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1.
Adv Sci (Weinh) ; : e2104613, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018748

RESUMO

The donor/acceptor interaction in non-fullerene organic photovoltaics leads to the mixing domain that dictates the morphology and electronic structure of the blended thin film. Initiative effort is paid to understand how these domain properties affect the device performances on high-efficiency PM6:Y6 blends. Different fullerenes acceptors are used to manipulate the feature of mixing domain. It is seen that a tight packing in the mixing region is critical, which could effectively enhance the hole transfer and lead to the enlarged and narrow electron density of state (DOS). As a result, short-circuit current (JSC ) and fill factor (FF) are improved. The distribution of DOS and energy levels strongly influences open-circuit voltage (VOC ). The raised filling state of electron Fermi level is seen to be key in determining device VOC . Energy disorder is found to be a key factor to energy loss, which is highly correlated with the intermolecular distance in the mixing region. A 17.53% efficiency is obtained for optimized ternary devices, which is the highest value for similar systems. The current results indicate that a delicate optimization of the mixing domain property is an effective route to improve the VOC , JSC , and FF simultaneously, which provides new guidelines for morphology control toward high-performance organic solar cells.

2.
Nano Lett ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35019656

RESUMO

The three-precursors approach has proven to be advantageous for obtaining high-quality metal halide perovskite nanocrystals (PNCs). However, the current halide precursors of choice are mainly limited to those highly toxic organohalides, being unfavorable for large-scale and sustainable use. Moreover, most of the resulting PNCs still suffer from low quality in terms of photoluminescence quantum yield (PLQY). Herein we present all-inorganic germanium salts, GeX4 (X = Cl, Br, I), serving as robust and less hazardous alternatives that are capable of ensuring improved material properties for both Pb-based and Pb-free PNCs. Importantly, unlike most of the other inorganic halide sources, the GeX4 compound does not deliver the Ge element into the final compositions, whereas the PLQY and phase stability of the resulting nanocrystals are significantly improved. Theoretical calculations suggest that Ge halide precursors provide favorable conditions in both dielectric environment and thermodynamics, which jointly contribute to the formation of size-confined defect-suppressed nanoparticles.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34981382

RESUMO

Soil microbial stoichiometry reflects carbon (C) and nutrient (e.g., nitrogen (N) and phosphorus (P)) elemental balances under land-use change (LUC). However, how soil microbial community (SMC) structure and stoichiometry respond to long-term LUC in forests is still unclear. Here, we investigated three 36-year-old typical plantations, Cryptomeria fortunei, Metasequoia glyptostroboides, and Cunninghamia lanceolata, and the natural forest to assess their soil microbial stoichiometry and SMC structure. Three plots (30×30 m2) were randomly set in each forest site. In each plot of every forest site, soil samples of three depths (0-10, 10-30, and 30-60 cm) were collected. Dissolved organic C, N, and P (abbreviated as DOC, DON, and DOP, respectively) and environmental factors were measured. We also detected microbial biomass C, N, and P as well as SMC structure. The results showed that the soil microbial C:N:P stoichiometry had a strong or strict homeostasis regardless of soil depth and exhibited decoupling from the SMC structure at each depth. The SMC structure across forest types was mainly driven by mean annual soil temperature (MAST) and DOC at 0-10 cm depth, by soil water content and MAST at 10-30 cm depth, and by DOC to DOP ratio at 30-60 cm depth. Thus, SMC structure could be jointly regulated by available resources and environment. These results suggest that the C dynamics in forests tend to gain resilience or re-equilibrium over more than three decades after forest conversion. These findings highlight the importance of reforested plantations forest management for sustaining soil C over a long term.

