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Cerebrospinal fluid (CSF) rhinorrhea is one of the most common complications after trans-sphenoidal surgery. At present, transcranial or endoscopic surgery for CSF leakage requires general anesthesia to remove autologous fat or fascia to repair the leak, which is traumatic and costly. The authors present a case of a 25-year-old male patient with pituitary adenoma who experienced CSF rhinorrhea 10 days after undergoing endoscopic resection of the tumor. The authors innovatively sequential filled the leak with a gelatin sponge soaked in povidone-iodine solution and iodinated gauze under outpatient nasal endoscopy. The follow-up of 6 months showed no recurrence of CSF leakage. CSF leakage is the most common complication of trans-sphenoidal surgery. The authors suggest that for small cerebrospinal fluid leaks in the early stage after trans-sphenoidal surgery, the leakage should be first filled with gelatin sponge and iodoform gauze sequentially under outpatient nasal endoscopy, which may achieve a complete cure.
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Rinorrea de Líquido Cefalorraquídeo , Endoscopía , Neoplasias Hipofisarias , Humanos , Masculino , Rinorrea de Líquido Cefalorraquídeo/cirugía , Adulto , Neoplasias Hipofisarias/cirugía , Endoscopía/métodos , Adenoma/cirugía , Povidona Yodada/uso terapéutico , Complicaciones Posoperatorias , Esponja de Gelatina Absorbible/uso terapéuticoRESUMEN
An assembled-aptasensor based on Fe3O4@Au@Ag nanocomposites grafting onto the gold foil was prepared, which can be developed into a universal approach for sensitive and rapid detection of various pathogenic bacteria, such as Escherichia coli (E. coli), Salmonella typhimurium (S. typhimurium), Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Pseudomonas aeruginosa (P. aeruginosa), and Shigella flexneri (S. flexneri). Firstly, the gold foil paper was modified with thiolated capture probe and SERS tag in proportion, and at the same time, the specific thiolated aptamer probe for corresponding pathogenic bacteria was fixed with Fe3O4@Au@Ag nanocomposites. An obvious Raman signal can be subsequently increased about 106 times by the external electromagnetic field enhancement at the "hot spots" caused by the hybridization of aptamer and capture probe. But in the presence of target pathogenic bacteria, Raman intensity will decrease as Fe3O4@Au@Ag nanocomposites are dissociated from gold foil. Thus, all of the concentrations of the six kinds of pathogenic bacteria both in PBS and liquorice extract showed an obvious negative linear correlation with the Raman intensity of SERS tag in the range of 10-107 CFU/mL with detection limits were all lower than 10 CFU/mL. And there was no significant difference between our method and the plate counting method. Besides, the assembled-aptasensor had superior specific recognition ability even in the mixed interfering bacteria. Our study showed that this assembled-aptasensor had good specific detection ability to a variety of foodborne pathogens based on magnetic field-assisted SERS technique, which can be used for rapid and sensitive detection of a variety of pathogens in complex substrates.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Nanopartículas del Metal/química , Aptámeros de Nucleótidos/química , Escherichia coli , Staphylococcus aureus , Espectrometría Raman/métodos , Bacterias , Oro/química , Límite de Detección , Técnicas Biosensibles/métodosRESUMEN
Starch and cellulose are the fundamental components of tobacco, while their excessive content will affect the quality of tobacco. Enzymatic treatment with different enzymes is a promising method to modulate the chemical composition and improve the sensory quality of tobacco leaves. In this study, enzymatic treatments, such as amylase, cellulase, and their mixed enzymes, were used to improve tobacco quality, which could alter the content of total sugar, reducing sugar, starch, and cellulose in tobacco leaves. The amylase treatment changed surface structure of tobacco leaves, increased the content of neophytadiene in tobacco by 16.48%, and improved the total smoking score of heat-not-burn (HnB) cigarette products by 5.0 points compared with the control. The Bacillus, Rubrobacter, Brevundimonas, Methylobacterium, Stenotrophomonas, Acinetobacter, Pseudosagedia-chlorotica, and Sclerophora-peronella were found to be significant biomarkers in the fermentation process by LEfSe analysis. The Basidiomycota and Agaricomycetes were significantly correlated with aroma and flavor, taste, and total score of HnB. The results showed that microbial community succession occurred due to amylase treatment, which promoted the formation of aroma compounds, and regulated the chemical composition of tobacco, and improved tobacco quality during tobacco fermentation. This study provides a method for enzymatic treatment to upgrade the quality of tobacco raw materials, thereby improving the quality of HnB cigarettes, and the potential mechanism is also revealed by chemical composition and microbial community analysis. KEY POINTS: Enzymatic treatment can change the chemical composition of tobacco leaves. The microbial community was significantly affected by enzymatic treatment. The quality of HnB cigarettes was significantly improved by amylase treatment.
