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1.
Nano Lett ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39365290

RESUMO

During the oxygen evolution reaction (OER), catalyst candidates that can fully trigger self-reconstruction to derive active species with favorable configurations are expected to overcome the sluggish reaction kinetics. Herein, we innovatively propose the introduction of heterogeneous vanadate dopants into nickel-iron alloy precatalysts, where the crystal mismatch structure induces local electron delocalization in the hexagonal close packed alloy phase, thereby facilitating adequate electrochemical reconstruction to form (oxy)hydroxides as the real catalytic species. Simultaneously, the participation of vanadate in the reconstruction also triggers mismatch in the derived (oxy)hydroxides, reinforcing the metal-oxygen covalence, so that lattice oxygen activation is kinetically favorable and facilitates the OER via the lattice oxygen pathway. Optimized reconstructed catalyst r-NiFeVOx-NF exhibits a low overpotential of 220 mV at current densities of 10 mA cm-2 and considerably stable operation. Our study opens up opportunities for achieving robust OER performance through the design and fabrication of the mismatch catalytic configuration.

3.
Opt Lett ; 49(19): 5563-5566, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353007

RESUMO

Metalenses, boasting outstanding focusing efficiency and high-resolution imaging capabilities, have generated widespread usage in fields such as integrated optics, achromatic imaging, and optical holography. In this study, we have developed a broadband achromatic metalens within the detection range from 3 to 5 µm, and it has a numerical aperture (NA) of 0.71 with a remarkable maximum focusing efficiency of 63.8% at the focal plane within the specified bandwidth. We have further delved into the dispersion control mechanism that combines the geometric and transmission phases and optimized the constructed phase response simulation database using the particle swarm optimization (PSO) algorithm, ensuring a precise phase matching between the actual wavefront and the ideal focusing wavefront. This metalens with its ability to expand the array size has the potential to create a compact infrared imager, which holds significant importance in achieving efficient detection and integration within infrared detectors.

4.
Bioact Mater ; 42: 573-586, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39308551

RESUMO

Mucosal vaccines offer potential benefits over parenteral vaccines for they can trigger both systemic immune protection and immune responses at the predominant sites of pathogen infection. However, the defense function of mucosal barrier remains a challenge for vaccines to overcome. Here, we show that surface modification of exosomes with the fragment crystallizable (Fc) part from IgG can deliver the receptor-binding domain (RBD) of SARS-CoV-2 to cross mucosal epithelial layer and permeate into peripheral lung through neonatal Fc receptor (FcRn) mediated transcytosis. The exosomes F-L-R-Exo are generated by genetically engineered dendritic cells, in which a fusion protein Fc-Lamp2b-RBD is expressed and anchored on the membrane. After intratracheally administration, F-L-R-Exo is able to induce a high level of RBD-specific IgG and IgA antibodies in the animals' lungs. Furthermore, potent Th1 immune-biased T cell responses were also observed in both systemic and mucosal immune responses. F-L-R-Exo can protect the mice from SARS-CoV-2 pseudovirus infection after a challenge. These findings hold great promise for the development of a novel respiratory mucosal vaccine approach.

5.
Photoacoustics ; 39: 100643, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39309020

RESUMO

Vaccine development requires high-resolution, in situ, and visual adjuvant technology. To address this need, this work proposed a novel adjuvant labeling that involved indocyanine green (ICG) and bovine serum albumin (BSA) with self-assembled aluminium adjuvant (Alum), which was called BSA@ICG@Alum. This compound exhibited excellent photoacoustic properties and has been confirmed its safety, biocompatibility, high antigen binding efficiency, and superior induction of immune response. Photoacoustic tomography (PAT) tracked the distribution of Alum in lymph nodes (LNs) and lymphatic vessels in real time after diverse injection modalities. The non-invasive imaging approach revealed that BSA@ICG@Alum was transported to the draining LNs 60 min after intramuscular injection and to distal LNs within 30 min after lymph node injection. In conclusion, PAT enabled real-time three-dimensional and quantitative visualization, thus offering a powerful tool for advancing vaccine design by providing critical insights into adjuvant transport and immune system activation.

