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BACKGROUND: Crohn's disease (CD) patients require varying levels of supportive care. In order to facilitate caregivers and nurses in precisely evaluating the caregiving requirements of these patients, we developed the CD-specific Care Needs Scale (CD-CNS). METHODS: This study employed a mixed-methods approach, integrating qualitative and quantitative methodologies. The initial items of the scale were developed through qualitative interviews, Delphi expert consultation, and literature review, while the final items were refined through clinical testing. Qualitative interviews were conducted based on the supportive care needs framework and Maslow's hierarchy of needs, and scale items were constructed through a literature search and qualitative interviews. The initial version of the scale with 45 items was obtained after the items were verified and modified by expert consultation. A total of 250 CD patients admitted to the gastroenterology department of a hospital in China were selected for verification of the initial version of the scale. A self-designed general questionnaire was used to obtain patients' medical history and sociodemographic data, and the Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) was used as the criterion. Exploratory factor analysis (EFA) was performed on the CD-CNS to evaluate the dimensions, factor structure, reliability, criterion validity, and construct validity. RESULTS: EFA identified 5 dimensions and retained 27 items with strong internal consistency reliability (α = 0.940). The Cronbach's α coefficients for each dimension ranged from 0.824 to 0.921. Criterion validity was assessed using Spearman's coefficient, which demonstrated a significant correlation with the IBDQ (P < 0.050). The test-retest reliability for each dimension after two weeks ranged from 0.655 to 0.895. CONCLUSIONS: We developed and validated a new scale that can be used to assess the care needs of CD patients. This new tool can guide the specific supportive care of CD patients. TRIAL REGISTRATION: This study was reviewed and approved by the Ethics Committee of the Second Hospital of Nanjing (2021-LS-ky-022). The study was duly registered and approved online through the Trial Center of the Second Hospital of Nanjing in 2021. Confidentiality was ensured by anonymizing all the data. The entire study process was conducted under the supervision of the Ethics Committee of Nanjing Second Hospital. Informed consent was obtained from the patients, and each patient volunteered and agreed to participate.
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Triple-negative breast cancer (TNBC) typically manifests as higher invasive carcinoma correlated with a worse prognosis that primarily relies on chemotherapy. There is growing evidence that nitric oxide (NO) donor drugs have the potential for anticancer therapy. On this basis, we constructed and evaluated a novel coumarin-furoxan hybrid 4A93 as an effective antitumor candidate drug. 4A93 exhibits low IC50 values in three TNBC cell lines and inhibits colony formation and DNA synthesis, probably due to the release of high concentrations of NO in mitochondria, which induces oxidative stress, mitochondrial dysfunction, and apoptosis. Further research suggests that 4A93 might destroy mitochondria by opening the mitochondrial permeability transition pore (mPTP), depolarizing the mitochondrial membrane potential (MMP), and promoting the release of cytochrome c into the cytoplasm. Intrinsic apoptosis is induced finally, along with Akt/Erk signaling suppression. Additionally, 4A93 underregulates the Epithelial-mesenchymal transition process to inhibit cell migration and invasion. In 4T1 subcutaneous and hematogenous models of mice, 4A93 therapy suppresses the tumor growth and prevented lung metastasis with favorable biosafety. Our results provide insights into 4A93 in TNBC treatment and validate the contribution of NO donors in tumor therapy.
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To improve the conventional germination process and improve the nutritional quality of red kidney beans, this study employed high-intensity ultrasound (HIU) supplemented with hydrogen peroxide as a pre-germination treatment. The results showed that the 350 W-10 min treatment yielded the highest germination rate (77.09%), with its sprout length 81.13% greater than that of the control group. The 350 W-10 min treatment increased total protein, soluble protein, and ash content, while simultaneously reducing the fat, starch, and soluble sugar content. The HIU treatment accelerated the accumulation of phenolic and flavonoid compounds, ascorbic acid, and γ-aminobutyric acid. The 350 W-10 min treatment also decreased the levels of phytic acid, trypsin inhibitor activity, and tannin by 42.71%, 65.58%, and 53.18%, respectively. Furthermore, ultrasonic cavitation enhanced antioxidative capacity and improved amino acid composition and protein digestibility. Consequently, HIU serves as a cost-efficient method to accelerate the germination process and enhance their nutritional composition.
