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A mixed oxidant of chlorine dioxide (ClO2) and NaClO was often used in water treatment. A novel UVA-LED (365 nm)-activated mixed ClO2/NaClO process was proposed for the degradation of micropollutants in this study. Carbamazepine (CBZ) was selected as the target pollutant. Compared with the UVA365/ClO2 process, the UVA365/ClO2/NaClO process can improve the degradation of CBZ, with the rate constant increasing from 2.11×10-4 sec-1 to 2.74×10-4 sec-1. In addition, the consumption of oxidants in the UVA365/ClO2/NaClO process (73.67%) can also be lower than that of UVA365/NaClO (86.42%). When the NaClO ratio increased, both the degradation efficiency of CBZ and the consumption of oxidants can increase in the UVA365/ClO2/NaClO process. The solution pH can affect the contribution of NaClO in the total oxidant ratio. When the pH range of 6.0-8.0, the combination process can generate more active species to promote the degradation of CBZ. The change of active species with oxidant molar ratio was investigated in the UVA365/ClO2/NaClO process. When ClO2 acted as the main oxidant, HO⢠and Cl⢠were the main active species, while when NaClO was the main oxidant, ClO⢠played a role in the system. Both chloride ion (Cl-), bicarbonate ion (HCO3-), and nitrate ion (NO3-) can promote the reaction system. As the concentration of NaClO in the reaction solution increased, the generation of chlorates will decrease. The UVA365/ClO2/NaClO process can effectively control the formation of volatile disinfection by-products (DBPs), and with the increase of ClO2 dosage, the formation of DBPs can also decrease.
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Carbamazepina , Compuestos de Cloro , Óxidos , Rayos Ultravioleta , Contaminantes Químicos del Agua , Purificación del Agua , Carbamazepina/química , Contaminantes Químicos del Agua/química , Compuestos de Cloro/química , Purificación del Agua/métodos , Óxidos/química , Cinética , Hipoclorito de Sodio/química , Modelos QuímicosRESUMEN
PWD (pine wilt disease) is a devastating forest disease caused by the Bursaphelenchus xylophilus, which is the major invasive species in Asian and European countries. To control this disease, fumigation, pesticide injection, and clear cutting of epidemic trees have been widely used. But these management strategies have many limitations in terms of the effectiveness and environmental impacts, especially for the overuse of chemical pesticides. Thus, PCs (phytochemicals), the various compounds extracted from plants, have drawn extensive attention owing to their special characteristics, including abundant sources, low toxicity, high efficacy, and easy degradation. This review provides an overview of the current status of using PCs as alternative approaches to manage PWD. It discusses the efficacy of various PCs, the factors influencing their nematicidal activity, and their mechanism of action against B. xylophilus. These results will reveal the application of PCs in combating these devastating diseases and the necessity for further research.
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BACKGROUND AND PURPOSE: Regorafenib was approved by the US Food and Drug Administration (FDA) for hepatocellular carcinoma (HCC) patients showing progress on sorafenib treatment. However, there is an inevitably high rate of drug resistance associated with regorafenib, which reduces its effectiveness in clinical treatment. Thus, there is an urgent need to find a potential way to solve the problem of regorafenib resistance. The metabolite of disulfiram complexed with copper, the Diethyldithiocarbamate-copper complex (CuET), has been found to be an effective anticancer drug candidate. In the present study, we aimed to evaluate the effect of CuET on regorafenib resistance in HCC and uncover the associated mechanism. EXPERIMENTAL APPROACH: Regorafenib-resistant HCC strains were constructed by applying an increasing concentration gradient. This study employed a comprehensive range of methodologies, including the cell counting kit-8 (CCK-8) assay, colony formation assay, cell cycle analysis, wound healing assay, Transwell assay, tumor xenograft model, and immunohistochemical analysis. These methods were utilized to investigate the antitumor activity of CuET, assess the combined effect of regorafenib and CuET, and elucidate the molecular mechanism underlying CuET-mediated regorafenib resistance. KEY RESULTS: The inhibitory effect of regorafenib on cell survival, proliferation and migration was decreased in regorafenib-resistant MHCC-97H (MHCC-97H/REGO) cells compared with parental cells. CuET demonstrated significant inhibitory effects on cell survival, proliferation, and migration of various HCC cell lines. CuET restored the sensitivity of MHCC-97H/REGO HCC cells to regorafenib in vitro and in vivo. Mechanistically, CuET reverses regorafenib resistance in HCC by suppressing epithelial-mesenchymal transition (EMT) through inhibition of the ERK signaling pathway. CONCLUSION AND IMPLICATIONS: Taken together, the results of this study demonstrated that CuET inhibited the activation of the ERK signaling pathway, leading to the suppression of the epithelial-mesenchymal transition (EMT) and subsequently reversing regorafenib resistance in HCC both in vivo and in vitro. This study provides a new idea and potential strategy to improve the treatment of regorafenib-resistant HCC.
