A one‐pot approach for the asymmetric synthesis of C2‐tetrasubstituted indolin‐3‐ones from 2‐substituted indoles was developed via merging transition metal catalysis with organocatalysis. This ...strategy involves two processes, including CuI catalyzed oxidative dearomatization of 2‐substituted indoles using O2 as green oxidant, and followed by an proline‐promoted asymmetric Mannich reaction with ketones or aldehydes. A series of C2‐tetrasubstituted indolin‐3‐ones were obtained in 35–86% yields, 2:1‐>20:1 dr and 48–99% ee. Moreover, the synthetic 2‐tetrasubstituted indolin‐3‐ones could be easily transformed into 1H‐1,3 oxazino 3,4‐aindol‐5(3H)‐ones via a 4+1 cyclization process. In addition, the synthetic compound 3 s show certain antibacterial activity against S. aureus ATCC25923 and multi‐drug resistance bacterial strain of S. aureus (20151027077) and its MIC values up to 8 μg/mL and 16 μg/mL, respectively.
Purpose
Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes, is linked to glycaemic derangements. Glycaemic variability, as a pattern of glycaemic derangements, is a ...key risk factor for diabetic complications. We investigated the association of glycaemic variability with DPN in a large-scale sample of type 2 diabetic patients.
Methods
In this cross-sectional study, we enrolled 982 type 2 diabetic patients who were screened for DPN and monitored by a continuous glucose monitoring (CGM) system between February 2011 and January 2017. Multiple glycaemic variability parameters, including the mean amplitude of glycaemic excursions (MAGE), mean of daily differences (MODD), standard deviation of glucose (SD), and 24-h mean glucose (24-h MG), were calculated from glucose profiles obtained from CGM. Other possible risks for DPN were also examined.
Results
Of the recruited type 2 diabetic patients, 20.1% (
n
= 197) presented with DPN, and these patients also had a higher MAGE, MODD, SD, and 24-h MG than patients without DPN (
p
< 0.001). Using univariate and multiple logistic regression analyses, MAGE and conventional risks including diabetic duration, HOMA-IR, and hemoglobin A1c (HbA1c) were found to be independent contributors to DPN, and the corresponding odds ratios (95% confidence interval) were 4.57 (3.48–6.01), 1.10 (1.03–1.17), 1.24 (1.09–1.41), and 1.33 (1.15–1.53), respectively. Receiver operating characteristic analysis indicated that the optimal MAGE cutoff value for predicting DPN was 4.60 mmol/L; the corresponding sensitivity was 64.47%, and the specificity was 75.54%.
Conclusions
In addition to conventional risks including diabetic duration, HOMA-IR and HbA1c, increased glycaemic variability assessed by MAGE is a significant independent contributor to DPN in type 2 diabetic patients.
Neovascularization is a key factor that contributes to tumor metastasis, and vasculogenic mimicry (VM) is an important form of neovascularization found in highly invasive tumors, including lung ...cancer. Despite the increasing number of studies focusing on VM, the mechanisms underlying VM formation remain unclear. Herein, our study explored the role of the HIF-1α/NRP1 axis in mediating lung adenocarcinoma metastasis and VM formation. HIF-1α, NRP1 expression, and VM in lung adenocarcinoma (LUAD) patient samples were examined by immunohistochemical staining. Quantitative real-time (qRT-PCR), western blot, transwell assay, wound healing assay, and tube formation assay were performed to verify the role of HIF-1α/NRP1 axis in LUAD metastasis and VM formation. ChIP and luciferase reporter assay were used to confirm whether NRP1 is a direct target of HIF-1α. In LUAD tissues, we confirmed a positive relationship between HIF-1α and NRP1 expression. Importantly, high HIF-1α and NRP1 expression and the presence of VM were correlated with poor prognosis. We also found that HIF-1α could induce LUAD cell migration, invasion, and VM formation by regulating NRP1. Moreover, we demonstrated that HIF-1α can directly bind to the NRP1 promoter located between -2009 and -2017 of the promoter. Mechanistically, MMP2, VE-cadherin, and Vimentin expression were affected. HIF-1α plays an important role in inducing lung adenocarcinoma cell metastasis and VM formation via upregulation of NRP1. This study highlights the potential therapeutic value of targeting NRP1 for suppressing lung adenocarcinoma metastasis and progression.
