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1.
Nature ; 618(7967): 1017-1023, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37316672

ABSTRACT

The discovery and application of genome editing introduced a new era of plant breeding by giving researchers efficient tools for the precise engineering of crop genomes1. Here we demonstrate the power of genome editing for engineering broad-spectrum disease resistance in rice (Oryza sativa). We first isolated a lesion mimic mutant (LMM) from a mutagenized rice population. We then demonstrated that a 29-base-pair deletion in a gene we named RESISTANCE TO BLAST1 (RBL1) caused broad-spectrum disease resistance and showed that this mutation caused an approximately 20-fold reduction in yield. RBL1 encodes a cytidine diphosphate diacylglycerol synthase that is required for phospholipid biosynthesis2. Mutation of RBL1 results in reduced levels of phosphatidylinositol and its derivative phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). In rice, PtdIns(4,5)P2 is enriched in cellular structures that are specifically associated with effector secretion and fungal infection, suggesting that it has a role as a disease-susceptibility factor3. By using targeted genome editing, we obtained an allele of RBL1, named RBL1Δ12, which confers broad-spectrum disease resistance but does not decrease yield in a model rice variety, as assessed in small-scale field trials. Our study has demonstrated the benefits of editing an LMM gene, a strategy relevant to diverse LMM genes and crops.


Subject(s)
Diacylglycerol Cholinephosphotransferase , Disease Resistance , Gene Editing , Oryza , Plant Breeding , Plant Diseases , Disease Resistance/genetics , Gene Editing/methods , Genome, Plant/genetics , Oryza/enzymology , Oryza/genetics , Oryza/microbiology , Phosphatidylinositols/metabolism , Plant Breeding/methods , Plant Diseases/genetics , Plant Diseases/microbiology , Alleles , Phosphatidylinositol 4,5-Diphosphate/metabolism , Diacylglycerol Cholinephosphotransferase/genetics , Diacylglycerol Cholinephosphotransferase/metabolism
2.
Hepatology ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39250438

ABSTRACT

BACKGROUND AIMS: Partial hepatectomy (PHx)-induced liver regeneration causes the increase in relative blood flow rate within the liver, which dilates hepatic sinusoids and applies mechanical stretch on liver sinusoidal endothelial cells (LSECs). Heparin-binding EGF-like growth factor (HB-EGF) is a crucial growth factor during liver regeneration. We aimed to investigate whether this sinusoidal dilation-induced stretch promotes HB-EGF secretion in LSECs and what the related molecular mechanism is. APPROACH RESULTS: In vivo PHx, ex vivo liver perfusion and in vitro LSEC mechanical stretch were applied to detect HB-EGF expression in LSECs and hepatocyte proliferation. Knockdown or inhibition of mechanosensitive proteins were used to unravel the molecular mechanism in response to stretch. This stretch triggers amplitude- and duration-dependent HB-EGF up-regulation in LSECs, which is mediated by Yes-associated protein (YAP) nuclear translocation and binding to TEAD. This YAP translocation is achieved in two ways: On one hand, F-actin polymerization-mediated expansion of nuclear pores promotes YAP entry into nucleus passively. On the other hand, F-actin polymerization up-regulates the expression of BAG family molecular chaperone regulator 3 (BAG-3), which binds with YAP to enter nucleus cooperatively. In this process, ß1-integrin serves as a target mechanosensory in stretch-induced signaling pathways. This HB-EGF secretion-promoted liver regeneration after 2/3 PHx is attenuated in endothelial cell-specific Yap1-deficient mice. CONCLUSIONS: Our findings indicate that mechanical stretch-induced HB-EGF up-regulation in LSECs via YAP translocation can promote the hepatocyte proliferation during liver regeneration through a mechanocrine manner, which deepens the understanding of the mechanical-biological coupling in liver regeneration.

