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1.
Mol Immunol ; 133: 1-13, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33610121

RESUMO

Transcription factor PU.1 is a regulator of macrophage function, however, the specific function of PU.1 in teleost monocytes/macrophages (MO/MФ) remains unknown. We determined the cDNA sequence of two PU.1 genes from ayu (Plecoglossus altivelis; PaPU.1a and PaPU.1b). Sequence comparisons showed that PaPU.1 were most closely related to the PU.1 of rainbow smelt (Osmerus mordax). The PU.1 transcripts were mainly expressed in the spleen, and their expression was altered in various tissues upon infection with Vibrio anguillarum. PaPU.1a and PaPU.1b proteins were upregulated in MO/MФ, after infection. RNA interference was employed to knockdown PaPU.1a and PaPU.1b to investigate their function in MO/MФ. The expression of inflammatory cytokines was regulated by PaPU.1a, but not PaPU.1b, in ayu MO/MФ upon V. anguillarum infection. Both PaPU.1a and PaPU.1b knockdown lowered the phagocytic activity of MO/MФ. Furthermore, PaPU.1b knockdown attenuated MO/MФ bacterial killing capability. Our results indicate that two PaPU.1 genes differentially modulate the immune response in ayu MO/MФ against bacterial infection.

2.
J Hematol Oncol ; 14(1): 30, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596982

RESUMO

Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

3.
Comp Biochem Physiol B Biochem Mol Biol ; 254: 110575, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609806

RESUMO

Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses and is important in controlling a variety of processes in monocytes and macrophages. However, the role of HIF-1α in the teleost immune system remains less known. In this study, we cloned the cDNA sequence of HIF-1α from the ayu (Plecoglossus altivelis, PaHIF-1α). Sequence and phylogenetic tree analysis showed that PaHIF-1α clustered within the fish HIF-1α tree and was closely related to that of Northern pike (Esox lucius). PaHIF-1α was expressed in all tested tissues and expression increased in liver, head kidney, and body kidney upon Vibrio anguillarum infection. PaHIF-1α was found to regulate the expression of cytokines in ayu monocytes/macrophages (MO/MФ). PaHIF-1α mediated hypoxia-induced enhancement of MO/MФ phagocytic and bactericidal activities to enhance host defenses. Compared with the control, intermittent hypoxia further increased the expression of PaHIF-1α mRNA, improved the survival rate, and reduced the bacterial load of V. anguillarum-infected ayu. Therefore, PaHIF-1α may play a predominant role in the modulation of ayu MO/MФ function.

4.
Int J Biol Macromol ; 164: 3204-3220, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860796

RESUMO

Melanoma is the most dangerous type of skin cancer because of its high invasion and metastasis ability. Bromodomain-containing protein 4 (BRD4), an acetylation-recognizing reader, mediates the proliferation, metastasis, and invasion of melanoma, and is thus a potential therapeutic target. Mounting evidence suggests that inhibition of single bromodomain of BRD4 would improve specificity and reduce cytotoxicity to non-tumor tissues or cells. In this study, a hierarchical virtual screening campaign was performed against BRD4 BD2 from a chemical database including over 90,000 natural/natural-like compounds. Using various biochemical assays, the 7-methoxycoumarin derivative N13 was identified as a potent inhibitor of BRD4 BD2. Compared with the well-known BRD4 inhibitor JQ1, N13 exhibited higher potency against BRD4 BD2 and much higher specificity for BRD4 BD2 over BRD4 BD1. Additionally, N13 inhibited the proliferation of two kinds of BRD4-overexpressing melanoma cell lines. Mechanistically, N13 impaired the protein-protein interaction (PPI) between BRD4 BD2 and its acetylated ligand proteins (Twist1 K73/K76Ac and FOXO3a K242/245Ac), leading to reducing levels of Wnt5A and CDK6 expression, inducing cell senescence of melanoma cancer cells, and ultimately weakening the adhesion, metastasis, and invasion ability of melanoma cancer cells. To our knowledge, N13 is the first 7-methoxybicoumarin-based BRD4 BD2 inhibitor described to date and may function as a new scaffold for developing more specific and potent therapeutic agents against BRD4 BD2. In addition, our research highlights the druggability of BRD4 BD2 as a target for BRD4-overexpressing melanoma and provides a potential mechanism for the anti-melanoma activity of BRD4 BD2 inhibitor.