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OBJECTIVE: To analyze patient satisfaction with letter-based communication of lung cancer screening (LCS) pulmonary nodule results. STUDY DESIGN: Prospective randomized controlled trial of LCS between May and December 2019. METHODS: All participants came from a prospective randomized controlled study on pulmonary nodule results in LCS with low-dose CT (LDCT) to analyze patient satisfaction, perception of information received via letters, preferred methods of receiving results, and dissatisfaction-related characteristics. RESULTS: A total of 153 patients were detected to have pulmonary nodules among 600 recruited participants in the lung cancer high-risk group screened using LDCT. Most of the patients were satisfied with receiving pulmonary nodule results via letters (78.4%; n = 120) and agreed that the letters contained an appropriate amount of information (83.7%; n = 128). Univariate logistic regression analysis revealed that satisfaction was related to age (OR, 0.905; 95% CI, 0.832-0.985), education level (OR, 0.367; 95% CI, 0.041-3.250), no family history of cancer (OR, 0.100; 95% CI, 0.011-0.914), and the number of nodules (OR, 6.028; 95% CI, 1.641-22.141). Of the patients who reported dissatisfaction with letter-based communication (7.2%; n = 11), the most common reasons cited were that they contained insufficient patient education materials and that it was difficult to comprehend the medical terminology. The majority of participants (61.4%; n = 94) reported that they would prefer the letter-based communication. No correlation was identified between satisfaction and gender, smoking status, alcohol consumption, risk factors, nodule size, or nodule location. CONCLUSIONS: Patients were generally satisfied with receiving their LCS pulmonary nodule results via letters, reporting that the letters included adequate information about their diagnosis and follow-up steps. This may provide a basis for feasible result communication via letters for cancer screening programs in underdeveloped regions in China.
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Neoplasias Pulmonares , Satisfacción del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estudios Prospectivos , Anciano , Detección Precoz del Cáncer , Comunicación , Tomografía Computarizada por Rayos X , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/patología , Correspondencia como Asunto , China , AdultoRESUMEN
The pharmacological mechanism of Phellodendri Chinensis cortex (PCC) against diseases, especially bladder cancer (BC), has never been reported systematically. This study was designed to explore potential mechanism of PCC in treatment of BC. First, we used network pharmacology to discover the potential mechanism of Phellodendri Chinensis cortex and phellodendrine against bladder cancer. Then, we used bioinformatics analysis to verify the correlation between gene expression analysis, survival analysis and common targets. Finally, molecular docking was used to calculate the binding energies of phellodendrine and common targets.A total of 264 targets for PCC were predicted, and 391 BC-related targets were obtained from 4 databases. There were 54 potential targets, 315 biological processes, and 120 signaling pathways involved for PCC against BC. The CDKN2A expression increased and the ESR1, JUN, IL6, AR, and PTGS2 levels decreased in BC according to Gene Expression Profiling Interactive Analysis version 2. The high expression of JUN, MYC, EGFR, and EGF and low expression of VEGFA and PPARG were associated with short overall survival (OS). The high expression of AKT1, EGFR, and EGF and low expression of IL1ß were associated with poor disease-free survival (DFS). The search of the intersection of phellodendrine and BC targets yielded 11 common targets, 50 biological processes, and 13 signaling pathways involved. High AURKA and FASN and low ESR1, JUN, ABCB1, and PTGS1 were expressed in BC. The high expression of FASN, ABCC1, PTGS1, JUN, and PIK3CA was associated with short OS, the high expression of PIK3CA and ABCC1 was associated with poor DFS prognosis. Phellodendrine showed a better binding affinity for PTGS2 protein with a docking score of -7.183 and a MM-GBSA result of -46.47 kcal/mol. This study revealed potential mechanism of PCC and phellodendrine against BC through network pharmacology and bioinformatics.
