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1.
Sci Total Environ ; 855: 158652, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36108864

RESUMO

Due to the public health concern of arsenic, environmental management measures in mining areas had been implemented. To assess the effect of environmental management measures in the mining area comprehensively, arsenic accumulation in the urine, hair, nails, and urinary metabolites of residents in a realgar mining area in Hunan province, China were investigated in 2019, and the changes in arsenic levels in the biomarkers during 2012-2019 were tracked. The importance of confounding factors (age, sex, occupation, residence, clinical history, vegetable source, cooking fuel, smoking, alcohol consumption, BMI) was analyzed using the Boruta algorithm. After the implementation of environmental management measures (including ceasing mining and smelting activities, building landfills, adjusting the planting structure, and soil restoration), urine, hair, and nail arsenic concentration decreased drastically but were still excessive. Arsenic accumulation was highest in older male miners who were long settled in the mining area and consumed homegrown vegetables. The only factor for changes in urinary arsenic levels was the cooking fuel type; residents using wood as cooking fuel experienced sustained arsenic exposure. Occupation and sex were important for determining arsenic changes in the hair and nails. Short-term arsenic accumulation in urine was affected by arsenic exposure, while long-term accumulation in hair and nails by arsenic metabolic capacity. The percentage of urinary arsenic metabolism and arsenic methylation indices of the participants in the mining area were within the normal range (%iAs: 10-30 %, %MMA: 10-20 %, % DMA: 60-80 %); samples indicated worse metabolic capacity than the reference population. The arsenic metabolic capacity of male miners was relatively weak, probably aggravated by alcohol drinking and smoking. Without soil remediation, arsenic exposure will continue. Homegrown vegetables and biomass fuels should be abandoned; reduced cigarette and alcohol consumption is recommended. Urinary arsenic would be more proper for assessing environmental remediation in mining areas.


Assuntos
Arsênio , Humanos , Masculino , Idoso , Arsênio/análise , Conservação dos Recursos Naturais , Exposição Ambiental/análise , Mineração , Solo
2.
Waste Manag ; 155: 338-347, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36417815

RESUMO

The widespread use of selective catalytic reduction (SCR) catalysts has resulted in a large accumulation of spent SCR catalysts. These spent catalysts present a significant risk of environmental hazards and potential for resource recovery. This paper presents a feasible process, which works using atmospheric pressure leaching, of tungsten and titanium recovery from spent SCR catalysts. In this new method, titanium and tungsten are simultaneously leached with sulfuric acid as the leaching agent. After hydrolysis and calcination, titanium-tungsten powder with low impurity and reconstructed pore properties was obtained. The optimal conditions for the leaching of Ti and W were as follows: temperature, 150 °C; reaction time, 60 min; H2SO4 concentration, 80 %; mass ratio of H2SO4/TiO2, 3:1; and diluted H2SO4 concentration, 20 % after reaction. With these optimum conditions, the leaching efficiency of Ti and W were found to be 95.92 % and 93.83 %, respectively. The ion speciation and reaction mechanism of W were studied by Raman spectroscopy, FTIR, and UV-vis. The formation of heteropolytungstate with a Keggin structure is essential for the synergistic leaching of Ti and W, as the heteropolytungstate can be stably dissolved in the acid solution. During the hydrolysis process, heteropolytungstate gradually decomposed into Ti4+ and WO42- due to the formation of insoluble Ti(OH)4 from Ti4+ in the solution. This study demonstrated an effective method for synergistic recovery of titanium and tungsten from the spent SCR catalyst.