5.
J Hematol Oncol ; 13(1): 102, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709244

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

6.
J Hematol Oncol ; 13(1): 26, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228680

RESUMO

Protein-protein interactions (PPIs) are central to a variety of biological processes, and their dysfunction is implicated in the pathogenesis of a range of human diseases, including cancer. Hence, the inhibition of PPIs has attracted significant attention in drug discovery. Covalent inhibitors have been reported to achieve high efficiency through forming covalent bonds with cysteine or other nucleophilic residues in the target protein. Evidence suggests that there is a reduced risk for the development of drug resistance against covalent drugs, which is a major challenge in areas such as oncology and infectious diseases. Recent improvements in structural biology and chemical reactivity have enabled the design and development of potent and selective covalent PPI inhibitors. In this review, we will highlight the design and development of therapeutic agents targeting PPIs for cancer therapy.

7.
J Biol Inorg Chem ; 24(8): 1159-1170, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31486954

RESUMO

Alzheimer's disease (AD) is a type of neurodegenerative malady that is associated with the accumulation of amyloid plaques. Metal ions are critical for the development and upkeep of brain activity, but metal dyshomeostasis can contribute to the development of neurodegenerative diseases, including AD. This review highlights the association between metal dyshomeostasis and AD pathology, the feasibility of rebalancing metal homeostasis as a therapeutic strategy for AD, and a survey of current drugs that action via rebalancing metal homeostasis. Finally, we discuss the challenges that should be overcome by researchers in the future to enable the practical use of metal homeostasis rebalancing agents for clinical application.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Quelantes/uso terapêutico , Cobre/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Zinco/metabolismo , Sequência de Aminoácidos , Peptídeos beta-Amiloides/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Multimerização Proteica/efeitos dos fármacos
8.
Int J Mol Sci ; 20(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509940

RESUMO

Due to role of the Keap1-Nrf2 protein-protein interaction (PPI) in protecting cells from oxidative stress, the development of small molecule inhibitors that inhibit this interaction has arisen as a viable approach to combat maladies caused by oxidative stress, such as cancers, neurodegenerative disease and diabetes. To obtain specific and genuine Keap1-Nrf2 inhibitors, many efforts have been made towards developing new screening approaches. However, there is no inhibitor for this target entering the clinic for the treatment of human diseases. New strategies to identify novel bioactive compounds from large molecular databases and accelerate the developmental process of the clinical application of Keap1-Nrf2 protein-protein interaction inhibitors are greatly needed. In this review, we have summarized virtual screening and other methods for discovering new lead compounds against the Keap1-Nrf2 protein-protein interaction. We also discuss the advantages and limitations of different strategies, and the potential of this PPI as a drug target in disease therapy.


Assuntos
Descoberta de Drogas/métodos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Bibliotecas de Moléculas Pequenas/uso terapêutico , Diabetes Mellitus/metabolismo , Diabetes Mellitus/prevenção & controle , Humanos , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos
9.
Cancers (Basel) ; 11(1)2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30650517

RESUMO

Breast cancer is the one of the most frequent causes of female cancer mortality. KDM5A, a histone demethylase, can increase the proliferation, metastasis, and drug resistance of cancers, including breast cancer, and is thus an important therapeutic target. In the present work, we performed hierarchical virtual screening towards the KDM5A catalytic pocket from a chemical library containing 90,000 compounds. Using multiple biochemical methods, the cyclopenta[c]chromen derivative 1 was identified as the top candidate for KDM5A demethylase inhibitory activity. Compared with the well-known KDM5 inhibitor CPI-455 (18), 1 exhibited higher potency against KDM5A and much higher selectivity for KDM5A over both KDM4A and other KDM5 family members (KDM5B and KDM5C). Additionally, compound 1 repressed the proliferation of various KDM5A-overexpressing breast cancer cell lines. Mechanistically, 1 promoted accumulation of p16 and p27 by blocking KDM5A-mediated H3K4me3 demethylation, leading to cell cycle arrest and senescence. To date, compound 1 is the first cyclopenta[c]chromen-based KDM5A inhibitor reported, and may serve as a novel motif for developing more selective and efficacious pharmacological molecules targeting KDM5A. In addition, our research provides a possible anti-cancer mechanism of KDM5A inhibitors and highlights the feasibility and significance of KDM5A as a therapeutic target for KDM5A-overexpressing breast cancer.

