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Through a copper-catalyzed oxidative three-component annulation reaction, a new method for direct and syn-selective construction of cyclic ether-fused tetrahydroquinolines from readily available feedstock was demonstrated.

Heterotrimeric GTP-binding proteins (G proteins) are a group of regulators essential for signal transmission into cells. Regulator of G protein signaling 1 (AtRGS1) possesses intrinsic GTPase-accelerating protein (GAP) activity and could suppress G protein and glucose signal transduction in Arabidopsis (Arabidopsis thaliana). However, how AtRGS1 activity is regulated is poorly understood. Here, we identified a knockout mutant of oxysterol binding protein-related protein 2A, orp2a-1, which exhibits similar phenotypes to the arabidopsis g-protein beta 1-2 (agb1-2) mutant. Transgenic lines overexpressing ORP2A displayed short hypocotyls, a hypersensitive response to sugar, and lower intracellular AtRGS1 levels than the control. Consistently, ORP2A interacted with AtRGS1 in vitro and in vivo. Tissue-specific expression of 2 ORP2A alternative splicing isoforms implied functions in controlling organ size and shape. Bioinformatic data and phenotypes of orp2a-1, agb1-2, and the orp2a-1 agb1-2 double mutant revealed the genetic interactions between ORP2A and Gβ in the regulation of G protein signaling and sugar response. Both alternative protein isoforms of ORP2A localized in the endoplasmic reticulum (ER), plasma membrane (PM), and ER–PM contact sites and interacted with vesicle-associated membrane protein-associated protein 27-1 (VAP27-1) in vivo and in vitro through their two phenylalanines in an acidic track-like motif. ORP2A also displayed differential phosphatidyl phosphoinositide binding activity mediated by the pleckstrin homology domain in vitro. Taken together, the Arabidopsis membrane protein ORP2A interacts with AtRGS1 and VAP27-1 to positively regulate G protein and sugar signaling by facilitating AtRGS1 degradation.

Idesia polycarpa Maxim is described as a dioecious species, in which flowers are female or male, but we have also found individuals with bisexual flowers. The study aimed to provide the theoretical basis for the artificial control on flowering, fruiting, and floral initiation of Idesia polycarpa Maxim species. The morphological and anatomical structure of female, male, and bisexual flowers of I. polycarpa was studied. In this study, the routine paraffin section and morphological observation methods were used. The flowering of I. polycarpa began in late July. Results showed that the short-branch terminal bud was the highest percentage of floral bud position both in the female and male plants compared to the other bud types, and the proportion was 68.6% and 76.3%, respectively. Evidence from floral structural analysis suggests that the female and male flowers of I. polycarpa are unisexual by abortion. The ovary of the male flower stops developing after the ovule primordium initiation. The female, male, and bisexual flowers of I. polycarpa had the same anatomical structure at the beginning of development, but differences emerge in the differentiation stage of the female and male. In the bisexual flowers, females and males develop normally and may produce fruits. The study suggests that the bisexual, male, and female flowers were produced on the separate plants of the same species; therefore, the species is trioecious.

Protein aggregation in the cell is often manifested by the formation of subcellular punctate structures. Herein, we modulated the solvatochromism and solubility of Nile Red fluorophore derivatives to quantitatively study the polarity inside pathogenic protein aggregates, revealing structure- and protein-dependent polarity heterogeneity.

Through a palladium-catalyzed reductive annulation reaction of resorcinols and 2-nitrobenzaldehydes, reported is a new synthesis of acridinones with the features of operational simplicity, broad substrate scope, and readily available feedstocks.