4.
Bioelectromagnetics ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35005795

RESUMO

In pediatric magnetic resonance imaging (MRI), infants are exposed to rapid, time-varying gradient magnetic fields, leading to electric fields induced in the body of infants and potential safety risks (e.g. peripheral nerve stimulation). In this numerical study, the in situ electric fields in infants induced by small-sized gradient coils for a 1.5 T MRI scanner were evaluated. The gradient coil set was specially designed for the efficient imaging of infants within a small-bore (baby) scanner. The magnetic flux density and induced electric fields by the small x, y, z gradient coils in an infant model (8-week-old with a mass of 4.3 kg) were computed using the scalar potential finite differences method. The gradient coils were driven by a 1 kHz sinusoidal waveform and also a trapezoidal waveform with a 250 µs rise time. The model was placed at different scan positions, including the head area (position I), chest area (position II), and body center (position III). It was found that the induced electric fields in most tissues exceeded the basic restrictions of the ICNIRP 2010 guidelines for both waveforms. The electric fields were similar in the region of interest for all coil types and model positions but different outside the imaging region. The y-coil induced larger electric fields compared with the x- and z- coils. © 2022 Bioelectromagnetics Society.

6.
J Agric Food Chem ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040327

RESUMO

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for discovering novel herbicides, and it causes bleaching symptoms by inhibiting the synthesis of chlorophyll and heme. In this study, the active fragments of several commercial herbicides were joined by substructure splicing and bioisosterism, and a series of novel diphenyl ether derivatives containing five-membered heterocycles were synthesized. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were discussed in detail. The results showed that most compounds had good PPO inhibitory activity, and target compounds containing trifluoromethyl groups tended to have higher activity. Among them, compound G4 showed the best inhibitory activity, with a half-maximal inhibitory concentration (IC50) of 0.0468 µmol/L, which was approximately 3 times better than that of oxyfluorfen (IC50 = 0.150 µmol/L). In addition, molecular docking indicated that compound G4 formed obvious π-π stacking interactions and hydrogen bond interactions with PHE-392 and ARG-98, respectively. Remarkably, compound G4 had good safety for corn, wheat, rice, and soybean, and the cumulative concentration in crops was lower than that of oxyfluorfen. Therefore, compound G4 can be used to develop potential lead compounds for novel PPO inhibitors.

7.
ACS Nano ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040624

RESUMO

The reduction of CO2 to useful chemicals by solar irradiation has been of great interest in recent years to tackle the greenhouse effect. Compared with inorganic metal oxide particles, carbonaceous materials, such as graphene, are excellent in light absorption; however, they lack in activity and selectivity because of the challenge to manipulate the band gap and optimize the electron-hole separation, which drives the photoreduction process. In this work, inspired by the delicate natural plant leaf structure, we fabricated orderly stacked graphene nanobubble arrays with nitrogen dopant for the coordination of noble metal atoms to mimic the natural photoreduction process in plant leaves. This graphene metamaterial not only mimics the optical structure of leaf cells, which scatter and absorb light efficiently, but also drives the CO2 reduction via nitrogen coordinated metal atoms as the chlorophyll does in plants. Our characterizations show that the band gap of nitrogen-doped graphene could be precisely tailored via substitution with different noble metal atoms on the doped site. The noble atoms coordinated on the doped site of graphene metamaterial not only enlarge the light absorption volume but also maximize the utilization of noble metals. The bionic optical leaf metamaterial coordinated with Au atoms exhibits high CO productivity up to 11.14 mmol gcat-1 h-1 and selectivity to 95%, standing as one of the best catalysts among the carbonaceous and metal-based catalysts reported to date. This catalyst also maintained a high performance at low temperatures, manifesting potential applications of this bionic catalyst at polar regions to reduce greenhouse gases.

