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1.
Pharmacogenomics ; : 1-10, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39263813

ABSTRACT

Aim: To investigate the association of DNA methylation, genetic polymorphisms and mRNA level of aminolevulinate synthase 1 (ALAS1) with antituberculosis drug-induced liver injury (AT-DILI) risk.Methods: Based on a 1:1 matched case-control study with 182 cases and 182 controls, one CpG island and three single nucleotide polymorphisms (SNPs) were detected. ALAS1 mRNA level was detected in 34 samples.Results: Patients with methylation status were at high risk of AT-DILI (odds ratio: 1.567, 95% CI: 1.015-2.421, p = 0.043) and SNP rs352169 was associated with AT-DILI risk (GA vs. GG, odds ratio: 1.770, 95% CI: 1.101-2.847, p = 0.019). ALAS1 mRNA level in the cases was significantly lower than that in the controls (0.75 ± 0.34 vs. 1.00 ± 0.42, p = 0.021).Conclusion: The methylation status and SNP rs352169 of ALAS1 were associated with AT-DILI risk.


[Box: see text].

2.
Sci Rep ; 14(1): 20382, 2024 09 02.
Article in English | MEDLINE | ID: mdl-39223186

ABSTRACT

CT and MR tools are commonly used to diagnose lumbar fractures (LF). However, numerous limitations have been found in practice. The aims of this study were to innovate and develop a spinal disease-specific neural network and to evaluate whether synthetic MRI of the LF affected clinical diagnosis and treatment strategies. A total of 675 LF patients who met the inclusion and exclusion criteria were included in the study. For each participant, two mid-sagittal CT and T2-weighted MR images were selected; 1350 pairs of LF images were also included. A new Self-pix based on Pix2pix and Self-Attention was constructed. A total of 1350 pairs of CT and MR images, which were randomly divided into a training group (1147 pairs) and a test group (203 pairs), were fed into Pix2pix and Self-pix. The quantitative evaluation included PSNR and SSIM (PSNR1 and SSIM1: real MR images and Pix2pix-generated MR images; PSNR2 and SSIM2: real MR images and Self-pix-generated MR images). The qualitative evaluation, including accurate diagnosis of acute fractures and accurate selection of treatment strategies based on Self-pix-generated MRI, was performed by three spine surgeons. In the LF group, PSNR1 and PSNR2 were 10.884 and 11.021 (p < 0.001), and SSIM1 and SSIM2 were 0.766 and 0.771 (p < 0.001), respectively. In the ROI group, PSNR1 and PSNR2 were 12.350 and 12.670 (p = 0.004), and SSIM1 and SSIM2 were 0.816 and 0.832 (p = 0.005), respectively. According to the qualitative evaluation, Self-pix-generated MRI showed no significant difference from real MRI in identifying acute fractures (p = 0.689), with a good sensitivity of 84.36% and specificity of 96.65%. No difference in treatment strategy was found between the Self-pix-generated MRI group and the real MRI group (p = 0.135). In this study, a disease-specific GAN named Self-pix was developed, which demonstrated better image generation performance compared to traditional GAN. The spine surgeon could accurately diagnose LF and select treatment strategies based on Self-pix-generated T2 MR images.


Subject(s)
Lumbar Vertebrae , Magnetic Resonance Imaging , Spinal Fractures , Humans , Magnetic Resonance Imaging/methods , Female , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Spinal Fractures/diagnostic imaging , Spinal Fractures/therapy , Adult , Aged , Tomography, X-Ray Computed/methods , Neural Networks, Computer
3.
J Clin Pharmacol ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39297668