The prognostic impact of long-term glycemic variability on clinical outcomes in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) remains unclear. We determined and compared ...hemoglobin A1c (HbA1c) variability and clinical outcomes for patients with HF with preserved ejection fraction (HFpEF), HF with mid-range ejection fraction (HFmrEF) and HF with reduced ejection fraction (HFrEF) in a prospective longitudinal study.
Patients with HF and T2DM, undergone 3 or more HbA1c determinations during the first 18 months, were then followed for 42 months. The primary outcome was death from any cause. Secondary outcome was composite endpoints with death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF and HFrEF.
Of 902 patients enrolled, 32.2% had HFpEF, 14.5% HFmrEF, and 53.3% HFrEF. During 42 months of follow-up, 270 (29.9%) patients died and 545 (60.4%) patients experienced composite endpoints of death and HF readmission. The risk of all-cause death or composite endpoints was lower for HFpEF than HFrEF. Moreover, higher HbA1c variability was associated with higher all-cause mortality or composite endpoints and HbA1c variability was an independent predictor of all-cause mortality or composite endpoints, regardless of EF.
This prospective longitudinal study showed that the all-cause death and composite events was lower for HFpEF than HFrEF. HbA1c variability was independently and similarly predictive of death or combined endpoints in the three HF phenotypes.
A copper-catalyzed difunctional cyano-, thiocyano-, and chlorophosphorylation reaction of alkynes with P(O)–H compounds and coupling partners (TBACN, TMSNCS, TMSCl) is described. The reaction ...introduces versatile groups (−P(O)R2 and −CN, −SCN, or −Cl) to form tri- and tetrasubstituted alkenyl phosphine oxides/phosphonates regio- and stereoselectively.
This study proposes a novel moving force neural identifier (MFNI), a deep neural network designed for accurately estimating dynamic vehicular axle loads without knowing the vehicle speed and axle ...configurations (i.e., axle number and spacing). The MFNI architecture comprises a multi-time resolution encoder/decoder (MRED) and a dynamic moving force correction block (DMF-corr block). Firstly, the MRED with hierarchical resolution is developed to adapt to the complex dynamic inverse problem-solving. It can capture the multi-time resolution features of bridge responses and dynamic moving forces, and perform stably under various lengths of identification sampling windows. Then, the DMF-corr block limits the range of identified values by assuming that the vehicular excitation on the bridge is unidirectional, which enables the MFNI model to better determine the axle number, vehicle speed, as well as whether the axle is acting on the bridge. Numerical studies are implemented to confirm the accuracy and efficiency of the proposed MFNI approach, and a parametric sensitivity analysis is conducted to evaluate the robustness of the approach. Finally, a laboratory experiment confirms the practicability of the MFNI in detecting vehicular moving forces with a limited number of sensors and training samples. Both numerical and experimental results demonstrate the potential of the proposed method to serve as a nothing-on-road bridge weigh-in-motion system in practical engineering.
•A deep-learning method for moving force identification is proposed, without the prior information on the axle configurations.•The proposed framework can adaptively determine the speed, axle count, and axle base during the moving force identification.•The feasibility of using simulated data for model training and subsequently predicting experimental loads is demonstrated.
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•AIE-active enantiomers show dual-mode afterglows and obvious mechanoluminescence.•Afterglow colour can be linearly tuned from yellow to sky blue by temperature.•Relatively stable ...warm-white afterglow is observed at around room temperature.•Effects of molecular arrangement on luminescence behaviors are demonstrated.
