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1.
Sci Total Environ ; 946: 174428, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38964390

ABSTRACT

Tris(2-chloroethyl) phosphate (TCEP), a chlorinated organophosphate ester, is commonly found in aquatic environments. Due to its various toxic effects, it may pose a risk to the health of aquatic organisms. However, the potential impacts of TCEP exposure on the intestinal microbiota and hepatic function in amphibians have not been reported. This study investigated the impact of long-term exposure to environmentally relevant concentrations of TCEP (0, 3, and 90 µg/L) on the intestinal microbiota and hepatic transcriptome of Polypedates megacephalus tadpoles. The results showed that the body size of the tadpoles decreased significantly with an increase in TCEP concentration. Additionally, TCEP exposure affected the diversity and composition of the intestinal microbiota in tadpoles, leading to significant changes in the relative abundance of certain bacterial groups (the genera Aeromonas decreased and Citrobacter increased) and potentially promoting a more even distribution of microbial species, as indicated by a significant increase in the Simpson index. Moreover, the impact of TCEP on hepatic gene expression profiles in tadpoles was significant, with the majority of differentially expressed genes (DEGs) (709 out of 906 total DEGs in 3 µg/L of TCEP versus control, and 344 out of 387 DEGs in 90 µg/L of TCEP versus control) being significantly down-regulated, which were primarily related to immune response and immune system process. Notably, exposure to TCEP significantly reduced the relative abundance of the genera Aeromonas and Cetobacterium in the tadpole intestine. This reduction was positively correlated with the down-regulated expression of immune-related genes in the liver of corresponding tadpoles. In summary, these findings provide empirical evidence of the potential health risks to tadpoles exposed to TCEP at environmentally relevant concentrations.


Subject(s)
Gastrointestinal Microbiome , Larva , Liver , Transcriptome , Water Pollutants, Chemical , Animals , Gastrointestinal Microbiome/drug effects , Transcriptome/drug effects , Water Pollutants, Chemical/toxicity , Larva/drug effects , Liver/drug effects , Anura , Organophosphates
2.
Sci Rep ; 14(1): 16697, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030254

ABSTRACT

This work introduces a quantum subroutine for computing the distance between two patterns and integrates it into two quantum versions of the kNN classifier algorithm: one proposed by Schuld et al. and the other proposed by Quezada et al. Notably, our proposed subroutine is tailored to be memory-efficient, requiring fewer qubits for data encoding, while maintaining the overall complexity for both QkNN versions. This research focuses on comparing the performance of the two quantum kNN algorithms using the original Hamming distance with qubit-encoded features and our proposed subroutine, which computes the distance using amplitude-encoded features. Results obtained from analyzing thirteen different datasets (Iris, Seeds, Raisin, Mine, Cryotherapy, Data Bank Authentication, Caesarian, Wine, Haberman, Transfusion, Immunotherapy, Balance Scale, and Glass) show that both algorithms benefit from the proposed subroutine, achieving at least a 50% reduction in the number of required qubits, while maintaining a similar overall performance. For Shuld's algorithm, the performance improved in Cryotherapy (68.89% accuracy compared to 64.44%) and Balance Scale (85.33% F1 score compared to 78.89%), was worse in Iris (86.0% accuracy compared to 95.33%) and Raisin (77.67% accuracy compared to 81.56%), and remained similar in the remaining nine datasets. While for Quezada's algorithm, the performance improved in Caesarian (68.89% F1 score compared to 58.22%), Haberman (69.94% F1 score compared to 62.31%) and Immunotherapy (76.88% F1 score compared to 69.67%), was worse in Iris (82.67% accuracy compared to 95.33%), Balance Scale (77.97% F1 score compared to 69.21%) and Glass (40.04% F1 score compared to 28.79%), and remained similar in the remaining seven datasets.

