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1.
BMC Genomics ; 25(1): 164, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38336605

ABSTRACT

BACKGROUND: Guizhou black goat is one of the indigenous black goat breeds in the southwest region of Guizhou, China, which is an ordinary goat for mutton production. They are characterized by moderate body size, black coat, favorite meat quality with tender meat and lower odor, and tolerance for cold and crude feed. However, little is known about the genetic characteristics or variations underlying their important economic traits. RESULTS: Here, we resequenced the whole genome of Guizhou black goat from 30 unrelated individuals breeding in the five core farms. A total of 9,835,610 SNPs were detected, and 2,178,818 SNPs were identified specifically in this breed. The population structure analysis revealed that Guizhou black goat shared a common ancestry with Shaanbei white cashmere goat (0.146), Yunshang black goat (0.103), Iran indigenous goat (0.054), and Moroccan goat (0.002). However, Guizhou black goat showed relatively higher genetic diversity and a lower level of linkage disequilibrium than the other seven goat breeds by the analysis of the nucleotide diversity, linkage disequilibrium decay, and runs of homozygosity. Based on FST and θπ values, we identified 645, 813, and 804 selected regions between Guizhou black goat and Yunshang black goat, Iran indigenous goat, and cashmere goats. Combined with the results of XP-EHH, there were 286, 322, and 359 candidate genes, respectively. Functional annotation analysis revealed that these genes are potentially responsible for the immune response (e.g., CD28, CD274, IL1A, TLR2, and SLC25A31), humility-cold resistance (e.g., HBEGF, SOSTDC1, ARNT, COL4A1/2, and EP300), meat quality traits (e.g., CHUK, GAB2, PLAAT3, and EP300), growth (e.g., GAB2, DPYD, and CSF1), fertility (e.g., METTL15 and MEI1), and visual function (e.g., PANK2 and NMNAT2) in Guizhou black goat. CONCLUSION: Our results indicated that Guizhou black goat had a high level of genomic diversity and a low level of linkage disequilibrium in the whole genome. Selection signatures were detected in the genomic regions that were mainly related to growth and development, meat quality, reproduction, disease resistance, and humidity-cold resistance in Guizhou black goat. These results would provide a basis for further resource protection and breeding improvement of this very local breed.


Subject(s)
Goats , Selection, Genetic , Humans , Animals , Goats/genetics , Genome , Genomics , Phenotype , Polymorphism, Single Nucleotide , Adaptor Proteins, Signal Transducing/genetics
2.
Respir Res ; 25(1): 16, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178098

ABSTRACT

BACKGROUND: Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional. METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method. RESULTS: In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. CONCLUSION: Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.


Subject(s)
Gastrointestinal Microbiome , Tuberculosis, Pulmonary , Tuberculosis , Humans , Gastrointestinal Microbiome/genetics , Mendelian Randomization Analysis , Genome-Wide Association Study , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/genetics
3.
BMC Public Health ; 24(1): 1333, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760740

ABSTRACT

BACKGROUND: Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. METHOD: Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. RESULTS: A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507-0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116-1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425-0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135-0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322-0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells < 200 cells/µL subgroup, temperature, precipitation, and PM10 had a significant hysteretic effect on TB incidence, while temperature and precipitation had a significant cumulative lag effect. However, these effects were not observed in the CD4(+) T cells ≥ 200 cells/µL subgroup. CONCLUSION: For PLWHA in subtropical Guangxi, temperature and precipitation had a significant cumulative effect on TB incidence among PLWHA, while air pollutants had little effect. Moreover, the influence of meteorological factors on the incidence of TB also depends on the immune status of PLWHA.


