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1.
J Colloid Interface Sci ; 675: 379-390, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38972125

ABSTRACT

Nowadays, the inherent re-stacking nature and weak d-p hybridization orbital interactions within MXene remains significant challenges in the field of electrocatalytic water splitting, leading to unsatisfactory electrocatalytic activity and cycling stability. Herein, this work aims to address these challenges and improve electrocatalytic performance by utilizing cobalt nanoparticles intercalation coupled with enhanced π-donation effect. Specifically, cobalt nanoparticles are integrated into V2C MXene nanosheets to mitigate the re-stacking issue. Meanwhile, a notable charge redistribution from cobalt to vanadium elevates orbital levels, reduces π*-antibonding orbital occupancy and alleviates Jahn-Teller distortion. Doping with tellurium induces localized electric field rearrangement resulting from the changes in electron cloud density. As a result, Co-V2C MXene-Te acquires desirable activity for hydrogen evolution reaction and oxygen evolution reaction with the overpotential of 80.8 mV and 287.7 mV, respectively, at the current density of -10 mA cm-2 and 10 mA cm-2. The overall water splitting device achieves an impressive low cell voltage requirement of 1.51 V to obtain 10 mA cm-2. Overall, this work could offer a promising solution when facing the re-stacking issue and weak d-p hybridization orbital interactions of MXene, furnishing a high-performance electrocatalyst with favorable electrocatalytic activity and cycling stability.

2.
Front Pharmacol ; 15: 1418549, 2024.
Article in English | MEDLINE | ID: mdl-39081957

ABSTRACT

Objective: SAF-189s is a potent ALK/ROS1 inhibitor that is currently in clinical development for treating advanced ALK+/ROS1+ non-small cell lung cancer (NSCLC). Comprehensive population pharmacokinetics (PopPK) and exposure-response models were developed to evaluate the efficacy and safety of SAF-189s by integrating data from two clinical studies. Methods: The PopPK model was developed using plasma concentration data collected from patients with ALK+/ROS1+ advanced NSCLC (n = 299) and healthy subjects (n = 24). The covariates (demographics, laboratory values, subject types, and concomitant medications) were evaluated to determine their potential influence on the between-patient variability in the pharmacokinetics of SAF-189s. Individual exposure values were then used to investigate the relationships with the efficacy endpoints (overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR)) and key safety endpoints (adverse events of interest). Results: The final PopPK model of SAF-189s was described by a one-compartment model with delayed first-order absorption and time-dependent elimination by allowing the clearance to decrease stepwise over time. Age was included as a covariate for apparent clearance (CL/F), while prior anti-cancer therapy in ALK+ patients (ALKPOT) was included for apparent volume of distribution (V/F). There were no apparent exposure-response relationships for any of the efficacy endpoints at doses of 80-210 mg. The relationship between exposure and safety suggested that a higher steady-state exposure was associated with more frequent incidences of hyperglycemia and proteinuria; the 210-mg dose group was also less tolerated than the other low-dose groups. Conclusion: PopPK and exposure-response models were developed for SAF-189s, and their results demonstrate that SAF-189s exposures are at the plateau of exposure-response for efficacy. The 210-mg dose group had a significantly higher safety risk, while the 160-mg dose group was well-tolerated. Thus, 160 mg of SAF-189s once daily was selected as the recommended phase III dose for the ALK+/ROS1+ or ROS1+ NSCLC patients.

