Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
Proc Natl Acad Sci U S A ; 121(11): e2313123121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437546

RESUMO

Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.


Assuntos
Hominidae , Tecnologia , Humanos , Animais , Ásia Oriental , China , África
2.
Bull Environ Contam Toxicol ; 112(4): 51, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556558

RESUMO

Esketamine (ESK) is the S-enantiomer of ketamine racemate (a new psychoactive substance) that can result in illusions, and alter hearing, vision, and proprioception in human and mouse. Up to now, the neurotoxicity caused by ESK at environmental level in fish is still unclear. This work studied the effects of ESK on behaviors and transcriptions of genes in dopamine and GABA pathways in zebrafish larvae at ranging from 12.4 ng L- 1 to 11141.1 ng L- 1 for 7 days post fertilization (dpf). The results showed that ESK at 12.4 ng L- 1 significantly reduced the touch response of the larvae at 48 hpf. ESK at 12.4 ng L- 1 also reduced the time and distance of larvae swimming at the outer zone during light period, which implied that ESK might potentially decrease the anxiety level of larvae. In addition, ESK increased the transcription of th, ddc, drd1a, drd3 and drd4a in dopamine pathway. Similarly, ESK raised the transcription of slc6a1b, slc6a13 and slc12a2 in GABA pathway. This study suggested that ESK could affect the heart rate and behaviors accompanying with transcriptional alterations of genes in DA and GABA pathways at early-staged zebrafish, which resulted in neurotoxicity in zebrafish larvae.


Assuntos
Dopamina , Ketamina , Humanos , Animais , Camundongos , Dopamina/metabolismo , Dopamina/farmacologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Ketamina/metabolismo , Ketamina/farmacologia , Larva , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia
3.
Environ Sci Technol ; 57(36): 13384-13396, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37651267

RESUMO

Imidacloprid (IMI) and thiamethoxam (THM) are ubiquitous in aquatic ecosystems. Their negative effects on parental fish are investigated while intergenerational effects at environmentally relevant concentrations remain unclear. In this study, F0 zebrafish exposed to IMI and THM (0, 50, and 500 ng L-1) for 144 days post-fertilization (dpf) was allowed to spawn with two modes (internal mating and cross-mating), resulting in four types of F1 generations to investigate the intergenerational effects. IMI and THM affected F0 zebrafish fecundity, gonadal development, sex hormone and VTG levels, with accumulations found in F0 muscles and ovaries. In F1 generation, paternal or maternal exposure to IMI and THM also influenced sex hormones levels and elevated the heart rate and spontaneous movement rate. LncRNA-mRNA network analysis revealed that cell cycle and oocyte meiosis-related pathways in IMI groups and steroid biosynthesis related pathways in THM groups were significantly enriched in F1 offspring. Similar transcriptional alterations of dmrt1, insl3, cdc20, ccnb1, dnd1, ddx4, cox4i1l, and cox5b2 were observed in gonads of F0 and F1 generations. The findings indicated that prolonged paternal or maternal exposure to IMI and THM could severely cause intergenerational toxicity, resulting in developmental toxicity and endocrine-disrupting effects in zebrafish offspring.


Assuntos
Exposição Materna , Peixe-Zebra , Animais , Feminino , Humanos , Tiametoxam , Ecossistema
4.
Small ; 18(1): e2105246, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34741426

RESUMO

Electrocatalytic CO2 reduction reaction (CO2 RR) toward formate production can be operated under mild conditions with high energy conversion efficiency while migrating the greenhouse effect. Herein, an integrated 3D open network of interconnected bismuthene arrays (3D Bi-ene-A/CM) is fabricated via in situ electrochemically topotactic transformation from BiOCOOH nanosheet arrays supported on the copper mesh. The resulted 3D Bi-ene-A/CM consists of 2D atomically thin metallic bismuthene (Bi-ene) in the form of an integrated array superstructure with a 3D interconnected and open network, which harvests the multiple structural advantages of both metallenes and self-supported electrodes for electrocatalysis. Such distinctive superstructure affords the maximized quantity and availability of the active sites with high intrinsic activity and superior charge and mass transfer capability, endowing the catalyst with good CO2 RR performance for stable formate production with high Faradaic efficiency (≈90%) and current density (>300 mA cm-2 ). Theoretical calculation verifies the superior intermediate stabilization of the dominant Bi plane during CO2 RR. Moreover, by further coupling anodic methanol oxidation reaction, an exotic electrolytic system enables highly energy-efficient and value-added pair-electrosynthesis for concurrent formate production at both electrodes, achieving substantially improved electrochemical and economic efficiency and revealing the feasibility for practical implementation.

