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1.
J Agric Food Chem ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39373658

RESUMO

Spodoptera frugiperda is a notorious pest that develops a high resistance to many insecticides. Recently, insect odorant-binding proteins (OBPs) have been proven to participate in insecticide resistance. However, the functional evidence supporting the cross-link between OBPs and insecticide resistance remains unexplored. Here, we identified 50 SfruOBPs from the larval transcriptome and genome. Notably, SfruOBP18 was highly expressed in the larval cuticle and could be induced to upregulate its expression by multi-insecticides. Ligand-binding assays revealed that SfruOBP18 bound strongly with four insecticides; RNAi and insecticide bioassay demonstrated that the knockdown of SfruOBP18 did not affect larval survival and development. However, it can significantly increase the larval susceptibility to multi-insecticides, suggesting an uncommon role of SfruOBP18 in multi-insecticide susceptibility. Our study provides a comprehensive understanding of SfruOBPs and furthermore proves that a larval cuticle-enriched OBP can bind with and confer larval tolerance to multi-insecticides. SfruOBP18 could be a new insecticidal target for controlling Lepidoptera pests.

2.
Small ; : e2407220, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39410732

RESUMO

Multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are applied in organic light-emitting diodes (OLEDs) due to their high efficiency and color purity. However, the inherent planar structure of MR emitters presents significant challenges, including concentration-induced emission quenching, spectral redshift and broadening. To address these issues, two orthorhombic asymmetric conformational materials, SBNO and SBNOS, have been developed. Both MR-TADF emitters incorporate a sterically hindered spiro-carbon bridge to minimize intermolecular chromophore interactions. Consequently, the spectra of the SBNOS-based devices exhibit only a 4 nm redshift and a 7 nm broadening of the full-width at half maximum (FWHM) across a doping ratio range of 1-100 wt%. The steric effect produces pure green OLEDs with a CIE y of 0.69 and enhances performance, achieving a maximum external quantum efficiency (EQEmax) of up to 32.7%. The referent BNO without spiro skeleton suffers from serious spectral redshift and broadening as well as a lower device efficiency. This research demonstrates a promising approach to developing MR-TADF devices that resist redshift and broadening while maintaining high color purity and efficiency.

3.
Inorg Chem ; 63(43): 20501-20509, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39403728

RESUMO

Nanocluster catalysts typically face challenges in balancing stability with catalytic efficiency. This study introduces a unique bismuth-oxo cluster, solely protected by two ring-opened calixarenes, which demonstrates not only enhanced structural stability but also superior catalytic performance in the sustained conversion of CO2 to HCOOH via electrocatalysis. For the first time, we reveal that under specific solvothermal conditions, tert-butylcalix[8]arene (TBC[8]) can undergo in situ oxidative cleavage of its C-C bond, leading to ring-opened polyphenolic molecules. These molecules serve as protective ligands for the bismuth-oxo cluster, bestowing exceptional structural stability and offering a more flexible and diverse configuration compared to intact TBC[8]. This adaptability promotes the exposure of active bismuth sites on the cluster surface, enhancing catalytic efficiency. Notably, the Bi10 cluster, featuring a monobismuth active site, achieves an exceptional formate production efficiency of 98.79% at -1.25 V vs RHE while maintaining superb durability over 8 h. The stability and catalytic processes of Bi10 surpass those of the Bi13 cluster, which is structurally reinforced by two intact TBC[8] molecules and stabilized by four benzoic ligands. Through in situ infrared spectroscopy and density functional theory calculations, we demonstrate that the monobismuth active site in Bi10 more effectively stabilizes the *OCHO intermediate, thereby promoting the electrocatalytic reduction of CO2 to HCOOH compared to Bi13. This comparative performance underscores the potential of ring-opened calixarene ligands in enhancing the functionality of nanocluster catalysts.