3.
J Integr Plant Biol ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354145

RESUMO

Although the Trithorax histone methyltransferases ATX1-5 are known to regulate development and stress responses by catalyzing histone H3K4 methylation in Arabidopsis thaliana, it is unknown whether and how these histone methyltransferases affect DNA methylation. Here, we found that the redundant ATX1-5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation. The expression and H3K4me3 levels of both RNA-directed DNA methylation (RdDM) genes (NRPE1, DCL3, IDN2, and IDP2) and active DNA demethylation genes (ROS1, DML2, and DML3) were down-regulated in the atx1/2/4/5 mutant. Consistent with the facts that the active DNA demethylation pathway mediates DNA methylation mainly at CG and CHG sites, and that the RdDM pathway mediates DNA methylation mainly at CHH sites, whole-genome DNA methylation analyses showed that hyper-CG and CHG DMRs in atx1/2/4/5 significantly overlap with those in the DNA demethylation pathway mutant ros1 dml2 dml3 (rdd), and that hypo-CHH DMRs in atx1/2/4/5 significantly overlap with those in the RdDM mutant nrpe1, suggesting that the ATX paralogs function redundantly to regulate DNA methylation by promoting the H3K4me3 and expression levels of both RdDM genes and active DNA demethylation genes. Given that the ATX proteins function as catalytic subunits of COMPASS histone methyltransferase complexes, we also demonstrated that the COMPASS complex components function as a whole to regulate DNA methylation. This study reveals a previously uncharacterized mechanism underlying the regulation of DNA methylation. This article is protected by copyright. All rights reserved.

4.
RSC Adv ; 12(51): 33340-33347, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36425164

RESUMO

Chemical substance identification is an indispensable step in research on therapeutic materials based on traditional Chinese medicine and its formulas. The successful characterization of chemical substances mainly relies on high-quality MS/MS spectra. However, to date, relatively few studies have specifically addressed the issues of improving the acquisition of MS/MS spectra of compounds for characterization. The current auto-MS/MS mode, where the precursor ions are selected depending on their signal intensity, encounters a drawback when the sample contains many overlapping signals, leading to compounds with a lower or much lower abundance missing identification. To solve this problem, a strategy in which molecular features oriented precursor ion selection was followed by targeted MS/MS analysis for structure elucidation was proposed. The precursor ions were selected according to their first and second molecular features, namely m/z and retention time, irrespective of their intensities. By performing targeted MS/MS analysis, the MS/MS spectra of many more compounds of interest can be obtained, leading to an improvement in natural product identification. As an example, the chemical substances in the Zhi-Ke-Yang-Yin extract were analyzed using this strategy, and as a result, 431 ingredients were tentatively characterized, including both known and unknown or new compounds.

5.
PeerJ ; 10: e14316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389426

RESUMO

Background: Cardiovascular disease (CVD) is a major cause of mortality in patients on haemodialysis. The development of a prediction model for CVD risk is necessary to help make clinical decisions for haemodialysis patients. This retrospective study aimed to develop a prediction model for the 5-year risk of CV events and all-cause mortality in haemodialysis patients in China. Methods: We retrospectively enrolled 398 haemodialysis patients who underwent dialysis at the dialysis facility of the General Hospital of Northern Theater Command in June 2016 and were followed up for 5 years. The composite outcome was defined as CV events and/or all-cause death. Multivariable logistic regression with backwards stepwise selection was used to develop our new prediction model. Results: Seven predictors were included in the final model: age, male sex, diabetes, history of CV events, no arteriovenous fistula at dialysis initiation, a monocyte/lymphocyte ratio greater than 0.43 and a serum uric acid level less than 436 mmol/L. Discrimination and calibration were satisfactory, with a C-statistic above 0.80. The predictors lay nearly on the 45-degree line for agreement with the outcome in the calibration plot. A simple clinical score was constructed to provide the probability of 5-year CV events or all-cause mortality. Bootstrapping validation showed that the new model also has similar discrimination and calibration. Compared with the Framingham risk score (FRS) and a similar model, our model showed better performance. Conclusion: This prognostic model can be used to predict the long-term risk of CV events and all-cause mortality in haemodialysis patients. An MLR greater than 0.43 is an important prognostic factor.