3.
Environ Pollut ; 359: 124608, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39053807

ABSTRACT

Hospital wastewater is known to contain various pathogenic microorganisms and harmful substances. During the hospital wastewater treatment process, the bioaerosols released may encapsulate these pathogens, leading to human infection. This study undertook an investigation to compare the dispersion characteristics and seasonal variations of bioaerosols from hospital and municipal sewage. The results indicated that the airborne bacterial concentration from hospital sewage (119 ± 118 CFU/m3) was higher than municipal sewage (46 ± 19 CFU/m3), with the highest concentration observed in summer. The dominant bacterial genera present in bioaerosols from both sewages were alike, with the proportions varied by sewage types and the structure mainly influenced by seasonal factors. Bacteroides, Escherichia-Shigella and Streptococcus were identified as the most prevalent pathogenic genera in spring, summer and winter bioaerosols, respectively, while Pseudomonas and Acinetobacter were abundant in autumn. Although the non-carcinogenic risk associated with bioaerosols was low (<1), the presence of pathogenic species and their potential synergistic interactions elevated the overall exposure risk. The diffusion modeling results demonstrated that bioaerosol emissions from the surface of hospital sewage can reach up to 10570 CFU/m3 in summer and can spread more than 300 m downwind. The potential pathogenicity of bioaerosols was also highest in summer, which may pose a health hazard to populations located downwind. Therefore, the management and control of bioaerosols from sewage should be strengthened, especially in summer.

4.
J Agric Food Chem ; 72(30): 16998-17007, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39016055

ABSTRACT

Butachlor is widely used in agriculture around the world and therefore poses environmental and public health hazards due to persistent and poor biodegradability. Ferroptosis is a type of iron-mediated cell death controlled by glutathione (GSH) and GPX4 inhibition. P62 is an essential autophagy adaptor that regulates Keap1 to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which effectively suppresses lipid peroxidation, thereby relieving ferroptosis. Here, we found that butachlor caused changes in splenic macrophage structure, especially impaired mitochondrial morphology with disordered structure, which is suggestive of the occurrence of ferroptosis. This was further confirmed by the detection of iron metabolism, the GSH system, and lipid peroxidation. Mechanistically, butachlor suppressed the protein level of p62 and promoted Keap1-mediated degradation of Nrf2, which results in decreased GPX4 expression and accelerated splenic macrophage ferroptosis. These findings suggest that targeting the p62-Nrf2-GPX4 signaling axis may be a promising strategy for treating inflammatory diseases.


Subject(s)
Ferroptosis , Macrophages , Mice, Inbred C57BL , NF-E2-Related Factor 2 , Phospholipid Hydroperoxide Glutathione Peroxidase , Signal Transduction , Spleen , Animals , Humans , Male , Mice , Ferroptosis/drug effects , Kelch-Like ECH-Associated Protein 1/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Lipid Peroxidation/drug effects , Macrophages/drug effects , Macrophages/metabolism , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Sequestosome-1 Protein/metabolism , Sequestosome-1 Protein/genetics , Signal Transduction/drug effects , Spleen/drug effects , Spleen/cytology , Spleen/metabolism
5.
Commun Biol ; 7(1): 854, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997510

ABSTRACT

The human subcortex plays a pivotal role in cognition and is widely implicated in the pathophysiology of many psychiatric disorders. However, the heritability of functional gradients based on subcortico-cortical functional connectivity remains elusive. Here, leveraging twin functional MRI (fMRI) data from both the Human Connectome Project (n = 1023) and the Adolescent Brain Cognitive Development study (n = 936) datasets, we construct large-scale subcortical functional gradients and delineate an increased principal functional gradient pattern from unimodal sensory/motor networks to transmodal association networks. We observed that this principal functional gradient is heritable, and the strength of heritability exhibits a heterogeneous pattern along a hierarchical unimodal-transmodal axis in subcortex for both young adults and children. Furthermore, employing a machine learning framework, we show that this heterogeneous pattern of the principal functional gradient in subcortex can accurately discern the relationship between monozygotic twin pairs and dizygotic twin pairs with an accuracy of 76.2% (P < 0.001). The heritability of functional gradients is associated with the anatomical myelin proxied by MRI-derived T1-weighted/T2-weighted (T1w/T2w) ratio mapping in subcortex. This study provides new insights into the biological basis of subcortical functional hierarchy by revealing the structural and genetic properties of the subcortical functional gradients.