ABSTRACT

The accumulation of protoporphyrin IX in the liver caused by isoniazid and rifampicin through the disorder of heme biosynthesis was considered an important mechanism of anti-tuberculosis drug-induced liver injury (ATLI). Alanine synthase 1 (ALAS1) is a rate-limiting enzyme in the process of heme synthesis. This study aimed to investigate the association between ALAS1 gene polymorphism, serum ALAS1 level, and the risk of ATLI. This study was a case-control study including 58 ATLI cases and 192 controls. Four single nucleotide polymorphisms (SNPs) of the ALAS1 gene were selected for genotyping and serum ALAS1 concentrations were detected using ELISA kits. There was no significant difference in the genotype distribution of four SNPs between the ATLI cases and the controls under different genetic models. Patients carrying the GG genotype of SNP rs352163 in controls had higher baseline ALAS1 levels than those in ATLI cases (243.6 vs 290.2 ng/L, P = .034), and patients with baseline ALAS1 < 337.85 ng/L had a higher risk of ATLI than those with ALAS1 ≥ 337.85 ng/L (HR = 2.679, 95% CI: 1.360-5.278, P = .004). Our findings indicated that the serum ALAS1 concentrations in the ATLI cases were lower than those in the controls, and the lower baseline ALAS1 levels can be associated with higher ATLI risk.

4.
ACS Sens ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39298721

ABSTRACT

Conventional methods for detecting unsaturated fatty acids (UFAs) pose challenges for rapid analyses due to the need for complex pretreatment and expensive instruments. Here, we developed an intelligent platform for facile and low-cost analysis of UFAs by combining a smartphone-assisted colorimetric sensor array (CSA) based on MnO2 nanozymes with "image segmentation-feature extraction" deep learning (ISFE-DL). Density functional theory predictions were validated by doping experiments using Ag, Pd, and Pt, which enhanced the catalytic activity of the MnO2 nanozymes. A CSA mimicking mammalian olfactory system was constructed with the principle that UFAs competitively inhibit the oxidization of the enzyme substrate, resulting in color changes in the nanozyme-ABTS substrate system. Through linear discriminant analysis coupled with the smartphone App "Quick Viewer" that utilizes multihole parallel acquisition technology, oleic acid (OA), linoleic acid (LA), α-linolenic acid (ALA), and their mixtures were clearly discriminated; various edible vegetable oils, different camellia oils (CAO), and adulterated CAOs were also successfully distinguished. Furthermore, the ISFE-DL method was combined in multicomponent quantitative analysis. The sensing elements of the CSA (3 × 4) were individually segmented for single-hole feature extraction containing information from 38,868 images of three UFAs, thereby allowing for the extraction of more features and augmenting sample size. After training with the MobileNetV3 small model, the determination coefficients of OA, LA, and ALA were 0.9969, 0.9668, and 0.7393, respectively. The model was embedded in the smartphone App "Intelligent Analysis Master" for one-click quantification. We provide an innovative approach for intelligent and efficient qualitative and quantitative analysis of UFAs and other compounds with similar characteristics.

6.
Clin Res Hepatol Gastroenterol ; 48(8): 102462, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39276858

ABSTRACT

BACKGROUND: Surgical site infection (SSI) is a significant concern due to its potential to cause delayed wound healing and prolonged hospital stays. This study aims to develop a predictive model in patients with Crohn's disease. METHODS: We conducted single-factor and multi-factor logistic regression analyses to identify risk factors, resulting in the development of a logistic regression model and the creation of a nomogram. The model's effect was validated by employing enhanced bootstrap resampling techniques, calibration curves, and DCA curves. Finally, we investigated the risk factors for wall and intra-abdominal infections separately. RESULTS: 90 of 675 patients (13.3 %) developed SSI. Several independent risk factors for SSI were identified, including higher postoperative day one neutrophil count (p = 0.033), higher relative blood loss (p = 0.018), female gender (p = 0.021), preoperative corticosteroid use (p = 0.007), Montreal classification A1 and L2 (p < 0.05), previous intestinal resection (p = 0.017), and remaining lesions (p = 0.015). Additionally, undergoing strictureplasty (p = 0.041) is a protective factor against SSI. These nine variables were used to develop an SSI prediction model presented as a nomogram. The model demonstrated strong discrimination (adjusted C-statistic=0.709, 95 % CI: 0.659∼0.757) and precise calibration. The decision curve showed that the nomogram was clinically effective within a probability threshold range of 3 % to 54 %. Further subgroup analysis revealed distinct risk factors for wall infections and intra-abdominal infections. CONCLUSION: We established a new predictive model, which can guide the prevention and postoperative care of SSI after Crohn's disease bowel resection surgery to minimize its occurrence rate.