3.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3031-3039, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041163

ABSTRACT

Haematitum is a commonly used mineral medicine. It is toxic, as recorded in the second volume of Chinese Materia Medica. Therefore, it should not be taken for a long time. In this study, the effects of Haematitum and calcined Haematitum on multiple organ injuries in mice were investigated, and the mechanism of the toxicity of the related organs was explored by metabolomics. The mice were randomly divided into the control group, Haematitum low-dose group(ZS-L group), Haematitum high-dose group(ZS-H group), and calcined Haematitum high-dose group(DZS-H group), with 12 mice in each group. Haematitum decoction was given by continuous intragastric administration for 10 days. Then the life situation was observed, and samples were taken to detect various indicators. The results showed that the ZS-H group showed obvious toxicity, with different degrees of toxicity damage in the intestinal tract,liver, spleen, and lung. ZS-L group had no toxic reaction. The toxicity of the DZS-H group was significantly reduced, and only the lung was damaged. Metabolomics technology was used to detect the lung tissue of mice in the control group and the ZS-H group, and a total of 15 kinds of significant difference metabolites were detected, mainly involved in choline metabolism in cancer, sphingolipid metabolism, and glycerophospholipid metabolism. Immunohistochemical results showed that the INSIG1 protein expression level in the lung tissue of mice in the ZS-H group was significantly higher than that in the control group. In summary, large doses and long-time use of Haematitum decoction will cause a variety of organ damage, and the same dose of calcined Haematitum is less toxic than Haematitum. In addition, a low dose of Haematitum has no obvious toxic effect. The dysfunction of lipid metabolic pathways such as sphingolipid and glycerophospholipid metabolism may be an important factor in Haematitum-induced pulmonary toxicity. This study provides a reference for further research on the mechanism of Haematitum pulmonary toxicity.


Subject(s)
Drugs, Chinese Herbal , Lung , Animals , Mice , Drugs, Chinese Herbal/administration & dosage , Male , Lung/drug effects , Lung/metabolism , Liver/drug effects , Liver/metabolism , Spleen/drug effects , Spleen/metabolism , Multiple Organ Failure/metabolism , Multiple Organ Failure/etiology , Multiple Organ Failure/chemically induced , Female , Metabolomics , Humans
4.
Comput Biol Med ; 179: 108913, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39047508

ABSTRACT

Machine learning has been employed in recognizing protein localization at the subcellular level, which highly facilitates the protein function studies, especially for those multi-label proteins that localize in more than one organelle. However, existing works mostly study the qualitative classification of protein subcellular locations, ignoring fraction of one multi-label protein in different locations. Actually, about 50 % proteins are multi-label proteins, and the ignorance of quantitative information highly restricts the understanding of their spatial distribution and functional mechanism. One reason of the lack of quantitative study is the insufficiency of quantitative annotations. To address the data shortage problem, here we proposed a generative model, PLocGAN, which could generate cell images with conditional quantitative annotation of the fluorescence distribution. The model was a conditional generative adversarial network, in which the condition learning utilized partial label learning to overcome the lack of training labels and allowed training with only qualitative labels. Meanwhile, it used contrastive learning to enhance diversity of the generated images. We assessed the PLocGAN on four pixel-fused synthetic datasets and one real dataset, and demonstrated that the model could generate images with good fidelity and diversity, outperforming existing state-of-the-art generative methods. To verify the utility of PLocGAN in the quantitative prediction of protein subcellular locations, we replaced the training images with generated quantitative images and built prediction models, and found that they had a boosting effect on the quantitative estimation. This work demonstrates the effectiveness of deep generative models in bioimage analysis, and provides a new solution for quantitative subcellular proteomics.

