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1.
J Hazard Mater ; 471: 134337, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38640674

RESUMEN

BACKGROUND: Hexafluoropropylene oxide trimer acid (HFPO-TA), a perfluorooctanoic acid (PFOA) substitute, exhibited strong affinity and capability to activate peroxisome proliferator activated receptor gamma (PPARγ), a lipid metabolism regulator, suggesting potential to induce metabolic toxicities. METHODS: Fertile chicken eggs were exposed to 0, 0.5, 1 or 2 mg/kg (egg weight) HFPO-TA and incubated until hatch. Serum from 0- and 3- month-old chickens were subjected to liquid chromatography ultra-high resolution mass spectrometry for HFPO-TA concentration, while liver, pancreas and adipose tissue samples were collected for histopathological assessments. In ovo PPARγ reporter and silencing system were established with lentivirus microinjection. qRT-PCR and immunohistochemistry were utilized to evaluate the expression levels of PPARγ downstream genes. RESULTS: In 3-month-old animals developmentally exposed to HFPO-TA, adipose tissue hyperplasia, hepatic steatosis, pancreas islet hypertrophy and elevated serum free fatty acid / insulin levels were observed. Results of reporter assay and qRT-PCR indicated HFPO-TA-mediated PPARγ transactivation in chicken embryo. Silencing of PPARγ alleviated HFPO-TA-induced changes, while PPARγ agonist rosiglitazone mimicked HFPO-TA-induced effects. qRT-PCR and immunohistochemistry revealed that FASN and GPD1 were upregulated following developmental exposure to HFPO-TA in 3-month-old animals. CONCLUSIONS: Developmental exposure to HFPO-TA induced persistent metabolic toxicities in chickens, in which PPARγ played a central role.


Asunto(s)
Fluorocarburos , PPAR gamma , Animales , PPAR gamma/genética , PPAR gamma/metabolismo , Fluorocarburos/toxicidad , Embrión de Pollo , Hígado/efectos de los fármacos , Hígado/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Pollos , Páncreas/efectos de los fármacos , Páncreas/metabolismo
2.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38612614

RESUMEN

Revealing the interaction mechanisms between anticancer drugs and target DNA molecules at the single-molecule level is a hot research topic in the interdisciplinary fields of biophysical chemistry and pharmaceutical engineering. When fluorescence imaging technology is employed to carry out this kind of research, a knotty problem due to fluorescent dye molecules and drug molecules acting on a DNA molecule simultaneously is encountered. In this paper, based on self-made novel solid active substrates NpAA/(ZnO-ZnCl2)/AuNPs, we use a surface-enhanced Raman spectroscopy method, inverted fluorescence microscope technology, and a molecular docking method to investigate the action of the fluorescent dye YOYO-1 and the drug DOX on calf thymus DNA (ctDNA) molecules and the influencing effects and competitive relationships of YOYO-1 on the binding properties of the ctDNA-DOX complex. The interaction sites and modes of action between the YOYO-1 and the ctDNA-DOX complex are systematically examined, and the DOX with the ctDNA-YOYO-1 are compared, and the impact of YOYO-1 on the stability of the ctDNA-DOX complex and the competitive mechanism between DOX and YOYO-1 acting with DNA molecules are elucidated. This study has helpful experimental guidance and a theoretical foundation to expound the mechanism of interaction between drugs and biomolecules at the single-molecule level.


Asunto(s)
Benzoxazoles , Colorantes Fluorescentes , Nanopartículas del Metal , Compuestos de Quinolinio , Oro , Simulación del Acoplamiento Molecular , Espectrometría Raman , ADN
3.
Orthop Surg ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658320

RESUMEN

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.

