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Ferroptosis is a recently identified form of programmed cell death that is iron-dependent and closely involved in the pathogenesis of breast cancer. Past studies have identified myricetin as being able to inhibit breast cancer growth through its targeting of apoptotic mechanisms, but the precise mechanisms whereby it exerts its antitumoral effects in breast cancer remain to be characterized in detail. Here, the effects of myricetin on the induction of ferroptosis in breast cancer cells were investigated. It was found that myricetin was able to significantly inhibit 4 T1 tumor cell viability and colony forming activity, increasing the level of MDA, Fe2+, and ROS within these cells. From a mechanistic perspective, myricetin was found to induce ferroptotic 4 T1 cell death via downregulating Nrf-2 and GPX4. In vivo experimentation demonstrated that myricetin treatment was sufficient to reduce the growth of subcutaneous breast tumors in female mice as evidenced by decreases in tumor weight and volume, while significantly inhibiting Nrf-2 and GPX4 expression within the tumors of treated mice. Myricetin is capable of readily suppressing breast tumor growth in mice via the induction of ferroptotic activity through the Nrf-2/GPX4 pathway. Myricetin may thus offer utility as a therapeutic agent for the management of breast cancer in clinical settings.
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Neoplasias da Mama , Ferroptose , Flavonoides , Fator 2 Relacionado a NF-E2 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Ferroptose/efeitos dos fármacos , Flavonoides/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Feminino , Camundongos , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células/efeitos dos fármacosRESUMO
Plants have, throughout evolution, developed a hydrophobic cuticle to protect them from various stresses in the terrestrial environment. The cuticle layer is mainly composed of cutin and cuticular wax, a mixture of very-long-chain fatty acids and their derivatives. With the progress of transcriptome sequencing and other research methods, the key enzymes, transporters and regulatory factors in wax synthesis and metabolism have been gradually identified, especially the study on the regulation of wax metabolism by transcription factors and others in response to plant stress has become a hot topic. Drought is a major abiotic stress that limits plant growth and crop productivity. Plant epidermal wax prevents non-stomatal water loss and improves water use efficiency to adapt to arid environments. In this study, the ways of wax synthesis, transport, metabolism and regulation at different levels are reviewed. At the same time, the regulation of wax by different transcription factors and plant hormones in response to drought is elaborated, and key research questions and important directions for future solutions are proposed to enhance the potential application of epidermal wax in agriculture and the environment.
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Secas , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas , Estresse Fisiológico , Fatores de Transcrição , Ceras , Ceras/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Epiderme Vegetal/metabolismo , Epiderme Vegetal/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMO
This study aims to experimentally compare the efficacy of different endodontic materials (iRoot BP Plus, Biodentine, MTA, Rootdent, and Trioxide) in the treatment of pulpitis and perforations on extracted tooth specimens. Additionally, the study aims to investigate the influence of iRoot BP Plus endodontic material on the regenerative processes following pulp amputation in laboratory animals. The secondary goal is to evaluate the effect of iRoot BP Plus on the restoration process in laboratory animals after pulp removal. The study presents a micropermeability analysis of the selected biomaterials performed on a sample of 50 single-rooted apical teeth in 2022. All teeth underwent endodontic treatment. Changes in molar morphology were investigated with eight laboratory animals (rabbits, 3 months old, all males) after simulated pulp removal and subsequent treatment with the iRoot BP Plus biomaterials. iRoot BP Plus appeared to be more effective in retrograde apical root filling than other biomaterials, as evidenced by its higher sealing effect. An experiment involving animal participants revealed the presence of protective adaptive mechanisms, which manifested in the form of an inflammatory process within 6 weeks after the dental pulp was removed. The connective tissue replaced the necrosis, and new capillaries began to form intensively. These dental outcomes suggest that iRoot BP Plus enables hermetical sealing in tooth restoration with good adhesion. Thus, it may have the ability to promote more active tissue regeneration after pulp removal.