5.
Proc Natl Acad Sci U S A ; 116(20): 9820-9824, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31036653

RESUMO

Middle to Late Pleistocene human evolution in East Asia has remained controversial regarding the extent of morphological continuity through archaic humans and to modern humans. Newly found ∼300,000-y-old human remains from Hualongdong (HLD), China, including a largely complete skull (HLD 6), share East Asian Middle Pleistocene (MPl) human traits of a low vault with a frontal keel (but no parietal sagittal keel or angular torus), a low and wide nasal aperture, a pronounced supraorbital torus (especially medially), a nonlevel nasal floor, and small or absent third molars. It lacks a malar incisure but has a large superior medial pterygoid tubercle. HLD 6 also exhibits a relatively flat superior face, a more vertical mandibular symphysis, a pronounced mental trigone, and simple occlusal morphology, foreshadowing modern human morphology. The HLD human fossils thus variably resemble other later MPl East Asian remains, but add to the overall variation in the sample. Their configurations, with those of other Middle and early Late Pleistocene East Asian remains, support archaic human regional continuity and provide a background to the subsequent archaic-to-modern human transition in the region.


Assuntos
Fósseis , Crânio , China , Humanos , Dente
6.
Bull Environ Contam Toxicol ; 110(1): 5, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36507940

RESUMO

Agricultural use of neonicotinoid insecticides, neuroactive nitroguanidine compounds, has been detected everywhere in the global, posing significant hazard to nontarget organisms. This work studied the developmental neurotoxicity of zebrafish larvae exposed to imidacloprid (IMI) and thiamethoxam (THM), ranging from 0.05 µg L- 1 to 50 µg L- 1 for 35 days. Transcriptions of genes belonging to the behavior, neurodevelopment and cortisol synthesis in zebrafish larvae were monitored. The qPCR data demonstrated that with exposure time increased, the transcription of behavior related genes was down-regulated in both IMI and THM groups, such as macf1, cdh6 and syt10. Additionally, IMI and THM significantly up-regulated the transcriptions of actha, and down-regulated il1rapl1b and pi4k2a at 35 dpf. Importantly, IMI markedly enhanced the transcripiton of gfap, shha, nkx2.2a and nestin in a time dependent manner. This work provided the foundation for understanding zebrafish larvae's neurotoxicity induced by IMI and THM.


Assuntos
Inseticidas , Peixe-Zebra , Animais , Tiametoxam/toxicidade , Larva , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Inseticidas/toxicidade , Inseticidas/análise
7.
Ecotoxicol Environ Saf ; 227: 112917, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34678628

RESUMO

Imidacloprid (IMI) and thiamethoxam (THM) are two commonly applied neonicotinoid insecticides. IMI and THM could cause negative impacts on non-target organisms like bees. However, the information about neurotoxicity of IMI and THM in fish is still scarce. Here we investigated the effects of IMI and THM on locomotor behavior, AChE activity, and transcription of genes related to synaptic transmission in zebrafish exposed to IMI and THM with concentrations of 50 ng L-1 to 50,000 ng L-1 at 14 day post fertilization (dpf), 21 dpf, 28 dpf and 35 dpf. Our results showed that IMI and THM significantly influenced the locomotor activity in larvae at 28 dpf and 35 dpf. THM elevated AChE activity at 28 dpf. The qPCR data revealed that IMI and THM affected the transcription of marker genes belonging to the synapse from 14 dpf to 35 dpf. Furthermore, IMI and THM mainly affected transcription of key genes in γ-aminobutyric acid, dopamine and serotonin pathways in larvae at 28 dpf and 35 dpf. These results demonstrated the neurotoxicity of IMI and THM in zebrafish. The findings from this study suggested that IMI and THM in the aquatic environment may pose potential risks to fish fitness and survival.


