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1.
Plant Dis ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238251

RESUMO

Amorphophallus konjac, commonly called voodoo lily, is a cash crop widely cultivated in southwest China (Gao et al. 2022). In August 2022, leaf spot symptoms were observed in a field (1 ha) located at Fuyuan (25.67°N; 104.25°E), Yunnan, China, resulting in substantial economic losses. Brown lesions, with an incidence ranging from 20 to 40%, typically had a whitish or gray center and were surrounded by yellow halos. Microscopic observations of the spots revealed anamorphic species Cercospora chevalieri. Conidiophores were 50-150 × 4-7 µm, cylindrical, unbranched, smooth-walled, pale brown and aggregated in dense fascicles arising from a brown stroma. The conidiogenous cells were integrated, terminal or intercalary, pale brown to brown and proliferated sympodially. The conidiogenous loci were thickened and darkened, and 2-3 µm in diam. The conidia were formed singly, obclavate-cylindrical, 90-160 × 5-7 µm, with an average of 130 × 6 µm (n = 30), 6-11 septa, thin-walled, smooth, hyaline or subhyaline, straight or curved with an obtuse apex and obconically truncate base, with thickened and darkened hilum. These morphological characteristics matched those of C. chevalieri, the causal agent of leaf spot on A. paeoniifolius (Braun et al. 2014; Saccardo et al. 1913). A conidial suspension in sterile water from lesions was used to inoculate water agar, and germinated conidia were transferred to potato dextrose agar(PDA) and incubated at 27°C for 7 days. Induction of sporulation was unsuccessful using PDA, as well as malt extract agar, potato sucrose agar and synthetic nutrient-poor agar. Two out of ten isolates were selected for molecular identification and pathogenicity assay. Genomic DNA from two pure isolates (KUNCC22-12536 and KUNCC22-12537) was extracted for PCR and amplified with primers for the internal transcribed spacers (ITS: ITS1/ITS4), calmodulin (CMD: CAL228F/CAL2Rd), translation elongation factor 1-alpha (TEF1-α: 728F/986R), actin (ACT: 512F/783R), histone H3 (HIS3: CYLH3F/CYLH3R), beta-tubulin gene (TUB2: BT-1F/BT-1R) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH: Gpd1/Gpd2), respectively (Vaghefi et al. 2021). The newly generated sequences for ITS (OP719153/OP719154), CMD(OP740904/OP740905), TEF1-α (OP740910/OP740911), ACT (OP740902/OP740903), HIS3 (OP740908/OP740909), TUB2 (OP740912/OP740913), GAPDH (OP740906/OP740907) of C. chevalieri were submitted to GenBank. So far, no sequence data of C. chevalieri were available in the GenBank database. As expected, most genes (TEF1-α, ACT, CMD, HIS, TUB2 and GAPDH) showed 91 to 95% identity to their best hits within species of the genus Cercospora. The phylogenetic tree showed that sequences retrieved from two isolates obtained from the A. konjac leaf spots clustered together within Cercospora forming a strongly supported clade. To test Koch's postulates, ten four-month-old healthy A. konjac plants grown in pots were used for a pathogenicity test in a greenhouse. One leaf of each plant was inoculated with mycelial plugs, and one leaf was inoculated with a sterile PDA plug. These plants were enclosed in plastic bags for 72 h. Only leaves inoculated with mycelium plugs produced brown lesions, which appeared after 10 to 14 days on inoculated leaves. Control plants treated with sterile PDA plugs remained asymptomatic. This experiment was repeated twice with the same results. C. chevalieri was reisolated from infected leaves and identified based on morphology and Sanger sequencing of the ITS region. To our knowledge, this is the first report of C. chevalieri causing leaf spot on A. konjac and the first report of this species from China (Braun et al. 2014), which provides key information for diagnosis and management of this disease.

