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1.
Virol Sin ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588947

RESUMO

African swine fever virus (ASFV) poses a significant threat to the global swine industry. Currently, there are no effective vaccines or treatments available to combat ASFV infection in pigs. The primary means of controlling the spread of the disease is through rapid detection and subsequent elimination of infected pig. Recently, a lower virulent ASFV isolate with a deleted EP402R gene (CD2v-deleted) has been reported in China, which further complicates the control of ASFV infection the pig farms. Furthermore, an EP402R-deleted ASFV variant has been developed as a potential live attenuated vaccine candidate strain. Therefore, it is crucial to develop detection methods that can distinguish wild-type and EP402R-deleted ASFV infections. In this study, two recombinant ASFV-p72 and -CD2v proteins were expressed using a prokaryotic system and used to immunize Bactrian camels. Subsequently, eight nanobodies against ASFV-p72 and ten nanobodies against ASFV-CD2v were screened. Following the production of these nanobodies with horse radish peroxidase (HRP) fusion proteins, the ASFV-p72-Nb2-HRP and ASFV-CD2v-Nb22-HRP fusions were selected for the development of two competitive ELISAs (cELISAs) to detect anti-ASFV antibodies. The two cELISAs exhibited high sensitivity, good specificity, repeatability, and stability. The coincidence rate between the two cELISAs and commercial ELISA kits was 98.6% and 97.6%, respectively. Collectively, the two cELISA for detecting antibodies against ASFV demonstrated ease of operation, a low cost, and a simple production process. The two cELISAs could determine whether pigs were infected with wild-type or CD2v-deleted ASFV, and they play an important role in monitoring ASFV infections in pig farms.

2.
Oncol Rep ; 51(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38639185

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive, heterogeneous tumour usually caused by alcohol and tobacco consumption, making it one of the most common malignancies worldwide. Despite the fact that various therapeutic approaches such as surgery, radiation therapy (RT), chemotherapy (CT) and targeted therapy have been widely used for HNSCC in recent years, its recurrence rate and mortality rate remain high. RT is the standard treatment choice for HNSCC, which induces reactive oxygen species production and causes oxidative stress, ultimately leading to tumour cell death. CT is a widely recognized form of cancer treatment that treats a variety of cancers by eliminating cancer cells and preventing them from reproducing. Immune checkpoint inhibitor and epidermal growth factor receptor are important in the treatment of recurrent or metastatic HNSCC. Iron death, a type of cell death regulated by peroxidative damage to phospholipids containing polyunsaturated fatty acids in cell membranes, has been found to be a relevant death response triggered by tumour RT in recent years. In the present review, an overview of the current knowledge on RT and combination therapy and iron death in HNSCC was provided, the mechanisms by which RT induces iron death in tumour cells were summarized, and therapeutic strategies to target iron death in HNSCC were explored. The current review provided important information for future studies of iron death in the treatment of HNSCC.


Assuntos
Ferroptose , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia Combinada , Ferro
3.
Cell Signal ; : 111186, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643945

RESUMO

Breast cancer is one of the most common cancers threatening women's health. Our previous study found that silibinin induced the death of MCF-7 and MDA-MB-231 human breast cancer cells. We noticed that silibinin-induced cell damage was accompanied by morphological changes, including the increased cell aspect ratio (cell length/width) and decreased cell area. Besides, the cytoskeleton is also destroyed in cells treated with silibinin. YAP/TAZ, a mechanical signal sensor interacted with extracellular pressure, cell adhesion area and cytoskeleton, is also closely associated with cell survival, proliferation and migration. Thus, the involvement of YAP/TAZ in the cytotoxicity of silibinin in breast cancer cells has attracted our interests. Excitingly, we find that silibinin inhibits the nuclear translocation of YAP/TAZ in MCF-7 and MDA-MB-231 cells, and reduces the mRNA expressions of YAP/TAZ target genes, ACVR1, MnSOD and ANKRD. More importantly, expression of YAP1 gene is negatively correlated with the survival of the patients with breast cancers. Molecular docking analysis reveals high probabilities for binding of silibinin to the proteins in the YAP pathways. DARTS and CETSA results confirm the binding abilities of silibinin to YAP and LATS. Inhibiting YAP pathway either by addition of verteporfin, an inhibitor of YAP/TAZ-TEAD, or by transfection of si-RNAs targeting YAP or TAZ further enhances silibinin-induced cell damage. While enhancing YAP activity by silencing LATS1/2 or overexpressing YAPS127/397A, an active form of YAP, attenuates silibinin-induced cell damage. These findings demonstrate that inhibition of the YAP/TAZ pathway contributes to cytotoxicity of silibinin in breast cancers, shedding lights on YAP/TAZ-targeted cancer therapies.