Assuntos
Inseticidas , Poluentes Químicos da Água , Animais , Abelhas , Inseticidas/análise , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Transmissão Sináptica , Tiametoxam , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
8.
Ecotoxicol Environ Saf ; 208: 111566, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396095

RESUMO

Androgens and estrogens often co-exist in aquatic environments and pose potential risks to fish populations. However, little is known about the endocrine disrupting effects of the mixture of androgens and estrogens in fish. In this study, transcriptional level of target genes related to the hypothalamic-pituitary-gonadal-liver (HPGL) axis, sex hormone level, VTG protein concentration, histology and secondary sex characteristic were assessed in the ovaries and livers of adult female western mosquitofish (Gambusia affinis) exposed to 17ß-estradiol (E2), testosterone (T), and mixtures of E2 and T for 91 days. The results showed that the transcriptional expression of cytochrome P450, family 19, subfamily A, polypeptide 1a (Cyp19a1a) was suppressed in the 200 ng/L T treatment and the 50 ng/L E2 + 200 ng/L T treatment in the ovaries. Steroidogenic acute regulatory protein (Star) and Cyp11a1 showed a similar expression pattern in the T treatment to its corresponding T + E2 mixtures. In the ovaries, the concentrations of 17ß-estradiol and testosterone were decreased in most treatments compared with the solvent control. VTG protein was induced in all steroid treatment. However, exposure to T or E2 + T mixture did not cause the abnormal cells of the ovaries and livers and an extension of the anal fins in female G. affinis. This study demonstrates that chronic exposure to E2, T and their mixtures affects the transcripts of genes in the HPGL axis, steroid hormone level and VTG protein concentration in the ovaries and livers, but fails to cause the histopathological effect of the ovaries and livers and alter the morphology of the anal fins in G. affinis.


Assuntos
Ciprinodontiformes/fisiologia , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Androgênios/metabolismo , Animais , Ciprinodontiformes/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Disruptores Endócrinos/metabolismo , Estradiol/metabolismo , Estrogênios/metabolismo , Feminino , Hormônios Esteroides Gonadais/metabolismo , Fígado/efeitos dos fármacos , Masculino , Ovário/efeitos dos fármacos , Testosterona/metabolismo , Vitelogeninas/metabolismo
9.
Environ Sci Technol ; 54(10): 6009-6020, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32324390

RESUMO

Perfluoroalkyl substances (PFASs) are persistent chemicals in the environment. So far, little is known about their uptake potential in wetland plants. Here, we investigated the uptake and translocation of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in eight common wetland plants, namely, Canna indica (Ci), Thalia dealbata (Td), Cyperus alternifolius (Ca), Phragmites australis (Pa), Arundo donax (Ad), Pontederia cordata (Pc), Cyperus papyrus (Cp), and Alisma orientale (Ao) by hydroponic experiments and visualized their tissue- and cell-level distribution with desorption electrospray ionization mass spectrometry (DESI-MS) and transmission electron microscopy equipped with energy-dispersive spectroscopy (TEM-EDS). The results showed that the PFASs accumulated in plants accounted for 1.67-16.7% of the total mass spiked into the hydroponic systems, and PFOS accumulated largely in roots (48.8-95.8%), while PFOA was stored mostly in the aboveground part (29.3-77.4%). DESI-MS and TEM-EDS analysis showed that PFASs in Ci, Td, Pa, and Ca were transported from the hydroponic solution to the root cortex via both apoplastic (e.g., across cell walls and/or intercellular spaces) and symplastic routes (e.g., across plasma membranes or via plasmodesmata) and further to the vascular bundle via symplastic route in Td and Pa and via both routes in Ci and Ca. These two chemicals were transported from roots to stems mainly through the cortex in Td and through both the cortex and vascular bundles in Ci and Ca.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos/análise , Caprilatos , Microscopia Eletrônica de Transmissão , Espectrometria de Massas por Ionização por Electrospray , Análise Espectral , Áreas Alagadas
10.
Ecotoxicol Environ Saf ; 193: 110371, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32114246

