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Colorectal cancer (CRC) is a prevalent malignancy with high mortality rates and poor prognosis. Shikonin (SHK) has demonstrated extensive anti-tumor activity across various cancers, yet its clinical application is hindered by poor solubility, limited bioavailability, and high toxicity. This study aims to develop SHK-loaded exosomes (SHK-Exos) and assess their efficacy in CRC progression. Exosomes were isolated using ultracentrifugation and characterized via TEM, NTA, and western blotting. Their cellular internalization was confirmed through confocal microscopy post PKH67 labeling. Effects on cell behaviors were assessed using CCK-8 and Transwell assays. Cell cycle and apoptosis were analyzed via flow cytometry. A xenograft tumor model evaluatedin vivotherapeutic potential, and tumor tissues were examined using H&E staining andin vivoimaging. SHK-Exos demonstrated effective cell targeting and internalization in CRC cells.In vitro, SHK-Exos surpassed free SHK in inhibiting aggressive cellular behaviors and promoting apoptosis, whilein vivostudies showed substantial efficacy in reducing tumor growth with excellent tumor targeting and minimal toxicity. Employing SHK-Exos effectively impedes CRC progressionin vitroandin vivo, offering significant therapeutic potential. This research underscores the advantages of using autologous exosomes as a drug carrier, enhancing efficacy and reducing toxicity.
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Apoptosis , Neoplasias Colorrectales , Exosomas , Naftoquinonas , Naftoquinonas/farmacología , Naftoquinonas/química , Exosomas/metabolismo , Exosomas/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Humanos , Animales , Apoptosis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Progresión de la Enfermedad , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéuticoRESUMEN
PURPOSE: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. METHODS: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. RESULTS: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). CONCLUSIONS: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids.
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Hemorreoidectomía , Hemorroides , Terapia por Láser , Humanos , Hemorroides/cirugía , Masculino , Ligadura/métodos , Femenino , Persona de Mediana Edad , Hemorreoidectomía/métodos , Adulto , Terapia por Láser/métodos , Resultado del Tratamiento , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , RecurrenciaRESUMEN
Due to the complexity of biomass structures, the conversion of raw biomass into value-added chemicals is challenging and often requires efficient pretreatment of the biomass. In this paper, a simple and green pre-oxidation method, which was conducted under the conditions of 2 wt% H2O2, 80 min, and 150 °C, was reported to significantly increase the production of levoglucosan (LG) from biomass pyrolysis. The result showed that the LG yield significantly increased from 2.3 wt% (without pre-oxidation) to 23.1 wt% when pine wood was employed as a sample for pyrolysis at 400 °C, resulting from the removal of hemicellulose fraction and the in-situ acid catalysis of lignin carboxyl groups formed during the pre-oxidation. When the conditions for pre-oxidation became harsher than the above, the LG yield reduced because the decomposition of cellulose fraction in biomass. The study supplies an effective method for utilization of biomass as chemicals.
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Biomasa , Glucosa , Glucosa/análogos & derivados , Peróxido de Hidrógeno , Oxidación-Reducción , Pirólisis , Peróxido de Hidrógeno/química , Glucosa/química , Madera/química , Pinus/química , Lignina/química , Lignina/análogos & derivadosRESUMEN
Intestinal Disease (ID) is often characterized by clinical symptoms such as malabsorption, intestinal dysfunction, and injury. If treatment is not timely, it will increase the risk of cancer. Early diagnosis of ID is the key to cure it. There are certain limitations of the conventional diagnostic methods, such as low sensitivity and specificity. Therefore, development of a highly sensitive, non-invasive diagnostic method for ID is extremely important. Urine samples are easier to collect and more sensitive to changes in biomolecules than other pathological diagnostic samples such as tissue and blood. In this paper, a diagnostic method of ID with urine by surface-enhanced Raman spectroscopy (SERS) is proposed. A classification model between ID patients and healthy controls (HC) and a classification model between different pathological types of ID (i.e., benign intestinal disease (BID) and colorectal cancer (CRC)) are established. Here, 830 urine samples, including 100 HC, 443 BID, and 287 CRC, were investigated by SERS. The ID/HC classification model was developed by analyzing the SERS spectra of 150 ID and 100 HC, while BID/CRC classification model was built with 300 BID and 150 CRC patients by principal component analysis (PCA)-support vector machines (SVM). The two established models were internally verified by leave-one-out-cross-validation (LOOCV). Finally, the BID/CRC classification model was further evaluated by 143 BID and 137 CRC patients as an external test set. It shows that the accuracy of the classification model validated by the LOOCV for ID/HC and BID/CRC is 86.4% and 85.56%, respectively. And the accuracy of the BID/CRC classification model with external test set is 82.14%. It shows that high accuracy can be achieved with these two established classification models. It indicates that ID patients in the general population can be identified and BID and CRC patients can be further classified with measuring urine by SERS. It shows that the proposed diagnostic method and established classification models provide valuable information for clinicians to early diagnose ID patients and analyze different stages of ID.
