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A noninvasive sampling technology was conceived, employing a disposable acupuncture needle in conjunction with high-resolution mass spectrometry (termed as noninvasive direct sampling extractive electrospray ionization mass spectrometry, NIDS-EESI-MS) to scrutinize the epidermal mucus of Nile tilapia for insights into the metabolic dysregulation induced by polypropylene nano- and microplastics. This analytical method initiates with the dispensing of an extraction solvent onto the needles coated with the mucus sample, almost simultaneously applying a high voltage to generate analyte ions. This innovative strategy obliterates the necessitation for laborious sample preparation, thereby simplifying the sampling process. Employing this technique facilitated the delineation of a plethora of metabolites, encompassing, but not confined to, amino acids, peptides, carbohydrates, ketones, fatty acids, and their derivatives. Follow-up pathway enrichment analysis exposed notable alterations within key metabolic pathways, including the biosynthesis of phenylalanine, tyrosine, and tryptophan, lysine degradation, as well as the biosynthesis and metabolism of valine, leucine, and isoleucine pathways in Nile tilapia, consequent to increased concentrations of polypropylene nanoplastics. These metabolic alterations portend potential implications such as immune suppression, among other deleterious outcomes. This trailblazing application of this methodology not only spares aquatic life from sacrifice but also inaugurates an ethical paradigm for conducting longitudinal studies on the same organisms, facilitating detailed investigations into the long-term effects of environmental pollutants. This technique enhances the ability to observe and understand the subtle yet significant impacts of such contaminants over time.
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Cíclidos , Microplásticos , Moco , Polipropilenos , Animales , Microplásticos/análisis , Polipropilenos/química , Cíclidos/metabolismo , Moco/metabolismo , Moco/química , Epidermis/metabolismo , Epidermis/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.
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Understanding the metabolic disorders induced by nano- and microplastics in aquatic organisms at the molecular level could help us understand the potential toxicity of nano- and microplastics more thoroughly and provide a fundamental scientific basis for regulating the usage and management of plastic products. In this research, the effect of polypropylene nanoplastics (PP-NPs) and microplastics (PP-MPs) on metabolites in the tilapia liver was comprehensively investigated by internal extractive electrospray ionization mass spectrometry (iEESI-MS). A partial least-squares discriminant analysis (PLS-DA) and a one-component analysis of variance (ANOVA) were used for selecting 46 differential metabolites, including phospholipids, amino acids, peptides, carbohydrates, alkaloids, purines, pyrimidines, and nucleosides. Pathway enrichment analysis showed significant effects on glycerophospholipid metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis after tilapia were exposed to PP-N/MPs. Dysregulation of these metabolites is mainly reflected in the possible induction of hepatitis, oxidative stress, and other symptoms. The application of iEESI-MS technology without sample pretreatment to the study of metabolic disorders in aquatic organisms under the interference of nano- and microplastics provides a promising analytical method for environmental toxicology research.
