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Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD.We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇oThe median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇oExercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

A new organic ligand was constructed by linking pyrimidine and tetrazole group through amide bond and used to build POM-based metal–organic complexes that can be used as catalysts for the catalytic oxidation of sulfides and electrochemical sensors.

Background: It is well known that Alzheimer's Disease (AD) is a neurodegenerative disease accompanied by memory impairment and major pathological changes of the extracellular Senile Plaque (SP) and intracellular Neurofibrillary Tangles (NFTs). However, many pieces of evidence indicate that neurogenesis disorders are also regarded as a new opinion in AD. Objective: This study aims to investigate the effects and regulatory mechanism of flavonoids from the stems and leaves of Scutellaria baicalensis Georgi in promoting neurogenesis and improving memory impairment mediated by BDNF-ERK-CREB signaling pathway in rats. Methods: Male Wistar rats were intracerebroventricularly injected with amyloid-beta protein 25-35 (Aβ25-35) in combination with Aluminum Trichloride (Alcl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ), to establish an AD model. Morris water maze was used to screen AD model rats and measure the learning and memory ability of model rats. The expression of Ki67 protein, which is involved in cell neurogenesis, in the hippocampal gyrus of rats was detected by the immunohistochemical method. The mRNA and protein expression levels of Grb2, SOS1, Ras, ERK, and BDNF, in the BDNF-ERK-CREB signaling pathway, in the hippocampus and cerebral cortex regions of rats were assayed by the Quantitative real-time PCR (qPCR) and Western blotting methods, respectively. Results: Intracerebroventricular injection of composited Aβ could induce rats’ memory impairment, decrease the protein expression of Ki67 in the hippocampal gyrus, and increase the mRNA and protein expression levels of Grb2, SOS1, Ras, ERK, and BDNF in the hippocampus and cerebral cortex. However, SSF could significantly ameliorate rats’ memory impairment induced by composited Aβ, lower the Ki67 protein expression in the hippocampal gyrus, and regulate the abnormal mRNA and protein expression levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus and cerebral cortex regions of rat brains. Conclusion: Composited Aβ induced memory impairment, decreased neurogenesis and initiated the abnormal mRNA and protein expressions of Grb2, SOS1, Ras, ERK, and BDNF in the BDNF- ERK-CREB signaling pathway. The effects of SSF in promoting neurogenesis and improving memory impairment may be related to the regulation of the abnormal expressions of Grb2, SOS1, Ras, ERK, and BDNF molecules in the BDNF-ERK-CREB signaling pathway.

Background China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. Methods This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. Results There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test–positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. Conclusions Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Vascular plants have evolved sophisticated mechanisms of long-distance signaling to cope with environmental stress. Reactive oxygen species (ROS) act as systemic signals in plant stress responses. However, it is not known whether ROS serve as root-to-shoot signals in the drought response. Here, we show thatferric reductase defective3(frd3) mutants exhibit enhanced drought resistance concomitant with increasedNCED3transcript levels and ABA contents in leaves. Thefrd3mutants also have an elevated hydrogen peroxide (H2O2) level in roots and leaves compared with the wild type. Grafting experiments demonstrate that drought resistance can be conferred by thefrd3rootstock, suggesting that long-distance signals derived infrd3roots trigger ABA level increases in leaves and thereby enhance drought resistance and that H2O2is a strong candidate for long-distance signals. Furthermore, comparative transcriptome and proteomics analyses revealed that many genes and proteins involved in the abiotic stress response, ROS homeostasis, and signaling pathways were affected in thefrd3mutant, supporting the drought resistance phenotype. Taken together, our findings suggest thatfrd3root-derived long-range signals activate ABA synthesis in leaves and enhance drought resistance, indicating possible root-to-shoot H2O2signaling in the plant drought response.

