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Background: Ultrasound plays a critical role in the early screening and diagnosis of cancers. Although deep neural networks have been widely investigated in the computer‐aided diagnosis (CAD) of different medical images, diverse ultrasound devices, and image modalities pose challenges for clinical applications, especially in the recognition of thyroid nodules having various shapes and sizes. More generalized and extensible methods need to be developed for the cross‐devices recognition of thyroid nodules. Purpose: In this work, a semi‐supervised graph convolutional deep learning framework is proposed for the domain adaptative recognition of thyroid nodules across several ultrasound devices. A deep classification network, trained on a source domain with a specific device, can be transferred to recognize thyroid nodules on the target domain with other devices, using only few manual annotated ultrasound images. Methods: This study presents a semi‐supervised graph‐convolutional‐network‐based domain adaptation framework, namely Semi‐GCNs‐DA. Based on the ResNet backbone, it is extended in three aspects for domain adaptation, that is, graph convolutional networks (GCNs) for the connection construction between source and target domains, semi‐supervised GCNs for accurate target domain recognition, and pseudo labels for unlabeled target domains. Data were collected from 1498 patients comprising 12 108 images with or without thyroid nodules under three different ultrasound devices. Accuracy, Sensitivity and Specificity were used for the performance evaluation. Results: The proposed method was validated on six groups of data for a single source domain adaptation task, the mean Accuracy was 0.9719 ± 0.0023, 0.9928 ± 0.0022, 0.9353 ± 0.0105, 0.8727 ± 0.0021, 0.7596 ± 0.0045, 0.8482 ± 0.0092, which achieved better performance in comparison with the state‐of‐the‐art. The proposed method was also validated on three groups of multiple source domain adaptation tasks. In particular, when using X60 and HS50 as the source domain data, and H60 as the target domain, it can achieve the Accuracy of 0.8829 ± 0.0079, Sensitivity of 0.9757 ± 0.0001, and Specificity of 0.7894 ± 0.0164. Ablation experiments also demonstrated the effectiveness of the proposed modules. Conclusion: The developed Semi‐GCNs‐DA framework can effectively recognize thyroid nodules on different ultrasound devices. The developed semi‐supervised GCNs can be further extended to the domain adaptation problems for other modalities of medical images. [ABSTRACT FROM AUTHOR]

Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism in these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density in the bone and reduced expression of the endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)‐specific deletion of Pkm2 impairs osteogenesis and worsens osteoporosis in mice. This is attributed to the impaired ability of bone mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. Mechanistically, EC‐specific deletion of Pkm2 reduces serum lactate levels secreted by ECs, which affect histone lactylation in BMSCs. Using joint CUT&Tag and RNA sequencing analyses, collagen type I alpha 2 chain (COL1A2), cartilage oligomeric matrix protein (COMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and transcription factor 7 like 2 (TCF7L2) as osteogenic genes regulated by histone H3K18la lactylation are identified. PKM2 overexpression in ECs, lactate addition, and exercise restore the phenotype of endothelial PKM2‐deficient mice. Furthermore, serum metabolomics indicate that patients with osteoporosis have relatively low lactate levels. Additionally, histone lactylation and related osteogenic genes of BMSCs are downregulated in patients with osteoporosis. In conclusion, glycolysis in ECs fuels BMSC differentiation into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis by increasing serum lactate levels. [ABSTRACT FROM AUTHOR]

