ABSTRACT
Perovskite quantum dots (PQDs) have attracted emerging attention as fluorescent and light-absorbing materials for next-generation optoelectronics due to their outstanding properties and cost-efficiency. However, PQD thin film suffers significant instability due to structure and material failures, which hinders their application in flexible and reliable PQD-based advanced wearable devices. Herein, we use commercial cellulose fiber-based filter paper as a substrate to synthesize PQDs in situ and fabricate PQD-paper free-standing flexible composite film. The abundant hydroxy capping ligands of cellulose fibers and the unique dense network structure of the filter paper can facilitate confined crystallization, forming strong interactions between the PQDs and substrate, the unpackaged PQD composite film showed extraordinary stability (>30 days) in the air with high humidity (90%). Meanwhile, the strong interaction between PQDs and paper enables an ultrasimple drop-cast synthesis process with excellent process tolerance, making it customizable and easy to scale up (10 cm in diameter). Due to the uniformly dispersed PQDs on cellulose fibers of the substrate, the composite demonstrates impressive photo-responsive properties. Photodetector (PD) arrays were designed on free-standing PQD paper and flexible graphitic electrodes, and circuits were fabricated by drawing. The PD arrays can work as optical and electrical dual-mode image sensors with incredible bending robustness, enduring up to 100,000 cycles at 180°.
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Immunogenic cell death (ICD) is a newly discovered form of cellular demise that triggers adaptive immune responses mediated by T cells. However, the immunogenic cell death-related lncRNAs (ICDRLs) involved in bladder cancer (BC) development and progression remain to be further elucidated. Molecular profiling data and clinicopathological information for BC patients were obtained from TCGA, and the ICDRGs list was obtained from published literature. For the identification of ICDRLs, Pearson co-expression analysis was performed, and a prognostic signature based on 13 ICDRLs was constructed by univariate assays and LASSO assays. Herein, an ICDRLSig consisting of 13 ICDRLs was constructed. KM curves and ROC curves demonstrated that the constructed signature in the TCGA training, testing, entire and external sets have good predictive performance. Multivariate assays illuminated that the signature is an independent predictor for BC patients' OS, exhibiting greater predictive power for the survival than traditional clinicopathological features. Additionally, patients in the high-ICDRLSig risk subgroup had more abundant immune infiltration, higher immune checkpoint gene expression, lower TMB and poorer response to immunotherapy. We have developed a novel ICDRLSig that can be exploited for survival prediction and provide a reference for further individualized treatment.
Subject(s)
Gene Expression Regulation, Neoplastic , Immunogenic Cell Death , RNA, Long Noncoding , Tumor Microenvironment , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/mortality , RNA, Long Noncoding/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Prognosis , Female , Male , Biomarkers, Tumor/genetics , Gene Expression Profiling , Middle Aged , ROC Curve , Aged , Kaplan-Meier EstimateABSTRACT
Leaf mass per area (LMA) is a key structural parameter that reflects the functional traits of leaves and plays a vital role in simulating the material and energy cycles of plant ecosystems. In this study, vertical whorl-by-whorl sampling of LMA was conducted in a young Larix principis-rupprechtii plantation during the growing season at the Saihanba Forest Farm. The vertical and seasonal variations in LMA were analysed. Subsequently, a predictive model of LMA was constructed. The results revealed that the LMA varied significantly between different crown whorls and growing periods. In the vertical direction of the crown, the LMA decreased with increasing crown depth, but the range of LMA values from the tree top to the bottom was, on average, 30.4 g/m2, which was approximately 2.5 times greater in the fully expanded phase than in the early leaf-expanding phase. During different growing periods, the LMA exhibited an allometric growth trend that increased during the leaf-expanding phase and then tended to stabilize. However, the range of LMA values throughout the growing period was, on average, 40.4 g/m2. Among the univariate models, the leaf dry matter content (LDMC) performed well (adjusted determination coefficient (Ra2) = 0.45, root mean square error (RMSE) = 13.48 g/m2) in estimating the LMA. The correlation between LMA and LDMC significantly differed at different growth stages and at different vertical crown whorls. The dynamic predictive model of LMA constructed with the relative depth in the crown (RDINC) and date of the year (DOY) as independent variables was reliable in both the assessments (Ra2 = 0.68, RMSE = 10.25 g/m2) and the validation (absolute mean error (MAE) = 8.05 g/m2, fit index (FI) = 0.682). Dynamic simulations of crown LMA provide a basis for elucidating the mechanism of crown development and laying the foundation for the construction of an ecological process model.