Aim: The aim of this study was to investigate the effect and molecular mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) in promoting neurogenesis and improving memory impairment induced by the PI3K-AKT-CREB signaling pathway. Methods: Alzheimer's disease (AD) was induced in the male Wistar rats by intracerebroventricular injection of amyloid beta peptide 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ). The Morris water maze was used to screen the successful establishment of the memory impairment model of rats. The screened successful model rats were randomly divided into a model group and three groups of three different doses of the drug (SSF). Rats in the drug group were treated with 35, 70, and 140 mg/kg of SSF for 43 days. The Eight-arm maze was used to measure the spatial learning and memory abilities of the rat, including working memory errors (WME) and reference memory errors (RME). Immunohistochemistry was used to detect the expression of BrdU, an indicator of neuronal proliferation, in the hippocampal gyrus of rats. The mRNA and protein expressions of TRKB, PI3K, AKT, P-AKT, and IGF2 in the PI3K-AKT-CREB signaling pathway in the hippocampus and cerebral cortex of the rats were determined by quantitative real-time PCR (qPCR) and Western blotting methods. Results: Compared to the sham group, the spatial memory ability of rats with composited Aβ was decreased, the number of WME and RME (P < 0.01) was increased, the expression of BrdU protein (P < 0.01) in the hippocampal gyrus was reduced, the mRNA and protein expression levels of TRKB, AKT, and IGF2 (P < 0.01, P < 0.05) in the hippocampus and cerebral cortex were lowered, and the mRNA expression level of PI3K (P < 0.01) in the cerebral cortex and the protein expression level of PI3K (P < 0.01) in the hippocampus were augmented. However, compared to the model group, the three-doses of SSF improved memory disorder induced by composited Aβ, reduced the number of WME and RME, increased the expression of BrdU protein in the hippocampal gyrus, and differently regulated the mRNA and protein expressions in composited Aβ rats. Conclusions: SSF improved memory impairment and neurogenesis disorder induced by composited Aβ in rats by activating the PI3K-AKT-CREB signaling pathway and up-regulating the mRNA and protein expressions of TRKB, PI3K, AKT, CREB, and IGF2.

Signal transduction pathways mediated by sensor histidine kinases and cognate response regulators control a variety of physiological processes in response to environmental conditions in most bacteria. Comparatively little is known about the mechanism(s) by which single-domain response regulators (SD-RRs), which lack a dedicated output domain but harbour a phosphoryl receiver domain, exert their various regulatory effects in bacteria. Here we have examined the role of the SD-RR proteins encoded by the phytopathogen Xanthomonas campestris pv. campestris (Xcc). We describe the identification and characterization of a SD-RR protein named McvR (motility, chemotaxis, and virulence-related response regulator) that is required for virulence and motility regulation in Xcc. Deletion of the mcvR open reading frame caused reduced motility, chemotactic movement, and virulence in Xcc. Global transcriptome analyses revealed the McvR had a broad regulatory role and that most motility and pathogenicity genes were down-regulated in the mcvR mutant. Bacterial two-hybrid and protein pull-down assays revealed that McvR did not physically interact with components of the bacterial flagellum but interacts with other SD-RR proteins (like CheY) and the subset of DNA-binding proteins involved in gene regulation. Site-directed mutagenesis and phosphor-transfer experiments revealed that the aspartyl residue at position 55 of the receiver domain is important for phosphorylation and the regulatory activity of McvR protein. Taken together, the findings describe a previously unrecognized class of SD-RR protein that contributes to the regulation of motility and virulence in Xcc.

Two new metal-organic compounds (MOCs) [Cu(L)0.5(3-nba)2] (1) and [Cu(L)(2,5-tdc)] (2) have been hydrothermally synthesized by employing the ligand N,N′-di(3-pyridyl)adipoamide (L) and two carboxylic acids (3-Hnba = 3-nitrobenzoic acid, 2,5-H2tdc = 2,5-thiophenedicarboxylic acid) as ligands. Compound 1 displays a metal-organic chain-like structure formed by the {Cu2(3-nba)4} double-paddle wheel units and the µ 2-bridging L ligands. The adjacent polymeric chains form a supramolecular layered structure through hydrogen bonding. Compound 2 shows a 3D metal-organic polymeric framework derived from Cu-L layers and µ 2-bridging 2,5-tdc ligands, which presents a 3,5-connected {4.62}{4.66.83} topology. The electrochemical and electrocatalytic behavior of the two compounds has been studied in detail. Carbon paste working electrodes modified with compounds 1 and 2 can be used as highly selective sensors for detecting traces Cr(VI). Both electrodes show also electrocatalytic performance in oxygen evolution reactions (OERs).

Four isostructural Anderson-type POM-based metal–organic complexes derived from a new bis(pyrimidine)-bis(amide) ligand were synthesized, showing multifunctional electrochemical sensing activities and good adsorption performances for organic dyes.

A diamond-like cuprous coordination polymer based on the [Cu8I6]2+ cluster has been successfully synthesized. This complex exhibits thermochromic and mechanochromic luminescence properties as well as good performance for the sorption and release of I2.

