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1.
Phytochemistry ; 223: 114121, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38697242

RESUMO

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

2.
J Colloid Interface Sci ; 668: 525-539, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691962

RESUMO

Economical oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalysts with high activity aimed at replacing precious metal catalysts for rechargeable zinc-air batteries (ZABs) must be developed. In this study, a multiple hierarchical-structural material is developed using a facile dielectric barrier discharge (DBD) plasma surface treatment, solvothermal reaction, and high-temperature carbonization strategy. This strategy allows for the construction of nanosheets using nitrogen-doped carbon (NC) material-encapsulated ternary CoNiFe alloy nanoparticles (NPs) on a network of NC nanotubes (NCNTs), denoted as CoNiFe-NC@p-NCNTs. Precisely, the presence of abundant CoNiFe alloy NPs and the formation of M-N-C active sites created by transition metals (cobalt, nickel, and iron) coupled with NC can provide superior OER/ORR bifunctional properties. Moreover, the prepared NC layers with a multilevel pore structure contribute to a larger specific surface area, exposing numerous active sites and enhancing the uniformity of electron and mass movement. The CoNiFe0.08-NC@p-NCNTs show remarkable dual functionality for electrochemical oxygen reactions (ORR half-wave potential of 0.811 V, limiting current density of 5.73 mA cm-2 measured with a rotating disk electrode at a rotation speed of 1600 rpm, and OER overpotential of 351 mV at 10 mA cm-2), which demonstrates similar ORR performance to 20 wt% Pt/C and better OER performance than the commercial RuO2. A liquid ZAB prepared using the proposed material has excellent bifunctionality with an open-circuit voltage of 1.450 V and long-term cycling stability of 230 h@10 mA cm-2.

3.
Nat Commun ; 15(1): 4317, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773086

RESUMO

Transition-metal catalyzed allylic substitution reactions of alkenes are among the most efficient methods for synthesizing diene compounds, driven by the inherent preference for an inner-sphere mechanism. Here, we present a demonstration of an outer-sphere mechanism in Rh-catalyzed allylic substitution reaction of simple alkenes using gem-difluorinated cyclopropanes as allyl surrogates. This unconventional mechanism offers an opportunity for the fluorine recycling of gem-difluorinated cyclopropanes via C - F bond cleavage/reformation, ultimately delivering allylic carbofluorination products. The developed method tolerates a wide range of simple alkenes, providing access to secondary, tertiary fluorides and gem-difluorides with 100% atom economy. DFT calculations reveal that the C - C bond formation goes through an unusual outer-sphere nucleophilic substitution of the alkenes to the allyl-Rh species instead of migration insertion, and the generated carbon cation then forms the C - F bond with tetrafluoroborate as a fluoride shuttle.

4.
ChemSusChem ; : e202400254, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743510

RESUMO

Environmental pollution caused by persistent organic pollutants has imposed big threats to the health of human and ecological systems. The development of efficient methods to effectively degrade and remove these persistent organic pollutants is therefore of paramount importance. Photocatalytic persulfate-based advanced oxidation technologies (PS-AOTs), which depend on the highly reactive SO4·- radicals generated by the activation of PS to degrade persistent organic pollutants, have shown great promise. This work discusses the application and modification strategies of common photocatalysts in photocatalytic PS-AOTs, and compares the degradation performance of different catalysts for pollutants. Furthermore, essential elements impacting photocatalytic PS-AOTs are discussed, including the water matrix, reaction process mechanism, pollutant degradation pathway, singlet oxygen generation, and potential PS hazards. Finally, the existing issues and future challenges of photocatalytic PS-AOTs are summarized and prospected to encourage their practical application. In particular, by providing new insights into the PS-AOTs, this review sheds light on the opportunities and challenges for the development of photocatalysts with advanced features for the PS-AOTs, which will be of great interests to promote better fundamental understanding of the PS-AOTs and their practical applications.