SUMMARYHeterotrimeric GTP-binding proteins (G proteins) are a group of regulators essential for signal transmission into cells. AtRGS1 (Regulator of G protein Signaling 1) with intrinsic GTPase-accelerating protein (GAP) activity could suppress G protein and glucose signal transduction inArabidopsis. However, how AtRGS1 activity is regulated is currently poor understood. Here we identified a knockout mutantorp2a-1(oxysterol-binding protein(OSBP)-related protein 2A) which shows phenotypes similar toagb1-2(arabidopsis g-protein beta 1). With overexpression of ORP2A, transgenic lines display short hypocotyl, hypersensitivity to sugar and lower intracellular AtRGS1 level than control. Consistently, ORP2A shows interaction with AtRGS1in vitroandvivo. Tissue specificity of ORP2A with two alternative protein forms imply its functions in organ size and shape controlling. Bioinformatic data and phenotypes oforp2a-1, agb1-2and double mutant reveal genetic interactions in the regulation of G protein signaling and sugar response between ORP2A and Gβ. Both alternative splicing forms of ORP2A locate in the ER, PM (Plasma Membrane) and EPCS (ER-PM Contact Sites), and interact with VAP27-1 mediated by a FFAT-like motifin vivoandvitro. ORP2A also displays differential phosphatidyl phosphoinositide binding activity mediated by its PH domain invitro. Taken together, it is suggested thatArabidopsismembrane protein ORP2A interacts with AtRGS1 and VAP27-1 to positively regulate G protein and sugar signaling by facilitating AtRGS1 degradation.

Covalent-type probes or sensors have been seldom reported for aggregated proteins. Herein, we reported a series of covalent solvatochromic probes to selectively modify and detect aggregated proteomes through the Schiff base reaction. Such covalent modification was discovered by serendipity using the P1 probe with an aldehyde functional group, exhibiting enhanced fluorescence intensity and unusually large blue shift upon protein aggregation. Supported by the biochemical and mass spectrometry results, we identified that this probe can modify the lysine residue of aggregated proteins selectively over folded ones via the Schiff base reaction. The generality of designing such a covalent-type probe was demonstrated in multiple probe scaffolds using different model proteins. Finally, we exploited the distinct solvatochromism of P1 after Schiff base linkage with aggregated proteins to visualize the distinct morphology of aggregated proteomes, as well as to quantify the polarity heterogeneity inside it. This work may intrigue the exploration of other chemical reaction types to covalently functionalize aggregated proteins that were difficult to analyze.

Aims To express the clinical predictor and epidemiology of patients with health care-associated meningitis (HAM) and launch a survival analysis to screen mortality predictors. Method A retrospective cohort analysis containing more than 70000 patients was evaluated. Clinical and microbial epidemiology, therapy and mortality of HAM patients were reviewed. Multivariable Cox proportional hazard models were applied to achieve survival analysis. Result 900 HAM patients from 3244 cases with cerebrospinal fluid(CSF) culture positivity were selected for epidemiology and survival analysis. The 90-day mortality was 12.4% (112 of 900) in people with HAM. Hypertension, external ventricular drainage (EVD), and lumbar drainage (LD) are mortality predictors for HAM, with a hazard ratio (HR) of 2.097 (95% C.I. 1.308–3.361, P = 0.002), 1.709 (95% C.I. 1.119–2.611, P = 0.013), and 1.614 (95% C.I. 1.083–2.405, P = 0.019). Reoperation was a factor favoring mortality, with an HR of 0.615 (95% C.I. 0.397–0.951, P = 0.029). In treatment, the outcome of patients receiving three or more antibiotic combinations is better than that of patients receiving dual-drug combinations. Conclusion The mortality of patients with HAM was relatively high, and the most important factors related to 90-days survival were hypertension, EVD and LD and treatment with three or more antibiotics are much better.

Herein, a new iodide-mediated three-component annulation reaction of secondary anilines, cyclohexanones, and elemental sulfur is demonstrated, which allows access to various phenothiazines with the merits of formation of multiple chemical bonds in one single operation, high step and atom efficiency, readily available feedstocks and catalyst system, and good substrate and functional group compatibility. The developed chemistry capable of constructing novel phenothiazines with structural diversity offers a significant basis for further applications.

