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1.
J Agric Food Chem ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39057603

RESUMO

Bioisosteric silicon replacement has proven to be a valuable strategy in the design of bioactive molecules for crop protection and drug development. Twenty-one novel carboxamides possessing a silicon-containing biphenyl moiety were synthesized and tested for their antifungal activity and succinate dehydrogenase (SDH) enzymatic inhibitory activity. Among these novel succinate dehydrogenase inhibitors (SDHIs), compounds 3a, 3e, 4l, and 4o possessing appropriate clog P and topological polar surface area values showed excellent inhibitory effects against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Fusarium graminearum at 10 mg/L in vitro, and the EC50 values of 4l and 4o were 0.52 and 0.16 mg/L against R. solani and 0.066 and 0.054 mg/L against S. sclerotiorum, respectively, which were superior to those of Boscalid. Moreover, compound 3a demonstrated superior SDH enzymatic inhibitory activity (IC50 = 8.70 mg/L), exhibiting 2.54-fold the potency of Boscalid (IC50 = 22.09 mg/L). Docking results and scanning electron microscope experiments revealed similar mode of action between compound 3a and Boscalid. The new silicon-containing carboxamide 3a is a promising SDHI candidate that deserves further investigation.

2.
Cancer Immunol Immunother ; 73(9): 177, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954046

RESUMO

Paclitaxel and anthracycline-based chemotherapy is one of the standard treatment options for breast cancer. However, only about 6-30% of breast cancer patients achieved a pathological complete response (pCR), and the mechanism responsible for the difference is still unclear. In this study, random forest algorithm was used to screen feature genes, and artificial neural network (ANN) algorithm was used to construct an ANN model for predicting the efficacy of neoadjuvant chemotherapy for breast cancer. Furthermore, digital pathology, cytology, and molecular biology experiments were used to verify the relationship between the efficacy of neoadjuvant chemotherapy and immune ecology. It was found that paclitaxel and doxorubicin, an anthracycline, could induce typical pyroptosis and bubbling in breast cancer cells, accompanied by gasdermin E (GSDME) cleavage. Paclitaxel with LDH release and Annexin V/PI doubule positive cell populations, and accompanied by the increased release of damage-associated molecular patterns, HMGB1 and ATP. Cell coculture experiments also demonstrated enhanced phagocytosis of macrophages and increased the levels of IFN-γ and IL-2 secretion after paclitaxel treatment. Mechanistically, GSDME may mediate paclitaxel and doxorubicin-induced pyroptosis in breast cancer cells through the caspase-9/caspase-3 pathway, activate anti-tumor immunity, and promote the efficacy of paclitaxel and anthracycline-based neoadjuvant chemotherapy. This study has practical guiding significance for the precision treatment of breast cancer, and can also provide ideas for understanding molecular mechanisms related to the chemotherapy sensitivity.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Piroptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Humanos , Piroptose/efeitos dos fármacos , Feminino , Terapia Neoadjuvante/métodos , Camundongos , Animais , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Gasderminas
3.
Artigo em Inglês | MEDLINE | ID: mdl-38860904

RESUMO

BACKGROUND: Sorafenib is currently the first choice for the treatment of patients with advanced hepatocellular carcinoma, but its therapeutic effect is still limited. OBJECTIVES: This study aims to examine whether WEE family kinase inhibitors can enhance the anticancer effect of sorafenib. METHODS: We analyzed the expression levels of PKMYT1 kinase and WEE1 kinase in HCC, studied the inhibitory effect of PKMYT1 kinase inhibitor RP-6306, WEE1 kinase inhibitor adavosertib combined with sorafenib on the proliferation of HCC cells, and detected the effect of drug combination on CDK1 phosphorylation. RESULTS: We found that PKMYT1 and WEE1 were upregulated in HCC and were detrimental to patient survival. Cell experiments showed that both RP-6306 and adavosertib (1-100 µM) inhibited the proliferation of HCC cell lines in a dose-dependent manner alone, and the combination of the two drugs had a synergistic effect. In HCC cell lines, sorafenib combined with RP-6306 or adavosertib showed a synergistic antiproliferation effect and less toxicity to normal cells. Sorafenib combined with RP-6306 and adavosertib further inhibited the proliferation of HCC cells and caused complete dephosphorylation of CDK1. CONCLUSION: Taken together, our findings provide experimental evidence for the future use of sorafenib in combination with RP-6306 or adavosertib for the treatment of HCC.