2.
Cell Metab ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39243758

RESUMO

During the progression of metabolic dysfunction-associated steatohepatitis (MASH), the accumulation of auto-aggressive CD8+ T cells significantly contributes to liver injury and inflammation. Empagliflozin (EMPA), a highly selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), exhibits potential therapeutic benefits for liver steatosis; however, the underlying mechanism remains incompletely elucidated. Here, we found that EMPA significantly reduced the hepatic accumulation of auto-aggressive CD8+ T cells and lowered granzyme B levels in mice with MASH. Mechanistically, EMPA increased ß-hydroxybutyric acid by promoting the ketogenesis of CD8+ T cells via elevating 3-hydroxybutyrate dehydrogenase 1 (Bdh1) expression. The ß-hydroxybutyric acid subsequently inhibited interferon regulatory factor 4 (Irf4), which is crucial for CD8+ T cell activation. Furthermore, the ablation of Bdh1 in T cells aggravated the manifestation of MASH and hindered the therapeutic efficacy of EMPA. Moreover, a case-control study also showed that SGLT2 inhibitor treatment repressed CD8+ T cell infiltration and improved liver injury in patients with MASH. In summary, our study indicates that SGLT2 inhibitors can target CD8+ T cells and may be an effective strategy for treating MASH.

3.
Pestic Biochem Physiol ; 204: 106091, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277418

RESUMO

The vegetable leafminer (Liriomyza sativae) is a devastating invasive pest of many vegetable crops and horticultural plants worldwide, causing serious economic loss. Conventional control strategy against this pest mainly relies on the synthetic chemical pesticides, but widespread use of insecticides easily causes insecticide resistance development and is harmful to beneficial organisms and environment. In this context, a more environmentally friendly pest management strategy based on RNA interference (RNAi) has emerged as a powerful tool to control of insect pests. Here we report a successful oral RNAi in L. sativae after feeding on pak choi (Brassica rapa ssp. chinensis) that transiently express hairpin RNAs targeting vital genes in this pest. First, potentially lethal genes are identified by searching an L. sativae transcriptome for orthologs of the widely used V-ATPase A and actin genes, then expression levels are assessed during different life stages and in different adult tissues. Interestingly, the highest expression levels for V-ATPase A are observed in the adult heads (males and females) and for actin in the abdomens of adult females. We also assessed expression patterns of the target hairpin RNAs in pak choi leaves and found that they reach peak levels 72 h post agroinfiltration. RNAi-mediated knockdown of each target was then assessed by letting adult L. sativae feed on agroinfiltrated pak choi leaves. Relative transcript levels of each target gene exhibit significant reductions over the feeding time, and adversely affect survival of adult L. sativae at 24 h post infestation in genetically unmodified pak choi plants. These results demonstrate that the agroinfiltration-mediated RNAi system has potential for advancing innovative environmentally safe pest management strategies for the control of leaf-mining species.


Assuntos
Brassica rapa , Folhas de Planta , Interferência de RNA , Folhas de Planta/parasitologia , Brassica rapa/genética , Brassica rapa/parasitologia , Animais , RNA Interferente Pequeno/genética , Feminino , Masculino
4.
Pestic Biochem Physiol ; 204: 106101, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277423

RESUMO

Riptortus pedestris (Hemiptera: Alydidae), a common agricultural pest, is the major causative agent of "soybean staygreen." However, the interactions between chemosensory proteins (CSPs) in R. pedestris and host plant volatiles have yet to be comprehensively studied. In this study, we performed real-time fluorescence quantitative polymerase chain reaction (PCR) to analyze the antennal expression of RpedCSP22 and subsequently analyzed the interactions between 21 soybean volatiles, five aggregation pheromones, and RpedCSP22 protein in vitro using a protein expression system, molecular docking, site-directed mutagenesis, and fluorescence competitive binding experiments. The RpedCSP22 protein showed binding affinity to three soybean volatiles (benzaldehyde, 4-ethylbenzaldehyde, and 1-octene-3-ol), with optimal binding observed under neutral pH conditions, and lost binding ability after site-directed mutagenesis. In subsequent RNA interference (RNAi) studies, gene silencing was more than 90 %, and in silenced insects, electroantennographic responses were reduced by more than 75 % compared to non-silenced insects. Moreover, Y-tube olfactory behavioral assessments revealed that the attraction of R. pedestris to the three soybean volatiles was significantly attenuated. These findings suggest that RpedCSP22 plays an important role in the recognition of host plant volatiles by R. pedestris andprovides a theoretical basis for the development of novel inhibitors targeting pest behavior.