4.
Hum Vaccin Immunother ; 20(1): 2333098, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38619056

RESUMO

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Vacinas contra Hepatite B , Criança , Humanos , Vacinas Combinadas , Estudos Transversais , China
5.
J Colloid Interface Sci ; 667: 425-432, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38640661

RESUMO

Developing an efficient and low-cost oxygen reduction electrocatalyst is essential for the application of aqueous zinc-air batteries (ZABs). Herein, we report a facile adsorption-confined pyrolysis strategy to fabricate the hybrid electrocatalyst (denoted as Co9S8/CoSA-PC) by embedding Co9S8 nanoparticles into Co single atoms (Co-SAs) anchored porous carbon sheets for boosting oxygen reduction reaction (ORR) durability. In this strategy, the Co2+ ions are first absorbed into oxygen-rich porous carbon nanosheets and further form the Co-SAs with the help of thiourea in the following pyrolysis procedure, which is believed to be able to confine the generated Co9S8 nanoparticles into carbon frameworks due to their interface interaction. Benefiting from the synergistic effect of different components, the obtained Co9S8/CoSA-PC electrocatalyst for ORR exhibits outstanding catalytic activity with a half-wave potential of 0.82 V and a distinguished long-term durability with a current retention of 80 % after cycling 80 h under alkaline conditions, which is superior to commercial Pt/C. Moreover, the assembled ZABs with Co9S8/CoSA-PC as cathodic catalyst deliver a high specific capacity of 764 mAh gZn-1 at 10 mA cm-2 and the outstanding peak power density of up to 221.4 mW cm-2. This work provides a novel structure design strategy to prepare transition metal sulfide-based electrocatalysts with superior durability for ORR.

6.
Plants (Basel) ; 13(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38592801

RESUMO

Mulching practices have been used to improve peach growth and production across the globe. However, the impact of mulching on the physiochemical properties and soil characteristics of orchards remains largely unknown. This study aimed to decipher the impacts of various mulching patterns on the soil environment and the quality of Prunus persica fruit in "Zijinhuangcui". Three treatments were set up, which included black ground fabric mulch (BF) and two living grass mulch treatments (HV: hairy vetch and RG: ryegrass). The results showed that different mulching treatments have different effects on soil, plant growth, and fruit quality. Living grass mulch treatments, especially the HV treatment, significantly improved soil nutrients by enhancing nitrogen-related indicators. Of note, the BF treatment had higher total phosphorus and available phosphorus contents than the HV and RG treatments. The HV treatment had the highest relative abundance of Proteobacteria (33.49%), which is associated with symbiotic nitrogen fixation, followed by RG (25.62%), and BF (22.38%) at the young fruit stage. Similarly, the abundance of Terrimonas, which has a unique nitrogen fixation system at the genus level, was significantly higher in the living grass mulch (HV, 1.30-3.13% and RG, 2.27-4.24%) than in the BF treatment. Living grass mulch also promoted tree growth, increased fruit sugar content, sugar-related components, and sugar-acid ratio, and reduced the acid content. Collectively, the findings of this study show that living grass mulch can promote tree growth and improve fruit quality by improving soil fertility, bacterial diversity, and richness.