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Cíclidos , Tilapia , Contaminantes Químicos del Agua , Animales , Microplásticos , Espectrometría de Masa por Ionización de Electrospray/métodos , Plásticos , Polipropilenos/toxicidad , Hígado , Organismos Acuáticos , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismoRESUMEN
BACKGROUND: Paying attention to the health-related quality of life (HRQOL) of rural residents in poverty-stricken areas is an important part of China's poverty alleviation, but most studies on health-related quality of life have focused on rural residents, elderly individuals, and patients; evidence on the HRQOL of rural minority residents is limited. Thus, this study aimed to assess the HRQOL of rural Uighur residents in remote areas of Xinjiang, China, and determine its influencing factors to provide policy opinions for realizing a healthy China strategy. METHODS: A cross-sectional study was performed on 1019 Uighur residents in rural areas. The EQ-5D and self-administered questionnaires were used to assess HRQOL. We applied Tobit and binary logit regression models to analyse the factors influencing HRQOL among rural Uighur residents. RESULTS: The health utility index of the 1019 residents was - 0.197,1. The highest proportion of respondents reporting any problem was for mobility (57.5%), followed by usual activity (52.8%). Low levels of the five dimensions were related to age, smoking, sleep time, Daily intake of vegetables and fruit per capita. Gender, age, marital status, physical exercise, sleep duration, daily intake of cooking oil per capita, daily intake of fruit per capita, distance to the nearest medical institution, non-infectious chronic diseases (NCDs), self-rated health score, and participation in community activities were correlated with the health utility index of rural Uighur residents. CONCLUSIONS: HRQOL was lower for rural Uyghur residents than for the general population. Improving health behavioural lifestyles and reducing the incidence of poverty (return to poverty) due to illness are effective means of promoting the health in Uyghur residents. The region must fulfil the health poverty alleviation policy and focus on vulnerable groups and low-income residents to improve the health, ability, opportunity, and confidence of this population to live well.
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Etnicidad , Calidad de Vida , Humanos , Anciano , Estudios Transversales , Minorías Étnicas y Raciales , Grupos Minoritarios , Encuestas y Cuestionarios , Población Rural , China/epidemiologíaRESUMEN
Prunus sibirica L. (Siberian apricot) is a member of the Rosaceae family and an ecologically important tree species in China (Buer et al., 2022). Shot hole symptoms on the leaves were observed in five Siberian apricot groves in Chengdu (103.81 E, 30.97 N), Sichuan province in July 2020. The symptoms first appeared as small purplish-brown spots with yellow rings around them. As the disease progressed, the damaged area (diameter 1.5-3.0 cm) became necrotic and fell off. The disease incidence was about 60% and the disease index was 28.6 of leaves in the grove. in most severe cases. Fifteen symptomatic leaves were collected from 5 different trees in an orchard. Pathogen isolation was performed from symptomatic leaf tissue (5 × 5 mm) though surface disinfection (in 70% ethanol and 2% NaClO) and incubation on Potato Dextrose Agar (PDA) at 28â for 3 days. Overall 10 isolates with similar colony morphology were obtained from the 15 infected tissue pieces, and three representative isolates (XCK 2-4) were selected for further study. Colonies of the isolates on PDA were initially cottony, pale white to grayish-green with abundant aerial hyphae and produced conidial masses after 7 days. Conidiogenous cells were clavate and aggregated in acervuli. Conidia were smooth-walled, single-celled, straight, and slightly obtusely rounded at both ends, 12.8 to 18.7 × 4.3 to 5.7 µm in size (Fig. 1). The morphological characteristics of the three isolates were consistent with the description of species in the Colletotrichum gloeosporioides complex. DNA was amplified using the following primers pairs for the internal transcribed spacer (ITS) region of rDNA and partial sequences of beta-tubulin (TUB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), chitin synthase (CHS-1), and translation elongation factor (TEF-1), respectively: ITS1/ITS4, T1/Bt2b, GDF/GDR, CHS-F/CHS-R, and EF-F/EF-R (Vieira et al., 2014). Accession numbers (MW228049, MW284974, MW284976, MW284975 and MW284977, respectively) were obtained afterepositing all the resulting sequences in GenBank. Nucleotide blast showed 99 to 100% identities with Colletotrichum fructicola (GenBank accessions nos. MZ961683, MW284974, MN525881, MN525860, MF627961). Phylogenetic analysis of combined ITS-TUB-GAPDH genes using the Mrbayes inference method showed that the three isolates clustered with three reference isolates of C. fructicola as a distinct clade (Fig. 2). To verify Koch's postulates, ten 3-year-old healthy potted plants of P. sibirica were inoculated by spraying a conidial suspension (6 × 105 conidia/mL) of isolate XCK2 on both sides of leaves, and the control leaves were sprayed with sterile water. Then, all treatments were placed in a moist environment (25±2°C, 80% relative humidity, natural light). The inoculated plants showed typical symptoms of plants with natural infections, while the controls remained asymptomatic after 14 days. The pathogen C. fructicola was re-isolated from all inoculated plants, and the culture and fungus characteristics were the same as those of the original isolate. Colletotrichum fructicola was not isolated from the control plants. The results indicated that C. fructicola is the causal agent of the disease. Colletotrichum fructicola was reported as a leaf pathogen on Camellia chrysantha in China (Zhao et al., 2021). This is the first report of C. fructicola causing P. sibirica leaf shot-hole in the world. The identification of C. fructicola could provide relevant information for applying management strategies and research on the Siberian apricot disease.