4.
Food Chem Toxicol ; 187: 114594, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38485042

RESUMEN

Trichloroethylene (TCE), extensively used as an organic solvent in various industrial applications, has been identified as a causative factor in inducing hypersensitivity syndrome (THS). Currently, there is no specific treatment for THS, and most patients experience serious adverse outcomes due to extensive skin damage leading to severe infection. However, the pathogenesis of THS-associated skin damage remains unclear. This study aims to elucidate the mechanism underlying skin damage from the perspective of intercellular communication and gap junctions in THS. Our results verified that hyperactivation of connexin43 gap junctions, caused by the aberrantly elevated expression of connexin43, triggers a bystander effect that promotes apoptosis and inflammation in THS via the TNF-TNFRSF1B and mitochondria-associated pathways. Additionally, we identified the gap junction inhibitor Carbenoxolone disodium (CBX) as a promising agent for the treatment of skin damage in THS. CBX protects against inflammatory cell infiltration in the skin and decreases immune cell imbalance in the peripheral blood of THS mice. Furthermore, CBX reduces connexin43 expression, apoptosis and inflammation in THS mice. The study reveals new insights into the mechanisms underlying TCE-induced skin damage, offering a potential treatment strategy for the development of effective therapies targeting severe dermatitis induced by chemical exposure.


Asunto(s)
Tricloroetileno , Humanos , Animales , Ratones , Tricloroetileno/toxicidad , Tricloroetileno/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Solventes , Uniones Comunicantes/metabolismo , Inflamación/metabolismo
5.
Ecotoxicol Environ Saf ; 274: 116174, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38471344

RESUMEN

Trichloroethylene (TCE)-induced hypersensitivity syndrome (THS) has been a concern for many researchers in the field of environmental and occupational health. Currently, there is no specific treatment for THS, leaving patients to contend with severe infections arising from extensive skin lesions, consequently leading to serious adverse effects. However, the pathogenesis of severe skin damage in THS remains unclear. This study aims to investigate the specific danger signals and mechanisms underlying skin damage in THS through in vivo and in vitro experiments. We identified that cell supernatant containing 15 kDa granulysin (GNLY), released from activated CD3-CD56+NK cells or CD3+CD56+NKT cells in PBMC induced by TCE or its metabolite, promoted apoptosis in HaCaT cells. The apoptosis level decreased upon neutralization of GNLY in the supernatant by a GNLY-neutralizing antibody in HaCaT cells. Subcutaneous injection of recombinant 15 kDa GNLY exacerbated skin damage in the THS mouse model and better mimicked patients' disease states. Recombinant 15 kDa GNLY could directly induce cellular communication disorders, inflammation, and apoptosis in HaCaT cells. In addition to its cytotoxic effects, GNLY released from TCE-activated NK cells and NKT cells or synthesized GNLY alone could induce aberrant expression of the E3 ubiquitin ligase PDZRN3, causing dysregulation of the ubiquitination of the cell itself. Consequently, this resulted in the persistent opening of gap junctions composed of connexin43, thereby intensifying cellular inflammation and apoptosis through the "bystander effect". This study provides experimental evidence elucidating the mechanisms of THS skin damage and offers a novel theoretical foundation for the development of effective therapies targeting severe dermatitis induced by chemicals or drugs.


Asunto(s)
Tricloroetileno , Ubiquitina-Proteína Ligasas , Animales , Ratones , Conexina 43/metabolismo , Hipersensibilidad/genética , Hipersensibilidad/metabolismo , Inflamación/patología , Células Asesinas Naturales , Leucocitos Mononucleares , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/genética , Tricloroetileno/toxicidad , Ubiquitina-Proteína Ligasas/metabolismo , Humanos
6.
Toxicol Lett ; 393: 47-56, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38242488

RESUMEN

Trichloroethylene-induced hypersensitivity dermatitis (TIHD) is a delayed hypersensitivity response that is affected by genetic and environmental factors. Occupational exposure to trichloroethylene (TCE) enhances antigen presentation, leading to hypersensitivity in workers with the HLA-B* 13:01 allele. Several studies have observed the activation of herpesviruses, such as EpsteinBarr virus (EBV), in TIHD patients. However, the underlying mechanisms remain unclear. Toll-like receptors (TLRs) play a pivotal role in the pathogenesis of herpesvirus infection. This study aimed to explore whether TLRs serve as a shared mechanism for both herpesvirus and allergenic chemicals. In this study, HLA-B* 13:01-transfected Hmy2. A C1R cell model was constructed, and cells were treated with TCOH and EBV to explore the possible mechanisms. We established a mouse model of dermatitis and used a TLR4 agonist to verify the effect of herpesvirus on TIHD. The results showed that EBV and TCOH synergistically enhance antigen processing and presentation via the TLR2/NF-κB axis. Furthermore, TLR4 agonist further aggravated skin lesions and liver damage in TCE-sensitized mice through TLR4/NF-κB axis-mediated antigen processing and presentation. Together, this study indicates that viral infection further aggravates the inflammatory response in TIHD based on environment-gene interactions.