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Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Productos de Tabaco/análisis , Fermentación , CalorRESUMEN
Uranium (U) phytotoxicity is an inherently difficult problem in the phytoremediation of U-contaminated environments. Plant chelating and antioxidant systems play an authoritative role in resistance to abiotic stress. To reveal the toxicity of U, the changes of chelating system, osmoregulatory substances and antioxidant systems in Vicia faba roots were studied after short-term (24 h) U exposure. The results indicated that the development of lateral roots and root activity of V. faba were significantly inhibited with U accumulation. Compared with the control, plant chelating systems showed significant positive effects after U exposure (15 - 25 µM). Osmoregulatory substances (proline and soluble protein) increasingly accumulated in roots with increasing U concentration, and O2- and H2O2 rapidly accumulated after U exposure (15 - 25 µM). Thus, the contents of malondialdehyde (MDA), a marker of lipid peroxidation, were also significantly increased. Antioxidant systems were activated after U exposure but were inhibited at higher U concentrations (15 - 25 µM). In summary, although the chelating, osmotic regulation and antioxidant systems in V. faba were activated after short-term U exposure, the antioxidases (CAT, SOD and POD) were inhibited at higher U concentrations (15 - 25 µM). Therefore, the root cells were severely damaged by peroxidation, which eventually resulted in inhibited activity and arrested root development.
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Contaminantes Radiactivos del Suelo , Uranio , Vicia faba , Antioxidantes/metabolismo , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo , Raíces de Plantas/metabolismo , Uranio/metabolismo , Uranio/toxicidad , Vicia faba/metabolismo , Vicia faba/efectos de la radiaciónRESUMEN
The glucocorticoid receptor (GR) is an important feedback regulator of the hypothalamic-pituitary-interrenal (HPI) axis. However, there are a limited number of studies focused on host-pathogen interactions in which an association between GR and immune response has been evaluated in monocytes/macrophages (MO/MФ) after being challenged with highly pathogenic bacteria. Here, we cloned the cDNA sequence of the glucocorticoid receptor (PaGR) gene from ayu fish. The PaGR transcript was expressed in all tissues, and changes in expression were observed in immune tissues and MO/MФ after live Vibrio anguillarum infection. Subsequently, PaGR was expressed and purified to prepare anti-PaGR antibodies. We analyzed the subcellular localization of PaGR. PaGR was expressed not only in the intracellular space but also in the plasma membrane. PaGR activation decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines. However, PaGR activation suppressed the phagocytosis activity of V. anguillarum-infected ayu MO/MФ via a non-genomic pathway. Interestingly, PaGR activation could enhance MO/MФ bacterial killing capability and apoptosis. Therefore, PaGR may modulate the immune response in ayu MO/MФ by genomic and non-genomic pathways.
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Macrófagos/inmunología , Monocitos/inmunología , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Vibriosis/veterinaria , Animales , Apoptosis/inmunología , Membrana Celular/metabolismo , Enfermedades de los Peces/inmunología , Osmeriformes , Fagocitosis/inmunología , Vibrio , Vibriosis/genética , Vibriosis/inmunologíaRESUMEN
Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T [primary tumor size], N [regional lymph nodes], M [distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival. Methods: DTC cases that were considered stage IV B in the AJCC 8th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6th standard) was categorized into T0-2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis. Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS. Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary. Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database.