Subject(s)
Connectome , Magnetic Resonance Imaging , Humans , Male , Female , Adolescent , Child , Young Adult , Adult , Twins, Monozygotic/genetics , Twins, Dizygotic/genetics , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiology , Nerve Net/physiology , Nerve Net/diagnostic imaging
6.
J Agric Food Chem ; 72(27): 15334-15344, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38916549

ABSTRACT

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.


Subject(s)
Aquaporin 1 , Intestinal Mucosa , Animals , Aquaporin 1/genetics , Aquaporin 1/metabolism , Mice , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Mice, Inbred C57BL , Inflammation/metabolism , Inflammation/genetics , Inflammation/chemically induced , Male , Epithelial Cells/drug effects , Epithelial Cells/metabolism , NF-kappa B/metabolism , NF-kappa B/genetics , Diethylhexyl Phthalate/toxicity , Phthalic Acids , Signal Transduction/drug effects
7.
Discov Med ; 36(185): 1268-1279, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38926113

ABSTRACT

BACKGROUND: Tuberculosis (TB) stands as the second most prevalent infectious agent-related cause of death worldwide in 2022, trailing only COVID-19. With 1.13 million reported deaths, this figure is more than half of the mortality associated with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), which accounted for 0.63 million deaths. Diagnosing Mycobacterium tuberculosis (MTB) infection remains a formidable challenge due to the inability to isolate and detect MTB in sputum and within the human body. The absence of universally reliable diagnostic criteria for MTB infection globally poses a significant obstacle to preventing the progression of tuberculosis from the MTB infection stage. METHODS: In this study, our objective was to formulate a diagnostic biomarker cluster capable of discerning the progression of MTB infection and disease. This was achieved through a comprehensive joint multiomics analysis, encompassing transcriptome, proteome, and metabolome, conducted on lung tissue samples obtained from both normal control mice and those infected with MTB. RESULTS: A total of 1690 differentially expressed genes and 94 differentially expressed proteins were systematically screened. From this pool, 10 core genes were singled out. Additionally, eight long non-coding ribonucleic acids and eight metabolites linked to these core genes were identified to establish a cohesive cluster of biomarkers. This multiomics-based biomarker cluster demonstrated its capability to differentiate uninfected samples from MTB-infected samples effectively in both principle component analysis and the construction of a random forest model. CONCLUSION: The outcomes of our study strongly suggest that the multiomics-based biomarker cluster holds significant potential for enhancing the diagnosis of MTB infection.


Subject(s)
Biomarkers , Disease Models, Animal , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Animals , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/metabolism , Mice , Biomarkers/metabolism , Mycobacterium tuberculosis/genetics , Transcriptome , Humans , Lung/microbiology , Lung/pathology , Lung/metabolism , Female , Metabolome , Proteomics/methods , Proteome/metabolism , Multiomics
8.
Biology (Basel) ; 13(6)2024 May 30.
Article in English | MEDLINE | ID: mdl-38927275

