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1.
Chemosphere ; 310: 136759, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36228729

RESUMO

In this work, graphene oxide (GO) sheets were prepared via a facile electrochemical exfoliation of graphite in acidic medium and subsequent oxidation with potassium permanganate. The GO sheets were employed for preparation of reduced GO adorned with nanosized silver (rGO/Ag NPs) using green reduction of GO and Ag(I) via olive fruit extract as a reducing and immobilizing agent. The crystal phase, morphology, and nanostructure of the prepared catalyst were characterized by XRD, SEM, EDX, UV-Vis and Raman spectroscopy techniques. The as-prepared rGO/Ag NPs showed superior catalytic performance towards the complete reduction (up to 99%) of 4-nitrophenol (4-NPH) to 4-aminophenol (4-APH) and rhodamine B (RhB) to Leuco RhB within 180 s using NaBH4 at ambient condition. The rate constant (k) values were found to be 0.021 and 0.022 s-1 for 4-NPH and RhB reduction, respectively. In addition, the regenerated catalyst could be reused after seven cycles without losing any apparent catalytic efficiency. Accounting for the excellent catalytic capability, chemical stability and environment-friendly synthesis protocol, the rGO/Ag NPs has great potential working as a heterogeneous catalyst in the transforming harmful organic contaminants into less harmful or harmless compounds.


Assuntos
Poluentes Ambientais , Grafite , Nanopartículas Metálicas , Olea , Grafite/química , Prata/química , Nanopartículas Metálicas/química
2.
Chemosphere ; 311(Pt 1): 136968, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36283429

RESUMO

The plastic concentration in terrestrial systems is orders of magnitude higher than that found in marine ecosystems, which has raised global concerns about their potential risk to agricultural sustainability. Previous research on the transport of nanoplastics in soil relied heavily on the qualitative prediction of the mean-field extended Derjaguin-Landau-Verwey-Overbeek theory (XDLVO), but direct and quantitative measurements of the interfacial forces between single nanoplastics and porous media are lacking. In this study, we conducted multiscale investigations ranging from column transport experiments to single particle measurements. The maximum effluent concentration (C/C0) of amino-modified nanoplastics (PS-NH2) was 0.94, whereas that of the carboxyl-modified nanoplastics (PS-COOH) was only 0.33, indicating PS-NH2 were more mobile than PS-COOH at different ionic strengths (1-50 mM) and pH values (5-9). This phenomenon was mainly attributed to the homogeneous aggregation of PS-COOH. In addition, the transport of PS-NH2 in the quartz sand column was inhibited with the increase of ionic strength and pH, and pH was the major factor governing their mobility. The transport of PS-COOH was inhibited with increasing ionic strength and decreasing pH. Hydrophilicity/hydrophobicity-mediated interactions and particle heterogeneity strongly interfered with interfacial forces, leading to the qualitative prediction of XDLVO, contrary to experimental observations. Through the combination of XDLVO and colloidal atomic force microscopy, accurate and quantitative interfacial forces can provide compelling insight into the fate of nanoparticles in the soil environment.


Assuntos
Ecossistema , Microplásticos , Porosidade , Quartzo , Areia
3.
J Environ Sci (China) ; 124: 205-214, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182132

RESUMO

Allelochemicals sustained-release microspheres (ACs-SMs) exhibited great inhibition effect on algae, however, few studies have focused on ACs-SMs toxicity on invertebrate. In this study, the effects of single high-concentration ACs (15 mg/L, SH-ACs), repeated low-concentration ACs (3 × 5 mg/L, RL-ACs) and ACs-SMs containing 15 mg/L ACs exposure on the ingestion, incorporation, and digestion of Daphnia magna Straus (DS) were investigated by stable isotope 15N labeling method. Meanwhile, the diversity and abundance of microflora in DS guts were determined by 16S rRNA genes and cloning methods. The results showed that SH-ACs exposure caused 50% and 33.3% death rates for newborn and adult DS, while RL-ACs exposure caused 10% death rate for newborn DS and no obvious effect on the activity of adult DS. And ACs-SMs exposure did not diminish the motility of both newborn and adult DS, indicating the lower acute toxicity of ACs-SMs. Furthermore, SH-ACs inhibited the ingestion (-6.45%), incorporation (-47.1%) and digestion (-53.8%) abilities of DS and reduced the microbial abundance (-27.7%) in DS guts. Compared with SH-ACs, RL-ACs showed relatively low impact on the ingestion (-3.23%), incorporation (-5.89%) and digestion (-23.9%) abilities of DS. Interestingly, ACs-SMs enhanced the ingestion (+9.68%), incorporation (+52.9%) and digestion (+51.3%) abilities of DS and increased the microbial abundance (+10.7%) in DS guts. Overall ACs and ACs-SMs reduced the diversity of microflora in DS guts. In conclusion, ACs-SMs can release ACs sustainably and prolong the sustained release time, which not only effectively reduce the toxicity of ACs, but also had positive effects on DS.