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Neoplasias de la Tiroides , Humanos , Ganglios Linfáticos , Estadificación de Neoplasias , PronósticoRESUMEN
The CC motif chemokine 19 (CCL19) functions in acute inflammation by recruiting lymphocytes and other cells. However, CCL19 has only been investigated in few fish species. In this study, we characterized a CCL19-like molecule (PaCCL19l) in ayu (Plecoglossus altivelis), a teleost fish. Sequence analysis revealed that PaCCL19l was most closely related to Atlantic salmon (Salmon salar) CCL19l1, which belonged to the fish CCL19a.1 subcluster. PaCCL19l was constitutively expressed in the tested ayu tissues and peripheral blood mononuclear cells (PBMCs), with the highest transcript level in PBMCs. Upon infection with Vibrio anguillarum, the expressions of PaCCL19l in the head kidney, liver, spleen, PBMCs, and monocytes/macrophages (MO/MΦ) were dramatically up-regulated. Recombinant PaCCL19l (rPaCCL19l) exhibited a significant effect on the chemotaxis of lymphocytes and MO/MΦ in vitro and in vivo. Meanwhile, rPaCCL19l exerted a high chemotaxic activity for lipopolysaccharide (LPS)-stimulated MO/MΦ (M1-type), but not for cyclic adenosine monophosphate (cAMP)-stimulated MO/MΦ (M2-type). When ayu MO/MΦ was treated with rPaCCL19l along with Vibrio anguillarum infection, the mRNA expression of proinflammatory cytokines (IL-1ß, TNFα, IL-6, IL-12b, and IFN-γ) was up-regulated, while that of anti-inflammatory cytokines (IL-10, TGFß, and IL-22) was down-regulated. Ayu MO/MΦ treated with anti-PaCCL19l IgG gave the opposite result. These results implicated that PaCCL19l is involved in the selective chemotaxis of ayu immune cells and promotes the host at a pro-inflammatory state.
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Quimiocina CCL19/genética , Quimiocina CCL19/inmunología , Enfermedades de los Peces/inmunología , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Osmeriformes/genética , Osmeriformes/inmunología , Secuencia de Aminoácidos , Animales , Quimiocina CCL19/química , Proteínas de Peces/química , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Perfilación de la Expresión Génica , Leucocitos/metabolismo , Filogenia , Alineación de Secuencia/veterinaria , Vibrio/fisiología , Vibriosis/inmunologíaRESUMEN
OBJECTIVE: To detect potential mutations in two neonates suspected for Cornelia de Lange syndrome (CdLS). METHODS: Peripheral blood samples from the neonates and their parents were collected and analyzed for CdLS-related genes using targeted sequence capture and next-generation sequencing. Suspected mutations were confirmed by direct Sanger sequencing. RESULTS: The neonates were found to respectively carry mutations c.7219C to T and p.D2339Lfs*4 of the NIPBL gene, among which the p.D2339Lfs*4 mutation has not been reported previously. No pathogenic mutation was found in other CdLS-related genes including NIPBL, SMC1A, SMC3, RAD21 and HDAC8. CONCLUSION: The c.7219C to T and p.D2339Lfs*4 mutations of the NIPBL gene probably account for the disease in both patients.
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Síndrome de Cornelia de Lange/diagnóstico , Síndrome de Cornelia de Lange/genética , Proteínas de Ciclo Celular , Análisis Mutacional de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Recién Nacido , Mutación , Fenotipo , Proteínas/genéticaRESUMEN
OBJECTIVE: To explore the genetic cause of a female patient with severe mental retardation and a history of adverse pregnancy. METHODS: The patient was subjected to G-banded chromosome analysis and single nucleotide polymorphism array (SNP-array) assaying. The correlation between genomic variations and the phenotype was explored. RESULTS: The patient was found to have a complex chromosome rearrangement involving 5 chromosomes. The karyotypes of her parents were both normal. SNP-array assay has identified a 1.6 Mb microdeletion at chromosome 15q21.3 which involved 15 RefSeq genes and a 0.5 Mb microdeletion at 5q21.1 which involved one RefSeq gene. CONCLUSION: The microdeletions, which involved TCF12, ADMA10 and AQP9 genes, probably underlie the mental retardation shown by the patient.
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Cromosomas/genética , Discapacidad Intelectual/genética , Adulto , Bandeo Cromosómico/métodos , Deleción Cromosómica , Femenino , Pruebas Genéticas/métodos , Humanos , CariotipoRESUMEN
OBJECTIVE: To explore the genetic cause for a child with developmental delay. METHODS: The karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was analyzed with low-coverage massively parallel copy number variation sequencing (CNV-seq) and verified by single nucleotide polymorphism array (SNP-array). RESULTS: The karyotype of the child was ascertained as 46,XX,r(15)(p13q26.3), while both parents showed a normal karyotype. CNV-seq and SNP-array have identified a de novo 15q26.2-q26.3 deletion in the child with a size of approximately 3.60 Mb. CONCLUSION: The abnormal phenotype of the patient carrying the ring chromosome 15 may be attributed to the presence of the 15q26.2-q26.3 microdeletion. The deletion and haploinsufficiency of the IGF1R gene probably underlie the main clinical features of the patient.