4.
Org Biomol Chem ; 22(23): 4656-4661, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38804023

RESUMO

The intermolecular [4 + 2] cycloaddition of o-hydroxy benzyl alcohols with isochroman ketals was realized by CF3CO2H catalysis. A broad range of bisbenzannulated [6,6]-spiroketals were formed under the metal-free mild conditions in moderate to excellent yields (45-98%) with mostly excellent diastereoselectivities (up to >20 : 1 dr). Furthermore, the enantioselective version was also preliminarily investigated and the bisbenzannulated [6,6]-spiroketal was obtained with 61% ee in the presence of Sc(OTf)3/Feng's chiral N,N'-dioxide ligand. Some of the bisbenzannulated [6,6]-spiroketal products showed good in vitro antifungal activities against Sclerotinia sclerotiorum and Rhizoctonia solani.

5.
J Agric Food Chem ; 72(21): 11949-11957, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38757770

RESUMO

As the first marketed phenylpyrazole insecticide, fipronil exhibited remarkable broad-spectrum insecticidal activity. However, it poses a significant threat to aquatic organisms and bees due to its high toxicity. Herein, 35 phenylpyrazole derivatives containing a trifluoroethylthio group on the 4 position of the pyrazole ring were designed and synthesized. The predicted physicochemical properties of all of the compounds were within a reasonable range. The biological assay results revealed that compound 7 showed 69.7% lethality against Aedes albopictus (A. albopictus) at the concentration of 0.125 mg/L. Compounds 7, 7g, 8d, and 10j showed superior insecticidal activity for the control of Plutella xylostella (P. xylostella). Notably, compound 7 showed similar insecticidal activity against Aphis craccivora (A. craccivora) compared with fipronil. Potential surface calculation and molecular docking suggested that different lipophilicity and binding models to the Musca domestica (M. domestica) gamma-aminobutyric acid receptors may be responsible for the decreased activity of the tested derivatives. Toxicity tests indicated that compound 8d (LC50 = 14.28 mg/L) induced obviously 14-fold lower toxicity than fipronil (LC50 = 1.05 mg/L) on embryonic-juvenile zebrafish development.


Assuntos
Aedes , Desenho de Fármacos , Moscas Domésticas , Inseticidas , Simulação de Acoplamento Molecular , Pirazóis , Animais , Inseticidas/química , Inseticidas/síntese química , Inseticidas/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Aedes/efeitos dos fármacos , Aedes/crescimento & desenvolvimento , Relação Estrutura-Atividade , Moscas Domésticas/efeitos dos fármacos , Moscas Domésticas/crescimento & desenvolvimento , Afídeos/efeitos dos fármacos , Afídeos/crescimento & desenvolvimento , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Estrutura Molecular , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Peixe-Zebra/embriologia
6.
Environ Sci Technol ; 58(22): 9471-9486, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38776077

RESUMO

To date, dozens of pilot-scale microbial fuel cell (MFC) devices have been successfully developed worldwide for treating various types of wastewater. The availability and configurations of separators are determining factors for the economic feasibility, efficiency, sustainability, and operability of these devices. Thus, the concomitant advances between the separators and pilot-scale MFC configurations deserve further clarification. The analysis of separator configurations has shown that their evolution proceeds as follows: from ion-selective to ion-non-selective, from nonpermeable to permeable, and from abiotic to biotic. Meanwhile, their cost is decreasing and their availability is increasing. Notably, the novel MFCs configured with biotic separators are superior to those configured with abiotic separators in terms of wastewater treatment efficiency and capital cost. Herein, a highly comprehensive review of pilot-scale MFCs (>100 L) has been conducted, and we conclude that the intensive stack of the liquid cathode configuration is more advantageous when wastewater treatment is the highest priority. The use of permeable biotic separators ensures hydrodynamic continuity within the MFCs and simplifies reactor configuration and operation. In addition, a systemic comparison is conducted between pilot-scale MFC devices and conventional decentralized wastewater treatment processes. MFCs showed comparable cost, higher efficiency, long-term stability, and significant superiority in carbon emission reduction. The development of separators has greatly contributed to the availability and usability of MFCs, which will play an important role in various wastewater treatment scenarios in the future.