Asunto(s)
Dermatitis , Herpesviridae , Hipersensibilidad , Tricloroetileno , Humanos , Ratones , Animales , FN-kappa B , Tricloroetileno/toxicidad , Presentación de Antígeno , Receptor Toll-Like 4/genética , Antígenos HLA-B/genética
7.
J Hazard Mater ; 465: 133062, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38043425

RESUMEN

Cadmium (Cd) is the main heavy metal pollutant in sediments from East China. The biochar-sediment nexus can provide carbon sequestration and pollution control. In this work, an in situ study was conducted to investigate the long-term effects and control mechanism of biochar and the effect of biochar aging on Cd stabilization in overlying water-pore water-sediment. The Cd2+ concentration in the overlying water was positively correlated with total nitrogen (0.960, P < 0.05), total organic carbon (0.983, P < 0.05), and total phosphorus (0.993, P < 0.01) in pore water. Biochar stabilized Cd2+ by increasing the pH and oxidation-reduction potential of the sediment environment and promoting the formation of Cd1.25Ca0.75(P2O7) on the biochar surface in sediment from phosphorus-rich water. These changes were closely related to the Brunauer-Emmett-Teller surface area and average pore size of the biochar. Within 60 days, the biochar in the sediment underwent aging, which was closely related to the preparation temperature of the biochar. The organic composition of biochar prepared at a low temperature (≤ 300 °C) and the surface structure of biochar prepared at a high temperature (≥ 500 °C) were altered. The biochar parameter changes were in the order of pore volume > Brunauer-Emmett-Teller surface area > pore size. Our results show that biochar modification can enhance the remediation capacity of biochar, but may be unfavorable to biochar anti-aging. This knowledge will support policymakers and researchers when exploring long-term biochar use in contamination control and strengthen future research.


Asunto(s)
Cadmio , Contaminantes Químicos del Agua , Cadmio/química , Fósforo , Contaminantes Químicos del Agua/química , Carbón Orgánico/química
8.
Zool Res ; 45(1): 1-12, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38114428

RESUMEN

Changes in protein abundance and reversible protein phosphorylation (RPP) play important roles in regulating hypometabolism but have never been documented in overwintering frogs at high altitudes. To test the hypothesis that protein abundance and phosphorylation change in response to winter hibernation, we conducted a comprehensive and quantitative proteomic and phosphoproteomic analysis of the liver of the Xizang plateau frog, Nanorana parkeri, living on the Qinghai-Xizang (Tibet) Plateau (QTP). In total, 5 170 proteins and 5 695 phosphorylation sites in 1 938 proteins were quantified. Based on proteomic analysis, 674 differentially expressed proteins (438 up-regulated, 236 down-regulated) were screened in hibernating N. parkeri versus summer individuals. Functional enrichment analysis revealed that higher expressed proteins in winter were significantly enriched in immune-related signaling pathways, whereas lower expressed proteins were mainly involved in metabolic processes. A total of 4 251 modified sites (4 147 up-regulated, 104 down-regulated) belonging to 1 638 phosphoproteins (1 555 up-regulated, 83 down-regulated) were significantly changed in the liver. During hibernation, RPP regulated a diverse array of proteins involved in multiple functions, including metabolic enzymatic activity, ion transport, protein turnover, signal transduction, and alternative splicing. These changes contribute to enhancing protection, suppressing energy-consuming processes, and inducing metabolic depression. Moreover, the activities of phosphofructokinase, glutamate dehydrogenase, and ATPase were all significantly lower in winter compared to summer. In conclusion, our results support the hypothesis and demonstrate the importance of RPP as a regulatory mechanism when animals transition into a hypometabolic state.