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Chlorella has a variety of biological activities, and it is worth further exploring its pharmacological effects. In this study, we investigated the antioxidant and anti-ageing activities of Chlorella polysaccharide extract (CPE). Further studies revealed that CPE exhibited anti-ageing, and antioxidant activities in vivo, including an extended Caenorhabditis elegans stress resistance, decreased deposition of lipofuscin, and reduced effects of amyloid ß protein on mobility, decreased levels of reactive oxygen species and increased activity of antioxidant enzymes. Moreover, it dramatically increased the expression of anti-stress and longevity genes and reduced the expression of ageing-related genes; therefore, it was hypothesised that the mechanism of the age-delaying effect of CPE was related to the insulin signalling pathway. In summary, CPE could delay ageing and provide a new avenue for the application and development of CPE.
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To examine the influence of Body Mass Index (BMI) on laparoscopic gastrectomy (LG) short-term and long-term outcomes for gastric cancer. A retrospective analysis was conducted on gastric cancer patients undergoing LG at the Third Hospital of Nanchang City from January 2013 to January 2022. Based on WHO BMI standards, patients were categorized into normal weight, overweight, and obese groups. Factors such as operative time, intraoperative blood loss, postoperative complications, and overall survival were assessed. Across different BMI groups, it was found that an increase in BMI was associated with longer operative times (average times: 206.22 min for normal weight, 231.32 min for overweight, and 246.78 min for obese), with no significant differences noted in intraoperative blood loss, postoperative complications, or long-term survival among the groups. The impact of BMI on long-term survival following LG for gastric cancer was found to be insignificant, with no notable differences in survival outcome between different BMI groups. Although higher BMI is associated with increased operative time in LG for gastric cancer, it does not significantly affect intraoperative blood loss, postoperative complications, recovery, or long-term survival. LG is a feasible treatment choice for obese patients with gastric cancer.
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Índice de Masa Corporal , Gastrectomía , Laparoscopía , Complicaciones Posoperatorias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Gastrectomía/métodos , Gastrectomía/efectos adversos , Masculino , Laparoscopía/métodos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Tempo Operativo , Obesidad/complicaciones , Obesidad/cirugía , Adulto , Pérdida de Sangre QuirúrgicaRESUMEN
Krypton chloride (KrCl*) excimer lamps (222 nm) are used as a promising irradiation source to drive ultraviolet-based advanced oxidation processes (UV-AOPs) in water treatment. In this study, the UV222/peracetic acid (PAA) process is implemented as a novel UV-AOPs for the degradation of emerging contaminants (ECs) in water. The results demonstrate that UV222/PAA process exhibits excellent degradation performance for carbamazepine (CBZ), with a removal rate of 90.8 % within 45 min. Notably, the degradation of CBZ in the UV222/PAA process (90.8 %) was significantly higher than that in the UV254/PAA process (15.1 %) at the same UV dose. The UV222/PAA process exhibits superior electrical energy per order (EE/O) performance while reducing resource consumption associated with the high-energy UV254/PAA process. Quenching experiments and electron paramagnetic resonance (EPR) detection confirm that HO⢠play a dominant role in the reaction. The contributions of direct photolysis, HOâ¢, and other active species (RO⢠and 1O2) are estimated to be 5 %, 88 %, and 7 %, respectively. In addition, the effects of Cl-, HCO3-, and humic acid (HA) on the degradation of CBZ are evaluated. The presence of relatively low concentrations of Cl-, HCO3-, and HA can inhibit CBZ degradation. The UV222/PAA oxidation process could also effectively degrade several other ECs (i.e., iohexol, sulfamethoxazole, acetochlor, ibuprofen), indicating the potential application of this process in pollutant removal. These findings will propel the development of the UV222/PAA process and provide valuable insights for its application in water treatment.
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Ácido Peracético , Fotólisis , Rayos Ultravioleta , Contaminantes Químicos del Agua , Purificación del Agua , Contaminantes Químicos del Agua/química , Ácido Peracético/química , Purificación del Agua/métodos , Carbamazepina/química , Oxidación-ReducciónRESUMEN
Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants, the elderly, and immune-compromised patients. While a half-life extended monoclonal antibody and 2 vaccines have recently been approved for infants and the elderly, respectively, options to prevent disease in immune-compromised patients are still needed. Here, we describe spiro-azetidine oxindoles as small molecule RSV entry inhibitors displaying favorable potency, developability attributes, and long-acting PK when injected as an aqueous suspension, suggesting their potential to prevent complications following RSV infection over a period of 3 to 6 months with 1 or 2 long-acting intramuscular (IM) or subcutaneous (SC) injections in these immune-compromised patients.