Dual-mode persistent luminescence and helical-array-induced mechanoluminescence (ML) are observed for the first time from two different polymorphs (SCp and SCb) of a pair of AIE-active enantiomers, respectively. The impressive afterglows from the SCp crystals of (R)-ImNCz and (S)-ImNCz are composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence, and their colours can be tuned from yellow to sky blue by temperature in a mild window from 0 °C to 100 °C. In particular, the SCp crystals of (S)-ImNCz present relatively stable warm-white afterglows at around room temperature. The generation of dual-mode persistent luminescence from SCp crystals is probably associated with the charge separation and recombination as well as the small ΔEST values of enantiomer molecules and the strong intermolecular interactions in crystal structures. On the other hand, the conspicuous ML of (R)-ImNCz and (S)-ImNCz from SCb crystals likely results from their helical arrays and notable AIE properties, enabling the formation of crystals with polar space groups and high fluorescence quantum yields. The results from this polymorphic system may provide useful guidance for the development of new organic emitters with innovative applications.
This paper addresses the problem of time-varying formation tracking for a kind of second-order multi-agent systems with a switching topology, in which the dynamics of agents are modeled by double ...integrators and harmonic oscillators respectively. The control input of each agent is subject to saturation. First, depending on the low-gain state feedback technique, an algorithm is designed to solve semi-global time-varying formation tracking problem, where feasibility condition of formation tracking is introduced. Then, by utilizing the Lyapunov function and low-gain feedback theory, it is proved that second-order multi-agent system with a switching topology achieves the specified semi-global time-varying formation tracking if some sufficient conditions hold. Further, as an extension, jointly connected switching topology is considered, and the corresponding formation tracking problem is also explored. Subsequently, several simulation examples is worked out for illustration.
Investigations on the impact of drought stress on the reproductive growth of
have been relatively limited compared to the extensive research conducted on its nutritional growth. To study the effects ...of drought stress on the growth and development of
flower buds, we investigated the effects of drought stress on the bud anatomical structure, relative water content, relative electrical conductivity, antioxidant enzyme activity, osmoregulation substance content, and hormone contents of
using 4-year-old potted plants ('Huaxin' cultivar) as experimental materials. We observed
flower bud shrinkage, faded pollen colour, shortened style length, decreased relative water content, increased relative electrical conductivity, and decreased pollen germination rate under drought stress. As the stress treatment duration increased, the malondialdehyde (MDA), soluble sugar (SS), soluble protein (SP), and proline (Pro) contents, as well as peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activities increased. Moreover, the levels of the plant hormones indole acetic acid (IAA) and cytokinin (CTK) increased, whereas those of salicylic acid (SA) and jasmonic acid (JA) decreased, and those of abscisic acid (ABA) and gibberellin a
(GA
) first increased and then decreased. Compared to the control group, the drought treatment group exhibited stronger antioxidant capacity, water regulation ability, and drought stress protection. These results indicate that
is adaptable to drought-prone environments. The results of this study provide a theoretical basis for the evaluation of drought resistance in
, as well as the development of water management strategies for cultivation.
The international pesticide trade network (iPTN) is a key factor affecting global food production and food security. The trade relationship is a key component in iPTNs. In a complex international ...trade environment, we model the impacts of uncertain factors such as trade wars, economic blockades and local wars, as removing vital relationships in the trade network. There are many complex network studies on node centrality, but few on link centrality or link importance. We propose a new method for computing network link centrality. The main innovation of the method is in converting the original network into a dual graph, the nodes in the dual graph corresponding to the links of the original network. Through the dual graph, the node centrality indicators can measure the centrality of the links in the original network. We verify the effectiveness of the network link centrality indicator based on the dual graph in the iPTN, analyze the relationship between the existing network link centrality indicators and the indicator proposed in this paper, and compare their differences. It is found that the trade relationships with larger indicators (hub, outcloseness, outdegree) based on the dual graph have a greater impact on network efficiency than those based on the original pesticide trade networks.
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