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1.
J Ethnopharmacol ; 282: 114595, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517060

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tanshinone IIA (Tan), extracted from Salvia miltiorrhiza Bunge, is a perennial herbal plant widely used as a folk remedy in Asian countries. Several studies have proved that Tanshinone IIA possesses many biological activities, such as anti-inflammatory, free-radical scavenging abilities, antioxidant properties, liver protection, and anti-cancer properties. AIM OF THE STUDY: The objective of the present study was to examine the anti-inflammatory effects of Tan. MATERIALS AND METHODS: The in vitro infection model of Mycobacterium tuberculosis-infected macrophages with the H37Ra strain was established. Murine macrophage Raw 264.7 and human monocyte THP-1 were used for the experiments. Cell viability was determined by the MTT assay. Western blot and lactate dehydrogenase (LDH) activity assays were used to detect the effects of Tan on cell pyroptosis and the level of NLRP3 inflammasome activation. Western blot, Co-immunoprecipitation and Immunofluorescence assays were used to observe the effect of Tan on the expression level of TXNIP. Immunofluorescence assays were applied to explore the effect of Tan on mtROS. Western blot and agarose gel electrophoresis were adopted to observe the effect of Tan on endoplasmic reticulum stress. The siRNA technique was applied to knockdown the expression levels of PERK/peIF2α, IRE1α and ATF6, and Western blot assay was employed to explore the NLRP3 inflammasome activation and possible molecular regulation mechanism of Tan. RESULTS: This study demonstrated that Tan decreased Mtb-induced cell pyroptosis by measuring GSDMD-N and LDH release provoked by NLRP3 inflammasome activation. Additionally, Tan inhibited endoplasmic reticulum stress (ERS), mitochondrial damage, and TXNIP protein expression, all of which acted as upstream signals of NLRP3 inflammasome activation in Mtb-infected macrophages. Significantly, NLRP3 inflammasome activation was suppressed by knocking down ERS pathway proteins, which further clarified that Tan partly targeted ERS to exert anti-inflammatory and immunoregulatory actions. CONCLUSION: This research confirms Tan's anti-inflammatory and immunoregulatory mechanisms in Mtb-infected macrophages by downregulating NLRP3 inflammasome activation-mediated pyroptosis provoked by ERS. Tan may function as an adjuvant drug to treat TB by adjusting host immune responses.

2.
J Colloid Interface Sci ; 606(Pt 2): 1205-1218, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492459

RESUMO

Flexible polyurethane foam (FPUF) is the most commonly used polyurethane, but its highly flammable characteristics makes it ignite easily and release a lot of heat and toxic gases. Here, the effect of different forms of copper salt modified graphene (rGO@CuO, rGO@Cu2O and rGO@CSOH) on improving the fire protection efficiency and mechanical property of FPUF is explored. Hybrid FPUF is characterized by thermogravimetric analysis (TGA), cone calorimeter, thermogravimetric analysis/Fourier transform infrared spectroscopy (TG-IR), tension, compression, and falling ball rebound testing. Compared with pure FPUF, the FPUF/rGO@CSOH show a significant decreasement in reducing the heat release of FPUF, the PHRR and THR are reduced by 36.9% and 29.4%, respectively. While the FPUF/rGO@Cu2O demonstrate excellent smoke and toxic gases suppression in FPUF, the PSPR and TSR are reduced by 24.6% and 51.9%, and the COP and COY are also reduced by 51.9% and 55.3%, respectively. After adding the copper salt hybrid, the buffering performance of FPUF did not change. Fortunately, the tensile and compressive strength increase obviously. The flame retardant and smoke suppression mechanism of hybrid FPUF has also been studied. This article gives a effective strategy for the preparation of FPUF with outstanding mechanical property, flame retardant and smoke suppression properties.


Assuntos
Retardadores de Chama , Grafite , Cobre , Poliuretanos
3.
Sci Total Environ ; 805: 150324, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34818808