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Antivirales , Azetidinas , Oxindoles , Infecciones por Virus Sincitial Respiratorio , Compuestos de Espiro , Humanos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Animales , Oxindoles/química , Oxindoles/farmacología , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Compuestos de Espiro/farmacocinética , Compuestos de Espiro/administración & dosificación , Antivirales/farmacología , Antivirales/química , Antivirales/administración & dosificación , Azetidinas/química , Azetidinas/farmacología , Azetidinas/administración & dosificación , Azetidinas/farmacocinética , Profilaxis Pre-Exposición/métodos , Inyecciones Intramusculares , Indoles/química , Indoles/administración & dosificación , Indoles/farmacología , Inyecciones Subcutáneas , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Internalización del Virus/efectos de los fármacosRESUMEN
Monolithic distributed Bragg reflector (DBR) cavity which directly integrates fiber Bragg gratings (FBGs) into the photosensitive RE-doped fibers is a promising configuration in constructing compact and efficient single frequency fiber lasers (SFFLs). Yet, the doping level of rare-earth (RE) ions has generally to be sacrificed in the classical Ge-photosensitized RE-doped silica fibers because of the dramatic refractive index increase caused by the introduction of Ge. Here, we demonstrate an approach to realize the trade-off between photosensitivity and RE doping concentration. We validate that the addition of a small amount of cerium (0.37wt.%) instead of Ge could photosensitize Yb3+-doped silica fiber (YDF), while maintaining fiber numerical aperture (NA) at 0.12 under a high 2.5-wt.% Yb doping level. Based on the short monolithic DBR cavity constructed by this germanium-free photosensitive highly YDF, a 1064â nm fiber laser with a 48.6% slope efficiency and an over 200â mW power on two orthogonally polarized modes could be realized. Further stable and linear-polarized 1064â nm SFFL is also demonstrated in a designed monolithic polarization maintaining cavity with an output power of 119â mW and an efficiency of 26.4%. Our results provide an alternative way to develop photosensitive highly RE-doped fibers towards monolithic laser cavity application.
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BACKGROUND: The technology of capturing circulating tumor cells (CTCs) plays a crucial role in the diagnosis, evaluation of therapeutic efficacy, and prediction of prognosis in lung cancer. However, the presence of complex blood environment often results in severe nonspecific protein adsorption and interferences from blood cells, which negatively impacts the specificity of CTCs capture. There is a great need for development of novel nanomaterials for CTCs capture with prominent anti-nonspecific adsorptions from proteins or blood cells. RESULTS: We present a novel immune magnetic probe Fe3O4@(PEI/AA)4@Apt. The surface of Fe3O4 particles was modified with four layers of PEI/AA composite by layer-by-layer assembly. Furthermore, aptamers targeting epithelial marker EpCAM (SYL3C) and mesenchymal marker CSV (ZY5C) were simultaneously connected on Fe3O4@(PEI/AA)4 to improve the detection of different phenotypic CTCs and reduce false negatives. The results demonstrated that the (PEI/AA)4 coatings not only minimized non-specific protein adsorptions, but also significantly reduced the adsorption rate of red blood cells to a mere 1 %, as a result of which, the Fe3O4@(PEI/AA)4@Apt probe achieved a remarkably high capture efficiency toward CTCs (95.9 %). In the subsequent validation of clinical samples, the probe was also effective in capturing rare CTCs from lung cancer patients. SIGNIFICANCE AND NOVELTY: A (PEI/AA) polymerized composite with controllable layers was fabricated by layer-by-layer self-assembly technique, which displayed remarkable anti-nonspecific adsorption capabilities toward proteins and cells. Importantly, Fe3O4@(PEI/AA)4@Apt probe significantly improved CTCs capture purity in lung cancer patients to 89.36 %. For the first time, this study combined controllable (PEI/AA) layers with magnetic separation to innovatively build a resistant interface that significantly improves the specific capture performances of CTCs, broadening the application of this polymerized composite.