Assuntos
Glycine max , Proteínas de Insetos , Compostos Orgânicos Voláteis , Animais , Glycine max/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/química , Compostos Orgânicos Voláteis/metabolismo , Mutagênese Sítio-Dirigida , Simulação de Acoplamento Molecular , Hemípteros/metabolismo , Hemípteros/genética , Antenas de Artrópodes/metabolismo , Feromônios/metabolismo , Heterópteros/metabolismo , Heterópteros/genética
5.
Nat Commun ; 15(1): 8221, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300135

RESUMO

The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Ae. albopictus, with Ae. aegypti being more competent. However, the underlying mechanisms remain unclear. Here, we find Ae. albopictus shows comparable vector competence to ZIKV/DENV with Ae. aegypti by blood-feeding after antibiotic treatment or intrathoracic injection. This suggests that midgut microbiota can influence vector competence. Enterobacter hormaechei_B17 (Eh_B17) is isolated from field-collected Ae. albopictus and conferred resistance to ZIKV/DENV infection in Ae. aegypti after gut-transplantation. Sphingosine, a metabolite secreted by Eh_B17, effectively suppresses ZIKV infection in both Ae. aegypti and cell cultures by blocking viral entry during the fusion step, with an IC50 of approximately 10 µM. A field survey reveals that Eh_B17 preferentially colonizes Ae. albopictus compared to Ae. aegypti. And field Ae. albopictus positive for Eh_B17 are more resistant to ZIKV infection. These findings underscore the potential of gut symbiotic bacteria, such as Eh_B17, to modulate the arbovirus vector competence of Aedes mosquitoes. As a natural antiviral agent, Eh_B17 holds promise as a potential candidate for blocking ZIKV/DENV transmission.


Assuntos
Aedes , Vírus da Dengue , Enterobacter , Microbioma Gastrointestinal , Mosquitos Vetores , Esfingosina , Simbiose , Zika virus , Aedes/virologia , Aedes/microbiologia , Aedes/efeitos dos fármacos , Animais , Mosquitos Vetores/microbiologia , Mosquitos Vetores/virologia , Mosquitos Vetores/efeitos dos fármacos , Zika virus/fisiologia , Zika virus/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Esfingosina/farmacologia , Enterobacter/efeitos dos fármacos , Enterobacter/fisiologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia , Dengue/transmissão , Dengue/virologia , Dengue/prevenção & controle , Feminino , Internalização do Vírus/efeitos dos fármacos , Humanos
6.
Mol Ther ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217415

RESUMO

As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins (GPs), have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of EBOV-like vesicles (eVLVs) incorporating both EBOV GP and VP40. The eVLVs exhibited similar antigenicity as EBOV. In murine models, eVLVs were highly attenuated and elicited robust GP-specific antibodies with neutralizing activities. Importantly, a single dose of eVLVs conferred complete protection in a surrogate EBOV lethal mouse model. Furthermore, our VLVs strategy was also successfully applied to Marburg virus (MARV), the representative member of the genus Marburgvirus. Taken together, our findings indicate the feasibility of an alphavirus-derived VLVs strategy in combating infection of filoviruses represented by EBOV and MARV, which provides further evidence of the potential of this platform for universal live-attenuated vaccine development.

7.
Sci Rep ; 14(1): 21101, 2024 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256540

RESUMO

This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.


Assuntos
Doenças Pulmonares Intersticiais , Humanos , Feminino , Masculino , Doenças Pulmonares Intersticiais/diagnóstico , Projetos Piloto , Idoso , Pessoa de Meia-Idade , Frequência Cardíaca , Saturação de Oxigênio , Monitorização Fisiológica/métodos , Progressão da Doença
8.
J Psychosom Res ; 187: 111881, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39288470

RESUMO

OBJECTIVE: This cross-sectional research aimed to examine how reproductive factors influence depression and suicidal ideation among postmenopausal women. METHODS: Data from the 2007 to 2018 US National Health and Nutrition Examination Survey were analyzed for this study. The Patient Health Questionnaire (PHQ-9) was adopted to measure depression and suicidal ideation in the participants. RESULTS: Out of 3076 participants, 9.5% (348/3076) experienced depression, and 3.4% (128/3076) reported suicidal ideation. Following the adjustment for confounding factors, premature menopause (OR = 1.81, 95% CI: 1.03-3.15) was significantly associated with an increased risk of depression. Moreover, postmenopausal women with a higher number of pregnancies exhibited a greater risk of depression (OR = 1.29, 95% CI: 1.09-1.53; P < 0.001). Conversely, a longer reproductive lifespan (OR = 0.96, 95% CI: 0.93-0.99) and a higher number of livebirths (OR = 0.68, 95% CI: 0.54-0.86; P < 0.001) were linked to a decreased risk of depression. Furthermore, the use of oral contraceptives (OR = 0.52, 95% CI: 0.28-0.97; P = 0.021) was significantly associated with a decreased likelihood of experiencing suicidal ideation, while the number of livebirths (OR = 0.68, 95% CI: 0.48-0.97; P = 0.018) exhibited a negative correlation with suicidal ideation. CONCLUSION: Our results indicate that reproductive factors are significantly associated with the risk of depression and suicidal ideation in postmenopausal women. Further longitudinal studies with repeated measures of depression are necessary to establish causal relationships.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39289935