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Preescolar , Bandeo Cromosómico , Cromosomas Humanos Par 15/genética , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Cariotipificación , Mosaicismo , Cromosomas en Anillo , Eliminación de SecuenciaRESUMEN
MicroRNA (miRNA) plays a key role in development and specific biological processes, such as cell proliferation, differentiation, and apoptosis. Extensive studies of mammary miRNAs have been performed in different species and tissues. However, little is known about porcine mammary gland miRNAs. In this study, we report the identification and characterization of miRNAs in the lactating mammary gland in two distinct pig breeds, Jinhua and Yorkshire. Many miRNAs were detected as significantly differentially expressed between the two libraries. Among the differentially expressed miRNAs, many are known to be related to mammary gland development and lactation by interacting with putative target genes in previous studies. These findings suggest that miRNA expression patterns may contribute significantly to target mRNA regulation and influence mammary gland development and peak lactation performance. The data we obtained provide useful information about the roles of miRNAs in the biological processes of lactation and the mechanisms of target gene expression and regulation.
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Glándulas Mamarias Animales/metabolismo , MicroARNs/metabolismo , Animales , Femenino , Perfilación de la Expresión Génica , Lactancia , Glándulas Mamarias Animales/patología , Anotación de Secuencia Molecular , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ARN , PorcinosRESUMEN
OBJECTIVE To analyze a neonate with multiple malformations and to correlate its genotype with phenotype. METHODS The karotypes of the child and her parents were subjected to G-banding chromosome analysis, and array comparative genomic hybridization (array-CGH) was used for fine mapping of the aberrant region. RESULTS The karyotype of the child was ascertained as 46,XX,del(18)(p11.2). Array CGH has identified a 9.8 Mb deletion at 18p11.32-p11.22. The patient has presented features such as holoprosencephaly, choanal atresia, heart defect, and craniofacial dysmorphisms. CONCLUSION The de novo 18p deletion probably underlies the main clinical manifestations of the child.
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Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 18 , Bandeo Cromosómico , Femenino , Humanos , Recién Nacido , FenotipoRESUMEN
This study aims to evaluate the genetic basis and activity of lecithin cholesterol acyltransferase (LCAT) in a novel Mongolian gerbil model for hyperlipidemia. Gerbils may be susceptible to high fat and cholesterol (HF/HC) diets, which can rapidly lead to the development of hyperlipidemia. Approximately 10-30% of gerbils that are over 8months old and fed controlled diets spontaneously develop hyperlipidemia. Using the HF/HC diet model, we detected triglycerides (TG), total cholesterol (TC), HDL (high density lipoprotein)-C, LDL (low density lipoprotein)-C and LCAT in both old (>8months) and young gerbils. The TC and HDL-C levels were two times higher in old gerbils compared with young gerbils (P<0.01). However, in the old group the LCAT activity fell slightly compared with the normal lipidemia group. It is reasonable to hypothesize that this may be associated with single nucleotide polymorphisms of the LCAT gene. We cloned this gene to investigate the sensitivity of the gerbil to the HF/HC diet and spontaneous hyperlipidemia. The entire LCAT gene was cloned by splicing sequences of RACE (rapid amplification of cDNA ends) and nest-PCR products (AN: KC533867.1). The results showed that the 3683base pair gene consists of six exons and five introns. The LCAT protein consists of 444 amino acid (AA) residues, which are analogous to the human LCAT gene, and includes 24 signal peptide AA and 420 mature protein AA. Expression of LCAT was detected in the kidney, spleen and adrenal tissue, apart from the liver, by immunohistochemistry. The abundance of the protein was greater in the older group compared with the control group. Polymorphisms were analyzed by PCR-SSCP (PCR-single-strand conformation polymorphism) but none were found in 444 animals of the ZCLA closed population (a Chinese cultured laboratory gerbil population).