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Alginatos , Células Neoplásicas Circulantes , Polietileneimina , Humanos , Células Neoplásicas Circulantes/patología , Polietileneimina/química , Alginatos/química , Nanopartículas de Magnetita/química , Neoplasias Pulmonares/patología , Aptámeros de Nucleótidos/química , Adsorción , Propiedades de Superficie , Molécula de Adhesión Celular Epitelial/inmunologíaRESUMEN
Circulating tumor cells (CTCs) are widely considered as a reliable and promising class of markers in the field of liquid biopsy. As CTCs undergo epithelial-mesenchymal transition (EMT), phenotype detection of heterogeneous CTCs based on EMT markers is of great significance. In this report, an integrated analytical strategy that can simultaneously capture and differentially detect epithelial- and mesenchymal-expressed CTCs in bloods of non-small cell lung cancer (NSCLS) patients is proposed. First, a commercial biomimetic polycarbonate (PCTE) microfiltration membrane is employed as the capture interface for heterogenous CTCs. Meanwhile, differential detection of the captured CTCs is realized by preparing two distinct CdTe quantum dots (QDs) with red and green emissions, attached with EpCAM and Vimentin aptamers, respectively. For combined analysis, a polydimethylsiloxane (PDMS) chip with simple structure is designed, which integrates the membrane capture and QDs-based phenotype detection of CTCs. This chip not only implements the analysis of the number of CTCs down to 2 cells mL-1, but enables EMT process tracking according to the specific signals of the two QDs. Finally, this method is successfully applied to inspect the correlations of numbers or proportions of heterogenous CTCs in 94 NSCLS patients with disease stage and whether there is distant metastasis.
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Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.
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Autofagia , Herpesvirus Humano 3 , Neuronas , Humanos , Herpesvirus Humano 3/fisiología , Herpesvirus Humano 3/patogenicidad , Neuronas/virología , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Replicación Viral , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Infección por el Virus de la Varicela-Zóster/virología , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Línea Celular , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Interacciones Huésped-PatógenoRESUMEN
Welded steel plates are widely used in various structural applications, and the presence of inclined welds is often encountered in practical scenarios. Carbon fiber reinforced polymer (CFRP) has been proven to be effective for strengthening steel structures. However, the behavior of CFRP-strengthened welded steel plates with inclined welds, particularly considering the influence of welding residual stress, is limited. This paper aims to investigate the tensile behavior of CFRP-strengthened welded Q355 steel plates with inclined welds considering welding residual stress (WRS). First, WRS data were obtained by the X-ray diffraction (XRD) method at different locations. The maximum tensile and compressive residual stresses are 0.39 and 0.14 times the yield strength of the steel, respectively. Then, finite element models were established to investigate the effects of weld angles, weld width, and height on the WRS distribution of welded steel plates. Finally, the tensile performance of CFRP-strengthened welded plates with WRS was studied by numerical simulation. The results showed that the weld angles have little effect on the distribution pattern of residual stress but significantly affect the peak tensile WRS. When the weld angle changes from 0° to 60°, the peak tensile WRS decreases significantly from 0.32 to 0.06 times the yield strength of steel; furthermore, the influence of weld width and height on WRS is relatively limited. Under tension loading, the maximum stress occurs near the weld. The ends of the weld enter the yielding state later than the middle part of the weld due to the distribution of the WRS. As the weld angle increases and the length of the weld increases, the stress in the weld zone decreases, while the stress in the base material zone correspondingly increases. In addition, CFRP strengthening can reduce the magnitude of stress. This study provides preliminary references for understanding the tensile behavior of CFRP-strengthened welded steel plates with inclined welds.
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Indole acetic acid (IAA) as a plant hormone, was one of the valuable products of anaerobic fermentation. However, the enriching method remained unknown. Moreover, whether zero valent iron (ZVI) could enhance IAA production was unexplored. In this work, IAA producing bacteria Klebsiella (63 %) was enriched successfully. IAA average production rate and concentration were up to 3 mg/L/h and 56 mg/L. With addition of 1 g/L ZVI, IAA average production rate and concentration was increased for 2 and 3 folds. Mechanisms indicated ZVI increased Na+K+-ATP activity and electron transport activity for 2 folds and 1 fold. Moreover, macro transcription determined indole pyruvate pathway activity like primary-amine oxidase, indole pyruvate decarboxylase and aldehyde dehydrogenase were increased for 146 %, 187 %, and 557 %, respectively. Therefore, ZVI was suitable for enhancement IAA production from mixed culture anaerobic fermentation.
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Fermentación , Ácidos Indolacéticos , Hierro , Triptófano , Ácidos Indolacéticos/metabolismo , Triptófano/metabolismo , Anaerobiosis , Hierro/metabolismo , Klebsiella/metabolismoRESUMEN
This study presents the development of an in-situ background-free Raman fiber probe, employing two customized double-cladding anti-resonant hollow-core fibers (AR-HCFs). The Raman background noise measured in the AR-HCF probe is lower than that of a conventional multi-mode silica fiber by two orders of magnitude. A plug-in device for fiber coupling optics was designed that was compatible with a commercially available confocal Raman microscope, enabling in-situ Raman detection. The numerical aperture (NA) of both AR-HCF claddings exceeds 0.2 substantially enhancing the collection efficiency of Raman signals at the distal end of the fiber probe. The performance of our Raman fiber probe is demonstrated by characterizing samples of acrylonitrile-butadiene-styrene (ABS) plastics, alumina ceramics, and ethylene glycol solution.