Hydrophobic conjugated polymers have poor ionic transport property, so hydrophilic side chains are often grafted for their application as organic electrochemical transistors (OECTs). However, this modification lowers their charge transport ability. Here, an ionic gel interfacial layer is applied to improve the ionic transport while retaining the charge transport ability of the polymers. By using the ionic gels comprising gel matrix and ionic liquids as the interfacial layers, the hydrophobic polymer achieves the OECT feature with high transconductance, low threshold voltage, high current on/off ratio, short switching time, and high operational stability. The working mechanism is also revealed. Moreover, the OECT performance can be tuned by varying the types and ratios of ionic gels. With the proposed ionic gel strategy, OECTs can be effectively realized with hydrophobic conjugated polymers. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases associated with the degradation of memory and cognitive ability. Current pharmacotherapies show little therapeutic effect in AD treatment and still cannot prevent the pathological progression of AD. Deep brain stimulation (DBS) has shown to enhance memory in morbid obese, epilepsy and traumatic brain injury patients, and cognition in Parkinson's disease (PD) patients deteriorates during DBS off. Some relevant animal studies and clinical trials have been carried out to discuss the DBS treatment for AD. Reviewing the fornix trials, no unified conclusion has been reached about the clinical benefits of DBS in AD, and the dementia ratings scale has not been effectively improved in the long term. However, some patients have presented promising results, such as improved glucose metabolism, increased connectivity in cognition‐related brain regions and even elevated cognitive function rating scale scores. The fornix plays an important regulatory role in memory, attention, and emotion through its complex fibre projection to cognition‐related structures, making it a promising target for DBS for AD treatment. Moreover, the current stereotaxic technique and various evaluation methods have provided references for the operator to select accurate stimulation points. Related adverse events and relatively higher costs in DBS have been emphasized. In this article, we summarize and update the research progression on fornix DBS in AD and seek to provide a reliable reference for subsequent experimental studies on DBS treatment of AD. [ABSTRACT FROM AUTHOR]

KRAS mutation is the most frequent type of genetic mutation in non‐small cell lung cancer (NSCLC), especially in lung adenocarcinoma. However, KRAS mutation can affect many biological processes and the mechanisms underlying KRAS mutation‐mediate carcinogenesis in NSCLC have not been fully understood. In this research, we found that KRASG12C mutation was associated with the upregulation of T‐LAK cell‐originated protein kinase (TOPK), which is a well‐known serine/threonine MAPK‐like protein kinase implicated in tumorigenesis. The overexpression of TOPK significantly promoted the malignant phenotype of A549 cells, and TOPK silencing impaired the malignant phenotype with KRASG12C mutation. Moreover, we demonstrated that TOPK level was regulated by MAPK/ERK signalling and the transcription factor Elk1. TOPK was also found to promote the activation of NF‐κB signalling in A549 cells with KRASG12C mutation via facilitating the phosphorylation of TAK1. In the in vivo tumorigenesis model, the administration of TOPK inhibitor OTS514 enhanced the anticancer effect of 5‐FU, and the combinatory use of OTS514 and KRASG12C inhibitor AMG510 showed synergistic anti‐tumour effect. These results suggest that KRAS‐TOPK axis contributes to the progression of NSCLC and targeting this axis could synergize with anticancer effect of the existing chemotherapeutics. [ABSTRACT FROM AUTHOR]

Problem: Preeclampsia (PE) is the main factor threatening the life of primipara. Defective migration and invasion of trophoblast cells was one of the causes of PE. Circ_0111277 had been reported to be related to the development of PE, but the mechanism of its effect on trophoblast cells needed further study. Method of Study: The expression of circ_0111277, microRNA‐188‐3p (miR‐188‐3p) and grainyhead‐like 2 (GRHL2) mRNA were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Cell Counting Kit‐8 (CCK‐8) assay, 5‐Ethynyl‐20‐deoxyuridine (EdU) and colony formation assay were used to examine cell proliferation ability. Tube formation and transwell assay were performed to assess the angiogenesis and metastasis ability of cells. Western blot was applied to measure the levels of epithelial‐mesenchymal transition (EMT)‐related proteins (E‐cadherin and Vimentin) and GRHL2 protein. The relationship between miR‐188‐3p and circ_0111277 or GRHL2 was verified by the dual luciferase reporter experiment. Results: Circ_0111277 and GRHL2 were elevated, and miR‐188‐3p was declined in PE patients. Overexpression of circ_0111277 could inhibit the proliferation, angiogenesis, migration, invasion and EMT of trophoblast cells (HTR‐8/Svneo). Circ_0111277 was the molecular sponge of miR‐188‐3p. MiR‐188‐3p up‐regulation could reduce the inhibition of HTR‐8/Svneo cell growth caused by overexpression of circ_0111277. GRHL2 was a target gene of miR‐188‐3p, and GRHL2 silencing relieved the adverse effects of miR‐188‐3p inhibitors on HTR‐8/Svneo. In general, circ_0111277 up‐regulated GRHL2 expression through sponge miR‐188‐3p. Conclusion: Highly expressed circ_0111277 up‐regulated the expression of GRHL2 through sponge miR‐188‐3p, thereby inhibiting trophoblast cells function, which suggested a new molecular mechanism for the pathogenesis of PE. [ABSTRACT FROM AUTHOR]

