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1.
J Environ Sci (China) ; 147: 244-258, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003044

RESUMO

4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, ß-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.


Assuntos
Caenorhabditis elegans , Estrogênios , Nitrofenóis , Reprodução , Transdução de Sinais , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Reprodução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Nitrofenóis/toxicidade , Estrogênios/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos
2.
J Environ Sci (China) ; 147: 617-629, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003076

RESUMO

The manganese-cobalt mixed oxide nanorods were fabricated using a hydrothermal method with different metal precursors (KMnO4 and MnSO4·H2O for MnOx and Co(NO3)2⋅6H2O and CoCl2⋅6H2O for Co3O4). Bamboo-like MnO2⋅Co3O4 (B-MnO2⋅Co3O4 (S)) was derived from repeated hydrothermal treatments with Co3O4@MnO2 and MnSO4⋅H2O, whereas Co3O4@MnO2 nanorods were derived from hydrothermal treatment with Co3O4 nanorods and KMnO4. The study shows that manganese oxide was tetragonal, while the cobalt oxide was found to be cubic in the crystalline arrangement. Mn surface ions were present in multiple oxidation states (e.g., Mn4+ and Mn3+) and surface oxygen deficiencies. The content of adsorbed oxygen species and reducibility at low temperature declined in the sequence of B-MnO2⋅Co3O4 (S) > Co3O4@MnO2 > MnO2 > Co3O4, matching the changing trend in activity. Among all the samples, B-MnO2⋅Co3O4 (S) showed the preeminent catalytic performance for the oxidation of toluene (T10% = 187°C, T50% = 276°C, and T90% = 339°C). In addition, the B-MnO2⋅Co3O4 (S) sample also exhibited good H2O-, CO2-, and SO2-resistant performance. The good catalytic performance of B-MnO2⋅Co3O4 (S) is due to the high concentration of adsorbed oxygen species and good reducibility at low temperature. Toluene oxidation over B-MnO2⋅Co3O4 (S) proceeds through the adsorption of O2 and toluene to form O*, OH*, and H2C(C6H5)* species, which then react to produce benzyl alcohol, benzoic acid, and benzaldehyde, ultimately converting to CO2 and H2O. The findings suggest that B-MnO2⋅Co3O4 (S) has promising potential for use as an effective catalyst in practical applications.


Assuntos
Cobalto , Compostos de Manganês , Oxirredução , Óxidos , Tolueno , Óxidos/química , Compostos de Manganês/química , Catálise , Cobalto/química , Tolueno/química , Poluentes Atmosféricos/química
3.
Neural Regen Res ; 20(3): 858-872, 2025 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38886958

RESUMO

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

4.
BMC Public Health ; 24(1): 2136, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39107742

RESUMO

OBJECTIVE: To explore the association between cardiovascular health (CVH) measured by Life's Essential 8 (LE8) and the prevalence of urinary incontinence (UI). METHOD: A cross-section study was conducted using data from the National Health and Nutrition Examination Survey 2007-2012. 22,609 people aged ≥ 20 years with complete information on LE8 metrics and UI questionnaires were enrolled. Participants were divided into three groups (low: < 50, moderate: ≥ 50 and < 80, high: ≥ 80) based on the cut-off of LE8. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were performed to examine the association between LE8 and the prevalence of three types of UI separately (stress UI (SUI), urge UI (UUI), mixed UI (MUI)) by confounding factors adjusted. Spline smooth was conducted to find whether a linear relationship existed. In addition, sensitive analyses were also conducted to observe the stability. RESULT: A total of 22,609 adults were involved in the study, and participants were divided into three groups (low 42.2 ± 6.3, moderate 66.1 ± 8.1, high 86.8 ± 5.1) according to the cut-off points of LE8. The multivariable logistic regression suggested that LE8 is inversely associated with the prevalence of SUI (OR = 0.98, 95%CI 0.98 to 0.99), UUI (OR = 0.98, 95%CI 0.98 to 0.99), and MUI (OR = 0.98, 95%CI 0.97 to 0.98) in the fully-adjusted model. Compared with the low group, people with high scores of LE8 had a lower prevalence of SUI (OR = 0.45, 95%CI 0.37 to 0.55), UUI (OR = 0.49, 95%CI 0.40 to 0.60), and MUI (OR = 0.41, 95%CI 0.30 to 0.55). The result of the sensitive analysis showed the robustness of the main analysis. CONCLUSION: The prevalence of UI (SUI, UUI, or MUI) is inversely associated with the LE8 score, which suggests that maintaining a good CVH with a higher LE8 score is accompanied by lower prevalence rates of UUI, SUI, and MUI.