Subject(s)
Air Pollutants , HIV Infections , Meteorological Concepts , Tuberculosis , Humans , China/epidemiology , Incidence , Tuberculosis/epidemiology , Air Pollutants/analysis , Air Pollutants/adverse effects , HIV Infections/epidemiology , Female , Male , Adult , Acquired Immunodeficiency Syndrome/epidemiology , Middle Aged
4.
Behav Pharmacol ; 34(6): 350-361, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37462148

ABSTRACT

BACKGROUND: Psychoactive drugs produce interoceptive stimuli that can guide appropriate behaviors by initiating or inhibiting responding. OBJECTIVE: The current study investigated whether an interoceptive morphine state produces similar patterns of serial feature positive (FP) and feature negative (FN) discrimination learning under comparable conditions in a taste avoidance design. METHODS: Male Sprague-Dawley rats were trained under 10 cycles of FP or FN discrimination. In the FP task, morphine (10 mg/kg, IP) signaled that a saccharin solution was followed by LiCl (1.2 mEq, IP), while the vehicle (saline) signaled that the LiCl was withheld. In the FN task, the contingency was reversed. RESULTS: The FP-trained rats acquired the discrimination after three training cycles, consuming significantly less saccharin on morphine, than on vehicle, sessions ( P  < 0.05). The FN-trained rats acquired the discrimination after six training cycles, consuming more on morphine than on vehicle sessions ( P < 0.05). However, FN-trained rats never recovered saccharin consumption to baseline levels and 40% of the rats continued to avoid saccharin (consuming 0 ml) on morphine sessions. Control rats that never received LiCl consumed high levels of saccharin on morphine and vehicle sessions, indicating that morphine did not produce unconditioned suppression of saccharin consumption. CONCLUSION: The difficulty to acquire FN discrimination might reflect the limitations of learning about safety contingencies in the taste avoidance design. The rapidity of FP learning when a drug state signals an aversive contingency may have implications for the general role of interoceptive stimuli in the control of behavior.


Subject(s)
Discrimination Learning , Taste , Rats , Male , Animals , Rats, Sprague-Dawley , Avoidance Learning , Saccharin , Morphine/pharmacology
5.
Avian Pathol ; 52(1): 51-61, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36200987

ABSTRACT

Eimeria tenella (E. tenella), an important intestinal parasite of chicken caeca, causes coccidiosis and brings large economic losses to the poultry industry annually. Gut microorganismal alterations directly affect the health of the body. To understand how E. tenella affects its host, we analysed the changes in caecal microbial diversity and the physiological and morphological changes during the peak of oocyst shedding. Infected and healthy chickens differed significantly in caecal pathology and blood indicators. At the genus level, the abundances of Faecalibacterium, Clostridium, Lachnoclostridium, Gemmiger, Flavonifractor, Pseudoflavonifractor and Oscillibacter were significantly decreased in the infected samples, whereas Escherichia, Nocardia and Chlamydia were significantly increased. Functional gene pathways related to replication, recombination and repair, and transcription were significantly decreased, and functional genes related to metabolism were highly significantly reduced in the infected samples. Furthermore, in the infected samples, E. tenella reduced the haemoglobin levels and red blood cell counts, greatly reduced the beneficial bacteria and increased the potentially pathogenic bacteria. This study provides a research basis for further understanding the pathogenic mechanisms of E. tenella and provides insight for potential new drug development.RESEARCH HIGHLIGHTS First simultaneous description of caecal microbiota and physiological indicators during E. tenella infection.Metagenomics used to explore functional properties of chicken caecal microbiota during E. tenella infection.Caecal microbial compositions and functional genes altered significantly after infection.Blood indicators and caecal morphology were significantly altered in the infected group.