Assuntos
Águas Residuárias , Purificação da Água , Eletrodos , Projetos Piloto , Eliminação de Resíduos Líquidos/métodos
7.
Cell Death Dis ; 15(5): 350, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773070

RESUMO

Seipin is one key mediator of lipid metabolism that is highly expressed in adipose tissues as well as in the brain. Lack of Seipin gene, Bscl2, leads to not only severe lipid metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly of lipids, facilitates nerve transmission and is important for motor coordination and learning. Whether Seipin deficiency-leaded defects in learning and motor coordination is underlined by lipid dysregulation and its consequent myelin abnormalities remains to be elucidated. In the present study, we verified the expression of Seipin in oligodendrocytes (OLs) and their precursors, oligodendrocyte precursor cells (OPCs), and demonstrated that Seipin deficiency compromised OPC differentiation, which led to decreased OL numbers, myelin protein, myelinated fiber proportion and thickness of myelin. Deficiency of Seipin resulted in impaired spatial cognition and motor coordination in mice. Mechanistically, Seipin deficiency suppressed sphingolipid metabolism-related genes in OPCs and caused morphological abnormalities in lipid droplets (LDs), which markedly impeded OPC differentiation. Importantly, rosiglitazone, one agonist of PPAR-gamma, substantially restored phenotypes resulting from Seipin deficiency, such as aberrant LDs, reduced sphingolipids, obstructed OPC differentiation, and neurobehavioral defects. Collectively, the present study elucidated how Seipin deficiency-induced lipid dysregulation leads to neurobehavioral deficits via impairing myelination, which may pave the way for developing novel intervention strategy for treating metabolism-involved neurological disorders.


Assuntos
Diferenciação Celular , Disfunção Cognitiva , Subunidades gama da Proteína de Ligação ao GTP , Bainha de Mielina , Células Precursoras de Oligodendrócitos , Animais , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/genética , Camundongos , Células Precursoras de Oligodendrócitos/metabolismo , Bainha de Mielina/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/genética , Metabolismo dos Lipídeos , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo , PPAR gama/genética , Camundongos Knockout , Masculino , Rosiglitazona/farmacologia
8.
Am J Pathol ; 194(7): 1294-1305, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38657836

RESUMO

Mesothelial cells with reactive hyperplasia are difficult to distinguish from malignant mesothelioma cells based on cell morphology. This study aimed to identify and validate potential biomarkers that distinguish mesothelial cells from mesothelioma cells through machine learning combined with immunohistochemistry. It integrated the gene expression matrix from three Gene Expression Omnibus data sets (GSE2549, GSE12345, and GSE51024) to analyze the differently expressed genes between normal and mesothelioma tissues. Then, three machine learning algorithms, least absolute shrinkage and selection operator, support vector machine recursive feature elimination, and random forest were used to screen and obtain four shared candidate markers, including ACADL, EMP2, GPD1L, and HMMR. The receiver operating characteristic curve analysis showed that the area under the curve for distinguishing normal mesothelial cells from mesothelioma was 0.976, 0.943, 0.962, and 0.956, respectively. The expression and diagnostic performance of these candidate genes were validated in two additional independent data sets (GSE42977 and GSE112154), indicating that the performances of ACADL, GPD1L, and HMMR were consistent between the training and validation data sets. Finally, the optimal candidate marker ACADL was verified by immunohistochemistry assay. Acyl-CoA dehydrogenase long chain (ACADL) was stained strongly in mesothelial cells, especially for reactive hyperplasic mesothelial cells, but was negative in malignant mesothelioma cells. Therefore, ACADL has the potential to be used as a specific marker of reactive hyperplasic mesothelial cells in the differential diagnosis of mesothelioma.


Assuntos
Biomarcadores Tumorais , Biologia Computacional , Aprendizado de Máquina , Mesotelioma Maligno , Mesotelioma , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Biologia Computacional/métodos , Mesotelioma Maligno/genética , Mesotelioma Maligno/patologia , Mesotelioma Maligno/metabolismo , Mesotelioma Maligno/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Epitélio/metabolismo , Epitélio/patologia
9.
Water Res ; 255: 121530, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38564897

RESUMO

A huge chemical potential difference exists between the acid mine drainage (AMD) and the alkaline neutralization solution, which is wasted in the traditional AMD neutralization process. This study reports, for the first time, the harvest of this chemical potential energy through a controlled neutralization of AMD using H+-conductive films. Polyamide films with controllable thickness achieved much higher H+ conductance than a commercially available cation exchange membrane (CEM). Meanwhile, the optimal polyamide film had an excellent H+/Ca2+ selectivity of 63.7, over two orders of magnitude higher than that of the CEM (0.3). The combined advantages of fast proton transport and high proton/ion selectivity greatly enhanced the power generation of the AMD battery. The power density was 3.1 W m-2, which is over one order of magnitude higher than that of the commercial CEM (0.2 W m-2). Our study provides a new sustainable solution to address the environmental issues of AMD while simultaneously enabling clean energy production.