Assuntos
Daphnia , Poluentes Químicos da Água , Animais , Preparações de Ação Retardada/farmacologia , Digestão , Ingestão de Alimentos , Microesferas , Feromônios , RNA Ribossômico 16S , Poluentes Químicos da Água/toxicidade
4.
J Hazard Mater ; 441: 129905, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36113348

RESUMO

The structural defects and heteroatom dopants of carbonaceous materials play critical roles in their activation of peroxymonosulfate (PMS) for organic pollutants' removal. This study uses plasma-etching technology to control the levels of structural defects and nitrogen species in nitrogen-doped carbon nanotubes (N-CNTs) for excellent PMS activation. The vacancy defects, CO, pyrrolic N and graphitic N could be rationally designed by controlling the plasma-etching time. Obviously, the ID/IG (from 0.56 to 0.94) and CO contents (from 0.07 to 0.44 at%) of N-CNTs increase with rising etching time, exhibiting good linear positive correlations with phenol oxidation rates. Furthermore, through active species identification, quantitative structure-activity relationships analysis and theoretical calculations, vacancy defects (adsorbing PMS O1 site) and CO are confirmed to be the active sites for the generation of 1O2, which is major pathway (82%) for phenol degradation. While radicals induced by pyrrolic N and graphitic N adsorbing PMS O2 site are the minor pathway (18%). Overall, this study sheds new light on the crucial roles of defects and N species in inducing PMS non-radical/radical activation by carbocatalyst via efficiently controlled plasma-etching technology.

5.
Front Nutr ; 9: 999489, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337642

RESUMO

Obesity and vitamin D deficiency are both considered risk factors for mortality, but the potential additive effects of vitamin D status and obesity on mortality has not been well-studied. We aimed to examine the possible additive effects of obesity and vitamin D status on all-cause and cause-specific mortality. The data from the NHANES III (1988-1994) and NHANES 2001-2014 surveys were used, and multivariate Cox regression models were performed to assess the additive effects of vitamin D status and overweight/obesity/abdominal obesity on the all-cause, cardiovascular and cancer mortality, by stratifying Cox Hazard Ratios (HRs) across different categories of vitamin D status and body mass index (BMI) and waist circumference (WC) categories. The models were adjusted for age, race/ethnicity, gender, educational level, family income to poverty ratio, leisure-time physical activity, smoking, and drinking. Across all BMI/WC categories, there was an additive effect of the vitamin D both insufficiency and deficiency on all mortality rates, with deficiency having much stronger effect than insufficiency. Interestingly, the effect of vitamin D deficiency overcame the effect of obesity on all mortality rates. The highest HRs for overall and cardiovascular mortality were observed among vitamin D deficient obese/abdominally obese subjects, while for cancer mortality among vitamin D deficient normal weight/non-abdominally obese subjects. In stratified analyses, regarding all-cause mortality, there was an additive effect of the vitamin D both insufficiency and deficiency in all BMI/WC categories. Regarding cardiovascular mortality, there was an additive effect of vitamin D deficiency in all BMI/WC categories, but the additive effect of vitamin D insufficiency reached significance only in normal weight subjects. Regarding cancer mortality, the effect did not reach significance among obese subjects for vitamin D deficiency, while for insufficiency, significance was reached only among non-abdominally obese subjects. Interestingly, vitamin D surplus was associated with increased risk for cancer mortality in obese subjects, but there was an inadequate number of subjects in this category to make proper judgment. In conclusion, vitamin D insufficiency and deficiency gradually increase risk for mortality across all BMI/WC categories. In our analyses, vitamin D deficiency overcame the effect of obesity on mortality rates.