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Varicose veins of the lower extremities (VVLEs) are prevalent globally. This study aims to identify prognostic factors and develop a prediction model for recurrence survival (RS) in VVLEs patients after surgery. A retrospective analysis of VVLEs patients from the Third Hospital of Nanchang was conducted between April 2017 and March 2022. A LASSO (Least Absolute Shrinkage and Selection Operator) regression model pinpointed significant recurrence predictors, culminating in a prognostic nomogram. The model's performance was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). The LASSO regression identified seven predictors for the nomogram predicting 1-, 2-, and 5-year RS. These predictors were age, body mass index (BMI), hypertension, diabetes, the Clinical Etiological Anatomical Pathophysiological (CEAP) grade, iliac vein compression syndrome (IVCS), and postoperative compression stocking duration (PCSD). The nomogram's C-index was 0.716, with AUCs (Area Under the Curve scores) of 0.705, 0.725, and 0.758 for 1-, 2-, and 5-year RS, respectively. Calibration and decision curve analyses validated the model's predictive accuracy and clinical utility. Kaplan-Meier analysis distinguished between low and high-risk groups with significant prognostic differences (P < 0.05). This study has successfully developed and validated a nomogram for predicting RS in patients with VVLEs after surgery, enhancing personalized care and informing clinical decision-making.
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Nomogramas , Várices , Humanos , Pronóstico , Estudios Retrospectivos , Extremidad Inferior , Várices/cirugíaRESUMEN
The cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification. This facilitates ER membrane curvature and STING trafficking to Golgi. Notably, we identify two cholesterol-binding motifs in STING and confirm their contribution to ER-retention of STING. Consequently, depletion of intracellular cholesterol levels enhances STING pathway activation upon cGAMP stimulation. In a preclinical tumour model, intratumorally administered cholesterol depletion therapy potentiated STING-dependent anti-tumoral responses, which, in combination with anti-PD-1 antibodies, promoted tumour remission. Collectively, we demonstrate that ER cholesterol sets a threshold for STING signalling through cholesterol-binding motifs in STING and we propose that this could be exploited for cancer immunotherapy.
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Proteínas de la Membrana , Neoplasias , Humanos , Proteínas de la Membrana/metabolismo , Transducción de Señal/fisiología , Interferones/metabolismo , Nucleotidiltransferasas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo , Retículo Endoplásmico/metabolismo , Microambiente TumoralRESUMEN
Meloidogyne javanica is one of the most widespread and economically important sedentary endoparasites. In this study, a comparative transcriptome analysis of M. javanica between pre-parasitic second-stage juveniles (Pre-J2) and parasitic juveniles (Par-J3/J4) was conducted. A total of 48,698 unigenes were obtained, of which 18,826 genes showed significant differences in expression (p < 0.05). In the differentially expressed genes (DEGs) from transcriptome data at Par-J3/J4 and Pre-J2, a large number of unigenes were annotated to the C-type lectin (CTL, Mg01965), the cathepsin L-like protease (Mi-cpl-1), the venom allergen-like protein (Mi-mps-1), Map-1 and the cellulase (endo-ß-1,4-glucanase). Among seven types of lectins found in the DEGs, there were 10 CTLs. The regulatory roles of Mj-CTL-1, Mj-CTL-2 and Mj-CTL-3 in plant immune responses involved in the parasitism of M. javanica were investigated. The results revealed that Mj-CTL-2 could suppress programmed cell death (PCD) triggered by Gpa2/RBP-1 and inhibit the flg22-stimulated ROS burst. In situ hybridization and developmental expression analyses showed that Mj-CTL-2 was specifically expressed in the subventral gland of M. javanica, and its expression was up-regulated at Pre-J2 of the nematode. In addition, in planta silencing of Mj-CTL-2 substantially increased the plant resistance to M. javanica. Moreover, yeast co-transformation and bimolecular fluorescence complementation assay showed that Mj-CTL-2 specifically interacted with the Solanum lycopersicum catalase, SlCAT2. It was demonstrated that M. javanica could suppress the innate immunity of plants through the peroxide system, thereby promoting parasitism.