6.
Huan Jing Ke Xue ; 45(9): 5538-5547, 2024 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-39323170

RESUMO

Considering the extremely high content of soil mineral elements in high geological background areas, it is crucial to understand the transportation and health risks of mineral elements in soil-plant systems. In this study, 30 soil and apple-paired samples were collected from the main apple production areas of Yunnan's high geological background region to determine the contents of mineral elements. The aim was to research the enrichment characteristics, nutritional values, and health risks associated with 12 mineral elements in apples. The results revealed that Cd, As, Pb and Cr contents in soil samples exceeded their corresponding risk screening values with percentages of 50%, 17%, 48%, and 30%, respectively. However, only 13.3% of Pb content in apple samples exceeded the safety limit (0.1 mg·kg-1, fresh fruit). In addition to the toxic elements, apples had higher contents of K, Ca, Mg, Mn, and Zn, with average contents of 1.241 g·kg-1, 0.045 g·kg-1, 0.061 g·kg-1, 0.648 mg·kg-1, and 0.944 mg·kg-1, respectively. The nutritional evaluation results showed that the index (INQ) of K and Cu were higher than 2 through the consumption of apples, suggesting that apple consumption was one of the primary sources of K and Cu intake. The health risk assessment revealed that the target hazard quotient (THQ) of a single heavy metal was: Cu > As > Cr > Pb > Zn > Cd; the hazard index (HI) of all heavy metals was far lower than 1, indicating that apple consumption did not pose significant heavy metal exposure risks. The results of this study will provide a scientific insight into the nutritional aspects and health risks associated with mineral elements in soil-plant systems within high geological background areas.


Assuntos
Malus , Minerais , Poluentes do Solo , Malus/química , China , Medição de Risco , Poluentes do Solo/análise , Minerais/análise , Contaminação de Alimentos/análise , Solo/química , Metais Pesados/análise , Oligoelementos/análise , Arsênio/análise , Frutas/química , Cádmio/análise , Valor Nutritivo , Monitoramento Ambiental , Chumbo/análise
7.
Med Phys ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39298684

RESUMO

BACKGROUND: Cone beam computed tomography (CBCT) provides critical anatomical information for adaptive radiotherapy (ART), especially for tumors in the pelvic region that undergo significant deformation. However, CBCT suffers from inaccurate Hounsfield Unit (HU) values and lower soft tissue contrast. These issues affect the accuracy of pelvic treatment plans and implementation of the treatment, hence requiring correction. PURPOSE: A novel stacked coarse-to-fine model combining Denoising Diffusion Probabilistic Model (DDPM) and spatial-frequency domain convolution modules is proposed to enhance the imaging quality of CBCT images. METHODS: The enhancement of low-quality CBCT images is divided into two stages. In the coarse stage, the improved DDPM with U-ConvNeXt architecture is used to complete the denoising task of CBCT images. In the fine stage, the deep convolutional network model jointly constructed by fast Fourier and dilated convolution modules is used to further enhance the image quality in local details and global imaging. Finally, the accurate pseudo-CT (pCT) images consistent with the size of the original data are obtained. Two hundred fifty paired CBCT-CT images from cervical and rectal cancer, combined with 200 public dataset cases, were used collectively for training, validation, and testing. RESULTS: To evaluate the anatomical consistency between pCT and real CT, we have used the mean(std) of structure similarity index measure (SSIM), peak signal to noise ratio (PSNR), and normalized cross-correlation (NCC). The numerical results for the above three metrics comparing the pCT synthesized by the proposed model against real CT for cervical cancer cases were 87.14% (2.91%), 34.02 dB (1.35 dB), and 88.01% (1.82%), respectively. For rectal cancer cases, the corresponding results were 86.06% (2.70%), 33.50 dB (1.41 dB), and 87.44% (1.95%). The paired t-test analysis between the proposed model and the comparative models (ResUnet, CycleGAN, DDPM, and DDIM) for these metrics revealed statistically significant differences (p < 0.05). The visual results also showed that the anatomical structures between the real CT and the pCT synthesized by the proposed model were closer. For the dosimetric verification, mean absolute error of dosimetry (MAEdoes) values for the maximum dose (Dmax), the minimum dose (Dmin), and the mean dose (Dmean) in the planning target volume (PTV) were analyzed, with results presented as mean (lower quartile, upper quartile). The experimental results show that the values of the above three dosimetry indexes (Dmin, Dmax, and Dmean) for the pCT images synthesized by the proposed model were 0.90% (0.48%, 1.29%), 0.82% (0.47%, 1.17%), and 0.57% (0.44%, 0.67%). Compared with 10 cases of the original CBCT image by Mann-Whitney test (p < 0.05), it also proved that pCT can significantly improve the accuracy of HU values for the dose calculation. CONCLUSION: The pCT synthesized by the proposed model outperforms the comparative models in numerical accuracy and visualization, promising for ART of pelvic cancers.