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Hiperlipidemias/genética , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Polimorfismo de Nucleótido Simple , Animales , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Exones , Gerbillinae , Hiperlipidemias/etiología , Hiperlipidemias/metabolismo , Intrones , Masculino , Especificidad de Órganos , Fosfatidilcolina-Esterol O-Aciltransferasa/química , Fosfatidilcolina-Esterol O-Aciltransferasa/metabolismoRESUMEN
Improving our knowledge of future dynamics of ecosystem services (ESs) in the face of climate change and human activities provides a crucial foundation to navigate complex environmental challenges, which are essential to attaining sustainable development particularly in urban regions. However, an existing dearth persists in thoroughly forecasting the intricate interplay of trade-offs and synergies, as well as ecosystem services bundling under distinct future scenarios. This study adopts an integrated research framework to understand the spatiotemporal dynamics of ESs in the Changsha-Zhuzhou-Xiangtan Urban Agglomeration (CZTUA) under three Shared Socioeconomic Pathway and Representative Concentration Pathway (SSP-RCP) scenarios (i.e., SSP126, SSP245 and SSP585). Our future scenarios suggest that the core urban area of CZTUA is projected to expand at the cost of forests and croplands by 2050. Furthermore, human-induced urbanization, particularly the high-intensity LUCC along the Xiangjiang river, significantly impacts ESs, resulting in lower ESs values. The trade-off effects between ESs are primarily observed between WY (water yield) and other ESs. Ecosystem service bundles (ESB) previously dominated by WY have significantly transitioned to CS (carbon storage)-HQ (habitat quality) bundle, especially in the urban core of CZTUA, which serves as an early warning of potential challenges related to water resources. Our study utilizes the latest climate and land use change predictions to evaluate ecosystems in urban agglomerations, and adopts a layered zoning strategy based on ESs, which provides decision-makers with reproducible tools to explore ecosystem changes.
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Ovarian cancer, the eleventh most prevalent cancer among women and a significant cause of cancer-related mortality, poses considerable challenges. While the Myc oncogene is implicated in diverse cancers, its impact on tumours expressing Myc during immune therapy processes remains enigmatic. Our study investigated Myc overexpression in a murine ovarian cancer cell line, focusing on alterations in HIF1a function. Seahorse experiments were utilized to validate metabolic shifts post-Myc overexpression. Moreover, we explored macrophage polarization and immunosuppressive potential following coculture with Myc-overexpressing tumour cells by employing Gpr132-/- mice to obtain mechanistic insights. In vivo experiments established an immune-competent tumour-bearing mouse model, and CD8 T cell, Treg, and macrophage infiltration post-Myc overexpression were evaluated via flow cytometry. Additionally, adoptive transfer of OTI CD8 T cells was conducted to investigate antigen-specific immune response variations after Myc overexpression. The findings revealed a noteworthy delay in HIF1a degradation, enhancing its functionality and promoting the classical Warburg effect upon Myc overexpression. Lactic acid secretion by Myc-overexpressing tumour cells promoted Gpr132-dependent M2 macrophage polarization, leading to the induction of macrophages capable of significantly suppressing CD8 T cell function. Remarkably, heightened macrophage infiltration in tumour microenvironments post-Myc overexpression was observed alongside impaired CD8 T cell infiltration and function. Interestingly, CD4 T-cell infiltration remained unaltered, and immune-suppressive effects were alleviated when Myc-overexpressing tumour cells were administered to Gpr132-/- mice, shedding light on potential therapeutic avenues for ovarian cancer management.
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Portable Raman spectroscopy coupled with partial least squares regression (PLSR) model was performed for monitoring and predicting four quality indicators, moisture content, water activity, polysaccharide content and microbial content of the fresh-cut Chinese yam at different storage temperatures. The variations in the four key indicators were first depicted through a spider web diagram as the storage temperature changed. More importantly, the four key indicators can be accurately monitored and predicted through optimized PLSR models combining with Raman spectroscopy. Among all of the PLSR models for the four indicators, the regression model for moisture content was relatively the best. In addition, storage temperature played a significant role on the model performance of PLSR. The model performance for all indicators at room temperature and high temperature was better than the corresponding PLSR models at refrigeration and freezing conditions. Especially at 25 â, the R2 in the calibration set basically reached 0.9. These observations indicated that portable Raman spectroscopy, a simple and easy-to-use detection technique, can monitor and predict the multiple quality indicators of fresh-cut Chinese yam combined with effectively PLSR model, which would be conducive to their applications in food industry.
