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1.
Nat Commun ; 15(1): 7299, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39181897

ABSTRACT

The free-field switching of the perpendicular magnetization by the out-of-plane polarized spin current induced spin-orbit torque makes it a promising technology for developing high-density memory and logic devices. The materials intrinsically with low symmetry are generally utilized to generate the spin current with out-of-plane spin polarization. However, the generation of the out-of-plane polarized spin current by engineering the symmetry of materials has not yet been reported. Here, we demonstrate that paramagnetic CaRuO3 films are able to generate out-of-plane polarized spin current by engineering the crystal symmetry. The non-uniform oxygen octahedral tilt/rotation along film's normal direction induced by oxygen octahedral coupling near interface breaks the screw-axis and glide-plane symmetries, which gives rise to a significant out-of-plane polarized spin current. This spin current can drive field-free spin-orbit torque switching of perpendicular magnetization with high efficiency. Our results offer a promising strategy based on crystal symmetry design to manipulate spin current and could have potential applications in advanced spintronic devices.

2.
Sci Bull (Beijing) ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39155196

ABSTRACT

In medical image segmentation, it is often necessary to collect opinions from multiple experts to make the final decision. This clinical routine helps to mitigate individual bias. However, when data is annotated by multiple experts, standard deep learning models are often not applicable. In this paper, we propose a novel neural network framework called Multi-rater Prism (MrPrism) to learn medical image segmentation from multiple labels. Inspired by iterative half-quadratic optimization, MrPrism combines the task of assigning multi-rater confidences and calibrated segmentation in a recurrent manner. During this process, MrPrism learns inter-observer variability while taking into account the image's semantic properties and finally converges to a self-calibrated segmentation result reflecting inter-observer agreement. Specifically, we propose Converging Prism (ConP) and Diverging Prism (DivP) to iteratively process the two tasks. ConP learns calibrated segmentation based on multi-rater confidence maps estimated by DivP, and DivP generates multi-rater confidence maps based on segmentation masks estimated by ConP. Experimental results show that the two tasks can mutually improve each other through this recurrent process. The final converged segmentation result of MrPrism outperforms state-of-the-art (SOTA) methods for a wide range of medical image segmentation tasks. The code is available at https://github.com/WuJunde/MrPrism.

3.
New Phytol ; 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103987

ABSTRACT

Plant phenology, the timing of recurrent biological events, shows key and complex response to climate warming, with consequences for ecosystem functions and services. A key challenge for predicting plant phenology under future climates is to determine whether the phenological changes will persist with more intensive and long-term warming. Here, we conducted a meta-analysis of 103 experimental warming studies around the globe to investigate the responses of four phenophases - leaf-out, first flowering, last flowering, and leaf coloring. We showed that warming advanced leaf-out and flowering but delayed leaf coloring across herbaceous and woody plants. As the magnitude of warming increased, the response of most plant phenophases gradually leveled off for herbaceous plants, while phenology responded in proportion to warming in woody plants. We also found that the experimental effects of warming on plant phenology diminished over time across all phenophases. Specifically, the rate of changes in first flowering for herbaceous species, as well as leaf-out and leaf coloring for woody species, decreased as the experimental duration extended. Together, these results suggest that the real-world impact of global warming on plant phenology will diminish over time as temperatures continue to increase.

4.
Article in English | MEDLINE | ID: mdl-39180870

ABSTRACT

The growth and development of myofibers, as the fundamental units comprising muscle tissue, and their composition type are indeed among the most crucial factors influencing skeletal muscle types. Muscle fiber adaptation is closely associated with alterations in physiological conditions. Muscle fiber types undergo dynamic changes in fetus and adult horses. Our aim is to investigate the mechanisms influencing the differences in muscle fiber types between fetal and adult stages of Mongolian horses. The study investigated the distribution of muscle fiber types within longissimus dorsi muscle of fetus and adult Mongolian horses. A total of 652 differentially expressed genes (DEGs), 476 Differentially expressed lncRNAs (DELs), and 174 Differentially expressed miRNAs (DEMIRs) were identified using deep RNA-seq analysis. The results of functional analysis reveal the transformations in muscle fiber type from the fetal to adult stage in Mongolian horses. The up-regulated DEGs were implicated in the development and differentiation of muscle fibers, while down-regulated DEGs were associated with muscle fiber contraction, transformation, and metabolism. Additionally, connections between non-coding RNA and mRNA landscapes were identified based on their functional alterations, some non-coding RNA target genes may be associated with immunity. These data have broadened our understanding of the specific roles and interrelationships among regulatory molecules involved in Mongolian horse development, this provides new perspectives for selecting and breeding superior individuals and for disease prevention.