7.
Sheng Li Xue Bao ; 76(2): 257-265, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38658375

RESUMO

The present study aims to observe the change in expression of heat shock protein 90 (HSP90) along with amyloid-ß (Aß) and phosphorylated Tau (p-Tau) protein levels in the hippocampus tissue of Alzheimer's disease (AD) transgenic animal model with age. APP/PS1 transgenic mice at age of 6-, 9- and 12-month and C57BL/6J mice of the same age were used. The cognitive abilities of these animals were evaluated using a Morris water maze. Western blot or immunohistochemistry was used to detect the expressions of HSP90 and Aß1-42, as well as the phosphorylation levels of Tau protein in the hippocampus. The hsp90 mRNA levels and the morphology and number of cells in the hippocampus were detected with real-time quantitative polymerase chain reaction (qRT-PCR) and Nissl staining, respectively. The results showed that compared with C57BL/6J mice of the same age, HSP90 and hsp90 mRNA expression were decreased (P < 0.05 or P < 0.01), while Aß1-42 and p-Tau protein levels were increased (P < 0.05 or P < 0.01) in the hippocampal tissue of APP/PS1 transgenic mice. Meanwhile, the decrease in HSP90 and hsp90 mRNA expression (P < 0.05 or P < 0.01), the increase in Aß1-42 and p-Tau levels (P < 0.01 or P < 0.05) in hippocampal tissue and the reduction in behavioral ability showed a progressive development with the advancing of age in the APP/PS1 transgenic mice. In conclusion, in the hippocampal tissue of APP/PS1 mice, the decrease in HSP90 expression and the increase in Aß1-42 and p-Tau levels together with the decline of their cognitive ability are age-dependent.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide , Proteínas de Choque Térmico HSP90 , Hipocampo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas tau , Animais , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Hipocampo/metabolismo , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Masculino , Modelos Animais de Doenças , Fosforilação , Fatores Etários , Envelhecimento/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/genética , Presenilina-1/genética , Presenilina-1/metabolismo
8.
BMC Plant Biol ; 24(1): 323, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658848

RESUMO

BACKGROUND: Water stress seriously affects the survival of plants in natural ecosystems. Plant resistance to water stress relies on adaptive strategies, which are mainly based on plant anatomy with following relevant functions: (1) increase in water uptake and storage; (2) reduction of water loss; and (3) mechanical reinforcement of tissues. We measured 15 leaf-stem anatomical traits of five dominant shrub species from 12 community plots in the eastern Qaidam Basin to explore adaptive strategies based on plant leaf-stem anatomy at species and community levels. and their relationship with environmental stresses were tested. RESULTS: Results showed that the combination of leaf-stem anatomical traits formed three types of adaptive strategies with the drought tolerance of leaf and stem taken as two coordinate axes. Three types of water stress were caused by environmental factors in the eastern Qaidam Basin, and the established adaptive strategy triangle could be well explained by these environmental stresses. The interpretation of the strategic triangle was as follows: (1) exploitative plant strategy, in which leaf and stem adopt the hydraulic efficiency strategy and safety strategy, respectively. This strategy is mostly applied to plants in sandy desert (i.e., Nitraria tangutorum, and Artemisia sphaerocephala) which is mainly influenced by drought stress; (2) stable plant strategy, in which both leaf/assimilation branches and stem adopt hydraulic safety strategy. This strategy is mostly applied to plants in salty desert (i.e., Kalidium foliatum and Haloxylon ammodendron) which aridity has little effect on them; and (3) opportunistic plant strategy, in which leaf and stem adopt hydraulic safety strategy and water transport efficiency strategy. This strategy is mostly applied to plants in multiple habitats (i.e., Sympegma regelii) which is mainly affected by coldness stress. CONCLUSION: The proposed adaptive strategy system could provide a basis for elucidating the ecological adaptation mechanism of desert woody plants and the scientific management of natural vegetation in the Qinghai-Tibet Plateau.


Assuntos
Adaptação Fisiológica , Folhas de Planta , Caules de Planta , Folhas de Planta/anatomia & histologia , Folhas de Planta/fisiologia , Caules de Planta/anatomia & histologia , Caules de Planta/fisiologia , Secas , Água/metabolismo , China , Ecossistema , Estresse Fisiológico
9.
BMC Vet Res ; 20(1): 141, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582846