5.
Environ Pollut ; 358: 124494, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38968982

ABSTRACT

Tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) phosphate (TCPP) are common chlorinated organophosphorus flame retardants (OPFRs) used in industry. They have been frequently detected together in aquatic environments and associated with various hazardous effects. However, the ecological risks of prolonged exposure to these OPFRs at environmentally relevant concentrations in non-model aquatic organisms remain unexplored. This study investigated the effects of long-term exposure (up to 25 days) to TCEP and TCPP on metamorphosis, hepatic antioxidants, and endocrine function in Polypedates megacephalus tadpoles. Exposure concentrations were set at 3, 30, and 90 µg/L for each substance, conducted independently and in equal-concentration combinations, with a control group included for comparison. The integrated biomarker response (IBR) method developed an optimal linear model for predicting the overall ecological risks of TCEP and TCPP to tadpoles in potential distribution areas of Polypedates species. Results showed that: (1) Exposure to environmentally relevant concentrations of TCEP and TCPP elicited variable adverse effects on tadpole metamorphosis time, hepatic antioxidant enzyme activity and related gene expression, and endocrine-related gene expression, with their combined exposure exacerbating these effects. (2) The IBR value of TCEP was consistently greater than that of TCPP at each concentration, with an additive effect observed under their combined exposure. (3) The ecological risk of tadpoles exposed to the combined presence of TCEP and TCPP was highest in China's Taihu Lake and Vietnam's Hanoi than in other distribution locations. In summary, prolonged exposure to environmentally relevant concentrations of TCEP and TCPP presents potential ecological risks to amphibian tadpoles, offering insights for the development of policies and strategies to control TCEP and TCPP pollution in aquatic ecosystems. Furthermore, the methodology employed in establishing the IBR prediction model provides a methodological framework for assessing the overall ecological risks of multiple OPFRs.

6.
J Bone Joint Surg Am ; 106(13): 1189-1196, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958660

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Diabetes Mellitus, Type 2 , Mendelian Randomization Analysis , Humans , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/complications , Polymorphism, Single Nucleotide , Female , Male , Case-Control Studies , Middle Aged , Genetic Predisposition to Disease , Cross-Sectional Studies , Prospective Studies , Observational Studies as Topic , Aged , Genome-Wide Association Study
7.
Biol Psychiatry ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838841

ABSTRACT

BACKGROUND: Past research has illuminated pivotal roles of dopamine D3 receptors (D3R) in the rewarding effects of cocaine and opioids. However, the cellular and neural circuit mechanisms that underlie these actions remain unclear. METHODS: We employed Cre-LoxP techniques to selectively delete D3R from presynaptic dopamine neurons or postsynaptic dopamine D1 receptor (D1R)-expressing neurons in male and female mice. We utilized RNAscope in situ hybridization, immunohistochemistry, real-time polymerase chain reaction, voltammetry, optogenetics, microdialysis, and behavioral assays (n ≥ 8 animals per group) to functionally characterize the roles of presynaptic versus postsynaptic D3R in cocaine and opioid actions. RESULTS: Our results revealed D3R expression in ∼25% of midbrain dopamine neurons and ∼70% of D1R-expressing neurons in the nucleus accumbens. While dopamine D2 receptors (D2R) were expressed in ∼80% dopamine neurons, we found no D2R and D3R colocalization among these cells. Selective deletion of D3R from dopamine neurons increased exploratory behavior in novel environments and enhanced pulse-evoked nucleus accumbens dopamine release. Conversely, deletion of D3R from D1R-expressing neurons attenuated locomotor responses to D1-like and D2-like agonists. Strikingly, deletion of D3R from either cell type reduced oxycodone self-administration and oxycodone-enhanced brain-stimulation reward. In contrast, neither of these D3R deletions impacted cocaine self-administration, cocaine-enhanced brain-stimulation reward, or cocaine-induced hyperlocomotion. Furthermore, D3R knockout in dopamine neurons reduced oxycodone-induced hyperactivity and analgesia, while deletion from D1R-expressing neurons potentiated opioid-induced hyperactivity without affecting analgesia. CONCLUSIONS: We dissected presynaptic versus postsynaptic D3R function in the mesolimbic dopamine system. D2R and D3R are expressed in different populations of midbrain dopamine neurons, regulating dopamine release. Mesolimbic D3R are critically involved in the actions of opioids but not cocaine.