ABSTRACT

In this study, juvenile crayfish hatched from the same population were cultured in different growing environments: pond (D1), paddy field (D2), and aquaculture barrel (D3), and fed for 60 days. Crayfishes were selected randomly, females and males, 50 tails each from six groups (D1-♀, D1-♂, D2-♀, D2-♂, D3-♀, D3-♂) to measure the following morphological traits: full length (X1), body length (X2), chelicerae length (X3), chelicerae weight (X4), cephalothorax length (X5), cephalothorax width (X6), cephalothorax height (X7), eye spacing (X8), caudal peduncle length (X9), and caudal peduncle weight (X10). We found that the coefficient of variation (CV) of X4 was the largest in each culture mode, and males (28.58%~38.67%) were larger than females (37.76%~66.74%). The CV of X4 of crayfish cultured in D1 and D2 was larger than that of D3. All traits except X8 were positively correlated with body weight (p < 0.05). After pathway analysis, we found that X4, X5, X7, and X10 were significantly correlated with the body weight of D1-♀; the equation was YD1-♀ = -29.803 + 1.249X4 + 0.505X5 + 0.701X7 + 1.483X10 (R2 = 0.947). However, X2, X4, and X6 were significantly correlated with the body weight of D1-♂; the equation was YD1-♂ = -40.881 + 0.39X2 + 0.845X4 + 1.142X6 (R2 = 0.927). In D2-♀, X1, X4, X5, and X10 were significantly correlated with body weight; the equation was YD2-♀ = -12.248 + 0.088X1 + 1.098X4 + 0.275X5 + 0.904X10 (R2 = 0.977). X4 and X5 played a major role in the body weight of D2-♂ with the equation: YD2-♂ = -24.871 + 1.177X4 + 0.902X5 (R2 = 0.973). X3 and X10 mainly contributed to the body weight of D3-♀ with the equation: YD3-♀ = -22.476 + 0.432X3 + 3.153X10 (R2 = 0.976). X1 and X4 mainly contributed to the body weight of D3-♂ with the equation: YD3-♂ = -34.434 + 0.363X1 + 0.669X4 (R2 = 0.918). Comparing the pathway analysis with the gray relation analysis, we could conclude that the traits most correlated with body weight in D1-♀ were X10 and X7; in D1-♂, X6; in D2-♀, X10, X1, and X5; in D2-♂, X5; in D3-♀, X10; and in D3-♂, X4 and X1.

9.
Molecules ; 29(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38893547

ABSTRACT

Hemorrhoid disease is a common anorectal disorder affecting populations worldwide, with high prevalence, treatment difficulties, and considerable treatment costs. Compared to other treatment options, medical therapy for hemorrhoids offers minimal harm, more dignity to patients, and is more economical. Unfortunately, there are few chemical hemorrhoid medications available clinically, which makes the search for efficacious, cost-effective, and environmentally friendly new medication classes a focal point of research. In this context, searching for available natural products to improve hemorrhoids exhibits tremendous potential. These products are derived from nature, predominantly from plants, with a minor portion coming from animals, fungi, and algae. They have excellent coagulation pathway regulation, anti-inflammatory, antibacterial, and tissue regeneration activities. Therefore, we take the view that they are a class of potential hemorrhoid drugs, prevention products, and medication add-on ingredients. This article first reviews the factors contributing to the development of hemorrhoids, types, primary symptoms, and the mechanisms of natural products for hemorrhoids. Building on this foundation, we screened natural products with potential hemorrhoid improvement activity, including polyphenols and flavonoids, terpenes, polysaccharides, and other types.


Subject(s)
Biological Products , Hemorrhoids , Hemorrhoids/drug therapy , Humans , Biological Products/therapeutic use , Biological Products/pharmacology , Biological Products/chemistry , Animals , Polyphenols/therapeutic use , Polyphenols/chemistry , Polyphenols/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
10.
Sensors (Basel) ; 24(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38894269

ABSTRACT

Train wheels are crucial components for ensuring the safety of trains. The accurate and fast identification of wheel tread defects is necessary for the timely maintenance of wheels, which is essential for achieving the premise of conditional repair. Image-based detection methods are commonly used for detecting tread defects, but they still have issues with the misdetection of water stains and the leaking of small defects. In this paper, we address the challenges posed by the detection of wheel tread defects by proposing improvements to the YOLOv8 model. Firstly, the impact of water stains on tread defect detection is avoided by optimising the structure of the detection layer. Secondly, an improved SPPCSPC module is introduced to enhance the detection of small targets. Finally, the SIoU loss function is used to accelerate the convergence speed of the network, which ensures defect recognition accuracy with high operational efficiency. Validation was performed on the constructed tread defect dataset. The results demonstrate that the enhanced YOLOv8 model in this paper outperforms the original network and significantly improves the tread defect detection indexes. The average precision, accuracy, and recall reached 96.95%, 96.30%, and 95.31%.