3.
Mol Cell Proteomics ; 22(8): 100616, 2023 08.
Article in English | MEDLINE | ID: mdl-37442371

ABSTRACT

Lysine ß-hydroxybutyrylation (Kbhb) is an evolutionarily conserved and widespread post-translational modification that is associated with active gene transcription and cellular proliferation. However, its role in phytopathogenic fungi remains unknown. Here, we characterized Kbhb in the rice false smut fungus Ustilaginoidea virens. We identified 2204 Kbhb sites in 852 proteins, which are involved in diverse biological processes. The mitogen-activated protein kinase UvSlt2 is a Kbhb protein, and a strain harboring a point mutation at K72, the Kbhb site of this protein, had decreased UvSlt2 activity and reduced fungal virulence. Molecular dynamic simulations revealed that K72bhb increases the hydrophobic solvent-accessible surface area of UvSlt2, thereby affecting its binding to its substrates. The mutation of K298bhb in the septin UvCdc10 resulted in reduced virulence and altered the subcellular localization of this protein. Moreover, we confirmed that the NAD+-dependent histone deacetylases UvSirt2 and UvSirt5 are the major enzymes that remove Kbhb in U. virens. Collectively, our findings identify regulatory elements of the Kbhb pathway and reveal important roles for Kbhb in regulating protein localization and enzymatic activity. These findings provide insight into the regulation of virulence in phytopathogenic fungi via post-translational modifications.


Subject(s)
Hypocreales , Oryza , Virulence , Hypocreales/genetics , Protein Processing, Post-Translational , Mutation , Plant Diseases/microbiology
4.
J Biol Chem ; 299(12): 105476, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37981207

ABSTRACT

Circadian rhythm disruption leads to dysregulation of lipid metabolism, which further drive the occurrence of insulin resistance (IR). Exosomes are natural carrier systems that advantageous for cell communication. In the present study, we aimed to explore whether and how the exosomal microRNAs (miRNAs) in circulation participate in modulating skeletal muscle IR induced by circadian rhythm disruption. In the present study, 24-h constant light (12-h light/12-h light, LL) was used to establish the mouse model of circadian rhythm disruption. Bmal1 interference was used to establish the cell model of circadian rhythm disruption. And in clinical experiments, we chose a relatively large group of rhythm disturbance-shift nurses. We showed that LL-induced circadian rhythm disruption led to increased body weight and visceral fat volume, as well as occurrence of IR in vivo. Furthermore, exosomal miR-22-3p derived from adipocytes in the context of circadian rhythm disruption induced by Bmal1 interference could be uptaken by skeletal muscle cells to promote IR occurrence in vitro. Moreover, miR-22-3p in circulation was positively correlated with the clinical IR-associated factors. Collectively, these data showed that exosomal miR-22-3p in circulation may act as potential biomarker and therapeutic target for skeletal muscle IR, contributing to the prevention of diabetes in the context of rhythm disturbance.


Subject(s)
Circadian Rhythm , Exosomes , Insulin Resistance , MicroRNAs , Animals , Mice , Adipocytes/metabolism , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Exosomes/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle, Skeletal/metabolism
5.
J Am Chem Soc ; 146(36): 25101-25107, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39196903

ABSTRACT

Tailoring the surface ligands of metal nanoclusters is important for engineering unique configurations of metal nanoclusters. Thiacalix[4]arene has found extensive applications in the construction of metal nanoclusters. In this investigation, we present the synthesis and characterization of the first all-calixarene-protected silver nanoclusters, [Ag(CH3CN)4]2[Ag44(BTCA)6] (Ag44, H4BTCA = p-tert-butylthiacalix[4]arene). Single-crystal X-ray structural analysis reveals that all silver atoms are in a face-centered cubic (fcc) arrangement. The formation of such an fcc structure is attributed to the selectively passivation on {100} facets by BTCA4-. Thiacalixarene substantially facilitates the stability of Ag44 due to its multiple coordination sites and bulkiness. Mass spectrometry and theoretical calculations reveal that Ag44 is a superatomic silver nanocluster with 22 free electrons in the following configuration: 1S21P61D61F22S21D4. This work not only elucidates the impact of macrocyclic ligands on the stabilization of silver clusters but also furnishes an approach for assembling atomically precise fcc nanoclusters.