10.
J Ethnopharmacol ; 329: 118157, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38588987

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AMB) is a herb with wide application in traditional Chinese medicine, exerting a wealth of pharmacological effects. AMB has been proven to have an evident therapeutic effect on ischemic cerebrovascular diseases, including cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism underlying AMB in CIRI remains unclear. AIM OF THE STUDY: This study aimed to investigate the potential role of AMB in CIRI through a comprehensive approach of network pharmacology and in vivo experimental research. METHODS: The intersection genes of drugs and diseases were obtained through analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network was created through the string website. Meanwhile, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out using R studio, and thereafter the key genes were screened. Then, the molecular docking prediction was made between the main active ingredients and target genes, and hub genes with high binding energy were obtained. In addition, molecular dynamic (MD) simulation was used to validate the result of molecular docking. Based on the results of network pharmacology, we used animal experiments to verify the predicted hub genes. First, the rat middle cerebral artery occlusion and reperfusion (MACO/R) model was established and the effective dose of AMB in CIRI was determined by behavioral detection and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Then the target proteins corresponding to the hub genes were measured by Western blot. Moreover, the level of neuronal death was measured using hematoxylin and eosin (HE) and Nissl staining. RESULTS: Based on the analysis of the TCMSP database and GEO database, a total of 62 intersection target genes of diseases and drugs were obtained. The KEGG enrichment analysis showed that the therapeutic effect of AMB on CIRI might be realized through the advanced glycation endproduct-the receptor of advanced glycation endproduct (AGE-RAGE) signaling pathway in diabetic complications, nuclear factor kappa-B (NF-κB) signaling pathway and other pathways. Molecular docking results showed that the active ingredients of AMB had good binding potential with hub genes that included Prkcb, Ikbkb, Gsk3b, Fos and Rela. Animal experiments showed that AWE (60 g/kg) could alleviate CIRI by regulating the phosphorylation of PKCß, IKKß, GSK3ß, c-Fos and NF-κB p65 proteins. CONCLUSION: AMB exerts multi-target and multi-pathway effects against CIRI, and the underlying mechanism may be related to anti-apoptosis, anti-inflammation, anti-oxidative stress and inhibiting calcium overload.


Assuntos
Astrágalo , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Astrágalo/química , Masculino , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Infarto da Artéria Cerebral Média/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Simulação de Dinâmica Molecular
11.
Heliyon ; 10(5): e26774, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439882

RESUMO

The chemokine 20 (CCL20) is a member of the CC chemokine family and plays a role in tumor immunity and autoimmune disease. This work investigated the value of CCL20 as a serum diagnostic marker for primary hepatocellular carcinoma (HCC). Based on the data of hepatocellular carcinoma patients in the TCGA database, the up-regulated genes encoding secretory proteins were analyzed in each pathological stage, and the candidate marker CCL20 gene was selected. Serum concentrations of CCL20 in patients with primary HCC, benign liver disease, and healthy subjects were analyzed by enzyme-linked immunosorbent assay (ELISA). The ROC curve evaluated the efficacy of CCL20 alone or in combination with AFP in the diagnosis of HCC. It was found the expression of CCL20 in HCC patients was significantly higher than that in the benign liver disease group and healthy controls (P < 0.05); The AUC of ROC curve to distinguish HCC patients from healthy controls was 0.859, the sensitivity was 73.42%, and the specificity was 86.84%. After combination with AFP, the AUC increased to 0.968, the sensitivity was 88.16%, and the specificity was 97.37%. Although CCL20 was increased in the serum of patients with benign liver diseases, combined with AFP, the AUC to distinguish HCC patients from non-HCC cohorts (benign liver disease group and healthy control group) was 0.902, with a sensitivity of 91.67% and a specificity of 75.26%. Collectively, serum CCL20 is closely related to the occurrence of HCC, and detection of serum CCL20 can assist AFP in improving the diagnostic sensitivity of HCC.