Asunto(s)
Anuros , Proteómica , Humanos , Animales , Fosforilación , Tibet
9.
Sci Rep ; 13(1): 21338, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049510

RESUMEN

The introduction of defect layers into one-dimensional parity-time (PT) symmetric photonic crystals gives rise to resonances within the photonic bandgaps. These resonances can be effectively explained by our generalized temporal coupled mode theory. The scattering properties and dispersion relation of defect modes exhibit distinct characteristics compared to conventional one-dimensional Hermitian photonic crystals with defect layers. By tuning the non-Hermiticity or other model parameters, the modulus of the generalized decay rate can be reduced, consequently, the electric field concentrated within the defect layer strengthens. This arises due to the unique band structure of one-dimensional PT-symmetric photonic crystals, which differs significantly from that of traditional one-dimensional Hermitian photonic crystals. Furthermore, the interaction between multiple resonances is investigated through the introduction of multiple defect layers. Our study not only provides insights into resonance phenomena in defective non-Hermitian systems but also contributes to the design of relevant optical resonance devices.

10.
Ibrain ; 9(2): 236-242, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37786554

RESUMEN

Decubitus ulcers are a common spinal cord injury (SCI) complication that puts patients' lives in danger and has emerged as a more prevalent issue in modern clinical rehabilitation and care. Decubitus ulcers in humans can currently be treated in a number of different ways, but there are fewer studies on how to treat and care for decubitus ulcers in macaques. To treat a 20-year-old adult male macaque monkey with SCI and decubitus ulcers after a quarter transection of the thoracic spinal cord, a number of scientific care procedures and pharmaceutical treatments, such as dietary changes and topical or intravenous administration of medication, were carried out and continuously monitored in real-time. In comparison to the untreated group, we observed a significant improvement in decubitus wound healing in the macaques. In this article, we provide a good protocol for decubitus ulcer care after SCI and suggest that future experimental animal modeling needs to focus on issues such as care for postoperative complications.

11.
Ibrain ; 9(3): 349-356, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37786753

RESUMEN

Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI.

12.
Zhongguo Gu Shang ; 36(10): 926-31, 2023 Oct 25.
Artículo en Chino | MEDLINE | ID: mdl-37881923

RESUMEN

OBJECTIVE: To compare the posterior cruciate ligament(PCL) index with six different measurement methods, and analyze and verify its clinical diagnostic value in anterior cruciate ligament (ACL) injury. METHODS: The Magnetic resonance imaging (MRI) data of 225 knee joints in our hospital from May 2018 to March 2022 were retrospectively analyzed, aged from 18 to 60 years old, with a median of 32 years old. On the sagittal MRI images of 114 patients with ACL injury and 111 patients with intact ACL, Measure the straight-line distance (A) between the femoral attachment point and the tibial attachment point of the PCL on the MRI sagittal image and the maximum vertical distance (B) between the straight line and the arcuate mark point of the PCL on the sagittal image, calculate the PCL index and evaluate the diagnostic value of the PCL index for ACL injury. RESULTS: The PCL index of the ACL normal group and the ACL injury group were statistically described. There was no significant difference in PCL index 1, 2, 3 and 6 between the two groups(P>0.05). The difference of PCL index 4 and 5 between the two groups was statistically significant (P<0.001). This study only found that the PCL index 2, 6 in the ACL normal group had a negative correlation with the patient's age (correlation coefficient=-0.213, -0.819;P<0.05), and the PCL index 5 in the ACL injury group was significantly correlated with the patient's body mass index(BMI)had a negative correlation (correlation coefficient=-0.277, P<0.05). CONCLUSION: The change of PCL index is helpful for the diagnosis of ACL injury, PCL index 4 and 5 can be used as effective reference indexes for diagnosing ACL injury in clinic.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Posterior , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Ligamento Cruzado Posterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior , Estudios Retrospectivos , Articulación de la Rodilla , Imagen por Resonancia Magnética/métodos
13.
Environ Pollut ; 338: 122672, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37797926