6.
J Am Chem Soc ; 146(25): 17508-17516, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38861394

ABSTRACT

The electron-rich characteristic and low work function endow electrides with excellent performance in (opto)electronics and catalytic applications; these two features are closely related to the structural topology, constituents, and valence electron concentration of electrides. However, the synthesized electrides, especially two-dimensional (2D) electrides, are limited to specific structural prototypes and anionic p-block elements. Here we synthesize and identify a distinct 2D electride of BaCu with delocalized anionic electrons confined to the interlayer spaces of the BaCu framework. The bonding between Cu and Ba atoms exhibits ionic characteristics, and the adjacent Cu anions form a planar honeycomb structure with metallic Cu-Cu bonding. The negatively charged Cu ions are revealed by the theoretical calculations and experimental X-ray absorption near-edge structure. Physical property measurements reveal that BaCu electride has a high electronic conductivity (ρ = 3.20 µΩ cm) and a low work function (2.5 eV), attributed to the metallic Cu-Cu bonding and delocalized anionic electrons. In contrast to typical ionic 2D electrides with p-block anions, density functional theory calculations find that the orbital hybridization between the delocalized anionic electrons and BaCu framework leads to unique isotropic physical properties, such as mechanical properties, and work function. The freestanding BaCu monolayer with half-metal conductivity exhibits low exfoliation energy (0.84 J/m2) and high mechanical/thermal stability, suggesting the potential to achieve low-dimensional BaCu from the bulk. Our results expand the space for the structure and attributes of 2D electrides, facilitating the discovery and potential application of novel 2D electrides with transition metal anions.

7.
Clin Immunol ; 261: 109925, 2024 04.
Article in English | MEDLINE | ID: mdl-38310993

ABSTRACT

BACKGROUND: Inflammatory factors are being recognized as critical modulators of host antitumor immunity in liver cancer. We have previously shown that tumor cell-released LC3B positive extracellular vesicles (LC3B+ EVs) are responsible for malignant progression by dampening antitumor immunity. However, the relationship between LC3B+ EVs and inflammatory factors in the regulation of the liver cancer microenvironment remains unclear. METHODS: Flow cytometry analyses were performed to examine the panel of 12 cytokines, the main source of positive cytokines, and plasma LC3B+ EVs carrying HSP90α in peripheral blood of liver cancer patients. We correlated the levels of plasma IL-6, IL-8 with LC3B+ EVs carrying HSP90α and with prognosis. In vitro culture of healthy donor leukocytes with liver cancer-derived LC3B+ EVs was performed to evaluate the potential effect of blocking HSP90α, IL-6 or IL-8 alone or in combination with PD-1 inhibitor on CD8+ T cell function. We also investigated the potential associations of MAP1LC3B, HSP90AA1, IL6 or IL8 with immunotherapy efficacy using the TCGA databases. RESULTS: In liver cancer patients, plasma IL-6 and IL-8 levels were significantly higher than in healthy controls and associated with poor clinical outcome. In peripheral blood, levels of plasma LC3B+ EVs carrying HSP90α were significantly elevated in HCC patients and positively associated with IL-6 and IL-8 levels, which are predominantly secreted by monocytes and neutrophils. Moreover, LC3B+ EVs from human liver cancer cells promoted the secretion of IL-6 and IL-8 by leukocytes through HSP90α. Besides, we show that the cytokines IL-6 and IL-8 secreted by LC3B+ EVs-induced leukocytes were involved in the inhibition of CD8+ T-cell function, while blockade of the HSP90α on the LC3B+ EVs, IL-6, or IL-8 could enhance anti-PD-1-induced T cell reinvigoration. Finally, patients who received anti-PD-1/PD-L1 immunotherapy with high MAP1LC3B, HSP90AA1, IL6, or IL8 expression had a lower immunotherapy efficacy. CONCLUSIONS: Our data suggest that liver cancer-derived LC3B+ EVs promote a pro-oncogenic inflammatory microenvironment by carrying membrane-bound HSP90α. Targeting HSP90α on the LC3B+ EVs, IL-6, or IL-8 may synergize with anti-PD-1 treatment to enhance the CD8+ T-cell functions, which may provide novel combination strategies in the clinic for the treatment of liver cancer.