12.
Org Lett ; 26(2): 508-513, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38179928

RESUMO

The enantioselective allylic alkylation of nitro ketene aminals with racemic allylic alcohols was realized by iridium/acid dual catalysis. An allyl group was installed on the α-position of nitro ketene aminals in a branched-selective manner in high efficiency with excellent enantioselectivities (93-99% ee). The protocol was applied to the late-stage modification of neonicotinoid insecticides, which directly furnished a novel neonicotinoid analogue with good insecticidal activity against Aphis craccivora (LC50 = 6.40 mg/L). On the basis of the control experiment, an aza-ene-type allylic alkylation reaction mechanism was proposed.

13.
ACS Appl Mater Interfaces ; 16(5): 5999-6007, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38278553

RESUMO

With the synergies of multiple elements, bimetallic sulfides exhibit excellent performance as splendid electrode materials and effective catalysts. However, large-scale synthesis of high-performance single-phase multicomponent sulfides has always been a challenge. Based on thermodynamic calculations, the intermediate phases NiS2 and Co3S4 are devoted to the synthesis of single-phase Ni0.5Co0.5S2. Because the reaction from NiS2 and Co3S4 to Ni0.5Co0.5S2 goes through a lower energy, it thermodynamically contributes to achieving a single-phase structure. Thus, single-phase Ni0.5Co0.5S2 can be simply and quickly prepared by two-step sintering and successfully scalable for mass production. This technique can extend to the whole ingredients Ni1-xCoxS2. Ni0.5Co0.5S2 demonstrates excellent thermal stability and good conductivity. It delivers a specific capacity of 671 mAh·g-1 and a specific energy of 1173 Wh·kg-1 when applied to a thermal battery cathode, which are increased by 18.6% and 25.0%, respectively, compared to pristine NiS2 (566 mAh·g-1) and CoS2 (537 mAh·g-1). This work proposes an innovative sintering method, which is applicable for cost-efficient and large-scale synthesis of single-phase multicomponent sulfides.

14.
Environ Sci Technol ; 57(48): 19891-19901, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38000046

RESUMO

Electroactive biofilms (EBs) engage in complex electron transfer and storage processes involving intracellular and extracellular mediators with temporary electron storage capabilities. Consequently, electroactive biofilms exhibit pseudocapacitive behaviors during substrate degradation processes. However, comprehensive systematic research in this area has been lacking. This study demonstrated that the pseudocapacitive property was an intrinsic characteristic of EBs. This property represents dynamic-controlled electron transfer and is critical in current generation, unlike noncapacitive responses. Nontransient charge and discharge experiments revealed a correlation between capacitive charge accumulation and current generation in EBs. Additionally, analysis of substrate degradation suggested that the maximum power density (Pmax) changed with the kinetic constants of COD degradation, with pseudocapacitances of EBs directly proportional to Pmax. The interaction networks of key latent variables were evaluated through partial least-squares path modeling analysis. The results indicated that cytochrome c was closely associated with the formation of pseudocapacitance in EBs. In conclusion, pseudocapacitance can be considered a valuable indicator for assessing the complex electron transfer behavior of EBs. Pseudocapacitive biofilms have the potential to efficiently regulate biological reactions and serve as a promising carbon-neutral and renewable strategy for energy generation and storage. An in-depth understanding of the intrinsic property of pseudocapacitive behavior in EBs can undoubtedly advance the development of this concept in the future.


Assuntos
Elétrons , Purificação da Água , Transporte de Elétrons , Biofilmes , Carbono , Eletrodos
15.
Stem Cell Res Ther ; 14(1): 239, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37674230

RESUMO

BACKGROUND: Lipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored. METHODS: In the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior. RESULTS: It was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect. CONCLUSION: This study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders.


Assuntos
Metabolismo dos Lipídeos , Lipodistrofia , Camundongos , Animais , Camundongos Knockout , Metabolismo dos Lipídeos/genética , Proteína Quinase C-alfa/genética , Obesidade , Neurogênese/genética
17.
J Agric Food Chem ; 71(30): 11396-11403, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37471065