RESUMO

Glaesserella parasuis, an important respiratory bacterial pathogen, causes Glässer's disease in piglets, with potential immunosuppression. We established a piglet infection model and explored the immunosuppression mechanism to improve our understanding of the host immune response to G. parasuis. Twenty piglets were randomly divided into two groups (n = 10). The infection group was intraperitoneally challenged with 2 × 108 CFU of G. parasuis in 2 mL TSB. The control group was intraperitoneally injected with equivalent TSB. After 72 h, the piglets were sacrificed, and spleen tissue was collected. PD-1/PD-L1 expression was determined. The splenocytes were isolated to detect CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD21+cell differentiation. Via data-independent acquisition (DIA), we compared the proteomics of healthy and infected spleen tissues. Glaesserella parasuis modified CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD21+ cell differentiation and PD-1/PD-L1 expression in the spleen. The infection group had 596 proteins with significant differences in expression, of which 301 were significantly upregulated and 295 downregulated. Differentially expressed proteins (DEPs) were mainly related to immune responses. This is the first study on PD-1/PD-L1 expression in the spleen associated with immunosuppression in a piglet model to explore the protein changes related to immune responses via DIA.


Assuntos
Infecções por Haemophilus , Haemophilus parasuis , Doenças dos Suínos , Animais , Antígeno B7-H1 , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/veterinária , Terapia de Imunossupressão/veterinária , Fosfatidilinositol 3-Quinases , Receptor de Morte Celular Programada 1 , Proteínas Proto-Oncogênicas c-akt , Suínos , Doenças dos Suínos/microbiologia , Serina-Treonina Quinases TOR
10.
Blood ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457773

RESUMO

Haemoglobin Bart's hydrops fetalis syndrome (BHFS) represents the most severe form of α-thalassaemia, arising from deletion of the duplicated α-globin genes from both alleles. The absence of α-globin leads to the formation of non-functional haemoglobin Bart's (γ4) or haemoglobin H (HbH: ß4) resulting in severe anaemia, tissue hypoxia, and, in some cases, variable congenital or neurocognitive abnormalities. BHFS is the most common cause of hydrops fetalis in Southeast Asia; however, owing to global migration, the burden of this condition is increasing worldwide. With the availability of intensive perinatal care and intrauterine transfusions, an increasing number of patients survive with this condition. The current approach to long-term management of survivors involves regular blood transfusions and iron chelation, a task made challenging by the need for intensified transfusions to suppress the production of non-functional HbH-containing erythrocytes. While our knowledge of outcomes of this condition is evolving, it seems, in comparison to individuals with transfusion-dependent ß-thalassaemia, those with BHFS may face an elevated risk of complications arising from chronic anaemia and hypoxia, ongoing haemolysis, iron overload, and from their respective treatments. Although stem cell transplantation remains a viable option for a select few, it is not without potential side effects. Looking ahead, potential advancements in the form of genetic engineering and innovative therapeutic approaches, such as the reactivation of embryonic α-like globin gene expression, hold promise for furthering the treatment of this condition. Prevention remains a crucial aspect of care, particularly in areas with high prevalence or limited resources.

11.
Angew Chem Int Ed Engl ; 63(18): e202402010, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38462490

RESUMO

The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon-bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis as compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatization/dimerization remains unknown. In this study, an unusual "gene-within-gene" thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with α/ß-hydrolase and 4-hydroxybenzoyl-CoA thioesterase (4-HBT)-like enzyme domains, and a nested YsfFHBT (4-HBT-like enzyme). Using an intracellular tagged carrier-protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6π-electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP-tethered dearomatization/dimerization process, possibly through an unprecedented Michael-type addition reaction. Moreover, site-directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6π-electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family.


Assuntos
Lipídeos , Tioléster Hidrolases , Dimerização , Tioléster Hidrolases/química , Mutagênese Sítio-Dirigida
12.
Sci Total Environ ; 927: 172008, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547993