Subject(s)
Coccidiosis , Eimeria tenella , Microbiota , Poultry Diseases , Animals , Eimeria tenella/genetics , Chickens/microbiology , Poultry Diseases/microbiology , Oocysts/physiology , Coccidiosis/parasitology , Coccidiosis/veterinary
6.
Clin Oral Investig ; 27(8): 4493-4501, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37219608

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the clinical outcomes of diode laser as an adjunct to nonsurgical periodontal therapy (NSPT) for residual periodontal pockets in mandibular second molars. MATERIALS AND METHODS: Sixty-seven mandibular second molars (154 residual periodontal pockets) were recruited into the study and randomly assigned to the Laser + NSPT group and the NSPT group. The Laser + NSPT group underwent NSPT adjunct with diode laser radiation (wavelength: 810 nm, power: 1.5 W, 40 s maximum), while the NSPT group underwent nonsurgical periodontal therapy alone. Clinical parameters were measured at baseline (T0) and 4(T1), 12(T2), and 24(T3), weeks after treatment. RESULTS: Periodontal pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP) in both groups showed significant improvements at the end of study compared to baseline. The reductions of PPD, CAL, and BOP in the Laser + NSPT group were significantly greater than NSPT group. At T3, the Laser + NSPT group had a mean PPD of 3.06 ± 0.86 mm, CAL of 2.58 ± 0.94 mm and BOP of 15.49%, while the NSPT group had a mean PPD of 4.46 ± 1.57 mm, CAL of 3.03 ± 1.25 mm and BOP of 64.29%. CONCLUSIONS: The diode laser as an adjunct to nonsurgical periodontal therapy may contribute to clinical outcomes for residual periodontal pockets. However, the approach may cause reduction of keratinized tissue width. TRIAL REGISTRATION NUMBER: This study was registered in the Chinese Clinical Trial Registry ChiCTR2200061194. CLINICAL RELEVANCE: Diode laser as an adjunct to nonsurgical periodontal therapy may contribute to the clinical outcomes for residual periodontal pockets in mandibular second molars.


Subject(s)
Chronic Periodontitis , Laser Therapy , Low-Level Light Therapy , Humans , Chronic Periodontitis/radiotherapy , Periodontal Pocket/radiotherapy , Lasers, Semiconductor/therapeutic use , Dental Scaling
7.
Int J Mol Sci ; 24(4)2023 Feb 18.
Article in English | MEDLINE | ID: mdl-36835542

ABSTRACT

Skeletal muscle is the most abundant tissue in mammals, and myogenesis and differentiation require a series of regulatory factors such as microRNAs (miRNAs). In this study, we found that miR-103-3p was highly expressed in the skeletal muscle of mice, and the effects of miR-103-3p on skeletal muscle development were explored using myoblast C2C12 cells as a model. The results showed that miR-103-3p could significantly reduce myotube formation and restrain the differentiation of C2C12 cells. Additionally, miR-103-3p obviously prevented the production of autolysosomes and inhibited the autophagy of C2C12 cells. Moreover, bioinformatics prediction and dual-luciferase reporter assays confirmed that miR-103-3p could directly target the microtubule-associated protein 4 (MAP4) gene. The effects of MAP4 on the differentiation and autophagy of myoblasts were then elucidated. MAP4 promoted both the differentiation and autophagy of C2C12 cells, which was contrary to the role of miR-103-3p. Further research revealed that MAP4 colocalized with LC3 in C2C12 cell cytoplasm, and the immunoprecipitation assay showed that MAP4 interacted with autophagy marker LC3 to regulate the autophagy of C2C12 cells. Overall, these results indicated that miR-103-3p regulated the differentiation and autophagy of myoblasts by targeting MAP4. These findings enrich the understanding of the regulatory network of miRNAs involved in the myogenesis of skeletal muscle.


Subject(s)
Cell Differentiation , MicroRNAs , Microtubule-Associated Proteins , Myoblasts , Animals , Mice , Cell Differentiation/genetics , Cell Line , Cell Proliferation/genetics , MicroRNAs/genetics , Microtubule-Associated Proteins/metabolism , Muscle Development , Myoblasts/cytology
8.
Pharmacol Res ; 175: 106040, 2022 01.
Article in English | MEDLINE | ID: mdl-34954029