RESUMO

Microbial extracellular electron transfer (EET) at microbe-mineral interface has been reported to play a significant role in pollutant biotransformation. Different metals often co-exist with organic pollutants and are immobilized on mineral surfaces. However, little is known about the influence of mineral surface metal ions on organic pollutant biodegradation and the involved electron transfer mechanism. To address this knowledge gap, pyrene was used as a model compound to investigate the biodegradation of polycyclic aromatic hydrocarbon on montmorillonite mineral saturated with metal ions (Na(I), Ni(II), Co(II), Cu(II) and Fe(III)) by Mycobacteria strain NJS-1. Further, the possible underlying electron transfer mechanism by electrochemical approaches was investigated. The results show that pyrene biodegradation on montmorillonite was markedly influenced by surface metal ions, with degradation efficiency following the order Fe(III) > Na(I) ≈ Co(II) > Ni(II) ≈ Cu(II). Bioelectrochemical analysis showed that electron transfer activities (i.e., electron donating capacity and electron transport system activity) varied in different metal-modified montmorillonites and were closely related to pyrene biodegradation. Fe(III) modification greatly stimulated degrading enzyme activities (i.e., peroxidase and dioxygenase) and electron transfer activities resulting in enhanced pyrene biodegradation, which highlights its potential as a technique for pollutant bioremediation. The bacterial extracellular protein and humic substances played important roles in EET processes. Membrane-bound cytochrome C protein and extracellular riboflavin were identified as the electron shuttles responsible for transmembrane and cross extracellular matrix electron transfer, respectively. Additions of exogenetic electron mediators of riboflavin, humic acid and potassium ferricyanide accelerated pyrene biodegradation which further verified the critical role of EET in PAH transformation at bacteria-mineral interfaces. These results support the development of clay mineral based advanced bioremediation techniques through regulating the electron transfer processes at the microbe-mineral interfaces by mineral surface modification.


Assuntos
Bentonita , Hidrocarbonetos Policíclicos Aromáticos , Biodegradação Ambiental , Compostos Férricos , Íons , Pirenos
4.
Entropy (Basel) ; 23(11)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34828109

RESUMO

We investigated a comprehensive analysis of the mutual exciting mechanism for the dynamic of stock price trends. A multi-dimensional Hawkes-model-based approach was proposed to capture the mutual exciting activities, which take the form of point processes induced by dual moving average crossovers. We first performed statistical measurements for the crossover event sequence, introducing the distribution of the inter-event times of dual moving average crossovers and the correlations of local variation (LV), which is often used in spike train analysis. It was demonstrated that the crossover dynamics in most stock sectors are generally more regular than a standard Poisson process, and the correlation between variations is ubiquitous. In this sense, the proposed model allowed us to identify some asymmetric cross-excitations, and a mutually exciting structure of stock sectors could be characterized by mutual excitation correlations obtained from the kernel matrix of our model. Using simulations, we were able to substantiate that a burst of the dual moving average crossovers in one sector increases the intensity of burst both in the same sector (self-excitation) as well as in other sectors (cross-excitation), generating episodes of highly clustered burst across the market. Furthermore, based on our finding, an algorithmic pair trading strategy was developed and backtesting results on real market data showed that the mutual excitation mechanism might be profitable for stock trading.

5.
Antioxidants (Basel) ; 10(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34829539

RESUMO

Radiation therapy is a common treatment for head and neck cancers. However, because of the presence of nerve structures (brain stem, spinal cord, and brachial plexus), salivary glands (SGs), mucous membranes, and swallowing muscles in the head and neck regions, radiotherapy inevitably causes damage to these normal tissues. Among them, SG injury is a serious adverse event, and its clinical manifestations include changes in taste, difficulty chewing and swallowing, oral infections, and dental caries. These clinical symptoms seriously reduce a patient's quality of life. Therefore, it is important to clarify the mechanism of SG injury caused by radiotherapy. Although the mechanism of radiation-induced SG injury has not yet been determined, recent studies have shown that the mechanisms of calcium signaling, microvascular injury, cellular senescence, and apoptosis are closely related to oxidative stress. In this article, we review the mechanism by which radiotherapy causes oxidative stress and damages the SGs. In addition, we discuss effective methods to prevent and treat radiation-induced SG damage.

