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1.
Chemistry ; : e202402085, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926940

RESUMO

We described a copper(I)-catalyzed atom economic and selective hydroamination-cyclization of alkynyl-tethered quinazolinones to prepare a variety of indole-fused pyrazino[1,2-a]quinazolinones in good to excellent yields ranging from 39% to 99% under mild reaction conditions. Control experiments revealed that coordination-directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination-cyclization of alkynes at the N1-atom instead of N3-atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole-fused pyrazino[1,2-a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions.

2.
J Mater Chem B ; 12(23): 5722-5733, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38764419

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.


Assuntos
NF-kappa B , PPAR gama , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Animais , NF-kappa B/metabolismo , PPAR gama/metabolismo , Camundongos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Polímeros/química , Polímeros/farmacologia , Povidona/química , Povidona/farmacologia , Indóis/química , Indóis/farmacologia , Masculino , Antioxidantes/farmacologia , Antioxidantes/química , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Nanopartículas de Magnetita/química , Humanos
3.
Nat Commun ; 15(1): 3970, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730227

RESUMO

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.


Assuntos
Doença da Altitude , Altitude , Regulação da Expressão Gênica , Hipóxia , Animais , Doença da Altitude/genética , Doença da Altitude/metabolismo , Ovinos , Hipóxia/genética , Hipóxia/metabolismo , Humanos , Aclimatação/genética , Transcrição Gênica , Análise de Célula Única , Feminino , Multiômica
4.
Org Lett ; 26(15): 3060-3064, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38552180

RESUMO

We described an iron(III) and BF3·OEt2-promoted oxygen transfer reaction of N-aryl-α,ß-unsaturated nitrones to prepare various N,O-difluoroboron ß-ketoiminates in good yields ranging from 24% to 87%. Control experiments revealed that the enaminone was the vital intermediate for the formation of N,O-difluoroboron ß-ketoiminates, and iron(III) combined with BF3·OEt2 played as cocatalyst to promote the oxygen transfer reaction through intramolecular cyclization and N-O bond cleavage. More importantly, an estrone-derived N,O-difluoroboron ß-ketoiminate was easily prepared in 40% yield from estrone in four steps.

5.
Org Lett ; 26(2): 519-524, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38190623

RESUMO

Herein, we described a copper(I)-catalyzed dearomatization of benzofurans with 2-(chloromethyl)anilines to prepare various tetrahydrobenzofuro[3,2-b]quinolines and 2-(quinolin-2-yl)phenols in good to excellent yields through radical addition and an intramolecular cyclization process. Mechanistic studies revealed that 2-(chloromethyl)anilines served as radical precursors. The present method features broad substrate scope, good functional group tolerance, quinoline scaffold diversity, and radical addition dearomatization of benzofurans.

6.
Org Biomol Chem ; 22(7): 1386-1390, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38276964

RESUMO

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6-endo-dig cyclization and trichloromethylation of N3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinone was prepared over five steps. The present method features broad substrate scope, good functional group tolerance, new dearomatization of pyridine rings, and chloroform as the trichloromethylation reagent.

7.
Wien Klin Wochenschr ; 136(1-2): 67-72, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37389688

RESUMO

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare highly heterogeneous disease. In this paper, we present a case of NIID featured in cortical involvement in left hemisphere of brain and the imaging changes in the process of the disease. CASE PRESENTATION: A 57-year-old female was hospitalized due to recurrent attacks of headache with cognitive impairment and tremor for 2 years. The symptoms of headache episodes were reversible. The characteristic radiologic change was high intensity signal involving the grey matter-white matter junction on the brain diffusion-weighted imaging (DWI), which existed in the frontal lobe and then extended backwards. Atypical features on fluid-attenuated inversion recovery (FLAIR) sequences showing small patchy high signals in the cerebellar vermis. High signals and edema were detected on FLAIR images along the cortex of the left occipito-parieto-temporal lobes, expanding and gradually shrinking in the follow-up visit. Besides, cerebral atrophy and bilateral symmetrical leukoencephalopathy were also detected. Skin biopsy and genetic testing confirmed the diagnosis of NIID. CONCLUSION: Except for typical radiological change strongly suggesting NIID, it is also necessary to notice the insidious symptoms of NIID combining with some atypical imaging features to make an early diagnosis. Skin biopsies or genetic testing should be carried out early in patients with highly suspected NIID.