RESUMO

OBJECTIVE: This study aimed to investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on autoimmune encephalomyelitis. METHODS: C57BL/6 mice were randomly divided into the blank control group, EAE group, and APS intervention group (n=15/group). The Experimental Autoimmune Encephalomyelitis (EAE) mouse model was established by active immunization. The pathological changes in the spinal cord were evaluated by Hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining. The number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in the spleen tissues of mice in each group was determined by immunofluorescence staining. The expression of Arginase-1 in the spinal cord and spleen of each group was detected by immunofluorescence double staining. The TNF-α, IL-6, and Arginase-1 levels in the spleen were detected by ELISA assay. A western blot was used to detect the protein expression of the AMPK/JAK/STAT3/Arginase-1 signaling pathway. RESULTS: After the intervention of APS, the incidence of autoimmune encephalomyelitis in mice of the APS group was significantly lower than that in the EAE group, and the intervention of APS could significantly delay the onset time in the EAE mice, and the score of neurological function deficit in mice was significantly lower than that in EAE group (P < 0.05). APS intervention could reduce myelin loss and improve the inflammatory response of EAE mice. Moreover, it could induce the expression of CD11b+ GR-1 + bone MDSCs in the spleen and increase the expression of Arginase-1 in the spinal cord and spleen. This study further demonstrated that APS can protect EAE mice by activating the AMPK/JAK/STAT3/Arginase-1 signaling pathway. CONCLUSION: After the intervention of APS, myelin loss and inflammatory response of EAE mice were effectively controlled. APS promoted the secretion of Arginase-1 by activating MDSCs and inhibited CD4+T cells by activating AMPK/JAK/STAT3/Arginase-1 signaling pathway, thus improving the clinical symptoms and disease progression of EAE mice.

10.
Plant Dis ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39306686

RESUMO

Magnolia delavayi, known as Delavay's magnolia or Chinese evergreen magnolia, is an enchanting deciduous tree native to southwestern China (Xu et al. 2020). In March 2024, leaf spots were observed on M. delavayi plants at Qujing Normal University (25.527°N, 103.744°E), Qujing, Yunnan, China. About 80% of the trees (n=92) on campus were infected, with infected leaves accounting for about 10 to 30% of all leaves. The leaf spots exhibited a round or oval shape, with a yellowish-brown center and a brown outer ring. As the spots expanded, the leaves gradually dried up and fell off. Five symptomatic leaves were collected from the middle sections of five diseased plants. Tissue samples (5 × 5 mm) were excised from the lesion margins and subjected to surface sterilization in 75% ethanol for 30 seconds and 1% sodium hypochlorite for 60 seconds. They were then rinsed three times with sterile water and dried on sterilized paper. The samples were plated on potato dextrose agar (PDA) and incubated at 28 °C for 3 days. Developing colonies were retransferred to new PDA and purified by the hyphal tip technique (Senanayake et al. 2020). Two representative isolates (SYL1 and SYL2) were selected and confirmed to be the same species based on morphological characteristics and molecular identification. On PDA, the fungal colonies initially appeared grayish-white and turned dark gray over time with cotton-like aerial hyphae on the surface. The conidia are light brown, pear-shaped or rod-shaped, with 1 to 4 transverse septa and 0 to 1 oblique septa, and measured 5.4 to 12.7 × 10.4 to 25.7 µm (n = 50). Molecular identification was performed by partial sequencing of the internal transcribed spacer (ITS: ITS4/ITS5) region, glyceraldehyde 3-phosphate dehydrogenase (GAPDH:gpd1/gpd2), translation elongation factor 1-alpha (TEF1:EF1/EF2), and Alternaria major allergen (Alt a 1:Alt-for/Alt-rev) (Woudenberg et al. 2015). The resulting sequences of ITS (PP951882, PP951883), GAPDH (PP968942, PP968943), Alt a 1(PP968940, PP968941) and TEF1 (PP968938, PP968939) were deposited in GenBank. BLAST analyses revealed that the sequences from these two isolates showed 100% identity with those from Alternaria alternata strains for each gene. Additionally, a multigene phylogenetic analysis revealed a distinct group containing SYL1, SYL2 and other A. alternata strains with a posterior probability of 100%. The morphological and phylogenetic evidence collectively suggested that the two isolates belonged to A. alternata. Strain SYL1 was used for the pathogenicity test on three 5-year-old M. delavayi plants on campus. Three healthy leaves of each plant were punctured with a sterile needle and sprayed with 20 µl of spore suspension (1 × 106 conidia/ml). Similarly, another nine wounded leaves were sprayed with 20 µl of sterile water. All inoculated leaves were enclosed in plastic bags for 48 hours. Disease symptoms were observed on leaves inoculated with spore suspension after 7 days, while control plants remained healthy. This experiment was repeated three times with same results. To fulfill Koch's postulates, A. alternata was reisolated from the inoculated leaves and identified based on morphological characteristics and ITS sequencing. To our knowledge, this is the first report of A. alternata causing leaf spot on M. delavayi in China. This research expands the known host range of this pathogen and provides relevant information to the design of disease management strategies.