6.
Antioxidants (Basel) ; 10(11)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34829721

RESUMO

This article mainly observed the protective effect of sulforaphane (SFN) on radiation-induced skin injury (RISI). In addition, we will discuss the mechanism of SFN's protection on RISI. The RISI model was established by the irradiation of the left thigh under intravenous anesthesia. Thirty-two C57/BL6 mice were randomly divided into control group (CON), SFN group, irradiation (IR) group, and IR plus SFN (IR/SFN) group. At eight weeks after irradiation, the morphological changes of mouse skin tissues were detected by H&E staining. Then, the oxidative stress and inflammatory response indexes in mouse skin tissues, as well as the expression of Nrf2 and its downstream antioxidant genes, were evaluated by ELISA, real-time PCR, and Western blotting. The H&E staining showed the hyperplasia of fibrous tissue in the mouse dermis and hypodermis of the IR group. Western blotting and ELISA results showed that the inflammasome of NLRP3, caspase-1, and IL-1ß, as well as oxidative stress damage indicators ROS, 4-HNE, and 3-NT, in the skin tissues of mice in the IR group were significantly higher than those in the control group (p < 0.05). However, the above pathological changes declined sharply after SFN treatment (p < 0.05). In addition, the expressions of Nrf2 and its regulated antioxidant enzymes, including CAT and HO-1, were higher in the skin tissues of SFN and IR/SFN groups, but lower in the control and IR groups (p < 0.05). SFN may be able to suppress the oxidative stress by upregulating the expression and function of Nrf2, and subsequently inhibiting the activation of NLRP3 inflammasome and DNA damage, so as to prevent and alleviate the RISI.

7.
J Microbiol ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826097

RESUMO

As a microsymbiont of soybean, Bradyrhizobium japonicum plays an important role in symbiotic nitrogen fixation and sustainable agriculture. However, the survival of B. japonicum cells under water-deplete (e.g., drought) and water-replete (e.g., flood) conditions is a major concern affecting their nitrogen-fixing ability by establishing the symbiotic relationship with the host. In this study, we isolated a water stress tolerant rhizobium from soybean root nodules and tested its survival under water-deplete conditions. The rhizobium was identified as Bradyrhizobium japonicum and named strain 5038. Interestingly, both plate counting and live/dead fluorescence staining assays indicate that a number of viable but non-culturable cells exist in the culture medium upon the rehydration process which could cause dilution stress. Bradyrhizobium japonicum 5038 cells increased production of exopolysaccharide (EPS) and trehalose when dehydrated, suggesting that protective responses were stimulated. As expected, cells reduced their production upon the subsequent rehydration. To examine differential gene expression of B. japonicum 5038 when exposed to water-deplete and subsequent water-replete conditions, whole-genome transcriptional analysis was performed under 10% relative humidity (RH), and subsequent 100% RH, respectively. A total of462 differentially expressed genes (DEGs, > 2.0-fold) were identified under the 10% RH condition, while 3,776 genes showed differential expression during the subsequent rehydration (100% RH) process. Genes involved in signal transduction, inorganic ion transport, energy production and metabolisms of carbohydrates, amino acids, and lipids were far more up-regulated than down-regulated in the 10% RH condition. Notably, trehalose biosynthetic genes (otsAB, treS, and treYZ), genes ligD, oprB, and a sigma factor rpoH were significantly induced by 10% RH. Under the subsequent 100% RH condition, genes involved in transcription, translation, cell membrane regulation, replication and repair, and protein processing were highly up-regulated. Interestingly, most of 10%-RH inducible genes displayed rehydration-repressed, except three genes encoding heat shock (Hsp20) proteins. Therefore, this study provides molecular evidence for the switch of gene expression of B. japonicum cells when encountered the opposite water availability from water-deplete to water-replete conditions.

8.
Dalton Trans ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787158

RESUMO

Polyoxometalate-based organic-inorganic hybrids have attracted considerable attention due to their fascinating structures and wide application prospects. In this work, using the same building blocks, ligands and metal ions (ZnW12O406-(ZnW12), 2,2'-bipyridine (2,2'-bipy), and Cu2+), we synthesized three new POM-based hybrids by controlling the pH values of the reaction systems. These three compounds {(Zn0.6(H2)0.4W12O40)[Cu(2,2'-bipy)(H2O)][Cu(2,2'-bipy)(H2O)2][Cu(2,2'-bipy)(H2O)3]}2·6H2O (1), (Me4N)2{ZnW12O40[Cu(2,2'-bipy)(H2O)][Cu(2,2'-bipy)(H2O)3]}·5H2O (2), and {(Zn0.5(H2)0.5W12O40)[Cu(2,2'-bipy)][Cu(2,2'-bipy)(H2O)][Cu(2,2'-bipy)(H2O)2]}·5H2O (3) have been structurally characterized by single-crystal X-ray diffraction. Compound 1 appears as a dimeric cluster structure, while compounds 2 and 3 appear as a 1D chain structure and a 2D network, respectively. The semiconducting properties of compounds 1-3 are different, which was demonstrated by band gap (Eg) and photocurrent response measurements. Compound 3 can efficiently catalyze the photooxidation of toluene to benzaldehyde with high selectivity using molecular oxygen as the oxidant component. Moreover, compound 3 was recycled and reused three times without significant degradation in conversion and selectivity. In addition, the mechanism of the photocatalytic reaction was also investigated.