11.
Nat Prod Res ; : 1-7, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913076

ABSTRACT

Two new limonoid glycosides, named limonosides A (1) and B (2), along with four known limonoids (3-6) were obtained from the seeds of Citrus limon. Their structures were deduced based on extensive spectroscopic analysis. Limonoside A (1) and nomilin (4) were found to possess moderate phosphodiesterase type 4D (PDE4D) inhibitory effect with values of 89.8 ± 2.4% and 98.9 ± 3.0% at 10 µM, respectively.

12.
BMC Plant Biol ; 24(1): 542, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872107

ABSTRACT

BACKGROUND: Hydrogen gas (H2), a novel and beneficial gaseous molecule, plays a significant role in plant growth and development processes. Hydrogen-rich water (HRW) is regarded as a safe and easily available way to study the physiological effects of H2 on plants. Several recent research has shown that HRW attenuates stress-induced seed germination inhibition; however, the underlying modes of HRW on seed germination remain obscure under non-stress condition. RESULTS: In this current study, we investigated the possible roles of gibberellin (GA) and abscisic acid (ABA) in HRW-regulated seed germination in wax gourd (Benincasa hispida) through pharmacological, physiological, and transcriptome approaches. The results showed that HRW application at an optimal dose (50% HRW) significantly promoted seed germination and shortened the average germination time (AGT). Subsequent results suggested that 50% HRW treatment stimulated GA production by regulating GA biosynthesis genes (BhiGA3ox, BhiGA2ox, and BhiKAO), whereas it had no effect on the content of ABA and the expression of its biosynthesis (BhiNCED6) and catabolism genes (BhiCYP707A2) but decreased the expression of ABA receptor gene (BhiPYL). In addition, inhibition of GA production by paclobutrazol (PAC) could block the HRW-mediated germination. Treatment with ABA could hinder HRW-mediated seed germination and the ABA biosynthesis inhibitor sodium tungstate (ST) could recover the function of HRW. Furthermore, RNA-seq analysis revealed that, in the presence of GA or ABA, an abundance of genes involved in GA, ABA, and ethylene signal sensing and transduction might involve in HRW-regulated germination. CONCLUSIONS: This study portrays insights into the mechanism of HRW-mediated seed germination, suggesting that HRW can regulate the balance between GA and ABA to mediate seed germination through ethylene signals in wax gourd.


Subject(s)
Abscisic Acid , Germination , Gibberellins , Hydrogen , Plant Growth Regulators , Seeds , Signal Transduction , Gibberellins/metabolism , Germination/drug effects , Abscisic Acid/metabolism , Seeds/growth & development , Seeds/drug effects , Seeds/genetics , Seeds/physiology , Plant Growth Regulators/metabolism , Hydrogen/metabolism , Gene Expression Regulation, Plant/drug effects
13.
Research (Wash D C) ; 7: 0378, 2024.
Article in English | MEDLINE | ID: mdl-38766643

ABSTRACT

The accumulation of senescent cells in kidneys is considered to contribute to age-related diseases and organismal aging. Mitochondria are considered a regulator of cell senescence process. Atrazine as a triazine herbicide poses a threat to renal health by disrupting mitochondrial homeostasis. Melatonin plays a critical role in maintaining mitochondrial homeostasis. The present study aims to explore the mechanism by which melatonin alleviates atrazine-induced renal injury and whether parkin-mediated mitophagy contributes to mitigating cell senescence. The study found that the level of parkin was decreased after atrazine exposure and negatively correlated with senescent markers. Melatonin treatment increased serum melatonin levels and mitigates atrazine-induced renal tubular epithelial cell senescence. Mechanistically, melatonin maintains the integrity of mitochondrial crista structure by increasing the levels of mitochondrial contact site and cristae organizing system, mitochondrial transcription factor A (TFAM), adenosine triphosphatase family AAA domain-containing protein 3A (ATAD3A), and sorting and assembly machinery 50 (Sam50) to prevent mitochondrial DNA release and subsequent activation of cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase pathway. Furthermore, melatonin activates Sirtuin 3-superoxide dismutase 2 axis to eliminate the accumulation of reactive oxygen species in the kidney. More importantly, the antisenescence role of melatonin is largely determined by the activation of parkin-dependent mitophagy. These results offer novel insights into measures against cell senescence. Parkin-mediated mitophagy is a promising drug target for alleviating renal tubular epithelial cell senescence.