11.
PLoS One ; 19(9): e0310391, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39302935

RESUMO

Hepatocellular carcinoma (HCC) is characterized by a lack of obvious clinical features in the early stages and is likely to progress to advanced HCC. Advanced HCC is a highly malignant tumor. However, there are few treatment options for advanced HCC. Therefore, screening for new drugs that target HCC will provide a new approach to the treatment of HCC. The CCK8 assay was performed to screen compounds inhibiting HCC cell proliferation and to evaluate the IC50 (half-maximal inhibitory concentration) of compounds on cell lines. Colony formation assay was used to determine HCC cell proliferation. The effect of compounds on HCC cell migration and invasion were analyzed using wound healing and transwell assays, respectively. Tumor growth and metastasis were assessed in vivo in a xenograft mouse model. Flow cytometry was carried out to measure apoptotic cells. Reverse transcription and quantitative real-time polymerase chain reaction (RT‒qPCR) and Western blot were performed to examine the expression of epithelial-mesenchymal transition (EMT)- and apoptosis-related genes. Through large-scale screening, we have discovered the anti-tumor activity of cetylpyridinium chloride (CPC) against HCC cells. CPC inhibited the proliferation, invasion and metastasis of HCC cells. Cancer cells are more sensitive to CPC than normal cells. CPC suppressed HCC tumor growth and metastasis in vivo. Mechanistically, CPC promoted apoptosis of HCC cells by affecting the expression of apoptosis-related genes, and inhibited HCC invasion and metastasis by suppressing EMT and expression of EMT markers. Our investigation showed that CPC significantly inhibited HCC cell proliferation, invasion and metastasis in vivo and in vitro, by inducing the expression of apoptosis-related genes and inhibiting expression of EMT markers, suggesting that CPC is a potential agent for HCC treatment.


Assuntos
Apoptose , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Cetilpiridínio , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Apoptose/efeitos dos fármacos , Animais , Humanos , Proliferação de Células/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Cetilpiridínio/farmacologia , Movimento Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Metástase Neoplásica , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Masculino
12.
iScience ; 27(9): 110811, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39286508

RESUMO

Mesenchymal stem cells (MSCs) are heterogeneous in morphology and transcriptome, resulting in varying therapeutic outcomes. In this study, we found that 3D spheroid culture of heterogeneous MSCs, which have undergone conventional 2D monolayer culture for 5-6 passages, synchronized the cells into a uniform cell population with dramatically reduced cell size, and considerably increased levels of immunosuppressive genes and growth factors. Single-cell RNA sequencing (scRNA-seq) analysis of the cells revealed that 3D MSCs consisted of 2 major cell subpopulations and both expressed high levels of immunosuppressive factors, compared to 6 subpopulations in 2D MSCs. In addition, 3D MSCs showed a greater suppressive effect on T cells. Moreover, intravenous infusion of a large dose of 3D MSCs prior to imiquimod (IMQ) treatment significantly improved psoriatic lesion. Thus, our results indicate that 3D spheroid culture reprograms heterogeneous MSCs into a uniform immunosuppressive phenotype and promises a novel therapeutic potential for inflammatory diseases.