RESUMO

OBJECTIVE: Little has been known on the effect of chronic glyphosate exposure on osteoarthritis (OA). The aim of this study was to investigate the association between glyphosate exposure and OA and to further investigate the different moderating effects of leisure time physical activity (LTPA) and body mass index (BMI) types on the association between glyphosate exposure and OA. METHODS: Cross-sectional data from 2540 participants in the 2015-2018 National Health and Nutrition Examination Survey (NHANES) were used to explore the association between glyphosate exposure and OA. Multivariate logistic regression models and restricted cubic spline models were used to investigate the association between glyphosate exposure and OA, and further analyses were conducted to determine the association between glyphosate exposure and OA under different LTPA and BMI types. RESULTS: Of the 2540 participants, 346 had OA. Participants with the highest glyphosate concentration (Q4) had a higher incidence of OA compared to participants with the lowest glyphosate concentration (Q1) (OR, 1.88; 95 % confidence interval [CI]: 1.13, 3.13), there was no nonlinear association between glyphosate and OA (non-linear P = 0.343). In the no LTPA group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.65; 95%CI: 1.27, 5.51). In the obese group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.74; 95 % CI: 1.48, 5.07). Among people with high BMI and inactive in LTPA, glyphosate concentrations in Q4 were associated with OA (OR, 2.19; 95 % CI: 1.07, 4.48). CONCLUSIONS: Glyphosate is associated with OA odd, and physical activity and moderate weight loss can mitigate this association to some degree. This study provides a scientific basis for rational prevention of OA by regulation of LTPA and BMI under glyphosate exposure.


Assuntos
Exercício Físico , Glicina , 60658 , Obesidade , Osteoartrite , Humanos , Glicina/análogos & derivados , Osteoartrite/epidemiologia , Masculino , Feminino , Obesidade/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Estados Unidos/epidemiologia , Herbicidas , Exposição Ambiental/estatística & dados numéricos , Atividades de Lazer , Índice de Massa Corporal , Inquéritos Nutricionais , Idoso
13.
J Agric Food Chem ; 72(14): 8189-8199, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38551197

RESUMO

Protein from Sichuan peppers can elicit mild to severe allergic reactions. However, little is known about their allergenic proteins. We aimed to isolate, identify, clone, and characterize Sichuan pepper allergens and to determine its allergenicity and cross-reactivities. Sichuan pepper seed proteins were extracted and then analyzed by SDS-PAGE. Western blotting was performed with sera from Sichuan pepper-allergic individuals. Proteins of interest were purified using hydrophobic interaction chromatography and gel filtration and further analyzed by analytical ultracentrifugation, circular dichroism spectroscopy, and mass spectrometry (MS). Their coding region was amplified in the genome. IgE reactivity and cross-reactivity of allergens were evaluated by dot blot, enzyme-linked immunosorbent assay (ELISA), and competitive ELISA. Western blot showed IgE binding to a 55 kDa protein. This protein was homologous to the citrus proteins and has high stability and a sheet structure. Four DNA sequences were cloned. Six patients' sera (60%) showed specific IgE reactivity to this purified 11S protein, which was proved to have cross-reactivation with extracts of cashew nuts, pistachios, and citrus seeds. A novel allergen in Sichuan pepper seeds, Zan b 2, which belongs to the 11S globulin family, was isolated and identified. Its cross-reactivity with cashew nuts, pistachios, and citrus seeds was demonstrated.


Assuntos
Alérgenos , Hipersensibilidade a Noz , Humanos , Alérgenos/genética , Alérgenos/química , 60654 , Proteínas de Plantas/genética , Proteínas de Plantas/química , Reações Cruzadas , Clonagem Molecular , Imunoglobulina E/metabolismo
14.
Physiol Mol Biol Plants ; 30(1): 137-152, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38435851

RESUMO

Autophagy, a conserved degradation and reuse process, plays a crucial role in plant cellular homeostasis during abiotic stress. Although numerous autophagy-related genes (ATGs) that regulate abiotic stress have been identified, few functional studies have shown how they confer tolerance to copper (Cu) stress. Here, we cloned a novel Vitis vinifera ATG6 gene (VvATG6) which was induced by 0.5 and 10 mM Cu stress based on transcriptomic data, and transgenic Arabidopsis thaliana, tobacco (Nicotiana tabacum), and grape calli were successfully obtained through Agrobacterium-mediated genetic transformation. The overexpression of VvATG6 enhanced the tolerance of transgenic lines to Cu. After Cu treatment, the lines that overexpressed VvATG6 grew better and increased their production of biomass compared with the wild-type. These changes were accompanied by higher activities of antioxidant enzymes and a lower accumulation of deleterious malondialdehyde and hydrogen peroxide in the transgenic plants. The activities of superoxide dismutase, peroxidase, and catalase were enhanced owing to the elevation of corresponding antioxidant gene expression in the VvATG6 overexpression plants under Cu stress, thereby promoting the clearance of reactive oxygen species (ROS). Simultaneously, there was a decrease in the levels of expression of RbohB and RbohC that are involved in ROS synthesis in transgenic plants under Cu stress. Thus, the accelerated removal of ROS and the inhibition of its synthesis led to a balanced ROS homeostasis environment, which alleviated the damage from Cu. This could benefit from the upregulation of other ATGs that are necessary for the production of autophagosomes under Cu stress. To our knowledge, this study is the first to demonstrate the protective role of VvATG6 in the Cu tolerance of plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01415-y.