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Taxus chinensis var. mairei is the endemic, endangered, and first-class protected tree species in China. This species is considered as an important resource plant because it can produce Taxol which is an effective medicinal compound against various cancers (Zhang et al., 2010). Stem blight was observed in two plant nurseries in Ya'an (102°44'E,30°42'N), Sichuan province in April 2021. The symptoms first appeared as round brown spots on the stem. As the disease progressed, the damaged area gradually expanded into an oval or irregular shape, which was dark brown. About 800 square meters of planting area were investigated and the disease incidence was up to approximately 64.8%. Twenty obviously symptomatic stems which exhibited the same symptoms as above were collected from 5 different trees in the nursery. To isolate the pathogen, the symptom margin was cut into small blocks (5 x 5 mm), and the blocks were surface sterilized in 75% ethanol for 90 s and 3% NaClO solution for 60 s . Finally incubated on Potato Dextrose Agar (PDA) at 28â for 5 days. Ten pure cultures were isolated by transferring hyphal and the three strains (HDS06, HDS07 and HDS08) were selected as representative isolates for further study. Initially, colonies on the PDA of three isolates were white and cotton-like, and then gradually turned gray-black from the center. After 21 days, conidia were produced and were smooth-walled, single-celled, black, oblate, or spherical, measuring 9.3 to 13.6 × 10.1 to 14.5 µm in size (n = 50). Conidia were present at the tip of conidiophores on hyaline vesicles. These morphological features were generally consistent with those of N. musae (Wang et al., 2017). To validate the identification, DNA were extracted from the three isolates, followed by the amplification of transcribed spacer region of rDNA (ITS), the translation elongation factor EF-1 (TEF-1), and the Beta-tubulin (TUB2) sequences with the respective primer pairs ITS1/ITS4 (White et al., 1990), EF-728F/EF-986R (Vieira et al., 2014) and Bt2a/Bt2b (O'Donnell et al., 1997) .The sequences were deposited in GenBank with the accession numbers ON965533, OP028064, OP028068, OP060349, OP060353, OP060354, OP060350, OP060351 and OP060352, respectively. Phylogenetic analysis of combined ITS, TUB2, and TEF genes using the Mrbayes inference method showed that the three isolates clustered with Nigrospora musae as a distinct clade (Fig. 2). Combine with morphological characteristics and phylogenetic analysis, three isolates were identified as N. musae. 30 2-year-old healthy potted plants of T. chinensis were used for pathogenicity test. 25 of these plants were inoculated by injecting 10 µL of the conidia suspension (1 × 106 conidia/mL) into stems and then wrap around the seal to moisturize. The remaining 5 plants were injected with the same amount of sterilized distilled water as a control. Finally, all potted plants were placed in a greenhouse at 25°C and 80% relative humidity. After 2 weeks, the inoculated stems developed lesions similar to those observed in the field, whereas controls were asymptomatic. N. musae was re-isolated from the infected stem and identified by both morphological characteristics and DNA sequence analysis. The experiments repeated three times showed similar results. As far as we know, this is the first report of N. musae causing T. chinensis stem blight in the world. The identification of N. musae could provide a certain theoretical basis for field management and further research of T. chinensis.