6.
Front Oncol ; 12: 945867, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338747

RESUMO

In recent years, many clinical trials have shown the safety and efficacy of Gemogenovatucel-T (Vigil) in the treatment of advanced OC patients. The purpose of this study was to explore the safety and efficacy of Gemogenovatucel-T (Vigil) in the first-line maintenance of advanced ovarian carcinoma based on the randomized controlled trials (RCTs). Randomized controlled trials (RCTs) on Gemogenovatucel-T (Vigil) immunotherapy for advanced ovarian carcinoma were searched in PubMed, Embase, Cochrane Library and Web of Science up to December 31, 2021. The following study characteristics were investigated: baseline study characteristics, overall survival, recurrence free survival, recurrence free survival median time, and complication. A total of 36 articles were obtained, and seven suitable RCTs with a total sample size of 322 patients were eventually included in this meta-analysis. Overall survival (OS): from time of randomization: HR=0.48 (95% CI: 0.32 to 0.72), Z=3.55, P<0.001; from time of tissue procurement: HR=0.51 (95% CI: 0.33 to 0.78), Z=3.07, P=0.002. Recurrence free survival (RFS): from time of randomization: HR=0.43 (95% CI: 0.30 to 0.62), Z=4.61, P<0.001; from time of tissue procurement: HR=0.45 (95% CI: 0.31 to 0.65), Z=4.26, P<0.001. RFS median time: from time of randomization: HR=1.57 (95% CI: 1.16 to 2.11), Z=2.95, P=0.003; from time of tissue procurement: HR=2.16 (95% CI: 1.12 to 4.17), Z=2.29, P=0.022. This study found that Gemogenovatucel-T (Vigil) immunotherapy provided significant OS and RFS benefits, particularly in advanced OC patients with BRCA wild type. At the same time, treatment with the Gemogenovatucel-T (Vigil) is safer than other treatment modalities and does not have any toxic effects. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42022300367).

7.
Digit Health ; 8: 20552076221136362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339902

RESUMO

Objective: Due to the complexity of face images, tongue segmentation is susceptible to interference from uneven tongue texture, lips and face, resulting in traditional methods failing to segment the tongue accurately. To address this problem, RAFF-Net, an automatic tongue region segmentation network based on residual attention network and multiscale feature fusion, was proposed. It aims to improve tongue segmentation accuracy and achieve end-to-end automated segmentation. Methods: Based on the UNet backbone network, different numbers of ResBlocks combined with the Squeeze-and-Excitation (SE) block was used as an encoder to extract image layered features. The decoder structure of UNet was simplified and the number of parameters of the network model was reduced. Meanwhile, the multiscale feature fusion module was designed to optimize the network parameters by combining a custom loss function instead of the common cross-entropy loss function to further improve the detection accuracy. Results: The RAFF-Net network structure achieved Mean Intersection over Union (MIoU) and F1-score of 97.85% and 97.73%, respectively, which improved 0.56% and 0.46%, respectively, compared with the original UNet; ablation experiments demonstrated that the improved algorithm could contribute to the enhancement of tongue segmentation effect. Conclusion: This study combined the residual attention network with multiscale feature fusion to effectively improve the segmentation accuracy of the tongue region, and optimized the input and output of the UNet network using different numbers of ResBlocks, SE block, multiscale feature fusion and weighted loss function, increased the stability of the network and improved the overall effect of the network.

8.
Front Plant Sci ; 13: 1029722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352878

RESUMO

In the Atractylodes lancea (A. lancea)-maize intercropping system, maize can promote the growth of A. lancea, but it is unclear whether this constitutes an aboveground or belowground process. In this study, we investigated the mechanisms of the root system interaction between A. lancea and maize using three different barrier conditions: no barrier (AI), nylon barrier (AN), and plastic barrier (AP) systems. The biomass, volatile oil concentration, physicochemical properties of the soil, and rhizosphere microorganisms of the A. lancea plant were determined. The results showed that (1) the A. lancea - maize intercropping system could promote the growth of A. lancea and its accumulation of volatile oils; (2) a comparison of the CK, AI, and AP treatments revealed that it was the above-ground effect of maize specifically that promoted the accumulation of both atractylon and atractylodin within the volatile oils of A. lancea, but inhibited the accumulation of hinesol and ß-eudesmol; (3) in comparing the soil physicochemical properties of each treatment group, intercropping maize acidified the root soil of A. lancea, changed its root soil physicochemical properties, and increased the abundance of the acidic rhizosphere microbes of A. lancea at the phylum level; (4) in an analysis of rhizosphere microbial communities of A. lancea under different barrier systems, intercropping was found to promote plant growth-promoting rhizobacteria (PGPR) enrichment, including Streptomyces, Bradyrhizobium, Candidatus Solibacter, Gemmatirosa, and Pseudolabrys, and the biomass of A. lancea was significantly influenced by PGPR. In summary, we found that the rhizosphere soil of A. lancea was acidified in intercropping with maize, causing the accumulation of PGPR, which was beneficial to the growth of A. lancea.