4.
ACS Omega ; 9(42): 43264-43271, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39464475

RESUMO

Based on UHPLC-QTOF-MSE analysis and quantized processing, combined with machine learning algorithms, data modeling was carried out to realize digital identification of bear bile powder (BBP), chicken bile powder (CIBP), duck bile powder (DBP), cow bile powder (CBP), sheep bile powder (SBP), pig bile powder (PBP), snake bile powder (SNBP), rabbit bile powder (RBP), and goose bile powder (GBP). First, 173 batches of bile samples were analyzed by UHPLC-QTOF-MSE to obtain the retention time-exact mass (RTEM) data pair to identify bile acid-like chemical components. Then, the data were modeled by combining support vector machine (SVM), random forest (RF), artificial neural network (ANN), gradient boosting (GB), AdaBoost (AB), and Naive Bayes (NB), and the models were evaluated by the parameters of accuracy (Acc), precision (P), and area under the curve (AUC). Finally, the bile medicines were digitally identified based on the optimal model. The results showed that the RF model constructed based on the identified 12 bile acid-like chemical constituents and random forest algorithm is optimal with ACC, P, and AUC > 0.950. In addition, the accuracy of external identification verification of 42 batches of bile medicines detected at different times is 100.0%. So based on UHPLC-QTOF-MSE analysis and combined with the RF algorithm, it can efficiently and accurately realize the digital identification of bile medicines, which can provide reference and assistance for the quality control of bile medicines. In addition, hyodeoxycholic acid, glycohyodeoxycholic acid, and taurochenodeoxycholic acid, and so forth are the most important bile acid constituents for the identification of nine bile medicines.

5.
World J Gastrointest Oncol ; 16(10): 4177-4193, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39473941

RESUMO

BACKGROUND: Hepatobiliary and pancreatic (HBP) cancers impose a considerable burden on young populations (aged 15 to 49 years), resulting in a substantial number of new cases and fatalities each year. In young populations, the HBP cancers shows extensive variance worldwide and the updated data in China is lacking. AIM: To investigate the current status, trends, projections, and underlying risk factors of HBP cancers among young populations in China. METHODS: The Global Burden of Disease Study 2019 provided data on the annual incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rate (ASIR), mortality rate (ASMR), and DALYs rate (ASDR) of HBP cancers in young Chinese adults between 1990 and 2019. Temporal trends were assessed using estimated annual percentage change and hierarchical clustering. Sex-specific mortality and DALYs caused by various risks were analyzed across China and other regions, with future trends until 2035 projected using the Bayesian age-period-cohort model. RESULTS: From 1990 to 2019, incident cases, deaths, DALYs, ASIR, ASMR, and ASDR for liver cancer (LC) in young Chinese individuals decreased, classified into 'significant decrease' group. Conversely, cases of gallbladder and biliary tract cancer and pancreatic cancer rose, categorized as either 'significant increase' or 'minor increase' groups. The contribution of risk factors to mortality and DALYs for HBP tumors increased to varying degrees. Healthy lifestyle behaviors, such as tobacco control, weight management, alcohol moderation, and drug avoidance, could lower HBP cancers incidence. Moreover, except for LC in females, which is likely to initially decline slightly and then rise, the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young adults. CONCLUSION: HBP cancers burden among young adults in China is expected to increase until 2035, necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these cancers.

6.
World J Gastroenterol ; 30(37): 4132-4148, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39474397

RESUMO

BACKGROUND: Primary liver cancer is the sixth most common cancer worldwide, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite the current availability of multiple immune or immune combination treatment options, the prognosis is still poor, so how to identify a more suitable population is extremely important. AIM: To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus (HBV)-related HCC in Barcelona Clinic Liver Cancer (BCLC) stages B/C, considering various body mass index (BMI) in different categories. METHODS: Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab. Patients were divided into two groups based on BMI: The non-overweight group (BMI < 25 kg/m2, n = 51) and the overweight/obese group (BMI ≥ 25 kg/m2, n = 75). Short-term prognosis was evaluated using mRECIST criteria, with subgroup analyses for non-overweight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2) patients. A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival (OS), leading to the development of a column-line graph model. RESULTS: Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group. Similarly, the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group. The objective remission rate and disease control rate for the two groups of patients were, respectively, objective remission rate (5.88% vs 28.00%) and disease control rate (39.22% vs 62.67%). Fatigue was more prevalent in the obese/overweight group, while other adverse effects showed no statistically significant differences (P > 0.05). Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients, with obese patients showing the best outcomes. Multifactorial regression analysis identified BCLC grade, alpha-fetoprotein level, portal vein tumor thrombosis, and BMI as independent prognostic factors for OS. The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis, followed by alpha-fetoprotein level, BCLC classification, and portal vein tumor thrombosis. CONCLUSION: BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab, and obese/overweight patients have a better prognosis.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Índice de Massa Corporal , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Compostos de Fenilureia/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Quinolinas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Obesidade/complicações , Obesidade/diagnóstico , Estadiamento de Neoplasias , Adulto , Resultado do Tratamento , Intervalo Livre de Progressão , Hepatite B/complicações , Sobrepeso/complicações
7.
World J Gastroenterol ; 30(35): 3954-3958, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39351057