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Enfermedades Intestinales , Espectrometría Raman , Humanos , Espectrometría Raman/métodos , Sensibilidad y Especificidad , Enfermedades Intestinales/diagnóstico , Análisis de Componente PrincipalRESUMEN
BACKGROUND: The current study aimed to investigate the molecular mechanism of long non-coding RNA (lncRNA) MEG3 in the development of breast cancer. METHODS: The regulating relationships among lncRNA MEG3, miRNA-330 and CNN1 were predicted by bioinformatics analysis of breast cancer samples in the Cancer Genome Atlas database. The differential expression of lncRNA MEG3, miRNA-330 and CNN1 was first validated in breast cancer tissues and cells. The effects of lncRNA MEG3 on breast cancer malignant properties were evaluated by manipulating its expression in MCF-7 and BT-474 cells. Rescue experiments, dual-luciferase assays, and RNA immunoprecipitation (RIP) experiments were further used to validate the relationships among lncRNA MEG3, miRNA-330 and CNN1. RESULTS: Bioinformatics analysis showed that lncRNA MEGs and CNN1 were significantly downregulated in breast cancer tissues, while miR-330 was upregulated. These differential expressions were further validated in our cohort of breast cancer samples. High expression levels of lncRNA MEG3 and CNN1 as well as low expression of miR-330 were significantly associated with favorable overall survival. Overexpression of lncRNA MEG3 significantly inhibited cell viability, migration and invasion, decreased cells in S stage and promoted cell apoptosis. Dual-luciferase reporter gene assay and RIP experiments showed that lncRNA MEG3 could directly bind to miR-330. Moreover, miR-330 mimics on the basis of lncRNA MEG3 overexpression ameliorated the tumor-suppressing effects of lncRNA MEG3 in breast cancer malignant properties by decreasing CNN1 expression. CONCLUSION: Our study indicated lncRNA MEG3 is a breast cancer suppressor by regulating miR-330/CNN1 axis.
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Neoplasias de la Mama , MicroARNs , ARN Largo no Codificante , Humanos , Femenino , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Neoplasias de la Mama/genética , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , LuciferasasRESUMEN
Anammox is one of the most innovative nitrogen removal technologies, while its functional bacteria-anaerobic ammonia-oxidizing bacteria (AAOB) is sensitive to the impurities in the wastewater. In this study, the long-term effects of sulfide at different concentrations (0, 5, 10, 20, 30, 50, 25â mg L-1) on low substrate Anammox process were studied. The results showed that when the sulfide was 25-30â mg L-1, AAOB was well coupled with sulfide-denitrifying bacteria and the total nitrogen removal efficiency (TNRE) reached a maximum of 91.0%. The hydroxylamine oxidoreductase activity and Heme-c reached 1.678 EU g-1 SS and 0.0023â mmol g-1 SS, respectively, with the hzo and nosZ gene concentrations as 2.52 × 108 and 4.45 × 107 copies mL-1. 50â mg L-1 sulfide inhibited the nitrogen removal by AAOB, resulting in the TNRE decreasing to 81.7%. The experimental results provide a reference for the practical application of Anammox in treating sulfur-containing wastewater.