13.
Artigo em Inglês | MEDLINE | ID: mdl-39129165

RESUMO

INTRODUCTION: One of the many reasons for cancer treatment failure and recurrence is acquired Multidrug Resistance (MDR). Overcoming cancer drug resistance has been the focus of researchers' studies. Cellular prion protein (PrPC) is a glycophosphatidylinositol-anchored cell-surface glycoprotein that has been implicated in tumor behavior, including proliferation, apoptosis, invasion, metastasis, and chemoresistance. >Method: Lupiwighteone (Lup), a natural isoflavone found in the root of Glycyrrhiza glabra, has anticancer activity against prostate cancer cells, neuroblastoma cells, and human breast cancer cells. However, its pharmacological effects and mechanisms in drug-resistant cancer cells have not been reported. In this study, we used an adriamycin- resistant leukemia K562 cell model, and for the first time, we investigated the reversal effect of Lup on its MDR and the potential mechanism. RESULT: The results indicated that Lup could induce apoptosis through the mitochondrial pathway while upregulating the expression of related apoptotic proteins, such as Bax, Cyto C, Caspase-3, and PARP1. Autophagy is commonly recognized as a protective mechanism that mediates MDR during treatment. We found that Lup induced cellular autophagy while upregulating the expression of related autophagy proteins such as Beclin 1 and LC3 II. CONCLUSION: In addition, when Lup was combined with adriamycin, Lup decreased the IC50 of K562/ADR cells; moreover, Lup can downregulate the expression of drug-resistant proteins, suggesting that Lup can reverse drug resistance. Further studies have shown that Lup can downregulate the expression of PrPC-PI3K-Akt axis proteins and PrPC-Oct4 axis proteins. This study demonstrated that Lup has the potential to inhibit the proliferation of K562/ADR cells by targeting PrPC, and further study of the signaling pathway associated with PrPC may provide the experimental basis for the treatment of drug-resistant leukemia.

14.
Biol Trace Elem Res ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180631

RESUMO

The present study aimed to optimize the combined effect of dietary selenium (SE) and iodine (ID) on the productive and reproductive performance and antioxidant capacity of Longyuan breeding ducks. A total of 288 Longyan duck breeders aged 20 wk were randomly assigned to four groups with six replicates (n = 72 ducks/group; 12 ducks/replicate). A 2 × 2 factorial arrangement experiment was performed and included 2 supplementation levels of each SE and ID for 200 days of the experimental period. The first group (SE0/ID0) received a basal diet without SE or ID supplementation and was considered to be the control group, whereas the other three groups, SE0/ID4, SE2/ID0 and SE2/ID4, received a basal diet supplemented with 0.4 mg ID/kg, 0.2 mg SE/kg or 0.2 mg SE supplemented with 0.4 mg ID/kg, respectively. The results indicated that the albumin height of the SE2/ID0 group was lower (P < 0.05) than that of the control group, that the egg shape index of the SE2/ID4 and SE0/ID4 groups were lower (P < 0.05) than that of the control group (SE0/ID0), and that the SE concentration significantly increased (P < 0.05) in the SE2/ID0 and SE2/ID4 groups. Hatchability and embryonic mortality improved (P < 0.05) in the SE2/ID0 group. Plasma GSH-Px activity was increased (P < 0.05) by reducing the concentration of malondialdehyde (MDA) in the SE groups. In addition, the tibia length significantly increased (P < 0.05) in the ID (SE0/ID4 and SE2/ID4) groups compared with that in the control group, the plasma content of IGF-1 in the SE2/ID4 and SE0/ID4 groups were greater (P < 0.05) than that in the control group, and the bone mineral content increased (P > 0.05) in the SE2/ID0 and SE0/ID0 groups. Compared with those in the other groups, the mRNA expression of antioxidant-related genes, including Nrf2 and SHMT1 in the SE2/ID4 group was upregulated (P > 0.05), especially in the SE2/ID4 group. Overall, dietary treatment with SE2/ID4 (0.2 mg SE in 0.4 mg ID/kg diet) could be a suitable feed supplement for improving the the egg quality, health status, endogenous antioxidant content, antioxidant-related gene expression and pre-hatching quality of Longyuan duck breeders.