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Dioscorea , Análisis de los Mínimos Cuadrados , Temperatura , Espectrometría RamanRESUMEN
BACKGROUND: Pathogenic variants in BRCA genes play a crucial role in the pathogenesis of ovarian cancer. Intronic variants of uncertain significance (VUS) may contribute to pathogenicity by affecting splicing. Currently, the significance of many intronic variants in BRCA has not been clarified, impacting patient treatment strategies and the management of familial cases. METHOD: A retrospective study was conducted to analyze BRCA intronic VUS in a cohort of 707 unrelated ovarian cancer patients at a single institution from 2018 to 2023. Three splicing predictors were employed to analyze detected intronic VUS. Variants predicted to have splicing alterations were selected for further validation through minigene assays. Patient and familial investigations were conducted to comprehend cancer incidence within pedigrees and the application of poly (ADP-ribose) polymerase inhibitors (PARPi) by the patients. In accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG), the intronic VUS were reclassified based on minigene assay results and clinical evidence. RESULT: Approximately 9.8% (69/707) of patients were identified as carriers of 67 different VUS in BRCA1/2, with four intronic variants accounting for 6% (4/67) of all VUS. Splicing predictors indicated potential splicing alterations in splicing for BRCA1 c.4358-2A>G and BRCA2 c.475+5G>C variants. Minigene assays utilizing the pSPL3 exon trapping vector revealed that these variants induced changes in splicing sites and frameshift, resulting in premature termination of translation (p. Ala1453Glyfs and p. Pro143Glyfs). According to ACMG guidelines, BRCA1 c.4358-2A>G and BRCA2 c.475+5G>C were reclassified as pathogenic variants. Pedigree investigations were conducted on patients with BRCA1 c.4358-2A>G variant, and the detailed utilization of PARPi provided valuable insights into research on PARPi resistance. CONCLUSION: Two intronic VUS were reclassified as pathogenic variants. A precise classification of variants is crucial for the effective treatment and management of both patients and healthy carriers.
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Proteína BRCA2 , Neoplasias Ováricas , Humanos , Femenino , Proteína BRCA2/genética , Proteína BRCA1/genética , Estudios Retrospectivos , Neoplasias Ováricas/genéticaRESUMEN
Heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) is considered a cancer-promoting heterogeneous nuclear ribonucleoprotein in many cancers, but its function in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. HnRNPAB was highly expressed in PDAC tissues compared to normal pancreatic tissues, and high expression of hnRNPAB was associated with poor overall survival and recurrence-free survival in PDAC patients. HnRNPAB promotes migration and invasion of PDAC cells in vitro. In xenograft tumor mouse models, hnRNPAB deprivation significantly attenuated liver metastasis. HnRNPAB mRNA and protein levels are positively associated with MYC in PDAC cells. Mechanistically, hnRNPAB bound to MYC mRNA and prolonged its half-life of MYC mRNA. HnRNPAB induced PDAC cells to secret CXCL8 via MYC, which promoted neutrophils recruitment and facilitated tumor cells entrancing into the hepatic parenchyma. These findings point to a novel regulatory mechanism via which hnRNPAB promotes PDAC metastasis. Implications: Hnrnpab participates in the post-transcriptional regulation of the oncogene MYC by binding and stabilizing MYC mRNA, thereby promoting liver metastasis in PDAC.
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BACKGROUND: Lingguizhugan (LGZG) decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet (HFD)-induced insulin resistance (IR) in animal studies. AIM: To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism. METHODS: To establish an IR rat model, a 12-wk HFD was administered, followed by a 4-wk treatment with LGZG. The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests. Using a targeted meta-bolomics platform to analyze changes in serum metabolites, quantitative real-time PCR (qRT-PCR) was used to assess the gene expression of the ribosomal protein S6 kinase beta 1 (S6K1). RESULTS: In IR rats, LGZG decreased body weight and indices of hepatic steatosis. It effectively controlled blood glucose and food intake while protecting islet cells. Metabolite analysis revealed significant differences between the HFD and HFD-LGZG groups. LGZG intervention reduced branched-chain amino acid levels. Levels of IR-related metabolites such as tryptophan, alanine, taurine, and asparagine decreased significantly. IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression, as shown by qRT-PCR. CONCLUSIONS: Our study strongly suggests that LGZG decoction reduces HFD-induced IR. LGZG may activate S6K1 via metabolic pathways. These findings lay the groundwork for the potential of LGZG as an IR treatment.