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2.
Digit Health ; 10: 20552076241277713, 2024.
Article in English | MEDLINE | ID: mdl-39247098

ABSTRACT

Aim: To optimize gastric cancer screening score and reduce screening costs using machine learning models. Methods: This study included 228,634 patients from the Taizhou Gastric Cancer Screening Program. We used three machine learning models to optimize Li's gastric cancer screening score: Gradient Boosting Machine (GBM), Distributed Random Forest (DRF), and Deep Learning (DL). The performance of the binary classification models was evaluated using the area under the curve (AUC) and area under the precision-recall curve (AUCPR). Results: In the binary classification model used to distinguish low-risk and moderate- to high-risk patients, the AUC in the GBM, DRF, and DL full models were 0.9994, 0.9982, and 0.9974, respectively, and the AUCPR was 0.9982, 0.9949, and 0.9918, respectively. Excluding Helicobacter pylori IgG antibody, pepsinogen I, and pepsinogen II, the AUC in the GBM, DRF, and DL models were 0.9932, 0.9879, and 0.9900, respectively, and the AUCPR was 0.9835, 0.9716, and 0.9752, respectively. Remodel after removing variables IgG, PGI, PGII, and G-17, the AUC in GBM, DRF, and DL was 0.8524, 0.8482, 0.8477, and AUCPR was 0.6068, 0.6008, and 0.5890, respectively. When constructing a tri-classification model, we discovered that none of the three machine learning models could effectively distinguish between patients at intermediate and high risk for gastric cancer (F1 scores in the GBM model for the low, medium and high risk: 0.9750, 0.9193, 0.5334, respectively; F1 scores in the DRF model for low, medium, and high risks: 0.9888, 0.9479, 0.6694, respectively; F1 scores in the DL model for low, medium, and high risks: 0.9812, 0.9216, 0.6394, respectively). Conclusion: We concluded that gastric cancer screening indicators could be optimized when distinguishing low-risk and moderate to high-risk populations, and detecting gastrin-17 alone can achieve a good discriminative effect, thus saving huge expenditures.

3.
Biochem Biophys Res Commun ; 734: 150732, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39340924

ABSTRACT

This study aims to explore the regulating effect and mechanism of naringenin (NGN) on the hepatic stellate cells (HSCs) apoptosis and its preventive effects on MASH fibrosis. C57BL/6 mice were subjected to either high-fat diet (HFD) plus carbon tetrachloride (CCl4) injection (HFD + CCl4) for 8 weeks to induce a MASH fibrosis model or bile duct ligation (BDL) to establish a liver fibrosis model, NGN was administered by gavage. LX2 cells were stimulated by oleic acid (OA) and lipopolysaccharide (LPS) (OA + LPS) to study the effects of NGN on activated hepatic stellate cell (HSC). Additionally, LO2 cells stimulated with OA + LPS were used to assess the protective effects of NGN on lipotoxicity of hepatocytes. Our in vivo results showed that NGN administration effectively inhibited mouse liver fibrosis in both of the MASH model and BDL model. The in vitro results indicate that NGN directly inhibited HSCs activation and promoted apoptosis of the activated HSCs, while it suppressed the apoptosis of LO2 cells induced by OA + LPS. The underlying mechanisms were mainly elucidated through the reduction of TAK1 phosphorylation, leading to the downregulation of p-JNK and p-ERK expression. This in turn, inhibited the phosphorylation of FoxO3a and promoted the nuclear localization of FoxO3a. Consequently, this may enhance the transcription of apoptosis-related genes, resulting in the apoptosis of activated HSCs. In conclusion, NGN ameliorates MASH fibrosis by enhancing apoptosis of the activated HSCs. The inhibitory effects of NGN on the TAK1/MAPK/FoxO3a pathway were demonstrated as its preventive mechanisms against MASH fibrosis.

4.
bioRxiv ; 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39185226

ABSTRACT

Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.