The coverage path planning (CPP) technique attracts growing interest in studies on underwater search and rescue (SAR) conducted with an autonomous underwater vehicle (AUV) equipped with a side‐scan sonar (SSS). In SAR missions, prior information is crucial. Aiming at the underwater SAR mission with prior information, a new coverage path planner (SAR‐A*) is proposed. The ultimate goal is to generate a feasible path for completely covering the task area and preferentially visiting more valuable cells with fewer turns. First, the whole task area is decomposed into hexagon cells as waypoints to be visited for complete coverage. Second, the probability of discovering the target is obtained according to the target presence probability and the SSS detection ability. Under the assumption of prior target information, the target presence probability is modelled as a two‐dimension Gaussian distribution based on predicted target locations or trajectories. Then, an optimal next‐waypoint selection process is formulated as a multi‐objective decision‐making problem and solved by the weighted metric method. Finally, simulation and experimental results demonstrate that the generated path can improve the cumulative probability of discovering the target with fewer turns. [ABSTRACT FROM AUTHOR]

Study Objectives: This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. Design: Prospective pharmacokinetics study. Setting: The intensive care unit in a tertiary‐care medical center. Patients: A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. Methods: Model‐based simulations with therapeutic range of 2–6 mg/L as the plasma trough concentration (Cmin) target and the free area under the concentration‐time curve from 0 to 24 h (ƒAUC24) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24/MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child‐Pugh class A and B (CP‐A/B) and Child‐Pugh class C (CP‐C) patients. Results: A two‐compartment model with first‐order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child‐Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP‐A/B and CP‐C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP‐A/B patients and 50 mg q12h or 100 mg q24h for CP‐C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP‐A/B and CP‐C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. Conclusions: For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP‐A/B and CP‐C patients. [ABSTRACT FROM AUTHOR]

Background: Excitation‐to‐inhibition (E/I) imbalance is believed to be a key contributor of synaptic and network degeneration in Alzheimer’s disease (AD)(Frere and Slutsky, 2018). Extensive preclinical research on transgenic animal models of AD have demonstrated neuronal and circuit level E/I imbalance mediated by amyloid‐beta (Aβ) and abnormally phosphorylated tau proteins (Harris et al., 2020; Palop and Mucke, 2016). However, the mechanisms of E/I imbalance leading to disrupted networks and their relationships to Aβ and tau in humans remain poorly understood. Method: In this multimodal imaging study in patients with AD (n=20 AD patients; n=35 age‐matched controls; Table‐1), we first examined the spectral changes in oscillatory brain rhythms using magnetoencephalography and their relationships to tau and amyloid‐beta (Aβ) accumulation in PET imaging (flortaucipir and 11C‐PiB, for tau and Aβ, respectively). Next, we estimated parameters of a linear neural mass model (Raj et al., 2020) that best fit the observed spectra, and examined the relationships between model parameters for excitatory and inhibitory neural sub‐populations, and tau and Aβ accumulations. Result: We found that neuronal hypoactivity was associated with tau while hyperactivity was associated with Aβ (Figure 1). We also demonstrated E/I imbalance in patients with AD, depicted as abnormal excitatory and inhibitory neuronal parameters in a linear neural mass model that reproduced the empirical macroscopic power spectra (Figure 2). The abnormal excitatory and inhibitory neuronal parameters showed distinct associations with tau and Aβ—higher tau correlated with a longer excitatory time‐constant, whereas higher Aβ correlated with a longer inhibitory time‐constant (Figure 3). Conclusion: The unique contribution of the collective finding in the current study is to demonstrate how abnormalities in the oscillatory power spectrum in AD is mechanistically linked to impaired function of excitatory and inhibitory neuronal populations that are in turn associated with tau and Aβ accumulations. Neural oscillations are modulators of rate and timing of neuronal spiking and have a key role in governing the neuronal excitability (Siegel et al., 2012). The multimodal neuroimaging in AD patients in the current study demonstrate how different frequency oscillations are distinctly affected by Aβ and tau, and offer new perspectives for network stabilizing therapies. [ABSTRACT FROM AUTHOR]