Assuntos
Doenças Cardiovasculares , Inquéritos Nutricionais , Incontinência Urinária , Humanos , Feminino , Masculino , Prevalência , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Incontinência Urinária/epidemiologia , Doenças Cardiovasculares/epidemiologia , Idoso , Adulto Jovem , Inquéritos e Questionários
5.
Molecules ; 29(15)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39125085

RESUMO

Dendrobium sinense, an endemic medicinal herb in Hainan Island, is rich in bibenzyl compounds. However, few studies have explored the molecular mechanisms of bibenzyl biosynthesis. This study presents a comprehensive analysis of DsBBS1 and DsBBS2 function in D. sinense. A molecular docking simulation revealed high-resolution three-dimensional structural models with minor domain orientation differences. Expression analyses of DsBBS1 and DsBBS2 across various tissues indicated a consistent pattern, with the highest expression being found in the roots, implying that they play a pivotal role in bibenzyl biosynthesis. Protein expression studies identified optimal conditions for DsBBS2-HisTag expression and purification, resulting in a soluble protein with a molecular weight of approximately 45 kDa. Enzyme activity assays confirmed DsBBS2's capacity to synthesize resveratrol, exhibiting higher Vmax and lower Km values than DsBBS1. Functional analyses in transgenic Arabidopsis demonstrated that both DsBBS1 and DsBBS2 could complement the Atchs mutant phenotype. The total flavonoid content in the DsBBS1 and DsBBS2 transgenic lines was restored to wild-type levels, while the total bibenzyl content increased. DsBBS1 and DsBBS2 are capable of catalyzing both bibenzyl and flavonoid biosynthesis in Arabidopsis. This study provides valuable insights into the molecular mechanisms underlying the biosynthesis of bibenzyl compounds in D. sinense.


Assuntos
Bibenzilas , Dendrobium , Proteínas de Plantas , Dendrobium/genética , Dendrobium/metabolismo , Dendrobium/química , Bibenzilas/química , Bibenzilas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Simulação de Acoplamento Molecular , Regulação da Expressão Gênica de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas Geneticamente Modificadas , Flavonoides/biossíntese , Flavonoides/química , Flavonoides/metabolismo
6.
Polymers (Basel) ; 16(15)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39125171

RESUMO

Human physical activity monitoring plays a crucial role in promoting personalized health management. In this work, inspired by an ancient Chinese belt, a belt-type wearable sensor (BWS) based on a triboelectric nanogenerator (TENG) is presented to monitor daily movements and collect the body motion mechanical energy. The developed BWS consists of a soft silicone sheet and systematically connected sensing units made from triboelectric polymer materials including polytetrafluoroethylene (PTFE) and polyamide (PA). A parameter study of the sensing units is firstly conducted to optimize the structure of BWS. The experimental studies indicate that the parameter-optimized BWS unit achieves a maximum output voltage of 47 V and a maximum current of 0.17 µA. A BWS with five sensing units is manufactured to record body movements, and it is able to distinguish different physical activities including stillness, walking, running, jumping, normal breathing, cessation of breathing, and deep breathing. In addition, the developed BWS successfully powers electronic devices including a smartphone, digital watch, and LED lights. We hope this work provides a new strategy for the development of wearable self-powered intelligent devices.