Guillain-Barré syndrome (GBS) is an acute inflammatory autoimmune and demyelinating disease of the peripheral nervous system. Currently, valid biomarkers are unavailable for the diagnosis of GBS.A comparative proteomics analysis was performed on the cerebrospinal fluid (CSF) from 10 patients with GBS and 10 patients with noninflammatory neurological disease (NND) using the tandem mass tags technique. The differentially expressed proteins were analyzed by bioinformatics, and then the candidate proteins were validated by the enzyme-linked immunosorbent assay method in another cohort containing 160 samples (paired CSF and plasma of 40 patients with GBS, CSF of 40 NND patients and plasma of 40 healthy individuals).In all, 298 proteins were successfully identified in the CSF samples, of which 97 differentially expressed proteins were identified in the GBS and NND groups. Three key molecules were identified as candidate molecules for further validation. The CSF levels of TGOLN2 and NCAM1 decreased in GBS patients compared with NND patients, whereas the CSF levels of APOC3 increased. The enzyme-linked immunosorbent assay results were consistent with our proteomics analysis. Interestingly, in the validation cohort, serum APOC3 levels in the GBS group were consistent with those in the CSF samples and significantly higher than those in the healthy control group.Our preliminary data suggest that the CSF protein expression profile of patients with GBS is different from that of patients with NND. Moreover, alterations of TGOLN2, NCAM1and APOC3 may be used as novel biomarkers for identifying patients with GBS.

The incorporation of a coupling step into the reduction of unsaturated systems offers a desirable way for diverse synthesis of functional molecules, but it remains to date a challenge due to the difficulty in controlling the chemoselectivity. Herein, by developing a new heterogeneous iridium catalyst composed of Ir-species (Irδ+) and N-doped SiO2/TiO2 support (Ir/N-SiO2/TiO2), we describe its application in reductive electrophilic mono and dialkylations of quinolines with various 2- or 4-functionalized aryl carbonyls or benzyl alcohols by utilizing renewable formic acid as the reductant. This catalytic transformation offers a practical platform for direct access to a vast range of alkyl THQs, proceeding with excellent step and atom-efficiency, good substrate scope and functional group tolerance, a reusable catalyst and abundantly available feedstocks, and generation of water and carbon dioxide as by-products. The work opens a door to further develop more useful organic transformations under heterogeneous reductive catalysis., By developing a heterogeneous iridium catalyst composed of a N-doped SiO2/TiO2 support and Ir-species (Ir/N-SiO2/TiO2), its application in reductive electrophilic alkylation of quinolines with various aryl carbonyls or benzyl alcohols is presented.

The propensity of glioblastoma multiforme (GBM) cells to migrate along white matter tracts and blood vessels suggests that topographical cues associated with brain parenchyma greatly influence GBM motility and invasion.

In recent years, the Chinese government has issued a series of deepening reform policies around smart healthcare, established a diversified technical basis and environmental protection, and deeply excavated the derivative value of healthcare information, aiming to provide high-quality healthcare services for patients. Information interaction in the context of smart healthcare is a kind of health information interaction completed by users with smart healthcare applications as the hub. It is an application form of social behavior and has an impact on value cocreation. Based on the theory of information interaction and value cocreation, this paper systematically reviews the research on information interaction and value cocreation in the smart healthcare context, analyzes the information interaction mode and information interaction mechanism in the smart healthcare context, constructs a theoretical model of the impact of information interaction on value cocreation, and empirically tests the relationship between information interaction and value cocreation in the smart healthcare context. The research of this paper aims to provide high-quality information interaction services for smart healthcare users, promote the dimensional management of information behavior in the context of smart healthcare, and promote the continuous improvement of the operation and management of smart healthcare.