5.
Int J Older People Nurs ; 19(3): e12609, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38622947

RESUMO

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) offers a standardized international terminology to operationalize function management across multiple domains, but the summary score of the ICF qualifier scale provides limited information on the comparison of personal abilities and functioning difficulties. OBJECTIVES: To enhance the interpretative power of the ICF-based Health-oriented Personal Evaluation for the community-dwelling older person (iHOPE-OP) scale through the implementation of the item response theory (IRT) modelling. METHODS: This cross-sectional, multi-centre study administrated 161 ICF categories (58 on body functions, 15 on body structures, 60 on activities or participation and 28 on environmental factors) to evaluate the functional level of 338 older citizens (female = 158, male = 180) residing in community or supportive living facilities. The validation process encompassed assessing the IRT model fitness and evaluating the psychometric properties of the IRT-derived iHOPE-OP scale. RESULTS: The age of participants ranged from 60 to 94.57, with the mean age of 70. The analysis of non-parametric and parametric models revealed that the three-parameter logistic IRT model, with a dichotomous scoring principle, exhibited the best fit. The 53-item iHOPE-OP scale demonstrated high reliability (Cronbach's α = 0.9729, Guttman's lambda-2 = 0.9749, Molenaar-Sijtsma Statistic = 0.9803, latent class reliability coefficient = 0.9882). There was a good validity between person abilities and the Barthel Index (p < .001, r = .83), as well as instrumental activities of daily living (p < .001, r = .84). CONCLUSIONS: IRT methods generate the reliable and valid iHOPE-OP scale with the most discriminable and minimal items to represent the older person's functional performance at a comprehensive level. The use of the Wright map can aid in presby-functioning management by visualizing item difficulties and person abilities. IMPLICATIONS FOR PRACTICE: Considering the intricate and heterogeneous health status of older persons, a single functional assessment tool might not fulfil the need to fully understand the multifaceted health status. For use in conjunction with the IRT and ICF framework, the reliable and valid iHOPE-OP scale was developed and can be applied to capture presby-functioning. The Wright map depicts the distribution of item difficulties and person abilities on the same scale that facilitates person-centred goal setting and tailors intervention.


Assuntos
Atividades Cotidianas , Vida Independente , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Classificação Internacional de Funcionalidade, Incapacidade e Saúde , Avaliação da Deficiência , Estudos Transversais , Reprodutibilidade dos Testes
6.
Med Sci Monit ; 30: e942509, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561932

RESUMO

BACKGROUND Diabetic peripheral neuropathy (DPN) is a prevalent complication affecting over 60% of type 2 diabetes patients. Early diagnosis is challenging, leading to irreversible impacts on quality of life. This study explores the predictive value of combining HbA1c and Neutrophil-to-Lymphocyte Ratio (NLR) for early DPN detection. MATERIAL AND METHODS An observational study was conducted at the First People's Hospital of Linping District, Hangzhou spanning from May 2019 to July 2020. Data on sex, age, biochemical measurements were collected from electronic medical records and analyzed. Employing multivariate logistic regression analysis, we sought to comprehend the factors influencing the development of DPN. To assess the predictive value of individual and combined testing for DPN, a receiver operating characteristic (ROC) curve was plotted. The data analysis was executed using R software (Version: 4.1.0). RESULTS The univariate and multivariate logistic regression analysis identified the level of glycated hemoglobin (HbA1C) (OR=1.94, 95% CI: 1.27-3.14) and neutrophil-to-lymphocyte ratio (NLR) (OR=4.60, 95% CI: 1.15-22.62, P=0.04) as significant risk factors for the development of DPN. Receiver operating characteristic (ROC) curve analysis demonstrated that HbA1c, NLR, and their combined detection exhibited high sensitivity in predicting the development of DPN (71.60%, 90.00%, and 97.2%, respectively), with moderate specificity (63.8%, 45.00%, and 50.00%, respectively). The area under the curve (AUC) for these predictors was 0.703, 0.661, and 0.733, respectively. CONCLUSIONS HbA1c and NLR emerge as noteworthy risk indicators associated with the manifestation of DPN in patients with type 2 diabetes. The combined detection of HbA1c and NLR exhibits a heightened predictive value for the development of DPN.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/etiologia , Hemoglobinas Glicadas , Linfócitos , Neutrófilos , Qualidade de Vida , Curva ROC , Masculino , Feminino
7.
BMC Pediatr ; 24(1): 243, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580968

RESUMO

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Cisto do Colédoco , Masculino , Humanos , Pré-Escolar , Cisto do Colédoco/complicações , Cisto do Colédoco/diagnóstico por imagem , Cisto do Colédoco/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia
8.
Biomed Pharmacother ; 174: 116518, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565057

RESUMO

BACKGROUND: The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). METHODS: CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. FINDINGS: Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. INTERPRETATION: CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo, although the direct effects of CaSR inhibition on GI muscle strips were suppressive.


Assuntos
Modelos Animais de Doenças , Motilidade Gastrointestinal , Camundongos Endogâmicos C57BL , Naftalenos , Receptores de Detecção de Cálcio , Animais , Receptores de Detecção de Cálcio/antagonistas & inibidores , Receptores de Detecção de Cálcio/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Esvaziamento Gástrico/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia
9.
Angew Chem Int Ed Engl ; 63(22): e202403602, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38515395

RESUMO

The use of gem-difluorinated cyclopropanes (gem-DFCPs) as fluoroallyl surrogates under transition-metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono-fluoroalkenes. Herein, we report the first enantioselective allylation of indoles under rhodium catalysis with gem-DFCPs. This reaction shows exceptional branched regioselectivity towards rhodium catalysis with gem-DFCPs, which provides an efficient route to enantioenriched fluoroallylated indoles with wide substrate scope and good functional group tolerance.

