-1+ Mye were found to have a morphology of macrophage and highly express macrophage marker gene MCSFR, indicating that they are macrophages. In addition, functional analysis revealed that CD4-1+ Mye possess phagocytic ability and great antigen-processing ability. Taken together, our study sheds further light on the composition and function of CD4+ cells in teleost fish.


Subject(s)
Carps , Fish Proteins , Animals , Carps/immunology , Carps/genetics , Fish Proteins/genetics , Fish Proteins/immunology , CD4-Positive T-Lymphocytes/immunology , CD4 Antigens/genetics , CD4 Antigens/immunology , CD4 Antigens/metabolism , Head Kidney/immunology , Head Kidney/cytology , Myeloid Cells/immunology , Immunity, Innate/genetics
15.
Fish Shellfish Immunol ; 152: 109775, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39019126

ABSTRACT

Bacterial intestinal inflammation frequently occurs in cultured fish. Nevertheless, research on intestinal barrier dysfunction in the process of intestinal inflammation is deficient. In this study, we explored the changes of intestinal inflammation induced by Aeromonas hydrophila (A. hydrophila) in snakehead and the relationship between intestinal barrier and inflammation. Snakehead [(13.05 ± 2.39) g] were infected via anus with A. hydrophila. Specimens were collected for analysis at 0, 1, 3, 7 and 21 d post-injection. The results showed that with the increase of exposure time, the hindgut underwent stages of normal function, damage, damage deterioration, repair and recovery. Relative to 0 d, the levels of IL-1ß and TNF-α in serum, and the expression of nod1, tlr1, tlr5, nf-κb, tnf-α and il-1ß in intestine were significantly increased, and showed an upward then downward pattern over time. However, the expression of tlr2 and il-10 were markedly decreased, and showed the opposite trend. In addition, with the development of intestinal inflammation, the diversity and richness of species, and the levels of phylum and genus in intestine were obviously altered. The levels of trypsin, LPS, AMS, T-SOD, CAT, GPx, AKP, LZM and C3 in intestine were markedly reduced, and displayed a trend of first decreasing and then rebounding. The ultrastructure observation showed that the microvilli and tight junction structure of intestinal epithelial cells experienced normal function initially, then damage, and finally recovery over time. The expression of claudin-3 and zo-1 in intestine were significantly decreased, and showed a trend of first decreasing and then rebounding. Conversely, the expression of mhc-i, igm, igt and pigr in intestine were markedly increased, and displayed a trend of increasing first and then decreasing. The above results revealed the changes in intestinal barrier during the occurrence and development of intestinal inflammation, which provided a theoretical basis for explaining the relationship between the two.


Subject(s)
Aeromonas hydrophila , Fish Diseases , Gram-Negative Bacterial Infections , Intestines , Animals , Aeromonas hydrophila/physiology , Fish Diseases/immunology , Fish Diseases/microbiology , Fishes/immunology , Fishes/microbiology , Gastrointestinal Microbiome , Gram-Negative Bacterial Infections/immunology , Gram-Negative Bacterial Infections/veterinary , Inflammation/immunology , Inflammation/veterinary , Intestinal Mucosa/immunology , Intestines/immunology , Intestines/pathology
16.
Pathobiology ; : 1-14, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38718783

ABSTRACT

INTRODUCTION: Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent. METHODS: Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole-slide images (WSIs) and is composed of two deep learning models to locate the lymph nodes and detect cancers. RESULTS: It achieved an area under the receiver operating characteristic curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 WSIs from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical centre, with an AUC of 0.925. CONCLUSION: Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.

17.
Biol Cybern ; 118(1-2): 21-37, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38472417

ABSTRACT

Motor imagery electroencephalogram (EEG) is widely employed in brain-computer interface (BCI) systems. As a time-frequency analysis method for nonlinear and non-stationary signals, multivariate empirical mode decomposition (MEMD) and its noise-assisted version (NA-MEMD) has been widely used in the preprocessing step of BCI systems for separating EEG rhythms corresponding to specific brain activities. However, when applied to multichannel EEG signals, MEMD or NA-MEMD often demonstrate low robustness to noise and high computational complexity. To address these issues, we have explored the advantages of our recently proposed fast multivariate empirical mode decomposition (FMEMD) and its noise-assisted version (NA-FMEMD) for analyzing motor imagery data. We emphasize that FMEMD enables a more accurate estimation of EEG frequency information and exhibits a more noise-robust decomposition performance with improved computational efficiency. Comparative analysis with MEMD on simulation data and real-world EEG validates the above assertions. The joint average frequency measure is employed to automatically select intrinsic mode functions that correspond to specific frequency bands. Thus, FMEMD-based classification architecture is proposed. Using FMEMD as a preprocessing algorithm instead of MEMD can improve the classification accuracy by 2.3% on the BCI Competition IV dataset. On the Physiobank Motor/Mental Imagery dataset and BCI Competition IV Dataset 2a, FMEMD-based architecture also attained a comparable performance to complex algorithms. The results indicate that FMEMD proficiently extracts feature information from small benchmark datasets while mitigating dimensionality constraints resulting from computational complexity. Hence, FMEMD or NA-FMEMD can be a powerful time-frequency preprocessing method for BCI.