Subject(s)
Carcinoma, Hepatocellular , Extracellular Vesicles , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Interleukin-6/metabolism , Interleukin-8/metabolism , Liver Neoplasms/drug therapy , Tumor Microenvironment , Cytokines/metabolism , Immunotherapy , Extracellular Vesicles/metabolism , Extracellular Vesicles/pathology
8.
Plant Biotechnol J ; 22(1): 148-164, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37715970

ABSTRACT

Rice false smut caused by Ustilaginoidea virens is a devastating rice (Oryza sativa) disease worldwide. However, the molecular mechanisms underlying U. virens-rice interactions are largely unknown. In this study, we identified a secreted protein, Uv1809, as a key virulence factor. Heterologous expression of Uv1809 in rice enhanced susceptibility to rice false smut and bacterial blight. Host-induced gene silencing of Uv1809 in rice enhanced resistance to U. virens, suggesting that Uv1809 inhibits rice immunity and promotes infection by U. virens. Uv1809 suppresses rice immunity by targeting and enhancing rice histone deacetylase OsSRT2-mediated histone deacetylation, thereby reducing H4K5ac and H4K8ac levels and interfering with the transcriptional activation of defence genes. CRISPR-Cas9 edited ossrt2 mutants showed no adverse effects in terms of growth and yield but displayed broad-spectrum resistance to rice pathogens, revealing a potentially valuable genetic resource for breeding disease resistance. Our study provides insight into defence mechanisms against plant pathogens that inactivate plant immunity at the epigenetic level.


Subject(s)
Hypocreales , Oryza , Oryza/genetics , Oryza/microbiology , Histones , Plant Breeding , Hypocreales/genetics , Plant Diseases/microbiology
9.
New Phytol ; 242(3): 1257-1274, 2024 May.
Article in English | MEDLINE | ID: mdl-38481385

ABSTRACT

Plant pathogenic fungi elaborate numerous detoxification strategies to suppress host reactive oxygen species (ROS), but their coordination is not well-understood. Here, we show that Sirt5-mediated protein desuccinylation in Magnaporthe oryzae is central to host ROS detoxification. SIRT5 encodes a desuccinylase important for virulence via adaptation to host oxidative stress. Quantitative proteomics analysis identified a large number of succinylated proteins targeted by Sirt5, most of which were mitochondrial proteins involved in oxidative phosphorylation, TCA cycle, and fatty acid oxidation. Deletion of SIRT5 resulted in hypersuccinylation of detoxification-related enzymes, and significant reduction in NADPH : NADP+ and GSH : GSSG ratios, disrupting redox balance and impeding invasive growth. Sirt5 desuccinylated thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate their enzyme activity, likely by affecting proper folding. Altogether, this work demonstrates the importance of Sirt5-mediated desuccinylation in controlling fungal process required for detoxifying host ROS during M. oryzae infection.


Subject(s)
Ascomycota , Magnaporthe , Oryza , Reactive Oxygen Species/metabolism , Lysine/metabolism , Oxidative Stress , Ascomycota/metabolism , Fungal Proteins/metabolism , Oryza/metabolism , Plant Diseases/microbiology
10.
Plant Cell Environ ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946254

ABSTRACT

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

11.
Cytokine ; 177: 156555, 2024 05.
Article in English | MEDLINE | ID: mdl-38387232

ABSTRACT

Interferon-alpha (IFN-α) is widely used in the clinical treatment of patients with chronic hepatitis B and hepatocellular carcinoma (HCC). However, high levels of CXCL8 are associated with resistance to IFN-α therapy and poorer prognosis in advanced cancers. In this study, we investigated whether IFN-α could directly induce the production of CXCL8 in HCC cells and whether CXCL8 could antagonize the antitumor activity of IFN-α. We found that IFN-α not only upregulated the expression of the inducible genes CXCL9, CXCL10, CXCL11 and PD-L1, but also significantly stimulated CXCL8 secretion in HCC cells. Mechanically, IFN-α induces CXCL8 expression by activating the AKT and JNK pathways. In addition, our results demonstrate that IFN-α exposure significantly increases the differentiation of HCC stem cells, but this effect is reversed by the addition of the CXCL8 receptor CXCR1/2 inhibitor Reparixin and STAT3 inhibitor Stattic. Besides, our study reveals that the cytokine CXCL8 secreted by IFN-α-induced HCC cells inhibits T-cell function. Conversely, inhibition of CXCL8 promotes TNF-α and IFN-γ secretion by T cells. Finally, liver cancer patients who received anti-PD-1/PD-L1 immunotherapy with high CXCL8 expression had a lower immunotherapy efficacy. Overall, our findings clarify that IFN-α triggers immunosuppression and cancer stem cell differentiation in hepatocellular carcinoma by upregulating CXCL8 secretion. This discovery provides a novel approach to enhance the effectiveness of HCC treatment in the future.