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While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette-Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.
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Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Animales , Cobayas , Proteínas Recombinantes de Fusión/genética , Tuberculina , Linfocitos T CD8-positivos , Tuberculosis/diagnóstico , Eritema , Antígenos BacterianosRESUMEN
Many natural products could induce apoptosis through mitochondrial pathways. However, direct interactions between natural products and mitochondria have rarely been reported. In this work, the effects and regulatory mechanisms of Jaceosidin on the isolated rat liver mitochondria have been studied. The results of the experiments which by introducing exogenous Ca2+ illustrated that Jaceosidin has the protective effects on the structure and function of the isolated mitochondria. These protective effects were related to the chelation of Ca2+ with Jaceosidin. Besides, Jaceosidin could scavenge reactive oxygen species produced during electron transport, and weaken the mitochondrial lipid peroxidation rate, which may be attributed to the antioxidant effect of phenolic hydroxyl groups of Jaceosidin. In addition, Jaceosidin has some damage effects on mitochondrial function, such as the inhibition of mitochondrial respiration and the increase of mitochondrial membrane fluidity. These results of this work provided comprehensive information to clarify the mechanisms of Jaceosidin on mitochondria, which may be the bidirectional regulatory mechanisms.
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Flavonoides/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Calcio/metabolismo , Transporte de Electrón/efectos de los fármacos , Flavonoides/química , Hidrógeno/metabolismo , Peroxidación de Lípido , Fluidez de la Membrana , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/ultraestructura , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/metabolismo , Estructura Molecular , Permeabilidad/efectos de los fármacos , Potasio/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
In this work, the effects of two non-ionic, non-hydroxyl organic solvents, dimethyl sulfoxide (DMSO) and dimethyl formamide (DMF) on the morphology and function of isolated rat hepatic mitochondria were investigated and compared. Mitochondrial ultrastructures impaired by DMSO and DMF were clearly observed by transmission electron microscopy. Spectroscopic and polarographic results demonstrated that organic solvents induced mitochondrial swelling, enhanced the permeation to H+/K+, collapsed the potential inner mitochondrial membrane (IMM), and increased the IMM fluidity. Moreover, with organic solvents addition, the outer mitochondrial membrane (OMM) was broken, accompanied with the release of Cytochrome c, which could activate cell apoptosis signaling pathway. The role of DMSO and DMF in enhancing permeation or transient water pore formation in the mitochondrial phospholipid bilayer might be the main reason for the mitochondrial morphology and function impaired. Mitochondrial dysfunctions induced by the two organic solvents were dose-dependent, but the extents varied. Ethanol (EtOH) showed the highest potential damage on the mitochondrial morphology and functions, followed by DMF and DMSO.
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Dimetilsulfóxido/toxicidad , Dimetilformamida/toxicidad , Mitocondrias/ultraestructura , Animales , Citocromos c/metabolismo , Relación Dosis-Respuesta a Droga , Etanol/toxicidad , Membranas Intracelulares/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Dilatación Mitocondrial/efectos de los fármacos , Permeabilidad/efectos de los fármacos , RatasRESUMEN
Liver mitochondria are involved in several important life processes; mitochondrial dysfunction and disorders are implicated in several human diseases. Alcohol permeates all tissues of the body and exerts some intrinsic hepatotoxicity. In this work, our results demonstrated that ethanol caused a series of mitochondria permeability transition pore (MPTP) opening factors such as mitochondrial swelling, increased permeability of H+ and K+, collapsed membrane potential, and increased membrane fluidity. Furthermore, mitochondrial ultrastructure alternation observed clearly by transmission electron microscopy and the release of Cytochrome c could explain the MPTP opening from another aspect. Moreover, ethanol damaged the mitochondrial respiration system and induced disturbance of mitochondrial energy metabolism which was monitored by polarographic and microcalorimetric methods, respectively. Considered together, these damages may promote both apoptotic and necrotic cell death and contribute to the onset or progression alcohol-induced liver diseases.