RESUMO

Medroxyprogesterone acetate (MPA) is a widely used synthetic progestin in contraception pills and hormone replacement therapy. However, its effects on eye growth and development and function were largely unknown. In this study, the transcription of genes in the Notch signaling pathway and the visual cycle network were evaluated after chronic MPA exposure at 4.32 (L), 42.0 (M), and 424 (H) ng L-1 for 120 days in zebrafish. Meanwhile, the histology of the eyes was also examined. Transcriptional results showed that MPA at all three concentrations significantly increased the transcription of notch1a, dll4, jag1a, ctbp1 and rbpjb (key genes in the Notch signaling pathway) in the eyes of females. The up-regulation of noth1a, ctbp1 and kat2b was also observed in the eyes of males exposed to MPA at 424 ng L-1. In the visual cycle pathway, MPA increased the transcription of opn1sw1, opn1sw2, arr3a and rpe65a in the eyes of females from the M and H treatments. Histopathological analysis showed that exposure to 42.0 ng L-1 of MPA increased the thicknesses of inner nuclear layer in females and outer segment in males. Moreover, exposure to 424 ng L-1 of MPA increased the lens diameter in females. These results indicated that chronic MPA exposure affected the transcription of genes in the Notch signaling and in the visual cycle pathways, resulting in overgrowth of the eyes and interference of the eye functions. This study suggests that MPA pose a risk to fitness and survival of zebrafish in areas where MPA contamination exists.


Assuntos
Contraceptivos Hormonais/toxicidade , Olho/efeitos dos fármacos , Acetato de Medroxiprogesterona/toxicidade , Animais , Olho/crescimento & desenvolvimento , Olho/patologia , Feminino , Masculino , Receptores Notch/metabolismo , Retina , Transdução de Sinais/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
11.
Angew Chem Int Ed Engl ; 59(35): 15014-15020, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32421894

RESUMO

Electrochemical reduction of CO2 to valuable fuels is appealing for CO2 fixation and energy storage. However, the development of electrocatalysts with high activity and selectivity in a wide potential window is challenging. Herein, atomically thin bismuthene (Bi-ene) is pioneeringly obtained by an in situ electrochemical transformation from ultrathin bismuth-based metal-organic layers. The few-layer Bi-ene, which possesses a great mass of exposed active sites with high intrinsic activity, has a high selectivity (ca. 100 %), large partial current density, and quite good stability in a potential window exceeding 0.35 V toward formate production. It even deliver current densities that exceed 300.0 mA cm-2 without compromising selectivity in a flow-cell reactor. Using in situ ATR-IR spectra and DFT analysis, a reaction mechanism involving HCO3 - for formate generation was unveiled, which brings new fundamental understanding of CO2 reduction.

12.
Small ; 15(35): e1902218, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31293075

RESUMO

Controllable synthesis of ultrathin metal-organic framework (MOF) nanosheets and rational design of their nano/microstructures in favor of electrochemical catalysis is critical for their renewable energy applications. Herein, an in situ growth method is proposed to prepare the ultrathin NiFe MOF nanosheets with a thickness of 1.5 nm, which are vertically inlaid into a 3D ordered macroporous structure of NiFe hydroxide. The well-designed composite delivers an efficient electrocatalytic performance with a low overpotential of 270 mV at a current density of 10 mA cm-2 and stable electrolysis as long as 10 h toward the electrochemical oxygen evolution reaction, much superior to the state-of-the-art RuO2 electrocatalyst. A comprehensive analysis demonstrates that the excellent performance originates from the desirable combination of the highly exposed active centers in the ultrathin bimetallic MOF nanosheets, effective electron conduction between MOF nanosheets and ordered macroporous hydroxide, and efficient mass transfer across the hierarchically porous hybridization. This study sheds light on the exploration of powerful protocols to gain diverse high-performance MOF nanosheets and may open a perspective to achieve their efficient electrocatalytic performance.