Subject(s)
Carcinoma, Hepatocellular , Interferon-alpha , Interleukin-8 , Liver Neoplasms , Humans , B7-H1 Antigen/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Differentiation , Immunosuppression Therapy , Interferon-alpha/pharmacology , Interferon-gamma/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Interleukin-8/metabolism
12.
Vox Sang ; 119(6): 572-580, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38622920

ABSTRACT

BACKGROUND AND OBJECTIVES: National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. MATERIALS AND METHODS: This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. RESULTS: A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. CONCLUSION: Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.


Subject(s)
Erythrocyte Transfusion , Humans , China/epidemiology , Infant, Newborn , Male , Female , Intensive Care Units, Neonatal , Infant , Infant, Premature , Cohort Studies , Infant, Extremely Premature
13.
Cerebrovasc Dis ; 53(1): 88-97, 2024.
Article in English | MEDLINE | ID: mdl-36996763

ABSTRACT

INTRODUCTION: Intracranial branch atheromatous disease (BAD) has been applied to occlusions that occur at the origin of large caliber penetrating arteries due to the microatheromas or large parent artery plaques. This study aimed to explore the association between culprit plaques of large parent arteries, neuroimaging markers of cerebral small vessel disease (CSVD), and the risk of early neurological deterioration (END) in stroke patients with BAD. METHODS: A total of 97 stroke patients with BAD in the vascular territories of the lenticulostriate arteries or paramedian pontine arteries, diagnosed using high-resolution magnetic resonance imaging, were prospectively recruited in this observational study. A culprit plaque in the middle cerebral artery was defined as the only arterial plaque on the ipsilateral side of an infarction visible on diffusion-weighted imaging. A culprit plaque in the basilar artery (BA) was identified when it was observed within the same axial slices of an infarction or on the adjacent upper or lower slice, whereas a plaque within the BA located in the ventral region was considered non-culprit. If more than one plaque was present in the same vascular territory, the most stenotic plaque was chosen for the analysis. Four CSVD neuroimaging markers, including white matter hyperintensity, lacunes, microbleeds, and enlarged perivascular spaces, were evaluated in accordance with the total CSVD score. The associations between neuroimaging features of lesions within large parent arteries, neuroimaging markers of CSVD, and the risk of END in stroke patients with BAD were investigated using logistic regression analysis. RESULTS: END occurred in 41 stroke patients (42.27%) with BAD. The degree of large parent artery stenosis (p < 0.001), culprit plaques of large parent arteries (p < 0.001), and plaque burden (p < 0.001) were significantly different between the END and non-END groups in stroke patients with BAD. In logistic regression analysis, culprit plaques of large parent arteries (odds ratio, 32.258; 95% confidence interval, 4.140-251.346) were independently associated with the risk of END in stroke patients with BAD. CONCLUSIONS: Culprit plaques of large parent arteries could predict the risk of END in stroke patients with BAD. These results suggest that lesions in the large parent arteries, rather than damage to the cerebral small vessels, contribute to END in stroke patients with BAD.


