RESUMEN
Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta-(ethylene glycol) to form three new side-chain-braided (SCB) CPs: PCz2S-OCt, PCz2S-EG, and PCz2S-PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S-PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small- and wide-angle X-ray scattering (SAXS/WAXS) analyses reveal that these three SCB-CPs form cross-linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S-PEG demonstrates the best HER, reaching up to 126.9 µmol h-1 in pure water-based photocatalytic solution. Moreover, PCz2S-PEG exhibits comparable performance in seawater-based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation-dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S-PEG under light illumination.
RESUMEN
BACKGROUND: Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. PURPOSE: To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. MATERIAL AND METHODS: All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. RESULTS: In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). CONCLUSION: It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.
Asunto(s)
Medios de Contraste , Neoplasias de la Vesícula Biliar , Vesícula Biliar , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Adulto , Vesícula Biliar/diagnóstico por imagen , Estudios Retrospectivos , Anciano de 80 o más Años , Nomogramas , Intensificación de Imagen Radiográfica/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , RadiómicaRESUMEN
The current bottleneck in the development of efficient photocatalysts for hydrogen evolution is the limited availability of high-performance acceptor units. Over the past nine years, dibenzo[b,d]thiophene sulfone (DBS) has been the preferred choice for the acceptor unit. Despite extensive exploration of alternative structures as potential replacements for DBS, a superior substitute remains elusive. In this study, a symmetry-breaking strategy was employed on DBS to develop a novel acceptor unit, BBTT-1SO. The asymmetric structure of BBTT-1SO proved beneficial for increasing multiple moment and polarizability. BBTT-1SO-containing polymers showed higher efficiencies for hydrogen evolution than their DBS-containing counterparts by up to 166 %. PBBTT-1SO exhibited an excellent hydrogen evolution rate (HER) of 222.03â mmol g-1 h-1 and an apparent quantum yield of 27.5 % at 500â nm. Transient spectroscopic studies indicated that the BBTT-1SO-based polymers facilitated electron polaron formation, which explains their superior HERs. PBBTT-1SO also showed 14 % higher HER in natural seawater splitting than that in deionized water splitting. Molecular dynamics simulations highlighted the enhanced water-PBBTT-1SO polymer interactions in salt-containing solutions. This study presents a pioneering example of a substitute acceptor unit for DBS in the construction of high-performance photocatalysts for hydrogen evolution.
RESUMEN
Conjugated polymers (CPs) have recently gained increasing attention as photocatalysts for sunlight-driven hydrogen evolution. However, they suffer from insufficient electron output sites and poor solubility in organic solvents, severely limiting their photocatalytic performance and applicability. Herein, solution-processable all-acceptor (A1 -A2 )-type CPs based on sulfide-oxidized ladder-type heteroarene are synthesized. A1 -A2 -type CPs showed upsurging efficiency improvements by two to three orders of magnitude, compared to their donor-acceptor -type CP counterparts. Furthermore, by seawater splitting, PBDTTTSOS exhibited an apparent quantum yield of 18.9% to 14.8% at 500 to 550 nm. More importantly, PBDTTTSOS achieved an excellent hydrogen evolution rate of 35.7 mmol h-1 g-1 and 150.7 mmol h-1 m-2 in the thin-film state, which is among the highest efficiencies in thin film polymer photocatalysts to date. This work provides a novel strategy for designing polymer photocatalysts with high efficiency and broad applicability.
RESUMEN
BACKGROUND: Cervical cancer microenvironment is involved in the regulation of the behavior, morphology, and mechanical properties of the cervical cancer cells. Integrins expressed on the cell membrane combine with the factors of the microenvironment to determine cervical cancer cells' properties. The mechanical properties of integrin-extracellular matrix (ECM) interactions are important for the mechanotransduction of cervical cancer cells. However, the quantified study on the adhesion force and binding probabilities between collagen and integrins on cervical cancer cells grown on different stiffness substrates have not been reported. METHODS: Polyacrylamide (PA) gel was used as substrate to mimic the mechanical microenvironment of cancer cells. ImageJ software was used to measure the perimeter and area of the cells. SiHa cells were stained with FITC phalloidine to observe the cytoskeleton. Atomic force microscopy (AFM) was used to measure the cell mechanical properties. RESULT: The perimeters of SiHa cells grown on different stiffness substrates were 63.4 ± 1.3, 102.8 ± 4.0, and 152.6 ± 4.1 µm, for soft, intermediate, and stiff substrates, respectively. These areas were 277.2 ± 13.3, 428.9 ± 26.0, and 1166.0 ± 63.2 µm2, for soft, intermediate, and stiff substrates, respectively. The Young's modulus of SiHa cells grown on stiff substrates (3.0 ± 0.02 kPa) was higher compared with those on soft substrates (0.6 ± 0.01 kPa) or intermediate substrates (bimodal distribution, 1.36 and 1.67 kPa). The adhesion force between the functionalized probe and SiHa cells grown on glass (55.65 ± 0.78 pN) was significantly greater than that on stiff (47.03 ± 0.85 pN), intermediate (34.07 ± 0.58 pN) and soft (27.94 ± 0.47 pN) substrates. The binding probabilities of the collagen-integrin of the four rigid substrates were significantly differed. CONCLUSION: The changes in substrate stiffness can obviously regulate SiHa cells' mechanical properties, such as the Young's modulus. The adhesion force and binding probabilities of SiHa cells both increased with increasing substrate strength.