8.
Biosci Rep ; 42(1)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34988580

RESUMO

BACKGROUND: The role of DnaJ heat shock protein family (Hsp40) member C10 (DNAJC10) in cancers has been reported but its function in glioma is not clear. We reveal the prognostic role and underlying functions of DNAJC10 in glioma in the present study. METHODS: Reverse Transcription and Quantitative Polymerase Chain Reaction (RT-qPCR) was used to quantify the relative DNAJC10 messenger RNA (mRNA) expression of clinical samples. Protein expressions of clinical samples were tested by Western blot. The overall survival (OS) of glioma patients with different DNAJC10 expression was compared by Kaplan-Meier method (two-sided log-rank test). Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the immune cell infiltrations and immune-related function levels. The independent prognostic role of DNAJC10 was determined by univariate and multivariate Cox regression analyses. The DNAJC10-based nomogram model was established using multivariate Cox regression by R package 'rms'. RESULTS: Higher DNAJC10 is observed in gliomas and it is up-regulated in higher grade, isocitrate dehydrogenase (IDH)-wild, 1p/19q non-codeletion, O(6)-methylguanine-DNA methyltransferase (MGMT) unmethylated gliomas. Gliomas with higher DNAJC10 expression present poorer prognosis compared with low-DNAJC10 gliomas. The predictive accuracy of 1/3/5-OS of DNAJC10 is found to be stable and robust using time-dependent ROC model. Enrichment analysis recognized that T-cell activation and T-cell receptor signaling were enriched in higher DNAJC10 gliomas. Immune/stromal cell infiltrations, tumor mutation burden (TMB), copy number alteration (CNA) burden and immune checkpoint genes (ICPGs) were also positively correlated with DNAJC10 expression in gliomas. DNAJ10-based nomogram model was established and showed strong prognosis-predictive ability. CONCLUSION: Higher DNAJC10 expression correlates with poor prognosis of glioma and it was a potential prognostic biomarker for glioma.

9.
Lipids Health Dis ; 21(1): 10, 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034646

RESUMO

BACKGROUND: Lipocalin-2 (LCN2) has a critical effect on obesity as well as its associated comorbidities. The present study focused on analyzing serum LCN2 levels of obese patients with nonalcoholic fatty liver disease (NAFLD) and on determining relationship of hepatic steatosis improvement with LCN2 levels after laparoscopic sleeve gastrectomy (LSG). METHODS: This work enrolled ninety patients with obesity and NAFLD. Twenty-three of them underwent LSG. Anthropometric and biochemical parameters and serum LCN2 levels were determined at baseline and those at 6-month post-LSG. Controlled attenuation parameter (CAP) measured by FibroScan was adopted for evaluating hepatic steatosis. RESULTS: Among severe obesity patients, serum LCN2 levels were significantly increased (111.59 ± 51.16 ng/mL vs. 92.68 ± 32.68 ng/mL, P = 0.035). The CAP value was higher indicating higher liver fat content (360.51 ± 45.14 dB/m vs. 340.78 ± 45.02 dB/m, P = 0.044). With regard to surgical patients, liver function, glucose, and lipid levels were significantly improved after surgery. Serum LCN2 levels significantly decreased (119.74 ± 36.15 ng/mL vs. 87.38 ± 51.65 ng/mL, P = 0.001). Decreased CAP indicated a significant decrease in liver fat content (358.48 ± 46.13 dB/m vs. 260.83 ± 69.64 dB/m, P < 0.001). The decrease in LCN2 levels was significantly related to the reduced hepatic fat content and improvement in steatosis grade after adjusting for gender, age, and BMI decrease. CONCLUSIONS: Serum LCN2 levels are related to obesity and NAFLD. The decreased serum LCN2 levels could be an indicator of hepatic steatosis improvement.