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Germinación , Valor Nutritivo , Semillas/química , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Phaseolus/crecimiento & desarrollo , Phaseolus/química , Phaseolus/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Antioxidantes/química , Antioxidantes/análisis , Antioxidantes/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Aminoácidos/análisis , Ácido Ascórbico/análisis , Ácido Ascórbico/química , Fenoles/química , Fenoles/metabolismo , Fenoles/análisisRESUMEN
OBJECTIVES: To investigate the association between baseline hemoglobin level and early neurologic deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation (CASE-â ¡, NCT04487340). Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy, and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis. RESULTS: A total of 8162 patients were included. Patients with END had lower baseline hemoglobin levels (136 and 140 g/L, P<0.01) and higher rates of anemia (24.2% and 16.9%, P<0.01) compared with non-END patients. Binary logistic regression analysis showed that baseline hemoglobin level (OR=0.995, 95%CI: 0.991-0.999, P<0.05) and anemia (OR=1.238, 95%CI: 1.055-1.454, P<0.01) were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients. Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients (P<0.01), although this relationship was only significant in male patients (P<0.05) and not in female patients (P>0.05). CONCLUSIONS: There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis, especially in male patients, in whom both lower and higher hemoglobin level may increase the risk of END.
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Anemia , Hemoglobinas , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/sangre , Hemoglobinas/análisis , Terapia Trombolítica/efectos adversos , Anemia/etiología , Anemia/tratamiento farmacológico , Persona de Mediana Edad , Administración Intravenosa , Anciano , Modelos Logísticos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Isquemia Encefálica/tratamiento farmacológicoRESUMEN
The purpose of this study was to investigate the marital adjustment of patients with Crohn's disease and their spouses, and to analyze its influencing factors. It lays the investigation foundation for the follow-up binary study of Crohn's disease patients and their spouses. Using convenience sampling, 177 pairs of patients and their spouses from a tertiary hospital in Nanjing, China were selected. With face-to-face electronic questionnaires to survey the patient and spouse, the contents include the Lock-Wollance Marriage Adjustment Test, Subjective Well-Being Scale for Chinese Citizens, Couple Support Questionnaire, and Distress Self-Disclosure Scale. The marital adjustment score of patients was (99.03â ±â 24.25), and the marital adjustment score of spouses was (99.61â ±â 25.39). The proportions of patients with marital disorders and their spouses with marital disorders were 52.5% and 46.9%, respectively. Multiple linear regression showed that the spouse's age, family monthly income, time of diagnosis of Crohn's, distress self-disclosure, marital support, and subjective well-being were important factors influencing the marital adjustment of patients. Self-disclosure of spousal distress, marital support, age, and subjective well-being were important factors that influenced spouses' marital adjustment. Most couples with Crohn's disease have marital disorders, and their marital adjustment affects each other. However, the assessment results of one partner should not be limited to replacing those of the couple. In clinical practice, patient age, monthly family income, self-disclosure of distress, marital support, and subjective well-being should be considered. Spouses should be encouraged to participate in patient care and patient-spouse interventions should be implemented as a whole to improve marital stability.