14.
Sci Rep ; 14(1): 10220, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702424

ABSTRACT

The purpose of the study was to determine whether changes in body mass index (BMI) and waist circumference (WC) in middle-aged and elderly Chinese are associated with metabolic syndrome. In this cohort investigation, 3697 middle-aged and elderly people aged 45 or over were recruited from the China Health and Retirement Longitudinal Study (CHARLS). The National Cholesterol Education Program Adult Treatment Panel III (2005) defined metabolic syndrome (MetS). With Cox regression analysis, we calculated hazard ratio (HR) and 95% confidence intervals (CIs) for MetS based on BMI-WC change categories. To assess the prevalence of MetS, the changes in BMI and WC levels were classified into four quartiles based on their relative and absolute changes. In subjects whose BMI and WC decreased (HR = 0.338; 95% CIs 0.264, 0.433) as well as those whose BMI increased and their WC decreased (HR = 0.375; 95% CIs 0.228, 0.499), metabolic syndrome risk was significantly lower compared with those with increases in both BMI and WC. Regarding the absolute changes in BMI, the lowest percentile of BMI was significantly lower in both males (HR = 0.302; 95% CIs 0.204, 0.448) and females (HR = 0.486; 95% CIs 0.354, 0.667) for the risk of metabolic syndrome. Similar results were observed in the absolute changes in WC, with the lowest quantile of WC having a significant impact on MetS risk in males (HR = 0.170; 95% CIs 0.107, 0.270) and females (HR = 0.303; 95% CIs 0.217, 0.424). The risk of metabolic syndrome was significantly associated with changes in BMI and WC in middle-aged and elderly Chinese. A reduced BMI and WC are associated with lower metabolic syndrome risks in middle-aged and elderly people.


Subject(s)
Body Mass Index , Metabolic Syndrome , Waist Circumference , Humans , Metabolic Syndrome/epidemiology , Male , Female , Middle Aged , Aged , China/epidemiology , Longitudinal Studies , Risk Factors , Prevalence , Asian People , East Asian People
15.
J Agric Food Chem ; 72(26): 14956-14966, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38820047

ABSTRACT

Atrazine (ATR) is a widely used herbicide worldwide that can cause kidney damage in humans and animals by accumulation in water and soil. Lycopene (LYC), a carotenoid with numerous biological activities, plays an important role in kidney protection due to its potent antioxidant and anti-inflammatory effects. The current study sought to investigate the role of interactions between mtDNA and the cGAS-STING signaling pathway in LYC mitigating PANoptosis and inflammation in kidneys induced by ATR exposure. In our research, 350 mice were orally administered LYC (5 mg/kg BW/day) and ATR (50 or 200 mg/kg BW/day) for 21 days. Our results reveal that ATR exposure induces a decrease in mtDNA stability, resulting in the release of mtDNA into the cytoplasm through the mPTP pore and the BAX pore and the mobilization of the cGAS-STING pathway, thereby inducing renal PANoptosis and inflammation. LYC can inhibit the above changes caused by ATR. In conclusion, LYC inhibited ATR exposure-induced histopathological changes, renal PANoptosis, and inflammation by inhibiting the cGAS-STING pathway. Our results demonstrate the positive role of LYC in ATR-induced renal injury and provide a new therapeutic target for treating renal diseases in the clinic.