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Metal organic framework (MOF)-derived nanostructures display remarkable characteristics and have broad application potential. Os@ZIF-8 nanocomposites were prepared by a depositional method. The Os nanoparticles distributed on the surface of ZIF-8. The nanocomposites displayed enhanced peroxidase-like activity with smaller Km for both 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 compared to Os NPs due to the confinement effect and large surface area that ZIF-8 provided. From the average reaction rate constants obtained from three different temperatures, the activation energy values were determined. The kinetic data indicated that the Os@ZIF-8 NCs are catalytically more active than Os NPs. In addition, quantitative measurement of Hg2+ was performed based on the formation of Os-Hg alloy. Os@ZIF-8 NCs had a wide detection range between 0 µM and 71.43 µM for Hg2+ with a limit of detection (LOD) of 2.29 µM. Using a MOF with a large surface area to load Os nanoparticles to achieve enhanced nanozyme activity is the novelty of this work.
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A large area of coarse-grained saline soil is distributed in saline soil areas, and chlorine saline soil with a high salt content is a typical representative. The dynamic resilient modulus was accurately predicted using the California-bearing ratio (CBR) value to determine the relationship between the dynamic resilient modulus of coarse-grained chloride saline soil and its CBR value. Indoor dynamic triaxial tests and CBR tests were conducted to investigate the evolution of the dynamic resilient modulus (MR) and CBR of coarse-grained chlorine saline soil under the influence of the stress level, water content, and salt content. The test results showed that the dynamic resilient modulus increased with an increase in the confining pressure and bulk stress and decreased as the deviator stress increased; however, the CBR increased with an increase in the corresponding unit pressure. The higher the salt and water contents, the more obvious the influence of stress on the dynamic resilient modulus and CBR value. Under the same stress level, the decrease in the dynamic resilient modulus and CBR gradually increased with increasing salt and moisture content, and the effect of salt tended to be more significant than that of water. Based on the correlation between the dynamic resilient modulus and CBR revealed by the experiment, a more widely applicable model was selected from the existing theoretical models related to CBR for the regression analysis of the test data, and a prediction model of the dynamic resilient modulus based on the CBR value was proposed (MR = 21.06CBR0.52). This prediction model had a high correlation coefficient (R2 = 0.893) and could effectively predict the dynamic resilient modulus of coarse-grained chlorine saline soil using CBR values. The results provide a simple and reliable method for determining the design parameters of a coarse-grained saline soil subgrade.
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In this study, fcSe@TiO2 and [Cu2I2(fcSe)2]n@TiO2 nanosystems based on ferrocenylselenoether and its cuprous cluster were developed and characterized by X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray spectroscopy (EDX), and electron paramagnetic resonance (EPR). Under optimized conditions, 0.2 g L-1 catalyst, 20 mM H2O2, and initial pH 7, good synergistic visible light photocatalytic tetracycline degradation and Cr(vi) reduction were achieved, with 92.1% of tetracycline and 64.5% of Cr(vi) removal efficiency within 30 minutes. Mechanistic studies revealed that the reactive species ËOH, ËO2-, and h+ were produced in both systems through the mutual promotion of Fenton reactions and photogenerated charge separation. The [Cu2I2(fcSe)2]n@TiO2 system additionally produced 1O2 from Cu+ and ËO2-. The advantages of the developed nanosystems include an acidic surface microenvironment provided by Seâ¯H+, resourceful product formation, tolerance of complex environments, and excellent adaptability in refractory N-cyclic organics.