Subject(s)
Brain-Computer Interfaces , Electroencephalography , Imagination , Humans , Electroencephalography/methods , Imagination/physiology , Algorithms , Signal Processing, Computer-Assisted , Multivariate Analysis , Brain/physiology , Computer Simulation
18.
BMC Vet Res ; 20(1): 147, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643185

ABSTRACT

BACKGROUND: Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits. RESULTS: Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.7 ± 10.7%) and low plasma protein binding (18.5-31.9%). PK analysis identified a mean plasma peak concentration (Cmax) of 1.64 ± 0.86 mg/L and terminal half-life (T1/2) of 31.5 ± 5.74 h after subcutaneous injection. For P. multocida, short post-antibiotic effects (PAE) (1.1-5.3 h) and post-antibiotic sub-inhibitory concentration effects (PA-SME) (6.6-9.1 h) were observed after exposure to gamithromycin at 1 to 4× minimal inhibitory concentration (MIC). Gamithromycin demonstrated concentration-dependent bactericidal activity and the PK/PD index area under the concentration-time curve over 24 h (AUC24h)/MIC correlated well with efficacy (R2 > 0.99). The plasma AUC24h/MIC ratios of gamithromycin associated with the bacteriostatic, bactericidal and bacterial eradication against P. multocida were 15.4, 24.9 and 27.8 h in rabbits, respectively. CONCLUSIONS: Subcutaneous administration of 6 mg/kg gamithromycin reached therapeutic concentrations in rabbit plasma against P. multocida. The PK/PD ratios determined herein in combination with ex vivo activity and favorable rabbit PK indicate that gamithromycin may be used for the treatment of rabbit pasteurellosis.


Subject(s)
Cattle Diseases , Lagomorpha , Pasteurella Infections , Pasteurella multocida , Swine Diseases , Rabbits , Animals , Cattle , Swine , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacokinetics , Pasteurella Infections/drug therapy , Pasteurella Infections/veterinary , Pasteurella Infections/microbiology , Macrolides/therapeutic use , Macrolides/pharmacokinetics , Microbial Sensitivity Tests/veterinary , Cattle Diseases/drug therapy , Swine Diseases/drug therapy
19.
J Nanobiotechnology ; 22(1): 361, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38910236

ABSTRACT

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.


Subject(s)
Autophagy , Cold Temperature , Exosomes , Mice, Inbred C57BL , MicroRNAs , Osteogenesis , Animals , Autophagy/drug effects , Mice , Exosomes/metabolism , MicroRNAs/metabolism , MicroRNAs/genetics , Osteogenesis/drug effects , Mesenchymal Stem Cells/metabolism , Osteoporosis/pathology , Cell Differentiation/drug effects , Bone and Bones/metabolism , Female , Bone Density , Sirolimus/pharmacology
20.
Psychol Res ; 88(4): 1389-1398, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38478053

ABSTRACT

Attention can be captured by the presence of distractors that match the current content of working memory in the visual field. This memory-driven capture is well established when observers adopt diffused attentional settings prior to the onset of memory-matching distractors. However, it remains unclear whether memory-driven capture can occur when observers are in a state of focused attention. The present study attempted to address this question by examining whether memory-matching distractors can disrupt performance on a focused attention task. Participants were asked to hold a sample word in working memory and then had to name a central color while ignoring an irrelevant distractor word in the visual display. In Experiments 1 and 2, the distractor word was always presented centrally within the focus of attention. In Experiment 3, the distractor word could be presented either at the center or at the periphery (i.e., outside the focus of attention). The results showed that the irrelevant distractor word within the focus of attention interfered with color-naming performance when it matched the sample word held in working memory. However, no interference effect was observed when the distractor word was presented outside the attentional focus. The present findings indicate that working memory-driven capture during a state of focused visual attention depends crucially on whether or not memory-matching distractors are positioned within the focus of attention.


Subject(s)
Attention , Memory, Short-Term , Humans , Attention/physiology , Memory, Short-Term/physiology , Young Adult , Male , Female , Adult , Visual Perception/physiology , Reaction Time/physiology , Color Perception/physiology
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