RESUMO

In this editorial, we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology, with a specific focus on the delayed diagnosis of inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a chronic intestinal disorder. A time lag may exist between the onset of inflammation and the appearance of signs and symptoms, potentially leading to an incorrect or delayed diagnosis, a situation referred to as the delayed diagnosis of IBD. Early diagnosis is crucial for effective patient treatment and prognosis, yet delayed diagnosis remains common. The reasons for delayed diagnosis of IBD are numerous and not yet fully understood. One key factor is the nonspecific nature of IBD symptoms, which can easily be mistaken for other conditions. Additionally, the lack of specific diagnostic methods for IBD contributes to these delays. Delayed diagnosis of IBD can result in numerous adverse consequences, including increased intestinal damage, fibrosis, a higher risk of colorectal cancer, and a decrease in the quality of life of the patient. Therefore, it is essential to diagnose IBD promptly by raising physician awareness, enhancing patient education, and developing new diagnostic methods.


Assuntos
Colite Ulcerativa , Diagnóstico Tardio , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Prognóstico , Doenças Inflamatórias Intestinais/diagnóstico , Qualidade de Vida , Fatores de Tempo , Educação de Pacientes como Assunto , Diagnóstico Diferencial
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 326: 125256, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39388935

RESUMO

In this work, a fluorescence chemical sensor continuous detection Al3+ and phosphates by a Salamo-Salen-Salamo type compound (SL) was employed. The sensor continuously recognized Al3+ and phosphates with good selectivity and fast response time, and a low limit of detection of 0.25 µΜ and 0.96 µM, at the same time accompanied by a naked-eye identification specificity. The detection mechanism of SL towards Al3+ is due to the chelating fluorescence enhancement effect and ICT effect, and continuously towards phosphates is due to the collapse of the SL-Al3+ and coordination interaction between Al3+ and phosphates, by Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, other spectral characterization and DFT calculation as evidence. In addition, the sensor had good recyclability and reusability. The distribution of Al3+ and phosphates in zebrafish cells was effectively monitored by confocal microscopy based on the good biocompatibility and tissue permeability of SL. Furthermore, the feasibility of using sensor SL to detect the content of Al3+ and phosphate ions in certain drugs was quantitatively analyzed through experiments. It was found SL had a good result in practical application.

10.
Eur J Pharmacol ; 983: 177002, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39293571

RESUMO

Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration in vitro and tumor growth in vivo. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Compostos Benzidrílicos , Proliferação de Células , Glucosídeos , Neoplasias Gástricas , Fatores de Transcrição , Ubiquitinação , Proteínas de Sinalização YAP , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Humanos , Ubiquitinação/efeitos dos fármacos , Proteínas de Sinalização YAP/metabolismo , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Camundongos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Camundongos Nus , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteases Específicas de Ubiquitina/metabolismo
11.
ACS Appl Mater Interfaces ; 16(38): 50321-50334, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39264683

RESUMO

The sophisticated environment of chronic wounds, characterized by prolonged exudation and recurrent bacterial infections, poses significant challenges to wound recovery. Recent advancements in multifunctional wound dressings fall short of providing comprehensive, accurate, and comfortable treatment. To address these issues, a battery-free and multifunctional microfluidic Janus wound dressing (MM-JWD) capable of three functions, including exudate management, antibacterial properties, and multiple indications of wound infection detection, has been developed. During the treatment, the fully soft microfluidic Janus membrane not only demonstrated stable unidirectional fluid transport capabilities under various skin deformations for a longer period but also provided antibacterial effects through surface treatment with chitosan quaternary ammonium salts and poly(vinyl alcohol). Furthermore, integrating multiple colorimetric sensors within the Janus membrane's microchannels and a dual-layer structure enabled simultaneous monitoring of the wound's pH, uric acid, and temperature. The monitoring was facilitated by smartphone recognition of color changes in the sensors. In vivo and in vitro tests confirmed the exudate management, antibacterial, and sensing capabilities of the MM-JWD, proving its efficacy in monitoring and promoting the healing of wounds. Overall, this study provides a valuable method for the design of multifunctional wound dressings for chronic wound care.