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PURPOSE: To investigate the value of ultrasound-guided percutaneous nephrostomy and nephrostomy tube replacement for treating a solitary kidney with hydronephrosis due to renal tuberculosis. METHODS: Clinical data of patients with a solitary kidney with hydronephrosis caused by renal tuberculosis who underwent ultrasound-guided percutaneous nephrostomy in our hospital from January 2011 to December 2022 were retrospectively analyzed. The associated success rate and complications were statistically analyzed, pre- and post-catheterization changes in serum creatinine and blood urea nitrogen levels were compared, success rate and complications of nephrostomy tube replacement in patients with long-term catheterization were statistically analyzed, and the impact of long-term catheterization on patient life was investigated. RESULTS: Overall, 32 patients aged 17-75 years (average age: 44.1 ± 16.9 years) underwent ultrasound-guided percutaneous nephrostomy. Sixty-three punctures were performed; the puncture success rate was 100%. The levels of serum creatinine and blood urea nitrogen of patients decreased after catheterization, and the differences between the pre-catheterization and post-catheterization were significant (P < 0.05). There were 1, 3, and 12 cases of serious, minor, and fistula-related complications, respectively. The mean duration of the indwelling catheter was 56.7 ± 36.2 (range, 13-120) months. The number of nephrostomy tube replacements was 344 times, and the success rate was 100%. All patients could take care of the puncture point by themselves. CONCLUSION: Ultrasound-guided percutaneous nephrostomy and nephrostomy tube replacement have a high success rate and few complications, which can improve the renal function of patients. It is of great value for treating a solitary kidney with hydronephrosis caused by renal tuberculosis.
Subject(s)
Hydronephrosis , Nephrostomy, Percutaneous , Solitary Kidney , Tuberculosis, Renal , Humans , Adult , Middle Aged , Nephrostomy, Percutaneous/adverse effects , Solitary Kidney/complications , Retrospective Studies , Creatinine , Hydronephrosis/diagnostic imaging , Hydronephrosis/etiology , Hydronephrosis/surgery , Catheterization , Ultrasonography, Interventional/adverse effectsABSTRACT
The development of efficient blue thermally activated delayed fluorescence (TADF) emitters with an aggregation-induced emission (AIE) nature, for the construction of organic light-emitting diodes (OLEDs), is still insufficient. This can be attributed to the challenges encountered in molecular design, including the inherent trade-off between radiative decay and reverse intersystem crossing (RISC), as well as small singlet-triplet energy splitting (ΔEST) and the requirement for high photoluminescence quantum yields (ΦPL). Herein, we present the design of three highly efficient blue TADF molecules with AIE characteristics by combining π-extended donors with different acceptors to modulate the differences in the electron-donating and electron-withdrawing abilities. This approach not only ensures high emission efficiency by suppressing close π-π stacking, weakening nonradiative relaxation, and enhancing radiative transition but also maintains the equilibrium ratio between the triplet and singlet excitons by facilitating the process of RISC. These emitters exhibit AIE and TADF properties, featuring quick radiative rates and low nonradiative rates. The ΦPL of these emitters reached an impressive 88%. Based on their excellent comprehensive performance, nondoped PICzPMO and PICzPMO OLEDs achieved excellent electroluminescence performance, exhibiting maximum external quantum efficiency (EQEmax) of up to 19.5%, while the doped device achieved a higher EQEmax of 20.8%. This work demonstrated that by fusing π-extended large rigid donors with different acceptors, it is possible to regulate the difference in electron-donating and electron-withdrawing abilities, resulting in a small ΔEST, high ΦPL, and fast RISC process, which is a highly feasible strategy for designing efficient TADF molecules.
ABSTRACT
In order to reduce the environmental pollution caused by plastic packaging, the development of biodegradable high-performance packaging materials has become a research hotspot. Cellulose is a promising food packaging material, but it usually lacks sufficient ultraviolet (UV) shielding property and mechanical strength. In this work, rectorite microplates were incorporated into the cellulose matrix by a facile blending method to fabricate the composite films. The structure and properties of the composite films were characterized by FT-IR, X-ray diffraction, scanning electron microscopy, UV-vis and mechanical properties test etc. The results indicated that rectorite microplates were uniformly distributed in the cellulose matrix. The blocking percentages for UVA and UVB for the cellulose/rectorite composite film with 14 wt% rectorite content (RCRF-14) could reach as high as 97.8 % and 96.0 %, respectively, showing a good UV shielding property. Meanwhile, the addition of rectorite obviously improved the mechanical properties and decreased the water vapor and oxygen permeabilities of the cellulose film, showing a potential application as a sustainable food packaging material.