5.
Front Plant Sci ; 15: 1413653, 2024.
Article in English | MEDLINE | ID: mdl-38952846

ABSTRACT

Reduced glutathione (γ-glutamyl-cysteinyl-glycine, GSH), the primary non-protein sulfhydryl group in organisms, plays a pivotal role in the plant salt stress response. This study aimed to explore the impact of GSH on the photosynthetic apparatus, and carbon assimilation in tomato plants under salt stress, and then investigate the role of nitric oxide (NO) in this process. The investigation involved foliar application of 5 mM GSH, 0.1% (w/v) hemoglobin (Hb, a nitric oxide scavenger), and GSH+Hb on the endogenous NO levels, rapid chlorophyll fluorescence, enzyme activities, and gene expression related to the Calvin cycle in tomato seedlings (Solanum lycopersicum L. cv. 'Zhongshu No. 4') subjected short-term salt stress (100 mM NaCl) for 24, 48 and 72 hours. GSH treatment notably boosted nitrate reductase (NR) and NO synthase (NOS) activities, elevating endogenous NO signaling in salt-stressed tomato seedling leaves. It also mitigated chlorophyll fluorescence (OJIP) curve distortion and damage to the oxygen-evolving complex (OEC) induced by salt stress. Furthermore, GSH improved photosystem II (PSII) electron transfer efficiency, reduced QA - accumulation, and countered salt stress effects on photosystem I (PSI) redox properties, enhancing the light energy absorption index (PIabs). Additionally, GSH enhanced key enzyme activities in the Calvin cycle and upregulated their genes. Exogenous GSH optimized PSII energy utilization via endogenous NO, safeguarded the photosynthetic reaction center, improved photochemical and energy efficiency, and boosted carbon assimilation, ultimately enhancing net photosynthetic efficiency (Pn) in salt-stressed tomato seedling leaves. Conversely, Hb hindered Pn reduction and NO signaling under salt stress and weakened the positive effects of GSH on NO levels, photosynthetic apparatus, and carbon assimilation in tomato plants. Thus, the positive regulation of photosynthesis in tomato seedlings under salt stress by GSH requires the involvement of NO.

6.
Expert Rev Clin Immunol ; 20(9): 1127-1133, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39072430

ABSTRACT

BACKGROUND: We aimed to explore simple and effective clinical parameters or combinations to predict coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease (KD). DESIGN AND METHODS: This retrospective cohort study included pediatric patients with KD from January, 2013 to December, 2022. Multiple demographic and clinical data were collected, collated, and calculated from the medical records. Then they were divided into the coronary artery dilation and aneurysm formation group or the non-coronary artery dilation and aneurysm formation group. Lymphocyte-C-reactive protein ratio (LCR) was transformed into its natural logarithm and expressed as lnLCR. RESULTS: A total of 64 pediatric patients with KD were enrolled in this cohort study after 1:3 propensity score matching (PSM). For each unit increase in lnLCR, the possibility of coronary artery dilation and aneurysm formation decreased to 0.419 times the original value. The areas under the receiver operating characteristic (ROC) curves of lnLCR combined with albumin (ALB), ALB, and lnLCR to classify pediatric patients with KD into the coronary artery dilation and aneurysm formation group were 0.781, 0.692, and 0.743, respectively. CONCLUSION: LCR combined with ALB upon admission is a promising predictor of coronary artery dilation and aneurysm formation in pediatric patients with KD.