ABSTRACT

Inducing homologous recombination (HR) deficiency is a promising strategy to broaden the indication of PARP1/2 inhibitors in pancreatic cancer treatment. In addition to inhibition kinases, repression of the transcriptional function of FOXM1 has been reported to inhibit HR-mediated DNA repair. We found that FOXM1 inhibitor FDI-6 and PARP1/2 inhibitor Olaparib synergistically inhibited the malignant growth of pancreatic cancer cells in vitro and in vivo. The results of bioinformatic analysis and mechanistic study showed that FOXM1 directly interacted with PARP1. Olaparib induced the feedback overexpression of PARP1/2, FOXM1, CDC25A, CCND1, CDK1, CCNA2, CCNB1, CDC25B, BRCA1/2 and Rad51 to promote the acceleration of cell mitosis and recovery of DNA repair, which caused the generation of adaptive resistance. FDI-6 reversed Olaparib-induced adaptive resistance and inhibited cell cycle progression and DNA damage repair by repressing the expression of FOXM1, PARP1/2, BUB1, CDC25A, BRCA1 and other genes-involved in cell cycle control and DNA damage repair. We believe that targeting FOXM1 and PARP1/2 is a promising combination therapy for pancreatic cancer without HR deficiency.


Subject(s)
Forkhead Box Protein M1/antagonists & inhibitors , Pancreatic Neoplasms/drug therapy , Phthalazines/therapeutic use , Piperazines/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Pyridines/therapeutic use , Thiophenes/therapeutic use , Animals , Apoptosis/drug effects , BRCA1 Protein/genetics , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Comet Assay , Female , Forkhead Box Protein M1/genetics , Forkhead Box Protein M1/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice, Inbred BALB C , Mice, Nude , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Phthalazines/pharmacology , Piperazines/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/genetics , Pyridines/pharmacology , Signal Transduction/drug effects , Thiophenes/pharmacology , cdc25 Phosphatases/genetics
9.
Molecules ; 27(19)2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36235174

ABSTRACT

Protein arginine methyltransferases 5 (PRMT5) is a clinically promising epigenetic target that is upregulated in a variety of tumors. Currently, there are several PRMT5 inhibitors under preclinical or clinical development, however the established clinical inhibitors show favorable toxicity. Thus, it remains an unmet need to discover novel and structurally diverse PRMT5 inhibitors with characterized therapeutic utility. Herein, a series of tetrahydroisoquinoline (THIQ) derivatives were designed and synthesized as PRMT5 inhibitors using GSK-3326595 as the lead compound. Among them, compound 20 (IC50: 4.2 nM) exhibits more potent PRMT5 inhibitory activity than GSK-3326595 (IC50: 9.2 nM). In addition, compound 20 shows high anti-proliferative effects on MV-4-11 and MDA-MB-468 tumor cells and low cytotoxicity on AML-12 hepatocytes. Furthermore, compound 20 possesses acceptable pharmacokinetic profiles and displays considerable in vivo antitumor efficacy in a MV-4-11 xenograft model. Taken together, compound 20 is an antitumor compound worthy of further study.


Subject(s)
Neoplasms , Tetrahydroisoquinolines , Arginine/pharmacology , Cell Line, Tumor , Cell Proliferation , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Humans , Neoplasms/drug therapy , Protein-Arginine N-Methyltransferases , Tetrahydroisoquinolines/pharmacology
10.
Acta Cardiol Sin ; 38(6): 691-699, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36440241