7.
Article in English | MEDLINE | ID: mdl-39191144

ABSTRACT

Procambarus clarkii is an economically important species in China; however, its high mortality rate due to pathogenic bacteria, particularly Vibrio parahaemolyticus, results in significant economic loss. This study aimed to understand the immune response of crayfish to bacterial infection by comparing and analyzing transcriptome data of hepatopancreatic tissue from P. clarkii challenged with V. parahaemolyticus or treated with PBS. Physiological indices (TP, Alb, ACP, and AKP) were analyzed, and tissue sections were prepared. After assembling and annotating the data, 18,756 unigenes were identified. A comparison of the expression levels of these unigenes between the control and V. parahaemolyticus groups revealed 4037 DEGs, with 2278 unigenes upregulated and 1759 downregulated in the V. parahaemolyticus group. GO (Gene Ontology) enrichment analysis shows that the DGEs are mainly enriched in cellular anatomical activity, bindinga and cellular process, enrichment analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways showed that DGEs were mainly enriched in Base excision repair, Phagosome and Longevity regulating pathway. At the same time, lysosome was also enriched. The phagosome and lysosome pathways play a crucial role in the immune defense of crayfish against V. parahaemolyticus injection that will be highlighted. In addition, the expression levels of six selected immune-related DEGs were measured using qRT-PCR, which validated the results of RNA-seq analysis. This study provides a new perspective on the immune system and defense mechanisms of P. clarkii and a valuable foundation for further investigation of the molecular immune mechanisms of this species.

8.
SAGE Open Med Case Rep ; 12: 2050313X241271818, 2024.
Article in English | MEDLINE | ID: mdl-39161923

ABSTRACT

Malignant peritoneal mesothelioma is an exceedingly rare malignant tumor. Herein, we present a case of malignant peritoneal mesothelioma in a 59-year-old Chinese female patient who was stable after treatment for multiple relapses. Imaging revealed massive ascites and an irregular thickening of the peritoneal mesangium. Laparoscopic biopsy revealed heterogeneous cell nests in the parietal peritoneal fibrous tissue, which were confirmed by immunohistochemical staining for Calretinin, WT-1, and D2-40. In terms of genetic screening, BAP1, CSF1R, and other key driver gene variants closely related to malignant peritoneal mesothelioma have been explored in tumor tissues. Notably, CARD11 driver mutation was first found in all malignant peritoneal mesothelioma patients, and ATM A1159T gene mutation found in recurrent focal tissue may be associated with recurrent tumor recurrence.

9.
Biosens Bioelectron ; 263: 116604, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39094293

ABSTRACT

Achieving rapid, cost effective, and intelligent identification and quantification of flavonoids is challenging. For fast and uncomplicated flavonoid determination, a sensing platform of smartphone-coupled colorimetric sensor arrays (electronic noses) was developed, relying on the differential competitive inhibition of hesperidin, nobiletin, and tangeretin on the oxidation reactions of nanozymes with a 3,3',5,5'-tetramethylbenzidine substrate. First, density functional theory calculations predicted the enhanced peroxidase-like activities of CeO2 nanozymes after doping with Mn, Co, and Fe, which was then confirmed by experiments. The self-designed mobile application, Quick Viewer, enabled a rapid evaluation of the red, green, and blue values of colorimetric images using a multi-hole parallel acquisition strategy. The sensor array based on three channels of CeMn, CeFe, and CeCo was able to discriminate between different flavonoids from various categories, concentrations, mixtures, and the various storage durations of flavonoid-rich Citri Reticulatae Pericarpium through a linear discriminant analysis. Furthermore, the integration of a "segmentation-extraction-regression" deep learning algorithm enabled single-hole images to be obtained by segmenting from a 3 × 4 sensing array to augment the featured information of array images. The MobileNetV3-small neural network was trained on 37,488 single-well images and achieved an excellent predictive capability for flavonoid concentrations (R2 = 0.97). Finally, MobileNetV3-small was integrated into a smartphone as an application (Intelligent Analysis Master), to achieve the one-click output of three concentrations. This study developed an innovative approach for the qualitative and simultaneous multi-ingredient quantitative analysis of flavonoids.