8.
Neuropharmacology ; 257: 110051, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38917939

ABSTRACT

Impulsive decision-making has been linked to impulse control disorders and substance use disorders. However, the neural mechanisms underlying impulsive choice are not fully understood. While previous PET imaging and autoradiography studies have shown involvement of dopamine and D2/3 receptors in impulsive behavior, the roles of distinct D1, D2, and D3 receptors in impulsive decision-making remain unclear. In this study, we used a food reward delay-discounting task (DDT) to identify low- and high-impulsive rats, in which low-impulsive rats exhibited preference for large delayed reward over small immediate rewards, while high-impulsive rats showed the opposite preference. We then examined D1, D2, and D3 receptor gene expression using RNAscope in situ hybridization assays. We found that high-impulsive male rats exhibited lower levels of D2 and D3, and particularly D3, receptor expression in the nucleus accumbens (NAc), with no significant changes in the insular, prelimbic, and infralimbic cortices. Based on these findings, we further explored the role of the D3 receptor in impulsive decision-making. Systemic administration of a selective D3 receptor agonist (FOB02-04) significantly reduced impulsive choices in high-impulsive rats but had no effects in low-impulsive rats. Conversely, a selective D3 receptor antagonist (VK4-116) produced increased both impulsive and omission choices in both groups of rats. These findings suggest that impulsive decision-making is associated with a reduction in D3 receptor expression in the NAc. Selective D3 receptor agonists, but not antagonists, may hold therapeutic potentials for mitigating impulsivity in high-impulsive subjects.


Subject(s)
Choice Behavior , Decision Making , Delay Discounting , Impulsive Behavior , Receptors, Dopamine D2 , Receptors, Dopamine D3 , Animals , Male , Receptors, Dopamine D3/metabolism , Impulsive Behavior/drug effects , Impulsive Behavior/physiology , Rats , Delay Discounting/drug effects , Delay Discounting/physiology , Receptors, Dopamine D2/metabolism , Decision Making/drug effects , Decision Making/physiology , Choice Behavior/drug effects , Choice Behavior/physiology , Reward , Nucleus Accumbens/metabolism , Nucleus Accumbens/drug effects , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D1/antagonists & inhibitors , Dopamine Antagonists/pharmacology , Rats, Sprague-Dawley
9.
Sci Rep ; 14(1): 12667, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831094

ABSTRACT

The glutenite reservoir in an exploration area in eastern China is well-developed and holds significant exploration potential as an important oil and gas alternative layer. However, due to the influence of sedimentary characteristics, the glutenite reservoir exhibits strong lateral heterogeneity, significant vertical thickness variations, and low accuracy in reservoir space characterization, which affects the reasonable and effective deployment of development wells. Seismic data contains the three-dimensional spatial characteristics of geological bodies, but how to design a suitable transfer function to extract the nonlinear relationship between seismic data and reservoirs is crucial. At present, the transfer functions are concentrated in low-dimensional or high-dimensional fixed mathematical models, which cannot accurately describe the nonlinear relationship between seismic data and complex reservoirs, resulting in low spatial description accuracy of complex reservoirs. In this regard, this paper first utilizes a fusion method based on probability kernel to fuse seismic attributes such as wave impedance, effective bandwidth, and composite envelope difference. This provide a more intuitive reflection of the distribution characteristics of glutenite reservoirs. Moreover, a hybrid nonlinear transfer function is established to transform the fused attribute cube into an opaque attribute cube. Finally, the illumination model and ray casting method are used to perform voxel imaging of the glutenite reservoirs, brighten the detailed characteristics of reservoir space, and then form a set of methods for ' brightening reservoirs and darkening non-reservoirs ', which improves the spatial engraving accuracy of glutenite reservoirs.

10.
Transl Res ; 272: 1-18, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823438

ABSTRACT

OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.