Assuntos
Doenças Neurodegenerativas , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/patologia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Cefaleia
8.
Bioorg Chem ; 143: 107015, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086241

RESUMO

Conventional topoisomerase (Topo) inhibitors typically usually exert their cytotoxicity by damaging the DNAs, which exhibit high toxicity and tend to result in secondary carcinogenesis risk. Molecules that have potent topoisomerase inhibitory activity but involve less DNA damage provide more desirable scaffolds for developing novel chemotherapeutic agents. In this work, we broke the rigid pentacyclic system of luotonin A and synthesized thirty-three compounds as potential Topo inhibitors based on the devised molecular motif. Further investigation disclose that two compounds with the highest antiproliferation activity against cancer cells, 5aA and 5dD, had a distinct Topo I inhibitory mechanism different from those of the classic Topo I inhibitors CPT or luteolin, and were able to obviate the obvious cellular DNA damage typically associated with clinically available Topo inhibitors. The animal model experiments demonstrated that even in mice treated with a high dosage of 50 mg/kg 5aA, there were no obvious signs of toxicity or loss of body weight. The tumor growth inhibition (TGI) rate was 54.3 % when 20 mg/kg 5aA was given to the T24 xenograft mouse model, and 5aA targeted the cancer tissue precisely without causing damage to the liver and other major organs.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Animais , Camundongos , Antineoplásicos/farmacologia , Quinonas , Pirróis , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/uso terapêutico , Dano ao DNA , DNA Topoisomerases Tipo I/metabolismo , Inibidores da Topoisomerase II/farmacologia , DNA Topoisomerases Tipo II , Linhagem Celular Tumoral
9.
J Inorg Biochem ; 251: 112443, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38100902

RESUMO

Fourteen novel tumor-targeting copper(II) and zinc(II) complexes, [Cu(ONQ)(QD1)(NO3)]·CH3OH (NQ3), [Cu(ONQ)(QD2)(NO3)] (NQ2), [Cu(NQ)(QD2)Cl] (NQ3), [Cu(ONQ)(QD1)Cl] (NQ4), [Cu(ONQ)(QD3)](NO3) (NQ5), [Cu(ONQ)(QD3)Cl] (NQ6), [Zn(ONQ)(QD4)Cl] (NQ7), [Zn(ONQ)(QD1)Cl] (NQ8), [Zn(ONQ)(QD5)Cl] (NQ9), [Zn(ONQ)(QD2)Cl] (NQ10), [Zn(ONQ)(QD6)Cl] (NQ11), [Zn(ONQ)(QD7)Cl] (NQ12), and [Zn(ONQ)(QD3)Cl] (NQ13) supported on 8-hydroxyquinoline-N-oxide (H-ONQ), 2,2'-dipyridyl (QD1), 5,5'-dimethyl-2,2'-bipyridyl (QD2), 1,10-phenanthroline (QD3), 4,4'-dimethoxy-2,2'-bipyridyl (QD4), 4,4'-dimethyl-2,2'-bipyridyl (QD5), 5-chloro-1,10-phenanthroline (QD6), and bathophenanthroline (QD7), were first synthesized and characterized using various spectroscopic techniques. Furthermore, NQ1-NQ13 exhibited higher antiproliferative activity and selectivity for cisplatin-resistant SK-OV-3/DDP tumor cells (CiSK3) compared to normal HL-7702 cells based on results obtained from the cell counting Kit-8 (CCK-8) assay. The complexation of copper(II) ion with QD2 and ONQ ligands resulted in an evident increase in the antiproliferation of NQ1-NQ6, with NQ6 exhibiting the highest antitumor potency against CiSK3 cells compared to NQ1-NQ5, H-ONQ, QD1-QD7, and NQ7-NQ13 as well as the reference cisplatin drug with an IC50 value of 0.17 ± 0.05 µM. Mechanistic studies revealed that NQ4 and NQ6 induced apoptosis of CiSK3 cells via mitophagy pathway regulation and adenosine triphosphate (ATP) depletion. Further, the differential induction of mitophagy decreased in the order of NQ6 > NQ4, which can be attributed to the major impact of the QD3 ligand with a large planar geometry and the Cl leaving group within the NQ6 complex. In summary, these results confirmed that the newly synthesized H-ONQ copper(II) and zinc(II) coordination metal compounds NQ1-NQ13 exhibit potential as anticancer drugs for cisplatin-resistant ovarian CiSK3 cancer treatment.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Humanos , Cisplatino/farmacologia , Cobre/química , Complexos de Coordenação/química , Oxiquinolina , 2,2'-Dipiridil/química , Zinco/química , Fenantrolinas/farmacologia , Antineoplásicos/química , Ligantes
10.
Biomaterials ; 305: 122435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38150771