ABSTRACT

Background: Di(2-ethylhexyl) phthalate (DEHP) may produce toxicity, posing a risk to human health. Medical devices composed of DEHP are frequently used in catheterization, but few studies have investigated DEHP exposure during catheterization. The aim of this prospective series was to characterize the exposure pattern of DEHP during catheterization. Methods: We enrolled 16 patients with congenital heart disease undergoing catheterization. Collection of urine was done to measure DEHP metabolites on hospitalization, before catheterization, after catheterization, and at discharge. The following DEHP metabolites were measured: mono-(2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and the ratio of MEHP to overall metabolites (MEHP%) was determined. DEHP exposure from polyvinyl chloride (PVC)-containing catheter and infusion systems were recorded in detail. Differences in DEHP levels before and after catheterization were analyzed. Results: Urinary levels of MEHP, MEHHP, and MEOHP significantly decreased from before catheterization to after catheterization (all p < 0.01), but did not change significantly from initial hospitalization to before catheterization. Urinary MEHP% significantly decreased from initial hospitalization to before catheterization (p < 0.001), then increased after catheterization (p < 0.001), and decreased gradually at discharge (p = 0.03). Urinary MEHP% after catheterization and at discharge was significantly positively related to the duration of using PVC-containing catheter systems. There was a significant positive correlation between urinary MEHP% and the duration of using PVC-containing infusion system before catheterization, and a borderline significant correlation at both post-catheterization time slots. Conclusions: Our results demonstrated that urinary MEHP% may be a potential biomarker of DEHP contamination from the use of PVC-containing catheters or infusion systems.

11.
Environ Res ; 196: 110934, 2021 05.
Article in English | MEDLINE | ID: mdl-33647294

ABSTRACT

Estuaries are important in terms of biodiversity, biogeochemical function, and ecological balance due to their intense land-sea interactions. The sustainability of estuarine ecosystem function relies on a good understanding of the ecological processes related to microbial communities. However, microbial community assembly in such ecosystems is still not well understood. Here, based on 16S rRNA sequencing, we investigated the bacterioplankton community structure in the Pearl River Estuarine system during the wet and dry seasons. Results showed that there were significant seasonal and spatial variations in the bacterioplankton communities of the estuary, with seasonal variations being more remarkable. Multiple bacterioplankton with different abundances in the wet and dry seasons were observed, e.g., the class Actinobacteria and Oxyphotobacteria were enriched in the wet season, whereas Alphaproteobacteria and Saccharimonadia were more abundant in the dry season. Both variation partitioning and null model analysis revealed that environmental filtering dominated the bacterioplankton community assembly in the Pearl River Estuary. Water physical properties (e.g., salinity and temperature), nutrient content (e.g., nitrate), and upstream land use (e.g., urban land cover) together determined the distribution of the bacterioplankton composition in this highly urbanized estuarine ecosystem. These findings would help improve our understanding of the bacterioplankton communities in estuarine ecosystems and provide a theoretical foundation for estuarine ecological health management.


Subject(s)
Ecosystem , Estuaries , Aquatic Organisms , Biodiversity , RNA, Ribosomal, 16S/genetics , Rivers , Seasons
12.
Molecules ; 26(11)2021 Jun 02.
Article in English | MEDLINE | ID: mdl-34199417

ABSTRACT

Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study.


Subject(s)
B7-H1 Antigen/metabolism , Programmed Cell Death 1 Receptor/metabolism , Small Molecule Libraries/pharmacology , T-Lymphocytes/cytology , B7-H1 Antigen/chemistry , Cell Line , Crystallography, X-Ray , Humans , Interferon-gamma/metabolism , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Primary Cell Culture , Programmed Cell Death 1 Receptor/chemistry , Protein Binding/drug effects , Small Molecule Libraries/chemistry , Structure-Activity Relationship , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism
13.
Article in English | MEDLINE | ID: mdl-29797367

ABSTRACT

Copy number variation (CNV) is a major proportion of genetic variation, which changes the gene structure and dosage and affects gene expression and function. To validate the presence and the function of CNV in pig, we used real-time quantitative polymerase chain reaction (qPCR) method to validate a 496 kb CNV region comprising MTHFSD gene on chromosome 6 of Xiang pig detected by single nucleotide polymorphism (SNP) array. Then we investigated the distribution of the MTHFSD CNV in a total of 545 pigs in four breeds. About 46.2% and 32.7% individuals in the four pig breeds were detected to be types of loss and gain of MTHFSD locus. The relative copy numbers of MTHFSD gene showed the largest variation range (0-55 copies) in the Xiang pig population. The copy numbers of MTHFSD gene presented the positive correlations with the transcript level of MTHFSD gene in adult ovaries. Statistical analysis indicated that CNVs of MTHFSD gene was significantly changed the litter size traits of Xiang pigs, and the individuals with CNV gain showed more litter size than the CNV loss pigs. We have reasons to believe that the MTHFSD as RNA-binding protein play an important role in pig reproduction as a result of regulating MTHFS mRNA metabolism.