Subject(s)
Cellulose , Minerals , Cellulose/chemistry , Spectroscopy, Fourier Transform Infrared , Food Packaging/methodsABSTRACT
High-color purity organic emitters with a simultaneous combination of aggregation-induced emission (AIE) and thermally activated delayed fluorescence (TADF) characteristics are in great demand due to their excellent comprehensive performances toward efficient organic light-emitting diodes (OLEDs). In this work, two D-π-A-structure emitters, ICz-DPS and ICz-BP, exhibiting AIE and TADF properties were developed, and both the emitters have narrow singlet (S1)-triplet (T1) splitting (ΔEST) and excellent photoluminescence (PL) quantum yields (ΦPL), derived from the distorted configurations and weak intra/intermolecular interactions, suppressing exciton annihilation and concentration quenching. Their doped OLEDs based on ICz-BP provide an excellent electroluminescence external quantum efficiency (ηext) and current efficiency (ηC) of 17.7% and 44.8 cd A-1, respectively, with an ηext roll-off of 2.9%. Their nondoped OLEDs based on ICz-DPS afford high efficiencies of 11.7% and 30.1 cd A-1, with pure-blue emission with Commission Internationale de l'Éclairage (CIE) coordinates of (0.15, 0.08) and a low roll-off of 6.0%. This work also shows a strategy for designing AIE-TADF molecules by rational use of steric hindrance and weak inter/intramolecular interactions to realize high ΦPL values, fast reverse intersystem crossing process, and reduced nonradiative transition process properties, which may open the way toward highly efficient and small-efficiency roll-off devices.
ABSTRACT
Social recognition is an ability of animals to identify and distinguish conspecifics, which is essential for nearly all social species to establish social relationships. Social recognition provides the basis for a variety of social behaviors. Because of modulated by gonadal hormones, it is possible that social cognition is affected by environmental endocrine disruptors (EEDs). In the present study, after being pubertal exposed to bisphenol A (BPA, 0.04, 0.4, and 4 mg/kg) for 18 days, adult male mice did not show significant dishabituation to a novel female stimulus in habituation-dishabituation task. The capacity for discriminating the odors between familiar and novel female urine or between male and female urine was suppressed in BPA-exposed male. In addition, BPA (0.4, 4 mg/kg) decreased the number of immunoreaction of AVP (AVP-ir) neurons in both the bed nucleus of the stria terminalis (BNST) and the medial amygdala (MeA), and BPA (0.04, 0.4, 4 mg/kg) reduced the level of V1αR in the lateral septum (LS) of adult male. Further, BPA decreased the levels of testosterone (T) in the brain and androgens receptor (AR) in the LS, the amygdala, and BNST, as well the levels of estrogen receptor α and ß (ERα/ß) in the amygdala and BNST. These results indicate that pubertal exposure to BPA affected the actions of both androgens and estrogens in the brain and inhibited AVP system of social circuits, and these alterations may be associated with impaired social recognition of adult male mice.
Subject(s)
Arginine Vasopressin , Benzhydryl Compounds , Animals , Arginine Vasopressin/metabolism , Benzhydryl Compounds/toxicity , Brain/metabolism , Female , Male , Mice , Phenols/toxicityABSTRACT
Hydrogels have been widely used in many fields including biomedicine and water treatment. Significant achievements have been made in these fields due to the extraordinary properties of hydrogels, such as facile processability and tissue similarity. However, based on the in-depth study of the microstructures of hydrogels, as a result of the enhancement of biomedical requirements in drug delivery, cell encapsulation, cartilage regeneration, and other aspects, it is challenge for conventional homogeneous hydrogels to simultaneously meet different needs. Fortunately, heterogeneous multilayer hydrogels have emerged and become an important branch of hydrogels research. In this review, their main preparation processes and mechanisms as well as their composites from different resources and methods, are introduced. Moreover, the more recent achievements and potential applications are also highlighted, and their future development prospects are clarified and briefly discussed.