Subject(s)
Biosensing Techniques , Colorimetry , Deep Learning , Flavonoids , Smartphone , Colorimetry/instrumentation , Colorimetry/methods , Flavonoids/analysis , Flavonoids/chemistry , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Citrus/chemistry , Electronic Nose , Cerium/chemistry , Limit of Detection , Benzidines/chemistry
10.
Cancer Biomark ; 41(1): 41-54, 2024.
Article in English | MEDLINE | ID: mdl-39177588

ABSTRACT

BACKGROUND: Gastric cancer (GC) is one of the most common tumors. There were several classifications of GC recently. The value of Lauren classification in evaluating the prognosis after radical gastrectomy was still unclear and the prognosis of gastric cancer remained relatively poor in the absence of prognostic biomarkers. This study aimed to explore microRNA (miRNA) in the prognosis of GC with different Lauren classification. METHODS: A retrospective study of 1144 patients was performed in this study. Quantificational reverse transcription-PCR (qRT-PCR) was used to examine the expression of miRNAs. Univariate and multivariate analysis were performed to evaluate prognosis value of Lauren classification. RESULTS: Total 1144 GC patients were recruited in this cohort, including 302 diffuse type (26.4%), 436 intestinal type (38.1%) and 406 mixed type (35.5%) GC. Multivariate analysis showed that Lauren classification, patients' age, tumor size, tumor infiltrating depth, vascular nerve infiltrating and metastatic lymph nodes ration were significantly correlated with GC patients' OS and DFS. The miR-141-3p, miR-200b-3p and miR-133a-5p were significantly down-regulated in diffuse type compared to intestinal type GC tissues, the miR-105-5p had significant lower expression in diffuse type compared with intestinal type and mixed type GC tissues. As a consequence of univariate analysis, low miR-141-3p in diffuse type GC showed significant worse OS and DFS than high miR-141-3p. CONCLUSIONS: Lauren classification was an independent prognostic factor in GC. MiR-141-3p was an independent prognostic factor and a promising prognostic biomarker in Lauren classification GC.


Subject(s)
Biomarkers, Tumor , MicroRNAs , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , MicroRNAs/genetics , Male , Female , Prognosis , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Aged , Retrospective Studies , Gene Expression Regulation, Neoplastic , Neoplasm Staging , Adult
11.
Fish Shellfish Immunol ; 153: 109852, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39173982

ABSTRACT

Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1ß, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-ß. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1ß signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish.


Subject(s)
Animal Feed , Cichlids , Fish Diseases , Gossypol , Pediococcus pentosaceus , Probiotics , Signal Transduction , Animals , Cichlids/immunology , Fish Diseases/immunology , Fish Diseases/chemically induced , Fish Diseases/prevention & control , Probiotics/pharmacology , Probiotics/administration & dosage , Animal Feed/analysis , Signal Transduction/drug effects , Gossypol/administration & dosage , Gossypol/pharmacology , Diet/veterinary , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Aeromonas hydrophila/physiology , NF-kappa B/metabolism , NF-kappa B/genetics , Gastrointestinal Microbiome/drug effects , Intestines/drug effects , Intestines/immunology , Inflammation/veterinary , Inflammation/chemically induced , Inflammation/immunology , Gram-Negative Bacterial Infections/veterinary , Gram-Negative Bacterial Infections/immunology , Fish Proteins/genetics , Fish Proteins/metabolism , Fish Proteins/immunology , Enteritis/veterinary , Enteritis/prevention & control , Enteritis/chemically induced , Enteritis/immunology , Enteritis/microbiology
12.
Science ; 385(6711): eado1022, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39172836

ABSTRACT

Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that form during spindle bipolarization and elucidated the mechanism underlying this process. We found that the minor poles formed in multiple kinetochore clusters contribute to the generation of multipolar intermediates. We further determined the essential roles of HAUS6, KIF11, and KIF18A in spindle bipolarization and identified mutations in these genes in infertile patients characterized by oocyte or embryo defects. These results provide insights into the physiological and pathological mechanisms of spindle bipolarization in human oocytes.