Asunto(s)
Mecanotransducción Celular , Neoplasias del Cuello Uterino , Colágeno/química , Módulo de Elasticidad/fisiología , Femenino , Humanos , Integrinas , Microscopía de Fuerza Atómica , Microambiente TumoralRESUMEN
Effect of temperature on synthesis of Clavulanic acid (CA) and impurity substance G during fermentation by Streptomyces clavuligerus were investigated. Results show that fermentation at 24 °C is the most favorable for CA synthesis though the fermentation duration was 20-30 hours longer than fermentation at 26 and 28 °C. Meanwhile, the impurity substance G was only 110 mg/L in the end broth of fermentation at 24 °C, which was significantly lower than 148 and 180 mg/L of fermentation at 26 and 28 °C, respectively. Correlation of specific growth rate and CA synthesis was statistically analyzed based on data of 10 batches of industrial fermentation. Two temperature-shift strategies were investigated in 50 L fermenter. Fermentation with 26-24 °C temperature strategy achieved 5097 mg/L CA titer, meanwhile the fermentation duration was shortened 24 hours comparing with fermentation at constant 24 °C. Fermentation with 26-24 °C control strategy was validated in a 60 m3 industrial fermenter, in which 4960 mg/L of CA was achieved while impurity G substance was decreased to titer 65 mg/L from 200 to 300 mg/L of normal production.
Asunto(s)
Streptomyces , Ácido Clavulánico/farmacología , Fermentación , TemperaturaRESUMEN
BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) is an important cofactor ensuring intracellular redox balance, anabolism and cell growth in all living systems. Our recent multi-omics analyses of glucoamylase (GlaA) biosynthesis in the filamentous fungal cell factory Aspergillus niger indicated that low availability of NADPH might be a limiting factor for GlaA overproduction. RESULTS: We thus employed the Design-Build-Test-Learn cycle for metabolic engineering to identify and prioritize effective cofactor engineering strategies for GlaA overproduction. Based on available metabolomics and 13C metabolic flux analysis data, we individually overexpressed seven predicted genes encoding NADPH generation enzymes under the control of the Tet-on gene switch in two A. niger recipient strains, one carrying a single and one carrying seven glaA gene copies, respectively, to test their individual effects on GlaA and total protein overproduction. Both strains were selected to understand if a strong pull towards glaA biosynthesis (seven gene copies) mandates a higher NADPH supply compared to the native condition (one gene copy). Detailed analysis of all 14 strains cultivated in shake flask cultures uncovered that overexpression of the gsdA gene (glucose 6-phosphate dehydrogenase), gndA gene (6-phosphogluconate dehydrogenase) and maeA gene (NADP-dependent malic enzyme) supported GlaA production on a subtle (10%) but significant level in the background strain carrying seven glaA gene copies. We thus performed maltose-limited chemostat cultures combining metabolome analysis for these three isolates to characterize metabolic-level fluctuations caused by cofactor engineering. In these cultures, overexpression of either the gndA or maeA gene increased the intracellular NADPH pool by 45% and 66%, and the yield of GlaA by 65% and 30%, respectively. In contrast, overexpression of the gsdA gene had a negative effect on both total protein and glucoamylase production. CONCLUSIONS: This data suggests for the first time that increased NADPH availability can indeed underpin protein and especially GlaA production in strains where a strong pull towards GlaA biosynthesis exists. This data also indicates that the highest impact on GlaA production can be engineered on a genetic level by increasing the flux through the pentose phosphate pathway (gndA gene) followed by engineering the flux through the reverse TCA cycle (maeA gene). We thus propose that NADPH cofactor engineering is indeed a valid strategy for metabolic engineering of A. niger to improve GlaA production, a strategy which is certainly also applicable to the rational design of other microbial cell factories.