7.
Chemosphere ; : 143095, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39146995

RESUMO

The presence of organic compounds on the particulate matter (PM) or aerosols can arise from the condensation of gaseous organic compounds on the existing aerosols, or from organic precursors to form secondary organic aerosols (SOA) through photochemistry. The objective of this study is to characterize organic constituents on aerosols relevant to their emission sources and the key compounds revealing the evolution of aerosols with the use of a novel analytical technique. A time-of-flight mass spectrometry (TOFMS) coupled with comprehensive two-dimensional gas chromatography (GC×GC) was developed using a flow type of modulator instead of a thermal type as a prelude to field applications without the need for cryogen. The methodology of GC×GC-TOFMS is discussed in this study in detail. Since the coarse PM (PM10-2.5) may exhibit with a relatively high OC content compared to PM2.5, the GC×GC results have been obtained by analyzing PM10 samples collected in parallel with OC/EC analysis of PM2.5 samples at the Lulin Atmospheric Background Station (LABS, 23.47°N, 120.87°E, 2,862 m ASL) as the high-mountain background site in East Asia. We found that the organic analytes were in a majority in the range of 12 - 30 carbon numbers falling in the category of semi-volatile organic compounds (SVOCs) with 43 compounds of alcohol, aldehyde, ketone, and ester varieties if excluding alkanes. Intriguingly, trace amounts of plasticizers and phosphorus flame retardants such as phthalates (PAEs) and triphenyl phosphate (TPP) were also found, likely originating from regions involved in open burning of household solid waste in Southeast Asia or e-waste recycling in southern China and along the long-range transport route. Compounds such as these are unique to the specific sources, demonstrating the wide spread of these hazardous compounds in the environment.

8.
Life Sci ; : 122974, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147318

RESUMO

BACKGROUND: Basic helix-loop-helix ARNT like 2 (ARNTL2) is a transcription factor that controls the circadian rhythm. Amounts of studies have demonstrated the carcinogenic function of ARNTL2 in human malignant tumors albeit the underlying mechanisms remain poorly understood. We aimed to study the significance of ARNTL2 in bladder cancer (BLCA). METHODS: Immunohistochemical staining, immunoblotting and the database from TCGA were used to analyze the clinical relevance of ARNTL2, enolase 1 (ENO1) and solute carrier family 31 member 1 (SLC31A1) in BLCA. The function of ARNTL2 was explored by cell proliferation assay, apoptosis, colony formation and xenografted tumorigenesis. The molecular mechanisms of ARNTL2-driving BLCA development were investigated by RT-qPCR, immunoblotting and luciferase assays. Glycolysis was checked by measuring glucose consumption and lactate production. ENO1 activity was assessed by using indicated assay kit. RESULTS: Overexpression of ARNTL2 facilitates the proliferation and tumorigenesis of BLCA cells through suppression of apoptosis and enhancement of glycolysis. Up-regulation of SLC31A1, ENO1, and enhancement of SLC31A1-mediated ENO1 activity were critical for ARNTL2-triggered glycolysis and malignant growth in BLCA cells. ARNTL2 was positively correlated with SLC31A1 and ENO1 in BLCA patients. High expression of ARNTL2, SLC31A1 or ENO1 predicted the poor prognosis of BLCA patients. Depletion of SLC31A1 and inhibition of glycolysis completely blunted the growth ability of BLCA cells. CONCLUSION: In summary, ARNTL2 facilitates the progression of BLCA via activating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner. Inhibiting SLC31A1 and glycolysis may be an aspirational approach for the treatment of BLCA patients with overexpression of ARNTL2.

9.
Anal Chim Acta ; 1320: 342883, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39142764

RESUMO

BACKGROUND: In this study, exhaled breath testing has been considered a promising method for the detection and monitoring of breast cancer (BC). METHODS: A high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform was used to detect volatile organic compounds (VOCs) in breath samples. Then, machine learning (ML) models were constructed on VOCs for the diagnosis of BC and its progression monitoring. Ultimately, 1981 women with useable breath samples were included in the study, of whom 937 (47.3 %) had been diagnosed with BC. VOC panels were used for ML model construction for BC detection and progression monitoring. RESULTS: On the blinded testing cohort, this VOC-based model successfully differentiated patients with and without BC with sensitivity, specificity, and area under receiver operator characteristic curve (AUC) values of 85.9 %, 90.4 %, and 0.946. The corresponding AUC values when differentiating between patients with and without lymph node metastasis (LNM) or between patients with tumor-node-metastasis (TNM) stage 0/I/II or III/IV disease were 0.840 and 0.708, respectively. While developed VOC-based models exhibited poor performance when attempting to differentiate between patients based on pathological patterns (Ductal carcinoma in situ (DCIS) vs Invasive BC (IBC)) or molecular subtypes (Luminal vs Human epidermal growth factor receptor 2 (HER2+) vs Triple-negative BC (TNBC)) of BC. CONCLUSION: Collectively, the HPPI-TOFMS-based breathomics approaches may offer value for the detection and progression monitoring of BC. Additional research is necessary to explore the fundamental mechanisms of the identified VOCs.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Testes Respiratórios , Compostos Orgânicos Voláteis , Humanos , Neoplasias da Mama/diagnóstico , Feminino , Compostos Orgânicos Voláteis/análise , Biomarcadores Tumorais/análise , Testes Respiratórios/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Aprendizado de Máquina , Fótons , Espectrometria de Massas , Progressão da Doença
10.
J Prosthet Dent ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142993