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Microbiota , Aguas Residuales , Desnitrificación , Nitrógeno/análisis , Oxidación Anaeróbica del Amoníaco , Reactores Biológicos/microbiología , Oxidación-Reducción , Bacterias/genética , Sulfuros , Aguas del AlcantarilladoRESUMEN
This study aimed to evaluate the potential prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid carcinoma (PTC). Based on The TCGA database, lncRNAs and ferroptosis-related genes with differential expression levels in PTC tumors vs. normal tissues were screened. After the co-expression network construction, ferroptosis-related lncRNAs (FRLs) were screened. Kaplan-Meier analysis was conducted to compare the survival performance of patients with PTC in the high- and low-risk groups. Furthermore, a nomogram was created to enhance PTC prognosis. CIBERSORT was used to investigate the infiltration of various immune cells in high- and low-risk groups. In total, 10 lncRNA pairs with differential expression levels were obtained. There were significant differences in the histological subtype and pathological stage between the high- and low-risk groups, and age (P = 7.39E-13) and FRLM model status (P = 1.09E-04) were identified as independent prognostic factors. Subsequently, the nomogram survival model showed that the predicted one-, three-, and five-year survival rates were similar to the actual one- (c-index = 0.8475), three- (c-index = 0.7964), and five-year (c-index = 0.7555) survival rates. Subjects in the low-risk group had significantly more CD4 + memory T cells and resting myeloid dendritic cells, and subjects in the high-risk group had more plasma B cells and monocytes. The risk assessment model constructed using FRLs showed good predictive value for the prognosis of patients with PTC.
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Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing and spatial transcriptome sequencing to examine the cell dynamics in 29 patients with RC, who are sampled pairwise before and after treatment. We construct a high-resolution cellular dynamic landscape remodeled by NAC and their associations with therapeutic response. NAC markedly reshapes the populations of cancer-associated fibroblasts (CAFs), which is strongly associated with therapeutic response. The remodeled CAF subsets regulate the TME through spatial recruitment and crosstalk to activate immunity and suppress tumor progression through multiple cytokines, including CXCL12, SLIT2, and DCN. In contrast, the epithelial-mesenchymal transition of malignant cells is upregulated by CAF_FAP through MIR4435-2HG induction, resulting in worse outcomes. Our study demonstrates that NAC inhibits tumor progression and modulates the TME by remodeling CAFs.
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Fibroblastos Asociados al Cáncer , Neoplasias del Recto , Humanos , Fibroblastos Asociados al Cáncer/patología , Terapia Neoadyuvante , Transcriptoma/genética , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Proliferación Celular , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND AND AIMS: The assessment of muscle mass using technology-based methods is less commonly performed when applying the Global Leadership Initiative on Malnutrition (GLIM) criteria due to the lack of skilled clinical nutrition practitioners and/or equipment. Based on the predictive validity of poor health outcomes and feasibility in clinical practice, this study aimed to analyze whether the measurement of calf circumference (CC), mid-upper arm circumference (MAC), and the physical examination could be used as substitutes for muscle mass assessment, as well as handgrip strength (HGS) used as a substitution when applying the GLIM criteria in hospitalized HF patients. METHODS AND RESULTS: From June 2022 to January 2023, a single-center prospective study including 216 patients was performed. Additionally, covariates were identified by a directed acyclic graph. The multivariate logistic regression analysis was also used to analyze and compare the association between poor health outcomes and malnutrition (based on 5 types of GLIM criteria). Cohen-kappa coefficient and TELOS-feasibility score were calculated. The prevalence of malnutrition ranged from 35.2% to 42.6%, depending on the tool used. After adjusting for covariates, malnutrition assessed using CC, MAC, or physical examination within the GLIM criteria was independently associated with poor clinical outcomes (90-day HF-related readmission or all-cause mortality and prolonged hospital stay) but not with HGS. CONCLUSION: CC, MAC and results from physical examination but not HGS may serve as a substitutive metric of muscle mass contained in the GLIM criteria to diagnose malnutrition and predict poor clinical outcomes among HF patients. REGISTRATION NUMBER: This study was registered at Chinese Clinical Trial Registry. (ChiCTR2200057876) on 20 Mar. 2022.
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Insuficiencia Cardíaca , Desnutrición , Humanos , Fuerza de la Mano , Liderazgo , Estudios Prospectivos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Examen Físico , Desnutrición/diagnóstico , Desnutrición/epidemiología , Evaluación Nutricional , Estado NutricionalRESUMEN
ZnS/CuFe2O4/MXene (ZSCFOM) composite with ternary heterostructures was prepared by solvothermal methods for the first time to effectively adsorb and photodegrade the azo dyes. ZSCFOM mainly adsorbed azo dyes through the hydrogen bonding and electrostatic interactions, with saturated adsorption capacities of 377 mg g-1 for direct brown M and 390 mg g-1 for direct black RN. ZSCFOM exhibited both characteristics of Schott heterostructure and p-n heterostructure, but it is not a simple superposition of the two heterostructures, but rather achieves better photocatalytic property. ZSCFOM performed a higher separation efficiency of electrons and holes than pure CuFe2O4 and pure ZnS. Under visible light, ZSCFOM was more effective in removing the azo dyes than MXene, CuFe2O4, ZnS, CuFe2O4/MXene, ZnS/MXene, and ZnS/CuFe2O4. The migration pathways of photogenerated carriers in ZSCFOM were inferred as that the electrons were concentrated in MXene and conduction band of ZnS, and holes were gathered in valence band of CuFe2O4. MXene served as a cocatalyst to accelerate the separation of electrons and holes. ZSCFOM mainly degraded DBM and DBRN by catalyzing the generation of holes, superoxide radicals, and hydroxyl radicals. The 100% of 0.05 g L-1 azo dyes were removed by ZSCFOM within 30 min from the environmental water systems.