15.
Physiol Rev ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451235

RESUMO

The endomembrane system consists of organellar membranes in the biosynthetic pathway: endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles, as well as those in the degradative pathway: early endosomes, macropinosomes, phagosomes, autophagosomes, late endosomes, and lysosomes. These endomembrane organelles/vesicles work together to synthesize, modify, package, transport, and degrade proteins, carbohydrates, and lipids, regulating the balance between cellular anabolism and catabolism. Large ion concentration gradients exist across endomembranes - Ca2+ gradients for most endomembrane organelles and H+ gradients for the acidic compartments. Ion (Na+, K+, H+, Ca2+, and Cl-) channels on the organellar membranes control ion flux in response to cellular cues, allowing rapid informational exchange between the cytosol and organelle lumen. Recent advances in organelle proteomics, organellar electrophysiology, luminal and juxta-organellar ion imaging have led to molecular identification and functional characterization of about two dozen endomembrane ion channels. For example, whereas IP3R1-3 channels mediate Ca2+ release from the ER in response to neurotransmitter and hormone stimulation, TRPML1-3 and TMEM175 channels mediate lysosomal Ca2+ and H+ release, respectively, in response to nutritional and trafficking cues. This review aims to summarize the current understandings of these endomembrane channels, with a focus on their subcellular localizations, ion permeation properties, gating mechanisms, cell biological functions, and disease relevance.

16.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38396983

RESUMO

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.


Assuntos
Avena , Grão Comestível , Avena/genética , Avena/metabolismo , Grão Comestível/genética , Filogenia , Genoma de Planta , Melhoramento Vegetal , Estresse Fisiológico/genética , Proteínas de Choque Térmico HSP90/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo
17.
Discov Med ; 36(181): 343-354, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38409839

RESUMO

BACKGROUND: Oxidative stress, propelled by reactive oxygen species (ROS), serves as a significant catalyst for atherosclerosis (AS), a primary contributor to vascular diseases on a global scale. Antioxidant therapy via nanomedicine has emerged as a pivotal approach in AS treatment. Nonetheless, challenges such as inadequate targeting, subpar biocompatibility, and limited antioxidant effectiveness have restrained the widespread utilization of nanomedicines in AS treatment. This study aimed to synthesize a specialized peptide-modified liposome capable of encapsulating two antioxidant enzymes, intending to enhance targeted antioxidant therapy for AS. METHODS: The film dispersion method was employed for liposome preparation. Fluorescence quantification was conducted to assess the drug encapsulation rate. Characterization of liposome particle size was performed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Laser confocal microscopy and flow cytometry were utilized to analyze liposome cell uptake and target foam cells. Antioxidant analysis was conducted using 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining, while pro-lipid efflux analysis utilized Oil Red O (ORO) staining. Safety evaluation was performed using Hematoxylin and Eosin (H&E) staining. The level of inflammatory factors was determined through enzyme-linked immunosorbent assay (ELISA). The degree of lipid oxidation at the cellular level was assessed using the malonaldehyde (MDA) assay. In vivo targeting analysis was conducted using small animal live imaging. RESULTS: Our in vitro and in vivo findings substantiated that the modification of Lyp-1 led to increased delivery of antioxidant enzymes into foam cells (p < 0.05), the primary pathological cells within AS plaques. Upon accumulation in foam cells, liposomes loaded with superoxide dismutase (SOD) and catalase (CAT) (LyP-lip@SOD/CAT) effectively mitigated excess ROS and shielded macrophages from ROS-induced damage (p < 0.01). Furthermore, the reduction in ROS levels notably hindered the endocytosis of oxidized low-density lipoprotein (Ox-LDL) by activated macrophages, subsequently alleviating lipid accumulation at atherosclerotic lesion sites, evident from both in vitro and in vivo ORO staining results (p < 0.01). LyP-lip@SOD/CAT significantly curbed the secretion of inflammatory factors at the plaque site (p < 0.001). Additionally, LyP-lip@SOD/CAT demonstrated commendable biological safety. CONCLUSIONS: In this study, we effectively synthesized LyP-lip@SOD/CAT and established its efficacy as a straightforward and promising nano-agent for antioxidant therapy targeting atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Células Espumosas , Lipossomos/farmacologia , Superóxido Dismutase/farmacologia , Catalase/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Estresse Oxidativo , Aterosclerose/tratamento farmacológico , Lipoproteínas LDL/farmacologia
18.
Sci Total Environ ; 919: 170694, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325477