11.
Aquat Toxicol ; 272: 106979, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823072

ABSTRACT

Tris(2-chloroethyl) phosphate (TCEP) and tris(1­chloro-2-propyl) phosphate (TCPP) are widely used as chlorinated organophosphate flame retardants (OPFRs) due to their fire-resistance capabilities. However, their extensive use has led to their permeation and pollution in aquatic environments. Using amphibians, which are non-model organisms, to test the toxic effects of OPFRs is relatively uncommon. This study examined the acute and chronic toxicity differences between TCEP and TCPP on Polypedates megacephalus tadpoles and evaluated the potential ecological risks to tadpoles in different aquatic environments using the risk quotient (RQ). In acute toxicity assay, the tadpole survival rates decreased with increased exposure time and concentrations, with TCEP exhibiting higher LC50 values than TCPP, at 305.5 mg/L and 70 mg/L, respectively. In the chronic assay, prolonged exposure to 300 µg/L of both substances resulted in similar adverse effects on tadpole growth, metamorphosis, and hepatic antioxidant function. Based on RQ values, most aquatic environments did not pose an ecological risk to tadpoles. However, the analysis showed that wastewater presented higher risks than rivers and drinking water, and TCPP posed a higher potential risk than TCEP in all examined aquatic environments. These findings provide empirical evidence to comprehend the toxicological effects of OPFRs on aquatic organisms and to assess the safety of aquatic environments.


Subject(s)
Anura , Flame Retardants , Larva , Organophosphates , Organophosphorus Compounds , Water Pollutants, Chemical , Animals , Flame Retardants/toxicity , Larva/drug effects , Larva/growth & development , Water Pollutants, Chemical/toxicity , Organophosphorus Compounds/toxicity , Risk Assessment , Organophosphates/toxicity , Anura/growth & development , Metamorphosis, Biological/drug effects , Toxicity Tests, Acute , Lethal Dose 50
12.
Mol Cell ; 84(12): 2304-2319.e8, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38838666

ABSTRACT

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.


Subject(s)
Active Transport, Cell Nucleus , Adenosine , Cell Nucleus , Neurogenesis , Neurons , Poly(A)-Binding Protein I , RNA, Circular , RNA , RNA, Circular/metabolism , RNA, Circular/genetics , Neurons/metabolism , Adenosine/metabolism , Cell Nucleus/metabolism , Humans , Poly(A)-Binding Protein I/metabolism , Poly(A)-Binding Protein I/genetics , Animals , RNA/metabolism , RNA/genetics , Cell Line , Cell Differentiation , Cytoplasm/metabolism , Prosencephalon/metabolism
13.
Animals (Basel) ; 14(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891605

ABSTRACT

Haemaphysalis longicornis is a common tick species that carries several pathogens. There are few reports on the influence of different hosts on the structure of midgut microflora in H. longicornis. In this study, midgut contents of fully engorged female H. longicornis were collected from the surface of tiger (Panthera tigris) and deer (Dama dama). The bacterial genomic DNA of each sample was extracted, and the V3-V4 regions of the bacterial 16S rRNA were sequenced using the Illumina NovaSeq sequencing. The diversity of the bacterial community of the fully engorged female H. longicornis on the surface of tiger was higher than that of deer. In total, 8 phyla and 73 genera of bacteria annotations were detected in the two groups. At the phylum level, the bacterial phyla common to the two groups were Proteobacteria, Firmicutes, and Actinobacteriota. At the genus level, there were 20 common bacterial genera, among which the relative abundances of Coxiella, Morganella, Diplorickettsia, and Acinetobacter were high. The Morganella species was further identified to be Morganella morganii. The alpha diversity index indicated that the bacterial diversity of the tiger group was higher than that of the deer group. Bacteroidota, Patescibacteria, Desulfobacterota, Verrucomicrobiota, and Cyanobacteria were solely detected in the tiger group. A total of 52 bacterial genera were unique in the tiger group, while one bacterial genus was unique in the deer group. This study indicates that there are differences in the structure of the gut bacteria of the same tick species among different hosts. Further culture-based methods are needed to provide a more comprehensive understanding of the tick microbiota parasitizing different hosts.