15.
J Food Sci ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150703

RESUMO

Mesona chinensis Benth (MCB) is the source of the most commonly consumed herbal beverage in Southeast Asia and China and is thus an economically important agricultural plant. Therefore, optimal extraction and production procedures have significant commercial value. Currently, in terms of green chemistry, researchers are investigating the use of greener solvents and innovative extraction techniques to increase extract yields. This study represents the first investigation of the optimal conditions for ultrasound-assisted deep eutectic solvent (DES) extraction from MCB. The major factors influencing ultrasound-assisted DESs were optimized using the response surface methodcentral-genetic algorithm-back propagation neural networks. This model demonstrated superior predictability and accuracy compared to the RSM model. Various types of DESs were used for the extraction of MCB constituents, with choline chloride-ethylene glycol resulting in the highest yield. The optimal conditions for maximal extraction were the use of choline chloride-ethylene glycol (1:4) as the solvent with a 40% water content, an extraction duration of 60 min at 60°C, and maintaining a leaf-to-solvent ratio of 20 mL/g. Noticeable enhancements in Van der Waals forces and more robust interactions between DESs and the target chemicals were observed relative to those seen with ethanol (70%, v/v) or water. This investigation not only introduced an environmentally friendly approach for highly efficient extraction from MCB but also identified the mechanisms underlying the improved extraction efficacy. These findings have the potential to contribute to the broader utilization of MCB and provide valuable insights into the extraction mechanisms utilizing deep eutectic solvents. PRACTICAL APPLICATION: This work describes an efficient and green ultrasound-assisted deep eutectic solvent (DES) method for Mesona chinensis Benth (MCB) extraction. Molecular dynamics was used to examine the intermolecular interactions between the solvent and the extracted compounds. It is anticipated that green and environmentally friendly solvents, such as DESs, will be used in further research on foods and their bioactive components. With the development of the herbal tea industry, new products made of MCB are becoming increasingly popular, thus gradually making it a research hotspot.

16.
New Phytol ; 243(6): 2311-2331, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39091140

RESUMO

Chloroplasts play a crucial role in plant defense against pathogens, making them primary targets for pathogen effectors that suppress host immunity. This study characterizes the Plasmopara viticola CRN-like effector, PvCRN20, which interacts with DEG5 in the cytoplasm but not with its interacting protein, DEG8, which is located in the chloroplast. By transiently overexpressing in tobacco leaves, we show that PvCRN20 could inhibit INF1- and Bax-triggered cell death. Constitutive expression of PvCRN20 suppresses the accumulation of reactive oxygen species (ROS) and promotes pathogen colonization. PvCRN20 reduces DEG5 entry into chloroplasts, thereby disrupting DEG5 and DEG8 interactions in chloroplasts. Overexpression of VvDEG5 and VvDEG8 induces ROS accumulation and enhances grapevine resistance to P. viticola, whereas knockout of VvDEG8 represses ROS production and promotes P. viticola colonization. Consistently, ectopic expression of VvDEG5 and VvDEG8 in tobacco promotes chloroplast-derived ROS accumulation, whereas co-expression of PvCRN20 counteracted this promotion by VvDEG5. Therefore, DEG5 is essential for the virulence function of PvCRN20. Although PvCRN20 is located in both the nucleus and cytoplasm, only cytoplasmic PvCRN20 suppresses plant immunity and promotes pathogen infection. Our results reveal that PvCRN20 dampens plant defenses by repressing the chloroplast import of DEG5, thus reducing host ROS accumulation and facilitating pathogen colonization.


Assuntos
Cloroplastos , Nicotiana , Doenças das Plantas , Imunidade Vegetal , Proteínas de Plantas , Transporte Proteico , Espécies Reativas de Oxigênio , Vitis , Cloroplastos/metabolismo , Vitis/microbiologia , Vitis/genética , Vitis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Nicotiana/microbiologia , Nicotiana/genética , Nicotiana/imunologia , Regulação da Expressão Gênica de Plantas , Oomicetos/patogenicidade , Folhas de Planta/microbiologia , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas , Resistência à Doença/genética
17.
Sci Total Environ ; 951: 175625, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39163933