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Amputação Cirúrgica , Materiais Biocompatíveis , Silicatos , Animais , Masculino , Humanos , Coelhos , Lactente , Dente Molar , NecroseRESUMO
OBJECTIVE: To explore the main factors affecting early dental caries among preschool children aged 3-6 years in Xingtai City to formulate effective preventive measures. METHODS: A cross-sectional study was conducted on 570 preschool children aged 3-6 years in Xingtai City through questionnaire surveys and oral examinations to understand their dental caries situation. Multifactorial logistic regression analysis was used to analyse the main influencing factors for the occurrence of dental caries in preschool children. RESULTS: Univariate analysis showed statistically significant differences in age (χ2 = 2.636, p = 0.008), father's education level (χ2 = 4.207, p < 0.001), mother's education level (χ2 = 4.217, p < 0.001), daily tooth brushing frequency (χ2 = 3.160, p = 0.002), age of starting tooth brushing (χ2 = 8.756, p < 0.001), mouth rinsing after meals (χ2 = 89.401, p < 0.001), Streptococcus mutans positivity (χ2 = 133.503, p < 0.001), non-sweet snack consumption frequency (χ2 = 5.962, p < 0.001), snack flavour preference (χ2 = 116.119, p < 0.001), use of fluoridated toothpaste (χ2 = 75.639, p < 0.001), regular oral examinations (χ2 = 98.711, p < 0.001), sugary drink consumption frequency (χ2 = 10.370, p < 0.001) and sweet food consumption frequency (χ2 = 9.261, p < 0.001) between the caries and non-caries groups. Multifactorial analysis revealed that older age (odds ratio [OR] = 5.342, 95% confidence interval [CI]: 1.434-6.631), later initiation of tooth brushing (OR = 3.244, 95% CI: 2.413-5.424), S. mutans positivity (OR = 5.357, 95% CI: 4.529-8.563), high snack consumption frequency (OR = 3.452, 95% CI: 2.634-5.442), high sugary drink consumption frequency (OR = 4.414, 95% CI: 2.534-6.451) and high sweet food consumption frequency (OR = 4.531, 95% CI: 3.421-6.354) were risk factors for dental caries. Higher father's educational level (OR = 0.724, 95% CI: 0.564-0.891), higher mother's educational level (OR = 0.641, 95% CI: 0.601-0.813), high daily tooth brushing frequency (OR = 0.572, 95% CI: 0.423-0.864), mouth rinsing after meals (OR = 0.743, 95% CI: 0.643-0.813), use of fluoridated toothpaste (OR = 0.657, 95% CI: 0.553-0.931) and regular oral examinations (OR = 0.443, 95% CI: 0.352-0.747) were protective factors against dental caries (all p < 0.05). CONCLUSION: Multiple factors result in early dental caries in preschool children aged 3-6 years; however, the most influential factors are older age and high snack consumption, as well as high sugary and sweet food/drink consumption.
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Cárie Dentária , Escovação Dentária , Humanos , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Pré-Escolar , Estudos Transversais , Masculino , Feminino , Criança , Escovação Dentária/estatística & dados numéricos , Fatores de Risco , Escolaridade , Lanches , Inquéritos e Questionários , Fatores Etários , Streptococcus mutans/isolamento & purificaçãoRESUMO
This randomized, controlled clinical trial compares the clinical performance of glass-fibre and resorbable polylactic acid (PLA) intracanal posts used to restore carious primary incisors in young patients. The study sample includes 180 primary upper central incisors of 90 children aged 3 to 4 years. All patients were randomly divided into two equal groups of 45 children who received PLA and glass-fibre (GFP) intracanal posts. The clinical assessment of incisor restorations was carried out immediately upon completion and at months 3, 6 and 12 according to the following criteria: anatomical form, marginal adaptation, surface roughness, marginal pigmentation, colour match, secondary caries and contact point. The Gingival Index (GI), the Bleeding Index (Cowell modification; mBI), and bite force (BF) were measured. At the 3-month follow-up, the occlusal BF of patients who received PLA posts was higher than the baseline; the GI and mBI scores were lower, by contrast (p < 0.05). This tendency was even more pronounced 6 and 12 months after the restoration. The incidence of side effects or symptoms (apical inflammation, cervical fracture, loosening of the crown) after the PLA posts was significantly lower than after the GFP (p < 0.05). No statistically significant differences were present between the two groups with respect to colour matching, anatomical form, marginal adaptation, marginal pigmentation, surface roughness, occlusal contact and secondary caries. Based on the results, applying PLA intracanal posts and cyanoacrylate to residual anterior crowns in young children can improve their gingival health, reduce side effects, and increase the likelihood of successful restoration.