14.
Sci Rep ; 14(1): 13834, 2024 06 15.
Article in English | MEDLINE | ID: mdl-38879709

ABSTRACT

Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan-Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the "ssGSEA" algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer.


Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Pancreatic Neoplasms , Female , Humans , Male , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Kaplan-Meier Estimate , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Prognosis , Protein Interaction Maps , ROC Curve
15.
Adv Mater ; : e2403848, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837906

ABSTRACT

All-solid-state lithium batteries with polymer electrolytes suffer from electrolyte decomposition and lithium dendrites because of the unstable electrode/electrolyte interfaces. Herein, a molecule crowding strategy is proposed to modulate the Li+ coordinated structure, thus in situ constructing the stable interfaces. Since 15-crown-5 possesses superior compatibility with polymer and electrostatic repulsion for anion of lithium salt, the anions are forced to crowd into a Li+ coordinated structure to weaken the Li+ coordination with polymer and boost the Li+ transport. The coordinated anions prior decompose to form LiF-rich, thin, and tough interfacial passivation layers for stabilizing the electrode/electrolyte interfaces. Thus, the symmetric Li-Li cell can stably operate over 4360 h, the LiFePO4||Li full battery presents 97.18% capacity retention in 700 cycles at 2 C, and the NCM811||Li full battery possesses the capacity retention of 83.17% after 300 cycles. The assembled pouch cell shows excellent flexibility (stand for folding over 2000 times) and stability (89.42% capacity retention after 400 cycles). This work provides a promising strategy to regulate interfacial chemistry by modulating the ion environment to accommodate the interfacial issues and will inspire more effective approaches to general interface issues for polymer electrolytes.

16.
Front Neurorobot ; 18: 1374531, 2024.
Article in English | MEDLINE | ID: mdl-38911604

ABSTRACT

The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs).

17.
Aesthetic Plast Surg ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740626

ABSTRACT

BACKGROUND: Each year, tens of thousands of people worldwide choose to undergo cosmetic surgery in order to alter their appearance. In recent years, young people have gradually emerged to comprise the main driving force behind the increasing demand for cosmetic surgery. Previous studies have found that sexism may motivate young people to undergo such surgeries. However, few studies have been conducted to determine if this psychological mechanism influences the acceptance of cosmetic surgery among Chinese university students. METHODS: A total of 579 Chinese university students (280 girls and 299 boys, 17-20 years) volunteered to participate in the online survey. They completed a questionnaire containing the Ambivalent Sexism Inventory, the 12-item General Health Questionnaire, the Gender-Role Attitudes Questionnaire and the Acceptance of Cosmetic Surgery Scale. We firstly evaluated the underlying factor structure of the Acceptance of Cosmetic Surgery Scale using exploratory and confirmatory factor analyses, and exploring pattern of associations between the constructs was analyzed via path analysis. RESULTS: According to the findings, hostile sexism was associated with greater levels of acceptance toward cosmetic surgery. Moreover, gender-role attitudes mediated the link between hostile sexism and the acceptance of cosmetic surgery, and this mediation was positively influenced by general mental health. CONCLUSION: Our study contributes to a deeper understanding of Chinese university students' attitudes toward cosmetic surgery, hostile sexism may contribute to normalizing traditional gender stereotypes and encourage cosmetic surgery acceptability among Chinese university students. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