Subject(s)
Cerebral Small Vessel Diseases , Plaque, Atherosclerotic , Stroke , Humans , Stroke/etiology , Stroke/complications , Plaque, Atherosclerotic/complications , Magnetic Resonance Imaging/methods , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/diagnostic imaging , Middle Cerebral Artery , Infarction
14.
BMC Pregnancy Childbirth ; 24(1): 7, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166840

ABSTRACT

BACKGROUND: Antepartum depression has been reported to be associated with the intensity of maternal prenatal noise exposure; however, the association between noise exposure duration and the development of antepartum depression has not been established. This study aimed to determine the total and trimester-specific association of prenatal noise exposure duration with the development of antepartum depression. METHODS: From May 2018 to June 2021, we recruited 2,166 pregnant women from Shengjing Hospital, northeast China. We used a standardized questionnaire to assess women's prenatal noise exposure and used the Edinburgh Postnatal Depression Scale to assess pregnant women's antepartum depression during the 1st -, 2nd -, and 3rd - trimesters. We calculated a cumulative noise exposure score ranging from 0 to 3, with a higher score reflecting higher frequency and longer duration of noise exposure during pregnancy. RESULTS: Women who were exposed to noise for ≥ 15 min per day had an increased risk of antepartum depression compared with women who were not exposed to noise during pregnancy [odds ratio (OR) = 1.83, 95%CI:1.18, 2.83]. Noise exposure in a specific trimester was associated with higher risk of depression in the same trimester and subsequent trimesters. We observed increases in antepartum depression risk with increasing cumulative noise exposure scores (P for trend < 0.05 for all). Pregnant women with the highest scores had the highest risk of antepartum depression during the first (OR = 1.30, 95%CI:1.02, 1.65), second (OR = 1.75, 95%CI:1.23, 2.50) trimesters. Women with a cumulative noise exposure score of 2 had the highest risk of antepartum depression during the third trimester (OR = 1.79, 95%CI:1.14, 2.80), as well as during the whole pregnancy (OR = 1.94, 95%CI:1.14, 3.30). CONCLUSIONS: Maternal prenatal noise exposure duration was positively associated with antepartum depression risk in a dose-response manner. It is necessary to develop strategies by which pregnant women can avoid excessive exposure to noise to prevent antepartum depression.


Subject(s)
Depression, Postpartum , Depression , Noise , Female , Humans , Pregnancy , Depression/etiology , Depression/complications , Depression, Postpartum/epidemiology , Depression, Postpartum/etiology , Maternal Exposure , Pregnancy Trimester, Third , Pregnancy Trimesters , Pregnant Women , Noise/adverse effects
15.
Lipids Health Dis ; 23(1): 180, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862993

ABSTRACT

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.


Subject(s)
Autophagy , Blood-Testis Barrier , Busulfan , Caprylates , Oxidative Stress , Sertoli Cells , Spermatogenesis , Male , Animals , Blood-Testis Barrier/drug effects , Blood-Testis Barrier/metabolism , Busulfan/adverse effects , Caprylates/pharmacology , Oxidative Stress/drug effects , Mice , Sertoli Cells/drug effects , Sertoli Cells/metabolism , Humans , Spermatogenesis/drug effects , Autophagy/drug effects , Infertility, Male/drug therapy , Infertility, Male/chemically induced , Infertility, Male/pathology , Testis/drug effects , Testis/pathology , Testis/metabolism , Spermatozoa/drug effects , Spermatozoa/metabolism , Adult
16.
Biochem Genet ; 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38261157

ABSTRACT

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.

17.
Mikrochim Acta ; 191(4): 216, 2024 03 22.
Article in English | MEDLINE | ID: mdl-38517549

ABSTRACT

A photoelectrochemical (PEC) sensor for the sensitive detection of thrombin (TB) was established. Co-sensitized combination of TiO2 nanoparticles combined with modified cadmium sulfide and cadmium telluride quantum dots (CdS/CdTe QDs) was utilized as a photoactive material. Successful growth of CdS/CdTe quantum dots on mesoporous TiO2 films occured by successive ion-layer adsorption and reaction. This interesting formation of co-sensitive structure is conducive to enhancing the photocurrent response by improving the use rate of light energy. Additionally, the step-level structure of CdS/CdTe QDs and TiO2 NPs shows a wide range of visible light absorption, facilitating the dissociation of excitons into free electrons and holes. Consequently, the photoelectric response of the PEC analysis platform is significantly enhanced. This constructed PEC aptasensor shows good detection of thrombin with a low detection limit (0.033 pM) and a wide linear range (0.0001-100 nM) in diluted actual human serum samples. In addition, this PEC aptasensor also has the characteristics of good stability and good reproducibility, which provides a novel insight for the quantitative measurement of other similar analytes.