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Cárie Dentária , Técnica para Retentor Intrarradicular , Criança , Humanos , Pré-Escolar , Resinas Compostas/uso terapêutico , Incisivo , Coroas , Poliésteres , Cárie Dentária/tratamento farmacológico , Falha de Restauração Dentária , Restauração Dentária Permanente/métodosRESUMO
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata(Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota.
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Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Camundongos , Camundongos Endogâmicos C57BL , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Dextranos , Inflamação , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de DoençasRESUMO
KEY MESSAGE: New translocation lines with T6V#4S·6AL in the Ph1 and ph1b backgrounds were developed with improved inheritance of powdery mildew resistance. The wheat-Dasypyrum villosum T6V#4S·6DL translocation line Pm97033, which exhibits strong powdery mildew (PM) resistance, was developed many years ago, but has limited application in wheat breeding. One of the major reasons for this is that the translocation chromosome has low transmission rate, which makes it difficult to obtain ideal genotype through recombination with other elite agronomic traits in a limited segregating population. Further modifications are thus needed to make better use of this genetic resource. In this study, Pm97033 and the T6V#2S·6AL translocation line NY-W were hybridized with the CS ph1b mutant, and two F1 hybrids were hybridized with each other. Then, plants homozygous for the ph1b deletion carrying the alien chromosome arm(s) 6V#2S and 6V#4S were identified from the segregating populations using molecular markers. New T6V#4S·6AL and T6V#2-6V#4S·6AL translocations were identified by molecular markers and confirmed by genomic in situ hybridization (GISH). Individuals that were heterozygous or homozygous for the translocation chromosome in Ph1 and ph1b backgrounds were obtained. The ratio of PM resistance vs. susceptibility in the self-pollinated heterozygous plants was 3:1, and the phenotype was completely consistent with the KASP genotyping. Thus, the new translocation chromosomes had higher transmission rate than the original T6V#4S·6DL, and so can be effectively applied in breeding programs.
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Melhoramento Vegetal , Triticum , Cromossomos de Plantas/genética , Resistência à Doença/genética , Doenças das Plantas/genética , Poaceae/genética , Translocação Genética , Triticum/genéticaRESUMO
Normal pairing and exchanging is an important basis to evaluate the genetic relationship between homologous chromosomes in a wheat background. The pairing behavior between 6V#2 and 6V#4, two chromosomes from different Dasypyrum villosum accessions, is still not clear. In this study, two wheat alien substitution lines, 6V#2 (6A) and 6V#4 (6D), were crossed to obtain the F1 hybrids and F2 segregating populations, and the testcross populations were obtained by using the F1 as a parent crossed with wheat variety Wan7107. The chromosomal behavior at meiosis in pollen mother cells (PMCs) of the F1 hybrids was observed using a genomic in situ hybridization (GISH) technique. Exchange events of two alien chromosomes were investigated in the F2 populations using nine polymerase chain reaction (PCR) markers located on the 6V short arm. The results showed that the two alien chromosomes could pair with each other to form ring- or rod-shaped bivalent chromosomes in 79.76% of the total PMCs, and most were pulled to two poles evenly at anaphase I. Investigation of the F2 populations showed that the segregation ratios of seven markers were consistent with the theoretical values 3:1 or 1:2:1, and recombinants among markers were detected. A genetic linkage map of nine PCR markers for 6VS was accordingly constructed based on the exchange frequencies and compared with the physical maps of wheat and barley based on homologous sequences of the markers, which showed that conservation of sequence order compared to 6V was 6H and 6B > 6A > 6D. In the testcross populations with 482 plants, seven showed susceptibility to powdery mildew (PM) and lacked amplification of alien chromosomal bands. Six other plants had amplification of specific bands of both the alien chromosomes at multiple sites, which suggested that the alien chromosomes had abnormal separation behavior in about 1.5% of the PMCs in F1, which resulted in some gametes containing two alien chromosomes. In addition, three new types of chromosome substitution were developed. This study lays a foundation for alien allelism tests and further assessment of the genetic relationship among 6V#2, 6V#4, and their wheat homoeologous chromosomes.