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Compuestos Azo , Luz , AdsorciónRESUMEN
PURPOSE: There is a lack of studies that systematically evaluate the clinical factors of PICC-RVT such as treatment, tumor stage, metastasis, and chemotherapy drugs in cancer patients. This study, therefore, aims to evaluate the clinical factors of catheter-related venous thrombosis in cancer patients with indwelling PICC to provide a basis for the clinical prevention and reduction of thrombosis. METHODS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from their earliest available dates until July 2022. If two or more studies had the same outcome, a meta-analysis using RevMan 5.4.1 was performed. This systematic review was registered at PROSPERO (number CRD42022358426). RESULTS: A total of 19 articles involving 19,824 patients were included for quantitative analysis. Meta-analysis of these studies indicated that a history of chemotherapy, tumor type, tumor stage, presence or absence of metastasis, and use of fluorouracil, etoposide, platinum drugs, and taxane were all risk factors for PICC catheter thrombosis in cancer patients. CONCLUSION: In clinical PICC catheter thrombosis prevention, patients with the above characteristics should be watched more closely than other patients, as they have a higher risk for PICC catheter thrombosis. Based on the present evidence at hand, radiotherapy cannot be considered to be related to the formation of PICC-RVT in cancer patients.
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Catéteres , Neoplasias , Humanos , China , Bases de Datos Factuales , Etopósido , Neoplasias/tratamiento farmacológicoRESUMEN
Pilonidal sinus is a chronic infectious disease with large incision and high risk of relapse after surgical management. Therefore, effective intervention strategies are urgently needed to reduce the relapse and shorten the wound healing time. Hydrogels have been widely used in regenerative medicine for its great biocompatibility, however, it remains challenging to integrate the material with wound tissues. Here, we reported a case of pilonidal sinus patient using a novel tissue integration material, Photo-crosslinking hydrogel after open surgery. A 38-year-old man with a pilonidal sinus for Ë5 years underwent open surgery. When the surgery was finished, the wound was injected with hydrogel that was irradiated with a ultraviolet light source until covered and solidified completely. Hydrogel needed to be changed 1-2 times per week. We evaluated the healing time as primary outcome and then followed up for Ë1 year to observe the relapse. The wound healed completely in 46 days after open surgery, which was shorter than that reported in other studies. Meanwhile, no recurrence was detected during follow-up. Photo-crosslinking hydrogel effectively promoted wound healing and has the potential to be easily applied in Pilonidal sinus patients after open surgery.
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Lasiodiplodiapyrones A and B (1 and 2), two new preussomerin derivatives, possessing an unexpected 6-methyl-4H-furo[3,2-c]pyran-4-one moiety and a highly functionalized conjoint and complicated polycyclic ring system, along with two known congeners (3 and 4), were isolated from the fungus Lasiodiplodia pseudotheobromae. Their structures including absolute configurations were determined by spectroscopic analyses, Mosher's method, and ECD calculations. A biosynthetic pathway was proposed to explain the origin of lasiodiplodiapyrones A and B as well as their relationship with preussomerins. Compounds 1-4 showed suppressive effects on the production of NO with IC50 values of 4.8 ± 0.3, 8.5 ± 1.1, 5.9 ± 0.8, and 12.8 ± 1.3 µM, respectively.