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Etanol/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Depresores del Sistema Nervioso Central/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Dilatación Mitocondrial/efectos de los fármacosRESUMEN
Feedback-induced switching between two nonlinear dynamical states is observed in a semiconductor laser. The single-mode laser is subject to optical feedback in the long-cavity regime. In every round-trip time τ, the feedback is found to switch the laser from a stable state to a periodic state. The stable state corresponds to a continuous-wave emission at a single optical frequency. The periodic state corresponds to emission at another optical frequency with sidebands generated from a sustained relaxation oscillation. Such regular switching between the stable and periodic states is first unveiled numerically. Experimentally, the resultant intensity time series is confirmed as comprising of a square-wave envelope repeating in τ, which is modulated on a microwave carrier near the relaxation resonance frequency. Additionally, the duty cycle for the periodic state is found as continuously tunable by adjusting the feedback strength. The tunable state switching is applicable to square-wave modulated photonic microwave generation.
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Novel adjuvants and innovative combinations of adjuvants (Adjuvant Systems) have facilitated the development of enhanced and new vaccines against re-emerging and challenging pathogenic microorganisms. Nonetheless, the efficacy of adjuvants is influenced by various factors, and the same adjuvant may generate entirely different immune responses when paired with different antigens. Herein, we combined the MPXV-B6R antigen with BC02, a novel adjuvant with proprietary technology, to assess its capability to induce both cellular and humoral immunity in mouse models. Mice received two intramuscular injections of B6R-BC02, which resulted in the production of MPXV-specific IgG, IgG1, and IgG2a antibodies. Additionally, it elicited strong MPXV-specific Th1-oriented cellular immunity and persistent effector memory B-cell responses. The advantages of BC02 were further validated, including rapid initiation of the immune response, robust recall memory, and sustained immune response induction. Although the potential of immunized mice to produce serum-neutralizing antibodies against the vaccinia virus requires further improvement, the exceptional performance of BC02 as an adjuvant for the MPXV-B6R antigen has been consistently demonstrated.
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Cadmium (Cd) pollution seriously affects marine organisms' health and poses a threat to food safety. Although Cd pollution has attracted widespread attention in aquaculture, little is known about the toxic mechanisms of chronic Cd exposure on shrimp growth performance. The study investigated the combined effects of chronic exposure to Cd of different concentrations including 0, 75, 150, and 300 µg/L for 30 days on the growth performance, tissue bioaccumulation, intestinal microbiology, and metabolic responses of Litopenaeus vannamei. The results revealed that the growth was significantly inhibited under exposure to 150 and 300 µg/L Cd2+. The bioaccumulation in gills and intestines respectively showed an increasing and inverted "U" shaped trend with increasing Cd2+ concentration. Chronic Cd altered the intestinal microflora with a significant decrease in microbial richness and increasing trends in the abundances of the potentially pathogenic bacteria Vibrio and Maribacter at exposure to 75 and 150 µg/L Cd2+, and Maribacter at 300 µg/L. In addition, chronic Cd interfered with intestinal metabolic processes. The expressions of certain metabolites associated with growth promotion and enhanced antioxidant power, including N-methyl-D-aspartic acid, L-malic acid, guanidoacetic acid, betaine, and gluconic acid were significantly down-regulated, especially at exposure to 150 and 300 µg/L Cd2+, and were negatively correlated with Vibrio and Maribacter abundance levels. In summary, chronic Cd exposure resulted in severe growth inhibition and increased Cd accumulation in shrimp tissues. Increased levels of intestinal pathogenic bacteria and decreased levels of growth-promoting metabolites may be the key causes of growth inhibition. Harmful bacteria Vibrio and Maribacter may be associated with the inhibition of growth-promoting metabolite expression and may be involved in disrupting intestinal metabolic functions, ultimately impairing shrimp growth potential. This study sheds light on the potential toxicological mechanisms of chronic Cd inhibition on shrimp growth performance, offering new insights into Cd toxicity studies in aquaculture.