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Pareamento Cromossômico , Cromossomos de Plantas , Cruzamentos Genéticos , Melhoramento Vegetal , Translocação Genética , Triticum , Cromossomos de Plantas/genética , Cromossomos de Plantas/metabolismo , Triticum/genética , Triticum/metabolismoRESUMO
Inherited syndromes provide unique opportunities to identify key regulatory mechanisms governing human disease. We previously identified germline loss-of-function DICER1 mutations in a human syndrome defined by the childhood lung neoplasm pleuropulmonary blastoma (PPB), which arises during lung development. DICER1 regulates many biological processes critical in development and disease pathogenesis. Significant challenges in defining the role of DICER1 in human disease are identifying cause-effect relationships and generating manipulatable systems that model the complexity of organ development and disease pathogenesis. Here we report the generation of a murine model for PPB and demonstrate that precise temporal and cell type-specific Dicer1 ablation is necessary and sufficient for the development of cystic lungs that histologically and phenotypically model PPB. Dicer1 ablation in the distal airway epithelium during early stages of lung development resulted in a cystic lung phenotype indistinguishable from PPB, whereas DICER1 function was not required for development of the proximal airway epithelium or during later stages of organogenesis. Mechanistic studies demonstrate that Dicer1 loss results in epithelial cell death, followed by cystic airway dilatation accompanied by epithelial and mesenchymal proliferation. These studies define precise temporal and epithelial cell type-specific DICER1 functions in the developing lung and demonstrate that loss of these DICER1 functions is sufficient for the development of cystic PPB. These results also provide evidence that PPB arise through a novel mechanism of non-cell-autonomous tumour initiation, in which the genetic abnormality initiating the neoplasm does not occur in the cells that ultimately transform, but rather occurs in a benign-appearing epithelial cell component that predisposes underlying mesenchymal cells to malignant transformation.
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RNA Helicases DEAD-box/metabolismo , Mutação em Linhagem Germinativa/genética , Neoplasias Pulmonares/metabolismo , Blastoma Pulmonar/metabolismo , Ribonuclease III/metabolismo , Animais , RNA Helicases DEAD-box/genética , Modelos Animais de Doenças , Epitélio/metabolismo , Epitélio/patologia , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Blastoma Pulmonar/patologia , Ribonuclease III/genéticaRESUMO
Background: A previous meta-analysis showed that exercise training improves patients' physical function and health status. However, the efficacy of resistance exercise (RE) in improving patients' physical function and nutritional status is uncertain. Objective: To evaluate the effect of RE on sarcopenia and nutritional indicators in maintenance hemodialysis (MHD) patients. Design: A meta-analysis. Methods: Randomized controlled trials up to March 28, 2023 were searched from eight databases, including PubMed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure, Wan Fang, China Science and Technology Journal Database, and CBM. The risk of bias of the literature eligible for inclusion was assessed using the Cochrane risk-of-bias tool. When a high heterogeneity was detected, a random-effects model was used. Egger's tests were used to assess publication bias. This review was conducted in accordance with the PRISMA guidelines. The reliability of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation method, and a meta-analysis of the collected data was performed using Review Manager 5.4.1 software. Results: Nine studies that met the criteria were identified, and 541 patients were included in these research. Subjects: The results of this review showed that RE improved patients' grip strength levels (mean difference (MD) = 4.39, 95% confidence interval (CI) [3.14-5.64]; P < 0.00001), 6 min walking distance (MD = 40.71, 95% CI [8.92-72.49]; P = 0.01), muscle mass (MD = 4.50, 95% CI [2.01-6.99]; P = 0.0004), and serum albumin level (MD = 3.16, 95% CI [1.13-5.19]; P = 0.002) compared with the controls. However, the improvement caused by RE on hemoglobin (MD = 1.69, 95% CI [-1.49 to 4.87], P = 0.30) and cholesterol (MD = 2.33, 95% CI [-5.00 to 9.65], P = 0.53) levels was not statistically significant. Conclusion: RE showed a significant effect on muscle function and strength of MHD patients. This meta-analysis provides new ideas on the efficacy of RE in muscle function and strength of MHD patients. The use of consistent RE patterns and nutritional interventions should be considered in future studies for further assessment of its effects. In the future, more high-quality studies will be required to verify these results. Implications for practice: This meta-analysis identified the effect of RE on muscle strength, muscle function, and walking ability of HD patients, and provided a basis for clinical formulation of the optimal timing of intervention and the optimal frequency, intensity, modality, and content of intervention. Patient or public contribution: No patient or public contribution because it does not apply to my work. This review has been registered at the International Platform of Registered Systematic Review and Meta-analysis (INPLASY) (registration number: INPLASY202340078).