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Enfermedad de Crohn , Esposos , Humanos , Matrimonio , Estudios de Seguimiento , Proyectos de Investigación , Adaptación PsicológicaRESUMEN
The construction of protein-based nano-gels as curcumin delivery system effectively enhances the stability and bioavailability of curcumin. In this study, acylation modification and self-assembly techniques were jointly employed to construct acylated kidney bean protein isolate (AKBPI)-nanogels. Optimal conditions for AKBPI-nanogels were determined to be pH 7, concentration of 2 mg/mL, and temperature at 90â for 30 min. The optimized AKBPI-nanogels exhibited excellent uniformity as evidenced by decreasing average particle size (137.35 nm) and polydispersity index (0.38). Acylation enhanced the intermolecular interactions within the nanogel by reducing the polarity of tyrosine microenvironment and free sulfhydryl groups. AKBPI-nanogels demonstrated remarkable characteristics in terms of pH sensitivity, salt concentration, and storage tolerance. The curcumin-loaded AKBPI-nanogels exhibited an encapsulation efficiency of 92.30 % and maintained high antioxidant activity. In simulated gastrointestinal digestion, AKBPI-nanogels facilitated the controlled release and higher bioavailability of curcumin. Therefore, AKBPI-nanogels can be a stable tool for delivering curcumin.
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Curcumina , Phaseolus , Nanogeles , Curcumina/química , Geles , Temperatura , Portadores de Fármacos/químicaRESUMEN
Ultrasonic-assisted precipitation was employed to sustainably isolate Fe in the hydrochloric acid lixivium of low-grade laterite for the synthesis of battery-grade iron phosphate. The recovery efficiency of Ni and Co exceeded 99%, while the removal efficiency of the Fe impurity reached a maximum of 95%. Precipitation parameters for the selective isolation of Fe (MgO precipitant, pH 1, 70-80 °C) were optimized and used in ultrasonic precipitation experiments. The use of ultrasonic waves in the precipitation process enhanced micromixing by reducing the size of primary grains and mitigating particle agglomeration, thereby significantly improving the purity of the isolated compound and providing high-quality iron phosphate (FePO4·2H2O). The LiFePO4/C composite prepared from as-precipitated FePO4 exhibited excellent electrochemical performance, with a discharge capacity of 149.7 mAh/g at 0.1 C and 136.3 mAh/g at 0.5 C after 100 cycles, retaining almost 100% cycling efficiency. This novel and facile method for iron removal from laterite acid lixivium not only efficiently removes excess iron impurities leached due to the poor selectivity of hydrochloric acid, but also enables the high-value utilization of these iron impurities. It enhances economic benefits while simultaneously alleviating environmental pressure.
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The COVID-19 pandemic highlights the urgent need to develop effective small-molecule antivirals. Thirty-three novel biaryl amide derivatives were synthesized and evaluated for anti-coronaviral activity. Some significant SARs were uncovered and the intensive structure modifications led to the most active compounds 8b and 8h. The broad-spectrum anti-coronaviral effects of 8h were validated at RNA and protein levels. 8h inhibits coronavirus replication at multiple stages, from virus entry to virus dsRNA synthesis. The mechanism of action showed that 8h may simultaneously act on 3CLpro and TMPRSS2 to display anti-coronaviral effects. 8h combined with RdRp inhibitor showed synergistic inhibitory activity against coronavirus. This study confirmed that biaryl amide derivatives may be a new class of potential therapeutic agents against coronavirus with multiple target effect, worthy of further investigation.
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COVID-19 , SARS-CoV-2 , Humanos , Amidas/farmacología , Pandemias , Antivirales/química , Inhibidores de Proteasas/farmacologíaRESUMEN
Ovalbumin (OVA), characterized by its high concentration in eggs, possesses remarkable foaming properties. Nevertheless, OVA is highly sensitive to thermal changes and acid-base conditions, substantially hampering its application potential for foaming purposes within the food industry. This experiment aimed to examine the effects of preheating and high-intensity ultrasound (HIU) treatment at different powers on OVA foaming properties and explore the underlying mechanisms. The results revealed that OVA exhibited the highest foaming capacity (31.5 %) and foaming stability (96.7 %) under the treatment condition of 200w + 60°C. Additionally, significant improvements were observed in the content of free sulfhydryl groups (37.27 µmg/g), solution viscosity (142.33 mPa·s), and surface hydrophobicity (37.27 µg BPB) under this condition. The absolute value of the zeta potential (-10.28 mV) was significantly increased in the 200w + 60°C treatment group. Moreover, the polymer dispersity index of OVA (0.6045) was significantly reduced, resulting in improved dispersion than the control group. The structural analysis revealed significant changes in the α-helix and ß-sheet content of OVA after treatment at 200w + 60 °C. The X-ray diffraction pattern exhibited sharper peaks, indicating a crystal structure, and the fluorescence peak displayed a slight blue shift along with increased hydrophobicity. Moreover, the preheating and HIU treatment induced a continuous uneven and irregular pore structure in OVA, which ultimately enhanced its foaming properties. In conclusion, the preheating and HIU treatment offers a novel approach to enhance the foaming properties of OVA.