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Cadmio , Metaboloma , Penaeidae , Contaminantes Químicos del Agua , Animales , Cadmio/toxicidad , Penaeidae/efectos de los fármacos , Penaeidae/crecimiento & desarrollo , Penaeidae/microbiología , Penaeidae/metabolismo , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismo , Metaboloma/efectos de los fármacos , Microbiota/efectos de los fármacos , Acuicultura , Microbioma Gastrointestinal/efectos de los fármacos , Branquias/metabolismo , Branquias/efectos de los fármacosRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) has a high mortality rate. Ferroptosis is linked to tumor initiation and progression. AIMS: This study aims to develop prognostic models of ferroptosis-related lncRNAs, evaluate the correlation between differentially expressed genes and tumor microenvironment, and identify prospective drugs for managing LUAD. METHODS AND RESULTS: In this study, transcriptomic and clinical data were downloaded from the TCGA database, and ferroptosis-related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the LASSO algorithm for constructing a prognostic model, we found that ferroptosis-related lncRNA-based gene signatures (FLncSig) had a strong prognostic predicting ability in the LUAD patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments reconfirmed that ferroptosis is related to receptor-ligand activity, enzyme inhibitor activity, and the IL-17 signaling pathway. Next, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) algorithms, and pRRophetic were used to predict immunotherapy response and chemotherapy sensitivity. The IMvigor210 cohort was also used to validate the prognostic model. In the tumor microenvironment, Type_II_IFN_Response and HLA were found to be a group of low-risk pathways, while MHC_class_I was a group of high-risk pathways. Patients in the high-risk subgroup had lower TIDE scores. Exclusion, MDSC, CAF, and TAMM2 were significantly and positively correlated with risk scores. In addition, we found 15 potential therapeutic drugs for LUAD. Finally, differential analysis of stemness index based on mRNA expression (mRNAsi) indicated that mRNAsi was correlated with gender, primary tumor (T), distant metastasis (M), and the tumor, node, and metastasis (TNM) stage in LUAD patients. CONCLUSIONS: In conclusion, the prognostic model based on FLncSig can alleviate the difficulty in predicting the prognosis and immunotherapy of LUAD patients. The identified FLncSig and the screened drugs exhibit potential for clinical application and provide references for the treatment of LUAD.
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Adenocarcinoma , Ferroptosis , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Estudios Retrospectivos , Ferroptosis/genética , Pronóstico , Transformación Celular Neoplásica , Pulmón , Microambiente Tumoral/genéticaRESUMEN
Iron phosphide/carbon (FeP/C) serving as electrocatalysts exhibit excellent activity in oxygen reduction reaction (ORR) process. H2O2 catalyzed by peroxidase (POD) is similar to the formation of new electron transfer channels and the optimization of adsorption of oxygen-containing intermediates or desorption of products in ORR process. However, it is still a challenge to discover FeP/C with enhanced POD-like catalytic activity in the electrocatalytic database for biocatalysis. The discovery of FeP/carbon dots (FeP/CDs) nanozymes driven by electrocatalytic activity for enhanced POD-like ability is demonstrated. FeP/CDs derived from CDs-Fe3+ chelates show enhanced POD-like catalytic and antibacterial activity. FeP/CDs exhibit enhanced POD-like activities with a specific activity of 31.1 U mg-1 that is double higher than that of FeP. The antibacterial ability of FeP/CDs nanozymes with enhanced POD-like activity is 98.1%. The antibacterial rate of FeP/CDs nanozymes (250 µg mL-1) increased by 5%, 15%, and 36% compared with FeP, Fe2O3/CDs, and Cu3P/CDs nanozymes, respectively. FeP/CDs nanozymes will attract more efforts to discover or screen transition metal phosphide/C nanozymes with enhanced POD-like catalytic activity for biocatalysis in the electrocatalytic database.