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Pine wilt disease (PWD) is a devastating disease affecting trees belonging to the genus Pinus. To control the spread of PWD in the Masson pine forest in China, PWD resistant Masson pine clones have been selected by the Anhui Academy of Forestry. However, because Masson pine is a difficult-to-root species, producing seedlings is challenging, especially from trees older than 5 years of age, which impedes the application of PWD resistant clones. In this study, we investigated the factors affecting rooting of PWD resistant clones and established a cheap, reliable, and simple method that promotes rooting. We tested the effects of three management methods, four substrates, two cutting materials, two cutting treatments, and three collection times on the rooting of cuttings obtained from 9-year-old PWD resistant clones. Rooting was observed only in stem cuttings treated with the full-light automatic spray management method. Additionally, stem cuttings showed a significantly higher rooting rate and root quality than needles cuttings. Compared with other substrates, stem cuttings planted in perlite produced the longest adventitious root and the highest total root length and lateral root number. Moreover, stem cuttings of PWD resistant clones collected in May showed a significantly higher rooting rate and root quality than those collected in June and July. Moreover, stem cuttings prepared with a horizontal cut while retaining the needles showed significantly higher rooting rate and root quality than those prepared with a diagonal cut while partly removing the needles. This study promotes the reproduction of seedlings of PWD-resistant Masson pine clones which helps control the spread of PWD, meanwhile, provides a technical reference for the propagation of mature pine trees via cuttings.
Subject(s)
Agriculture/methods , Disease Resistance , Pinus/growth & development , Plant Roots/growth & development , Agriculture/instrumentation , Pinus/microbiology , Plant Breeding , Plant Proteins , Plant Roots/microbiology , Plant Stems/growth & development , Plant Stems/microbiology , Seasons , Selective BreedingABSTRACT
The cyano-group (-C[triple bond, length as m-dash]N) is an electron-withdrawing group, which has been widely used to construct high-performance fused-ring electron acceptors (FREAs). Benefiting from these FREAs, the power conversion efficiency of organic solar cells has recently exceeded 18%. However, malononitrile is a highly toxic substance used to introduce -C[triple bond, length as m-dash]N during the synthesis of these FREAs. Therefore, the synthesis processes of most high-performance FREAs are typically harmful to the environment. Our previous work demonstrated that the electron-withdrawing ability of -C[triple bond, length as m-dash]N is necessary for FREAs. Thus, the use of other electron-withdrawing groups instead of -C[triple bond, length as m-dash]N to design environmentally friendly FREAs is feasible. We utilized seven electron-withdrawing groups, namely, -C[double bond, length as m-dash]NH, -N[double bond, length as m-dash]O, -CH[double bond, length as m-dash]O, -CO-CH3, -CO-OH, -CO-Cl, and -CO-Br, to replace -C[triple bond, length as m-dash]N in the commonly used acceptor Y6 to design new FREAs (Y6-CNH, Y6-NO, Y6-CHO, Y6-COCH3, Y6-COOH, Y6-COCl, and Y6-COBr). Multi-scale theoretical calculation methods were used to investigate the photoelectronic properties of these new FREAs, including energy level, absorption spectrum, exciton binding energy, and electron mobility. The results showed that Y6-CNH, Y6-COCH3 and Y6-COOH are unsuitable for use as acceptor materials because of their high frontier molecular orbital energy level and weak electron affinity. The strong absorption intensity and weak exciton binding energy of Y6-CHO, Y6-COCl, and Y6-COBr indicated that they can absorb more solar energy than Y6 and excitons are easier to separate into free charges. The electron mobility of Y6-CHO (3.53 × 10-4 cm2 V-1 s-1) was found to be approximately 28 times that of Y6-COCl (1.24 × 10-5 cm2 V-1 s-1) and Y6-COBr (1.28 × 10-5 cm2 V-1 s-1). The possible synthetic routes to Y6-CHO are environmentally friendly. Therefore, -CH[double bond, length as m-dash]O is the most suitable electron-withdrawing group for constructing high-performance environmentally friendly FREAs. This work can provide a new molecular design perspective in experimental science for developing high-performance environmentally friendly FREAs.