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Ascomicetos , Pironas , Estructura Molecular , Ascomicetos/química , PiranosRESUMEN
Aflatoxin is a carcinogenic secondary metabolite that poses a serious threat to human and animal health. Some C2H2 transcription factors are associated with fungal growth and secondary metabolic regulation. In this study, we characterized the role of AflZKS3, a putative C2H2 transcription factor based on genome annotation, in the growth and aflatoxin biosynthesis of A. flavus and explored its possible mechanisms of action. Surprisingly, the protein was found to be located in the cytoplasm, and gene deletion in A. flavus resulted in defective growth and conidia formation, as well as increased sensitivity to the fluorescent brightener Calcofluor white, Congo red, NaCl, and sorbitol stress. Notably, the biosynthesis of aflatoxin B1 was completely inhibited in the ΔAflZKS3 deletion strain, and its ability to infect peanut and corn seeds was also reduced. RNA sequencing showed that differentially expressed genes in the ΔAflZKS3 strain compared with the control and complementation strains were mainly associated with growth, aflatoxin biosynthesis, and oxidative stress. Thus, AflZKS3 likely contributes to growth, cell development, and aflatoxin synthesis in A. flavus. These findings lay the foundation for a deeper understanding of the roles of C2H2 transcription factors in A. flavus and provide a potential biocontrol target for preventing aflatoxin contamination.
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Aflatoxinas , Animales , Humanos , Aspergillus flavus/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Virulencia/genética , Proteínas Fúngicas/metabolismo , Aflatoxina B1/metabolismoRESUMEN
Lysine acetylation (Kac) is a protein post-translational modification (PTM) widely found in plants that plays vital roles in metabolic pathways. Although seed germination and development are regulated by Kac, its potential function in seed ageing remains to be investigated. Our preliminary study demonstrated that Kac levels were altered during wheat seed artificial ageing. However, its specific role in this process still needs to be elucidated. Here, we performed quantitative acetylation proteomics analysis of soft wheat seeds with different germination rates during artificial ageing. A total of 175 acetylation proteins and 255 acetylation modification sites were remarkably changed. The differentially acetylated proteins were enriched in metabolism; response to harsh intracellular environment, such as ROS; protein storage and processing. Notably, expression, point mutation to mimic Kac by K to Q mutation at K80 and K138, protein purification and enzyme activity detection revealed that the Kac of ROS-scavenging glutathione transferase attenuated its activity, indicating that the defense ability of wheat seeds to stress gradually diminished, and the ageing process was inevitable. Collectively, our data provide a basis for further understanding the roles of Kac in seed ageing and might aid in the development of new techniques to prolong seed viability and food quality.
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A document investigation on the fungus Trichoderma virens led to the isolation of thirteen undescribed carotane sesquiterpenes and homologous. All structures were elucidated on the basis of NMR and HRESIMS data, and their absolute configurations were assigned by ECD calculation. Especially, virenscarotins A and B were first ramifications forged by aldol condensation of 4-hydroxy-3-isopentenyl-benzaldehyde with two hydroxyl groups in ring A of traditional carotane sesquiterpenes. Ring rearrangement/expansion and oxidative cleavage of normal carotane sesquiterpenes lead to the six-membered ring A of compound virenscarotin C and the ring A cleavage of compound virenscarotin D. All compounds were evaluated for cytotoxic, anti-inflammatory, and seed germination inhibitory activities.
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Hypocrea , Sesquiterpenos , Trichoderma , Benzaldehídos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Sesquiterpenos/química , Trichoderma/químicaRESUMEN
Aspergillus flavus contaminates crops and produces carcinogenic aflatoxins that pose severe threat to food safety and human health. To identify potential targets to control aflatoxin contamination, we characterized a novel Afper1 protein, which regulates cell development and secondary metabolite biosynthesis in A. flavus. Afper1 is localized in the nucleus and is required for hyphal growth, conidial and sclerotial production, and responses to osmotic stress and essential oils such as cinnamaldehyde and thymol. More importantly, aflatoxin production was impaired in the Afper1 deletion mutant. Proteomics analysis revealed that extracellular hydrolases and proteins involved in conidial development, endoplasmic reticulum (ER) homeostasis, and aflatoxin biosynthesis were differentially regulated in ΔAfper1. Unexpectedly, enzymes participated in reactive oxygen species (ROS) scavenging, including catalase (catA, catB) and superoxide dismutase (sodM) were significantly downregulated, and the ROS accumulation and sensitivity to hydrogen peroxide were confirmed experimentally. Additionally, Afper1 deletion significantly upregulated heterochromatin protein HepA and downregulated acetyltransferases involved in heterochromatin formation. Accompanying ROS accumulation and chromatin remodeling, proteins related to aflatoxins, ustiloxin B and gliotoxin were downregulated. These results implied that Afper1 deletion affected chromatin remodeling and disturbed ER homeostasis, leading to ROS accumulation, and ultimately resulting in defective growth and impaired secondary metabolite biosynthesis.