RESUMEN

Synthetic musks (SMs), the widely used odor component in personal care products have attracted attention due to their environmental impacts, especially the abortion risks. Given that women comprise a significant consumer demographic for personal care products, it is imperative to promptly initiate research on avoidance strategies for pregnant women concerning their exposure to synthetic chemicals (SMs). This study tried to establish novel theoretical approaches to eliminate the abortion risks of SM-contained body wash by designing the SM-contained proportioning scheme and analyzing the abortion risk mechanisms. The binding energy of SMs to estrogen-progesterone protein complex was used as an indicator of the abortion risk. A total of 324 SM-contained body wash proportioning schemes were designed using full factorial design and No. 218 was found as the most effective formula for body wash proportioning with the binding energy value of 68.6 kJ/mol. Results showed the abortion risk could be effectively alleviated (reduced 0.6%-163.4%) by regulating the proportioning scheme of SM-contained body wash. In addition, the mechanism analysis of SM-contained proportioning scheme proportioning scheme found that xanthan gum and disodium EDTA played essential roles in reducing the abortion risk in pregnant women after exposure. The selection of proper body wash components for reducing the abortion risk of SMs on pregnant women was first proposed. It sheds lights on the potential risks of people's daily life and proposes risk-eliminating strategies.


Asunto(s)
Cosméticos , Mujeres Embarazadas , Humanos , Femenino , Embarazo , Ácidos Grasos Monoinsaturados , Medición de Riesgo
14.
J Fungi (Basel) ; 9(9)2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37755042

RESUMEN

Plant endophytic fungi and rhizosphere soil fungi are often reported as biocontrol agents against plant pathogens or with plant growth promotion potential. Four treatments were performed in field and greenhouse experiments where cucumber plants were inoculated with Trichoderma harzianum and Fusarium oxysporum in 2022. The roots, stems and leaves of cucumber plants and their rhizosphere soil were collected twice individually from the field and greenhouse for isolation of cucumber endophytic and rhizosphere soil fungi. All fungal strains were identified through sequence similarity of the ITS1-5.8s-ITS2 rDNA region. The potato dextrose agar (PDA) media yielded the highest number of genera isolated from cucumber plants, rhizosphere soil and both compared to other media. There were no significant differences among the four media for the isolation of all cucumber endophytic fungi. However, in the roots, the number of endophytic fungi isolated by MRBA was significantly higher than that isolated on malt extract agar (MEA), while in the stems, the number of fungi isolated with PDA was significantly higher than that isolated with Martin's rose bengal agar medium (MRBA). PDA had significantly higher isolation efficiency for the rhizosphere soil fungi than MRBA. The 28 fungal genera had high isolation efficiency, and the endophytic Trichoderma strains were significantly more isolated by MEA than those of MRBA. It is suggested that PDA can be used as a basic medium, and different cultural media can be considered for specific fungal genera.

15.
Int J Hyg Environ Health ; 253: 114223, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37557062

RESUMEN

Diesel exhaust has long been of health concern due to established toxicity including carcinogenicity in humans. However, the precise components of diesel engine emissions that drive carcinogenesis are still unclear. Limited work has suggested that nitrated polycyclic aromatic hydrocarbons (NPAHs) such as 1-nitropyrene and 2-nitrofluorene may be more abundant in diesel exhaust. The present study aimed to examine whether urinary amino metabolites of these NPAHs were associated with high levels of diesel engine emissions and urinary mutagenicity in a group of highly exposed workers including both smokers and nonsmokers. Spot urine samples were collected immediately following a standard work shift from each of the 54 diesel engine testers and 55 non-tester controls for the analysis of five amino metabolites of NPAHs, and cotinine (a biomarker of tobacco smoke exposure) using liquid chromatography-mass spectrometry. An overnight urine sample was collected in a subgroup of non-smoking participants for mutagenicity analysis using strain YG1041 in the Salmonella (Ames) mutagenicity assay. Personal exposure to fine particles (PM2.5) and more-diesel-specific constituents (elemental carbon and soot) was assessed for the engine testers by measuring breathing-zone concentrations repeatedly over several full work shifts. Results showed that it was 12.8 times more likely to detect 1-aminopyrene and 2.9 times more likely to detect 2-aminofluorene in the engine testers than in unexposed controls. Urinary concentrations of 1-aminopyrene were significantly higher in engine testers (p < 0.001), and strongly correlated with soot and elemental carbon exposure as well as mutagenicity tested in strain YG1041 with metabolic activation (p < 0.001). Smoking did not affect 1-aminopyrene concentrations and 1-aminopyrene relationships with diesel exposure. In contrast, both engine emissions and smoking affected 2-aminofluorene concentrations. The results confirm that urinary 1-aminopyrene may serve as an exposure biomarker for diesel engine emissions and associated mutagenicity.