5.
J Fungi (Basel) ; 10(8)2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39194912

ABSTRACT

Phyllachora (Phyllachoraceae, Phyllachorales) species are parasitic fungi with a wide global distribution, causing tar spots on plants. In this study, we describe three newly discovered species: Phyllachora chongzhouensis, Phyllachora neidongensis, and Phyllachora huiliensis from Poaceae in China. These species were characterized using morphological traits and multi-locus phylogeny based on the internal transcribed spacer region (ITS) with the intervening 5.8S rRNA gene, the large subunit of the rRNA gene (LSU), and the 18S ribosomal RNA gene (SSU). Three known species of P. chloridis, P. graminis, and P. miscanthi have also been redescribed, because, in reviewing the original references of P. chloridis, P. graminis, and P. miscanthi, these were found to be relatively old and in Chinese or abbreviated. In addition, the illustrations were simple. In molecular identification, the ITS sequence is short, while the ITS, LSU, and SSU are incomplete. Therefore, this study provides new important references for the redescription of three known species and provides further evidence for the identification of new taxa.

6.
Nat Neurosci ; 27(10): 2009-2020, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39179884

ABSTRACT

The human brain experiences functional changes through childhood and adolescence, shifting from an organizational framework anchored within sensorimotor and visual regions into one that is balanced through interactions with later-maturing aspects of association cortex. Here, we link this profile of functional reorganization to the development of ventral attention network connectivity across independent datasets. We demonstrate that maturational changes in cortical organization link preferentially to within-network connectivity and heightened degree centrality in the ventral attention network, whereas connectivity within network-linked vertices predicts cognitive ability. This connectivity is associated closely with maturational refinement of cortical organization. Children with low ventral attention network connectivity exhibit adolescent-like topographical profiles, suggesting that attentional systems may be relevant in understanding how brain functions are refined across development. These data suggest a role for attention networks in supporting age-dependent shifts in cortical organization and cognition across childhood and adolescence.


Subject(s)
Attention , Cerebral Cortex , Cognition , Magnetic Resonance Imaging , Nerve Net , Humans , Child , Attention/physiology , Male , Female , Cognition/physiology , Adolescent , Cerebral Cortex/physiology , Cerebral Cortex/growth & development , Nerve Net/physiology , Nerve Net/growth & development , Nerve Net/diagnostic imaging , Neural Pathways/physiology , Neural Pathways/growth & development , Brain Mapping , Child Development/physiology , Connectome
7.
Phytomedicine ; 134: 155956, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39216301

ABSTRACT

BACKGROUND: Alcoholic liver disease (ALD) significantly contributes to global liver-related morbidity and mortality. Natural products play a crucial role in the prevention and treatment of ALD. Hydroxysafflor yellow A (HSYA), a unique and primary component of Safflower (Carthamus tinctorius l.), exhibits diverse pharmacological activities. However, the impact and mechanism of HSYA on ALD have not been fully elucidated. PURPOSE: The purpose of this study was to employ an integrative pharmacology approach to assess the multi-targeted mechanism of HSYA against ALD. METHODS: Network pharmacology and molecular docking techniques were used to analyze the potential therapeutic signaling pathways and targets of HSYA against ALD. An ALD model in zebrafish larvae was established. Larvae were pretreated with HSYA and then exposed to ethanol. Liver injury was measured by fluorescence expression analysis in the liver-specific transgenic zebrafish line Tg (fabp10a:DsRed) and liver tissue H&E staining. Liver steatosis was determined by whole-mount oil red O staining and TG level. Additionally, an ethanol-induced hepatocyte injury model was established in vitro to observe hepatocyte damage (cell viability, ALT level), lipid accumulation (oil red O staining, TC and TG), and oxidative stress (ROS, MDA, GPx and SOD) in HepG2 cells treated with or without HSYA. Finally, qRT-PCR combined with network pharmacology and molecular docking was employed to validate the effects of HSYA on targets. RESULTS: HSYA exhibited a significant, dose-dependent improvement in ethanol-induced liver injury in zebrafish larvae and HepG2 cells. Network pharmacology analysis revealed that HSYA may exert pharmacological effects against ALD through 341 potential targets. These targets are involved in various signaling pathways, including lipid metabolism and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and ALD itself. Molecular docking studies displayed that HSYA had a strong binding affinity toward the domains of IL1B, IL6, TNF, PPARA, PPARG, HMGCR and ADH5. qRT-PCR assays demonstrated that HSYA effectively reversed the ethanol-induced aberrant gene expression of SREBF1, FASN, ACACA, CPT1A, PPARA, IL1B, IL6, TNFα, ADH5, and ALDH2 in vivo and in vitro. CONCLUSION: This study offers a comprehensive investigation into the anti-ALD mechanisms of HSYA using an integrative pharmacology approach. The potential targets of HSYA may be implicated in enhancing ethanol catabolism, reducing lipid accumulation, mitigating oxidative stress, and inhibiting inflammatory response.