18.
Development ; 151(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38770916

ABSTRACT

Prolyl hydroxylase domain (PHD) proteins are oxygen sensors that use intracellular oxygen as a substrate to hydroxylate hypoxia-inducible factor (HIF) α proteins, routing them for polyubiquitylation and proteasomal degradation. Typically, HIFα accumulation in hypoxic or PHD-deficient tissues leads to upregulated angiogenesis. Here, we report unexpected retinal phenotypes associated with endothelial cell (EC)-specific gene targeting of Phd2 (Egln1) and Hif2alpha (Epas1). EC-specific Phd2 disruption suppressed retinal angiogenesis, despite HIFα accumulation and VEGFA upregulation. Suppressed retinal angiogenesis was observed both in development and in the oxygen-induced retinopathy (OIR) model. On the other hand, EC-specific deletion of Hif1alpha (Hif1a), Hif2alpha, or both did not affect retinal vascular morphogenesis. Strikingly, retinal angiogenesis appeared normal in mice double-deficient for endothelial PHD2 and HIF2α. In PHD2-deficient retinal vasculature, delta-like 4 (DLL4, a NOTCH ligand) and HEY2 (a NOTCH target) were upregulated by HIF2α-dependent mechanisms. Inhibition of NOTCH signaling by a chemical inhibitor or DLL4 antibody partially rescued retinal angiogenesis. Taken together, our data demonstrate that HIF2α accumulation in retinal ECs inhibits rather than stimulates retinal angiogenesis, in part by upregulating DLL4 expression and NOTCH signaling.


Subject(s)
Animals, Newborn , Basic Helix-Loop-Helix Transcription Factors , Endothelial Cells , Hypoxia-Inducible Factor-Proline Dioxygenases , Receptors, Notch , Retinal Neovascularization , Signal Transduction , Up-Regulation , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Mice , Receptors, Notch/metabolism , Receptors, Notch/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Retinal Neovascularization/metabolism , Retinal Neovascularization/genetics , Retinal Neovascularization/pathology , Endothelial Cells/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Retina/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/genetics , Retinal Vessels/metabolism , Angiogenesis
19.
Mol Phylogenet Evol ; 197: 108113, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38796071

ABSTRACT

A robust and stable phylogenetic framework is a fundamental goal of evolutionary biology. As the third largest insect order in the world following Coleoptera and Diptera, Lepidoptera (butterflies and moths) play a central role in almost every terrestrial ecosystem as indicators of environmental change and serve as important models for biologists exploring questions related to ecology and evolutionary biology. However, for such a charismatic insect group, the higher-level phylogenetic relationships among its superfamilies are still poorly resolved. Compared to earlier phylogenomic studies, we increased taxon sampling among Lepidoptera (37 superfamilies and 68 families containing 263 taxa) and acquired a series of large amino-acid datasets from 69,680 to 400,330 for phylogenomic reconstructions. Using these datasets, we explored the effect of different taxon sampling with significant increases in the number of included genes on tree topology by considering a series of systematic errors using maximum-likelihood (ML) and Bayesian inference (BI) methods. Moreover, we also tested the effectiveness in topology robustness among the three ML-based models. The results showed that taxon sampling is an important determinant in tree robustness of accurate lepidopteran phylogenetic estimation. Long-branch attraction (LBA) caused by site-wise heterogeneity is a significant source of bias giving rise to unstable positions of ditrysian groups in phylogenomic reconstruction. Phylogenetic inference showed the most comprehensive framework to reveal the relationships among lepidopteran superfamilies, and presented some newly relationships with strong supports (Papilionoidea was sister to Gelechioidea and Immoidea was sister to Galacticoidea, respectively), but limited by taxon sampling, the relationships within the species-rich and relatively rapid radiation Ditrysia and especially Apoditrysia remain poorly resolved, which need to increase taxon sampling for further phylogenomic reconstruction. The present study demonstrates that taxon sampling is an important determinant for an accurate lepidopteran tree of life and provides some essential insights for future lepidopteran phylogenomic studies.


Subject(s)
Bayes Theorem , Butterflies , Moths , Phylogeny , Animals , Moths/genetics , Moths/classification , Likelihood Functions , Butterflies/genetics , Butterflies/classification , Models, Genetic
20.
Front Cell Infect Microbiol ; 14: 1356353, 2024.
Article in English | MEDLINE | ID: mdl-38601741

ABSTRACT

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.


Subject(s)
Acinetobacter baumannii , Tetracyclines , Multilocus Sequence Typing , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Carbapenems/pharmacology , RNA, Antisense , China/epidemiology , Microbial Sensitivity Tests
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