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INTRODUCTION: Long noncoding RNAs (lncRANs) as suppressive or oncogenic genes have been substantiated in prostate cancer (PCa). In the current study, the role and molecular mechanism of lncRNA AATBC in the progression of PCa was evaluated. METHODS: LncRNA AATBC and miR-1245b-5p expression were evaluated using RT-qPCR. CCK-8, colony-formation, apoptosis and transwell assay were used to analyze the in vitro role. The xenograft model was used to explore the in vivo role. Bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down were used to confirm the interaction between lncRNA AATBC and 1245b-5p, as well as 1245b-5p and CASK. RESULTS: Firstly, we certified that the expression of AATBC was augmented in PCa, and knockdown of AATBC could significantly inhibit the growth of PCa in vitro and in vivo. Mechanistically, our results manifested that AATBC could directly bind to miR-1245b-5p. In addition, miR-1245b-5p played cancer-suppressive role in PCa cells. Moreover, CASK was attested as the target of miR-1245b-5p, and CASK was demonstrated to exert as oncogene in the progression of PCa. Finally, rescue assays illustrated that miR-1245b-5p downregulation or CASK restoration could greatly resist the restrained effects of AATBC knockdown on PCa progression. CONCLUSION: AATBC could accelerate the progression of PCa through regulating miR-1245b-5p/CASK axis, which provided a potential therapeutic target for PCa treatment.
ABSTRACT
Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.
Subject(s)
Caveolin 1 , Glioma , Caveolin 1/genetics , Cell Line, Tumor , Cell Proliferation , Humans , Neovascularization, PathologicABSTRACT
Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.
Subject(s)
Humans , Caveolin 1/genetics , Glioma , Cell Line, Tumor , Cell Proliferation , Neovascularization, PathologicABSTRACT
BACKGROUND: Previous studies have investigated the association between the use of bisphosphonates and the development of breast cancer, which presented controversial results. Thus, this meta-analysis was conducted to summarize the current evidence of the association of bisphosphonate use with breast cancer risk. METHODS: A comprehensive search was conducted in PubMed, ISI Web of Knowledge, the Cochrane Library, and Embase from inception to March 2019 by two researches, who independently selected trials, retrieved relevant data, and assessed study quality. The summary relative risk (RR) for the use of bisphosphonates on the risks of developing breast cancer was calculated using a random-effect model. RESULTS: The present meta-analysis, which included four case-control studies, involving 55052 breast cancer cases, and seven retrospective cohort studies, involving 14641 breast cancer cases, assessed the effect of bisphosphonates on breast cancer risk. The random-effect model meta-analysis found a reduced risk of breast cancer with exposure to bisphosphonates with pooled RR of 0.87 (95% confidence interval [CI]: 0.80 to 0.94). The short-term use of bisphosphonates (<1 year) did not render significant alteration (RR = 0.92, 95% CI: 0.82 to 1.03), while a significant 26% risk reduction of breast cancer was noted with long-term use (>1 year) (RR = 0.74, 95% CI: 0.62 to 0.90). A protective effect of bisphosphonates was shown in contralateral breast cancer (RR = 0.41, 95% CI: 0.20 to 0.84). In terms of the type of bisphosphonates, a significant inverse relationship was noted for etidronate, with pooled RR of 0.87 (95% CI: 0.80 to 0.96). CONCLUSION: This meta-analysis suggested that the use of bisphosphonates was associated with reduced risk of breast cancer, including contralateral breast cancer. Compared to other types of bisphosphonates, only etidronate showed a significant inverse relationship. Additionally, the long-term use (>1 year) of bisphosphonates was more significant in lowering breast cancer risk. Further randomized controlled trials are needed to verify this association. This trial is registered with PROSPERO (registration number: CRD42018105024) (registered on 29 August 2018).