Subject(s)
Chalcone , Liver Diseases, Alcoholic , Molecular Docking Simulation , Network Pharmacology , Quinones , Zebrafish , Animals , Liver Diseases, Alcoholic/drug therapy , Chalcone/pharmacology , Chalcone/analogs & derivatives , Chalcone/chemistry , Quinones/pharmacology , Quinones/chemistry , Humans , Carthamus tinctorius/chemistry , Ethanol , Animals, Genetically Modified , Signal Transduction/drug effects , Hepatocytes/drug effects , Disease Models, Animal , Larva/drug effects , Liver/drug effects , Liver/metabolism , Oxidative Stress/drug effects , Hep G2 Cells
8.
World J Clin Cases ; 12(18): 3497-3504, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38983434

ABSTRACT

BACKGROUND: An increasing number of studies have begun to discuss the relationship between gut microbiota and diseases, yet there is currently a lack of corresponding articles describing the association between gut microbiota and hepatocellular carcinoma (HCC) and biliary tract cancer (BTC). This study aims to explore the relationship between them using Mendelian randomization (MR) analysis method. AIM: To assess the relationship between gut microbiota and HCC and BTC. METHODS: We obtained Genome-wide association study (GWAS) data for the gut microbiome from the intestinal microbiota genomic library (MiBioGen, https://mibiogen.gcc.rug.nl/). Additionally, we accessed data pertaining to HCC and BTC from the IEU open GWAS platform (https://gwas.mrcieu.ac.uk/). Our analysis employed fundamental instrumental variable analysis methods, including inverse-variance weighted, MR and Egger. To ensure the dependability of the results, we subjected the results to tests for multiple biases and heterogeneity. RESULTS: During our investigation, we discovered 11 gut microbiota linked to an increased risk to BTC and HCC. The former included the genus Eubacterium hallii group (P = 0.017), Candidatus Soleaferrea (P = 0.034), Flavonifractor (P = 0.021), Lachnospiraceae FCS020 (P = 0.034), the order Victivallales (P = 0.018), and the class Lentisphaeria (P = 0.0.18). The latter included the genus Desulfovibrio (P = 0.042), Oscillibacter (P = 0.023), the family Coriobacteriaceae (P = 0.048), the order Coriobacteriales (P = 0.048), and the class Coriobacteriia (P = 0.048). Furthermore, in BTC, we observed 2 protective gut microbiota namely the genus Dorea (P = 0.041) and Lachnospiraceae ND3007 group (P = 0.045). All results showed no evidence of multiplicity or heterogeneity. CONCLUSION: This study explores a causal link between gut microbiota and HCC and BTC. These insights may enhance the mechanistic knowledge of microbiota-related HCC and BTC pathways, potentially informing therapeutic strategies.

9.
Article in English | MEDLINE | ID: mdl-38822974

ABSTRACT

Vascular remodeling is the adaptive response of the vessel wall to physiological and pathophysiological changes, closely linked to vascular diseases. Vascular smooth muscle cells (VSMCs) play a crucial role in this process. Pyroptosis, a form of programmed cell death characterized by excessive release of inflammatory factors, can cause phenotypic transformation of VSMCs, leading to their proliferation, migration, and calcification-all of which accelerate vascular remodeling. Inhibition of VSMC pyroptosis can delay this process. This review summarizes the impact of pyroptosis on VSMCs and the pathogenic role of VSMC pyroptosis in vascular remodeling. We also discuss inhibitors of key proteins in pyroptosis pathways and their effects on VSMC pyroptosis. These findings enhance our understanding of the pathogenesis of vascular remodeling and provide a foundation for the development of novel medications that target the control of VSMC pyroptosis as a potential treatment strategy for vascular diseases.