Subject(s)
C-Reactive Protein , Coronary Aneurysm , Mucocutaneous Lymph Node Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/diagnosis , Retrospective Studies , Male , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Female , Child, Preschool , Infant , Coronary Aneurysm/etiology , Coronary Aneurysm/immunology , Child , Lymphocytes/immunology , Coronary Vessels/pathology , Biomarkers/blood , ROC Curve
7.
Plant Physiol Biochem ; 214: 108878, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38968841

ABSTRACT

In this paper, we discussed the physiological mechanism of enhanced chilling tolerance with combined treatment of nitric oxide (NO) and reduced glutathione (GSH) in cucumber seedlings. With prolonged low temperature (10 °C/6 °C), oxidative stress improved, which was manifested as an increase the hydrogen peroxide (H2O2) and malondialdehyde (MDA), causing cell membrane damage, particularly after 48 h of chilling stress. Exogenous sodium nitroprusside (SNP, NO donor) enhanced the activity of nitric oxide synthase NOS-like, the contents of GSH and polyamines (PAs), and the cellular redox state, thus regulating the activities of mitochondrial oxidative phosphorylation components (CI, CII, CIV, CV). However, buthionine sulfoximine (BSO, a GSH synthase inhibitor) treatment drastically reversed or attenuated the effects of NO. Importantly, the combination of SNP and GSH treatment had the best effect in alleviating chilling-induced oxidative stress by upregulating the activities of antioxidant enzyme, including superoxidase dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD) and improved the PAs content, thereby increased activities of CI, CII, CIII, CIV, and CV. This potentially contributes to the maintenance of oxidative phosphorylation originating from mitochondria. In addition, the high activity of S-nitrosoglutathione reductase (GSNOR) in the combined treatment of SNP and GSH possibly mediates the conversion of NO and GSH to S-nitrosoglutathione. Our study revealed that the combined treatment with NO and GSH to synergistically improve the cold tolerance of cucumber seedlings under prolonged low-temperature stress.


Subject(s)
Antioxidants , Cold Temperature , Cucumis sativus , Glutathione , Mitochondria , Nitric Oxide , Polyamines , Cucumis sativus/metabolism , Cucumis sativus/drug effects , Cucumis sativus/physiology , Nitric Oxide/metabolism , Mitochondria/metabolism , Mitochondria/drug effects , Polyamines/metabolism , Antioxidants/metabolism , Glutathione/metabolism , Oxidative Stress/drug effects , Hydrogen Peroxide/metabolism , Seedlings/drug effects , Seedlings/metabolism
8.
J Asian Nat Prod Res ; : 1-8, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963349

ABSTRACT

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

9.
Sensors (Basel) ; 24(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-39001115

ABSTRACT

In the field of autofocus for optical systems, although passive focusing methods are widely used due to their cost-effectiveness, fixed focusing windows and evaluation functions in certain scenarios can still lead to focusing failures. Additionally, the lack of datasets limits the extensive research of deep learning methods. In this work, we propose a neural network autofocus method with the capability of dynamically selecting the region of interest (ROI). Our main work is as follows: first, we construct a dataset for automatic focusing of grayscale images; second, we transform the autofocus issue into an ordinal regression problem and propose two focusing strategies: full-stack search and single-frame prediction; and third, we construct a MobileViT network with a linear self-attention mechanism to achieve automatic focusing on dynamic regions of interest. The effectiveness of the proposed focusing method is verified through experiments, and the results show that the focusing MAE of the full-stack search can be as low as 0.094, with a focusing time of 27.8 ms, and the focusing MAE of the single-frame prediction can be as low as 0.142, with a focusing time of 27.5 ms.