6.
Front Bioeng Biotechnol ; 10: 1027619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36394017

RESUMO

Toll-like receptors (TLRs) are important pattern recognition receptor(s) known to mediate the sensing of invading pathogens and subsequent immune responses. In this study, we investigate whether TLRs could be explored for the preparation of human CD8+ T cell products used in adoptive cell therapy (ACT). Following characterization of TLRs expression on human CD8+ T cells, we screened TLR-specific agonists for their ability to act in concert with anti-CD3 to stimulate the proliferation of these cells and corroborated the observed co-stimulatory effect by transcriptional profiling analyses. Consequently, we developed an optimal formulation for human CD8+ T cell amplification by combining CD3/CD28 antibody, interleukin 7 (IL-7), interleukin 15 (IL-15), and three agonists respectively targeting TLR1/2, TLR2/6, and TLR5. This new formulation performed better in amplifying PD-1+CD8+ T cells, a potential repertoire of tumor-reactive CD8+ T cells, from tumor patients than the conventional formulation. Importantly, the expanded CD8+ T cells showed restored functionality and consequently a robust anti-tumor activity in an in vitro co-culturing system. Together, our study established the utility of TLR agonists in ex vivo expansion of tumor-targeting CD8+ T cells, thus providing a new avenue toward a more effective ACT.

7.
Sci Adv ; 8(45): eadd0510, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36351020

RESUMO

The fundamental understanding of the elusive evolution behavior of the buried solid-solid interfaces is the major barrier to exploring solid-state electrochemical devices. Here, we uncover the interfacial void evolution principles in solid-state batteries, build a solid-state void nucleation and growth model, and make an analogy with the bubble formation in liquid phases. In solid-state lithium metal batteries, the lithium stripping-induced interfacial void formation determines the morphological instabilities that result in battery failure. The void-induced contact loss processes are quantified in a phase diagram under wide current densities ranging from 1.0 to 10.0 milliamperes per square centimeter by rational electrochemistry calculations. The in situ-visualized morphological evolutions reveal the microscopic features of void defects under different stripping circumstances. The electrochemical-morphological relationship helps to elucidate the current density- and areal capacity-dependent void nucleation and growth mechanisms, which affords fresh insights on understanding and designing solid-solid interfaces for advanced solid-state batteries.

9.
Cell Death Dis ; 13(11): 932, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344492

RESUMO

Osteoarthritis (OA) is a degenerative joint disorder causing pain and functional disability. Emerging evidence reveals that circular RNAs (circRNAs) play essential roles in OA progression and development. This study aimed to investigate the role of a novel circRNA factor, circFOXO3, in the progression of OA and elucidate its underlying molecular mechanism. The function of circFOXO3 in OA and interaction between circFOXO3 and its downstream mRNA target, forkhead box O3 (FOXO3), were evaluated by western blot (WB), immunofluorescence (IF), RNA immunoprecipitation, reverse transcription-quantitative PCR (RT-qPCR), and fluorescence in situ hybridization (FISH). Upregulation of circFOXO3 and autophagic flux were detected both in vivo and in vitro by WB, transmission electron microscopy (TEM), IF, and immunohistochemistry (IHC). A mouse model of OA was also used to confirm the role of circFOXO3 in OA pathogenesis in vivo. Decreased expression of circFOXO3 in OA cartilage tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of the extracellular matrix (ECM). Mechanistically, circFOXO3 functioned in cartilage by targeting its parental gene FOXO3 and activating autophagy. Intra-articular injection of lentivirus-circFOXO3 alleviated OA in the mouse model. In conclusion, our results reveal the key role played by circFOXO3 in OA progression; circFOXO3 overexpression may alleviate apoptosis of chondrocytes and promote anabolism of the ECM via activation of FOXO3 and autophagy, providing a potentially effective novel therapeutic strategy for OA.


Assuntos
Proteína Forkhead Box O3 , Osteoartrite , RNA Circular , Animais , Camundongos , Apoptose/genética , Autofagia/genética , Condrócitos/metabolismo , Hibridização in Situ Fluorescente , Osteoartrite/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , Proteína Forkhead Box O3/genética
10.
Sci Rep ; 12(1): 19609, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380080