RESUMO

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.


Assuntos
Carcinoma Hepatocelular , Indóis , Neoplasias Hepáticas , Nanopartículas , Polímeros , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Fototerapia , Imunidade , Microambiente Tumoral , Linhagem Celular Tumoral
11.
J Org Chem ; 88(23): 16155-16166, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37975833

RESUMO

A variety of spirooxindole-1,2-oxazinan-5-one derivatives were prepared in moderate to excellent yields through 2,2,2-trifluoroethanol (TFE)-promoted [3 + 3] cycloaddition of N-vinyl oxindole nitrones with oxyallyl cations generated from α-tosyloxy ketones under mild reaction conditions. Mechanistic studies revealed that [3 + 3] cycloaddition might involve two possible reaction pathways, including direct [3 + 3] cycloaddition of N-vinyl oxindole ntirones with oxyallyl cations, or the addition of TFE to N-vinyl oxindole nitrones, sequential addition to oxyallyl cations, elimination, and cyclization. The present method features mild reaction conditions, broad substrate scope, good functional group tolerance, easy gram scalable preparation, and new applications of TFE.

12.
Biochem Genet ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910330

RESUMO

Leukoaraiosis (LA) appears as white matter hyperintensities on T2-weighted brain magnetic resonance imaging scans. Age and hypertension are considered the primary risk factors for LA, but its pathogenesis remains uncertain. This study aims to investigate the correlation between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and LA. A total of 140 patients with LA and 136 neuroimaging alteration-free controls were recruited in a case-control study. ACE I/D polymorphism was determined using the polymerase chain reaction method. The allele and genotype distributions of the ACE I/D polymorphism were significantly different between subjects with and without LA. Significant difference was observed in the genotypic distribution between LA patients and controls for recessive and additive models. A statistically significant association remained apparent after adjusting for potential risk factors (D/D vs. I/D + I/I: adjusted OR 3.251, 95% CI 1.185-8.918; D/D vs. I/I: adjusted OR 3.277, 95% CI 1.187-9.047). Our results indicate that the D/D genotype and D allele are important risk factors for LA. Future studies with larger populations are needed to validate our results.

13.
Adv Sci (Weinh) ; 10(35): e2303819, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37875399

RESUMO

Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first-line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti-tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Animais , Camundongos , Hidrogéis/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Antineoplásicos/farmacologia , Oxaliplatina/uso terapêutico , Imunoterapia
14.
Materials (Basel) ; 16(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37512212

RESUMO

An abundant hollow nanostructure is crucial for fast Li+ and K+ diffusion paths and sufficient electrolyte penetration, which creates a highly conductive network for ionic and electronic transport. In this study, we successfully developed a molecular-bridge-linked, organic-inorganic hybrid interface that enables the preparation of in situ nitrogen-doped hollow carbon nanospheres. Moreover, the prepared HCNSs, with high nitrogen content of up to 10.4%, feature homogeneous and regular morphologies. The resulting HCNSs exhibit excellent lithium and potassium storage properties when used as electrode materials. Specifically, the HCNS-800 electrode demonstrates a stable reversible discharge capacity of 642 mA h g-1 at 1000 mA g-1 after 500 cycles for LIBs. Similarly, the electrode maintains a discharge capacity of 205 mA h g-1 at 100 mA g-1 after 500 cycles for KIBs. Moreover, when coupled with a high-mass-loading LiFePO4 cathode to design full cells, the HCNS-800‖LiFePO4 cells provide a specific discharge capacity of 139 mA h g-1 at 0.1 C. These results indicate that the HCNS electrode has promising potential for use in high-energy and environmentally sustainable lithium-based and potassium-based batteries.