RESUMO

The toxic effects of tire wear particles (TWPs) in the environment are a growing concern for a variety of aquatic organisms. However, studies about TWPs toxicity on aquatic organisms are limited. This study investigated the accumulation and depuration of TWPs in zebrafish at three different concentrations (5 mg/L, 10 mg/L, and 20 mg/L), as well as the toxic effects on the gill, liver, and gut. We found that TWPs could accumulate in the gill and gut for a long time, and the number of TWPs at the high-concentration (20 mg/L) was higher than at the low-concentration (5 mg/L). TWPs induced oxidative stress in the gill and liver. The liver transcriptome profiles indicated that the high concentration of TWPs tended to up-regulate metabolic processes, whereas the low concentration of TWPs was inclined to down-regulate cellular processes. The high-concentration treatment significantly increased xenobiotic biodegradation and metabolism, and lipid metabolism-related pathways, whereas the low-concentration treatment distinctly altered amino acid metabolism-related pathways. The expression of gstt1b, ugt1a1, mgst3b, miox, hsd17b3, and cyp8b1 gene was up-regulated in all TWPs treatments. In addition, Gemmobacter and Shinella enriched in the high-concentration treatment were closely correlated with the degradation of TWPs. These findings provided objective evidence for the toxicity evaluation of TWPs on zebrafish.


Assuntos
Brânquias , Fígado , Poluentes Químicos da Água , Peixe-Zebra , Animais , Brânquias/metabolismo , Brânquias/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/efeitos dos fármacos
18.
J Hazard Mater ; 479: 135668, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39197284

RESUMO

In this study, MgFe2O4-loaded biochar (MFBC) was used as a three-dimensional particle electrode to active peroxymonosulfate (EC/MFBC/PMS) for the removal of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). The results demonstrated that, under the conditions of 1.0 mM PMS concentration, 0.4 g/L material dosage, 5 V voltage intensity, and MFBC preparation temperature of 600 °C, the EC/MFBC600/PMS system achieved complete inactivation of E. coli DH5α within 5 min and the intracellular sul1 was reduced by 81.5 % after 30 min of the treatment. Compared to EC and PMS alone treatments, the conjugation transfer frequency of sul1 rapidly declined by 92.9 % within 2 min. The cell membrane, proteins, lipids, as well as intracellular and extracellular ARGs in E. coli DH5α were severely damaged by free radicals in solution and intracellular reactive oxygen species (ROS). Furthermore, up-regulation was observed in genes associated with oxidative stress, SOS response and cell membrane permeability in E. coli DH5α, however, no significant changes were observed in functional genes related to gene conjugation and transfer mechanisms. This study would contribute to the underlying of PMS activation by three-dimensional particle electrode, and provide novel insights into the mechanism of ARB inactivation and ARGs degradation under PMS advanced oxidation treatment.


Assuntos
Carvão Vegetal , Eletrodos , Escherichia coli , Carvão Vegetal/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Técnicas Eletroquímicas , Peróxidos/química , Catálise , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Antibacterianos/química , Genes Bacterianos , Compostos Férricos/química , Purificação da Água/métodos , Espécies Reativas de Oxigênio/metabolismo
19.
Adv Healthc Mater ; : e2402453, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39118587

RESUMO

Gram-positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The ß-lactamase (Bla) secreted by methicillin-resistant S. aureus (MRSA) hydrolyzes nearly all ß-lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla-responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin-6. The BLAP comprising a self-assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug-resistant gram-positive bacterial infections.

20.
Materials (Basel) ; 17(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39124329

RESUMO

Photodetectors have a wide range of applications across various fields. Self-powered photodetectors that do not require external energy have garnered significant attention. The photoelectrochemical type of photodetector is a self-powered device that is both simple to fabricate and offers high performance. However, developing photoelectrochemical photodetectors with superior quality and performance remains a significant challenge. The electrolyte, which is a key component in these detectors, must maintain extensive contact with the semiconductor without degrading its material quality and efficiently catalyze the redox reactions of photogenerated electrons and holes, while also facilitating rapid charge carrier transport. In this study, α-Ga2O3 nanorod arrays were synthesized via a cost-effective hydrothermal method to achieve a self-powered solar-blind photodetector. The impacts of different electrolytes-Na2SO4, NaOH, and Na2CO3-on the photodetector was investigated. Ultimately, a self-powered photodetector with Na2SO4 as the electrolyte demonstrated a stable photoresponse, with the maximum responsivity of 0.2 mA/W at 262 nm with the light intensity of 3.0 mW/cm2, and it exhibited rise and decay times of 0.16 s and 0.10 s, respectively. The α-Ga2O3 nanorod arrays and Na2SO4 electrolyte provided a rapid pathway for the transport of photogenerated carriers and the built-in electric field at the semiconductor-liquid heterojunction interface, which was largely responsible for the effective separation of photogenerated electron-hole pairs that provided the outstanding performance of our photodetector.

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