RESUMO

The removal of fiber posts for the retreatment of root canals can be challenging. An autonomous robotic (ATR) system was used for accurate and minimally invasive endodontic retreatment in a patient who presented with symptomatic apical periodontitis and pain emanating from the mandibular left first molar, which had been previously restored with 3 fiber posts. Intraoral scanning data, radiographic data, and bur sizes were integrated into preoperative software program to design a treatment plan. The ATR system enabled precise and efficient post removal. The remnant filling material was removed before endodontic retreatment, and radiographs at 3 months after the procedure showed satisfactory healing. This treatment demonstrated the accuracy and efficiency of the ATR system for the removal of fiber posts from pretreated teeth, while minimizing the duration of the procedure and avoiding excessive tissue removal.

11.
Angew Chem Int Ed Engl ; : e202402543, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143504

RESUMO

Colorectal cancer (CRC) is one of the most common malignant tumours. Identification of new effective drug targets for CRC and exploration of bioactive small-molecules are clinically urgent. The human dCTP pyrophosphatase 1 (DCTPP1) is a newly identified pyrophosphatase regulating the cellular nucleotide pool but remains unexplored as potential target for CRC treatment. Here, twelve unprecedented chemical architectures terpene-nonadride heterodimers (1-12) and their monomers (13-20) were isolated from endophyte Bipolaris victoriae S27. Compounds 1-12 represented the first example of terpene-nonadride heterodimers, in which nonadride monomers of 1 and 2 were also first example of 5/6 bicyclic nonadrides. A series of assays showed that 2 could repress proliferation and induce cell cycle arrest, apoptotic and autophagic CRC cell death in vitro and in vivo. Clinical cancer samples data revealed that DCTPP1 was a novel target associated with poor survival in CRC. DCTPP1 was also identified as a new target protein of 2. Mechanistically, compound 2 bound to DCTPP1, inhibited its enzymatic activity, intervened with amino acid metabolic reprogramming, and exerted anti-CRC activity. Our study demonstrates that DCTPP1 was a novel potential biomarker and therapeutic target in CRC, and 2 was the first natural anti-CRC drug candidate targeting DCTPP1.

12.
Int J Biol Macromol ; 278(Pt 2): 134811, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153681

RESUMO

Odorant binding proteins (OBPs) are involved in odorant discrimination and act as the first filter in the peripheral olfactory system. Previous studies have shown that BhorOBP29 is potentially involved in olfactory perception in an important wood-boring pest Batocera horsfieldi (Hope) (Coleoptera: Cerambycidae), however, its function remains unclear. Here, we investigated the ligand-binding profiles of recombinant BhorOBP29 with 22 compounds from its host plant using fluorescence competitive binding assays and fluorescence quenching assays. The results showed that BhorOBP29 could bind to five ligands relying mainly on hydrophobic interactions. Molecular docking analysis indicated that residues Ile48, Leu51, Met52, Trp57, Asn105, and Val119 were extensively involved in the interactions between BhorOBP29 and the five ligands. Furthermore, the site-directed mutagenesis analysis revealed that Leu51 and Met52 residues were indispensable for BhorOBP29-ligands binding. Finally, electroantennogram (EAG) assays confirmed that hexanal, (-)-limonene, and 2-methylbutyraldehyde elicited a concentration-dependent EAG response with a maximum at the concentration of 1/10 v/v. These findings suggest that BhorOBP29 may play a significant role in the perception of host plant volatiles by B. horsfieldi. This study may help to discover novel behavioral regulation and environmentally friendly strategies for controlling B. horsfieldi in the future.