RESUMO

Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of recovery of intestinal inflammation on broad-spectrum antibiotic-driven gut microbial dysbiosis in mice. Gut microbiota was elucidated by the Illumina MiSeq platform. Gas chromatography/mass spectrometry was used to investigate short-chain fatty acid content. Colon histology, expression of tight-junction associated proteins and pro-inflammatory cytokines levels were evaluated. The results showed that the gut microbiota of diversity and richness were reduced and various taxonomic levels of the gut microbiota were perturbed after antibiotics gavage. The abundance of Firmicutes and Bacteroidetes shifted to Proteobacteria and increased the relative abundance of harmful microbiota (Parabacteroides and Klebsiella) post-antibiotics, whereas lentinan administration reversed the dysbiosis and increased beneficial microbiota, including S24-7, Lactobacillus, Oscillospira, Ruminococcus and Allobaculum. The concentrations of propionic acid and butyric acid were significantly increased by treatment with lentinan. And lentinan improved colon tissue morphology and reduced pro-inflammatory cytokines via altering NF-κB signaling pathway in antibiotic-driven gut microbial dysbiosis mice. Taken together, the results proved that lentinan can be used as a prebiotic and the result provided a theoretical basis for improving the clinical treatment of broad-spectrum antibiotics side effects.


Assuntos
Disbiose , Lentinano , Camundongos , Animais , Disbiose/induzido quimicamente , Disbiose/tratamento farmacológico , Disbiose/metabolismo , Lentinano/farmacologia , Antibacterianos/efeitos adversos , Firmicutes/metabolismo , Bacteroidetes/metabolismo , Proteínas de Junções Íntimas , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Camundongos Endogâmicos C57BL
11.
Int J Mol Sci ; 23(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36361683

RESUMO

More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin's ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1.


Assuntos
Melatonina , MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Melatonina/farmacologia , Peróxido de Hidrogênio/toxicidade , Hipocampo/metabolismo , Apoptose/genética , Estresse Oxidativo , RNA Mensageiro/metabolismo , MicroRNAs/genética
12.
J Clin Med ; 11(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362748

RESUMO

The diagnosis of prosthetic joint infection (PJI) is still a challenge, the ratio of interleukin-6 (IL-6) to IL-4 in the joint fluid of knee or hip was used to analyze whether the diagnostic accuracy of PJI can be improved. Between January 2017 and May 2022, 180 patients who developed pain after revision total hip or knee arthroplasty were enrolled retrospectively. 92 patients of PJI and 88 of aseptic failure were included. PJI was as defined by the Musculoskeletal Infection Society (MSIS). The content of IL-6 and IL-4 in synovial fluid of knee or hip were measured, and the areas under the receiver operating characteristic curve (ROC) and IL-6/IL-4 curve were analyzed to obtain a better diagnostic effect. The area under the curve of IL-6/IL-4 in synovial fluid of knee or hip was 0.9623, which was more accurate than ESR 0.5994 and C-reactive protein 0.6720. The optimal threshold of IL-6/IL-4 ratio was 382.10. Its sensitivity and specificity were 81.32% and 98.86%, respectively. The positive predictive value for the diagnosis of PJI was 98.91%. This study showed that the level of IL-6/IL-4 in synovial fluid of knee or hip could further improve the diagnostic accuracy for PJI.

13.
Materials (Basel) ; 15(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36363190

RESUMO

Metal powder bed fusion (PBF) is an advanced metal additive manufacturing (AM) technology. Compared with traditional manufacturing techniques, PBF has a higher degree of design freedom. Currently, although PBF has received extensive attention in fields with high-quality standards such as aerospace and automotive, there are some disadvantages, namely poor process quality and insufficient stability, which make it difficult to apply the technology to the manufacture of critical components. In order to surmount these limitations, it is necessary to monitor the process. Online monitoring technology can detect defects in time and provide certain feedback control, so it can greatly enhance the stability of the process, thereby ensuring its quality of the process. This paper presents the current status of online monitoring technology of the metal PBF process from the aspects of powder recoating monitoring, powder bed inspection, building process monitoring, and melt layer detection. Some of the current limitations and future trends are then highlighted. The combination of these four-part monitoring methods can make the quality of PBF parts highly assured. We unanimously believe that this article can be helpful for future research on PBF process monitoring.