Asunto(s)
Mutágenos , Hidrocarburos Policíclicos Aromáticos , Humanos , Mutágenos/toxicidad , Emisiones de Vehículos/toxicidad , Emisiones de Vehículos/análisis , Hollín/análisis , Hidrocarburos Policíclicos Aromáticos/orina , Nitratos/análisis , Biomarcadores/orina
16.
BMC Genomics ; 24(1): 449, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37558985

RESUMEN

BACKGROUND: For Asian seabass (Lates calcarifer, Bloch 1790) cultured at sea cages various aquatic pathogens, complex environmental and stress factors are considered as leading causes of disease, causing tens of millions of dollars of annual economic losses. Over the years, we conducted farm-based challenges by exposing Asian seabass juveniles to complex natural environmental conditions. In one of these challenges, we collected a total of 1,250 fish classified as either 'sensitive' or 'robust' individuals during the 28-day observation period. RESULTS: We constructed a high-resolution linkage map with 3,089 SNPs for Asian seabass using the double digest Restriction-site Associated DNA (ddRAD) technology and a performed a search for Quantitative Trait Loci (QTL) associated with robustness. The search detected a major genome-wide significant QTL for increased robustness in pathogen-infected marine environment on linkage group 11 (ASB_LG11; 88.9 cM to 93.6 cM) with phenotypic variation explained of 81.0%. The QTL was positioned within a > 800 kb genomic region located at the tip of chromosome ASB_LG11 with two Single Nucleotide Polymorphism markers, R1-38468 and R1-61252, located near to the two ends of the QTL. When the R1-61252 marker was validated experimentally in a different mass cross population, it showed a statistically significant association with increased robustness. The majority of thirty-six potential candidate genes located within the QTL have known functions related to innate immunity, stress response or disease. By utilizing this ddRAD-based map, we detected five mis-assemblies corresponding to four chromosomes, namely ASB_LG8, ASB_LG9, ASB_LG15 and ASB_LG20, in the current Asian seabass reference genome assembly. CONCLUSION: According to our knowledge, the QTL associated with increased robustness is the first such finding from a tropical fish species. Depending on further validation in other stocks and populations, it might be potentially useful for selecting robust Asian seabass lines in selection programs.


Asunto(s)
Perciformes , Sitios de Carácter Cuantitativo , Animales , Mapeo Cromosómico , Perciformes/genética , Cromosomas , Genómica , Polimorfismo de Nucleótido Simple , Ligamiento Genético
17.
Appl Microbiol Biotechnol ; 107(20): 6299-6313, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37642716

RESUMEN

The application of clustered regularly interspaced short palindromic repeats-Cas (CRISPR-Cas9) technology in the genetic modification of Yarrowia lipolytica is challenged by low efficiency and low throughput. Here, a highly efficient CRISPR-iCas9 (with D147Y and P411T mutants) genetic manipulation tool was established for Y. lipolytica, which was further utilized to integrate carotene synthetic key genes and significantly improve the target product yield. First, CRISPR-iCas9 could shorten the time of genetic modification and enable the rapid knockout of nonsense suppressors. iCas9 can lead to more than 98% knockout efficiency for NHEJ-mediated repair after optimal target disruption of a single gene, 100% knockout efficiency for a single gene-guided version, and more than 80% knockout efficiency for multiple genes simultaneously in Y. lipolytica. Subsequently, this technology allowed for rapid one-step integration of large fragments (up to 9902-bp) of genes into chromosomes. Finally, YL-ABTG and YL-ABTG2Z were further constructed through CRISPR-iCas9 integration of key genes in a one-step process, resulting in a maximum ß-carotene and zeaxanthin content of 3.12 mg/g and 2.33 mg/g dry cell weight, respectively. Therefore, CRISPR-iCas9 technology provides a feasible approach to genetic modification for efficient biosynthesis of biological compounds in Y. lipolytica. KEY POINTS: • iCas9 with D147Y and P411T mutants improved the CRISPR efficiency in Y. lipolytica. • CRISPR-iCas9 achieved efficient gene knockout and integration in Y. lipolytica. • CRISPR-iCas9 rapidly modified Y. lipolytica for carotenoid bioproduction.