Subject(s)
Cadmium Compounds , Nanoparticles , Quantum Dots , Humans , Quantum Dots/chemistry , Cadmium Compounds/chemistry , Tellurium/chemistry , Thrombin , Reproducibility of Results , Electrochemical Techniques , Nanoparticles/chemistry
18.
Sensors (Basel) ; 24(16)2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39205116

ABSTRACT

Corn, as one of the three major grain crops in China, plays a crucial role in ensuring national food security through its yield and quality. With the advancement of agricultural intelligence, agricultural robot technology has gained significant attention. High-precision navigation is the basis for realizing various operations of agricultural robots in corn fields and is closely related to the quality of operations. Corn leaf and stalk recognition and ranging are the prerequisites for achieving high-precision navigation and have attracted much attention. This paper proposes a corn leaf and stalk recognition and ranging algorithm based on multi-sensor fusion. First, YOLOv8 is used to identify corn leaves and stalks. Considering the large differences in leaf morphology and the large changes in field illumination that lead to discontinuous identification, an equidistant expansion polygon algorithm is proposed to post-process the leaves, thereby increasing the average recognition completeness of the leaves to 86.4%. Secondly, after eliminating redundant point clouds, the IMU data are used to calculate the confidence of the LiDAR and depth camera ranging point clouds, and point cloud fusion is performed based on this to achieve high-precision ranging of corn leaves. The average ranging error is 2.9 cm, which is lower than the measurement error of a single sensor. Finally, the stalk point cloud is processed and clustered using the FILL-DBSCAN algorithm to identify and measure the distance of the same corn stalk. The algorithm combines recognition accuracy and ranging accuracy to meet the needs of robot navigation or phenotypic measurement in corn fields, ensuring the stable and efficient operation of the robot in the corn field.


Subject(s)
Algorithms , Plant Leaves , Zea mays , Zea mays/anatomy & histology , Plant Leaves/anatomy & histology , Robotics , Agriculture/methods , Crops, Agricultural , China
19.
Sensors (Basel) ; 24(5)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38475094

ABSTRACT

The identification and classification of traditional Chinese herbal medicines demand significant time and expertise. We propose the dual-teacher supervised decay (DTSD) approach, an enhancement for Chinese herbal medicine recognition utilizing a refined knowledge distillation model. The DTSD method refines output soft labels, adapts attenuation parameters, and employs a dynamic combination loss in the teacher model. Implemented on the lightweight MobileNet_v3 network, the methodology is deployed successfully in a mobile application. Experimental results reveal that incorporating the exponential warmup learning rate reduction strategy during training optimizes the knowledge distillation model, achieving an average classification accuracy of 98.60% for 10 types of Chinese herbal medicine images. The model boasts an average detection time of 0.0172 s per image, with a compressed size of 10 MB. Comparative experiments demonstrate the superior performance of our refined model over DenseNet121, ResNet50_vd, Xception65, and EfficientNetB1. This refined model not only introduces an approach to Chinese herbal medicine image recognition but also provides a practical solution for lightweight models in mobile applications.


Subject(s)
Drugs, Chinese Herbal , Mobile Applications , Knowledge , Learning , Recognition, Psychology
20.
Sensors (Basel) ; 24(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38610581

ABSTRACT

Real-time acquisition of location information for agricultural robotic systems is a prerequisite for achieving high-precision intelligent navigation. This paper proposes a data filtering and combined positioning method, and establishes an active screening model. The dynamic and static positioning drift points of the carrier are eliminated or replaced, reducing the complexity of the original Global Navigation Satellite System (GNSS) output data in the positioning system. Compared with the traditional Kalman filter combined positioning method, the proposed active filtering-Kalman filter algorithm can reduce the maximum distance deviation of the carrier along a straight line from 0.145 m to 0.055 m and along a curve from 0.184 m to 0.0640 m. This study focuses on agricultural robot positioning technology, which has an important influence on the development of smart agriculture.

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