14.
Water Sci Technol ; 86(9): 2336-2347, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36378183

RESUMO

The inherent periodic structure of montmorillonite limits the adsorption capacity of its endogenous active units such as Si-O tetrahedron and Al-O octahedron for pollutants. The high-intensity ultrasound method was used to release these active units and the layer-by-layer assembly was adopted to prepare carbon@chitosan@montmorillointe microsphere adsorbent (C@CS@Mt) to give full play to the adsorption capacity of montmorillonite. The montmorillonite nanosheet exhibited good hole-making ability, resulting in high surface area, pore volume and pore diameter of microspheres. Benefitting from the release of active sites in Si-O tetrahedron and Al-O octahedron of montmorillonite nanosheets, the adsorption capacity of C@CS@Mt was significantly improved. The maximum adsorption capacities of Pb2+ and methylene blue (MB) reached 884.19 mg·g-1 and 326.21 mg·g-1, respectively. The simultaneous adsorption experiments indicated that the occupation of active sites by Pb2+ caused the observed decrease of MB adsorption capacity. The theoretical calculations indicated that Pb was preferentially adsorbed by active adsorption units due to strong electron donating ability in comparison to MB. As an active unit, Si-O tetrahedron exhibited stronger adsorption capacity for cationic dyes than Al-O octahedron due to both the large electronegativity and lower adsorption binding energy.


Assuntos
Azul de Metileno , Poluentes Químicos da Água , Azul de Metileno/química , Bentonita , Chumbo , Domínio Catalítico , Poluentes Químicos da Água/química , Adsorção , Cinética
15.
Membranes (Basel) ; 12(11)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36363624

RESUMO

A flow channel structure design plays a significant role in an open-cathode proton exchange membrane fuel cell. The cell performance is sensitive to the structural parameters of the flow field, which mainly affects the heat and mass transfer between membrane electrode assembly and channel. This paper presents theoretical and experimental studies to investigate the impacts of anode flow field parameters (numbers of the serpentine channels, depths, and widths of the anode channel) on cell performance and temperature characteristics. The result indicates that the number of anode serpentine channels adjusts the pressure and flow rate of hydrogen in the anode flow channel effectively. The depth and width of the channel change the pressure, flow rate, and mass transfer capacity of hydrogen, especially under the high current density. There appears the best depth to achieve optimum cell performance. The velocity and concentration of hydrogen have important influences on the mass transfer which agrees with the anode channel structure design and performance changes based on the field synergy principle. This research has great significance for further understanding the relationship between anode flow field design and fuel cell performance in the open-cathode proton exchange membrane fuel cell stack.

16.
J Transl Med ; 20(1): 549, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435786

RESUMO

BACKGROUND: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation. METHODS: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon. RESULTS: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model. CONCLUSIONS: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.


Assuntos
COVID-19 , Osteoartrite , Animais , Camundongos , Humanos , Estresse do Retículo Endoplasmático , Pandemias , Oxirredução , Homeostase , Osteoartrite/tratamento farmacológico , Antivirais
17.
Sci Adv ; 8(47): eadd5189, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36427308

RESUMO

In the pursuit of energy-dense all-solid-state lithium batteries (ASSBs), Li-rich Mn-based oxide (LRMO) cathodes provide an exciting path forward with unexpectedly high capacity, low cost, and excellent processibility. However, the cause for LRMO|solid electrolyte interfacial degradation remains a mystery, hindering the application of LRMO-based ASSBs. Here, we first reveal that the surface oxygen instability of LRMO is the driving force for interfacial degradation, which severely blocks the interfacial Li-ion transport and triggers fast battery failure. By replacing the charge compensation of surface oxygen with sulfite, the overoxidation and interfacial degradation can be effectively prevented, therefore achieving a high specific capacity (~248 mAh g-1, 1.1 mAh cm-2; ~225 mAh g-1, 2.9 mAh cm-2) and excellent long-term cycling stability of >300 cycles with 81.2% capacity retention at room temperature. These findings emphasize the importance of irreversible anion reactions in interfacial failure and provide fresh insights into constructing stable interfaces in LRMO-based ASSBs.