Asunto(s)
Aspergillus niger/genética , Aspergillus niger/metabolismo , Coenzimas/metabolismo , Glucano 1,4-alfa-Glucosidasa/biosíntesis , Ingeniería Metabólica , Biosíntesis de Proteínas , Coenzimas/genética , NADP/metabolismo , Vía de Pentosa FosfatoRESUMEN
Aspergillus niger is widely used as a cell factory for homologous and heterologous protein production. As previous studies reported that reduced sporulation favors protein secretion in A. niger, in this study, we conducted a comparative genomic analysis of the non-sporulating industrially exploited A. niger strain LDM3 in China and the reference protein secretion strain CBS 513.88 to predict the key genes that might define the genetic basis of LDM3's high protein-producing potential in silico. After sequencing using a hybrid approach combining Illumina and PacBio sequencing platforms, a high-quality genome sequence of LDM3 was obtained which harbors 11,209 open reading frames (ORFs). LDM3 exhibits large chromosomal rearrangements in comparison to CBS 513.88. An alignment of the two genome sequences revealed that the majority of the 457 ORFs uniquely present in LDM3 possessed predicted functions in redox pathways, protein transport, and protein modification processes. In addition, bioinformatic analyses revealed the presence of 656 ORFs in LDM3 with non-synonymous mutations encoding for proteins related to protein translation, protein modification, protein secretion, metabolism, and energy production. We studied the impact of two of these on protein production in the established lab strain N402. Both tupA and prpA genes were selected because available literature suggested their involvement in asexual sporulation of A. niger. Our co-expression network analysis supportively predicted the role of tupA in protein secretion and the role of prpA in energy generation, respectively. By knockout experiments, we showed that the ΔtupA mutant displayed reduced sporulation (35%) accompanied by higher total protein secretion (65%) compared to its parental strain. Such an effect was, however, not observed in the ΔprpA mutant.
Asunto(s)
Aspergillus niger/genética , Proteínas Fúngicas/genética , Genómica , Vías Secretoras/genética , Biología Computacional , Simulación por Computador , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Genoma Fúngico , Transporte de Proteínas , Análisis de Secuencia de ADNRESUMEN
Microarray expression profiles of lncRNAs and mRNAs were investigated in HepG2 cells treated with 20 µg/ml ginsenoside Rh2 as well as in ginsenoside Rh2-untreated cells. Microarray analysis showed 618 upregulated lncRNAs and 161 downregulated lncRNAs in HepG2 cells treated with ginsenoside Rh2 compared with the control group. Moreover, three differentially expressed lncRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This may be beneficial to patients as an anti-cancer treatment and potentially provide novel targets for HCC (hepatocellular carcinoma) therapy.
Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Ginsenósidos/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Análisis por Micromatrices/métodos , ARN Largo no Codificante/análisis , Carcinoma Hepatocelular/genética , Ontología de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , ARN Largo no Codificante/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de SeñalRESUMEN
Objective: Although duloxetine has been approved for clinical therapy for diabetic peripheral neuropathic pain, the exact mechanism underlying the anti-allodynic effects in rat models of diabetes mellitus remains obscure. We attempted to identify whether duloxetine exerts anti-allodynic effects via inhibition of the TLR4-Myd88-dependent pathway in diabetic neuropathic pain (DNP) rats. Methods: An animal model of type 1 diabetic neuropathic pain was induced by intraperitoneal streptozotocin in 108 rats randomized into four groups: control, DNP, solvent control + DNP, and DNP + duloxetine. The DNP model establishment was validated, providing the MWT and TWL measurements were less than 80% of the baseline value on d14 after streptozotocin administration. The expressions of TLR4, Myd88, and NF-κB in the spinal dorsal horn were determined 21 days after streptozotocin injection by immunohistochemical assay and Western blot. Results: The results revealed that MWT and TWL in DNP, SC + DNP, and DLX + DNP groups were significantly decreased 14 days after STZ administration vs control (P < 0.05), while the pain thresholds in the DLX + DNP group were partially reversed. The expressions of TLR4, Myd88, and NF-κB in groups C, DNP, and SC + DNP were significantly increased, whereas duloxetine administration significantly downregulated the expressions of TLR4, Myd88, and NF-κB (P < 0.05). Conclusions: Our findings indicated that duloxetine mitigated mechanical and thermal withdrawal thresholds in STZ-injected rats and rescued the overexpression of the TLR4-Myd88-dependent pathway in the spinal dorsal horn in these rats. Whether these changes directly contributed to the reduction of thermal and mechanical withdrawal behavior needs to be further explored.