10.
ACS Appl Mater Interfaces ; 11(3): 3053-3060, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30585479

RESUMO

The eco-friendly Sn-based perovskites have attracted more and more attention in lead-free perovskite photovoltaic field. However, the device performance and reproducibility are greatly challenged in preparing high-quality perovskite films. Here, we fabricated uniform and dense Sn-based perovskite films via a green gas pump treatment technology. Remarkably, we successfully fabricated a large-area (>20 cm2) Sn-based perovskite film with a mirror-like surface, which is the largest Sn-based perovskite film ever reported. Besides, we found that the phase separation phenomenon induced by excess SnF2 was eliminated when the pressure is 1500 Pa. Finally, we fabricated highly reproducible Sn-based solar cells and obtained an inspiring efficiency of 1.85%, which is the highest reported efficiency for Sn-based devices with a configuration of fluorine-doped tin oxide/compact TiO2/perovskite/hole transport material/electrode. Our results demonstrate the feasibility of using gas pump treatment technique to prepare high-quality Sn-based perovskite films, which paves a way for large-scale green manufacturing of Sn-based perovskite solar cells in the future.

11.
Molecules ; 23(12)2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30518104

RESUMO

Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinogênese/efeitos dos fármacos , Feminino , Histonas/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo
12.
Angew Chem Int Ed Engl ; 57(40): 13091-13095, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29968419

RESUMO

Lysine-specific demethylase 5A (KDM5A) has recently become a promising target for epigenetic therapy. In this study, we designed and synthesized metal complexes bearing ligands with reported demethylase and p27 modulating activities. The Rh(III) complex 1 was identified as a direct, selective and potent inhibitor of KDM5A that directly abrogate KDM5A demethylase activity via antagonizing the KDM5A-tri-/di-methylated histone 3 protein-protein interaction (PPI) in vitro and in cellulo. Complex 1 induced accumulation of H3K4me3 and H3K4me2 levels in cells, causing growth arrest at G1 phase in the triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and 4T1. Finally, 1 exhibited potent anti-tumor activity against TNBC xenografts in an in vivo mouse model, presumably via targeting of KDM5A and hence upregulating p27. Moreover, complex 1 was less toxic compared with two clinical drugs, cisplatin and doxorubicin. To our knowledge, complex 1 is the first metal-based KDM5A inhibitor reported in the literature. We anticipate that complex 1 may be used as a novel scaffold for the further development of more potent epigenetic agents against cancers, including TNBC.


Assuntos
Complexos de Coordenação/química , Proteína 2 de Ligação ao Retinoblastoma/antagonistas & inibidores , Ródio/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular , Complexos de Coordenação/uso terapêutico , Complexos de Coordenação/toxicidade , Feminino , Histonas/antagonistas & inibidores , Histonas/metabolismo , Humanos , Irídio/química , Camundongos , Camundongos Endogâmicos BALB C , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Transplante Heterólogo , Neoplasias de Mama Triplo Negativas/patologia
13.
J Nanosci Nanotechnol ; 18(6): 4121-4126, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442752

RESUMO

Inter-particle bonding formation which determines qualities of nano-scale ceramic coatings is influenced by particle collision behaviors during high velocity collision processes. In this study, collision behaviors between nano-scale TiN particles with different diameters were illuminated by using Molecular Dynamics simulation through controlling impact velocities. Results show that nano-scale TiN particles exhibit three states depending on particle sizes and impact velocities, i.e., bonding, bonding with localized fracturing, and rebounding. These TiN particles states are summarized into a parameter selection map providing an overview of the conditions in terms of particle sizes and velocities. Microstructure results show that localized atoms displacement and partial fracture around the impact region are main reasons for bonding formation of nano-scale ceramic particles, which shows differences from conventional particles refining and amorphization. A relationship between the adhesion energy and the rebound energy is established to understand bonding formation mechanism for nano-scale TiN particle collision. Results show that the energy relationship is depended on the particle sizes and impact velocities, and nano-scale ceramic particles can be bonded together as the adhesion energy being higher than the rebound energy.