10.
Hepatol Int ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037228

RESUMO

BACKGROUND: No reports exist regarding the prevalence of different Na levels and their relationship with 90-day prognosis in hospitalized patients with acute-on-chronic liver disease (AoCLD) in China. Therefore, the benefit of hyponatremia correction in AoCLD patients remains unclear. METHODS: We prospectively collected the data of 3970 patients with AoCLD from the CATCH-LIFE cohort in China. The prevalence of different Na levels (≤ 120; 120-135; 135-145; > 145) and their relationship with 90-day prognosis were analyzed. For hyponatremic patients, we measured Na levels on days 4 and 7 and compared their characteristics, based on whether hyponatremia was corrected. RESULTS: A total of 3880 patients were involved; 712 of those developed adverse outcomes within 90 days. There were 80 (2.06%) hypernatremic, 28 (0.72%) severe hyponatremic, and 813 (20.95%) mild hyponatremic patients at admission. After adjusting for all confounding factors, the risk of 90-day adverse outcomes decreased by 5% (odds ratio [OR] 0.95; 95% confidence interval [CI] 0.93-0.97; p < 0.001), 24% (OR 0.76; 95% CI 0.70-0.84; p < 0.001), and 42% (OR 0.58; 95% CI 0.49-0.70; p < 0.001) as Na level increased by 1, 5, and 10 mmol/L, respectively. Noncorrection of hyponatremia on days 4 and 7 was associated with 2.05-fold (hazard ratio [HR], 2.05; 95% CI, 1.50-2.79; p < 0.001) and 1.46-fold (HR 1.46; 95% CI 1.05-2.02; p = 0.028) higher risk of adverse outcomes. CONCLUSIONS: Hyponatremia was an independent risk factor for a poor 90-day prognosis in patients with AoCLD. Failure to correct hyponatremia in a week after admission was often associated with increased mortality. (ClinicalTrials.gov number: NCT02457637, NCT03641872). CLINICAL TRIAL NUMBERS: This study is registered at Shanghai www.clinicaltrials.org (NCT02457637 and NCT03641872).

11.
Aging (Albany NY) ; 14(undefined)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037899

RESUMO

Drug resistance has become an obstacle to the further development of immunotherapy in clinical applications and experimental studies. In the current review, the acquired resistance to immunotherapy was examined. The mechanisms of acquired resistance were based on three aspects as follows: The change of the tumor functions, the upregulated expression of inhibitory immune checkpoint proteins, and the effects of the tumor microenvironment. The combined use of immunotherapy and other therapies is performed to delay acquired resistance. A comprehensive understanding of acquired drug resistance may provide ideas for solving this dilemma.

12.
Chemosphere ; : 133547, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998841

RESUMO

Bio-clogging of leachate collection systems has attracted much attention because of its threat to landfill slope stability and landfill landslide events. Calcium in leachate plays a vital role in the formation of bio-clogging. However, the influence of calcium on bio-clogging remains unclear. This study examined the effects of calcium concentration on bio-clogging, including 0, 1.25, 5, 25, and 75 mM CaCl2 groups. A technique involving quartz crystal microbalance with dissipation monitoring (QCM-D) was applied to evaluate the bacteria adhesion behaviors in real time. The results showed that the presence of Ca2+ accelerated the bacterial attachment and increased the viscoelasticity of deposited layers. The deposition mass for 75 mM CaCl2 was 1442 ±â€¯260 ng/cm2, which is 1.5 times that for 1.25 mM CaCl2. The Derjaguin-Landau-Verwey-Overbeek (DLVO) theory could explain the bacterial adhesion behaviors in low calcium concentrations (<25 mM). In comparison, the effect of calcium bridge was shown in high calcium concentrations (>25 mM). The development of biofilms was a dynamic process, and the Ca2+ concentration was positively related to the amount of biofilm generated. In low CaCl2 concentration (less than 5 mM) groups, the degree of bio-clogging increased from the exponential growth phase to the decline phase; in contrast, in high CaCl2 concentration (above 25 mM) groups, the degree of bio-clogging increased and later declined. Therefore, the calcium concentration should be controlled at a low level in leachate to mitigate bio-clogging in LCSs.

13.
Sci Rep ; 12(1): 878, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042894

RESUMO

Supervised machine learning is a traditionally remaining useful life (RUL) estimation tool, which requires a lot of prior knowledge. For the situation lacking labeled data, supervised methods are invalid for the issue of domain shift in data distribution. In this paper, a adversarial-based domain adaptation (ADA) architecture with convolution neural networks (CNN) for RUL estimation of bearings under different conditions and platforms, referred to as ADACNN, is proposed. Specifically, ADACNN is trained in source labeled data and fine-tunes to similar target unlabeled data via an adversarial training and parameters shared mechanism. Besides a feature extractor and source domain regressive predictor, ADACNN also includes a domain classifier that tries to guide feature extractor find some domain-invariant features, which differents with traditional methods and belongs to a unsupervised learning in target domain, which has potential application value and far-reaching significance in academia. In addition, according to different first predictive time (FPT) detection mechanisms, we also explores the impact of different FPT detection mechanisms on RUL estimation performance. Finally, according to extensive experiments, the results of RUL estimation of bearing in cross-condition and cross-platform prove that ADACNN architecture has satisfactory generalization performance and great practical value in industry.