We introduce convenience yields on dollar bonds into an incomplete-market equilibrium model of exchange rates and interest rates. The convenience yield enters as a stochastic wedge in the Euler equation for exchange rate determination. The model identifies a novel safe-asset convenience yield channel by which quantitative easing impacts the dollar exchange rate. Our model addresses three exchange rate puzzles. (1) The model can rationalize the low pass-through of SDF shocks to exchange rates and hence low exchange rate volatility. (2) It helps address but does not fully resolve the exchange rate disconnect puzzle. (3) The model generates an unconditional log currency expected return on the dollar that is in line with the data.

Recently, the study of underwater electric field has been attracted much attention that have interesting applications in a variety of measurement devices and equipment for marine electric field underwater. After the laboratory measurement of the underwater electric field being completed, a series of offshore verification in the coastal area are required to further verify the performance of test equipment in general. Therefore, the relevant electric field characterization of the coastal area needs to be measured explicitly. In this paper, we carries out a series of environmental observations in a certain coastal sea area of Dalian by using a long baseline observation device and obtains some important conclusions through statistical analysis, which has certain guiding significance for the study of the law of the low-frequency underwater electric field in specific sea area.

Under metal-free catalysis and external energy input-free conditions, there remain to date significant unmet challenges in precise C−H functionalization with controllable sites and numbers. Here, by establishing a low N-doped hierarchical porous graphitic carbon/hexafluoroisopropanol (HFIP) catalyst system, we demonstrate, for the first time, a direct construction of structurally novel π-extended N,O-heterocycles from tetrahydroquinoxalines and 2-naphthols via selective oxidative aryl C−H bifunctionalization at room temperature, proceeding with the striking features of good substrate and functional group compatibility, excellent step and atom-efficiency, and the use of easily accessible and reusable catalyst and naturally abundant oxidant. Mechanistic study reveals that the in situ formed catalyst-O2 species stabilized by HFIP enables a decent oxidation of substrates to match the coupling processes. The work highlights the potential practicality of the strategy merging suitable carbon material and hexafluoroisopropanol in further development of oxidative C−H functionalization reactions under sustainable catalysis.

The global effort against the COVID-19 pandemic dictates that routine quantitative detection of SARS-CoV-2 neutralizing antibodies is vital for assessing immunity following periodic revaccination against new viral variants. Here, we report a dual-detection fluorescent immunochromatographic assay (DFIA), with a built-in self-calibration process, that enables rapid quantitative detection of neutralizing antibodies that block binding between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2). Thus, this assay is based on the inhibition of binding between ACE2 and the RBD of the SARS-CoV-2 spike protein by neutralizing antibodies, and the affinity of anti-human immunoglobulins for these neutralizing antibodies. Our self-calibrating DFIA shows improved precision and sensitivity with a wider dynamic linear range, due to the incorporation of a ratiometric algorithm of two-reverse linkage signals responding to an analyte. This was evident by the fact that no positive results (0/14) were observed in verified negative samples, while 22 positives were detected in 23 samples from verified convalescent plasma. A comparative analysis of the ability to detect neutralizing antibodies in 266 clinical serum samples including those from vaccine recipients, indicated that the overall percent agreement between DFIA and the commercial ELISA kit was 90.98%. Thus, the proposed DFIA provides a more reliable and accurate rapid test for detecting SARS-CoV-2 infections and vaccinations in the community. Therefore, the DFIA based strategy for detecting biomarkers, which uses a ratiometric algorithm based on affinity and inhibition reactions, may be applied to improve the performance of immunochromatographic assays.

Summary Under non-metallic catalysis and conditions with no external energy input, there remain to date significant unmet challenges in precise C-H functionalization with controllable sites and numbers. Here, by establishing a hierarchical, porous, low N-doped graphitic carbon/hexafluoroisopropanol (HFIP) catalyst system, we report selective construction of structurally novel π-extended N,O-heterocycles from tetrahydroquinoxalines and 2-naphthols via oxidative aryl C-H bifunctionalization at room temperature. There is good substrate and functional group compatibility, as well as excellent step and atom efficiency, and the reaction uses an accessible catalyst and a naturally abundant oxidant. Mechanistic study reveals that the in situ-formed catalyst-O2 species stabilized by HFIP enables a decent substrate oxidation to match the coupling processes. The work highlights the potential practicality of a strategy merging suitable carbon material and HFIP in further development of oxidative transformations under sustainable catalysis.