Assuntos
Antibacterianos , Bandagens , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Cicatrização/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Álcool de Polivinil/química , Staphylococcus aureus/efeitos dos fármacos , Humanos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Concentração de Íons de Hidrogênio , Camundongos , Ácido Úrico/química , Colorimetria
12.
Chem Biodivers ; : e202401348, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230030

RESUMO

Cinnamic acid and geraniol are two well-known antifungal natural products and widely applied in food and cosmetics industries. To discover novel natural product-based fungicide candidates with more potent activity and good ecological compatibility for the management of plant diseases, a series of cinnamic acid-geraniol hybrids were prepared by means of molecular hybridization and their chemical structures were well confirmed by spectral analysis. The antifungal activities of the target compounds against three phytopathogenic fungi Fusarium graminearum, Gaeumannomyces graminis (Sacc.) Arx et Oliver var. tritici (Sacc.) Walker, and Valsa mali were evaluated. Among them, compounds 5 e and 5 f showed the remarkable antifungal activity against G. graminis with the EC50 values of 82.719 and 91.828 µg/mL, respectively; while compounds 5 f and 6 b exhibited the obvious antifungal activity against V. mali. It suggested that compound 5 f can be further optimized for the design of novel broad-spectrum fungicide molecules as the secondary lead compound. In addition, some interesting structure-antifungal activity relationships were obtained. This work will provide some reference and guidance for the further discovery of novel fungicide candidates based on cinnamic acid and geraniol.

13.
J Med Internet Res ; 26: e55576, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39348685

RESUMO

BACKGROUND: Osteoarthritis (OA) is a chronic musculoskeletal disease that causes pain, functional disability, and an economic burden. Nonpharmacological treatments are at the core of OA management. However, limited access to these services due to uneven regional local availability has been highlighted. Internet-based telehealth (IBTH) programs, providing digital access to abundant health care resources, offer advantages, such as convenience and cost-effectiveness. These characteristics make them promising strategies for the management of patients with OA. OBJECTIVE: This study aimed to evaluate the effectiveness of IBTH programs in the management of patients with hip or knee OA. METHODS: We systematically searched 6 electronic databases to identify trials comparing IBTH programs with conventional interventions for hip and knee OA. Studies were selected based on inclusion and exclusion criteria, focusing on outcomes related to function, pain, and self-efficacy. Standardized mean differences (SMDs) with 95% CIs were calculated to compare outcome measures. Heterogeneity was assessed using I² and χ² tests. The methodological quality of the selected studies and the quality of evidence were also evaluated. RESULTS: A total of 21 studies with low-to-high risk of bias were included in this meta-analysis. The pooled results showed that IBTH has a superior effect on increasing function (SMD 0.30, 95% CI 0.23-0.37, P<.001), relieving pain (SMD -0.27, 95% CI -0.34 to -0.19, P<.001), and improving self-efficacy for pain (SMD 0.21, 95% CI 0.08-0.34, P<.001) compared to the conventional intervention group. Subgroup analysis revealed that IBTH with exercise can significantly alleviate pain and improve function and self-efficacy, but IBTH with cognitive-behavioral therapy only had the effect of reducing pain. CONCLUSIONS: The meta-analysis provides moderate-quality evidence that IBTH programs have a beneficial effect on improving function, relieving pain, and improving self-efficacy compared to conventional interventions in patients with hip or knee OA. Limited evidence suggests that the inclusion of exercise regimens in IBTH programs is recommended. TRIAL REGISTRATION: PROSPERO CRD42024541111; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=541111.


Assuntos
Internet , Osteoartrite do Quadril , Osteoartrite do Joelho , Telemedicina , Humanos , Osteoartrite do Quadril/terapia , Osteoartrite do Joelho/terapia
14.
Ann Med ; 56(1): 2399867, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39258959

RESUMO

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making. MATERIALS AND METHODS: Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis. RESULTS: Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7-8.8%), the pooled DCR was 80.5% (95% CI, 72.2%-87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%). CONCLUSION: The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.