Objectives: Skeletal muscle dysfunction is one of the most common comorbidities in chronic obstructive pulmonary disease (COPD). The occurrence of respiratory failure in COPD is common and leads to the patient's death. The diaphragm is the most important muscle in the respiratory system and plays a key role in the onset of respiratory failure. This study explores the feasibility of ultrasound shear wave elastography (SWE) to measure diaphragmatic stiffness and evaluates its changes in COPD patients. Methods: In total, 77 participants (43 patients with stable COPD and 34 healthy controls) were enrolled. All subjects underwent complete diaphragmatic ultrasound SWE measurements and pulmonary function tests. The diaphragmatic stiffness was indicated via diaphragmatic shear wave velocity (SWV) at functional residual capacity (FRC). A trained operator performed the ultrasound SWE examinations of the first 15 healthy controls thrice to assess the reliability of diaphragmatic SWE. Results: A good to excellent reliability was found in diaphragmatic SWV at FRC (ICC = 0.93, 95%CI 0.82–0.98). As compared to the control group, the diaphragmatic SWV at FRC was considerably high in the COPD group (median 2.5 m/s versus 2.1 m/s, P =.008). Diaphragmatic SWV at FRC was linked to forced expiratory volume in one second (r = −0.30, P =.009), forced vital capacity (r = −0.33, P =.003), modified Medical Research Council score (r = 0.30, P =.001), and COPD assessment test score (r = 0.48, P <.001). Conclusions: Ultrasound SWE may be employed as an effective tool for quantitative evaluation of diaphragm stiffness and can help in personalized management of COPD, such as treatment guidance and follow‐up monitoring. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common form of dementia, progressively impairing memory and cognition. While various neuroimaging studies have revealed functional network abnormalities in patients with AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. In order to answer these questions, we employed a spectral graph‐theory based model (SGM) to identify abnormal biophysical markers of neuronal activity in AD. Method: SGM is an analytic model that describes how the long‐range fiber projections in the brain mediate and couple the excitatory and inhibitory activity of local neuronal subpopulations. Unlike other coupled models, the SGM is linear, available in closed‐form, and parameterized by a small set of global parameters. This facilitates their rapid and unambiguous inference which we performed here on a well characterized clinical population of patients with AD (N = 88) and a cohort of age‐matched healthy controls (N = 88). We estimated SGM parameters that best captured the regional magnetoencephalography (MEG) frequency spectra of patients with AD and age‐matched controls. Result: SGM was able to capture the regional MEG frequency spectra of patients with AD and healthy controls, specifically, the abnormal slowing of neural oscillations in AD (Fig 1A). Patients with AD have significantly elevated long‐range excitatory neuronal time constant (tG) compared to controls (p < 0.001). Time constant tG is also the most important feature for accurate classification of patients with AD from controls (Area Under Curve = 0.85; Fig 1B). Lastly, higher tG is negatively correlated with global cognitive decline score (p = 0.02; Fig 1C). Conclusion: These results indicate that a global impairment in the long‐range excitatory neuronal activity is associated with abnormal spectral signatures and cognitive deficits in AD. Intriguingly, our work is able to recapitulate the spatial and spectral patterns of AD‐related functional activity without introducing any spatial heterogeneity whatsoever; indeed, the SGM model is entirely global and spatially‐invariant. This raises the possibility that a global increase in the long‐range excitatory time constant might be a sufficient factor underlying observed spatiotemporal alterations of neuronal activity in AD. Our findings provide new insights into potential mechanistic links between abnormal neural oscillations and their cellular correlates in AD. [ABSTRACT FROM AUTHOR]