10.
Plants (Basel) ; 13(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38931104

ABSTRACT

In this study, processing tomato (Solanum lycopersicum L.) 'Ligeer 87-5' was hydroponically cultivated under 100 mM NaCl to simulate salt stress. To investigate the impacts on ion homeostasis, osmotic regulation, and redox status in tomato seedlings, different endogenous levels of ascorbic acid (AsA) were established through the foliar application of 0.5 mM AsA (NA treatment), 0.25 mM lycorine (LYC, an inhibitor of AsA synthesis; NL treatment), and a combination of LYC and AsA (NLA treatment). The results demonstrated that exogenous AsA significantly increased the activities and gene expressions of key enzymes (L-galactono-1,4-lactone dehydrogenase (GalLDH) and L-galactose dehydrogenase (GalDH)) involved in AsA synthesis in tomato seedling leaves under NaCl stress and NL treatment, thereby increasing cellular AsA content to maintain its redox status in a reduced state. Additionally, exogenous AsA regulated multiple ion transporters via the SOS pathway and increased the selective absorption of K+, Ca2+, and Mg2+ in the aerial parts, reconstructing ion homeostasis in cells, thereby alleviating ion imbalance caused by salt stress. Exogenous AsA also increased proline dehydrogenase (ProDH) activity and gene expression, while inhibiting the activity and transcription levels of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine-δ-aminotransferase (OAT), thereby reducing excessive proline content in the leaves and alleviating osmotic stress. LYC exacerbated ion imbalance and osmotic stress caused by salt stress, which could be significantly reversed by AsA application. Therefore, exogenous AsA application increased endogenous AsA levels, reestablished ion homeostasis, maintained osmotic balance, effectively alleviated the inhibitory effect of salt stress on tomato seedling growth, and enhanced their salt tolerance.

11.
Endocrine ; 85(2): 947-954, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38833202

ABSTRACT

PURPOSE: This study aims to analyze the distribution of plasma aldosterone, renin activity, deoxycorticosterone (DOC), cortisol, cortisone, and 24 h urinary aldosterone (24 h-uAld) levels based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. MATERIALS AND METHODS: Plasma and 24 h urine were collected from 129 healthy volunteers in Northeast China. The effect of sodium intake, age, gender, blood sampling time on plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio (ARR), DOC, cortisol, cortisone, cortisol to cortisone ratio, and 24 h-uAld were investigated by nonparametric test, multiple linear regression and Harris-Boyd's standard deviate test. RESULTS: There was no significant difference observed in 24 h-uAld, PAC (AM), PRA(AM), ARR (AM), DOC (AM), cortisol (AM), cortisone (AM), and cortisol to cortisone (AM) between high and low sodium intake group. Significant differences were observed between morning and afternoon sampling groups in terms of PAC, ARR, DOC, cortisol, and cortisone. Reference intervals (RIs) of 24 h-uAld, PAC (AM) were recommended to be partitioned by gender. RI of PRA was recommended age stratification. CONCLUSION: We recommend that the same reference interval could be used regardless of sodium intake. Gender is the main influence factor for 24 h-uAld, PAC, and ARR. Age is key influence factor for PRA.


Subject(s)
Aldosterone , Cortisone , Hydrocortisone , Renin , Tandem Mass Spectrometry , Humans , Female , Male , Adult , Cortisone/urine , Cortisone/blood , Hydrocortisone/blood , Hydrocortisone/urine , Middle Aged , Aldosterone/blood , Aldosterone/urine , Renin/blood , Tandem Mass Spectrometry/methods , Young Adult , Chromatography, Liquid/methods , Sex Factors , Age Factors , Sodium, Dietary , Desoxycorticosterone/urine , Desoxycorticosterone/blood , Aged , China , Adolescent , Liquid Chromatography-Mass Spectrometry
12.
Int J Mol Sci ; 25(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38892292