RESUMO

Phenylpyrazole insecticides are widely used for crop protection and public sanitation by blocking gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride (GluCl) channels. Herein, 36 novel phenylpyrazole derivatives containing a trifluoromethylselenyl moiety were designed and synthesized based on the strategy of introducing a selenium element. All derivative structures were characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The insecticidal activity results indicated that some derivatives had good insecticidal activities against Aedes albopictus (A. albopictus) and Plutella xylostella (P. xylostella). The larvicidal activity against mosquitos of compounds 5, 5a, 5k, and 5l at 0.5 mg/L was 60-80%. At a concentration of 500 mg/L, compounds 5, 5a, 5h, 5k, 5l, 5r, 6, 6j, 6k, and 7 showed a 70-100% mortality against P. xylostella. Among them, derivatives 5 and 6 had a better insecticidal effect with mortality rates of 87 and 93% at 50 mg/L, respectively. It was summarized that the different binding poses of fipronil and compounds 5 and 6 in the Musca domestica (M. domestica) GABARs might lead to the disparity in bioactivity from docking studies. Toxicity tests on zebrafish suggested that compound 6 may be slightly less toxic to the embryos than fipronil on hatching rate.


Assuntos
Inseticidas , Mariposas , Animais , Peixe-Zebra , Inseticidas/química , Relação Estrutura-Atividade
18.
J Agric Food Chem ; 71(30): 11332-11340, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37471653

RESUMO

Neonicotinoid insecticides acting on the insect nicotinic acetylcholine receptors (nAChRs) play an essential role in contemporary pest control. In the present study, a series of novel neonicotinoid analogues with conjugated diene were synthesized. Bioassays indicated that compounds A3 and A12 had LC50 values of 1.26 and 1.24 mg/L against Myzus persicae, respectively, which were comparable to that of imidacloprid (IMI, LC50 = 0.78 mg/L). Density functional theory (DFT) calculations were performed to explain the differences in the insecticidal activities of target compounds. Molecular docking results indicate that compounds A3 and A12 interact favorably with Lymnaea stagnalis AChBP. The hydrolysis experiments confirmed that the stability of compounds A3 and A12 was enhanced in water.


Assuntos
Inseticidas , Receptores Nicotínicos , Animais , Inseticidas/farmacologia , Simulação de Acoplamento Molecular , Neonicotinoides , Insetos , Nitrocompostos/farmacologia
19.
Org Lett ; 25(26): 4797-4802, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37347697

RESUMO

The compounds featuring α-difluorothiomethylated ketone skeleton derivatives are of particular interest in pharmaceuticals and agrochemicals. Herein, we designed novel electrophilic N-difluoromethylthiophthalimide reagents that can be easily prepared with commercially available and economical chemicals. These reagents could smoothly react with various nucleophiles, such as Grignard reagents, boronic acids, ß-keto esters, and anilines, which affords structurally diverse α-difluoromethylthiolated ketones in good to excellent yields. The formal synthesis of active antifungal compounds positively confirmed the practicability of these reagents.


Assuntos
Cetonas , Ftalimidas , Cetonas/química , Catálise , Compostos Radiofarmacêuticos
20.
Water Res ; 238: 120024, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37156102

RESUMO

Phosphorus recovery from incinerated sewage sludge ash (ISSA) is important but hindered by low selectivity. Here, a novel strategy of acid leaching followed by thermally induced precipitation was proposed for the efficient and selective recovery of FePO4 from ISSA samples. A high phosphorus leaching efficiency of ∼ 99.6% was achieved with 0.2 mol/L H2SO4 and liquid to solid (L/S) ratio of 50 mL/g. Without removing various co-existing ions (Al3+, Ca2+, SO42-, etc.), high-purity FePO4 of ∼ 92.9% could be facilely produced from this highly acidic H2SO4 leachate (pH = 1.2) by simple addition of Fe(III) at a molar ratio of 1:1 to the phosphorus and reacted at 80 °C for thermally induced precipitation. The remained acid leachate could be further reused for five times to continue leaching phosphorus from the ISSA samples and produce the FePO4 precipitates with a high phosphorus recovery efficiency of 81.1 ± 1.8%. The selective recovery of FePO4 from the acid leachate was demonstrated more thermodynamically favorable compared to other precipitates at this acidic pH of 1.2, and elevated temperature of 80 °C towards thermally induced precipitation. The estimated cost of this strategy was ∼$26.9/kg-P and lower than that of other existing technologies. The recovered FePO4 precipitates could be used as a phosphate fertilizer to promote the growth of ryegrass, and also as a precursor to synthesize high-value LiFePO4 battery material, demonstrating the high-value application potential of the phosphorus from the ISSA.


Assuntos
Compostos Férricos , Esgotos , Incineração , Fósforo , Fosfatos , Ferro
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