Purpose – The purpose of this paper is to explore the correlations among entrepreneurial environment, market-oriented strategies, and entrepreneurial performance. Design/methodology/approach – Entrepreneurial environment is measured by institutional environment and industrial environment. A survey of 176 large Chinese automobile firms is conducted. The structural equation model is applied to perform analysis. Findings – The uncertainty of the institutional environment is positively related with market-oriented strategies and market-oriented strategies are positively related with firms’ performance. The stronger the uncertainty of the industrial environment is, the larger impact that market-oriented strategies have on firms’ performance will be. There is no distinct positive relationship between the uncertainty of industrial environment and firms’ market-oriented strategies. The hypothesis, that the stronger the uncertainty of institutional environments is, the larger the impact that market-oriented strategies will be on firms’ performance, is not supported. Research limitations/implications – In terms of research design, this paper does not select survey samples randomly. This paper only takes institutional and industrial environments into consideration while the environmental characteristics are omitted. Originality/value – This paper expands entrepreneurship research by integrating previous studies. Findings in this paper are helpful for firms in emerging countries to implement “going abroad strategies,” to start up new businesses in other countries, and to achieve the goals of improving competitiveness and integrating with international firms.

The invasive and recurrent nature of glioblastoma multiforme (GBM) is linked to a small subpopulation of cancer cells, which are self-renewing, resistant to standard treatment regimens, and induce formation of new tumors. Matrix stiffness is implicated in the regulation of cell proliferation, drug resistance, and reversion to a more invasive phenotype. Therefore, understanding the relationship between matrix stiffness and tumor cell behavior is vital to develop appropriate in vitro tumor models. Here, chitosan-hyaluronic acid (CHA) polyelectrolyte complex scaffolds are fabricated with statistically significant stiffness variances to characterize the effect of scaffold stiffness on morphology, proliferation, drug resistance, and gene expression in human glioblastoma cells (U-87 MG). All scaffolds support GBM proliferation over a 12-day culture period, yet larger spheroids are observed in scaffolds with higher stiffness. Additionally, GBM cells cultured in stiffer CHA scaffolds prove significantly more resistant to the common chemotherapeutic temozolomide. Moreover, the stiffer 8% CHA scaffolds exhibit an increase in expression of drug resistance and invasion related genes compared to 2D culture. CHA scaffolds present a tunable microenvironment for enhanced tumor cell malignancy and may provide a valuable in vitro microenvironment for studying tumor progression and screening anticancer therapies.

Wireless-based Neighborhood Area Network (NAN) plays an important role in Smart Grid Communication Network (SGCN) with its wide coverage, flexible deployment and low cost. As the increasing demand for large amount data transmitting and massive devices accessing, wireless NAN is facing with the congestion problem. In this paper, we propose a Game Theory-based Admission Control Scheme for Supporting Multi-services to prevent NAN congestion. Firstly, a multi-sources NAN traffic model based on self-similarity are established so that the guaranteed bandwidth for different type of services can be obtained. Secondly, we propose a dynamic spectrum resources allocation model to obtain optimal bandwidth assignment among multi-services which is solved by the non-cooperative gaming. Finally, through using the optimally allocated bandwidth as the threshold, we develop a novel admission control scheme orienting the multi-services access in NAN. Numerical results show that the proposed admission control scheme is superior to others in the utilization of spectrum resources and throughput, which is more appropriate for wireless NAN.