ABSTRACT

Cuticular waxes are essential for protecting plants from various environmental stresses. Allium fistulosum serves as an excellent model for investigating the regulatory mechanisms underlying cuticular wax synthesis with notable epidermal wax characteristics. A combination of gas chromatography-mass spectrometry (GC-MS) metabolite analysis and transcriptomics was used to investigate variations in metabolites and gene expression patterns between the wild type (WT) and glossy mutant type (gl2) of A. fistulosum. The WT surface had a large number of acicular and lamellar waxy crystals, whereas the leaf surface of gl2 was essentially devoid of waxy crystals. And the results revealed a significant decrease in the content of 16-hentriacontanone, the principal component of cuticular wax, in the gl2 mutant. Transcriptomic analysis revealed 3084 differentially expressed genes (DEGs) between WT and gl2. Moreover, we identified 12 genes related to fatty acid or wax synthesis. Among these, 10 DEGs were associated with positive regulation of wax synthesis, whereas 2 genes exhibited negative regulatory functions. Furthermore, two of these genes were identified as key regulators through weighted gene co-expression network analysis. Notably, the promoter region of AfisC5G01838 (AfCER1-LIKE1) exhibited a 258-bp insertion upstream of the coding region in gl2 and decreased the transcription of the AfCER1-LIKE1 gene. This study provided insights into the molecular mechanisms governing cuticular wax synthesis in A. fistulosum, laying the foundation for future breeding strategies.


Subject(s)
Allium , Gas Chromatography-Mass Spectrometry , Gene Expression Profiling , Gene Expression Regulation, Plant , Transcriptome , Waxes , Waxes/metabolism , Gas Chromatography-Mass Spectrometry/methods , Gene Expression Profiling/methods , Allium/genetics , Allium/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism
13.
Nat Metab ; 6(6): 1161-1177, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38698281

ABSTRACT

Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.


Subject(s)
Diabetic Cardiomyopathies , Fatty Acids , Receptors, G-Protein-Coupled , Animals , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Diabetic Cardiomyopathies/metabolism , Mice , Male , Female , Fatty Acids/metabolism , Humans , Mice, Knockout , Bile Acids and Salts/metabolism , Diet, High-Fat , CD36 Antigens/metabolism , CD36 Antigens/genetics , Myocardium/metabolism , Lipid Metabolism , Myocytes, Cardiac/metabolism , Diabetes Mellitus, Experimental/metabolism
14.
Cell Host Microbe ; 32(6): 964-979.e7, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38754418

ABSTRACT

The gut microbiota is closely linked to atherosclerosis. However, the role of intestinal fungi, essential members of the complex microbial community, in atherosclerosis is poorly understood. Herein, we show that gut fungi dysbiosis is implicated in patients with dyslipidemia, characterized by higher levels of Candida albicans (C. albicans), which are positively correlated with plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Furthermore, C. albicans colonization aggravates atherosclerosis progression in a mouse model of the disease. Through gain- and loss-of-function studies, we show that an intestinal hypoxia-inducible factor 2α (HIF-2α)-ceramide pathway mediates the effect of C. albicans. Mechanistically, formyl-methionine, a metabolite of C. albicans, activates intestinal HIF-2α signaling, which drives increased ceramide synthesis to accelerate atherosclerosis. Administration of the HIF-2α selective antagonist PT2385 alleviates atherosclerosis in mice by reducing ceramide levels. Our findings identify a role for intestinal fungi in atherosclerosis progression and highlight the intestinal HIF-2α-ceramide pathway as a target for atherosclerosis treatment.


Subject(s)
Atherosclerosis , Basic Helix-Loop-Helix Transcription Factors , Candida albicans , Ceramides , Signal Transduction , Animals , Candida albicans/metabolism , Atherosclerosis/microbiology , Atherosclerosis/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Mice , Humans , Ceramides/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Male , Gastrointestinal Microbiome/physiology , Intestines/microbiology , Intestines/pathology , Dysbiosis/microbiology , Female , Candidiasis/microbiology , Candidiasis/metabolism
15.
Front Plant Sci ; 15: 1361959, 2024.
Article in English | MEDLINE | ID: mdl-38576787