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Terapia por Exercício , Sarcopenia , Humanos , Estado Nutricional , Reprodutibilidade dos Testes , Sarcopenia/terapiaRESUMO
BACKGROUND: Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus (T1DM). Teplizumab, a humanized anti-CD3 monoclonal antibody, may help T1DM. Its long-term implications on clinical T1DM development, safety, and efficacy are unknown. AIM: To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM. METHODS: A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. The odds ratio (OR) and risk ratio (RR) were calculated, along with their 95%CI. We assessed heterogeneity using Cochrane Q and I 2 statistics and the appropriate P value. RESULTS: There were 8 randomized controlled trials (RCTs) in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts, with 1361 patients receiving Teplizumab and 547 patients receiving a placebo. Teplizumab was found to have a substantial link with a decrease in insulin consumption, with an OR of 4.13 (95%CI: 1.72 to 9.90). Teplizumab is associated with an improved C-peptide response (OR 2.49; 95%CI: 1.62 to 3.81) and a significant change in Glycated haemoglobin A1c (HbA1c) levels in people with type 1 diabetes [OR 1.75 (95%CI: 1.03 to 2.98)], and it has a RR of 0.71 (95%CI: 0.53 to 0.95). CONCLUSION: In type 1 diabetics, teplizumab decreased insulin consumption, improved C-peptide response, and significantly changed HbA1c levels with negligible side effects. Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.
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Objectives: This study aimed to explore the core factors and configurations influencing parenting efficacy for fathers of children with ASD in Western China by using a configuration analysis. Background: Understanding the push-pull factors related to parenting efficacy for fathers raising children with ASD can support the fathers of children with ASD to participate in education affairs and improve the quality of family education, which is of significant importance to both individuals and society. This study recruited 156 fathers of children with ASD from China. Results: The results suggested that there was more than one (sub) configuration for achieving a high level of parenting efficacy among fathers of children with ASD. (b) The configurations could be summarized into three main types as follows: "working within the system*flexible working time," "high level of education*high level of other support," and "severe disability*fewer interaction with wife." (c) The two variables, "family income" and "community support," were not as important as they were shown in previous studies, and their effects often depended on how they interact with other variables. Conclusions: Findings highlighted the validity of deploying configuration analysis (based on the ecosystem theory) to establish the relationship between independent variables and the parenting efficacy of fathers of children with ASD. The discovery of more than one configuration led to a new consensus on how multiple factors influence parenting efficacy. Implications were suggested for practitioners, policymakers, and future research alike.