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Aflatoxinas , Aspergillus flavus , Aspergillus flavus/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Heterocromatina/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Esporas FúngicasRESUMEN
Lysine 2-hydroxyisobutyrylation (Khib ) is a recently identified post-translational modification (PTM) that regulates numerous cellular metabolic processes. In pathogenic microorganism, although glycolysis and fungal virulence are regulated by Khib , its potential roles in fungi remain to be elusive. Our preliminary results showed that levels of Khib fluctuate over time in Aspergillus flavus, which frequently contaminates crops and produces carcinogenic aflatoxins. However, the perception of Khib function in A. flavus is limited, especially in mycotoxin-producing strains. Here, we performed a comprehensive analysis of Khib in A. flavus, and 7156 Khib sites were identified in 1473 proteins. Notably, we demonstrated that Khib of AflM, a key enzyme in aflatoxin biosynthesis, affected conidia production and sclerotia formation. Furthermore, aflM deletion impaired aflatoxin biosynthesis, and more importantly, strains in which Khib was mimicked by K to T mutation at K49, K179 and K180 sites showed reduced aflatoxin production compared with wild type and ΔaflM complementation strains. These results indicate that Khib at these sites of AflM negatively regulates aflatoxin biosynthesis in A. flavus. In summary, our study revealed the potential roles of Khib in A. flavus, and particularly shed light on a new way to regulate aflatoxin production via Khib .
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Aflatoxinas , Aspergillus flavus , Aflatoxinas/genética , Aspergillus flavus/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Lisina/metabolismo , Procesamiento Proteico-Postraduccional , Esporas Fúngicas/metabolismoRESUMEN
BACKGROUND AND AIMS: In the absence of a gold standard or scientific consensus regarding the nutritional evaluation of heart failure (HF) patients, this study aimed to summarize and systematically evaluate the prognostic value of nutritional screening and assessment tools used for all-cause mortality in HF patients. METHODS AND RESULTS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from the earliest available date until July 2021. If three or more studies used the same tool, meta-analysis using RevMan 5.3 was performed. This systematic review was registered at PROSPERO (number CRD42021275575). A total of 36 articles involving 25,141 HF patients were included for qualitative analysis and 31 studies for quantitative analysis. Meta-analysis of these studies indicated, poor nutritional status evaluated by using 5 nutritional screening tools (Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status Score (CONUT), Nutritional Risk Index (NRI), and Short Form Mini Nutritional Assessment (MNA-SF)) or 2 nutritional assessment tools (the Mini Nutritional Assessment (MNA) and Generated Subjective Global Assessment (SGA)) predicted all-cause mortality in HF patients. Of all tools analyzed, MNA had the maximum HR for mortality [HR = 2.62, 95%CI 1.11-6.20, P = 0.03] and MNA-SF [HR = 1.94, 95%CI 1.40-2.70, Pï¼0.001] was the best nutritional screening tools. CONCLUSION: Poor nutritional status predicted all-cause mortality in HF patients. MNA may be the best nutritional assessment tool, and MNA-SF is most recommended for HF patient nutritional screening. The application value of MNA, especially in patients with reduced left ventricular ejection fraction (LVEF), needs to be further confirmed. The clinical application value of Mini-Nutrition Assessment Special for Heart Failure (MNA-HF) and Global Leadership Initiative on Malnutrition (GLIM) in HF patients needs to be confirmed.
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Insuficiencia Cardíaca , Desnutrición , Anciano , Evaluación Geriátrica/métodos , Humanos , Desnutrición/diagnóstico , Evaluación Nutricional , Estado Nutricional , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Bioorthogonal fluorogenic dyes are indispensable tools in wash-free bioimaging of specific biological targets. However, the fluorogenicity of existing tetrazine-based bioorthogonal probes deteriorates as the emission wavelength shifts towards the NIR window, greatly limiting their applications in live cells and tissues. Herein, we report a generalizable molecular design strategy to construct ultra-fluorogenic dyes via a simple substitution at the meso-positions of various far-red and NIR fluorophores. Our probes demonstrate significant fluorescence turn-on ratios (102 -103 -fold) in the range 586-806â nm. These results will greatly expand the applications of bioorthogonal chemistry in NIR bioimaging and biosensing.