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Ovalbúmina , Ovalbúmina/química , Interacciones Hidrofóbicas e Hidrofílicas , ViscosidadRESUMEN
Purpose: Intravenous thrombolysis has emerged as an effective approach to improve the long-term survival and functional status of patients with ischemic stroke. The aim of this study was to assess the impact of a national stroke project on the door-to-needle-time (DNT). Patients and Methods: The patients were divided into pre-construction and construction periods. Construction Measures were performed during the construction period. The DNT and onset-to-needle time (ONT) were compared in two period groups. Results: After participating in the National Stroke Center Project and effective measurements, the thrombolysis treatment metrics were improved significantly. The DNT (IQR) was shortened from 65.0 (54.5,85.0) minutes in the Pre-Construction period to 40.0 (33.0,53.0) minutes in the Construction period (p < 0.001). Similarly, the ONT was reduced from 157.0 (IQR) (115.0,184.0) minutes to 116.0 (87.8,170.0) minutes (p = 0.035). Conclusion: The DNT time and ONT time can be shortened by National Stroke Center Construction projects. More suitable hospitals should be encouraged to participate as the National Stroke Center.
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After the atmospheric hydrochloric acid leaching method is used to treat laterite ore and initially purify it, the extract that results often contains a significant amount of Fe2+ impurities. A novel metallurgical process has been proposed that utilizes microbubble aeration to oxidize Fe2+ ions in laterite hydrochloric acid lixivium, facilitating subsequent separation and capitalizing on the benefits of microbubble technology, including its expansive specific surface area, negatively charged surface attributes, prolonged stagnation duration, and its capacity to produce active oxygen. The study examined the impacts of aeration aperture, stirring speed, oxygen flow rate, pH value, and reaction temperature. Under optimized experimental conditions, which included an aeration aperture of 0.45 µm, stirring at 500 rpm, a bubbling flow rate of 0.4 L/min, pH level maintained at 3.5, and a temperature range of 75-85 °C, the oxidation efficiency of Fe2+ surpassed 99%. An analysis of the mass transfer process revealed that microbubble aeration markedly enhances the oxygen mass transfer coefficient, measured at 0.051 s-1. The study also confirmed the self-catalytic properties of Fe2+ oxidation and conducted kinetic studies to determine an apparent activation energy of 399 kJ/mol. At pH values below 3.5, the reaction is solely governed by chemical reactions; however, at higher pH values (>3.5), both chemical reactions and oxygen dissolution jointly control the reaction.
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Increasing rainstorms induced by climate change and modification in the land surface due to urbanization have greatly altered floods at different spatio-temporal scales. However, investigating flood events in urbanized plains is challenging as anthropogenic behaviors can change river flow without rainfall. In addition, while the frequency and magnitude of floods have been well examined, knowledge about variations in the rate of flood change is still limited. To fill these gaps, we proposed a scheme that focused on flood responses to rainfall to detect changes in flood characteristics in the Central Taihu Basin, a highly urbanized region in the Yangtze River Delta of China. Four characteristic metrics were adopted to summarize the flood hydrograph, including the peak, increment, rising rate, and falling rate. We then examined trends of these metrics based on the selected rainfall-flood events from ten hydrological stations during 1970-2020. Subsequently, the reduction method was used to separate the impacts of regional climate change and human activities on flood characteristics alterations. Furthermore, the importance of fifteen factors was quantified by the random forest model. We found that there is a significant upward trend in the evolution of flood characteristics, except for the increment of floods. Flood characteristics exhibit higher values when rainfall accumulates, indicating stronger responses of floods to a large amount of rainfall. The results also show that human activities dominate and impact the peak, rising rate, and falling rate of floods more than climate change. Meanwhile, although cumulative precipitation is the most important factor, flood characteristics are also susceptible to anthropogenic factors, such as land use change and hydraulic engineering construction. Our findings, which provide insights into flood event identification and enhance the understanding of regional flood changes, will serve as a reference for water resource management and flood mitigation in urbanized areas.