Subject(s)
Chromosome Segregation , Kinesins , Kinetochores , Microtubules , Oocytes , Spindle Apparatus , Humans , Oocytes/metabolism , Kinesins/metabolism , Kinesins/genetics , Kinetochores/metabolism , Spindle Apparatus/metabolism , Microtubules/metabolism , Female , Mutation , Spindle Poles/metabolism
13.
Lipids Health Dis ; 23(1): 268, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182089

ABSTRACT

BACKGROUND: The progression of tumours is related to abnormal phospholipid metabolism. This study is anticipated to present a fresh perspective for disease therapy targets of hepatocarcinoma caused by hepatitis B virus in the future by screening feature genes related to phospholipid metabolism. METHODS: This study analysed GSE121248 to pinpoint differentially expressed genes (DEGs). By examining the overlap between the metabolism-related genes and DEGs, the research focused on the genes involved in phospholipid metabolism. To find feature genes, functional enrichment studies were carried out and a network diagram was proposed. These findings were validated via data base of The Cancer Genome Atlas (TCGA). Further analyses included immune infiltration studies and metabolomics. Finally, the relationships between differentially abundant metabolites and feature genes were confirmed by molecular docking, providing a thorough comprehension of the molecular mechanisms. RESULTS: The seven genes with the highest degree of connection (PTGS2, IGF1, SPP1, BCHE, NR1I2, NAMPT, and FABP1) were identified as feature genes. In the TCGA database, the seven feature genes also had certain diagnostic efficiency. Immune infiltration analysis revealed that feature genes regulate the infiltration of various immune cells. Metabolomics successfully identified the different metabolites of the phospholipid metabolism pathway between patients and normal individuals. The docking study indicated that different metabolites may play essential roles in causing disease by targeting feature genes. CONCLUSIONS: In this study, for the first time, it reveals the possible involvement of genes linked to phospholipid metabolism-related genes using bioinformatics analysis. Identifying genes and probable therapeutic targets could provide clues for the further treatment of disease.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B virus , Hepatitis B , Liver Neoplasms , Molecular Docking Simulation , Phospholipids , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/virology , Liver Neoplasms/metabolism , Hepatitis B/genetics , Hepatitis B/complications , Hepatitis B/metabolism , Hepatitis B/virology , Hepatitis B virus/genetics , Phospholipids/metabolism , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Metabolomics/methods , Gene Expression Profiling
14.
Gene ; 928: 148770, 2024 Nov 30.
Article in English | MEDLINE | ID: mdl-39032703

ABSTRACT

Peptidoglycan recognition proteins (PGRPs) are a family of multifunctional proteins playing vital roles in PGN metabolism and antibacterial defense, and their functions have been well-characterized in mammals, bony fishes, and insects. However, the information about the functions of amphibian long-type PGRP is rather limited. Here, we identified and cloned a long-type PGRP gene (named Xl-PGRP-L) from African clawed frog, Xenopus laevis. Xl-PGRP-L gene was detected in all orangs/tissues examined, and was rapidly induced in intestine, liver, and lung following the stimulation of PGN. Sequence analysis showed that Xl-PGRP-L possesses four Zn2+-binding residues (His358, Tyr395, His470, and Cys478) required for amidase activity of catalytic PGRPs, and assays for amidase activity revealed that recombinant Xl-PGRP-L cloud degrade PGN in a Zn2+-dependent manner, indicating that Xl-PGRP-L is belonging to catalytic PGRPs. In addition, Xl-PGRP-L have antibacterial activity against Gram-negative bacteria Edwardsiella tarda and Gram-positive bacteria Streptococcus agalactiae. The present investigation represents the first characterization regarding the biological activities of amphibian long-type PGRPs, thus contributes to a better understanding of the functions of tetrapod PGRPs and the molecular mechanisms of amphibian antibacterial defense.