13.
Ecotoxicol Environ Saf ; 284: 116895, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39151370

RESUMO

Neonicotinoids are widely used pesticides around the world, but the photolysis of neonicotinoids in cold agricultural region are still in blank. This paper aimed to study the influence of cold temperature over photolysis of neonicotinoids. To this end, the photolysis rates and photoproducts of dinotefuran and nitenpyram in water, ice and freeze-thawing condition were determined. Coupled with quantum chemistry calculation, the influence mechanisms of temperature and medium were investigated. The results showed the photolysis rates of neonicotinoids in water condition slightly declined with the lowered temperature due to the photolysis reactions were endothermic reactions. However, the photolysis rates increased by 89.8 %, 59.2 %, 49.4 % and 9.5 % for dinotefuran and nitenpyram in ice and thawing condition, respectively. This phenomenon was posed by the concentration-enhancing effect and change of photo-chemical properties of neonicotinoids in ice condition, which included lowered bond cleavage energy, lowered first excited singlet state energy and expanded light absorption range. The photolysis pathways of the two neonicotinoids did not change in different medium, but the concentration of carboxyl products was relatively higher than that of water condition due to the more amounts of reactive oxygen species in ice medium, which might increase the secondary pollution risk after ice-off in spring due to the higher ecotoxicity to nontarget organism of these photoproducts. The influence of cold temperature and medium change should be considered for the environmental fate and risk assessment of neonicotinoids in cold agricultural region.

14.
Sci Total Environ ; : 175496, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151634

RESUMO

Psychrophilic bacteria, the dominant spoilage organisms in raw milk, secrete heat-stable extracellular proteases and lipases that lead to the decomposition of milk and dairy products. In this study, we investigated psychrophilic bacteria in 165 raw milk samples collected across four seasons and six regions in China using shotgun metagenomic sequencing and traditional culture methods. The isolated psychrophilic bacteria were classified into 40 genera and 185 species. Pseudomonas was the most prevalent, accounting for 51.13 % of the genera, while Lactococcus and Chryseobacterium were also notably abundant (> 6.0 %). Metagenomic sequencing revealed that Pseudomonas (47.9 %), Stenotrophomonas (9.75 %), Sphingomonas (6.73 %), Latilactobacillus (6.38 %) and Lactococcus (5.16 %) were the dominant genera in the raw milk samples. The diversity of psychrophilic bacteria in raw milk was strongly influenced by seasonal variations, with the sampling region being a less significant factor. KEGG annotation indicated that carbohydrate and amino acid metabolism were the primary metabolic pathways in these bacteria. Metagenomic sequencing not only accurately identifies species but also provides functional insights into psychrophilic bacteria in raw milk, aiding in understanding their activities, promoting their control on farms, and ultimately improving raw milk quality.

15.
Toxicology ; : 153928, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153657

RESUMO

Deoxynivalenol (DON) is a kind of widespread traditional Fusarium mycotoxins in the environment, and its intestinal toxicity has received considerable attention. Recently, the emerging Fusarium mycotoxin enniatins (ENNs) have also been shown to frequently coexist with DON in animal feed and food with large consumption. However, the mechanism of intestinal damage caused by the two mycotoxins co-exposure remains unclear. In this study, Caco-2 cell line was used to investigate the combined toxicity and potential mechanisms of four representative ENNs (ENA, ENA1, ENB, and ENB1) and DON. The results showed that almost all mixed groups showed antagonistic effects, particularly ENB at 1/4 IC50 (CI = 6.488). Co-incubation of ENNs mitigated the levels of signaling molecule levels disrupted by DON, including reactive oxygen species (ROS), calcium mobilization (Ca2+), adenosine triphosphate (ATP). The differentially expressed genes (DEGs) between the mixed and ENB groups were significantly enriched in the Ras/PI3K/Akt signaling pathway, including 28 up-regulated genes and 40 down-regulated genes. Quantitative real-time PCR further confirmed the lower expression of apoptotic gene in the mixed group, thereby reducing the cytotoxic effects caused by DON exposure. This study emphasizes that co-exposure of ENNs and DON reduces cytotoxicity by regulating the Ras/PI3K/Akt signaling pathway. Our results provide the first comprehensive evidence about the antagonistic toxicity of ENNs and DON on Caco-2 cells, and new insights into mechanisms investigated by transcriptomics.