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With the advancement of urbanization, the structure and connectivity of river networks have been changed by the interference of human activities, resulting in a series of water environment problems. Numerous studies have indicated that river networks are associated with water quality; unfortunately, few studies have revealed the contributions of the structure and connectivity of river networks to variations in water quality. Taking one water conservancy region with dense and braided rivers on the Taihu Plain as an example, we depicted the spatial aggregations of water quality using the Getis-Ord Gi* index, quantified the variations in polluted regions using the standard deviational ellipse method, and quantified the influence of river density and connectivity on water quality during the different seasons. The results showed that (1) the water quality during the flood season was better than that during the non-flood season, especially in the western region; (2) the spatial aggregations of most water quality indicators were higher and the polluted regions increased in size during the flood period compared to the non-flood period; and (3) the relative contribution rates of the river density and connectivity exhibited mean values of 62.5% (61.2%) and 37.5% (38.8%) in the flood (non-flood) period. Our results provide theoretical support for enhancing water environment management.
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Ríos , Calidad del Agua , Humanos , Inundaciones , Estaciones del Año , UrbanizaciónRESUMEN
OBJECTIVE: To investigate DNA methylation (DNAm) status of dickkopf-associated protein 1 (DKK-1) in ossified hip capsule synovium and serum among patients with ankylosing spondylitis (AS). METHODS: Western blot was applied to detect the level of DKK-1 protein expression in hip joint capsule tissues from four patients with AS as well as four patients with femoral neck fracture (FNF) caused by trauma as control. DKK-1 gene promoter methylation (GPM) was examined by methylation-specific polymerase chain reaction. Reverse transcription-polymerase chain reaction was performed to examine the messenger RNA (mRNA) levels of DKK-1, ß-catenin, and Wnt3a in both tissue and serum. The DNAm status of serum DKK-1 was measured among 36 patients with AS and syndesmophytes (AS + syndesmophytes group), 40 patients with AS but no syndesmophyte (AS group), and 42 healthy individuals (control group). Also, the serum levels of DKK-1 were measured by enzyme-linked immunosorbent assay. The modified New York criteria (mNYC) together with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were adopted to examine the radiographic progression of AS. The receiver operating characteristic (ROC) curve was applied to investigate the diagnostic value of the methylation rate of DKK-1 with regard to radiographic progression. RESULTS: The expressions of DKK-1 protein and mRNA in hip joint capsule tissues of AS patients were significantly lower, while DKK-1 GPM rate, ß-catenin mRNA, and Wnt3a mRNA were markedly higher when compared with FNF group. For serum samples, the DKK-1 methylation rate was significantly higher in AS+ syndesmophytes group in contrast to AS group and healthy controls. Serum levels of DKK-1 protein and mRNA in AS with syndesmophytes group were markedly decreased, while ß-catenin mRNA and Wnt3a mRNA expressions were significantly increased than AS with no syndesmophyte group and the healthy control group. AS patients in Grade 4 showed a significantly higher serum DKK-1 GPM rate than those in Grade 3 based on mNYC. Serum DKK-1 GPM level was markedly and positively correlated with mSASSS. Serum levels of DKK-1 in AS+ syndesmophytes group were markedly lower compared with AS but no syndesmophyte group and healthy controls. ROC curve analysis indicated that serum DKK-1 methylation rate serves as a decent indicator for AS radiographic progression. CONCLUSION: DNAm of DKK-1 may correlate with pathological bone formation in AS, which may provide new strategies for the treatment of AS abnormal bone formation.