14.
Pharmacol Biochem Behav ; 244: 173848, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39137873

ABSTRACT

Drug discrimination research has generated rich evidence for the capacity of interoceptive drug stimuli to control behavior by serving as discriminative cues. Owing to its neuropharmacological specificity, drug discrimination learning has been widely used to characterize the stimulus effects and neuropharmacological underpinning of drugs. Apart from such utility, discriminative drug stimuli may help regulate drug use by disambiguating conditioned associations and post-intake outcomes. First, this review summarizes the evidence supporting interoceptive regulation of drug intake from the literature of exteroceptive discriminative control of drug-related behavior, effects of drug priming, and self-titration of drug intake. Second, an overview of interoceptive control of reward-seeking and the animal model of discriminated goal-tracking is provided to illustrate interoceptive stimulus control of the initiation and patterning of drug intake. Third, we highlight the importance of interoceptive control of aversion-avoidance in the termination of drug-use episodes and describe the animal model of discriminated taste avoidance that supports such a position. In bridging these discriminative functions of drug stimuli, we propose that interoceptive drug stimuli help regulate intake by disambiguating whether intake will be rewarding, nonrewarding, or aversive. The reflection and discussion on current theoretical formulations of interoceptive control of drug intake may further scientific advances to improve animal models to study the mechanisms by which interoceptive stimuli regulate drug intake, as well as how alterations of interoceptive processes may contribute to the transition to dysregulated drug use.


Subject(s)
Discrimination Learning , Interoception , Animals , Discrimination Learning/drug effects , Humans , Interoception/drug effects , Interoception/physiology , Reward , Substance-Related Disorders/psychology , Avoidance Learning/drug effects
15.
Virulence ; 15(1): 2382762, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39092797

ABSTRACT

African swine fever (ASF) is a rapidly fatal viral haemorrhagic fever in Chinese domestic pigs. Although very high mortality is observed in pig farms after an ASF outbreak, clinically healthy and antibody-positive pigs are found in those farms, and viral detection is rare from these pigs. The ability of pigs to resist ASF viral infection may be modulated by host genetic variations. However, the genetic basis of the resistance of domestic pigs against ASF remains unclear. We generated a comprehensive set of structural variations (SVs) in a Chinese indigenous Xiang pig with ASF-resistant (Xiang-R) and ASF-susceptible (Xiang-S) phenotypes using whole-genome resequencing method. A total of 53,589 nonredundant SVs were identified, with an average of 25,656 SVs per individual in the Xiang pig genome, including insertion, deletion, inversion and duplication variations. The Xiang-R group harboured more SVs than the Xiang-S group. The F-statistics (FST) was carried out to reveal genetic differences between two populations using the resequencing data at each SV locus. We identified 2,414 population-stratified SVs and annotated 1,152 Ensembl genes (including 986 protein-coding genes), in which 1,326 SVs might disturb the structure and expression of the Ensembl genes. Those protein-coding genes were mainly enriched in the Wnt, Hippo, and calcium signalling pathways. Other important pathways associated with the ASF viral infection were also identified, such as the endocytosis, apoptosis, focal adhesion, Fc gamma R-mediated phagocytosis, junction, NOD-like receptor, PI3K-Akt, and c-type lectin receptor signalling pathways. Finally, we identified 135 candidate adaptive genes overlapping 166 SVs that were involved in the virus entry and virus-host cell interactions. The fact that some of population-stratified SVs regions detected as selective sweep signals gave another support for the genetic variations affecting pig resistance against ASF. The research indicates that SVs play an important role in the evolutionary processes of Xiang pig adaptation to ASF infection.