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Caffeic acid O-methyltransferase (COMT), as a multifunctional enzyme involved in various physiological and biochemical processes in lignin metabolism, plays an important role in a plant's response to stress. In this study, we isolated COMT family members from the walnut genome by bioinformatics and analyzed their physicochemical properties and their expression under drought stress to provide gene resources for drought resistance in walnut. The results showed that 33 COMT genes were identified from walnuts and distributed on different chromosomes. The molecular weight of proteins varies greatly. According to the phylogenetic tree, the family can be divided into seven subgroups, which are relatively conservative in evolution and closely related to Arabidopsis thaliana. Promoter analysis showed that the promoter of the walnut COMT gene contains rich cis-elements of plant hormone response and stress response, and the real-time fluorescence scale name can be significantly induced by drought stress. Compared with wild-type Arabidopsis, overexpression JrCOMT19 significantly increased the enzyme activity (SOD, POD, and CAT) and proline content. Meanwhile, overexpression of JrCOMT19 significantly increased the lignin content and expression of related genes. Therefore, JrCOMT plays an important role in responding to drought in walnuts, and overexpression JrCOMT19 can improve the resistance to drought stress by increasing lignin content, antioxidant enzyme activity, and osmotic substance content.
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Drought represents a major environmental threat to global agricultural productivity. Employing plant growth-promoting rhizobacteria (PGPR) offers a promising strategy to enhance plant growth and resilience under drought stress. In this study, the strain G124, isolated from the arid region of Qinghai, was characterized at the molecular level, and its ability to enhance plant drought tolerance was validated through pot experiments. The findings revealed that the strain G124 belongs to Bacillus pacificus, with a 99.93% sequence similarity with B. pacificus EB422 and clustered within the same clade. Further analysis indicated that the strain G124 demonstrated a variety of growth-promoting characteristics, including siderophore production, phosphate solubilization, and the synthesis of indole-3-acetic acid (IAA), among others. Moreover, inoculation with B. pacificus G124 resulted in significant enhancements in plant height, leaf area, chlorophyll content, relative water content, and root development in both Arabidopsis thaliana and Medicago sativa seedlings under drought conditions. Additionally, G124 boosted antioxidant enzyme activities and osmolyte accumulation, while reducing malondialdehyde (MDA) and reactive oxygen species (ROS) levels in M. sativa seedlings exposed to drought. These findings suggest that B. pacificus G124 holds significant promise for enhancing plant drought tolerance and could be effectively utilized in crop management strategies under arid conditions.
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Ferroptosis is a unique modality of regulated cell death that is driven by iron-dependent phospholipid peroxidation. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. However, it remains elusive whether m6A reader Fragile X Mental Retardation Protein (FMRP) are involved in the modulation of ferroptosis in breast cancer (BC). In this study, we found that FMRP expression was elevated and associated with poor prognosis and pathological stage in BC patients. Overexpression of FMRP induced ferroptosis resistance and exerted oncogenic roles by positively regulating a critical ferroptosis defense gene SLC7A11. Mechanistically, upregulated FMRP catalyzes m6A modification of SLC7A11 mRNA and further influences the SLC7A11 translation through METTL3-dependent manner. Further studies revealed that FMRP interacts with splicing factor hnRNPM to recognize the splice site and then modulated the exon skip splicing event of SLC7A11 transcript. Interestingly, SLC7A11-S splicing variant can effectively promote FMRP overexpression-induced ferroptosis resistance in BC cells. Moreover, our clinical data suggested that FMRP/hnRNPM/SLC7A11 expression were significantly increased in the tumor tissues, and this signal axis was important evaluation factors closely related to the worse survival and prognosis of BC patients. Overall, our results uncovered a novel regulatory mechanism by which high FMRP expression protects BC cells from undergoing ferroptosis. Targeting the FMRP-SLC7A11 axis has a dual effect of inhibiting ferroptosis resistance and tumor growth, which could be a promising therapeutic target for treating BC.