Subject(s)
Atrazine , DNA, Mitochondrial , Kidney , Lycopene , Membrane Proteins , Protective Agents , Animals , Mice , Atrazine/toxicity , Kidney/drug effects , Kidney/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Lycopene/pharmacology , Lycopene/administration & dosage , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Male , Protective Agents/pharmacology , Protective Agents/administration & dosage , Humans , Herbicides , Kidney Diseases/metabolism , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Kidney Diseases/genetics , Kidney Diseases/drug therapy , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism , Signal Transduction/drug effects
16.
Plant Commun ; 5(7): 100975, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38751121

ABSTRACT

Yield prediction is the primary goal of genomic selection (GS)-assisted crop breeding. Because yield is a complex quantitative trait, making predictions from genotypic data is challenging. Transfer learning can produce an effective model for a target task by leveraging knowledge from a different, but related, source domain and is considered a great potential method for improving yield prediction by integrating multi-trait data. However, it has not previously been applied to genotype-to-phenotype prediction owing to the lack of an efficient implementation framework. We therefore developed TrG2P, a transfer-learning-based framework. TrG2P first employs convolutional neural networks (CNN) to train models using non-yield-trait phenotypic and genotypic data, thus obtaining pre-trained models. Subsequently, the convolutional layer parameters from these pre-trained models are transferred to the yield prediction task, and the fully connected layers are retrained, thus obtaining fine-tuned models. Finally, the convolutional layer and the first fully connected layer of the fine-tuned models are fused, and the last fully connected layer is trained to enhance prediction performance. We applied TrG2P to five sets of genotypic and phenotypic data from maize (Zea mays), rice (Oryza sativa), and wheat (Triticum aestivum) and compared its model precision to that of seven other popular GS tools: ridge regression best linear unbiased prediction (rrBLUP), random forest, support vector regression, light gradient boosting machine (LightGBM), CNN, DeepGS, and deep neural network for genomic prediction (DNNGP). TrG2P improved the accuracy of yield prediction by 39.9%, 6.8%, and 1.8% in rice, maize, and wheat, respectively, compared with predictions generated by the best-performing comparison model. Our work therefore demonstrates that transfer learning is an effective strategy for improving yield prediction by integrating information from non-yield-trait data. We attribute its enhanced prediction accuracy to the valuable information available from traits associated with yield and to training dataset augmentation. The Python implementation of TrG2P is available at https://github.com/lijinlong1991/TrG2P. The web-based tool is available at http://trg2p.ebreed.cn:81.


Subject(s)
Crops, Agricultural , Neural Networks, Computer , Oryza , Zea mays , Crops, Agricultural/genetics , Crops, Agricultural/growth & development , Oryza/genetics , Oryza/growth & development , Zea mays/genetics , Zea mays/growth & development , Triticum/genetics , Triticum/growth & development , Phenotype , Plant Breeding/methods , Genotype , Machine Learning
17.
Microorganisms ; 12(5)2024 May 03.
Article in English | MEDLINE | ID: mdl-38792763

ABSTRACT

Pyridoxine, also known as vitamin B6, is an essential cofactor in numerous cellular processes. Its importance in various applications has led to a growing interest in optimizing its production through microbial biosynthesis. However, an imbalance in the net production of NADH disrupts intracellular cofactor levels, thereby limiting the efficient synthesis of pyridoxine. In our study, we focused on multiple cofactor engineering strategies, including the enzyme design involved in NAD+-dependent enzymes and NAD+ regeneration through the introduction of heterologous NADH oxidase (Nox) coupled with the reduction in NADH production during glycolysis. Finally, the engineered E. coli achieved a pyridoxine titer of 676 mg/L in a shake flask within 48 h by enhancing the driving force. Overall, the multiple cofactor engineering strategies utilized in this study serve as a reference for enhancing the efficient biosynthesis of other target products.