15.
Bioorg Chem ; 138: 106611, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37236073

RESUMO

Pseudo-natural products (PNPs) design strategy provides a great valuable entrance to effectively identify of novel bioactive scaffolds. In this report, novel pseudo-rutaecarpines were designed via the combination of several privileged structure units and 46 target compounds were synthesized. Most of them display moderate to potent inhibitory effect on LPS-induced NO production and low cytotoxicity in RAW264.7 macrophage. The results of the anti-inflammatory efficacy and action mechanism of compounds 7l and 8c indicated that they significantly reduced the release of IL-6, IL-1ß and TNF-α. Further studies revealed that they can strongly inhibit the activation of NF-κB and MAPK signal pathways. The LPS-induced acute liver injury mice model studies not only confirmed their anti-inflammatory efficacy in vivo but also could effectively relieve the liver injury in mice. The results suggest that compounds 7l and 8c might serve as lead compounds to develop therapeutic drugs for treatment of inflammation.


Assuntos
Lipopolissacarídeos , NF-kappa B , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fígado/metabolismo
16.
Sensors (Basel) ; 23(7)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37050567

RESUMO

In this study, the design of a Digital-twin human-machine interface sensor (DT-HMIS) is proposed. This is a digital-twin sensor (DT-Sensor) that can meet the demands of human-machine automation collaboration in Industry 5.0. The DT-HMIS allows users/patients to add, modify, delete, query, and restore their previously memorized DT finger gesture mapping model and programmable logic controller (PLC) logic program, enabling the operation or access of the programmable controller input-output (I/O) interface and achieving the extended limb collaboration capability of users/patients. The system has two main functions: the first is gesture-encoded virtual manipulation, which indirectly accesses the PLC through the DT mapping model to complete control of electronic peripherals for extension-limbs ability by executing logic control program instructions. The second is gesture-based virtual manipulation to help non-verbal individuals create special verbal sentences through gesture commands to improve their expression ability. The design method uses primitive image processing and eight-way dual-bit signal processing algorithms to capture the movement of human finger gestures and convert them into digital signals. The system service maps control instructions by observing the digital signals of the DT-HMIS and drives motion control through mechatronics integration or speech synthesis feedback to express the operation requirements of inconvenient work or complex handheld physical tools. Based on the human-machine interface sensor of DT computer vision, it can reflect the user's command status without the need for additional wearable devices and promote interaction with the virtual world. When used for patients, the system ensures that the user's virtual control is mapped to physical device control, providing the convenience of independent operation while reducing caregiver fatigue. This study shows that the recognition accuracy can reach 99%, demonstrating practicality and application prospects. In future applications, users/patients can interact virtually with other peripheral devices through the DT-HMIS to meet their own interaction needs and promote industry progress.


Assuntos
Gestos , Dispositivos Eletrônicos Vestíveis , Humanos , Interface Usuário-Computador , Dedos , Algoritmos
17.
J Org Chem ; 88(1): 690-700, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36485009

RESUMO

A variety of tetrahydro-5H-indolo[2,3-b]quinolines were prepared in 40-97% yields through a copper(II)-catalyzed cascade reaction of aza-o-quinone methides generated in situ from 2-(chloromethyl)anilines and indoles. Experimental results showed that the reaction underwent double 1,4-additions and sequential intramolecular cyclization. The present method features broad substrate scope, good functional group tolerance, and easy gram scalable preparation of indolo[2,3-b]quinolines.


Assuntos
Indóis , Quinolinas , Indóis/química , Estrutura Molecular , Cobre/química , Quinolinas/química , Catálise
18.
Org Lett ; 25(1): 267-271, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36583596

RESUMO

A variety of 1,2,4-oxadiazoline derivatives were synthesized in moderate to good yields through a deoxygenative cyclization cascade reaction of N-vinyl-α,ß-unsaturated nitrones and hydroxamoyl chlorides. Mechanistic studies revealed that the reaction underwent double additions of nitrile oxides to N-vinyl-α,ß-unsaturated nitrones, sequential elimination, and intramolecular cyclization to afford 1,2,4-oxadiazolines. Alternatively, 1,2,5-oxadiazolines were also obtained as major products in i-PrOH solvent through [3 + 3] cycloaddition and selective [3,3]-rearrangement. Moreover, the prepared 1,2,4-oxadiazolines were easily converted to polysubstituted pyrroles under thermal conditions.