Assuntos
Carcinoma Adenoide Cístico , Terapia de Alvo Molecular , Recidiva Local de Neoplasia , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Adenoide Cístico/tratamento farmacológico , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/secundário , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão
15.
J Agric Food Chem ; 72(36): 20101-20113, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39223077

RESUMO

The green peach aphid, Myzus persicae, is a worldwide agricultural pest. Chlorpyrifos has been widely used to control M. persicae for decades, thus leading to a high resistance to chlorpyrifos. Recent studies have found that insect odorant binding proteins (OBPs) play essential roles in insecticide resistance. However, the potential resistance mechanism underlying the cross-link between aphid OBPs and chlorpyrifos remains unclear. In this study, two OBPs (MperOBP3 and MperOBP7) were found overexpressed in M. persicae chlorpyrifos-resistant strains (CRR) compared to chlorpyrifos-sensitive strains (CSS); furthermore, chlorpyrifos can significantly induce the expression of both OBPs. An in vitro binding assay indicated that both OBPs strongly bind with chlorpyrifos; an in vivo RNAi and toxicity bioassay confirmed silencing either of the two OBPs can increase the susceptibility of aphids to chlorpyrifos, suggesting that overexpression of MperOBP3 and MperOBP7 contributes to the development of resistance of M. persicae to chlorpyrifos. Our findings provide novel insights into insect OBPs-mediated resistance mechanisms.


Assuntos
Afídeos , Clorpirifos , Proteínas de Insetos , Resistência a Inseticidas , Inseticidas , Receptores Odorantes , Animais , Afídeos/genética , Afídeos/efeitos dos fármacos , Afídeos/metabolismo , Clorpirifos/metabolismo , Clorpirifos/farmacologia , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/química , Resistência a Inseticidas/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Inseticidas/farmacologia , Inseticidas/metabolismo , Prunus persica/genética , Prunus persica/parasitologia , Prunus persica/metabolismo , Prunus persica/química
16.
PLoS Comput Biol ; 20(9): e1012491, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39348424

RESUMO

Understanding the mechanisms of the cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short cell cycle, and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. Recent experiments suggested the existence of two aging modes in yeast characterized by nucleolar and mitochondrial declines, respectively. By analyzing experimental data, this study shows that cells evolving into those two aging modes behave differently when they are young. While buds grow linearly in both modes, cells that consistently generate spherical buds throughout their lifespan demonstrate greater efficacy in controlling bud size and growth rate at young ages. A three-dimensional multiscale chemical-mechanical model was developed and used to suggest and test hypothesized impacts of aging on bud morphogenesis. Experimentally calibrated model simulations showed that during the early stage of budding, tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip, a process guided by the polarized Cdc42 signal. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage as observed in experiments in this work. The model simulation results suggest that the localization of new cell surface material insertion, regulated by chemical signal polarization, could be weakened due to cellular aging in yeast and other cell types, leading to the change and stabilization of the bud aspect ratio.


Assuntos
Senescência Celular , Modelos Biológicos , Morfogênese , Saccharomyces cerevisiae , Saccharomyces cerevisiae/crescimento & desenvolvimento , Morfogênese/fisiologia , Senescência Celular/fisiologia , Simulação por Computador , Biologia Computacional , Transdução de Sinais/fisiologia
17.
Biochem Biophys Res Commun ; 735: 150451, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39094233

RESUMO

Cerebral small vascular disease (CSVD) has a high incidence worldwide, but its pathological mechanisms remain poorly understood due to the lack of proper animal models. The current animal models of CSVD have several limitations such as high mortality rates and large-sized lesions, and thus it is urgent to develop new animal models of CSVD. Ultrasound can activate protoporphyrin to produce reactive oxygen species in a liquid environment. Here we delivered protoporphyrin into cerebral small vessels of rat brain through polystyrene microspheres with a diameter of 15 µm, and then performed transcranial ultrasound stimulation (TUS) on the model rats. We found that TUS did not affect the large vessels or cause large infarctions in the brain of model rats. The mortality rates were also comparable between the sham and model rats. Strikingly, TUS induced several CSVD-like phenotypes such as cerebral microinfarction, white matter injuries and impaired integrity of endothelial cells in the model rats. Additionally, these effects could be alleviated by antioxidant treatment with N-acetylcysteine (NAC). As control experiments, TUS did not lead to cerebral microinfarction in the rat brain when injected with the polystyrene microspheres not conjugated with protoporphyrin. In sum, we generated a rat model of CSVD that may be useful for the mechanistic study and drug development for CSVD.