18.
Sci Rep ; 14(1): 10901, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38740846

ABSTRACT

To investigate the screening and predicting functions of obesity- and lipid-related indices for type 2 diabetes (T2D) in middle-aged and elderly Chinese, as well as the ideal predicted cut-off value. This study's data comes from the 2011 China Health and Retirement Longitudinal Study (CHARLS). A cross-sectional study design was used to investigate the relationship of T2D and 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride- glucose index (TyG index) and its correlation index (TyG-BMI, TyG-WC, TyG-WHtR). The unadjusted and adjusted correlations between 13 indices and T2D were assessed using binary logistic regression analysis. The receiver operating characteristic curve (ROC) was used to determine the usefulness of anthropometric indices for screening for T2D and determining their cut­off value, sensitivity, specificity, and area under the curve (AUC). The study comprised 9488 people aged 45 years or above in total, of whom 4354 (45.89%) were males and 5134 (54.11%) were females. Among them were 716 male cases of T2D (16.44%) and 870 female cases of T2D (16.95%). A total of 13 obesity- and lipid-related indices were independently associated with T2D risk after adjusted for confounding factors (P < 0.05). According to ROC analysis, the TyG index was the best predictor of T2D among males (AUC = 0.780, 95% CI 0.761, 0.799) and females (AUC = 0.782, 95% CI 0.764, 0.799). The AUC values of the 13 indicators were higher than 0.5, indicating that they have predictive values for T2D in middle-aged and elderly Chinese. The 13 obesity- and lipid-related indices can predict the risk of T2D in middle­aged and elderly Chinese. Among 13 indicators, the TyG index is the best predictor of T2D in both males and females. TyG-WC, TyG-BMI, TyG-WHtR, LAP, and CVAI all outperformed BMI, WC, and WHtR in predicting T2D.


Subject(s)
Body Mass Index , Diabetes Mellitus, Type 2 , Obesity , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Male , Female , Middle Aged , Aged , Obesity/blood , Obesity/diagnosis , China/epidemiology , Cross-Sectional Studies , Waist Circumference , ROC Curve , Lipids/blood , Longitudinal Studies , Risk Factors , East Asian People
19.
BMC Psychiatry ; 24(1): 351, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730360

ABSTRACT

BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.


Subject(s)
Depression , Obesity , Humans , Male , Female , Middle Aged , China/epidemiology , Obesity/epidemiology , Depression/epidemiology , Depression/blood , Aged , Longitudinal Studies , Risk Factors , Body Mass Index , Lipids/blood , Waist Circumference , East Asian People
20.
Sci Total Environ ; 935: 173249, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38754502

ABSTRACT

Selenium (Se), a highly beneficial animal feed additive, exhibits remarkable antioxidant and anti-inflammatory properties. Nano­selenium (Nano-Se) is an advanced formulation of Se featuring a specialized drug delivery vehicle, with good bioavailability, higher efficacy, and lower toxicity compared to the traditional form of Se. With the advancement of industry, cadmium (Cd) contamination occurs in different countries and regions and thereby contaminating different food crops, and the degree of pollution is degree increasing year by year. The present investigation entailed the oral administration of CdCl2 and/or Nano-Se to male chickens of the Hy-Line Variety White breed, which are one day old, subsequent to a 7-day adaptive feeding period, for a duration of 90 days. The study aimed to elucidate the potential protective impact of Nano-Se on Cd exposure. The study found that Nano-Se demonstrates potential in mitigating the blood-brain barrier (BBB) dysfunction characterized by impairment of adherens junctions (AJS) and tight junctions (TJS) by inhibiting reactive oxygen species (ROS) overproduction. In addition, the data uncovered that Nano-Se demonstrates a proficient ability in alleviating BBB impairment and inflammatory reactions caused by Cd through the modulation of the Wnt7A/ß-catenin pathway, highlights its potential to maintain brain homeostasis. Hence, this research anticipates that the utilization of Nano-Se effectively mitigate the detrimental impacts associated with Cd exposure on the BBB.


Subject(s)
Blood-Brain Barrier , Cadmium , Chickens , Selenium , Animals , Cadmium/toxicity , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Male , beta Catenin/metabolism , Wnt Signaling Pathway/drug effects
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