Assuntos
Processamento Alternativo , Sistema y+ de Transporte de Aminoácidos , Neoplasias da Mama , Ferroptose , Proteína do X Frágil da Deficiência Intelectual , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo M , Ferroptose/genética , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Animais , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/genética , Camundongos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Linhagem Celular Tumoral , PrognósticoRESUMO
OBJECTIVE: The purpose of this study was to investigate the prevalence and relevant factors of taurodontism in North China. METHODS: We retrospectively analysed the cone beam computed tomography (CBCT) of 1025 patients (496 male and 529 female) aged between 10 and 59 years. The crown-body/root (CB/R) ratios of the maxillary and mandibular molars were measured. The prevalence of hypotaurodontism, mesotaurodontism, and hypertaurodontism was then calculated and the incidence of taurodontism along with its relevant factors, was evaluated. RESULTS: The overall rate of taurodontism in North China was as high as 78.9%. If the third molars (opsigenes) were excluded, which have a big morphological variation from each other, the rate was 52.4%. The mean CB/R ratio of taurodontism differs from tooth position: maxillary mandibular third molars > maxillary third molars > maxillary second molars > maxillary first molars > mandibular second molars > mandibular first molars (P < 0.05). In addition, the 1025 patients were divided into different age groups, and it was found that the mean CB/R ratio decreased with age (P < 0.05). Moreover, the CB/R ratio of the mandibular first and second molars in female patients was higher than males (P < 0.05). CONCLUSION: This study revealed that taurodontism is widely prevalent in North China. The incidence of taurodontism increases the closer the tooth is to the back end of the dental arch, and quite a few of the maxillary and mandibular third molars teeth have tapered roots. And the taurodontism is decreased by age, as there were more affected female than male patients.
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Raiz Dentária , Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Prevalência , Raiz Dentária/diagnóstico por imagem , China/epidemiologiaRESUMO
Macleaya cordata extract (MCE) is widely used for its diverse pharmacological actions and beneficial effects on farm animals. Modern pharmacological studies have shown that it has anti-inflammatory, anti-cancer, and anti-bacterial activities, and is gradually becoming a long-term additive veterinary drug used to improve animal intestinal health and growth performance. Although some evidence points to the DNA mutagenic potential of sanguinarine (SAN), a major component of MCE, there is a lack of sufficient basic toxicological information on the oral route, posing a potential safety risk for human consumption of food of animal origin. In this study, we assessed the acute oral toxicity, repeated 90-day oral toxicity and 180-day chronic toxicity of MCE in rats and mice and re-evaluated the genotoxicity of MCE using a standard combined in vivo and ex vivo assay. In the oral acute toxicity test, the LD50 for MCE in rats and mice was 1,564.55 mg/kg (95% confidence interval 1,386.97-1,764.95 mg/kg) and 1,024.33 mg/kg (95% confidence interval 964.27-1,087.30 mg/kg), respectively. The dose range tested had no significant effect on hematology, clinical chemistry, and histopathological findings in rodents in the long-term toxicity assessment. The results of the bacterial reverse mutation, sperm abnormality and micronucleus test showed negative results and lack of mutagenicity and teratogenicity; the results of the rat teratogenicity test showed no significant reproductive or embryotoxicity. The results indicate that MCE was safe in the dose range tested in this preclinical safety assessment. This study provides data to support the further development of maximum residue limits (MRLs) for MCE.
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Detection and recognition of latent fingerprints play crucial roles in identification and security. However, the separation of sensor, memory, and processor in conventional ex-situ fingerprint recognition system seriously deteriorates the latency of decision-making and inevitably increases the overall computing power. In this work, a photoelectronic reservoir computing (RC) system, consisting of DUV photo-synapses and nonvolatile memristor array, is developed to detect and recognize the latent fingerprint with in-sensor and parallel in-memory computing. Through the Ga-rich design, we achieve amorphous GaOx (a-GaOx) photo-synapses with an enhanced persistent photoconductivity (PPC) effect. The PPC effect, which induces nonlinearly tunable conductivity, renders the a-GaOx photo-synapses an ideal deep ultraviolet (DUV) photoelectronic reservoir, thus mapping the complex input vector into a dimensionality-reduced output vector. Connecting the reservoirs and a memristor array, we further construct an in-sensor RC system for latent fingerprint identification. The system maintains over 90% recognition accuracy for latent fingerprint within 15% stochastic noise level via the proposed dual-feature strategy. This work provides a subversive prototype system of DUV in-sensor RC for highly efficient recognition of latent fingerprints.
Assuntos
Sinapses , Condutividade ElétricaRESUMO
The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25-241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.