Subject(s)
Carrier Proteins , Xenopus Proteins , Xenopus laevis , Animals , Carrier Proteins/genetics , Carrier Proteins/metabolism , Xenopus Proteins/genetics , Xenopus Proteins/metabolism , Cloning, Molecular , Amino Acid Sequence , Peptidoglycan/metabolism , Amidohydrolases/genetics , Amidohydrolases/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Zinc/metabolism , Phylogeny , Streptococcus agalactiae/genetics
15.
Am J Physiol Cell Physiol ; 327(3): C737-C749, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39069827

ABSTRACT

The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on SLC25A1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of SLC25A1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for 4 wk, whereas Nile tilapia received intraperitoneal injections of dsRNA to knock down slc25a1b for 7 days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Of note, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride (TAG) accumulation by deacetylating carnitine palmitoyltransferase 1a (Cpt1a). In addition, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of nonhistone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD.NEW & NOTEWORTHY The mitochondrial citrate shuttle is a crucial physiological process for maintaining metabolic homeostasis. In the present study, we found that inhibition of mitochondrial citrate shuttle (Slc25a1) could alleviate metabolic syndromes induced by high-fat diet (HFD) through remodeling hepatic protein acetylation modification. Briefly, Slc25a1 inhibition reduces hepatic triglyceride deposition by deacetylating Cpt1a and reduces glucose oxidative catabolism by acetylating Pdhe1α. Our study provides new insights into the treatment of diet-induced metabolic syndromes.


Subject(s)
Citric Acid , Diet, High-Fat , Zebrafish , Animals , Diet, High-Fat/adverse effects , Citric Acid/metabolism , Metabolic Syndrome/metabolism , Metabolic Syndrome/prevention & control , Metabolic Syndrome/genetics , Metabolic Syndrome/etiology , Mitochondria/metabolism , Mitochondria/drug effects , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics , Obesity/metabolism , Obesity/prevention & control , Obesity/genetics , Obesity/etiology , Acetylation , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Liver/metabolism , Liver/drug effects , Liver/pathology , Male , Insulin Resistance , Fatty Liver/metabolism , Fatty Liver/prevention & control , Fatty Liver/pathology , Fatty Liver/etiology , Lipid Metabolism/drug effects
16.
Fish Shellfish Immunol ; 152: 109776, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39019128

ABSTRACT

Type I IFNs are a subset of cytokines exerting their antiviral effects mainly through the JAK-STAT signalling. Immunogenetic studies have shown that fish possess key components of IFN-JAK-STAT cascade, but the information about the distinct responses of STAT1 and STAT2 to different IFNs is rather limited in fish. Here, we identified and cloned STAT1 and STAT2 genes (named as On-STAT1 and On-STAT2) from tilapia, Oreochromis niloticus. On-STAT1 and On-STAT2 genes were detected in all orangs/tissues examined, and were rapidly induced in spleen, head kidney, and liver following the stimulation of poly(I:C). In addition, the stimulation of poly(I:C), poly(A:T), and different subgroups of recombinant IFNs could induce the expression of On-STAT1 and On-STAT2 in TA-02 cells with distinct induction levels. Importantly, On-STAT2 was rapidly phosphorylated by all three subgroups of IFNs, but the phosphorylation of On-STAT1 was only observed in IFNc- and IFNh-treated TA-02 cells, reflecting the distinct activation of STAT by different subgroups of fish IFNs. The present results thus contribute to better understanding of the JAK-STAT signalling mediated by different subgroups of IFNs in fish.


Subject(s)
Fish Proteins , STAT1 Transcription Factor , STAT2 Transcription Factor , Animals , STAT2 Transcription Factor/genetics , STAT2 Transcription Factor/metabolism , Fish Proteins/genetics , Fish Proteins/immunology , Fish Proteins/metabolism , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolism , Phosphorylation , Interferon Type I/genetics , Interferon Type I/immunology , Cichlids/immunology , Cichlids/genetics , Amino Acid Sequence , Gene Expression Regulation/immunology , Gene Expression Regulation/drug effects , Phylogeny , Poly I-C/pharmacology , Sequence Alignment/veterinary , Signal Transduction/drug effects
17.
BMC Psychiatry ; 24(1): 491, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977949

ABSTRACT

BACKGROUND: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. CASE PRESENTATION: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. CONCLUSIONS: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.