10.
J Nat Med ; 78(4): 849-862, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38724866

ABSTRACT

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.


Subject(s)
Diterpenes , Hypoglycemic Agents , Insulin-Secreting Cells , Regeneration , Zebrafish , Animals , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Diterpenes/chemistry , Diterpenes/pharmacology , Diterpenes/isolation & purification , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Molecular Structure , Regeneration/drug effects , Structure-Activity Relationship , Wood/chemistry , Animals, Genetically Modified , Thymelaeaceae/chemistry
11.
Biomaterials ; 309: 122600, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38718614

ABSTRACT

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases.


Subject(s)
Gelatin , Hydrogels , Ischemia , Neovascularization, Physiologic , Polyurethanes , Printing, Three-Dimensional , Animals , Gelatin/chemistry , Polyurethanes/chemistry , Hydrogels/chemistry , Ischemia/therapy , Neovascularization, Physiologic/drug effects , Mice , Humans , Myocytes, Smooth Muscle/cytology , Cross-Linking Reagents/chemistry , Human Umbilical Vein Endothelial Cells , Hindlimb/blood supply , Hindlimb/pathology , Male , Tissue Engineering/methods , Bioprinting/methods
12.
Indian J Med Microbiol ; 49: 100574, 2024.
Article in English | MEDLINE | ID: mdl-38561026

ABSTRACT

PURPOSE: The Shewanella genus is a rare pathogen of marine origin. In recent years, there has been a continuous increase in infection cases caused by this bacterium, and we have observed the uniqueness of infections caused by this microorganism. MATERIALS AND METHODS: This study conducted a retrospective analysis of the medical history and laboratory examination data of patients infected with the Shewanella genus over the past decade. Additionally, it employed bioinformatics methods to analyze the relevant virulence factors and antibiotic resistance genes associated with the Shewanella genus. RESULTS: Over the past 10 years, we have isolated 51 cases of Shewanella, with 68.82% being Shewanella putrefaciens (35/51 cases) and 31.37% being Shewanella algae (16/51 cases). Infected individuals often had underlying diseases, with 39.22% (20/51) having malignant tumors and 25.49% (13/51) having liver and biliary system diseases primarily characterized by stones. The majority of patients, 62.74% (32/51), exhibited mixed infections, including one case with a combination of infections from three other types of bacteria and five cases with a combination of infections from two other types of bacteria. The identified microorganisms were commonly resistant to ticarcillin-clavulanic acid (23.5%), followed by cefoperazone-sulbactam (19.6%), ciprofloxacin (17.6%), and cefotaxime (17.6%). Bioinformatics analysis indicates that Shewanella can express bile hydrolysis regulators and fatty acid metabolism regulators that aid in adapting to the unique environment of the biliary tract. Additionally, it expresses abundant catalase, superoxide dismutase, and two-component signal transduction system proteins, which may be related to environmental adaptation. Shewanella also expresses various antibiotic resistance genes, including beta-lactamases and aminoglycoside modification enzymes. Iron carriers may be one of its important virulence factors. CONCLUSIONS: We speculate that the Shewanella genus may exist as a specific colonizer in the human body, and under certain conditions, it may act as a pathogen, leading to biliary infections in the host.