14.
Drug Chem Toxicol ; : 1-10, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986718

RESUMO

The chemical warfare agent sulfur mustard (SM) causes severe cutaneous lesions characterized by epidermal cell death, apoptosis, and inflammation. At present, the molecular mechanisms underlying SM-induced injury are not well understood, and there is no standard treatment protocol for SM-exposed patients. Here, we conducted a high-content screening of the Food and Drug Administration (FDA)-approved drug library of 1018 compounds against SM injury on an immortal human keratinocyte HaCaT cell line, focusing on cell survival. We found that the B-Raf inhibitor vemurafenib had an apparent therapeutic effect on HaCaT cells and resisted SM toxicity. Other tested B-Raf inhibitors, both type-I (dabrafenib and encorafenib) and type-II (RAF265 and AZ628), also exhibited potent therapeutic effects on SM-exposed HaCaT cells. Both SM and vemurafenib triggered extracellular signal-related kinase (ERK) activation. The therapeutic effect of vemurafenib in HaCaT cells during SM injury was ERK-dependent, indicating a specific role of ERK in keratinocyte regulatory mechanisms. Furthermore, vemurafenib partially improved cutaneous damage in a mouse ear vesicant model. Collectively, our results provide evidence that the B-Raf inhibitor vemurafenib is a potential therapeutic agent against SM injury, and oncogenic B-Raf might be an exciting new therapeutic target following exposure to mustard vesicating agents.

15.
Arch Osteoporos ; 17(1): 14, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020038

RESUMO

Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. INTRODUCTION: Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. METHODS: This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. RESULTS: A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: - 0.71 to 1.00, equivalence margin: - 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and ß-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (ß-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. CONCLUSION: Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

16.
Proc Natl Acad Sci U S A ; 119(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35022240

RESUMO

The quasiperiodic structures in metal alloys have been known to depend on the existence of icosahedral order in the melt. Among different phases observed in intermetallics, decagonal quasicrystal (DQC) structures have been identified in many glass-forming alloys yet remain inaccessible in bulk-state condensed soft matters. Via annealing the mixture of two giant molecules, the binary system assemblies into an axial DQC superlattice, which is identified comprehensively with meso-atomic accuracy. Analysis indicates that the DQC superlattice is composed of mesoatoms with an unusually broad volume distribution. The interplays of submesoatomic (molecular) and mesoatomic (supramolecular) local packings are found to play a crucial role in not only the formation of the metastable DQC superlattice but also its transition to dodecagonal quasicrystal and Frank-Kasper σ superlattices.

17.
Brain Imaging Behav ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34997425

RESUMO

Abnormal functional connectivity (FC) has been reported in drug-naive first-episode adolescent-onset schizophrenia (AOS) with inconsistent results due to differently selected regions of interest. The voxel-wise global-brain functional connectivity (GFC) analysis can help explore abnormal FC in an unbiased way in AOS. A total of 48 drug-naive first-episode AOS as well as 31 sex-, age- and education-matched healthy controls were collected. Data were subjected to GFC, correlation analysis and support vector machine analyses. Compared with healthy controls, the AOS group exhibited increased GFC in the right middle frontal gyrus (MFG), and decreased GFC in the right inferior temporal gyrus, left superior temporal gyrus (STG)/precentral gyrus/postcentral gyrus, right posterior cingulate cortex /precuneus and bilateral cuneus. After the Benjamini-Hochberg correction, significantly negative correlations between GFC in the bilateral cuneus and Trail-Making Test: Part A (TMT-A) scores (r=-0.285, p=0.049), between GFC in the left STG/precentral gyrus/postcentral gyrus and TMT-A scores (r=-0.384, p=0.007), and between GFC in the right MFG and the fluency scores (r=-0.335, p=0.020) in the patients. GFC in the left STG/precentral gyrus/postcentral gyrus has a satisfactory accuracy (up to 86.08%) in classifying patients from controls. AOS shows abnormal GFC in the brain areas of multiple networks, which bears cognitive significance. These findings suggest potential abnormalities in processing self-monitoring and sensory prediction, which further elucidate the pathophysiology of AOS.