9.
Phys Chem Chem Phys ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817494

RESUMO

Room-temperature phosphorescence (RTP) from pure organic materials has been promising in next-generation OLEDs. Understanding the photophysical properties of RTP molecules is attractive but challenging. In this study, through a combined quantum mechanics and molecular mechanics (QM/MM) method taking 2-(3,4-dimethoxybenzyl)isoindoline-1,3-dione (complex b) as an example, we comparatively investigate the photophysical properties of complex b in diverse environments (solution, crystal, and amorphous). From solution to amorphous to crystal phase, the excited-state decay rates for the molecule indicate that the AIE phenomenon of complex b is mainly induced by the increased phosphorescence rates. However, the increased nonradiative decay rate knr of T1 → S0 from the solution to the crystal phase could be attributed to the different electron coupling in the crystal phase. Moreover, the theoretical results also show that the small energy gap between the lowest singlet excited state (S1) and triplet excited state (T1) and low reorganization energy can help enhance intersystem crossing to facilitate a more competitive radiative process from the T1 state to ground state (S0). Additionally, the stronger intermolecular π-π interaction can cause high phosphorescence quantum efficiency in the crystalline phase. Our study presents a rational explanation for aggregation-induced RTP, which is beneficial for the design of new organic RTP materials in the future.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34779543

RESUMO

In nature as well as life systems, the presence of asymmetrical and dissymmetrical structures with specific functions is extremely common. However, the construction of metallo-supramolecular assemblies based on dissymmetrical ligands still remains a considerable challenge for avoiding the generation of unexpected isomers with similar thermodynamic stabilities, especially for three-dimensional supramolecular structures. In this study, a strategy for the conformational control of metallo-supramolecular cages via the enhancement of ligand dissymmetry was proposed. Four dissymmetrical ditopic ligands were designed and synthesized. By increasing the dissymmetry of length or angle, conformations of assemblies were precisely controlled to form discrete cis-Pdn L2n molecular cages.

11.
Front Genet ; 12: 728764, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804115

RESUMO

Low-coverage whole genome sequencing is a low-cost genotyping technology. Combined with genotype imputation approaches, it is likely to become a critical component of cost-effective genomic selection programs in agricultural livestock. Here, we used the low-coverage sequence data of 617 Dezhou donkeys to investigate the performance of genotype imputation for low-coverage whole genome sequence data and genomic prediction based on the imputed genotype data. The specific aims were as follows: 1) to measure the accuracy of genotype imputation under different sequencing depths, sample sizes, minor allele frequency (MAF), and imputation pipelines and 2) to assess the accuracy of genomic prediction under different marker densities derived from the imputed sequence data, different strategies for constructing the genomic relationship matrixes, and single-vs. multi-trait models. We found that a high imputation accuracy (>0.95) can be achieved for sequence data with a sequencing depth as low as 1x and the number of sequenced individuals ≥400. For genomic prediction, the best performance was obtained by using a marker density of 410K and a G matrix constructed using expected marker dosages. Multi-trait genomic best linear unbiased prediction (GBLUP) performed better than single-trait GBLUP. Our study demonstrates that low-coverage whole genome sequencing would be a cost-effective approach for genomic prediction in Dezhou donkey.

12.
Front Cell Dev Biol ; 9: 732036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805143

RESUMO

Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

13.
Bioelectrochemistry ; 143: 107986, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34735912

RESUMO

At present, carcinoembryonic antigen (CEA) is considered a broad-spectrum cancer biomarker, and its accurate analysis in clinical samples can assist early cancer diagnosis and treatment. Herein, a novel electrochemical aptasensor has been proposed for CEA detection based on exonuclease III and hybrid chain reaction. The target CEA specifically binds to the aptamer region in hairpin probe 1 (defined as H1) by strong attraction, which leads the rest of the H1 triggering catalytic hairpin assembly to form a high quantity of H1 and hairpin probe 2 (defined as H2) double chain complex (denoted as H1@H2). Subsequently, the exonuclease III digests the complex of H1@H2 and liberates H1 to induce the first signal amplification. Simultaneously, a large number of generated trigger chains initiate a hybrid chain reaction and produce a second signal amplification. This proposed sensor exhibited excellent analytical performance for the detection of CEA, with wide linear range from 10 pg.mL-1 to 100 ng.mL-1 and low limit of detection of 0.84 pg.mL-1. Additionally, the biosensing strategy was successfully verified for direct measurement of CEA in human serum. Therefore, this elaborated sensor provides a new simple method for detecting CEA and exhibits great promise in the early screening of cancer.