Subject(s)
Gram-Negative Bacterial Infections , Shewanella , Virulence Factors , Humans , Shewanella/genetics , Shewanella/classification , Shewanella/isolation & purification , Shewanella/pathogenicity , Retrospective Studies , Gram-Negative Bacterial Infections/microbiology , Male , Female , Middle Aged , Adult , Virulence Factors/genetics , Aged , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Young Adult , Adolescent , Shewanella putrefaciens/genetics , Shewanella putrefaciens/isolation & purification , Shewanella putrefaciens/classification
13.
Circulation ; 149(23): 1833-1851, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38586957

ABSTRACT

BACKGROUND: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition. METHODS: Here, we leveraged 2 models of in vitro cultured adult mouse cardiomyocytes and in vivo adeno-associated virus serotype 9 cardiomyocyte-targeted delivery of reprogramming factors (Oct4, Sox2, Klf4, and Myc) in adult mice to study CMDD. We profiled their transcriptomes using RNA sequencing, in combination with multiple published data sets, with the aim of identifying a common denominator for tracking CMDD. RESULTS: RNA sequencing and integrated analysis identified Asparagine Synthetase (Asns) as a unique molecular marker gene well correlated with CMDD, required for increased asparagine and also for distinct fluxes in other amino acids. Although Asns overexpression in Oct4, Sox2, Klf4, and Myc cardiomyocytes augmented hallmarks of CMDD, Asns deficiency led to defective regeneration in the neonatal mouse myocardial infarction model, increased cell death of cultured adult cardiomyocytes, and reduced cell cycle in Oct4, Sox2, Klf4, and Myc cardiomyocytes, at least in part through disrupting the mammalian target of rapamycin complex 1 pathway. CONCLUSIONS: We discovered a novel gene Asns as both a molecular marker and an essential mediator, marking a distinct threshold that appears in common for at least 4 models of CMDD, and revealing an Asns/mammalian target of rapamycin complex 1 axis dependency for dedifferentiating cardiomyocytes. Further study will be needed to extrapolate and assess its relevance to other cell state transitions as well as in heart regeneration.


Subject(s)
Aspartate-Ammonia Ligase , Cell Dedifferentiation , Kruppel-Like Factor 4 , Myocytes, Cardiac , Animals , Mice , Aspartate-Ammonia Ligase/genetics , Aspartate-Ammonia Ligase/metabolism , Cells, Cultured , Myocytes, Cardiac/metabolism , Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor/genetics , Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor/metabolism
14.
J Gerontol Soc Work ; 67(4): 492-514, 2024.
Article in English | MEDLINE | ID: mdl-38590208

ABSTRACT

This pilot randomized controlled trial aimed to evaluate the feasibility and potential outcomes of an innovative 16-session multicomponent intervention model to improve cognitive abilities in older adults with mild cognitive impairment (MCI) by promoting healthy lifestyle, cognitive skills, tai chi and mindfulness practices. This study was a multicentre, randomized controlled, two-arm, parallel-group, unblinded trial in Hong Kong. 57 Chinese older adults with MCI recruited from three local elderly centers were randomly assigned to either the control or intervention group. The study results support the feasibility and efficacy of the multicomponent intervention, and recommend future larger-scale randomized control trials.


Subject(s)
Cognitive Dysfunction , Humans , Cognitive Dysfunction/therapy , Aged , Male , Female , Pilot Projects , Hong Kong , Aged, 80 and over , Tai Ji/methods , Mindfulness/methods , Cognition , Middle Aged
15.
Article in English | MEDLINE | ID: mdl-38573002

ABSTRACT

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34+ hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.

16.
Brain Res Bull ; 212: 110959, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38643887

ABSTRACT

Alpha-(1,6)-fucosyltransferase (FUT8) has been found to play a role in modulating the central immune system and inflammatory responses. Limited studies have assessed the correlations between serum FUT8 levels and various non-motor symptoms associated with early Parkinson's disease (PD). Therefore, our research aims to investigate the associations between serum FUT8 levels and symptoms such as smell dysfunction, sleep duration, sleep problems, and MMSE scores in PD patients. FUT8 and neurofilament light chain (NfL) levels were measured using enzyme-linked immunosorbent assays (ELISA). We analyzed the correlations between serum FUT8 levels, NfL, and early symptoms of PD using Spearman's correlation, multiple linear regression, and logistic regression models. The expression of FUT8 in CSF samples from PD patients was significantly upregulated, with its protein levels in CSF being positively associated with serum levels. Furthermore, there were significant positive associations between serum FUT8 levels with NfL levels, smell dysfunction, short sleep duration, and long sleep duration. However, a significant inverse relationship was observed between FUT8 levels and MMSE scores. Additionally, we explored gender and age differences in the correlations of FUT8 levels and early symptoms in patients. This study reveals that increased FUT8 levels are positively correlated with a higher risk of early PD-associated symptoms. These findings suggest that serum FUT8 could serve as a promising biomarker for the early detection of PD.