8.
bioRxiv ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39345460

RESUMO

Extrachromosomal, circular DNA (ecDNA) is a prevalent oncogenic alteration in cancer genomes, often associated with aggressive tumor behavior and poor patient outcome. While previous studies proposed a chromatin-based mobile enhancer model for ecDNA-driven oncogenesis, its precise mechanism and impact remains unclear across diverse cancer types. Our study, utilizing advanced multi-omics profiling, epigenetic editing, and imaging approaches in three cancer models, reveals that ecDNA hubs are an integrated part of nuclear condensates and exhibit cancer-type specific chromatin connectivity. Epigenetic silencing of the ecDNA-specific regulatory modules or chemically disrupting liquid-liquid phase separation breaks down ecDNA hubs, displaces MED1 co-activator binding, inhibits oncogenic transcription, and promotes cell death. These findings substantiate the trans -activator function of ecDNA and underscore a structural mechanism driving oncogenesis. This refined understanding expands our views of oncogene regulation and opens potential avenues for novel therapeutic strategies in cancer treatment.

9.
Micromachines (Basel) ; 15(9)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39337741

RESUMO

A textile bandwidth-enhanced half-mode substrate-integrated cavity (HMSIC) antenna based on embroidered shorting vias is designed. Based on the simulated results of the basic HMSIC antenna, two embroidered hollow posts with square cross-sections are added as shorting vias at the intersections of the zero-E traces of the TM210HM and TM020HM modes to shift the TM010HM-mode band to merge with the bands of the higher-order modes for bandwidth enhancement. A prototype is practically fabricated based on computerized embroidery techniques. Measurement results show that the prototype is of an expanded -10 dB impedance band of 4.87~6.17 GHz (23.5% fractional bandwidth), which fully covers the 5 GHz wireless local area network (WLAN) band. The simulated radiation efficiency and maximum gain of the proposed antenna are above 97% and 7.6 dBi, respectively. Furthermore, simulations and measurements prove its robust frequency response characteristic in the proximity of the human tissues or in bending conditions, and the simulations of the specific absorption rate (SAR) prove its electromagnetic safety on the human body.

11.
World J Gastrointest Surg ; 16(8): 2546-2554, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39220077

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence is highly correlated with increased mortality. Microvascular invasion (MVI) is indicative of aggressive tumor biology in HCC. AIM: To construct an artificial neural network (ANN) capable of accurately predicting MVI presence in HCC using magnetic resonance imaging. METHODS: This study included 255 patients with HCC with tumors < 3 cm. Radiologists annotated the tumors on the T1-weighted plain MR images. Subsequently, a three-layer ANN was constructed using image features as inputs to predict MVI status in patients with HCC. Postoperative pathological examination is considered the gold standard for determining MVI. Receiver operating characteristic analysis was used to evaluate the effectiveness of the algorithm. RESULTS: Using the bagging strategy to vote for 50 classifier classification results, a prediction model yielded an area under the curve (AUC) of 0.79. Moreover, correlation analysis revealed that alpha-fetoprotein values and tumor volume were not significantly correlated with the occurrence of MVI, whereas tumor sphericity was significantly correlated with MVI (P < 0.01). CONCLUSION: Analysis of variable correlations regarding MVI in tumors with diameters < 3 cm should prioritize tumor sphericity. The ANN model demonstrated strong predictive MVI for patients with HCC (AUC = 0.79).