9.
Anal Chem ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36395421

RESUMO

The development of facile, reliable, and accurate assays for pathogenic bacteria is critical to environmental pollution surveillance, traceability analysis, prevention, and control. Here, we proposed a rolling circle amplification (RCA) strategy-driven visual photothermal smartphone-based biosensor for achieving highly sensitive monitoring of Escherichia coli (E. coli) in environmental media. In this design, E. coli could specifically bind with its recognition aptamer for initiating the RCA process on a magnetic bead (MB). Owing to the cleaving of UV irradiation toward photoresponsive DNA on MB, the RCA products were released to further hybridize with near-infrared excited CuxS-modified DNA probes. As a result, the photothermal signal was enhanced by RCA, while the background was decreased by UV irradiation and magnetic separation. The correspondingly generated photothermal signals were unambiguously recorded on a smartphone, allowing for an E. coli assay with a low detection limit of 1.8 CFU/mL among the broad linear range from 5.0 to 5.0 × 105 CFU/mL. Significantly, this proposed biosensor has been successfully applied to monitor the fouling levels of E. coli in spring water samples with acceptable results. This study holds great prospects by integrating a RCA-driven photothermal amplification strategy into a smartphone to develop accurate, reliable, and efficient analytical platforms against pathogenic bacteria pollutions for safeguarding environmental health.

10.
Front Plant Sci ; 13: 938758, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388496

RESUMO

Desert shrubs play important roles in desertification control and vegetation restoration, which are particularly affected by droughts caused by climate change. However, the hydraulic strategies associated with hydraulic functional traits of desert shrubs remain unclear. Here, eight desert shrub species with different life forms and morphologies were selected for a common garden experiment at the southeast edge of the Tengger Desert in northern China to study the hydraulic strategies mediated by leaf hydraulic functional traits. Diurnal leaf water potential change, leaf hydraulic efficiency and safety, hydraulic safety margin, hydraulic capacitance, and water potential and relative water content at the turgor loss point were observed to significantly differ among species, suggesting that leaf hydraulic functional traits were strongly associated with species even when living in the same environment. Additionally, shrubs with greater leaf hydraulic efficiency had lower midday leaf water potential and leaf hydraulic safety, suggesting that leaf hydraulic efficiency had a strong trade-off with hydraulic safety and minimum leaf water potential, whereas there was also a coordination between leaf hydraulic safety and the leaf minimal water potential. Moreover, shrubs with higher leaf hydraulic capacitance had greater hydraulic safety margins, indicating coordination between leaf hydraulic capacitance and hydraulic safety margin. Overall, this study indicated that minimal daily leaf water potential, as an easily measured parameter, may be used preliminarily to predict leaf hydraulic conductivity and the resistance to embolism of desert shrubs, providing critical insights into hydraulic trade-off and coordination strategies for native shrubs as priority species in desert vegetation restoration and reconstruction.

13.
Neurol Sci ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369308

RESUMO

BACKGROUND AND OBJECTIVE: An acute exacerbation of myasthenia gravis (MG) can lead to the life-threatening myasthenia crisis which can increase the in-hospital mortality. This study aimed to clarify the correlative factor of the severity and activity of MG and the predictors of its exacerbation. METHODS: A prospective study was conducted to compare the clinical characteristics of acetylcholine receptor antibody (AChR-Ab)-positive generalized MG during acute exacerbation (AE) and in a stable state (SS). Logistic regression was used to determine risk factors, and a nomogram was developed. RESULTS: A total of 97 AChR-Ab MG patients were enrolled, of whom 44 had AE and 53 were in SS. The concentrations of AChR-Ab were 35.24 (23.26, 42.52) nmol/L and 19.51 (8.30, 36.93) nmol/L in the AE and SS groups (P = 0.005), respectively. The receiver operating characteristic curve showed that a single AChR-Ab predicted severity and acute exacerbation, with an area under the curve (AUC) of 0.679. Logistic regression analysis showed that, in addition to AChR-Ab (P = 0.018), bulbar symptoms (P = 0.001), interleukin (IL)-6 (P = 0.025), CD4+/CD8+ T cell ratio (P = 0.031), and CD19+ B cell proportion (P = 0.019) were independent risk factors for acute exacerbation of MG. The developed nomogram had an AUC of 0.878. The Hosmer and Lemeshow chi-square test was 4.37 (P = 0.929). CONCLUSION: AChR-Ab concentration was positively correlated with the severity and activity of MG. AChR-Ab concentration, alongside bulbar symptoms, IL-6 concentration, CD4+/CD8+ T cell ratio, and CD19+ B cell proportion can predict the acute exacerbation of MG.