Asunto(s)
Analgésicos/farmacología , Neuropatías Diabéticas/metabolismo , Clorhidrato de Duloxetina/farmacología , Umbral del Dolor/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Animales , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Neuropatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Ratas , Asta Dorsal de la Médula Espinal/efectos de los fármacosRESUMEN
BACKGROUND: Serum amyloid A (SAA) was involved in the pathogenesis of glucocorticoid resistance in lung diseases. However, their association with systemic corticosteroid insensitivity in chronic rhinosinusitis with nasal polyps (CRSwNP) patients remains to be assessed. METHODS: This study enrolled 32 CRSwNP patients to evaluate the association between SAA expression in NP and corticosteroid insensitivity, and the value of polyp SAA level for predicting the response to oral corticosteroids in CRSwNP patients. All patients were given a course of oral prednisone (30 mg daily for 2 weeks) and subdivided into glucocorticoid(GC)-sensitive and -insensitive subgroup according to the change in polyp size scores. The polyp specimens were obtained before and after corticosteroid treatment. SAA levels in polyp tissues were evaluated by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. Regression analysis was performed to analyze the association between SAA protein levels and corticosteroid insensitivity. RESULTS: 13/32 (40.62%) CRSwNP patients were insensitive to the oral corticosteroid therapy. SAA mRNA and protein levels were significantly increased in GC-insensitive NP compared to those in GC-sensitive NP. Tissue SAA protein levels were positively correlated with tissue neutrophil numbers. Regression analysis revealed tissue SAA levels were significantly correlated with corticosteroid insensitivity (P < 0.01). ROC curves indicated that the area under the curve was 0.87. When the polyp SAA protein level was 122.2 ng/ml or higher, the sensitivity and specificity were 76.92 and 73.68%, respectively. CONCLUSIONS: Our findings suggest that increased SAA in NP is associated with reduced response to oral corticosteroids in CRSwNP. SAA levels in NP may have potential value in predicting corticosteroid insensitivity in CRSwNP patients.
Asunto(s)
Antiinflamatorios/uso terapéutico , Resistencia a Medicamentos , Pólipos Nasales/tratamiento farmacológico , Prednisona/uso terapéutico , Rinitis/tratamiento farmacológico , Proteína Amiloide A Sérica/metabolismo , Sinusitis/tratamiento farmacológico , Administración Oral , Adulto , Biomarcadores/sangre , Enfermedad Crónica , Esquema de Medicación , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/sangre , Pólipos Nasales/complicaciones , Proyectos Piloto , Rinitis/sangre , Rinitis/complicaciones , Sinusitis/sangre , Sinusitis/complicaciones , Insuficiencia del TratamientoRESUMEN
Proliferation of anchorage-dependent cells occurs after adhesion to a suitable surface. Thus, quantitative information about the force of cells adhesion to microcarriers at early culture phases is vital for scaling up such system. In this work, a newly designed shear-generating device was proposed, based on a previously proposed contraction flow device designed for suspended cells. A design equation for the new device was also proposed to correlate the generated energy dissipation rate (EDR) with the cross-sectional area and flow rate. Microscopic-particle image velocimetry was measured to validate the simulation results, and good agreement was achieved. The newly designed device was then used to measure the adhesion force of MDCK and PK cells, and the results showed that the critical EDR was 3000 W/m3 for MDCK and 5000 W/m3 for PK cells. This quantitative information is of great value for better understanding shearing effects during the scaling up of anchorage-dependent cell cultures.