12.
J Mater Chem B ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39282740

RESUMO

Small interfering RNAs (siRNAs), comprising 21-23 nucleotides, function by complementary binding to specific mRNA sequences, thereby suppressing target protein expression. Despite their vast potential in disease therapy, siRNAs face challenges due to their susceptibility to degradation and high electronegativity, rendering them unstable in the bloodstream and impeding their passage across endothelial barriers. Moreover, successful intracellular delivery necessitates overcoming endosomal entrapment, posing a significant hurdle for carrier material development. In this study, leveraging the strong affinity of histidine oligomers (His6) for metal ions, we engineered nanoparticles (HmA) by gentle assembly with divalent zinc ions under pH = 8 conditions. We designed the RNA-binding functional peptide L2-NTD to enhance siRNA stability and delivery efficiency when complexed with HmA. The resulting siRNA+L2-NTD@HmA nanoparticles were formed via in situ encapsulation, ensuring efficient siRNA delivery into cells with minimal cytotoxicity and degradation. This approach presents a novel strategy for the design and artificial fabrication of carriers for effective RNA delivery.

13.
Neural Regen Res ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39248166

RESUMO

Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells. However, adult tissue-derived mesenchymal stem cells encounter various obstacles, including limited tissue sources, invasive acquisition methods, cellular heterogeneity, purification challenges, cellular senescence, and diminished pluripotency and proliferation over successive passages. In this study, we used induced pluripotent stem cell-derived mesenchymal stem cells, known for their self-renewal capacity, multilineage differentiation potential, and immunomodulatory characteristics. We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury. Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation. Furthermore, the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats. Additionally, our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization. Collectively, our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats, offering promising therapeutic strategies for clinical translation.

14.
Food Chem X ; 23: 101735, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39263338

RESUMO

Fresh yak meat is highly nutritious and prone to spoilage, so developing suitable preservation methods is crucial. In this study, hydrogel coatings composed of konjac glucomannan, Lactiplantibacillus plantarum and gallic acid (KGX) were applied to preserve fresh yak meat under ice temperature (-1 °C). After 16 days, KGX group showed lowest total viable count (5.3 ± 0.1 log cfu/g) and total volatile basic nitrogen (13.02 ± 1.40 mg/100 g), which did not exceed the relevant standards of fresh meat. Combined assessments of color, texture, pH, drip loss rate, and thiobarbituric acid reactive substances indicated that KGX coating effectively prolonged yak meat preservation. High-throughput sequencing revealed that KGX coating effectively reduced the abundance of Pseudomonas and Candida. The application of L. plantarum hydrogel coatings in conjunction with ice temperature increased the shelf life of fresh yak meat to 16-20 days, suggesting its potential as a viable preservation method for fresh meat.

