The trifluoromethylsulfinylation reaction of activated arenes with trifluoromethanesulfinyl chloride (CF3SOCl) in the presence of Lewis acid was achieved under mild and solvent‐free conditions. A ...series of aryl trifluoromethyl sulfoxides were obtained in moderate to high yields. The protocol could be extended to the perfluoroalkylsulfinylation of activated arenes, as well as the trifluoromethylsulfinylation of indoles without additive.
A facile method for the trifluoromethylsulfinylation of activated arenes with trifluoromethanesulfinyl chloride in the presence of Lewis acid was developed. The protocol could be expanded to the perfluoroalkylsulfinylation of activated arenes, as well as the trifluoromethylsulfinylation of indoles without additive.
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UPUK
To evaluate the prognostic effects of combining serum circulating tumor cells (CTCs) and squamous cell carcinoma antigen (SCC-Ag) levels on patients with locally advanced cervical cancer treated with ...radiotherapy.
Ninety-nine patients with locally advanced cervical cancer (FIGO stage IIB-IVA) undergoing radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) were identified. The association between serum CTC level and clinicopathological parameters was examined. Univariate and multivariate survival analyses were performed by using Cox's proportional hazards regression model.
Elevated CTC and SCC-Ag levels were significantly associated with poor disease-free survival (DFS). Multivariate analysis suggest that serum CTC level, FIGO stage and serum SCC-Ag level were independent prognostic factors for two-year DFS. When CTC and SCC-Ag levels were combined into a new risk model to predict disease progression of cervical cancer patients, it performed a significantly better predictive efficiency compared with either biomarker alone.
Serum CTC and SCC-Ag levels are potentially useful biomarkers for prediction of prognosis in locally advanced cervical cancer patients and their combination significantly improves predictive ability for survival in locally advanced cervical cancer patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nonobstructive azoospermia (NOA) is one of the most difficult forms of male infertility to treat, and its pathogenesis is still unclear. miRNAs can regulate autophagy by affecting their target gene ...expression. Our previous study found that miR-188-3p expression in NOA patients was low. There are potential binding sites between the autophagy gene ATG7 and miR-188-3p. This study aimed to verify the binding site between miR-188-3p and ATG7 and whether miR-188-3p affects autophagy and participates in NOA by regulating ATG7 to influence the autophagy marker genes LC3 and Beclin-1.
Testicular tissue from 16 NOA patients and 16 patients with normal spermatogenesis and 5 cases in each group of pathological sections were collected. High-throughput sequencing was performed to detect mRNA expression differences. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunohistochemical staining and immunofluorescence were used to detect protein localization and expression. Autophagosome changes were detected by electron microscopy. The targeting relationship between miR-188-3p and ATG7 was confirmed by a luciferase assay.
ATG7 protein was localized in the cytoplasm of spermatogenic cells at all levels, and the ATG7 gene (p = 0.019) and protein (p = 0.000) were more highly expressed in the NOA group. ATG7 expression after overexpression/inhibition of miR-188-3p was significantly lower (p = 0.029)/higher (p = 0.021) than in the control group. After overexpression of miR-188-3p, the ATG7 3'UTR-WT luciferase activity was impeded (p = 0.004), while the ATG7 3'UTR-MUT luciferase activity showed no significant difference (p = 0.46). LC3 (p = 0.023) and Beclin-1 (p = 0.041) expression in the NOA group was significantly higher. LC3 and Beclin-1 gene expression after miR-188-3p overexpression/inhibition was significantly lower (p = 0.010 and 0.024, respectively) and higher (p = 0.024 and 0.049, respectively). LC3 punctate aggregation in the cytoplasm decreased after overexpression of miR-188-3p, while the LC3 punctate aggregation in the miR-188-3p inhibitor group was higher. The number of autophagosomes in the miR-188-3p mimic group was lower than the number of autophagosomes in the mimic NC group.