18.
Cell Syst ; 15(8): 738-752.e5, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39173586

RESUMO

Cellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions but also revealed the theoretical principles underlying these interventions. We introduce the dynamical systems theory to capture two general means for promoting longevity-the creation of a stable fixed point in the "healthy" state of the cell and the "dynamic stabilization" of the system around this healthy state through environmental oscillations. Guided by the model, we investigate how both of these can be experimentally realized by dynamically modulating environmental glucose levels. The results establish a paradigm for theoretically analyzing the trajectories and perturbations of aging that can be generalized to aging processes in diverse cell types and organisms.


Assuntos
Glucose , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Glucose/metabolismo , Modelos Biológicos , Redes Reguladoras de Genes , Senescência Celular/fisiologia , Senescência Celular/genética , Longevidade/fisiologia , Longevidade/genética , Meio Ambiente
19.
Food Res Int ; 192: 114758, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39147491

RESUMO

The geographical origin of Panax ginseng significantly influences its nutritional value and chemical composition, which in turn affects its market price. Traditional methods for analyzing these differences are often time-consuming and require substantial quantities of reagents, rendering them inefficient. Therefore, hyperspectral imaging (HSI) in conjunction with X-ray technology were used for the swift and non-destructive traceability of Panax ginseng origin. Initially, outlier samples were effectively rejected by employing a combined isolated forest algorithm and density peak clustering (DPC) algorithm. Subsequently, random forest (RF) and support vector machine (SVM) classification models were constructed using hyperspectral spectral data. These models were further optimized through the application of 72 preprocessing methods and their combinations. Additionally, to enhance the model's performance, four variable screening algorithms were employed: SelectKBest, genetic algorithm (GA), least absolute shrinkage and selection operator (LASSO), and permutation feature importance (PFI). The optimized model, utilizing second derivative, auto scaling, permutation feature importance, and support vector machine (2nd Der-AS-PFI-SVM), achieved a prediction accuracy of 93.4 %, a Kappa value of 0.876, a Brier score of 0.030, an F1 score of 0.932, and an AUC of 0.994 on an independent prediction set. Moreover, the image data (including color information and texture information) extracted from color and X-ray images were used to construct classification models and evaluate their performance. Among them, the SVM model constructed using texture information from X -ray images performed the best, and it achieved a prediction accuracy of 63.0 % on the validation set, with a Brier score of 0.181, an F1 score of 0.518, and an AUC of 0.553. By implementing mid-level fusion and high-level data fusion based on the Stacking strategy, it was found that the model employing a high-level fusion of hyperspectral spectral information and X-ray images texture information significantly outperformed the model using only hyperspectral spectral information. This advanced model attained a prediction accuracy of 95.2 %, a Kappa value of 0.912, a Brier score of 0.027, an F1 score of 0.952, and an AUC of 0.997 on the independent prediction set. In summary, this study not only provides a novel technical path for fast and non-destructive traceability of Panax ginseng origin, but also demonstrates the great potential of the combined application of HSI and X-ray technology in the field of traceability of both medicinal and food products.


Assuntos
Algoritmos , Imageamento Hiperespectral , Panax , Máquina de Vetores de Suporte , Panax/classificação , Panax/química , Imageamento Hiperespectral/métodos , Luz , Raios X
20.
Chem Biodivers ; 21(9): e202401165, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38973453

RESUMO

Bisindole compounds constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the past four decades, researchers have isolated 229 animal-derived bisindole compounds (ADBCs) from various animals. These compounds demonstrate a wide range of pharmacological properties, including cytotoxicity, antibacterial, antifungal, antiviral, and other activities. Notably, among these activities, cytotoxicity emerges as the most prominent characteristic of ADBCs. This review also summarizes the structureactivity relationship (SAR) studies associated with the cytotoxicity of these compounds and explores the druggability of these compounds. In summary, our objective is to provide an overview of the research progress concerning ADBCs, with the aim of fostering their continued development and utilization.


Assuntos
Antineoplásicos , Indóis , Indóis/química , Indóis/farmacologia , Animais , Humanos , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Estrutura Molecular , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/isolamento & purificação , Antivirais/farmacologia , Antivirais/química , Proliferação de Células/efeitos dos fármacos
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