18.
Cancers (Basel) ; 14(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35008426

RESUMO

Current anticancer treatments are inefficient against glioblastoma multiforme (GBM), which remains one of the most aggressive and lethal cancers. Evidence has shown the presence of glioblastoma stem cells (GSCs), which are chemoradioresistant and associated with high invasive capabilities in normal brain tissues. Moreover, accumulating studies have indicated that radiotherapy contributes to abnormalities in cell cycle checkpoints, including the G1/S and S phases, which may potentially lead to resistance to radiation. Through computational simulations using bioinformatics, we identified several GBM oncogenes that are involved in regulating the cell cycle. Cyclin B1 (CCNB1) is one of the cell cycle-related genes that was found to be upregulated in GBM. Overexpression of CCNB1 was demonstrated to be associated with higher grades, proliferation, and metastasis of GBM. Additionally, increased expression levels of CCNB1 were reported to regulate activation of mitogen-activated protein kinase 7 (MAPK7) in the G2/M phase, which consequently modulates mitosis; additionally, in clinical settings, MAPK7 was demonstrated to promote resistance to temozolomide (TMZ) and poor patient survival. Therefore, MAPK7 is a potential novel drug target due to its dysregulation and association with TMZ resistance in GBM. Herein, we identified MAPK7/extracellular regulated kinase 5 (ERK5) genes as being overexpressed in GBM tumors compared to normal tissues. Moreover, our analysis revealed increased levels of the cell division control protein homolog (CDC42), a protein which is also involved in regulating the cell cycle through the G1 phase in GBM tissues. This therefore suggests crosstalk among CCNB1/CDC42/MAPK7/cluster of differentiation 44 (CD44) oncogenic signatures in GBM through the cell cycle. We further evaluated a newly synthesized small molecule, SJ10, as a potential target agent of the CCNB1/CDC42/MAPK7/CD44 genes through target prediction tools and found that SJ10 was indeed a target compound for the above-mentioned genes; in addition, it displayed inhibitory activities against these oncogenes as observed from molecular docking analysis.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35010716

RESUMO

Recent research has emphasized the crucial role of expressive flexibility in mental health. This study extended prior studies by further exploring the mediating mechanism and possible gender differences underlying the association between expressive flexibility and mental health indexed by depression and life satisfaction based on the dual-factor model of mental health. Specifically, we explored whether social support mediated the association between expressive flexibility and depression as well as life satisfaction, and whether there were gender differences in these relationships. A total of 711 voluntary college students (mean age = 20.98 years, SD = 2.28; 55.70% women) completed a set of scales assessing expressive flexibility, perceived social support, depression, and life satisfaction. Results showed that expressive flexibility had a positive direct effect on life satisfaction and social support mediated this association. Social support also mediated the relationship between expressive flexibility and depression. The mediation effect of social support was robust and consistent in men and women whereas expressive flexibility had a stronger direct effect on depression in women compared to men. The present study contributes to clarifying the relationship between expressive flexibility and mental health from a more comprehensive perspective. Last, the strengths and limitations of this study were discussed.

20.
J Exp Clin Cancer Res ; 41(1): 19, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012593

RESUMO

BACKGROUND: Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification. METHODS: Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression. RESULTS: M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain-containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown. CONCLUSIONS: M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A-CRB3-Hippo pathway.

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