Subject(s)
African Swine Fever Virus , African Swine Fever , Animals , African Swine Fever/virology , African Swine Fever/genetics , Swine , African Swine Fever Virus/genetics , Disease Resistance/genetics , Genetic Variation , Genome/genetics , Whole Genome Sequencing , Genomic Structural Variation , China , Sus scrofa
16.
PLoS One ; 19(8): e0309670, 2024.
Article in English | MEDLINE | ID: mdl-39208308

ABSTRACT

The antennal sensilla play an important role in many behavioral activities of insects. The fungivorous beetle Triplax ainonia Lewis (Erotylidae) is an important pest which prefers to feed on Pleurotus mushrooms. In order to clarify the types, number, and distribution of the antennal sensilla of male and female T. ainonia, scanning electron microscopy was used. The results showed that there were five sensillum types on the antennae of adults male and female, including Böhm's bristles (BB), sensilla chaetica (three subtypes: SC 1, SC 2, and SC 3), sensilla basiconica (three subtypes: SB 1, SB 2, and SB 3), sensilla trichodea (ST), and sensilla styloconica (SS). Among all the sensilla, the number of SB 2 was the most abundant in both sexes. We found that there was no sexually dimorphic in the sensillum types, but there were differences in the number, lengths, and diameters of some sensilla between males and females. Based on the information of the morphology and distribution of the sensilla, the potential functions of the antennal sensilla of T. ainonia adults were discussed. The results of this study provide a basis for further study on the behavioral ecology and electrophysiology of the fungivore beetles of the Erotylidae.


Subject(s)
Arthropod Antennae , Coleoptera , Sensilla , Animals , Coleoptera/physiology , Coleoptera/anatomy & histology , Coleoptera/ultrastructure , Male , Female , Sensilla/physiology , Sensilla/ultrastructure , Sensilla/anatomy & histology , Arthropod Antennae/physiology , Arthropod Antennae/ultrastructure , Arthropod Antennae/anatomy & histology , Microscopy, Electron, Scanning
17.
Sci Total Environ ; 930: 172561, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38641104

ABSTRACT

Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.


Subject(s)
Salinity , Animals , Stress, Physiological , Bivalvia/physiology , Salt Stress
18.
Front Nutr ; 11: 1359697, 2024.
Article in English | MEDLINE | ID: mdl-39161911

ABSTRACT

Background: Previous studies showed the conflicting associations between circulating micronutrient levels and systemic lupus erythematosus (SLE). Therefore, we aimed to clarify the causal association between circulating micronutrient levels and the risk of SLE by two-sample Mendelian randomization (MR) analysis. Methods: 56 single nucleotide polymorphisms (SNPs) significantly associated with 14 circulating micronutrients (vitamin A, B6, B9, B12, C, D and E, phosphorus, calcium, magnesium, copper, iron, zinc, and selenium) in published genome-wide association studies (GWAS) were used as instrumental variables (IVs). And summary statistics related to SLE were obtained from the IEU OpenGWAS database. We used the MR Steiger test to estimate the possible causal direction between circulating micronutrients and SLE. In the MR analysis, inverse variance weighting (IVW) method and the Wald ratio was as the main methods., Moreover, the MR-Pleiotropy residuals and outliers method (MR-PRESSO), Cochrane's Q-test, MR-Egger intercept method and leave-one-out analyses were applied as sensitivity analyses. Additionally, we conducted a retrospective analysis involving the 20,045 participants from the Third National Health and Nutritional Examination Survey (NHANES III). Weight variables were provided in the NHANES data files. Univariate and multivariate logistic regression analyses were performed to determine the associations between circulating micronutrients and SLE. Results: The MR estimates obtained from the IVW method revealed potential negative correlations between circulating calcium (OR: 0.06, 95% CI: 0.01-0.49, P = 0.009), iron levels (OR: 0.63, 95% CI: 0.43-0.92, P = 0.016) and the risk of SLE. The results remained robust, even under various pairs of sensitivity analyses. Our retrospective analysis demonstrated that the levels of vitamin D, serum total calcium, and serum iron were significantly lower in SLE patients (N = 40) when compared to the control group (N = 20,005). Multivariate logistic regression analysis further established that increased levels of vitamin D and serum total calcium served as protective factors against SLE. Conclusion: Our results provided genetic evidence supporting the potential protective role of increasing circulating calcium in the risk of SLE. Maintaining adequate levels of calcium may help reduce the risk of SLE.