Based on a facile and universal method using noncovalent bonding, here, polymer‐modified covalent organic framework materials (COFs) were rapidly prepared. PNIPAM‐modified COF (COF‐PNIPAM) was synthesized by electrostatic self‐assembly between COF prepared by low‐cost melamine and terephthalaldehyde and carboxyl‐terminated poly(N‐isopropylacrylamide) (PNIPAM) prepared via reversible addition‐fragmentation chain transfer polymerization. The carboxyl‐terminated PNIPAM was characterized by Gel Permeation Chromatography and Ultraviolet and Visible Spectroscopy (UV–vis). COF and COF‐PNIPAM were characterized by Fourier Transform Infrared Spectroscopes, Scanning Electron Microscope, Transmission Electron Microscope, X‐Ray Diffractomer (XRD), and Brunner‐Emmet‐Teller (BET) measurements. The results showed that the COF‐PNIPAM was successfully prepared. The Pickering emulsion properties of the COF‐PNIPAM in a water‐to‐toluene mixed system were studied, and when the water‐to‐oil ratio is 2:1, a stable emulsion can be obtained. However, the results show that the PNIPAM chains of COF‐PNIPAM nearly lose their temperature responsiveness. [ABSTRACT FROM AUTHOR]

A cross‐sectional survey was conducted from 2015 to 2018 to assess the risk of zoonotic influenza to humans at the human–pig interface in Guangdong Province, south China. One hundred and fifty‐three pig farmers, 21 pig traders and 16 pig trade workers were recruited using convenience sampling and surveyed at local pig farms, live pig markets and slaughterhouses, respectively. Questionnaires were administered to collect information on the biosecurity and trading practices adopted and their knowledge and beliefs about swine influenza (SI). Most (12 of 16) trade workers said they would enter piggeries to collect pigs and only six of 11 said they were always asked to go through an on‐farm disinfection procedure before entry. Only 33.7% of the interviewees believed that SI could infect humans, although pig farmers were more likely to believe this than traders and trade workers (p <.01). Several unsafe practices were reported by interviewees. 'Having vaccination against seasonal flu' (OR = 3.05, 95% CI: 1.19–8.93), 'Believe that SI can cause death in pigs' (no/yes: OR = 8.69, 95% CI: 2.71–36.57; not sure/yes: OR = 4.46, 95% CI: 1.63–14.63) and 'Keep on working when getting mild flu symptoms' (OR = 3.80, 95% CI: 1.38–11.46) were significantly and positively correlated to 'lacking awareness of the zoonotic risk of SI'. 'Lacking awareness of the zoonotic risk of SI' (OR = 3.19, 95% CI: 1.67–6.21), 'Keep on working when getting mild flu symptoms' (OR = 3.59, 95% CI: 1.57–8.63) and 'Don't know SI as a pig disease' (OR = 3.48, 95% CI: 1.02–16.45) were significantly and positively correlated to 'not using personal protective equipment when contacting pigs'. The findings of this study would benefit risk mitigation against potential pandemic SI threats in the human–pig interface in China. [ABSTRACT FROM AUTHOR]

The relationship between the brain's structural wiring and the functional patterns of neural activity is of fundamental interest in computational neuroscience. We examine a hierarchical, linear graph spectral model of brain activity at mesoscopic and macroscopic scales. The model formulation yields an elegant closed‐form solution for the structure–function problem, specified by the graph spectrum of the structural connectome's Laplacian, with simple, universal rules of dynamics specified by a minimal set of global parameters. The resulting parsimonious and analytical solution stands in contrast to complex numerical simulations of high dimensional coupled nonlinear neural field models. This spectral graph model accurately predicts spatial and spectral features of neural oscillatory activity across the brain and was successful in simultaneously reproducing empirically observed spatial and spectral patterns of alpha‐band (8–12 Hz) and beta‐band (15–30 Hz) activity estimated from source localized magnetoencephalography (MEG). This spectral graph model demonstrates that certain brain oscillations are emergent properties of the graph structure of the structural connectome and provides important insights towards understanding the fundamental relationship between network topology and macroscopic whole‐brain dynamics.. [ABSTRACT FROM AUTHOR]

Brain data processing has been embracing the big data era driven by the rapid advances of neuroscience as well as the experimental techniques for recording neuronal activities. Processing of massive brain data has become a constant in neuroscience research and practice, which is vital in revealing the hidden information to better understand the brain functions and malfunctions. Brain data are routinely non-linear and non-stationary in nature, and existing algorithms and approaches to neural data processing are generally complicated in order to characterize the non-linearity and non-stationarity. Brain big data processing has pressing needs for appropriate computing technologies to address three grand challenges: (1) efficiency, (2) scalability and (3) reliability. Recent advances of computing technologies are making non-linear methods viable in sophisticated applications of massive brain data processing. General-purpose Computing on the Graphics Processing Unit (GPGPU) technology fosters an ideal environment for this purpose, which benefits from the tremendous computing power of modern graphics processing units in massively parallel architecture that is frequently an order of magnitude larger than the modern multi-core CPUs. This article first recaps significant speed-ups of existing algorithms aided by GPGPU in neuroimaging and processing electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG) and etc. The article then demonstrates a series of successful approaches to processing EEG data in various dimensions and scales in a massively parallel manner: (1) decomposition: a massively parallel Ensemble Local Mean Decomposition (ELMD) algorithm aided by GPGPU can decompose EEG series, which forms the basis of further time-frequency transformation, in real-time without sacrificing the precision of processing; (2) synchronization measurement: a parallelized Nonlinear Interdependence (NLI) method for global synchronization measurement of multivariate EEG with speed-up of more than 1000 times, and it was successful in localization of epileptic focus; and (3) dimensionality reduction: a large-scale Parallel Factor Analysis which excels in run-time performance and scales far better by hundreds of times than conventional approach does, and it supports fast factorization of EEG with more than 1000 channels. Through these practices, the massively parallel computing technology manifests great potentials in addressing the grand challenges of brain big data processing. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Antarctic icefish, a family (Channichthyidae) of teleosts within the perciform suborder Notothenioidei, are the only known vertebrates without oxygen-transporting haemoglobins and that are largely devoid of circulating erythrocytes. To elucidate the evo-devo mechanisms underpinning the suppressed erythropoiesis in the icefish, we conducted comparative studies on the transcriptomes and micro RNAomes of the primary haematopoietic tissues between an icefish ( Chionodraco hamatus) and two red-blooded notothenioids ( Trematomus bernacchii and Gymnodraco acuticeps). We identified substantial remodelling of the haematopoietic programs in the icefish through which erythropoiesis is selectively suppressed. Experimental verification showed that erythropoietic suppression in the icefish may be attributable to the upregulation of TGF-β signalling, which coincides with reductions in multiple transcription factors essential for erythropoiesis and the upregulation of hundreds of micro RNAs, the majority (> 80%) of which potentially target erythropoiesis regulating factors. Of the six micro RNAs selected for verification, three mi RNAs (miR-152, miR-1388 and miR-16b) demonstrated suppressive functions on GATA1 and ALAS2, which are two factors important for erythroid differentiation, resulting in reduced numbers of erythroids in microinjected zebra fish embryos. Codon substitution analyses of the genes of the TGF-β superfamily revealed signs of positive selection in TGF -β 1 and endoglin in the lineages leading to Antarctic notothenioids. Both genes are previously known to function in erythropoietic suppression. These findings implied a general trend of erythropoietic suppression in the cold-adapted notothenioid lineages through evolutionary modulation of the multi-functional TGF-β signalling pathway. This trend is more pronounced in the haemoglobin-less icefish, which may pre-emptively hinder the otherwise defective erythroids from production. [ABSTRACT FROM AUTHOR]

Enantioselective Michael addition of oxazolones to in situ generated vinylogous imine intermediates is reported. A series of optically active 3-alkylindole derivatives with adjacent quaternary and tertiary stereocenters was obtained. The resulting adducts can readily be converted into syn-configured α,β-disubstituted tryptophan derivatives without compromising the stereoselectivities. [ABSTRACT FROM AUTHOR]

An organocatalytic asymmetric vinylogous Michael addition of dicyanoolefins to vinylogous imine intermediates generated in situ from arenesulfonylalkylindoles has been developed. This protocol provides an easy and convenient approach to C-3 alkyl-substituted indole derivatives with high yields (up to 93%), diastereomeric ratios (up to 99:1 dr) and enantioselectivities (up to 99% ee). The resulting adducts can be also readily converted to pyrazolo derivatives or α-alkylation products of ketones without any decrease of the diastereoselectivities and enantioselectivities. [ABSTRACT FROM AUTHOR]

Cai C-j, Lu M-q, Chen Y-h, Zhao H, Li M-r, Chen G-h. Clinical study on prevention of HBV re-infection by entecavir after liver transplantation. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01448.x. © 2011 John Wiley & Sons A/S. Abstract: Purpose: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re-infection after liver transplantation (LT). Methods: A retrospective matched case-control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. Results: Two hundred and fifty-two patients were enrolled. The average duration of follow-up was 38.5 and 41.2 months (LAM and ETV groups) (p > 0.05). Duration of pre-operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p > 0.05). The HBV DNA level decreased from 3.89 × 106 to 5.31 × 105 copies/mL before LT in the LAM group, and decreased from 8.74 × 106 to 5.49 × 104 copies/mL in the ETV group (p < 0.05). Eighteen patients in LAM group developed HBV re-infection and 0 in ETV group. Conclusion: ETV is superior to LAM for preventing HBV re-infection following LT. [ABSTRACT FROM AUTHOR]

Title compounds (VI) are synthesized in good overall yields by the new sequential three-component reaction of oxazolyliminophosphorane (III), isocyanates, and amines in the presence of catalytic amount of EtONa. [ABSTRACT FROM AUTHOR]

For the first time the highly stereoselective title Michael addition reaction is presented. [ABSTRACT FROM AUTHOR]

The title compound, C18H16FN3O2, was obtained via the aza-Wittig reaction. The quinazolinone ring system is almost planar and makes a dihedral angle of 67.09 (8)° with the substituent benzene ring. The structure is stabilized by a weak C—H...O hydrogen bond and C—H...π interactions. [ABSTRACT FROM AUTHOR]

A tandem aza-Wittig reaction of ethyl 3-triphenylphosphoranylideneamino-4-cyano-1-phenyl-1 H-pyrrole-2-carboxylate with 4-chlorophenyl isocyanate and diisobutylamine produced the title compound, C27H28ClN5O. In the molecule, the angles between the fused-ring system and the two benzene rings are 51.66 (2) and 65.79 (2)°. Intramolecular C—H...N hydrogen bonds determine the conformation of the molecule. The packing of the molecules in the crystal structure is governed mainly by intermolecular C—H...N hydrogen-bonding interactions. There are no π–π interactions. [ABSTRACT FROM AUTHOR]

KRAS mutation is the most frequent type of genetic mutation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma. However, KRAS mutation can affect many biological processes and the mechanisms underlying KRAS mutation-mediate carcinogenesis in NSCLC have not been fully understood. In this research, we found that KRAS G12C mutation was associated with the upregulation of T-LAK cell-originated protein kinase (TOPK), which is a well-known serine/threonine MAPK-like protein kinase implicated in tumorigenesis. The overexpression of TOPK significantly promoted the malignant phenotype of A549 cells, and TOPK silencing impaired the malignant phenotype with KRAS G12C mutation. Moreover, we demonstrated that TOPK level was regulated by MAPK/ERK signalling and the transcription factor Elk1. TOPK was also found to promote the activation of NF-κB signalling in A549 cells with KRAS G12C mutation via facilitating the phosphorylation of TAK1. In the in vivo tumorigenesis model, the administration of TOPK inhibitor OTS514 enhanced the anticancer effect of 5-FU, and the combinatory use of OTS514 and KRAS G12C inhibitor AMG510 showed synergistic anti-tumour effect. These results suggest that KRAS-TOPK axis contributes to the progression of NSCLC and targeting this axis could synergize with anticancer effect of the existing chemotherapeutics., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)