15.
Microbiol Spectr ; 12(10): e0402523, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39190634

RESUMO

The gut microbiota, a pivotal component of the intestinal mucosal barrier, is critical for host resistance to enteric pathogen infection. Here, we report a novel function of the potentially probiotic Lactococcus garvieae strain LG1 (L. garvieae strain LG1) in maintaining intestinal mucosal barrier integrity and protecting against foodborne Clostridium perfringens (C. perfringens) infection. L. garvieae was isolated from the intestinal contents of Chinese Mongolian sheep (MS) and exhibited potential probiotic properties. In a C. perfringens enterocolitis model, L. garvieae-pretreated mice were less susceptible to C. perfringens infection compared with Phosphate buffered solution (PBS)-pretreated mice, which manifested as higher survival rates, lower pathogen loads, less weight loss, mild clinical symptoms and intestinal damage, and minor inflammation. Further mechanistic analysis showed that L. garvieae could ameliorate the disruption of intestinal permeability and maintain the integrity of the intestinal mucosal barrier by promoting the expression of tight junction proteins and mucoproteins. Moreover, L. garvieae was also able to facilitate antimicrobial peptide expression and ameliorate dysbiosis of the gut microbiota caused by C. perfringens. Together, these findings highlight the prospect of immunomodulatory potentially probiotic L. garvieae and might offer valuable strategies for prophylaxis and/or treatment of pathogenic C. perfringens mucosal infection. IMPORTANCE: C. perfringens necrotic enteritis leads to losses of about US $2 billion to the poultry industry worldwide every year. Worse, US Centers for Disease Control and Prevention (CDC) has estimated that C. perfringens causes nearly 1 million foodborne illnesses in the United States annually. Nowadays, the treatment recommendation is a combination of a broad-spectrum synergistic penicillin with clindamycin or a carbapenem, despite growing scientific concern over antibiotic resistance. The global understanding of the gut microbiome for C. perfringens infection may provide important insights into the intervention. L. garvieae originated from Mongolian sheep intestine, exhibited potentially probiotic properties, and was able to limit C. perfringens enterocolitis and pathogenic colonization. Importantly, we found that L. garvieae limits C. perfringens invasion via improving intestinal mucosal barrier function. Also, L. garvieae alleviates C. perfringens-induced gut microbiota dysbiosis. It allowed us to convince that utilization of probiotics to promote protective immunity against pathogens infection is of pivotal importance.


Assuntos
Infecções por Clostridium , Clostridium perfringens , Microbioma Gastrointestinal , Mucosa Intestinal , Lactococcus , Probióticos , Animais , Clostridium perfringens/imunologia , Clostridium perfringens/fisiologia , Camundongos , Infecções por Clostridium/imunologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/microbiologia , Infecções por Clostridium/veterinária , Probióticos/administração & dosagem , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Ovinos , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/prevenção & controle , Feminino , Modelos Animais de Doenças , Disbiose/microbiologia , Disbiose/prevenção & controle , Disbiose/imunologia
16.
Sci Rep ; 14(1): 18931, 2024 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-39147803

RESUMO

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.


Assuntos
Aprendizado Profundo , Recidiva Local de Neoplasia , Neoplasias não Músculo Invasivas da Bexiga , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias não Músculo Invasivas da Bexiga/patologia , Curva ROC , Medição de Risco/métodos
17.
World J Gastroenterol ; 30(29): 3511-3533, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39156500

RESUMO

BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.


Assuntos
Neoplasias Hepáticas , Camundongos Nus , Simulação de Acoplamento Molecular , Microambiente Tumoral , Macrófagos Associados a Tumor , Via de Sinalização Wnt , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Humanos , Camundongos , Células Hep G2 , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Masculino , Farmacologia em Rede , beta Catenina/metabolismo , Medicina Tradicional Chinesa/métodos
18.
Insects ; 15(8)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39194775

RESUMO

Parasitoids have the potential to alter the gut microbiota of their host insects post-parasitization, thereby influencing the host's physiological functions and creating a more favorable environment for the survival of the parasitoid's progeny. Cotesia ruficrus is a native enemy of the important invasive fall armyworm (FAW) pest, Spodoptera frugiperda, in China, exhibiting significant pest control capabilities. To investigate the impact of C. ruficrus on the gut bacteria of FAW caterpillars following parasitism, we used 16S rRNA sequencing technology to analyze the diversity and richness of gut bacteria in both long-term laboratory and short-term laboratory FAW caterpillars. The results revealed Enterococcus as the predominant bacteria across all treatments, while no significant differences were observed in the diversity and richness of gut bacteria between non-parasitized and parasitized long-term laboratory FAW caterpillars. Similarly, while the diversity of gut bacteria in non-parasitized and parasitized short-term laboratory FAWs showed no significant variance, a marked discrepancy in richness was noted. Moreover, the richness of gut bacteria in short-term laboratory FAW caterpillars surpassed that of their long-term laboratory counterparts. In addition, it was found that Corynebacterium existed only in the intestinal tract of FAW caterpillars that were parasitized by C. ruficrus. These results substantiate that C. ruficrus parasitization can alter the gut microbiota of FAW caterpillars, providing valuable insights into the interplay between gut microbiota and the dynamics of parasitoid-host interactions.