LC3 and Beclin-1 were more highly expressed in NOA testes and negatively correlated with the expression of miR-188-3p, suggesting that miR-188-3p may be involved in the process of autophagy in NOA. miR-188-3p may regulate its target gene ATG7 to participate in autophagy anDual luciferase experiment d affect the development of NOA.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
External modulation on thermal convection has been studied extensively to achieve the control of flow structures and heat-transfer efficiency. In this paper, we carry out direct numerical simulations ...on Rayleigh–Bénard convection accounting for both the modulation of wall shear and roughness over the Rayleigh number range $1.0 \times 10^6 \le Ra \le 1.0 \times 10^8$, the wall shear Reynolds number range $0 \le Re_w \le 5000$, the aspect-ratio range $2 \le \varGamma \le 4{\rm \pi}$, and the dimensionless roughness height range $0 \le h \le 0.2$ at fixed Prandtl number $Pr = 1$. Under the combined actions of wall shear and roughness, with increasing $Re_w$, the heat flux is initially enhanced in the buoyancy-dominant regime, then has an abrupt transition near the critical shear Reynolds number $Re_{w,cr}$, and finally enters the purely diffusion regime dominated by shear. Based on the crossover of the kinetic energy production between the buoyancy-dominant and shear-dominant regimes, a physical model is proposed to predict the transitional scaling behaviour between $Re_{w,cr}$ and $Ra$, i.e. $Re_{w,cr} \sim Ra^{9/14}$, which agrees well with our numerical results. The reason for the observed heat-transport enhancement in the buoyancy-dominant regime is further explained by the fact that the moving rough plates introduce an external shear to strengthen the large-scale circulation (LSC) in the vertical direction and serve as a conveyor belt to increase the chances of the interaction between the LSC and secondary flows within cavities, which triggers more thermal plumes, efficiently transports the trapped hot (cold) fluids outside cavities.
This paper constructs a remaining useful life (RUL) prediction model combining a convolutional neural network and a long short‐term memory network (CNNLSTM) to support decision‐making, especially the ...safety of rotational equipment. It avoids the influence of personnel and realizes the complementary advantages of the network. With the assistance of Bayesian short‐term and long‐term memory neural networks, the remaining life prediction method is able to provide the confidence interval of the remaining life prediction of rolling bearings. The compression between the proposed method and existing state‐of‐the‐art methods validated the good performance of the proposed method. Overall, the proposed method contributes to life prediction and condition‐based maintenance of bearings and complex rotational systems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The tire-road peak adhesion coefficient (TRPAC) describes the tire adhesion limit that a road can provide. The TRPAC is a key parameter for precise vehicle motion control and an important basis for ...decision-making and planning of intelligent vehicles. Considering the critical and difficult problems in the estimation of TRPAC, such as slow convergence and low accuracy, a TRPAC estimation method based on the fusion of vehicle dynamics and machine vision is proposed in this paper. Based on the observability theory of nonlinear systems, local weak observability of the dynamics-based estimator is analyzed to explain the limitation of a single dynamics-based estimator. The framework of dynamics-image-based fusion estimator is then proposed, including the fusion of data, model and decision levels. A dynamics-based fusion estimator is designed by considering the coupling relationship of longitudinal and lateral tire forces to adapt the conditions of complex excitations. Start-and-stop strategy for the dynamics-based fusion estimator is designed by setting excitation thresholds for different types of road surfaces, which are identified using vision information. Parameter self-tuning for the dynamics-based fusion estimator based on the image-based estimator is proposed to improve convergence speed and reduce oscillation. The results of the simulation and vehicle test show that the road estimation error of the proposed method is within 0.03 and the convergence time is within 0.5 s. Compared with other existing estimators, the fusion estimator achieved better accuracy, sensitivity and stability, particularly when complex excitations were present.