19.
Sci Rep ; 14(1): 19695, 2024 08 24.
Article in English | MEDLINE | ID: mdl-39181933

ABSTRACT

Copy number variation (CNV) tends to occur in genetically enriched regions and is likely associated with a number of complex diseases such as skin aging. In this study, we investigated the genome-wide CNVs in 20 wrinkled skin cases (WSC) of Xiang pigs and 63 controls, and identified 7893 copy number variable regions (CNVRs). We estimated the F-statistic (Fst) at each locus and identified that 93 case-controls stratified CNVRs (Fst > = 0.15) overlapped with 87 known genes. Functional enrichment analysis showed that most of these genes were predominantly enriched in pathways and terms related to the extracellular matrix. Finally, we found that some CNVs were predicted to have high effects on genes such as VCAN, TIMP1 and FOXO1 through transcriptional amplification, transcript ablation and so on. Most of the genes overlapped with those CNVRs have been reported to be related to aging in human or animals. The copy numbers presented the positive correlations with the transcript level of the genes in skins between the cases and controls. Our results suggested that those 22 CNVRs, including 19 CNV losses and 3 CNV gains, were putatively associated with the skin wrinkle of Xiang pigs.


Subject(s)
DNA Copy Number Variations , Skin Aging , Animals , Swine/genetics , Skin Aging/genetics , Genome-Wide Association Study , Case-Control Studies , Skin/pathology , Skin/metabolism
20.
Sci Rep ; 14(1): 8486, 2024 04 11.
Article in English | MEDLINE | ID: mdl-38605105

ABSTRACT

In this study, we compared the transcriptome of longissimus dorsi muscle between Guizhou Xiang pigs (XP) and Western commercial Large White pigs (LW), which show diffirent meat quality between them. In terms of meat quality traits, the pH 45 min, color score, backfat thickness, and intramuscular fat (IMF) content were higher in Xiang pigs than in Large White pigs (P < 0.01), while the drip loss, lean meat percentage, shear force, and longissimus dorsi muscle area of Xiang pigs were lower than that of Large White pigs (P < 0.01). Nutrients such as monounsaturated fatty acid (MUFA), total amino acids (TAA), delicious amino acids (DAA) and essential amino acids (EAA) in Xiang pigs were higher than that in Large White pigs, and the proportion of polyunsaturated fatty acid (PUFA) of Xiang pigs was significantly lower than Large White pigs (P < 0.01). Transcriptome analysis identified 163 up-regulated genes and 88 genes down-regulated in Xiang pigs longissimus dorsi muscle. Combined with the correlation analysis and quantitative trait locis (QTLs) affecting meat quality, a total of 227 DEGs were screened to be significantly associated with meat quality values. Enrichment analysis indicated that numerous members of genes were gathered in muscle development, adipogenesis, amino acid metabolism, fatty acid metabolism and synthesis. Of those, 29 genes were identified to be hub genes that might be related with the meat quality of Xiang pig, such as MYOD1, ACTB, ASNS, FOXO1, ARG2, SLC2A4, PLIN2, and SCD. Thus, we screened and identified the potential functional genes for the formation of meat quality in Xiang pigs, which provides a corresponding theoretical basis for the study of the molecular regulatory mechanism of pork quality and the improvement of pork quality.


Subject(s)
Muscle, Skeletal , Transcriptome , Swine/genetics , Animals , Muscle, Skeletal/metabolism , Gene Expression Profiling , Meat , Amino Acids/metabolism , China
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