19.
Bioorg Chem ; 151: 107686, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111120

RESUMO

A series of novel quinazoline-derived EGFR/HER-2 dual-target inhibitors were designed and synthesized by heterocyclic-containing tail approach. The inhibitory activities against four human epidermal growth factor receptor (HER) isozymes (EGFR, HER-2, HER-3 and HER-4) of all new compounds so designed were investigated in vitro. Compound 12k was found to be the most effective and rather selective dual-target inhibitor of EGFR and HER-2 with inhibitory constant (IC50) values of 6.15 and 9.78 nM, respectively, which was more potent than the clinical used agent Lapatinib (IC50 = 8.41 and 9.41 nM). Meanwhile, almost all compounds showed excellent antiproliferative activities against four cancer cell models (A549, NCI-H1975, SK-BR-3 and MCF-7) and low damage to healthy cells. Among them, compound 12k also exhibited the most prominent antitumor activity. Moreover, the hit compound 12k could bind to EGFR and HER-2 stably in molecular docking and dynamics studies. The following wound healing assay revealed that compound 12k could inhibit the migration of SK-BR-3 cells. Further studies found that compound 12k could arrest cell cycle in the G0/G1 phase and induce SK-BR-3 cells apoptosis. Notably, compound 12k could effectively inhibit breast cancer growth with little toxicity in the SK-BR-3 cell xenograft model. Taken together, in vitro and in vivo results disclosed that compound 12k had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth.


Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Inibidores de Proteínas Quinases , Quinazolinas , Receptor ErbB-2 , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Quinazolinas/farmacologia , Quinazolinas/química , Quinazolinas/síntese química , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Animais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Camundongos , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Apoptose/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Compostos Heterocíclicos/síntese química , Feminino
20.
Huan Jing Ke Xue ; 45(8): 4812-4824, 2024 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-39168698

RESUMO

The contents of eight heavy metals (Cr, Ni, Cu, Zn, Cd, Pb, As, and Hg) were determined based on the surface soil samples of sewage irrigation and industrial complex in Kaifeng City. The absolute factor analysis-multiple linear regression (APCS-MLR) model and positive matrix factorization (PMF) model were used to analyze the sources and contribution rates of heavy metals in soil combined with correlation analysis and systematic cluster analysis. The results showed that: ① The average values of ω(Cr), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), ω(As), and ω(Hg) in the study area were 52.19, 25.00, 42.03, 323.53, 1.79, 53.45, 9.43, and 0.20 mg·kg-1, respectively, and Cr, Ni, and As are lower than the background values of tidal soil. Cu, Zn, Cd, Pb, and Hg are higher than the background values of the tidal soil. ② There were four sources of the eight heavy metals: natural sources, agricultural sewage irrigation sources, industrial atmospheric sedimentation sources, and transportation sources. Cr and Ni were mainly from natural sources; Cu, Zn, Cd, and Pb were mainly from agricultural sewage irrigation and transportation sources; As was mainly from natural sources and agricultural sewage irrigation; and Hg was mainly from industrial atmospheric sedimentation. ③ The APCS-MLR and PMF source analysis results indicated that industrial and agricultural activities were the main sources of heavy metals in the soil of the study area. The average contribution rates of APCS-MLR in the nine sampling areas of the research area were 76.01% (natural sources and agricultural sewage irrigation sources), 22.71% (industrial atmospheric sedimentation sources and transportation sources), and 1.28% (unknown sources). The average contribution rates of PMF were 59.66% (natural sources and agricultural sewage irrigation sources) and 40.34% (industrial atmospheric sedimentation sources and transportation sources). The source analysis results of the LZ, XZ, NLT, PT, YLZ, and BC models were basically consistent, and WL was better in the APCS-MLR model, whereas SG and QT were better in the PMF model. The research results can provide a scientific basis for the prevention and control of soil heavy metal pollution and environmental remediation.

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