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Espondilitis Anquilosante , Humanos , beta Catenina/genética , Metilación de ADN , Osteogénesis , Columna Vertebral/patología , Espondilitis Anquilosante/genéticaRESUMEN
Background: Cervical cancer is a common leading cause of cancer related to women death worldwide. Cylindromatosis (CYLD) is known as an important tumor suppressor in various human cancers, and a deubiquitination enzyme (DUB) as well. Previously, we identified Skp2 as an E3 ligase of Aurora B ubiquitination, but the DUB of Aurora B still remains unknown. Methods: Aurora B ubiquitination site is identified through in vivo ubiquitination assay. Activity of Aurora B and CENPA was detected by immunoblotting (IB) and immunofluorescence (IF) assay. Protein-to-protein interaction was investigated by immunoprecipitation (IP). Cell chromosome dynamics was monitored by live-cell time-lapse Imaging. Cancer cell proliferation, colony formation, apoptosis, and cell invasion and migration assays were also performed. Protein level was checked by immunohistochemical (IHC) staining in clinical cervical cancer samples. Results: We identified Lysine 115 (K115) as the main Aurora B ubiquitination site for Skp2. We could also detect an interaction of Aurora B with the DUB CYLD. We found that CYLD promoted deubiquitination of Aurora B, and regulated Aurora B activity and function as well. Compared with control, we found it took more time for the cells to finish cell mitosis with CYLD over-expression. Furthermore, we found that CYLD deficiency promoted cervical cancer cell proliferation, colony formation, cell migration and invasion, and inhibited apoptosis instead, whereas it is just opposite with CYLD over-expression. In clinical cervical cancer samples, we showed a negative correlation of CYLD expression with Aurora B activation and histological cancer cell invasion. Furthermore, there was less CYLD abundance and higher Aurora B activity in advanced cancer samples compared with early stage. Conclusions: Our findings uncover CYLD as a novel potential DUB of Aurora B, which inhibits Aurora B activation and its subsequent function in cell mitosis, and also provide more evidence for its tumor suppressor function in cervical cancer.
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River connectivity, which is key to the function of the river network, is deteriorating in highly urbanized areas. While previous studies have identified changes in the structure and connectivity of river networks, few studies have described the network structure of river connectivity and revealed the effects of urbanization on network structure. To this end, we detected the network structure and stability of river connectivity from a novel perspective of complex network theory. Taking the Taihu Plain as an example, we found that 1) the node degree of the river network was moderate (2.9), and the hub and connectivity were low (0.21 and 0.19, respectively). The hub and connectivity of the river network in the Yang-Cheng-Dian-Mao (YCDM) region were better than that in Wu-Cheng-Xi-Yu (WCXY) and Hang-Jia-Hu (HJH) regions. 2) The destruction of important nodes led to a dramatic decrease in the stability of river network connectivity. The river network structures on the Taihu Plain, HJH, WCXY, and YCDM were severely damaged when the removal rate of river network nodes exceeded 5 %, 7 %, 16 %, and 22 %, respectively. 3) The spatial response of the river network to urbanization was mainly negative, especially in highly urbanized regions. The effects of urbanization on network characteristics could be sorted as node degree (45 %), hub (21 %), and connectivity (18 %). Our results would provide theoretical support for the recognition, protection, and restoration of the river network in rapidly urbanizing regions.
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Weather system are spatially and temporally dependent, and these dependencies can result in flood events with similar behaviors. While it is well known that urbanization profoundly impacts the flood generation process, much less is known about the impacts of urbanization on the spatial dependence of floods, a major determinant of flood risk severity. To this end, a scheme was proposed to detect the flood dependence variations influenced by urbanization. Based on the scheme, we found that 1) the flood dependence can be weakened with extreme rainfall increasing from a short return period to a long return period; 2) The flood dependencies can be amplified in slightly urbanized regions and mitigated in highly urbanized regions due to intensifying urbanization. In addition, the change characteristics of the flood dependencies influenced by urbanization are first identified from the perspective of network structure. We found that urbanization can significantly affect the network structure (i.e., hub and connectivity) of flood dependence, especially in highly urbanized regions. The catchments with high hub and connectivity are prone to widespread floods and should be given more attention in flood warning and control management work, which can contribute to helping defend against floods in hazard-prone areas.