Subject(s)
Antipsychotic Agents , Bipolar Disorder , Exanthema , Lurasidone Hydrochloride , Humans , Lurasidone Hydrochloride/adverse effects , Lurasidone Hydrochloride/therapeutic use , Male , Bipolar Disorder/drug therapy , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Middle Aged , Exanthema/chemically induced , East Asian People
19.
Sci Rep ; 14(1): 17556, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080365

ABSTRACT

Studying the spatial and temporal changes of grassland soil organic carbon (SOC) is helpful in promote the management of regional ecosystem carbon sinks. Grazing is one of the main ways of rational utilization of grassland. Different grazing intensities will affect the change of SOC density. Under different grazing intensity and management measures in Zhangye grassland, this study uses the parameter localized CENTURY model to simulate the temporal and spatial variations of SOC density from 1970 to 2022. The results showed that long-term light grazing reduced the average SOC by 195.114 g·m-2 and 1.91%. Moderate and severe grazing, respectively, for a long time made the total SOC density loss of 5.21% and 17.69%. In a short period, mild and moderate grazing reduced total SOC first and then increased it. Under light grazing, total SOC density appeared higher relative changes in the southeast, and lower in the northwest and central. There was no significant difference in the relative changes of total SOC between steppe and desert grasslands under light grazing. The decrease range of steppe was gradually greater than that in desert grassland. Since different management measures were implemented in some sampling sites in 2017, we divided the study period into two periods, 1970-2016 and 2017-2022. The implementation of degraded grassland improvement, fallow grazing, and rotational grazing would increase the total SOC density and mild SOC density, rotational grazing > degraded grassland improvement > rest grazing. Rotational grazing and the improvement of degraded grassland increased the density of active and inert SOC, while resting grazing decreased the density of SOC.

20.
J Hazard Mater ; 476: 135140, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39002486

ABSTRACT

Microbially induced carbonate precipitation (MICP) is emerging as a favorable alternative to traditional soil remediation techniques for heavy metals, primarily due to its environmental friendliness. However, a significant challenge in using MICP for farmland is not only to immobilize heavy metals but also to concurrently enhance soil fertility. This study explores the innovative combination of artificial humic acid (A-HA), biochar (BC), and Sporosarcina pasteurii (S. pasteurii) to mitigate the bioavailability of cadmium (Cd) in contaminated agricultural soils through MICP. X-ray diffraction (XRD) and scanning electron microscope (SEM) analyses revealed that the integration of BC and A-HA significantly enhances Cd immobilization efficiency by co-precipitating with CaCO3. Moreover, this treatment also improved soil fertility and ecological functions, as evidenced by increases in total nitrogen (TN, 9.0-78.2 %), alkaline hydrolysis nitrogen (AN, 259.7-635.5 %), soil organic matter (SOM, 18.1-27.9 %), total organic carbon (TOC, 43.8-48.8 %), dissolved organic carbon (DOC, 36.0-88.4 %) and available potassium (AK, 176.2-193.3 %). Additionally, the relative abundance of dominant phyla such as Proteobacteria and Firmicutes significantly increased with the introduction of BC and A-HA in MICP. Consequently, the integration of BC and A-HA with MICP offers a promising solution for remediating Cd-contaminated agricultural soil and synergistically enhancing soil fertility.


Subject(s)
Cadmium , Calcium Carbonate , Charcoal , Humic Substances , Soil Pollutants , Soil , Sporosarcina , Cadmium/chemistry , Calcium Carbonate/chemistry , Charcoal/chemistry , Soil Pollutants/chemistry , Sporosarcina/metabolism , Soil/chemistry , Soil Microbiology , Chemical Precipitation , Environmental Restoration and Remediation/methods
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