13.
Ecotoxicol Environ Saf ; 183: 109556, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31509926

RESUMO

Dydrogesterone (DDG) is a synthetic progestin used in contraception and hormone replacement therapy. Our previous transcriptome data showed that the response to light stimulus, photoperiodism and rhythm related gene ontology (GO) terms were significantly enriched in the brain of zebrafish after chronic exposure to DDG. Here we investigated the effects of DDG on the eye of zebrafish. Zebrafish were exposed to DDG at three concentration levels (3.39, 33.1, and 329 ng L-1) for 120 days. Based on our previous transcriptome data, the transcription of genes involved in visual cycle and circadian rhythm network was examined by qPCR analysis. In the visual cycle network, exposure to all concentrations of DDG significantly decreased transcription of grk7a, aar3a and guca1d, while increased the transcription of opn1mw4 and opn1sw2 at the low concentration. Importantly, exposure to all concentrations of DDG down-regulated the transcription of rep65a that encodes a critical enzyme to catalyze the conversion from all-trans-retinal to 11-cis-retinal in the eye of male zebrafish. In the circadian rhythm network, DDG enhanced the transcription of clocka, arntl2 and nifil3-5 at all three concentrations, while it decreased the transcription of cry5, per1b, nr1d2b and si:ch211.132b12.7. In addition, DDG decreased the transcription of tefa in both males and females. Moreover, histological analysis showed the exposure to 329 ng L-1 of DDG decreased the thickness of retinal ganglion cell in the eye of male zebrafish. These results indicated that DDG exposure could affect the transcription of genes in visual cycle and circadian rhythm network in the eyes of zebrafish. This suggests that DDG has potential negative impact on the normal eye function.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Didrogesterona/toxicidade , Retina/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Ritmo Circadiano/genética , Relação Dose-Resposta a Droga , Feminino , Masculino , Retina/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
14.
Exploration (Beijing) ; 4(3): 20230043, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38939862

RESUMO

The coupling electrosynthesis involving CO2 upgrade conversion is of great significance for the sustainable development of the environment and energy but is challenging. Herein, we exquisitely constructed the self-supported bimetallic array superstructures from the Cu(OH)2 array architecture precursor, which can enable high-performance coupling electrosynthesis of formate and adipate at the anode and the cathode, respectively. Concretely, the faradaic efficiencies (FEs) of CO2-to-formate and cyclohexanone-to-adipate conversion simultaneously exceed 90% at both electrodes with excellent stabilities. Such high-performance coupling electrosynthesis is highly correlated with the porous nanosheet array superstructure of CuBi alloy as the cathode and the nanosheet-on-nanowire array superstructure of CuNi hydroxide as the anode. Moreover, compared to the conventional electrolysis process, the cell voltage is substantially reduced while maintaining the electrocatalytic performance for coupling electrosynthesis in the two-electrode electrolyzer with the maximal FEformate and FEadipate up to 94.2% and 93.1%, respectively. The experimental results further demonstrate that the bimetal composition modulates the local electronic structures, promoting the reactions toward the target products. Prospectively, our work proposes an instructive strategy for constructing adaptive self-supported superstructures to achieve efficient coupling electrosynthesis.

15.
Artigo em Inglês | MEDLINE | ID: mdl-39233286

RESUMO

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity.