16.
Vet Parasitol ; 331: 110279, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39116547

RESUMO

Cryptosporidium is among the top causes of life-threatening diarrheal infection in public health and livestock sectors. Despite its high prevalence and economic importance, currently, there is no vaccine. Control of this protozoan is difficult due to the excretion of many resistant oocysts in the feces of the infected host, which contaminate the environment. Paromomycin shows inconsistent results and isn't considered a reliable therapy for cryptosporidiosis. Nitazoxanide (NTZ), the only FDA-approved drug against this parasite, is less productive in impoverished children and PLWHA (people living with HIV/AIDS). The absence of mitochondria and apicoplast, its unique location inside enterocytes separated by parasitophorous vacuole, and, most importantly, challenges in its genetic manipulations are some hurdles to the drug-discovery process. A library of compounds has been tested against Cryptosporidium during in vitro and in vivo trials. However, there has still not been sufficient success in finding the drug of choice against this parasite. Recent genome editing technologies based on CRISPR/Cas-9 have explored the functions of the vital genes by producing transgenic parasites that help to screen a collection of compounds to find target-specific drugs, provided the sufficient availability of in vitro culturing platforms, efficient transfection methods, and analytic techniques. The use of herbal remedies against Cryptosporidium is also an emerging area of interest with sufficient clinical success due to enhanced concern regarding anthelmintic resistance. Here, we highlighted present treatment options with their associated limitations, the use of genetic tools and natural products against it to find safe, effective, and inexpensive drugs to control the ever-increasing global burden of this disease.

17.
JCI Insight ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088267

RESUMO

BACKGROUND: A polymorphism in the fat mass and obesity-associated gene (FTO) is linked to enhanced neural sensitivity to food-cues and attenuated ghrelin suppression. Risk allele carriers regain more weight than non-carriers after bariatric surgery. It remains unclear how FTO variation affects brain function and ghrelin following surgery. METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) and cue-reactivity fMRI with high-/low-caloric food-cues were performed at pre-surgery and 1-, 6-, and 12-months post-surgery to examine brain function in 16 carriers with one copy of the rs9939609 A allele (AT) and 26 non-carriers (TT). Behavioral assessments up to five years post-surgery were also conducted. RESULTS: AT relative to TT group had smaller BMI-loss at 12 to 60 months post-surgery and lower resting-state activity in posterior cingulate cortex following LSG (group-by-time interaction effects). Meanwhile, AT relative to TT group showed greater food-cue responses in dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC) and insula (group effects). There were negative associations of weight-loss with ghrelin and greater activation in DLPFC, DMPFC and insula in AT but not TT group. CONCLUSION: These findings indicate that FTO variation is associated with the evolution of ghrelin signaling and brain function after bariatric surgery, which might hinder weight-loss.