Asunto(s)
Hidrodinámica , Modelos Biológicos , Resistencia al Corte , Animales , Adhesión Celular , Perros , Células de Riñón Canino Madin Darby , PorcinosRESUMEN
Colorectal cancer is a common malignant tumor with high incidence affecting the digestive system. This study aimed to identify the key genes relating to prognosis of colorectal cancer and to construct a prognostic model for its risk evaluation. Gene expression profiling of colorectal cancer patients, GSE17537, was downloaded from Gene Expression Omnibus database (GEO). A total of 55 samples from patients ranging from stages 1 to 4 were available. Differentially expressed genes were screened, with which single factor survival analysis was performed to identify the response genes. Interacting network and KEGG enrichment analysis of responsive genes were performed to identify key genes. In return, Fisher enrichment analysis, literature mining, and Kaplan-Meier analysis were used to verify the effectiveness of the prognostic model. The 20-gene model generated in this study posed significant influences on the prognoses (P = 9.691065e-09). Significance was verified via independent dataset GSE38832 (P = 9.86581e-07) and GSE17536 (P = 2.741e-08). The verified effective 20-gene model could be utilized to predict prognosis of patients with colorectal cancer and would contribute to post-operational treatment and follow-up strategies. J. Cell. Biochem. 118: 3675-3685, 2017. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Modelos Genéticos , Neoplasias Colorrectales/metabolismo , HumanosRESUMEN
Background Atypical choroid plexus papilloma (APP) is a rare, newly introduced entity with intermediate characteristics. To date, few reports have revealed the magnetic resonance (MR) findings. Purpose To analyze the clinicopathological and MR features of APP. Material and Methods The clinicopathological data and preoperative MR images of six patients with pathologically proven APP were retrospectively reviewed. The MR features including tumor location, contour, signal intensity, degree of enhancement, intratumoral cysts, and necrosis; and flow voids, borders, peritumoral edema, and associated hydrocephalus were analyzed. Results The APP were located in the ventricle (n = 4) and cerebellopontine angle (CPA, n = 2). Tumor dissemination along the spinal subarachnoid space was found in one patient. The tumors appeared as milt-lobulated (n = 5) or round mass (n = 1), with slightly heterogeneous signals (n = 5) or mixed signals (n = 1) on T1-weighted and T2-weighted images. Heterogeneous and strong enhancement were found in five cases on contrast-enhanced images. Three of four intraventricular tumors had a partly blurred border with ventricle wall. Four tumors had mild to moderate extent of surrounding edema signals. A slight hydrocephalus was seen in four patients. Incomplete capsule was seen in four tumors at surgery. Histopathologically, mild nuclear atypia was seen in all tumors with a mitotic rate of 2-5 per 10 high-power fields. Conclusion APP should be included in the differential diagnosis when an intraventricular or CPA tumor appearing as a multi-lobulated solid mass with slight heterogeneity, heterogeneous strong enhancement, partly blurred borders, mild to moderate peritumoral edema, or slight hydrocephalus are present.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Papiloma del Plexo Coroideo/diagnóstico por imagen , Papiloma del Plexo Coroideo/patología , Adulto , Medios de Contraste , Diagnóstico Diferencial , Femenino , Gadolinio DTPA , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
MicroRNAs (miRNAs), which are characterized by highly conserved and small non-coding RNAs, have been a hot spot regarding biological processes such as cellular proliferation, apoptosis and metabolism as well as cellular differentiation, signal transduction and carcinogenesis. MiRNA-106a (miR-106a), a member of the miR-17 family, has been validated to be aberrantly regulated in the diversity of tumors. The purpose of this review is supposed to deliver an intricate overview of miR-106a, including its role in cell proliferation, apoptosis, cell cycle, invasion and metastasis, involvement in drug resistance as well as its interactions with the target proteins and signaling pathways involved.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias/genética , Animales , Proliferación Celular , Resistencia a Antineoplásicos , Humanos , MicroARNs/análisis , MicroARNs/metabolismo , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Transducción de SeñalRESUMEN
The aim of this paper is to investigate the general approximation structure, weak approximation operators, and Pawlak algebra in the framework of fuzzy lattice, lattice topology, and auxiliary ordering. First, we prove that the weak approximation operator space forms a complete distributive lattice. Then we study the properties of transitive closure of approximation operators and apply them to rough set theory. We also investigate molecule Pawlak algebra and obtain some related properties.