Assuntos
Etinilestradiol , Poluentes Químicos da Água , Peixe-Zebra , Animais , Etinilestradiol/toxicidade , Poluentes Químicos da Água/toxicidade , Disruptores Endócrinos/toxicidade , Transcriptoma/efeitos dos fármacos , Multiômica
16.
J Hazard Mater ; 465: 133463, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38219582

RESUMO

Azole antifungal climbazole has frequently been detected in aquatic environments and shows various effects in fish. However, the underlying mechanism of toxicity through the gut-brain axis of climbazole is unclear. Here, we investigated the effects of climbazole at environmental concentrations on the microbiota-intestine-brain axis in grass carp via histopathological observation, gene expression and biochemical analyses, and high-throughput sequencing of the 16 S rRNA. Results showed that exposure to 0.2 to 20 µg/L climbazole for 42 days significantly disrupted gut microbiota and caused brain neurotoxicity in grass carp. In this study, there was an alteration in the phylum and genus compositions in the gut microbiota following climbazole treatment, including reducing Fusobacteria (e.g., Cetobacterium) and increasing Actinobacteria (e.g., Nocardia). Climbazole disrupted intestinal microbial abundance, leading to increased levels of lipopolysaccharide and tumor necrosis factor-alpha in the gut, serum, and brain. They passed through the impaired intestinal barrier into the circulation and caused the destruction of the blood-brain barrier through the gut-brain axis, allowing them into the brain. In the brain, climbazole activated the nuclear factor kappaB pathway to increase inflammation, and suppressed the E2-related factor 2 pathway to produce oxidative damage, resulting in apoptosis, which promoted neuroinflammation and neuronal death. Besides, our results suggested that this neurotoxicity was caused by the breakdown of the microbiota-gut-brain axis, mediated by reduced concentrations of dopamine, short chain fatty acids, and intestinal microbial activity induced by climbazole.


Assuntos
Carpas , Fungicidas Industriais , Imidazóis , Animais , Eixo Encéfalo-Intestino , Azóis
17.
J Hazard Mater ; 468: 133844, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394900

RESUMO

Androgen receptor (AR) agonists have strong endocrine disrupting effects in fish. Most studies mainly investigate AR binding capacity using human AR in vitro. However, there is still few methods to rapidly predict AR agonists in aquatic organisms. This study aimed to screen AR agonists of fish species using machine learning and molecular models in water-relevant list from NORMAN, a network of reference laboratories for monitoring contaminants of emerging concern in the environment. In this study, machine learning approaches (e.g., Deep Forest (DF)), Random Forests and artificial neural networks) were applied to predict AR agonists. Zebrafish, fathead minnow, mosquitofish, medaka fish and grass carp are all important aquatic model organisms widely used to evaluate the toxicity of new pollutants, and the molecular models of ARs from these five fish species were constructed to further screen AR agonists using AlphaFold2. The DF method showed the best performances with 0.99 accuracy, 0.97 sensitivity and 1 precision. The Asn705, Gln711, Arg752, and Thr877 residues in human AR and the corresponding sites in ARs from the five fish species were responsible for agonist binding. Overall, 245 substances were predicted as suspect AR agonists in the five fish species, including, certain glucocorticoids, cholesterol metabolites, and cardiovascular drugs in the NORMAN list. Using machine learning and molecular modeling hybrid methods rapidly and accurately screened AR agonists in fish species, and helping evaluate their ecological risk in fish populations.


Assuntos
Androgênios , Disruptores Endócrinos , Peixes , Receptores Androgênicos , Animais , Humanos , Androgênios/química , Androgênios/toxicidade , Cyprinidae , Aprendizado de Máquina , Modelos Moleculares , Peixe-Zebra , Disruptores Endócrinos/química , Disruptores Endócrinos/toxicidade
18.
Sci Total Environ ; 923: 171475, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38453063