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Straw covering is a protective tillage measure in agricultural production, but there is relatively little research on the allelopathic effects of corn straw on weeds and foxtail millet. This experiment studied the allelopathic effects of corn straw on four weeds (Chenopodium album, Setaria viridis, Echinochloa crus-galli and Amaranthus retroflexus) in foxtail millet fields, and also measured the growth indicators of foxtail millet. The study consisted of Petri dish and field experiments. Five treatments were used in the Petri dish experiment: clear water as control (0 g/L, TCK) and four types of corn straw water extracts. They were, respectively, the stock solution (100 g/L, T1), 10 X dilution (10 g/L, T2), 50 X dilution (2 g/L, T3), and 100 X dilution (1 g/L, T4) of corn straw water extracts. Additionally, seven treatments were set up in the field experiment, consisting of three corn straw covering treatments, with covering amounts of 3000 (Z1), 6000 (Z2) and 12,000 kg/ha (Z3), and four control treatments-one treatment with no corn straw cover (CK) and three treatments involving the use of a black film to create the same shading area as the corn straw covered area, with black film coverage areas of 50% (PZ1), 70% (PZ2), and 100% (PZ3), respectively. The results showed that the corn straw water extract reduced the germination rate of the seeds of the four weeds. The T1 treatment resulted in the allelopathic promotion of C. album growth but the inhibition of S. viridis, E. crus-galli, and A. retroflexus growth. Treatments T2, T3, and T4 all induced the allelopathic promotion of the growth of the four weeds. The order of the effects of the corn straw water extracts on the comprehensive allelopathy index of the four weed seeds was as follows: C. album > S. viridis > A. retroflexus > E. crus-galli. With an increase in the corn straw mulching amount, the density and total coverage of the four weeds showed a gradual downward trend, whereas the plant control effect and fresh weight control effect showed a gradual upward trend. All indices showed the best results under 12,000 kg/ha of mulching and returning to the field. Overall, corn straw coverage significantly impacted the net photosynthetic rate and transpiration rate of foxtail millet and increased the yield of foxtail millet. Under coverages of 6000 and 12,000 kg/ha, the growth of foxtail millet is better. Based on our findings, we recommend a corn straw coverage of 12,000 kg/ha for the allelopathic control of weeds in foxtail millet fields.
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Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 104 times higher than that of Rapa (2.6 × 10-4 g). The half maximal inhibitory concentration (IC50) of Rapa-CDs toward hydroxyl radical (â¢OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPHâ¢) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.
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Transducción de Señal , Sirolimus , Humanos , Transducción de Señal/fisiología , Especies Reactivas de Oxígeno/metabolismo , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Senescencia Celular , Carbono/farmacologíaRESUMEN
Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.
Asunto(s)
Quitosano , Glaucoma , Daño por Reperfusión , Ratas , Animales , Ratones , Humanos , Microglía/patología , Quitosano/farmacología , Sirolimus/farmacología , Carbono/farmacología , Lipopolisacáridos/farmacología , Glaucoma/tratamiento farmacológico , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Autofagia , Citocinas/metabolismo , Agua , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
Three new furano-lactones, asperilactones A-C (1-3), and two known compounds silvaticol (4) and violaceic acid (5) were isolated from an ethanol extract of Aspergillus nidulans, a fungus isolated from the Annelida Whitmania pigra Whitman (Haemopidae). Their structures were elucidated by a combination of spectroscopy, ECD calculations, comparing optical rotation values, and single-crystal X-ray diffraction analyses. Asperilactone A (1) represented the first example of furano-lactone with an unusual 2-thia-6-oxabicyclo[3.3.0]octane ring system. Asperilactones A and B showed weak toxicity against the HL-60 and RKO.