14.
Sci Rep ; 11(1): 22125, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764393

RESUMO

To release more flexibility for users to charge their portable devices, researchers have increasingly developed compact wireless power transfer (WPT) systems in recent years. Also, a dual-band WPT system is proposed to transfer power and signal simultaneously, enriching the system's functionality. Moreover, a stacked metasurface has recently been proposed for a single band near-field WPT system. In this study, a novel multimode self-resonance-enhanced wideband metasurface is proposed for a robust dual-band WPT system, which significantly improves the performance of both bands. The size of the transmitter (Tx) and the receiver (Rx) are both 15 mm × 15 mm only. The proposed metasurface can improve efficiency from 0.04 up to 39% in the best case. The measured figure of merit (FoM) is 2.09 at 390 MHz and 2.16 at 770 MHz, respectively, in the balanced mode. Especially, the FoM can reach up to 4.34 in the lower mode. Compared to the previous state-of-the-art for similar applications, the WPT performance has significantly been improved.

15.
Sci Total Environ ; : 151386, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34742956

RESUMO

The overuse and misuse of antibiotics in animal breeding for disease treatment and growth enhancement have been major drivers of the occurrence, diffusion, and accumulation of antibiotic resistance genes (ARGs) in wastewater. Strategies to combat ARG dissemination are pressingly needed for human and ecological safety. To achieve this goal, a biochar-based polymer, magnetic biochar/quaternary phosphonium salt (MBQ), was applied in livestock wastewater and displayed a high performance in bacterial deactivation and ARG decrease. Efficient antibacterial effects were achieved by both MBQ and quaternary phosphonium salt; however, the abundance and fold change of ARGs in the MBQ treatment indicated a more powerful ARG dissemination control than quaternary phosphonium salt. The application of MBQ evidently reduced the microbial diversity and may primarily be responsible for altering the ARG profiles in wastewater. Network, redundancy, and variation partitioning analyses were further employed to reveal that the microbial community and the presence of mobile genetic elements were two critical factors shaping the pattern of the antibiotic resistome in livestock wastewater. Considered together, these findings extend the application field of biochar and have important implications for reducing ARG dissemination risks in livestock wastewater.

16.
Chemistry ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34757667

RESUMO

1,7-Di-tert-butyl-substituted aza-BODIPYs (tBu-azaBDP) were successfully obtained for the first time. The structures of tBu-azaBDP and Ph-azaBDP were confirmed by X-ray crystal analysis, and tBu-azaBDP 2 is more twisted than Ph-azaBDP 5. tBu-azaBDPs have significant photo-stability and enhanced water solubility. tBu-azaBDPs possess excellent optical properties, such as high molar extinction coefficients, broad full width half maxima, and large Stokes shifts, which is comparable to those of the parent dye Ph-azaBDP. Although the low-barrier rotation of the distal -tBu groups in tBu-azaBDPs results in low quantum yield, photothermal conversion efficiency and singlet oxygen generation ability of tBu-azaBDPs are more effective than those of Ph-azaBDP, which is highly desirable for a photothermal-photodynamic therapy agent.

17.
Mediators Inflamm ; 2021: 1805147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790063

RESUMO

Mycobacterium tuberculosis (Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL-1ß and tissue damage, promoting its spread. Here, we established an in vitro Mtb-infected macrophage model to seek an effective antipyroptosis agent. Baicalin, isolated from Radix Scutellariae, was found to reduce pyroptosis in Mtb-infected macrophages. Baicalin could inhibit activation of the PERK/eIF2α pathway and thus downregulates TXNIP expression and subsequently reduces activation of the NLRP3 inflammasome, resulting in reduced pyroptosis in Mtb-infected macrophages. In conclusion, baicalin reduced pyroptosis by inhibiting the PERK/TXNIP/NLRP3 axis and might thus be a new adjuvant host-directed therapy (HDT) drug.