18.
Artigo em Inglês | MEDLINE | ID: mdl-39089873

RESUMO

BACKGROUND AND PURPOSE: Material-specific reconstructions of dual-energy CTA (DECTA) can highlight iodinated contrast, subtract predefined materials, and reduce metal artifact. We present a technique to improve detection of residual aneurysms after endovascular coiling by which iodine-map DECTA (IM-DECTA) reconstructions subtract platinum coil artifacts in MIP images (MIP IM-DECTA) and assess if IM-DECTA offers improved detection over conventional CTA (CCTA) or monoenergetic DECTA. MATERIALS AND METHODS: We included consecutive patients who underwent endovascular aneurysm coiling with follow-up DECTA and DSA within 24 months. DECTA was performed at 80- and 150-kVp tube voltages on a rapid kV-switching single-source Revolution scanner. CCTA and IM-DECTA series were reconstructed. Reference-standard DSA was compared with CCTA, 50- and 70-keV virtual monochromatic DECTA, IM-DECTA, and MIP IM-DECTA. Blinded to DSA data, cross-section images were reviewed in consensus by 3 neurointerventionalists for residual aneurysms and assigned modified Raymond-Roy classifications (mRRC). Sensitivity, specificity, and accuracy of each series is reported relative to DSA, and single-factor ANOVA and pair-wise Spearman correlation coefficients compared the accuracy of each series. Readers provided ROI measurements of HU deviation adjacent to the aneurysm neck for quantitative noise assessment and qualitatively scored each series on a 3-point Likert-style scale ranging from uninterpretable to excellent image quality. RESULTS: Twenty-one patients with 25 coiled aneurysms were included. Mean time from DECTA to DSA was 286 ± 212 days. IM-DECTA and MIP IM-DECTA most sensitively (89% and 90%) and specifically (93% and 93%) detected residual aneurysms relative to CCTA (6% and 86%). Relative to DSA, IM-DECTA and MIP IM-DECTA most accurately detected (92% versus 28% for CCTA) and classified residual aneurysms by mRRC (ρC-CTA = -0.08; ρIM = 0.50; ρIM-MIP = 0.55; P < .001). Reader consensus reported the best image quality at the aneurysm neck with IM-DECTA and MIP IM-DECTA, with 56% of CCTAs considered uninterpretable versus 0% of IM-DECTAs, and image noise was significantly lower for IM-DECTA (27.9 ± 3.6 HU) or MIP IM-DECTA (26.8 ± 3.5 HU) than CCTA (103.2 ± 13.3 HU; P < .001). CONCLUSIONS: MIP IM-DECTA can subtract coil mass artifact and is more sensitive and specific than CCTA for the detection of residual aneurysms after endovascular coiling.

19.
Sensors (Basel) ; 24(15)2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39124098

RESUMO

DFOS (distributed fiber-optic sensing) technology has shown the potential to increase the accuracy of measurement after years of development and experimenting in geoengineering monitoring. To better understand the development of DFOS technology and its contribution to geoengineering, an objective and data-driven review of the development process of DFOS technology in construction was completed. The review was accomplished by using text mining methods on the Web of Science, covering a wide range of relevant data, including 3970 articles from 1989 to 2023. The results indicate that DFOS technology research demonstrates the typical characteristics of multi-author, multi-country, and multi-institution collaborations, spanning various research fields. Over the past 35 years, the number of published articles has exhibited exponential growth, with China making significant contributions and leading in terms of its total publication growth rate, which has been higher than that of the United States since 2016. In the analysis of author keywords, emerging technologies, such as machine learning and distributed acoustic sensing, have garnered attention. The findings contribute to a comprehensive understanding of the development, impact, and future trends of DFOS technology in geotechnical engineering, offering valuable insights for researchers, scholars, and students in the field and inspiring new approaches for research methods in this domain.

20.
Angew Chem Int Ed Engl ; : e202411753, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136332

RESUMO

Development of highly porous and robust HOFs for high-pressure methane and hydrogen storage remains a grand challenge due to the fragile nature of hydrogen bonds. Herein, we report a strategy of constructing double-walled framework to target highly porous and robust HOF (ZJU-HOF-5a) for extraordinary CH4 and H2 storage. ZJU-HOF-5a features a minimized twofold interpenetration with double-walled structure, in which multiple supramolecular interactions are existed between the interpenetrated walls. This structural configuration can notably enhance the framework robustness while maintaining its high porosity, affording one of the highest gravimetric and volumetric surface areas of 3102 m2 g-1 and 1976 m2 cm-3 among the reported HOFs so far. ZJU-HOF-5a exhibits an extremely high volumetric H2 uptake of 43.6 g L-1 at 77 K/100 bar and working capacity of 41.3 g L-1 under combined swing conditions, and also impressive methane storage performance with a 5-100 bar working capacity of 187 (or 159) cm3 cm-3 at 270 K (or 296 K). SCXRD studies on CH4-loaded ZJU-HOF-5a reveal that abundant supramolecular binding sites combined with ultrahigh porosities account for its high CH4 storage capacities. Combined with high stability, super-hydrophobicity, and easy-recovery, ZJU-HOF-5a is placed among the most promising materials for H2 and CH4 storage applications.

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