RESUMO

Climbazole is an azole biocide that has been widely used in formulations of personal care products. Climbazole can cause developmental toxicity and endocrine disruption as well as gut disturbance in aquatic organisms. However, the mechanisms behind gut toxicity induced by climbazole still remain largely unclear in fish. Here, we evaluate the gut effects by exposing grass carp (Ctenopharyngodon idella) to climbazole at levels ranging from 0.2 to 20 µg/L for 42 days by evaluating gene transcription and expression, biochemical analyses, correlation network analysis, and molecular docking. Results showed that climbazole exposure increased cyp1a mRNA expression and ROS level in the three treatment groups. Climbazole also inhibited Nrf2 and Keap1 transcripts as well as proteins, and suppressed the transcript levels of their subordinate antioxidant molecules (cat, sod, and ho-1), increasing oxidative stress. Additionally, climbazole enhanced NF-κB and iκBα transcripts and proteins, and the transcripts of NF-κB downstream pro-inflammatory factors (tnfα, and il-1ß/6/8), leading to inflammation. Climbazole increased pro-apoptosis-related genes (fadd, bad1, and caspase3), and decreased anti-apoptosis-associated genes (bcl2, and bcl-xl), suggesting a direct reaction to apoptosis. The molecular docking data showed that climbazole could form stable hydrogen bonds with CYP1A. Mechanistically, our findings suggested that climbazole can induce inflammation and oxidative stress through CYP450s/ROS/Nrf2/NF-κB pathways, resulting in cell apoptosis in the gut of grass carp.


Assuntos
Carpas , Suplementos Nutricionais , Imidazóis , Animais , Suplementos Nutricionais/análise , Dieta , NF-kappa B , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Imunidade Inata , Azóis/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Inflamação/induzido quimicamente , Inflamação/veterinária , Estresse Oxidativo , Apoptose , Carpas/metabolismo
19.
Sci Total Environ ; 955: 176895, 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39401594

RESUMO

Sodium p-perfluorous nonenoxybenzene sulfonate (OBS) is a prominent alternative to perfluorooctanesulfonic acid (PFOS). Numerous studies have demonstrated hepatotoxicity and neurotoxicity of OBS and PFOS in mammals. The lungs, as a sensitive organ, are among the potential target organs for OBS and PFOS exposure. However, their toxic effects on the lungs remain unclear. In the present study, three-dimensional (3D) spheroids constructed from A549 cells were exposed to OBS and PFOS for 7 days to evaluate pulmonary toxicity through morphological examination, growth kinetics, transcriptomic profiling, and biochemical assays. Our results showed that OBS significantly reduced the diameter, volume, and growth fraction of the spheroids compared to PFOS. Transcriptomic analysis revealed a notable enrichment of the IL-17 signaling pathway after 7 days of OBS exposure. Significant differences in the transcription of genes within this pathway were observed between OBS and PFOS exposure. OBS reduced the transcription of tnfaip3, nfkbiα, map3k8, enpp2, jun, il6, cxcl1, cxcl2, cxcl3, and cxcl8 in the IL-17 signaling pathway, while PFOS enhanced the transcription of nfkbiα. Additionally, OBS decreased the level of IL-8, whereas PFOS had a minor effect. Cluster analysis confirmed significant differences in the pulmonary toxicity between OBS and PFOS. Our study demonstrated the utility of spheroids as an in vitro cell model complemented with omics technology, for comparing the pulmonary toxicity of OBS and PFOS. It provided a novel approach for evaluating the pulmonary toxicity of new pollutants like OBS.

20.
J Colloid Interface Sci ; 640: 423-433, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36870218

RESUMO

Anodic oxidation assisted hydrogen production under mild conditions powered by renewable electricity represents a sustainable approach to energy conversion systems. Here, we fabricated a versatile and universal self-supported nanoarray platform that can be intelligently edited to achieve adaptive electrocatalysis for alcohol oxidation reactions and hydrogen evolution reaction (HER). The obtained self-supported nanoarray electrocatalysts exhibit excellent catalytic activity due to the integration of multiple merits of rich nanointerface-reconstruction and self-supported hierarchical structures. Particularly, the membrane-free pair-electrolysis system coupling HER and ethylene glycol oxidation reaction (EGOR) required an applied voltage of only 1.25 V to drive the current density of 10 mA cm-2, which is about 510 mV lower than that of the overall water splitting, showing the capability to simultaneously produce H2 and formate with high Faradic efficiency and stability. This work demonstrates a catalytic self-supported nanoarray platform for energy-efficient production of high-purity H2 and value-added chemicals.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA