Pd-Catalyzed Enantioselective Three-Component Carboamination of 1,3-Cyclohexadiene.

Asymmetric Pd-catalyzed three-component carboamination reactions of dienes to construct chiral cyclohexenylamines, which are of great importance in many fields of chemistry, have remained largely unexplored. Here, we demonstrate a highly enantio- and regioselective Pd/Ming-Phos-catalyzed carboamination reactions of 1,3-cyclohexadiene with readily available aryl iodides and anilines for facile access to diverse valuable chiral cyclohexenylamines. The process shows excellent functional group tolerance, easy scalability, and mild conditions. Moreover, mechanistic studies suggest that this reaction has a first-order dependence on the concentration of the palladium catalyst and aniline.

Ionic Covalent Organic Framework-Based Membranes for Selective and Highly Permeable Molecular Sieving.

Two-dimensional covalent organic frameworks (COFs) with uniform pores and large surface areas are ideal candidates for constructing advanced molecular sieving membranes. However, a fabrication strategy to synthesize a free-standing COF membrane with a high permselectivity has not been fully explored yet. Herein, we prepared a free-standing TpPa-SO3H COF membrane with vertically aligned one-dimensional nanochannels. The introduction of the sulfonic acid groups on the COF membrane provides abundant negative charge sites in its pore wall, which achieve a high water flux and an excellent sieving performance toward water-soluble drugs and dyes with different charges and sizes. Furthermore, the COF membrane exhibited long-term stability, fouling resistance, and recyclability in rejection performance. We envisage that this work provides new insights into the effect of ionic ligands on the design of a broad range of COF membranes for advanced separation applications.

Reference values for exhaled nitric oxide in healthy children aged 6-18 years in China: a cross-sectional, multicenter clinical study.

BACKGROUND: The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6-18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. METHODS: We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6-18. All persons were studied after obtaining informed consent from children and their parents. RESULTS: The mean FeNO50 of 5949 Chinese children and adolescents aged 6-18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6-11 age group, age and height were correlated with the logarithm of FeNO50 (P < 0.001, P < 0.05). There was no significant correlation between the logarithm of FeNO200 and gender, age, height and BMI (all P > 0.05). The logarithm of CaNO was correlated with gender (P < 0.05). In the 12-18 age group, gender, height, and region were correlated with the logarithm of FeNO50 (all P < 0.001). There was only a weak correlation between the logarithm of FeNO200 and height (P < 0.001). The logarithm of CaNO was negatively correlated with age (P < 0.05). CONCLUSIONS: Higher FeNO50, FeNO200 and CaNO values were found in healthy children and adolescents in China compared with foreign reports, and is affected by age, height, gender, and region. This study provides useful references for clinical application of eNO in children, especially Asian children.

Knockdown of Notch Suppresses Epithelial-mesenchymal Transition and Induces Angiogenesis in Oral Submucous Fibrosis by Regulating TGF-ß1.

Oral submucous fibrosis (OSF) is a chronic disorder with a high malignant transformation rate. Epithelial-mesenchymal transition (EMT) and angiogenesis are key events in OSF. The Notch signaling plays an essential role in the pathogenesis of various fibrotic diseases, including OSF. Our study aimed to explore the effects of Notch on the EMT and angiogenesis processes during the development of OSF. The expression of Notch in OSF tissues versus normal buccal mucosa samples was compared. Arecoline was used to induce myofibroblast transdifferentiation of buccal mucosal fibroblasts (BMFs). Short hairpin RNA technique was used to knockdown Notch in BMFs. Pirfenidone and SRI-011381 were used to inhibit and activate the TGF-ß1 signaling pathway in BMFs, respectively. The expression of Notch was markedly upregulated in OSF tissues and fibrotic BMFs. Knockdown of Notch significantly decreased the viability and promoted apoptosis in BMFs subjected to arecoline stimulation. Downregulation of Notch also significantly suppressed the EMT process, as shown by the reduction of N-cadherin and vimentin with concomitant upregulation of E-cadherin. In addition, knockdown of Notch upregulated VEGF and enhanced the angiogenic activity of fBMFs. Moreover, inhibition of TGF-ß1 suppressed viability and EMT, promoted apoptosis, and induced angiogenesis of fBMFs, while activation of TGF-ß1 significantly diminished the effects of Notch knockdown on fBMFs. Knockdown of Notch suppressed EMT and induced angiogenesis in OSF by regulating TGF-ß1, suggesting that the Notch-TGF-ß1 pathway may serve as a therapeutic intervention target for OSF.

Iterative learning control for differential inclusion systems with random fading channels by varying average technique.

The aim of this paper is to study iterative learning control for differential inclusion systems with random fading channels between the plant and the controller. In reality, the phenomenon of fading will inevitably occur in network transmission, which will greatly affect the tracking ability of output trajectory. This study discusses the impact of fading channel on tracking performance at the input and output sides, respectively. First, a set-valued mapping in a differential inclusion system with uncertainty is converted into a single-valued mapping by means of a Steiner-type selector. Then, to offset the effect of the fading channel and improve the tracking ability, a variable local average operator is constructed. The convergence of the learning control algorithm designed by the average operator is proved. The results show that the parameters in the varying local average operator can be adjusted to trade-off between the learning rate and the fading offset rate. Finally, the theoretical results are verified by numerical simulation of the switched reluctance motors.

Poly(I:C) Exacerbates Airway Goblet Cell Hyperplasia and Lung Inflammation in HDM-Exposed Balb/C Mice by YAP/FOXM1 Pathway.

INTRODUCTION: Respiratory viral infection in childhood is closely associated with asthmatic attacks. Of all predisposing factors, viral infection is the primary contributor to acute childhood asthma exacerbations. However, the mechanisms involved in viral asthma are unclear. This study attempted to provide insights into molecular mechanisms in respiratory virus-induced acute asthma exacerbations. METHODS: House dust mite (HDM) was given by intranasal administration to induce asthma in mice. Poly(I:C) was used to mimic the viral infection. A selective YAP inhibitor, verteporfin (VP), was used to investigate the role of the YAP/FOXM1 pathway. The expression of YAP, FOXM1, cytokines, and inflammatory cells in lung tissue, and bronchoalveolar lavage fluid (BALF) was determined using RT-PCR, immunohistochemical, ELISA, and flow cytometry studies. The methacholine challenge assesses airway hyperresponsiveness. In 16HBE cell experiments, we selectively inhibited YAP and FOXM1 by VP and RCM1, respectively, and detected the expression of YAP and FOXM1. RESULTS: The experimental studies have confirmed the YAP/FOXM1 pathway plays a vital role in the differentiation and proliferation of airway club cells into goblet cells and lung inflammation. Poly(I:C) upregulated the expression of FOXM1 by activating transcription factor YAP in mice airway epithelial cells and then promoted the expression of downstream transcription factors SPDEF/MUC5AC, resulting in airway mucus hypersecretion and hyperresponsiveness. In addition, Poly(I:C) facilitates the expression of inflammatory factors in lung tissue. All of these events induce asthma exacerbations. The in vitro studies have confirmed that YAP positively regulates FOXM1 in airway epithelial cells. CONCLUSION: Poly(I:C) promotes airway epithelial goblet cell hyperplasia, mucus hypersecretion, and airway hyperresponsiveness. It also upregulates the expression of inflammatory factors in lung tissue and BALF in asthmatic mice by the YAP/FOXM1 pathway, resulting in asthma attacks.

Countercurrent chromatography separation of vitamin E isomers in a co-current mode.

Vitamin E represents a group of lipophilic phenolic compounds, including α-tocopherol, ß-tocopherol, γ-tocopherol, and δ-tocopherol, and α-tocotrienol, ß-tocotrienol, γ-tocotrienol, and δ-tocotrienol isomers. Different forms of vitamin E have been proven to exhibit varying biological activities. However, due to their structural similarities, the separation of vitamin E isomers is a challenging task. Therefore, it is crucial to establish an efficient method for isolating individual isomers. In this study, co-current countercurrent chromatography was employed to isolate vitamin E isomers from commercial capsules using a n-heptane-methanol-water (10:9.5:0.5, v/v) solvent system. The partition coefficients of the main constituents in the capsules ranged from 0.94 to 6.23, requiring over 450 min for a complete separation. To improve separation efficiency, a co-current elution mode was implemented and the flow rates of the two liquid phases as well as sample amount were examined. The results suggested that increasing the flow rate of the stationary phase and sample size could result in more effective separation, shorter separation time, and higher yield. It proved that co-current countercurrent chromatography was an effective method for the separation of vitamin E isomers.

DNA methyltransferase 3A induces the occurrence of oral submucous fibrosis by promoting the methylation of the von Hippel-Lindau.

BACKGROUND: Oral submucous fibrosis (OSF) is associated with malignant disorders. DNA methyltransferase 3A (DNMT3A) is a DNA methylesterase reported to be upregulated in multiple organs and shown to inhibit fibrosis. However, the detailed effect of DNMT3A on OSF remains unclear. METHODS: To mimic OSF in vitro, oral fibroblasts were exposed to arecoline and molecular biological experiments were performed to detect the function of DNMT3A in OSF. RESULTS: We found that von Hippel-Lindau (VHL) was downregulated and highly methylated in OSF. Arecoline remarkably increased the viability, invasiveness, and migration of oral fibroblasts, but upregulation of VHL partially reversed these effects. DNMT3A induces DNA hypermethylation in the VHL promoter, and VHL markedly inhibits the level of tenascin-C (TNC) by inducing the ubiquitination of TNC. TNC reversed the inhibitory effect of VHL upregulation on the differentiation of oral fibroblasts into myofibroblasts. CONCLUSION: DNMT3A induces OSF by promoting methylation of the VHL promoter. Hence, our study provides novel insights into the discovery of novel strategies that can be employed against OSF.

Bifurcation analysis in an epidemic model on adaptive networks.

In this paper, we study a delayed adaptive network epidemic model in which the local spatial connections of susceptible and susceptible individuals have time-delay effects on the rate of demographic change of local spatial connections of susceptible and susceptible individuals. We prove that the Hopf bifurcation occurs at the critical value τ0 with delay τ as the bifurcation parameter. Then, by using the normal form method and the central manifold theory, the criteria for the bifurcation direction and stability are derived. Finally, numerical simulations are presented to show the feasibility of our results.

Executive function and attentional bias as serial mediators in the relationship between frailty and depressive symptoms among older inpatients: A cross-sectional study.

AIMS AND OBJECTIVES: To examine the serial mediating effect of executive function and attentional bias in the relationship between frailty and depressive symptoms. BACKGROUND: Although the role of frailty in predicting depression has been well documented, the underlying mechanisms remain unclear. DESIGN: A cross-sectional study was conducted with 667 older inpatients aged 60-90 years in the internal medicine wards of a hospital in China. METHODS: Attentional bias, frailty and depressive symptoms were assessed using the Attention to Positive and Negative Information Scale, the Physical Frailty Phenotype and the 5-item Geriatric Depression Scale. Executive function was measured using 3 tests, including digital backward, category Verbal Fluency Test and Trail Making Test. The study followed the STROBE guideline. RESULTS: The latent profile analysis (LPA) identified four patterns of attentional bias, namely "no positive bias & no negative bias" (class 1, 9.3%), "minor positive bias & no negative bias" (class 2, 48.0%), "major positive bias & minor negative bias" (class 3, 25.6%) and "major positive bias & no negative bias" (class 4, 17.1%). Regression analysis found that frailty was associated with depressive symptoms. Frailty was also negatively associated with executive function, which was a protective factor for attentional bias class 1, 2 and 3 with reference to class 4. Attentional bias class 1 and 2 but not class 3 was associated with depressive symptoms with reference to class 4. The joint significance test confirmed executive function and attentional bias as serial mediators linking frailty to depressive symptoms. DISCUSSION: Unlike robust older adults who have the age-related positivity effect, frail older adults have attentional bias deficits due to executive dysfunction, and consequently experience clinically relevant depressive symptoms. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should take executive function training and attentional bias regulation into consideration to reduce the detrimental effects of frailty on emotional well-being.

Ultrahigh Power Factor and Ultralow Thermal Conductivity at Room Temperature in PbSe/SnSe Superlattice: Role of Quantum-Well Effect.

Reduced dimension is one of the effective strategies to modulate thermoelectric properties. In this work, n-type PbSe/SnSe superlattices with quantum-well (QW) structure are fabricated by pulsed laser deposition. Here, it is demonstrated that the PbSe/SnSe multiple QW (MQW) shows a high power factor of ≈25.7 µW cm-1 K-2 at 300 K, four times larger than that of PbSe single layers. In addition, thermal conductivity falls below 0.32 ± 0.06 W m-1 K-1 due to the phonon scattering at interface when the PbSe well thickness is confined within the scale of phonon mean free path (1.8 nm). Featured with ultrahigh power factor and ultralow thermal conductivity, ZT at room temperature is significantly increased from 0.14 for PbSe single layer to 1.6 for PbSe/SnSe MQW.

Reference values of impulse oscillometry (IOS) for healthy Chinese children aged 4-17 years.

OBJECTIVE: To establish the predicted value of pulmonary function determined by impulse oscillometry (IOS) in children (4-17 years old) in China. METHODS: A total of 6270 healthy children aged 4-17 years in China were included. The Master Screen IOS pulmonary function device (Jaeger Co, Germany) was used to detect the respiratory impedance (Zrs), resonant frequency (Fres), respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at various oscillation frequencies, and the indices above were analysed. Stepwise multivariate regression was used to establish the regression equation of related parameters of IOS in different sexes, ages, height, and weight. RESULTS: The differences in the main IOS parameters between different age stages were statistically significant regardless of sex (P < 0.05). The stepwise multivariate regression analysis showed that IOS parameters were related to height, age, and weight, and most IOS parameters were most closely related to height (the absolute value of the regression coefficient was the largest). With increasing age and height, the values of Z5, R5, R20, R5-R20, and Fres decreased, while the value of X5 increased. Through height, age, and weight, we obtained the normal predicted values equation of children's IOS parameters. Compared with the other reference equations, our reference equation is more suitable for Chinese children. CONCLUSIONS: The study revealed the reference values of IOS parameters in healthy Chinese children. In the evaluation of results for lung function measurements, this predicted value equation is more consistent with the characteristics of Chinese children than other reference equations. CLINICAL TRIAL: ChiCTR: 1800019029.

Fractional dynamic analysis and optimal control problem for an SEIQR model on complex networks.

A fractional order susceptible-exposed-infected-quarantined-recovered model is established on the complex networks. We calculate a specific expression for the basic reproduction number R0, prove the existence and uniqueness with respect to the solution, and prove the Ulam-Hyers stability of the model. Using the Latin hypercube sampling-partial rank correlation coefficient method, the influence of parameters on the R0 is analyzed. Based on the results of the analysis, the optimal control of the model is investigated as the control variables with vaccination rate and quarantine rate applying Pontryagin's minimum principle. The effects of α, degree of nodes, and network size on the model dynamics are simulated separately by the prediction correction method.

On the averaging principle for stochastic differential equations involving Caputo fractional derivative.

In this paper, we investigate the averaging principle for Caputo-type fractional stochastic differential equations driven by Brownian motion. Different from the approach of integration by parts or decomposing integral interval to deal with the estimation of integral involving singular kernel in the existing literature, we show the desired averaging principle in the sense of mean square by using Hölder inequality via growth conditions on the nonlinear stochastic term. Finally, a simulation example is given to verify the theoretical results.

Dynamic stability and optimal control of SIS q I q RS epidemic network.

We develop a complex network-based SIS q I q RS model, calculate the threshold R 0 of infectious disease transmission and analyze the stability of the model. In the model, three control measures including isolation and vaccination are considered, where the isolation is structured in isolation of susceptible nodes and the isolation of infected nodes. We regard these three kinds of controls as time-varying variables, and obtain the existence and the solution of the optimal control by using the optimal control theory. With regard to the stability of the model, sensitivity analysis of the parameters and optimal control, we carry out numerical simulations. From the simulation results, it is obvious that when the three kinds of controls exist simultaneously, the scale and cost of the disease are minimal. Finally, we fit the real data of COVID-19 to the numerical solution of the model.

Expressive suppression and rumination mediate the relationship between frailty and depression among older medical inpatients.

OBJECTIVE: Frailty is common among older medical inpatients and has been found to be an independent risk factor for depression. However, few studies have explored the underlying mechanisms of the frailty-depression relationship. The present study was aimed to examine emotional regulation strategies as mediators in the frailty-depression relationship based on the process model of emotional regulation. METHODS: Older medical inpatients (N=684) completed questionnaires and tests on frailty, emotional regulation strategies, and depressive symptoms. RESULTS: Structural equation models showed that expressive suppression and rumination, but not cognitive reappraisal, mediated the relationship between frailty and depressive symptoms (RMSEA = 0.059, CFI = 0.963, TLI = 0.957). CONCLUSIONS: Frail older medical inpatients habitually use expressive suppression and rumination in their daily lives, which may lead to more psychological disturbance. Interventions targeting expressive suppression and rumination might be effective in reducing the detrimental effect of frailty on psychological well-being among older medical inpatients.

The regulatory role of antisense lncRNAs in cancer.

Antisense long non-coding RNAs (antisense lncRNAs), transcribed from the opposite strand of genes with either protein coding or non-coding function, were reported recently to play a crucial role in the process of tumor onset and development. Functionally, antisense lncRNAs either promote or suppress cancer cell proliferation, migration, invasion, and chemoradiosensitivity. Mechanistically, they exert their regulatory functions through epigenetic, transcriptional, post-transcriptional, and translational modulations. Simultaneously, because of nucleotide sequence complementarity, antisense lncRNAs have a special role on its corresponding sense gene. We highlight the functions and molecular mechanisms of antisense lncRNAs in cancer tumorigenesis and progression. We also discuss the potential of antisense lncRNAs to become cancer diagnostic biomarkers and targets for tumor treatment.

Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study. / æ§æžé»„é¢—ç²’è¾ åŠ©æ²»ç–—å„¿ç«¥æ”¯æ°”ç®¡å“®å–˜ç–—æ•ˆçš„çœŸå®žä¸–ç•Œç ”ç©¶.

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.