Asunto(s)
Sistemas CRISPR-Cas , Yarrowia , Carotenoides , Yarrowia/genética , Edición Génica/métodos , beta Caroteno
18.
Artículo en Inglés | MEDLINE | ID: mdl-37378810

RESUMEN

The diatom test has been used by forensic pathologist as standard for drowning, but the occurrence of false-positive results (presence of diatoms found in the tissues of subjects who died from causes other than drowning) draws criticism regarding the specificity of the test. Diatoms within food or water can be ingested through the gastrointestinal tract. However, the mechanisms of how the diatoms reach distant organs such as the lung, liver, and kidney have not been studied. In this article, we simulated the process of diatoms entering the gastrointestinal tract using gastric lavage on experimental rabbits. Diatoms are detected in lymph from a lymphatic vessel at the root of the mesentery, portal vein blood, aortic blood, lung, liver, and kidney samples in the gavage group. Of diatoms, 76.24% were the centric diatom, 99.86% of diatoms have a maximum size of less than 50 µm, and most of diatoms concentrate in the lung. Our study provided the evidence supporting the theory that the diatoms could pass through the gastrointestinal barrier and reach the rabbits' other internal organs. The diatoms could reach internal organs through the portal vein and lymphatic vessel at the root of the mesentery. This provides us new insight into our understanding of false-positive diatom test in forensic pathology.