14.
J Nanosci Nanotechnol ; 18(4): 2657-2664, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442940

RESUMO

Particle collision behavior influences significantly inter-nano particle bonding formation during the nano-ceramic coating deposition by vacuum cold spraying (or aerosol deposition method). In order to illuminate the collision behavior between nano-scale ceramic particles, molecular dynamic simulation was applied to explore impact process between nano-scale TiO2 particles through controlling impact velocities. Results show that the recoil efficiency of the nano-scale TiO2 particle is decreased with the increase of the impact velocity. Nano-scale TiO2 particle exhibits localized plastic deformation during collision at low velocities, while it is intensively deformed by collision at high velocities. This intensive deformation promotes the nano-particle adhesion rather than rebounding off. A relationship between the adhesion energy and the rebound energy is established for the bonding formation of the nano-scale TiO2 particle. The adhesion energy required to the bonding formation between nano-scale ceramic particles can be produced by high velocity collision.

15.
Chem Commun (Camb) ; 54(20): 2463-2466, 2018 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-29367998
16.
Nanoscale ; 9(41): 15778-15785, 2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-28858347

RESUMO

Organolead trihalide perovskite materials have been widely used as light absorbers in efficient photovoltaic cells. Solution engineering is a fast and effective method to fabricate perovskite films. Here, we report a fast precipitation of a pin-hole free perovskite film by small molecule-driven directed diffusion engineering. Solvent molecules diffuse easily and quickly by colliding with small molecules, e.g. helium. Fully compact perovskite films and highly efficient perovskite solar cells are achieved, and the devices show remarkable stability of ca. 90% original efficiency after more than 1000 hours of testing. The small molecule driving directed diffusion offers a promising fast precipitation of a perovskite film and highly efficient, stable perovskite solar cells.

17.
Sci Rep ; 7: 46141, 2017 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-28401890

RESUMO

To obtain high performance CH3NH3PbI3 perovskite solar cells, it is highly important to realise a high open-circuit voltage. Calculation results based on a modified diode model have indicated that a low bare ratio ϕ of the perovskite film is the most important factor determining the open-circuit voltage, where ϕ is defined as the ratio of the projection of the uncovered area of the perovskite film to the apparent area of the total substrate surface. To realise a low ϕ, we investigate the nucleation behaviour of crystals on rough substrates. The analysis results predict that, when CH3NH3PbI3 is deposited on conventional transparent conductive oxide substrates such as fluorine-doped tin oxide, preferential heterogeneous nucleation will occur on the concave regions of the substrate; then, depending on the subsequent growth step, full coverage of the perovskite film at both the macroscopic and microscopic scales is realised. As a result, an ultra-high open-circuit voltage, i.e., 1.20 V, can be achieved in devices using the full coverage CH3NH3PbI3 film. The thermodynamics theory of precipitation nucleation should shed light on solution engineering of thin films.

18.
Sci Rep ; 6: 36509, 2016 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-27812033

RESUMO

A long-lived aldol reaction-based iridium(III) chemosensor [Ir(ppy)2(5-CHOphen)]PF6 (1, where ppy = 2-phenylpyridine and 5-CHOphen = 1,10-phenanthroline-5-carbaldehyde) for proline detection has been synthesized. The iridium(III) complex 1, incorporating an aldehyde group in N^N donor ligand, can take part in aldol reaction with acetone mediated by proline. The transformation of the sp2-hybridized carbonyl group into a sp3-hybridized alcohol group influences the metal-to-ligand charge-transfer (MLCT) state of the iridium(III) complex, resulting in a change in luminescence in response to proline. The interaction of the iridium(III) complex 1 with proline was investigated by 1H NMR, HRMS and emission titration experiments. Upon the addition of proline to a solution of iridium(III) complex 1, a maximum 8-fold luminescence enhancement was observed. The luminescence signal of iridium(III) complex 1 could be recognized in strongly fluorescent media using time-resolved emission spectroscopy (TRES). The detection of proline in living cells was also demonstrated.