ABSTRACT

Artemisinin biosynthesis, unique to Artemisia annua, is suggested to have evolved from the ancestral costunolide biosynthetic pathway commonly found in the Asteraceae family. However, the evolutionary landscape of this process is not fully understood. The first oxidase in artemisinin biosynthesis, CYP71AV1, also known as amorpha-4,11-diene oxidase (AMO), has specialized from ancestral germacrene A oxidases (GAOs). Unlike GAO, which exhibits catalytic promiscuity toward amorpha-4,11-diene, the natural substrate of AMO, AMO has lost its ancestral activity on germacrene A. Previous studies have suggested that the loss of the GAO copy in A. annua is responsible for the abolishment of the costunolide pathway. In the genome of A. annua, there are two copies of AMO, each of which has been reported to be responsible for the different product profiles of high- and low-artemisinin production chemotypes. Through analysis of their tissue-specific expression and comparison of their sequences with those of other GAOs, it was discovered that one copy of AMO (AMOHAP) exhibits a different transcript compared to the reported artemisinin biosynthetic genes and shows more sequence similarity to other GAOs in the catalytic regions. Furthermore, in a subsequent in vitro enzymatic assay, the recombinant protein of AMOHAP unequivocally demonstrated GAO activity. This result clearly indicates that AMOHAP is a GAO rather than an AMO and that its promiscuous activity on amorpha-4,11-diene has led to its misidentification as an AMO in previous studies. In addition, the divergent expression pattern of AMOHAP compared to that of the upstream germacrene A synthase may have contributed to the abolishment of costunolide biosynthesis in A. annua. Our findings reveal a complex evolutionary landscape in which the emergence of a new metabolic pathway replaces an ancestral one.

16.
IEEE Trans Med Imaging ; PP2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38669168

ABSTRACT

Many of the tissues/lesions in the medical images may be ambiguous. Therefore, medical segmentation is typically annotated by a group of clinical experts to mitigate personal bias. A common solution to fuse different annotations is the majority vote, e.g., taking the average of multiple labels. However, such a strategy ignores the difference between the grader expertness. Inspired by the observation that medical image segmentation is usually used to assist the disease diagnosis in clinical practice, we propose the diagnosis-first principle, which is to take disease diagnosis as the criterion to calibrate the inter-observer segmentation uncertainty. Following this idea, a framework named Diagnosis-First segmentation Framework (DiFF) is proposed. Specifically, DiFF will first learn to fuse the multi-rater segmentation labels to a single ground-truth which could maximize the disease diagnosis performance. We dubbed the fused ground-truth as Diagnosis-First Ground-truth (DF-GT). Then, the Take and Give Model (T&G Model) to segment DF-GT from the raw image is proposed. With the T&G Model, DiFF can learn the segmentation with the calibrated uncertainty that facilitate the disease diagnosis. We verify the effectiveness of DiFF on three different medical segmentation tasks: optic-disc/optic-cup (OD/OC) segmentation on fundus images, thyroid nodule segmentation on ultrasound images, and skin lesion segmentation on dermoscopic images. Experimental results show that the proposed DiFF can effectively calibrate the segmentation uncertainty, and thus significantly facilitate the corresponding disease diagnosis, which outperforms previous state-of-the-art multi-rater learning methods.

17.
Cell ; 187(11): 2717-2734.e33, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38653239

ABSTRACT

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.


Subject(s)
Akkermansia , Bacteroides , Bile Acids and Salts , Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Symbiosis , Animals , Humans , Male , Mice , Akkermansia/metabolism , Bacteroides/metabolism , beta-Lactamases/metabolism , Bile Acids and Salts/metabolism , Biosynthetic Pathways/genetics , Fatty Liver/metabolism , Liver/metabolism , Mice, Inbred C57BL , Verrucomicrobia/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/microbiology
18.
BMC Geriatr ; 24(1): 284, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38532326