19.
Dis Colon Rectum ; 66(12): 1578-1586, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37379171

RESUMEN

BACKGROUND: Laparoscopic-assisted colorectal surgery is an effective surgery to treat colorectal cancer. During the laparoscopic-assisted colorectal surgery, a midline incision and several trocar insertions are required during the surgery. OBJECTIVE: To observe whether the rectus sheath block based on the locations of the surgical incision and trocars can significantly reduce the pain score on the first day after surgery. DESIGN: This study was a prospective, double-blinded, randomized controlled trial approved by the Ethics Committee of First Affiliated Hospital of Anhui Medical University (registration number: ChiCTR2100044684). SETTINGS: All patients were recruited from 1 hospital. PATIENTS: Forty-six patients aged 18 to 75 years undergoing elective laparoscopic-assisted colorectal surgery were successfully recruited, and 44 patients completed the trial. INTERVENTIONS: Patients in the experimental group received rectus sheath block, with 0.4% ropivacaine 40 to 50 mL, whereas the control group received an equal volume of normal saline. MAIN OUTCOME MEASURES: The primary outcome was pain score on postoperative day 1. Secondary outcomes included patient-controlled analgesia use at 24 and 48 hours after surgery and pain score at 6, 12, and 48 hours after surgery. RESULTS: Pain scores at rest and during activity at 6, 12, 24, and 48 hours after surgery and patient-controlled analgesia consumption of patients on the first day after surgery were significantly lower in the experimental group than those in the control group (all p < 0.05). LIMITATIONS: We did not separate pain into visceral and somatic pain because patients often had difficulty differentiating the source of pain. CONCLUSIONS: Our research indicates that in the context of multimodal analgesia, the rectus sheath block according to the midline incision and the positions of the trocars can reduce the pain scores and consumption of analgesic drugs on the first day after surgery for patients undergoing laparoscopic-assisted colorectal surgery. LA EFICIENCIA DEL BLOQUEO DE LA VAINA DEL RECTO DE VARIOS PUNTOS SEGN LA UBICACIN DE LA INCISIN EN LA CIRUGA COLORRECTAL ASISTIDA POR LAPAROSCOPIA UN ENSAYO CLNICO ALEATORIZADO: ANTECEDENTES:La cirugía colorrectal asistida por laparoscopia es una cirugía eficaz para tratar el cáncer colorrectal. Durante la cirugía colorrectal asistida por laparoscopia, se requiere una incisión en la línea media y varias inserciones de trócaresOBJETIVO:El propósito de nuestro estudio fue observar si el bloqueo de la vaina del recto basado en las ubicaciones de la incisión quirúrgica y los trocares puede reducir significativamente la puntuación del dolor en el primer día después de la cirugía.DISEÑO:Este estudio fue un ensayo controlado aleatorio prospectivo, doble ciego, aprobado por el Comité de Ética del Primer Hospital Afiliado de la Universidad Médica de Anhui (número de registro: ChiCTR2100044684).ESCENARIO:Todos los pacientes fueron reclutados en un hospital.PACIENTES:Cuarenta y seis pacientes de 18 a 75 años de edad que se sometieron a cirugía colorrectal electiva asistida por laparoscopía fueron reclutados con éxito y cuarenta y cuatro pacientes completaron el ensayo.INTERVENCIONES:Los pacientes del grupo experimental recibieron bloqueo de la vaina del recto con 40-50 ml de ropivacaína al 0.4%, mientras que el grupo de control recibió el mismo volumen de solución salina normal.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la puntuación del dolor en el día 1 postoperatorio. Los resultados secundarios incluyeron el uso de analgesia controlada por el paciente a las 24 y 48 horas después de la cirugía y la puntuación del dolor a las 6, 12, y 48 horas después de la cirugía.RESULTADOS:Las puntuaciones de dolor en reposo y durante la actividad a las 6, 12, 24, y 48 horas después de la cirugía, y el consumo de PCA de los pacientes el primer día después de la cirugía fueron significativamente más bajos en el grupo experimental que en el grupo control (todos p < 0.05).LIMITACIONES:No separamos el dolor en dolor visceral y somático porque los pacientes a menudo tenían dificultades para diferenciar la fuente del dolor.CONCLUSIONES:Nuestra investigación indica que, en el contexto de la analgesia multimodal, el bloqueo de la vaina del recto de acuerdo con la incisión de la línea media y las posiciones de los trócares pueden reducir los puntajes de dolor y el consumo de analgésicos en el primer día después de la cirugía para pacientes sometidos a cirugía colorrectal laparoscópica. (Traducción-Dr. Jorge Silva Velazco ).


Asunto(s)
Analgesia , Cirugía Colorrectal , Herida Quirúrgica , Humanos , Dolor , Estudios Prospectivos , Estudios Retrospectivos , Ropivacaína , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano
20.
J Hazard Mater ; 455: 131538, 2023 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-37156045

RESUMEN

The ribosomal DNA (rDNA) plays a crucial role in maintaining genome stability. So far, alterations of rDNA from airborne pollutants exposure remain unclear. Nasal epithelial cells are the earliest respiratory barrier, which has an accessible surrogate for evaluating respiratory impairment. We developed a mixture-centered biomarkers study integrated epidemiological and biological evidence among 768 subjects, a mixture of polycyclic aromatic hydrocarbons (PAHs) and metals. We identified the mixed exposure of PAHs and metals by environmental and biological monitoring, selected urinary 8-hydroxy-2'-deoxyguanosine as DNA oxidative stress marker, and measured their rDNA copy number (rDNA CN) in nasal epithelial cells. We performed linear regression, adaptive elastic net regression, BKMR, and mediation analyses to assess the direct and indirect effects. We found a 10% elevation in urinary 1-hydroxypyrene was correlated with a separate 0.31% and 0.82% amplification of nasal 5S and 45S rDNA CN, respectively (all P < 0.05). A 10% increment of urine nickel was associated with a separate 0.37% and 1.18% elevation of nasal 5S and 45S rDNA CN, respectively (all P < 0.05). BKMR results also confirmed our findings of PAHs and nickel. Our findings suggested that DNA oxidative stress might trigger rDNA instability induced by inhaled PAHs and metals.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Humanos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , ADN Ribosómico , Níquel , Variaciones en el Número de Copia de ADN , 8-Hidroxi-2'-Desoxicoguanosina , Metales/toxicidad , Estrés Oxidativo , Biomarcadores
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