10.
Angew Chem Int Ed Engl ; 63(22): e202403771, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38551448

RESUMO

The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS-responsive Fe3O4-based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune-activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune-suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α-PD-L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle-mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis-enhanced immunotherapy combined with non-radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.


Assuntos
Ferroptose , Imunoterapia , Imageamento por Ressonância Magnética , Espécies Reativas de Oxigênio , Ferroptose/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Isótopos de Xenônio/química , Nanopartículas de Magnetita/química , Linhagem Celular Tumoral
11.
Front Neurosci ; 18: 1346634, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525376

RESUMO

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

12.
Chem Commun (Camb) ; 60(28): 3764-3773, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38501197

RESUMO

Small-ring chemistry is a fascinating field in organic chemistry. gem-Difluorinated cyclopropanes, a unique class of cyclopropanes, have garnered significant interest due to their intrinsic high reactivity. In this context, gem-difluorinated cyclopropanes have been extensively investigated as fluoroallylic synthons in Pd-catalyzed ring-opening/cross-coupling reactions for the synthesis of monofluoroalkenes with linear or branched selectivity. In contrast, Rh-catalysis has revealed diverse selectivity in the reaction of gem-difluorinated cyclopropanes, such as regioselectivity, enantioselectivity, and chemoselectivity. This feature article aims to summarize our efforts towards developing Rh-catalyzed reactions of gem-difluorinated cyclopropanes, briefly discussing the design, selectivity, reaction mechanisms and future research prospects.

13.
Biomed Pharmacother ; 174: 116440, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518605

RESUMO

Rheumatoid arthritis (RA) is a complex autoimmune inflammatory rheumatic disease characterized by an imbalance between immunological reactivity and immune tolerance. Regulatory T cells (Tregs), which play a crucial role in controlling ongoing autoimmunity and maintaining peripheral tolerance, have shown great potential for the treatment of autoimmune inflammatory rheumatic diseases such as RA. This review aims to provide an updated summary of the latest insights into Treg-targeting techniques in RA. We focus on current therapeutic strategies for targeting Tregs based on discussing their subsets, surface markers, suppressive function, and signaling pathways in RA.


Assuntos
Artrite Reumatoide , Biomarcadores , Transdução de Sinais , Linfócitos T Reguladores , Humanos , Artrite Reumatoide/imunologia , Artrite Reumatoide/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Animais , Biomarcadores/metabolismo
14.
Chempluschem ; 89(5): e202300704, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38363060

RESUMO

Nanocomposite represents the backbone of many industrial fabrication applications and exerts a substantial social impact. Among these composites, metal nanostructures are often employed as the active constituents, thanks to their various chemical and physical properties, which offer the ability to tune the application scenarios in thermal management, energy storage, and biostable materials, respectively. Nanocellulose, as an emerging polymer substrate, possesses unique properties of abundance, mechanical flexibility, environmental friendliness, and biocompatibility. Based on the combination of flexible nanocellulose with specific metal fillers, the essential parameters involving mechanical strength, flexibility, anisotropic thermal resistance, and conductivity can be enhanced. Nowadays, the approach has found extensive applications in thermal management, energy storage, biostable electronic materials, and piezoelectric devices. Therefore, it is essential to thoroughly correlate cellulose nanocomposites' properties with different metallic fillers. This review summarizes the extraction of nanocellulose and preparation of metal modified cellulose nanocomposites, including their wide and particular applications in modern advanced devices. Moreover, we also discuss the challenges in the synthesis, the emerging designs, and unique structures, promising directions for future research. We wish this review can give a valuable overview of the unique combination and inspire the research directions of the multifunctional nanocomposites using proper cellulose and metallic fillers.