Assuntos
Irídio/metabolismo , Prolina/metabolismo , Linhagem Celular Tumoral , Humanos , Ligantes , Luminescência , Fenantrolinas/metabolismo , Piridinas/metabolismo
19.
Nat Commun ; 7: 12719, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27596364

RESUMO

Haematopoietic stem cells (HSCs) can differentiate into cells of all lineages in the blood. However, the mechanisms by which cytokines in the blood affect HSC homeostasis remain largely unknown. Here we show that leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional cytokine, induces HSC expansion and mobilization. Recombinant LECT2 administration results in HSC expansion in the bone marrow and mobilization to the blood via CD209a. The effect of LECT2 on HSCs is reduced after specific depletion of macrophages or reduction of osteolineage cells. LECT2 treatment reduces the tumour necrosis factor (TNF) expression in macrophages and osteolineage cells. In TNF knockout mice, the effect of LECT2 on HSCs is reduced. Moreover, LECT2 induces HSC mobilization in irradiated mice, while granulocyte colony-stimulating factor does not. Our results illustrate that LECT2 is an extramedullar cytokine that contributes to HSC homeostasis and may be useful to induce HSC mobilization.


Assuntos
Linhagem da Célula/fisiologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Células CHO , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Cricetulus , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Fator Estimulador de Colônias de Granulócitos , Células-Tronco Hematopoéticas/fisiologia , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Leucócitos Mononucleares , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
20.
Dongwuxue Yanjiu ; 37(3): 126-35, 2016 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-27265650

RESUMO

Ayu (Plecoglossus altivelis) fish, which are an amphidromous species distributed in East Asia, live in brackish water (BW) during their larval stage and in fresh water (FW) during their adult stage. In this study, we found that FW-acclimated ayu larvae exhibited a slower growth ratio compared with that of BW-acclimated larvae. However, the mechanism underlying FW acclimation on growth suppression is poorly known. We employed transcriptome analysis to investigate the differential gene expression of FW acclimation by RNA sequencing. We identified 158 upregulated and 139 downregulated transcripts in FW-acclimated ayu larvae compared with that in BW-acclimated larvae. As determined by Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway mapping, functional annotation of the genes covered diverse biological functions and processes, and included neuroendocrinology, osmotic regulation, energy metabolism, and the cytoskeleton. Transcriptional expression of several differentially expressed genes in response to FW acclimation was further confirmed by real-time quantitative PCR. In accordance with transcriptome analysis, iodothyronine deiodinase (ID), pro-opiomelanocortin (POMC), betaine-homocysteine S-methyltransferase 1(BHMT), fructose-bisphosphate aldolase B (aldolase B), tyrosine aminotransferase (TAT), and Na(+)-K(+) ATPase (NKA) were upregulated after FW acclimation. Furthermore, the mRNA expressions of b-type natriuretic peptide (BNP) and transgelin were downregulated after FW acclimation. Our data indicate that FW acclimation reduced the growth rate of ayu larvae, which might result from the expression alteration of genes related to endocrine hormones, energy metabolism, and direct osmoregulation.


Assuntos
Perfilação da Expressão Gênica , Larva/efeitos dos fármacos , Larva/genética , Osmeriformes/genética , Salinidade , Aclimatação/efeitos dos fármacos , Aclimatação/genética , Animais , Tamanho Corporal/efeitos dos fármacos , Tamanho Corporal/genética , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Água Doce/química , Larva/crescimento & desenvolvimento , Larva/fisiologia , Osmeriformes/crescimento & desenvolvimento , Osmeriformes/fisiologia
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