As a transfer member at the discontinuous place of vertical load, the deep beam has a complex stress mechanism and many influencing factors, such as compressive strength of concrete, shear span ...ratio, and reinforcement ratio. At the same time, the stress analysis principle of traditional shallow beams is no longer applicable to the design and calculation of deep-beam structure. The main purpose of this paper was to use the strut-and-tie model to analyze its stress mechanism, and to verify the applicability of the model. Nine high-strength concrete deep-beam specimens with longitudinal reinforcement with an anchor plate of the same size were tested by two-point concentrated loading method. The effects of shear span ratio (0.3, 0.6, and 0.9), longitudinal reinforcement ratio (0.67%, 1.05%, and 1.25%), horizontal reinforcement ratio (0.33%, 0.45%, and 0.50%), and stirrup reinforcement ratio (0.25%, 0.33%, and 0.50%) on the failure mode, deflection curve, characteristic load, crack width, steel bar, and concrete strain of the specimens were analyzed. The results showed that the failure mode of deep-beam specimens was diagonal compression failure. The normal section cracking load was about 15 to 20% of the ultimate load, and the inclined section cracking load was about 30~40% of the ultimate load. The shear span ratio increased from 0.3 to 0.9, and the bearing capacity decreased by 32.9%. When the longitudinal reinforcement ratio increased from 0.67% to 1.25%, the ultimate load increased by 42.6%. The shear span ratio and longitudinal reinforcement ratio have a significant effect on the bearing capacity of the high-strength concrete deep beams with longitudinal reinforcement with an anchor plate. The shear capacity of nine high-strength concrete deep-beam specimens with longitudinal reinforcement with an anchor plate was calculated by national standards, and the results were compared with the calculation results of the Tan–Tang model, the Tan–Cheng model, SSTM, and SSSTM. The analysis showed that the softened strut-and-tie model takes into account the softening effect of compressive concrete, and is a more accurate mechanical model, which can be applied to predict the shear capacity of high-strength concrete deep-beam members with longitudinal reinforcement with an anchor plate.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Colorectal cancer (CRC) continues to be one of the most malignant cancers with a high mortality rate to date. Promoting the radio‐responsiveness of CRC is of great importance for local control and ...prognosis. In this study, we examined the roles of exosomal microRNA‐19b (miR‐19b) in CRC radioresistance. The regulatory role of miR‐19b in CRC stem cells and radiotherapy‐resistant cells was determined using miRNA microarray analysis, and its prognostic value was probed using the TCGA database. It was found that miR‐19b was overexpressed in CRC tissues, which indicated a poor prognosis. CRC‐derived exosomes (EXOs) enhanced the radio‐resistance and stemness properties of CRC cells via delivery of miR‐19b in vitro and in vivo. FBXW7 was identified as a putative target of miR‐19b. On the contrary, reintroduction of FBXW7 reversed the effects of miR‐19b on radioresistance and stemness properties. Furthermore, the Wnt/β‐catenin pathway activity was elevated in CRC cells upon EXOs treatment, decreased after miR‐19b downregulation, and increased again after FBXW7 downregulation. These results suggest that miR‐19b inhibition could enhance the efficacy of radiotherapy while reducing the stemness properties, thus presenting a promising strategy for sensitizing CRC cells to radiotherapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Combretastatin-4 (CA-4) as a tubulin polymerization inhibitor draws extensive attentions. However, due to its weak stability of
-olefin and poor metabolic stability, structure modifications on
...-configuration are being performed. In this work, we constructed a series of novel CA-4 analogues with linkers on olefin containing diphenylethanone,
-locked dihydrofuran, α-substituted diphenylethanone, cyclobutane and cyclohexane on its
-olefin. Cytotoxic activity of all analogues was measured by an SRB assay. Among them, compound
, a by-product in the preparation of diphenylethanone analogues, was found to be the most potent cytotoxic agents against HepG2 cells with IC
values of less than 0.5 μM. The two isomers of
induced cellular apoptosis tested by Annexin V-FITC and propidium iodide (PI) double staining, arrested cells in the G2/M phase by PI staining analysis, and disrupted microtubule network by immunohistochemistry study in HepG2 cells. Moreover,
displayed a dose-dependent inhibition effect for tubulin assembly in in vitro tubulin polymerization assay. In addition, molecular docking studies showed that two isomers of
could bind efficiently at colchicine binding site of tubulin similar to CA-4.
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Rat hepatitis E virus (rat HEV) was first identified in wild rats and was classified as the species
in the genera
, which is genetically different from the genotypes HEV-1 to HEV-8, which are ...classified as the species
. Although recent reports suggest that rat HEV transmits to humans and causes hepatitis, the infectivity of rat HEV to non-human primates such as cynomolgus and rhesus monkeys remains controversial. To investigate whether rat HEV infects non-human primates, we inoculated one cynomolgus monkey and five rhesus monkeys with a V-105 strain of rat HEV via an intravenous injection. Although no significant elevation of alanine aminotransferase (ALT) was observed, rat HEV RNA was detected in fecal specimens, and seroconversion was observed in all six monkeys. The partial nucleotide sequences of the rat HEV recovered from the rat HEV-infected monkeys were identical to those of the V-105 strain, indicating that the infection was caused by the rat HEV. The rat HEV recovered from the cynomolgus and rhesus monkeys successfully infected both nude and Sprague-Dawley rats. The entire rat HEV genome recovered from nude rats was identical to that of the V-105 strain, suggesting that the rat HEV replicates in monkeys and infectious viruses were released into the fecal specimens. These results demonstrated that cynomolgus and rhesus monkeys are susceptible to rat HEV, and they indicate the possibility of a zoonotic infection of rat HEV. Cynomolgus and rhesus monkeys might be useful as animal models for vaccine development.
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