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Inundaciones , Urbanización , Tiempo (Meteorología) , Análisis EspacialRESUMEN
Thinopyrum intermedium possesses many desirable agronomic traits that make it a valuable genetic source for wheat improvement. The precise identification of individual chromosomes of allohexaploid Th. intermedium is a challenge due to its three sub-genomic constitutions with complex evolutionary ancestries. The non-denaturing fluorescent in situ hybridization (ND-FISH) using tandem-repeat oligos, including Oligo-B11 and Oligo-pDb12H, effectively distinguished the St, J and JS genomes, while Oligo-FISH painting, based on seven oligonucleotide pools derived from collinear regions between barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.), was able to identify each linkage group of the Th. intermedium chromosomes. We subsequently established the first karyotype of Th. intermedium with individual chromosome recognition using sequential ND-FISH and Oligo-FISH painting. The chromosome constitutions of 14 wheat-Th. intermedium partial amphiploids and addition lines were characterized. Distinct intergenomic chromosome rearrangements were revealed among Th. intermedium chromosomes in these amphiploids and addition lines. The precisely defined karyotypes of these wheat-Th. intermedium derived lines may be helpful for further study on chromosome evolution, chromatin introgression and wheat breeding programs.
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Genomic alteration can reshape tumor microenvironment to drive tumor malignancy. However, how PTEN deficiency influences microenvironment-mediated cell-cell interactions in glioblastoma (GBM) remains unclear. Here, we show that PTEN deficiency induces a symbiotic glioma-M2 macrophage interaction to support glioma progression. Mechanistically, PTEN-deficient GBM cells secrete high levels of galectin-9 (Gal-9) via the AKT-GSK3ß-IRF1 pathway. The secreted Gal-9 drives macrophage M2 polarization by activating its receptor Tim-3 and downstream pathways in macrophages. These macrophages, in turn, secrete VEGFA to stimulate angiogenesis and support glioma growth. Furthermore, enhanced Gal-9/Tim-3 expression predicts poor outcome in glioma patients. In GBM models, blockade of Gal-9/Tim-3 signaling inhibits macrophage M2 polarization and suppresses tumor growth. Moreover, α-lactose attenuates glioma angiogenesis by down-regulating macrophage-derived VEGFA, providing a novel antivascularization strategy. Therefore, our study suggests that blockade of Gal-9/Tim-3 signaling is effective to impair glioma progression by inhibiting macrophage M2 polarization, specifically for PTEN-null GBM.
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Glioblastoma , Glioma , Línea Celular Tumoral , Galectinas/genética , Galectinas/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Macrófagos/metabolismo , Neovascularización Patológica/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Microambiente TumoralRESUMEN
Intrahepatic cholangiocarcinoma (iCC) is a serious liver cancer threatening human health. However, there are a few chemotherapeutic drugs for the treatment of iCC in the clinic. It is extremely urgent to develop new drugs for iCC. In this study, twenty dinitroazetidine and coumarin hybrids were synthesized and evaluated anti-iCC bioactivity as a new type of nitric oxide (NO) donors. Among them, compounds 2-5 and 21 showed a higher antiproliferative activity against RBE cell lines (human intrahepatic cholangiocarcinoma cell lines) and low cytotoxicity in nontumor cells (HOSEpiC and T29). The preliminary study of pharmacology mechanism indicated that compounds 2-5 and 21 could release effective concentration of NO in RBE cell lines, which leaded to inhibit the proliferation of RBE cell lines. The research results revealed that compound 3 inhibited the proliferation of RBE cell lines by inducing apoptosis and arresting cell cycle at G2/M phase. Additionally, compound 3 had acceptable metabolic stability. Therefore, compound 3 was merited to further explore for developing a desirable NO donor lead with anti-iCC activity.