LTE-based Public Safety Network (PSN) is a wireless communication network which can provide efficient and reliable communication in disasters or emergencies for disaster relief and public protection. Therefore, ensuring that network congestion will not happen in PSN during an emergency is becoming increasingly important. LTE-based PSN is easy to be congested because part of spectrum resources is compressed to guarantee priority requirements of public safety users. In this paper, we develop a new method namely Selective Admission Control (SAC) mechanism to manage the radio bearers access to the commercial radio for Public Safety (PS) in LTE-based PSN. In the case of emergency, we select the traffic bearer with minimum estimated load increment accessing to the LTE-based PSN. The channel quality of new bearers should be taken into account, which means that in congestion, users who arrive earlier with poor channel quality will be rejected to reserve sufficient resources for users who arrive later with good channel quality. The simulation results show that the SAC mechanism can improve throughput by 36% and lower the rejection rate by 73% at most than reference method based on non-selective access control model, as a result effectively avoiding the network congestion and improving the utilization of spectrum resources for public safety communication.

Dear Editor, Porcine induced pluripotency stem cells (piPSCs) are promised in basic research, animal husbandry and regenerative medicine. However, the efficiency of the piPSCs induction has been low and the generated piPSCs varied in cell morphology and cell characteristics. Here we report a novel approach to improve efficiency of piPSCs generation. The induced piPSCs are dome-shaped mouse embryonic stem cells (ESCs)-like and display molecular properties of mouse ESCs. Electroporation study reveals that mouse ESCslike status facilitates genetic manipulating of piPSCs. Importantly, we demonstrate that the domed piPSC colonies are more suitable as donor cells for nuclear transfer (NT) to generate reconstructed embryos than those flattened piPSCs. The potential applications of the newly generated piPSCs in ungulate pluripotent research are discussed.

On-Road Sensor Networks (ORSNs) play an important role in capturing traffic flow data for predicting short-term traffic patterns, driving assistance and self-driving vehicles. However, this kind of network is prone to large-scale communication failure if a few sensors physically fail. In this paper, to ensure that the network works normally, an effective fault-tolerance mechanism for ORSNs which mainly consists of backup on-road sensor deployment, redundant cluster head deployment and an adaptive failure detection and recovery method is proposed. Firstly, based on the N − x principle and the sensors’ failure rate, this paper formulates the backup sensor deployment problem in the form of a two-objective optimization, which explains the trade-off between the cost and fault resumption. In consideration of improving the network resilience further, this paper introduces a redundant cluster head deployment model according to the coverage constraint. Then a common solving method combining integer-continuing and sequential quadratic programming is explored to determine the optimal location of these two deployment problems. Moreover, an Adaptive Detection and Resume (ADR) protocol is deigned to recover the system communication through route and cluster adjustment if there is a backup on-road sensor mismatch. The final experiments show that our proposed mechanism can achieve an average 90% recovery rate and reduce the average number of failed sensors at most by 35.7%.

Genetically modified pigs have become a popular model system in fundamental research, agricultural and biomedical applications. However, random integration often result in unstable expression of transgene and unpredictable phenotypes. The Rosa26 locus has been widely used to produce genetic modified animals with high and consistent expressing of transgene in mouse, human and rat, as it can be targeted efficiently and is not subject to gene-silencing effects. Recently, the first case of reporter gene targeting pigs in porcine Rosa26 (pRosa26) locus was reported. In the study, full sequence of pRosa26 locus was further characterized, and the pRosa26 promoter (pR26) was cloned and we evidenced that the new porcine endogenous promoter is suitable for driving transgene expression in a high and stable manner by avoiding DNA methylation. Furthermore, elongation factor 1a promoter (EF1a) -driven GFP reporter and Myostatin promoter (MyoP)-driven Follistatin (Fst) were successfully targeted into the pRosa26 locusby traditional homologous recombination (HR) strategy. EF1a showed high activity and hypomethylation at the locus. And, muscle-specific promoter MyoP was activated strictly in muscle of the pRosa26 targeted pigs, indicating Rosa26 locus supports tissue-specific promoter driving transgene expression in its own manner. The study provided further demonstration on biomedical and agricultural applications of porcine Rosa26 promoter and locus.