19.
Sci Total Environ ; 859(Pt 2): 160372, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36410481

RESUMO

Ammonia is a common pollutant in aquaculture system, and toxic to all aquatic animals. However, different aquatic animals exhibit diverse physiological responses to high-level ammonia exposure, potentially indicating their divergent resistance to ammonia stress. In this study, juveniles of three freshwater turtles (Mauremys reevesii, Pseudemys nelsoni and Trachemys scripta elegans) were exposed to different concentrations of ammonia (0, 0.3 and 3.0 mg/L) for 30 days, and their swimming, growth performance, gut microbiota, and hepatic metabolites were measured to evaluate the interspecific difference in physiological responses to ammonia stress. Despite no differences in swimming ability, growth rate, and gut microbial diversity, observable changes in microbial community composition and hepatic metabolite profiles were shown in ammonia-exposed turtles. A relatively higher abundance of potentially pathogenic bacteria was found in M. reevesii than in the other two species. Moreover, microbial compositions and metabolic responses differed significantly among the three species. M. reevesii was, out of the three tested species, the one in which exposure to ammonia had the greatest effect on changes in bacterial genera and hepatic metabolites. Conversely, only a few metabolites were significantly changed in T. scripta elegans. Integrating these findings, we speculated that native M. reevesii should be more vulnerable to ammonia stress compared to the invasive turtle species. Our results plausibly reflected divergent potential resistance to ammonia among these turtles, in view of differential physiological responses to ammonia exposure at environmentally relevant concentrations.


Assuntos
Microbioma Gastrointestinal , Tartarugas , Animais , Tartarugas/metabolismo , Amônia/toxicidade , Amônia/metabolismo , Água Doce , Espécies Introduzidas , Fígado
20.
Clin Appl Thromb Hemost ; 28: 10760296221144038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36503260

RESUMO

We aimed to investigate the efficacy and safety of rivaroxaban for acute and long-term management of cerebral venous sinus thrombosis (CVST). This study reviewed CVST-diagnosed patients admitted to the First Affiliated Hospital of Guangxi Medical University from January 2015 to December 2020. The primary outcome was a composite of recurrent thrombosis or major bleeding events. The secondary efficacy outcomes included a disease recovery time (DRT) presenting the time from admission to the endpoint as recovery (the modified Rankin scale [mRS] score [0-1]) within 30 and 90 days, and length of hospital stay (LHS). Patients treated with rivaroxaban (38) and warfarin (45) were enrolled in the final analysis. The primary outcome had no significant difference (5.3% vs 11.1%, P = .576) between the 2 groups. The secondary efficacy outcome regarding the median 30-d DRT was 17 days (95% confidence interval [CI], 14.6-19.4) in the rivaroxaban group, compared with 26.0 days (95% CI, 16.8-35.2) in the warfarin group (hazard ratio, 1.806; 95% CI, 1.051-3.103; log-rank P = .026). Two groups have a significant difference in LHS (P = .041). Patients with cerebral edema, intracerebral hemorrhage, and mild/moderate disability (admission mRS score [2-3]) treated with rivaroxaban recovered faster than those with warfarin (log-rank P < .05). Patients with cerebral edema, intracerebral hemorrhage, and mild/moderate disability treated with rivaroxaban had a shorter recovery time than those treated with warfarin within 1 month from admission, indicating that rivaroxaban a promising convenient therapy for CVST, helping them speedily restore social functions.


Assuntos
Edema Encefálico , Trombose dos Seios Intracranianos , Humanos , Rivaroxabana/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Anticoagulantes/efeitos adversos , Edema Encefálico/induzido quimicamente , Edema Encefálico/tratamento farmacológico , População do Leste Asiático , China , Varfarina/efeitos adversos , Hemorragia Cerebral/tratamento farmacológico , Trombose dos Seios Intracranianos/tratamento farmacológico , Resultado do Tratamento
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