Subject(s)
Fucosyltransferases , Parkinson Disease , Humans , Parkinson Disease/blood , Male , Female , Middle Aged , Aged , Cross-Sectional Studies , Retrospective Studies , Neurofilament Proteins/blood , Neurofilament Proteins/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Sleep Wake Disorders/blood , Sleep Wake Disorders/cerebrospinal fluid
17.
Sci Rep ; 14(1): 7361, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548780

ABSTRACT

Malicious attacks are often inevitable in cyber-physical systems (CPS). Accuracy in Cyber physical system for position tracking of servos is the major concern now a days. In high precision industrial automation, it is very hard to achieve accuracy in tracking especially under malicious cyber-attacks, control saturations, parametric perturbations and external disturbances. In this paper, we have designed a novel predefined time (PDT) convergence sliding mode adaptive controller (PTCSMAC) for such kind of cyber physical control system. Main key feature of our control is to cope these challenges that are posed by CPS systems such as parameter perturbation, control saturation, and cyber-attacks and the whole system then upgrade to a third-order system to facilitate adaptive control law. Then, we present an adaptive controller based on the novel PDT convergent sliding mode surface (SMS) combined with a modified weight updated Extreme Learning Machine (ELM) which is used to approximate the uncertain part of the system. Another significant advantage of our proposed control approach is that it does not require detailed model information, guaranteeing robust performance even when the system model is uncertain. Additionally, our proposed PTCSMAC controller is nonsingular regardless of initial conditions, and is capable of eradicating the possibility of singularity problems, which are frequently a concern in numerous CPS control systems. Finally, we have verified our designed PTCSMAC control law through rigorous simulations on CPS seeker servo positioning system and compared the robustness and performance of different existing techniques.

18.
Sci Rep ; 14(1): 5408, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443444

ABSTRACT

Achieving accurate position tracking for robotics and industrial servo systems is an extremely challenging task, particularly when dealing with control saturation, parameter perturbation, and external disturbance. To address these challenges, a predefined time convergent sliding mode adaptive controller (PTCSMAC) has been proposed for a permanent magnet linear motor (PMLM). A novel sliding mode surface (SMS) with predefined time convergence PDTC has been constructed, which ensures that the error converges to zero within the prescribed time. The system not only meets the expected performance standards but also has a uniformly bounded motor speed. The trajectory tracking error in SMS is proven to converge to zero within the predefined time. This predefined time stability of the closed-loop system has been demonstrated by using the Lyapunov stability criterion with PDTC. The convergence time (CT) can be arbitrarily set, and the upper bound of it is not affected by the initial value and control parameters of the system. A new updated version of extreme learning machine (ELM) is introduced to approximate the uncertain part of the system based on PDTC. The ELM is also provided with the hyperbolic tangent function to estimate the saturation constraint. This is done by converting the function into a linear function concerning the unconstrained control input variable. Then, based on established stability, a novel sliding mode adaptive controller (PTCSMAC) with predefined time convergence is designed. The convergence time (CT) of the controller is unaffected by the initial conditions as well as the control parameters. The rigorous numerical simulations on the PMLM model with complex disturbances verify the strong robustness and high-precision tracking characteristic of the proposed control law.

19.
Nat Prod Bioprospect ; 14(1): 23, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38517590

ABSTRACT

In this study, two new kaurane diterpenes (16, 17), together with 12 lignans (1-12), a triterpene (15), and two other compounds (13, 14) were isolated from the woods of Agathis dammara. The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy, and its absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. Compounds 5, 11, 14 exhibit significant hypoglycaemic activity in zebrafish, and their mechanism of action is to enhance glucose uptake in zebrafish.

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