18.
Sci Rep ; 11(1): 21879, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750457

RESUMO

Radiotherapy (RT) is one of the main treatment strategies of breast cancer. It is challenging to design RT plans that can completely cover the target area while protecting organs at risk (OAR). The Plan-IQ feasibility tool can estimate the best sparing dose of OAR before optimizing the Plan. A systematic quantitative evaluation of the quality change of intensity-modulated radiation therapy (IMRT) using the Plan-IQ feasibility tool was performed for modified radical mastectomy in this study. We selected 50 patients with breast cancer treated with IMRT. All patients received the same dose in the planning target volume (PTV). The plans are categorized into two groups, with each patient having one plan in each group: the clinically accepted normal plan group (NP group) and the repeat plan group (RP group). An automated planning strategy was generated using a Plan-IQ feasibility dose volume histogram (FDVH) in RP group. These plans were assessed according to the dosimetry parameters. A detailed scoring strategy was based on the RTOG9804 report and 2018 National Comprehensive Cancer Network guidelines, combined with clinical experience. PTV coverage in both groups was achieved at 100% of the prescribed dose. Except for the thyroid coverage, the dose limit of organs at risk (OAR) in RP group was significantly better than that in NP group. In the scoring analysis, the total scores of RP group decreased compared to that of NP group (P < 0.05), and the individual scores of PTV and OAR significantly changed. PTV scores in RP group decreased (P < 0.01); however, OAR scores improved (P < 0.01). The Plan-IQ FDVH was useful for evaluating a class solution for IMRT planning. Plan-IQ can automatically help physicians design the best OAR protection plan, which sacrifices part of PTV, but still meets clinical requirements.

19.
Cancer Res ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753771

RESUMO

Fibroblast growth factor receptor 3 (FGFR3) is frequently activated by mutation or overexpression, and it is a validated therapeutic target in urothelial carcinoma (UC) of the bladder. However, the role and detailed molecular mechanism of FGFR3 in the immune microenvironment of bladder cancer remain largely unknown. Here, we demonstrate that inhibition of FGFR3 in FGFR3-activated bladder cancer elevates PD-L1 protein levels by affecting its ubiquitination, thereby inhibiting the anti-tumor activity of CD8+ T cells. Tissue microarray analysis in human UC showed an inverse correlation between FGFR3 and PD-L1. Furthermore, NEDD4, an E3 ubiquitin ligase of the NEDD4 family of proteins, was phosphorylated by FGFR3 activation and served as a regulator of PD-L1 ubiquitination. Mechanistically, NEDD4 interacted with PD-L1 and catalyzed Lys48 (K48)-linked polyubiquitination of PD-L1. In mice bearing NEDD4 knockout bladder cancer, CD8+ T cell infiltration and antitumor activity were significantly inhibited due to PD-L1 upregulation in bladder cancer cells. Furthermore, multiple FGFR3-activated tumor-bearing mouse models suggested that attenuated CD8+ T cell-mediated antitumor efficacy following FGFR3-targeted therapy could be rescued by a combination with anti-PD-1 immunotherapy, which leads to effective tumor suppression. This study establishes a key molecular link between targeted therapy and immune surveillance and identifies NEDD4 as a crucial E3 ubiquitin ligase that targets PD-L1 for degradation in FGFR3-activated bladder cancer. These findings may potentially be exploited for combination therapies in UC of the bladder and possibly other malignancies with activated FGFR3.

20.
ACS Omega ; 6(43): 29184-29191, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34746607

RESUMO

In this study, two-dimensional Ti3C2 nanosheets were employed to improve the tribological and thermo-mechanical properties of epoxy resin. The Ti3C2 nanosheets were prepared by ultrasound-assisted delamination of multilayered Ti3C2 microparticles, and the Ti3C2 nanosheets/epoxy (Ti3C2/epoxy) nanocomposites were fabricated through physical blending and curing reaction. Scanning electron microscopy results showed that the Ti3C2 nanosheets were dispersed uniformly in the epoxy matrix. Tribological test results showed that the wear rate of Ti3C2/epoxy nanocomposites was only 6.61 × 10-14 m3/(N m) at a 1% mass fraction, which was reduced by 72.1% compared to that of neat epoxy. The morphologies of worn surfaces revealed that the wear form of Ti3C2/epoxy nanocomposites transformed gradually from fatigue wear to adhesive wear with the increase of mass fraction of Ti3C2 nanosheets. Moreover, the results of thermo-mechanical properties indicated that incorporation of Ti3C2 nanosheets effectively improved the storage modulus and glass-transition temperature (T g) of epoxy resin. This work provides guidance for improving the tribological and thermo-mechanical properties of epoxy resin.

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