ABSTRACT

BACKGROUND: Dyadic coping resources have been considered a potential explanatory mechanism of spousal interdependence in health, but the mediation of spousal collaboration for the relationship between self-rated health and depressive symptoms has yet to be examined. This study aimed to investigate the within- (actor effect) and between-partner effects of self-rated health on depressive symptoms in community-dwelling older couples facing physical functioning limitations and to examine the role of spousal collaboration in mediating the actor and cross-partner effects of self-rated health on depressive symptoms. METHOD: Data from 185 community-dwelling older Chinese married couples were analyzed using the actor-partner interdependence mediation model (APIMeM). Couples were interviewed through trained research assistants using the 5-item common dyadic coping subscale of the Dyadic Coping Inventory (DCI), the Visual Analog Scale (VAS) of the QoL questionnaire EQ-5D and the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Husbands' self-rated health had an actor effect on their own depressive symptoms and a partner effect on their wives' depressive symptoms. Wives' self-rated health had an actor effect on their own depressive symptoms. The actor effects between self-rated health and depressive symptoms were partially mediated by their own perception of spousal collaboration. Furthermore, husbands' self-rated health not only affects wives' depressive symptoms directly but also indirectly by influencing wives' perceptions of spousal collaboration. DISCUSSION: The findings from this study underscored the importance of viewing couples' coping processes from a dyadic and gender-specific perspective, since more (perceived) collaborative efforts have beneficial effects on both partners' mental health outcomes.


Subject(s)
Depression , Quality of Life , Humans , Depression/psychology , Spouses/psychology , Surveys and Questionnaires , China
19.
PLoS One ; 19(3): e0298555, 2024.
Article in English | MEDLINE | ID: mdl-38512902

ABSTRACT

Tracking and detection have brought great challenges to network security. Therefore, this paper proposes a monitoring method of stealthy complex network attacks considering security situation awareness. By constructing a tracking model of invisible complex network attacks, public monitoring nodes are selected for monitoring. The cost of a single monitoring node is calculated by the algorithm, and the monitoring node is determined by the monitoring node algorithm, so as to reduce the resource occupancy rate of the monitoring node and improve the monitoring accuracy. The simulation results show that this method is stable in the range of 1000 to 4000 nodes, and can effectively monitor the complex network attacks of stealing secrets.


Subject(s)
Awareness , Theft , Computer Security , Computer Simulation , Algorithms
20.
BMJ Open ; 14(3): e075834, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38485180

ABSTRACT

OBJECTIVES: This study aimed to identify long-term distinct trajectories of multimorbidity with ageing from 50 to 85 years among Chinese older adults and examine the relationship between exposure to early-life adversity (ELA; including specific types of adversity and accumulation of different adversities) and these long-term multimorbidity trajectories. DESIGN: The group-based trajectory models identified long-term multimorbidity trajectories. Multinomial logistic regression models were used to examine the relationship between ELA and the identified multimorbidity trajectories. SETTING: This study used data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018) and the 2014 Life History Survey. PARTICIPANTS: We used data from 9112 respondents (aged 60 and above) of the 2018 wave of CHARLS. OUTCOME MEASURES: Each respondent's history of chronic conditions and experiences of ELA were collected from the 2011-2018 waves of CHARLS and the 2014 Life History Survey. RESULTS: Four heterogeneous long-term trajectories of multimorbidity development were identified: 'maintaining-low' (19.1%), 'low onset-rapidly increasing' (23.3%), 'middle onset-moderately increasing' (41.5%) and 'chronically-high' (16.2%). Our findings indicated that the heterogeneity can be explained by ELA experiences. Across various types of different ELA experiences, exposure to food insufficiency (relative risk ratios from 1.372 (95% CI 1.190 to 1.582) to 1.780 (95% CI 1.472 to 2.152)) and parental quarrel/divorce (relative risk ratios from 1.181 (95% CI 1.000 to 1.394) to 1.262 (95% CI 1.038 to 1.536)) had the most prominent associations with health deterioration. The accumulation of more different ELA experiences was associated with a higher relative risk of developing more severe multimorbidity trajectories (relative risk ratio for five to seven ELAs and chronically high trajectory: 7.555, 95% CI 4.993 to 11.431). CONCLUSIONS: There are heterogeneous long-term trajectories of multimorbidity in Chinese older adults, and the risk of multimorbidity associated with ELA accumulates over the lifespan. Our findings highlight the role of a supportive early-life family environment in promoting health development across the lifespan, advocating for the integration of life-course approaches to implementing health disparity interventions.


Subject(s)
Adverse Childhood Experiences , Retirement , Humans , Aged , Longitudinal Studies , Multimorbidity , China/epidemiology
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