18.
Int J Biol Macromol ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36427615

RESUMO

Specificity and efficiency of plant virus transmission depend largely on protein-protein interactions of vectors and viruses. Cucurbit chlorotic yellows virus (CCYV), transmitted specifically by tobacco whitefly, Bemisia tabaci, in a semi-persistent manner, has caused serious damage on cucurbit and vegetable crops around the world. However, the molecular mechanism of interaction during CCYV retention and transmission are still lacking. CCYV was proven to bind particularly to the whitefly foregut, and here, we confirmed that the minor coat protein (CPm) of CCYV is participated in the interaction with the vector. In order to identify proteins of B. tabaci that interact directly with CPm of CCYV, the immunoprecipitation (IP) assay and DUALmembrane cDNA library screening technology were applied. The cytochrome c oxidase subunit 5A (COX), tubulin beta chain (TUB) and keratin, type I cytoskeletal 9-like (KRT) of B. tabaci shown strong interactions with CPm and are closely associated with the retention within the vector and transmission of CCYV. These findings on whitefly protein-CCYV CPm interactions are crucial for a much better understanding the mechanism of semi-persistent plant virus transmission by insect vectors, as well as for implement new strategies for effective management of plant viruses and their vector insects.

19.
Cancers (Basel) ; 14(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36428773

RESUMO

The development of drug resistance in malignant tumors leads to disease progression, creating a bottleneck in treatment. Bevacizumab is widely used clinically, and acts by inhibiting angiogenesis to "starve" tumors. Continuous treatment can readily induce rebound proliferation of tumor blood vessels, leading to drug resistance. Previously, we found that the fragment crystallizable (Fc) region of bevacizumab cooperates with the Toll-like receptor-4 (TLR4) ligand to induce M2b polarization in macrophages and secrete tumor necrosis factor-α (TNFα), which promotes immunosuppression, tumor metastasis, and angiogenesis. However, the downstream mechanism underlying TNFα-mediated bevacizumab resistance requires further investigation. Our RNA-Seq analysis results revealed that the expression of endothelial cell specific molecule-1 (ESM1) increased significantly in drug-resistant tumors and promoted metastasis and angiogenesis in vitro and in vivo. Furthermore, TNFα induced the upregulation of ESM1, which promotes metastasis and angiogenesis and regulates matrix metalloprotease-9 (MMP9), vascular endothelial growth factor (VEGF), and delta-like ligand-4 molecules (DLL4). Accordingly, the curative effect of bevacizumab improved by neutralizing ESM1 with high-affinity anti-ESM1 monoclonal antibody 1-2B7 in bevacizumab-resistant mice. This study provides important insights regarding the molecular mechanism by which TNFα-induced ESM1 expression promotes angiogenesis, which is significant for elucidating the mechanism of bevacizumab drug resistance and possibly identifying appropriate biosimilar molecules.

20.
Pest Manag Sci ; 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371599

RESUMO

BACKGROUND: Arylpyrazole insecticides display broad-spectrum insecticidal activity against insect pests. However, the high toxicity toward honeybees associated with fipronil prohibits its agronomic utility. To explore reducing the toxicity of aryl pyrazole analogs to bees, a series of new spiro-pyrazolo[1,5-a]quinazoline derivatives were designed and synthesized. RESULTS: Bioassay results showed that these compounds exhibited good insecticidal activity. In particular, the insecticidal activity of compound 5f against Plutella xylostella larvae (median lethal contentration, LC50  = 1.43 mg L-1 ) was equivalent to that of fipronil. Moreover, some compounds also showed good insecticidal activity against Solenopsis invicta. Importantly, the bee toxicity study confirmed that compound 5f had much lower acute oral toxicity, with a median lethal dose (LD50 ) = 1.15 µg bee-1 that was three to four orders of magnitude greater than that of fipronil (0.0012 µg bee-1 ). Electrophysiological studies were conducted using honeybee γ-aminobutyric acid receptor heterologously expressed in Xenopus oocytes to explain the reduced bee toxicity of compound 5f. The inhibitory effect of compound 5f (16.29 µmol L-1 ) was determined to be approximately 700-fold lower than that of fipronil (0.023 µmol L-1 ). CONCLUSION: These spiro-pyrazolo[1,5-a]quinazoline derivatives could be potential candidates and lead structures for the discovery of novel insecticides with low bee toxicity. © 2022 Society of Chemical Industry.

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