RESUMO

The uranium (U) containing leachate from uranium tailings dam into the natural settings, may greatly affect the downstream environment. To reveal such relationship between uranium contamination and microbial communities in the most affected downstream environment under drought stress, a 180 cm downstream artificial reservoir depth sediment profile was collected, and the microbial communities and related genes were analyzed by 16S rDNA and metagenomics. Besides, the sequential extraction scheme was employed to shed light on the distinct role of U geochemical speciations in shaping microbial community structures. The results showed that U content ranged from 28.1 to 70.1 mg/kg, with an average content of 44.9 mg/kg, significantly exceeding the value of background sediments. Further, U in all the studied sediments was related to remarkably high portions of mobile fractions, and U was likely deposited layer by layer depending on the discharge/leachate inputs from uranium-involving anthoropogenic facilities/activities upstream. The nexus between U speciation, physico-chemical indicators and microbial composition showed that Fe, S, and N metabolism played a vital role in microbial adaptation to U-enriched environment; meanwhile, the fraction of Ureducible and the Fe and S contents had the most significant effects on microbial community composition in the sediments under drought stress.


Assuntos
Urânio , Urânio/análise , Secas , Poluição Ambiental , Sedimentos Geológicos/química
19.
ISA Trans ; 147: 337-349, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342649

RESUMO

This paper proposes a novel iterative algorithm for the joint state and parameter estimation of bilinear state-space systems disturbed by colored noise. Estimating the states and parameters of such systems is challenging due to their nonlinearity and greater number of parameters compared to linear systems. Our method is to modify the Kalman filtering appropriately to estimate the unknown states of bilinear systems. Once the unknown states are estimated, we develop the Kalman filtering-based multi-innovation gradient-based iterative (KF-MIGI) algorithm for parameter estimation. To further improve estimation accuracy and cope with colored noises, we introduce a data filtering-based KF-MIGI algorithm that uses an adaptive filter to filter input-output data. Additionally, we compare the gradient-based iterative algorithm and the stochastic gradient algorithm. The effectiveness of the proposed algorithm is demonstrated through numerical examples.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38376700

RESUMO

Coronary atherosclerosis leading to ischemic artery disease is one of the etiological factors to develop heart failure (HF). This study aimed to investigate potential biomarkers for discriminating HF in atherosclerotic patients. This study included 40 consecutive atherosclerotic patients who underwent angiography. Concentrations of B-type natriuretic peptide (BNP), fibronectin type III domain containing 5 (FNDC5), and Phosphodiesterase 9A (PDE9A) were measured in 20 atherosclerotic patients with HF symptoms/signs and 20 without HF symptoms/signs. Circulating BNP levels were elevated, while FNDC5 levels were reduced in atherosclerotic patients with HF symptoms/signs compared to those without HF symptoms/signs. Pearson correlation analysis showed a significant correlation between FNDC5 and BNP. Receiver Operating Characteristics analysis indicated that both FNDC5 and BNP were able to discriminate HF in atherosclerotic patients. Our findings suggest that FNDC5, along with BNP, has independent value as a biomarker for discriminating HF in patients with coronary atherosclerosis.

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