15.
J Mater Chem B ; 12(9): 2373-2383, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38349037

RESUMO

Smart lipids with fluorescence emission, thermal response, and polyethylene glycolation (PEGylation) functions can be highly valuable for formulation, image-traceable delivery, and targeted release of payloads. Herein, a series of jellyfish-shaped amphiphiles with a tetraphenylethene (TPE) core and four symmetrical amphiphilic side chains were conveniently synthesized and systematically investigated as smart lipids. Compared with regular amphiphilic TPE lipids and phospholipids, the unprecedented jellyfish-shaped molecular geometry was found to enable a series of valuable capabilities, including sensitive and responsive aggregation-induced emission of fluorescence (AIE FL) and real-time FL monitoring of drug uptake. Furthermore, the jellyfish-shaped geometry facilitated the concentration-dependent aggregation from unimolecular micelles at low concentrations to "side-by-side" spherical aggregates at high concentrations and a unique mode of AIE. In addition, the size and the arrangement of the amphiphilic side chains were found to dominate the aggregate stability, cell uptake, and thus the cytotoxicity of the amphiphiles. This study has unprecedentedly developed versatile smart TPE lipids with precise structures, and unique physicochemical and biological properties while the peculiar structure-property relationship may shed new light on the design and application of AIE fluorophores and functional lipids in biomedicine and materials science.


Assuntos
Corantes Fluorescentes , Micelas , Fluorescência , Membrana Celular , Corantes Fluorescentes/química , Lipídeos
16.
Exp Cell Res ; 436(1): 113956, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341081

RESUMO

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Via de Sinalização Hippo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Compostos de Fenilureia/farmacologia
17.
Angew Chem Int Ed Engl ; 63(11): e202319647, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38198183

RESUMO

Here we present a modular, chemo-, regio-, and stereoselective synthesis of fully-substituted and configuration-defined alkyl vinyl ethers (AVEs) using simple chemical feedstocks. The distinctive approach involves the chemo- and regioselective functionalization of the CF2 unit in gem-difluorinated cyclopropanes with O-H and C-H nucleophiles in a specific order. The resulting highly functionalized cyclopropanyl ethers then undergo a stereoselective ring-opening process to produce fully-substituted and configuration-defined AVEs. These AVEs are rarely accessible through conventional methods and are easily transformable. Mechanistic experiments indicate that the success of this method relies on the use of dual-functional copper catalysis, which is involved in both the functionalization of the CF2 unit and the subsequent ring-opening process.

18.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38243850

RESUMO

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.


Assuntos
Lagartos , Melaninas , Animais , Melaninas/genética , Lagartos/genética , Peixe-Zebra , Regulação da Temperatura Corporal/genética , Pigmentação da Pele/genética , Cor
19.
J Fish Biol ; 104(2): 410-421, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36740452

RESUMO

The tapertail anchovy Coilia brachygnathus, a commercially important species mainly distributed along the mid-lower Chang-Jiang basin, is by far the most dominant species in Lake Honghu. To figure out its success in this semiclosed lake, some basic biological parameters of this anchovy were analysed based on samples seasonally collected from October 2020 to December 2021. The results demonstrated that the age classes of fished individuals varied from 0.5 to 3.5, with the majority (97.36%) being between 0.5 and 3 years old. The size at 50% maturity of 17.2 cm total length (TL) for females and 19.0 cm TL for males corresponded to 1 and 1.6 years, respectively. Coilia brachygnathus has a short life span, early sexual maturity and a relatively fast growth rate. The flourishing of the fish in the lake is mainly attributed to its short life span, early maturity, fast growth rate, closed fishing, pelagic spawners, the availability of plenty of food and low predation effect on it. Age 3.5 year occurs in an extremely small percentage of the total (<3%), indicating that a large number of larger-sized or older fish died after spawning, which is probably one of the major sources of water pollution if the closed fishing measure is adopted in Lake Honghu. Thus, individuals older than 2 years or more than 20.0 cm TL should be harvested. These findings have important management implications for the fish resources in Lake Honghu and beyond.


Assuntos
Peixes , Lagos , Masculino , Feminino , Animais , China
20.
Chem Rec ; 24(1): e202300206, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37736673

RESUMO

The development of sodium-ion battery (SIB) anodes is still hindered by their rapid capacity decay and poor rate capabilities. Although there have been some new materials that can be used to fabricate stable anodes, SIBs are still far from wide applications. Strategies like nanostructure construction and material modification have been used to prepare more robust SIB anodes. Among all the design strategies, the hollow structure design is a promising method in the development of advanced anode materials. In the past decade, research efforts have been devoted to modifying the synthetic route, the type of templates, and the interior structure of hollow structures with high capacity and stability. A brief introduction is made to the main material systems and classifications of hollow structural materials first. Then different morphologies of hollow structural materials for SIB anodes from the latest reports are discussed, including nanoboxes, nanospheres, yolk shells, nanotubes, and other more complex shapes. The most used templates for the synthesis of hollow structrual materials are covered and the perspectives are highlighted at the end. This review offers a comprehensive discussion of the synthesis of hollow structural materials for SIB anodes, which could be potentially of use to research areas involving hollow materials design for batteries.

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