Subject(s)
Bone Density Conservation Agents/adverse effects , Breast Neoplasms/chemically induced , Diphosphonates/adverse effects , Adult , Aged , Case-Control Studies , Etidronic Acid/adverse effects , Female , Humans , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND This study aimed to investigate the effects of RKI-1447, a selective inhibitor of Rho-associated ROCK kinases, in a mouse model of nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet, and in oleic acid-treated HepG2 human hepatocellular carcinoma cells in vitro. MATERIAL AND METHODS Four study groups of mice included: the control group; the high-fat diet (HFD) group; the HFD+RKI-1447 (2 mg/kg) group; and the HFD+RKI-1447 (8 mg/kg) group. Mice were fed a high-fat diet for 12 weeks. Mice in the HFD+RKI-1447 groups were fed a high-fat diet for 12 weeks and treated with RKI-1447 twice weekly for three weeks. The HepG2 human hepatocellular carcinoma cells were treated with or without RKI-1447 for 2 h and treated with oleic acid for 24 h. RESULTS In the mouse model of NAFLD, RKI-1447 reduced insulin resistance and the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol, triglyceride, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), and superoxide dismutase (SOD). RKI-1447 reduced the histological changes in the mouse model of NAFLD in mice fed a high-fat diet and significantly inhibited the generations of triglyceride, IL-6, and TNF-alpha. RKI-1447 reduced the levels of oxidative stress in HepG2 cells treated with oleic acid and significantly down-regulated the expression of RhoA, ROCK1, ROCK2, toll-like receptor 4 (TLR4), p-TBK1, and p-IRF3. RKI-1447 treatment also inhibited RhoA expression. CONCLUSIONS In a mouse model of NAFLD, RKI-1447 inhibited ROCK and modulated insulin resistance, oxidative stress, and inflammation through the ROCK/TLR4/TBK1/IRF3 pathway.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Diet, High-Fat , Liver Neoplasms/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Thiazoles/therapeutic use , Urea/analogs & derivatives , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Carcinoma, Hepatocellular/blood , Cholesterol/blood , Disease Models, Animal , Glucose Tolerance Test , Hep G2 Cells , Humans , Insulin Resistance , Interleukin-6/blood , Liver/metabolism , Liver/pathology , Liver Neoplasms/blood , Male , Malondialdehyde/blood , Mice, Inbred ICR , Models, Biological , Non-alcoholic Fatty Liver Disease/blood , Oleic Acid , Oxidative Stress/drug effects , Signal Transduction , Superoxide Dismutase/blood , Thiazoles/pharmacology , Triglycerides/blood , Tumor Necrosis Factor-alpha/blood , Urea/pharmacology , Urea/therapeutic use , rhoA GTP-Binding Protein/metabolismABSTRACT
Non-fullerene acceptors have been widely investigated for organic solar cells (OSCs). In particular, fused-ring electron acceptors (FREAs), composed of two strongly electron-withdrawing end groups connected by a planar fused-ring core, have been successfully applied to develop high-performance OSCs (>16%). In this work, we proposed two novel 3D FREAs named BFT-3D and BFTT-3D, which can reduce the formation of crystalline domains and increase the interface with donors to promote exciton separation. These 3D FREAs consist of three strongly electron-withdrawing end groups linked by a central triptycene hub to form a three-bladed propeller nanostructure. In comparison with high-performance FREA (ITOIC-2F), these FREAs have stronger absorption intensity and smaller exciton binding energy. These findings demonstrated that these three-bladed propeller-shaped FREAs can absorb abundant energy from sunlight to generate excitons, easily separate excitons to free electrons and holes, and reduce the recombination of excitons. In addition, the electron mobility of BFT-3D (8.4 × 10-4 cm2 V-1 s-1) is higher than that of BFTT-3D (1.0 × 10-4 cm2 V-1 s-1), which indicated that the appropriate 3D core structure was conducive to the electron mobility of the three-bladed propeller-shaped FREAs. It can effectively improve the current density to enhance the performance of OSCs. These findings will provide new perspectives for experimental scientists to synthesize high-performance FREAs.