14.
Animals (Basel) ; 12(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36359075

RESUMO

Swine enteric disease is the predominant cause of morbidity and mortality, and viral species involved in swine enteric disease include rotaviruses and coronaviruses, among others. Awareness of the circulating porcine rotavirus group C (PoRVC) in pig herds is critical to evaluate the potential impact of infection. At present, due to the lack of disease awareness and molecular diagnostic means, the research on RVC infection in China is not well-studied. In this study, diarrhea samples collected from pig farms were detected positive for RVC by PCR, and the full-length RVC was not previously reported for Chinese pig farms. This rotavirus strain was designated as RVC/Pig/CHN/JS02/2018/G6P6. A natural recombination event was observed with breakpoints at nucleotides (nt) 2509 to 2748 of the VP2 gene. Phylogenetic analysis based on nsp1 revealed that a new branch A10 formed. Collectively, our data suggest a potentially novel gene recombination event of RVC in the VP2 gene. These findings provide a new insight into the evolution of the rotavirus.

15.
Gene ; 851: 147007, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334619

RESUMO

The prevalence of porcine enteric coronaviruses (PECs), including transmissible gastroenteritis virus (TGEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine delta coronavirus (PDCoV), and porcine epidemic diarrhea virus (PEDV), poses a serious threat to animal and public health. Here, we aimed to further optimize the porcine aminopeptidase N (pAPN) gene editing strategy to explore the balance between individual antiviral properties and the biological functions of pAPN in pigs. Finally, APN-chimeric gene-edited pigs were produced through a CRISPR/Cas9-mediated knock-in strategy. Further reproductive tests indicated that these gene-edited pigs exhibited normal pregnancy rates and viability. Notably, in vitro viral challenge assays further demonstrated that porcine kidney epithelial cells isolated from F1-generation gene-edited pigs could effectively inhibit TGEV infection. This study is the first to report the generation of APN-chimeric pigs, which may provide a natural host animal for characterizing PEC infection with APN and help in the development of better antiviral solutions.

16.
ACS Appl Mater Interfaces ; 14(46): 51619-51629, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36346909

RESUMO

Metal-organic frameworks (MOFs) are advanced platforms for enzyme immobilization. Enzymes can be entrapped via either diffusion (into pre-formed MOFs) or co-crystallization. Enzyme co-crystallization with specific metals/ligands in the aqueous phase, also known as biomineralization, minimizes the enzyme loss compared to organic phase co-crystallization, removes the size limitation on enzymes and substrates, and can potentially broaden the application of enzyme@MOF composites. However, not all enzymes are stable/functional in the presence of excess metal ions and/or ligands currently available for co-crystallization. Furthermore, most current biomineralization-based MOFs have limited (acid) pH stability, making it necessary to explore other metal-ligand combinations that can also immobilize enzymes. Here, we report our discovery on the combination of five metal ions and two ligands that can form biocomposites with two model enzymes differing in size and hydrophobicity in the aqueous phase under ambient conditions. Surprisingly, most of the formed composites are single- or multiphase crystals, even though the reaction phase is aqueous, with the rest as amorphous powders. All 20 enzyme@MOF composites showed good to excellent reusability and were stable under weakly acidic pH values. The stability under weakly basic conditions depended upon the selection of enzyme and metal-ligand combinations, yet for both enzymes, 3-4 MOFs offered decent stability under basic conditions. This work initiates the expansion of the current "library" of metal-ligand selection for encapsulating/biomineralizing large enzymes/enzyme clusters, leading to customized encapsulation of enzymes according to enzyme stability, functionality, and optimal pH.


Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Biomineralização , Ligantes , Enzimas Imobilizadas/química , Estabilidade Enzimática , Metais
17.
Sci Adv ; 8(45): eabq2321, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36367940

RESUMO

Solution-processable all-inorganic CsPbI3-xBrx perovskite holds great potential for pure red light-emitting diodes. However, the widely existing defects in this mixed halide perovskite markedly limit the efficiency and stability of present light-emitting diode devices. We here identify that intragrain Ruddlesden-Popper planar defects are primary forms of such defects in the CsPbI3-xBrx thin film owing to the lattice strain caused by inhomogeneous halogen ion distribution. To eliminate these defects, we develop a stepwise metastable phase crystallization strategy to minimize the CsPbI3-xBrx perovskite lattice strain, which brings planar defect-free CsPbI3-xBrx thin film with improved radiative recombination, narrowed emission band, and enhanced spectral stability. Using these high-quality thin films, we fabricate spectrally stable pure red perovskite light-emitting diodes, showing 17.8% external quantum efficiency and 9000 candela meter-2 brightness with color coordinates required by Rec. 2020.

18.
Cancer Manag Res ; 14: 3175-3179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36411743

RESUMO

Background: Lorlatinib has been suggested as the therapeutic option for patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) after ROS1 tyrosine kinase inhibitor (TKI) failure. However, the mechanism mediating lorlatinib resistance has not been well elucidated in ROS1-rearranged NSCLC. Post- lorlatinib therapeutic options remain scarce. Case Presentation: Herein, we describe a 31-year-old female patient with stage IVB ROS1-rearranged NSCLC. She received 2nd line treatment with crizotinib after chemotherapy failure and achieved a partial response lasting for 15 months. An NF1 p.G127Ter mutation emerged as a potential crizotinib resistance mechanism. She subsequently received lorlatinib treatment and achieved a progression-free survival (PFS) of seven months. Based on the emergence of a resistant BRAF V600E, the patient was switched to a combinatorial targeted therapy with lorlatinib, dabrafenib, and trametinib and attained stable disease. She continued the treatment with a time-to-treatment failure of 5.5 months. The acquisition of NRAS p.Q61R and NTRK amplification may confer resistance to the combinatorial targeted therapy. Conclusion: To the best of our knowledge, we reported the first case demonstrating that BRAF p.V600E can mediate the lorlatinib resistance in ROS1-rearranged NSCLC and the combinational targeted therapy of ROS1 TKI with dabrafenib and trametinib may serve as an efficient therapeutic option for subsequent treatment.

19.
Front Immunol ; 13: 989972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389722

RESUMO

Metastatic castration-resistant prostate cancer (CRPC) has long been considered to be associated with patient mortality. Among metastatic organs, bone is the most common metastatic site, with more than 90% of advanced patients developing bone metastases (BMs) before 24 months of death. Although patients were recommended to use bone-targeted drugs represented by bisphosphonates to treat BMs of CRPC, there was no significant improvement in patient survival. In addition, the use of immunotherapy and androgen deprivation therapy is limited due to the immunosuppressed state and resistance to antiandrogen agents in patients with bone metastases. Therefore, it is still essential to develop a safe and effective therapeutic schedule for CRPC patients with BMs. To this end, we propose a multiplex drug repurposing scheme targeting differences in patient immune cell composition. The identified drug candidates were ranked from the perspective of M2 macrophages by integrating transcriptome and network-based analysis. Meanwhile, computational chemistry and clinical trials were used to generate a comprehensive drug candidate list for the BMs of CRPC by drug redundancy structure filtering. In addition to docetaxel, which has been approved for clinical trials, the list includes norethindrone, testosterone, menthol and foretinib. This study provides a new scheme for BMs of CRPC from the perspective of M2 macrophages. It is undeniable that this multiplex drug repurposing scheme specifically for immune cell-related bone metastases can be used for drug screening of any immune-related disease, helping clinicians find promising therapeutic schedules more quickly, and providing reference information for drug R&D and clinical trials.


Assuntos
Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Transcriptoma , Reposicionamento de Medicamentos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Macrófagos/patologia
20.
Fitoterapia ; : 105350, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36375687

RESUMO

Croton kongensis Gagnepain. belongs to the genus Croton, the Euphorbiaceae family, mainly distributed in Hainan and southern Yunnan, China. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the leaves and twigs of C. kongensis. Three new abietane-type diterpenoids, crokongenolides A-C (1-3), together with seven known diterpenoids (4-10), were isolated from the leaves and twigs of C. kongensis. The structures of the new compounds were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS), and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis or electronic circular dichroism (ECD) calculations. The absolute configuration of 4 was determined for the first time by single-crystal X-ray diffraction analysis with Cu-Kα irradiation. Some compounds were evaluated for their antimicrobial properties by assessing their inhibitory effects on Staphylococcus aureus, Candida albicans, and Escherichia coli. Compound 10 showed significant antimicrobial activity against S. aureus with MIC value of 1.56 µg/ml.

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