Asunto(s)
Algoritmos , Modelos TeóricosRESUMEN
OBJECTIVE: The aim of this study was to assess the prognostic significance of α-1,3-mannitrotransferase (ALG3) in triple-negative breast cancer (TNBC) and investigate its impact and potential mechanism on the efficacy of anti-PD-1 therapy. METHODS: Bioinformatics analysis was used to examine the expression of ALG3 in cancer patients using UACLAN and other databases. The associations of the ALG3 gene and the clinicopathological features of breast cancer were examined with bc-GenExMiner database. Correlation between ALG3 expression and survival was further established utilizing the Kaplan-Meier Plotter database. Immunohistochemistry (IHC) was used to analyze the expression of ALG3 in cohort of breast cancer patients from Hubei cancer hospital to confirmed the prognostic value of ALG3 in TNBC. The effect of ALG3 on the levels of infiltrating immune cells was also analyzed. And the mutation module within cBioPortal was utilized to visualize ALG3 mutations in BRCA. The CRISPR/Cas9 technique was used to establish ALG3 low-expression TNBC cell lines. Influence of ALG3 expression on cancer cell proliferation and chemotherapeutic responsiveness was scrutinized in vitro. Animal models were constructed to evaluate the alteration of tumor sensitivity to anti-PD-1 therapy with decreased ALG3 expression. And flow cytometry and IHC were used to investigate the tumor immune microenvironment. Association of PD-L1 Glycosylation and ALG3 expression were also investigated by western blot. RESULTS: ALG3 expression was elevated in TNBC and was strikingly linked to unfavorable clinical features such as lymphatic node metastasis, high NPI, advanced stage and age, etc. Furthermore, high ALG3 expression was associated with shorter OS in TNBC patients. Mechanistically, ALG3 expression was negatively correlated with the infiltration of CD8+ T cells, CD4+ T cells, and NK cells. ALG3-KO cells had increased sensitivity to chemotherapeutic agents. In animal models, the volume of ALG3-KO tumors was lower than the control group with immunotherapy. ALG3-KO tumors showed an increased proportion of CD8+ T cells, while a decreased proportion of regulatory T cells and M2-type macrophages. The expression level of PD-L1 protein was not affected by ALG3 level, but the glycosylation level was significantly decreased in tumor. Similarly, the glycosylation level of PD-L1 is reduced in ALG3-KO cell in vitro. Additionally, ALG3 knockout lead to reduced tolerance of tumor cells to IFN-γ, thereby enhancing the efficacy of immunotherapy. CONCLUSION: ALG3 is a potential biomarker for poor prognosis of TNBC and may reduce the efficacy of immunotherapy by modulating the tumor microenvironment and glycosylation of PD-L1.
RESUMEN
Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles published in or before June 2023 using PubMed, Google Scholar, and Web of Science. The searched keywords in scientific databases were ferroptosis, cancer, tumor, traditional Chinese medicine, botanical drugs, and phytomedicine. Only research related to ferroptosis, the metabolites from TCM, and cancer was considered. In this review, we introduce an overview of the current knowledge regarding the ferroptosis mechanisms and review the research advances on the metabolites of TCM inhibiting cancer by targeting ferroptosis.
RESUMEN
Our purpose was to develop and evaluate the clinical outcomes of a nursing plan as a rooming-in practice for enhanced recovery of women with preeclampsia following a cesarean section. The authors developed a postoperative enhanced recovery nursing plan as a rooming-in practice for women with preeclampsia based on summarizing evidence-based best practices. The authors used convenience sampling to select women with preeclampsia after a cesarean section from the obstetrics department of a Class A tertiary hospital in Nanjing, China, as the participants in our study. There were 30 women in the experimental group. The postoperative enhanced recovery nursing care plan was formulated for five postoperative time points and incorporated management of blood pressure, temperature, and fluids, as well as monitoring of complications, pain management, activity and rest, diet management, and breastfeeding. The control group consisted of 30 women who received routine nursing care and health education. The authors compared levels of maternal self-efficacy, breastfeeding efficacy, anxiety, pain scores, and deep vein thrombosis (DVT) prevention compliance before and after the intervention. Women in the experimental group had a self-efficacy score of 7.5 ± 0.63, which was higher than that in the control group (5.4 ± 0.85); they had a higher breastfeeding efficacy score of 7.13 ± 0.68 when compared to the control group (4.23 ± 0.86); the anxiety score was 6.7 ± 1.62, which was lower than that in the control group (10.03 ± 1.87); and the pain score was lower at 3.26 ± 0.52 when compared to the control group (3.83 ± 0.83). All the differences were statistically significant (P < 0.05). Postoperative blood pressure was controlled within the target range, and the rate of DVT prevention compliance increased in the experimental group. The implementation of a postoperative enhanced recovery nursing intervention for women with preeclampsia as part of the rooming-in practice was effective in helping manage the blood pressure, pain, and fluids of women with preeclampsia, improved their postoperative self-management ability and breastfeeding efficacy, reduced their anxiety levels, improved their compliance with the prevention of related complications, and ultimately promoted enhanced postoperative recovery, thereby guaranteeing the safety of mothers and newborns.