The strong mutual coupling of and even the opposite change in the key parameters, such as the band gap (Eg) and second-order harmonic generation (SHG), leads to the extreme scarcity in high-performance IR nonlinear optical (NLO) chalcogenides. Herein, we report 8 new sulfides, Na2Ba[(AgxNa1-x)2Sn2S7] (1, x = 0; 1 series, x = 0.1-0.6; Na2Ba[(Li0.58Na0.42)2Sn2S7], 1-0.6Li); Na2Sr[Cu2Sn2S7] (2); and Na2Ba[Cu2Sn2S7] (3). We use the structural tolerance factor ( [[EQUATION]] ) to connect the chemical composition, crystal structure, and NLO properties. Guided by these correlations, a better balance between Eg and SHG is realized in 1, which exhibits a large Eg of 3.42 eV and excellent NLO properties (SHG: 1.5 × AGS; laser-induced damage threshold: 12 × AGS), representing the best performance among the known Hg- or As-free sulfides to date.

Paraquat is one of the most widely used nonselective herbicides and has elicited the emergence of paraquat-resistant weeds. However, the molecular mechanisms of paraquat resistance are not completely understood. Here we report the Arabidopsis gain-of-function mutant pqt15-D with significantly enhanced resistance to paraquat and the corresponding gene PQT15, which encodes the Multidrug and Toxic Extrusion (MATE) transporter DTX6. A point mutation at +932 bp in DTX6 causes a G311E amino acid substitution, enhancing the paraquat resistance of pqt15-D, and overexpression of DTX6/PQT15 in the wild-type plants also results in strong paraquat resistance. Moreover, heterologous expression of DTX6 and DTX6-D in Escherichia coli significantly enhances bacterial resistance to paraquat. Importantly, overexpression of DTX6-D enables Arabidopsis plants to tolerate 4 mM paraquat, a near-commercial application level. DTX6/PQT15 is localized in the plasma membrane and endomembrane, and functions as a paraquat efflux transporter as demonstrated by paraquat efflux assays with isolated protoplasts and bacterial cells. Taken together, our results demonstrate that DTX6/PQT15 is an efflux transporter that confers paraquat resistance by exporting paraquat out of the cytosol. These findings reveal a molecular mechanism of paraquat resistance in higher plants and provide a promising candidate gene for engineering paraquat-resistant crops.

Two novel polyoxometalates (POMs)-based metal–organic complexes (MOCs) [Co3(4-H2dpye)(MnMo9O32)(H2O)10]·H2O (1) and [Co3(4-H2dpyb)(MnMo9O32)(H2O)12]·4H2O (2) have been designed and synthesized unde...

Aim: To investigate the effects and mechanism of flavonoids from stems and leaves of Scutellaria baicalensis Georgi (SSF) on the disorders in learning and memory and neuroplasticity induced by beta amyloid 25-35 (Aβ25-35) combined with aluminum trichloride (AlCl3) and human recombinant transfer factor-β1 (RHTGF-β1) (composited Aβ) in rats. Methods: A rat Alzheimer's disease (AD) model was established by intracerebroventricular injection of Aβ25-35 combined with AlCl3 and RHTGF-β1. The successful AD model of rats was screened with Morris water maze. The successful model rats were randomly divided into a model group and three doses of SSF treated group. The Morris water maze was used to detect the rats’ learning and memory abilities. The real-time fluorescence quantitative (qPCR) was applied to assay the mRNA expressions of CaM, CamkIV and Ferritin, as well as the neuroplasticity factors of HuB, HuC and HuD. The Western blotting was used to measure the protein expressions of CaM, CamkIV, HuB/D, HuC+HuD and Ferritin in CaM-CamkIV-CREB signal pathway. Results: Compared with sham group, the abilities of learning and memory in the model group were significantly impaired (P Conclusion: The improvement of SSF on the learning and memory disorder induced by composited Aβ is primarily derived from the positive regulation in CaM-CamkIV-CREB signal pathway and activation in neuroplasticity.

Background Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm. Methods One hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (47) and false-positive cases (107), according to their postnatal outcomes. Fetal echocardiographic measurements included the cardiac chambers sizes, valve annular diameters, and ascending aorta and pulmonary artery dimensions. The corresponding gestational age-related Z-scores were collected. The diameter of the transverse aortic arch and the aortic isthmus were measured. The TAO-DAO angle between the transverse aortic arch and isthmus was also measured. The receiver operating characteristic curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model.Results Confirmed CoA cases had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the left subclavian artery and left common carotid artery (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false-positive cases. The area under the curve was 0.947 (95% CI 0.91–0.98) for the TAO-DAO angle, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter, and 0.937 (95% CI 0.90–0.98) for the Z-score of the isthmus. Three important echocardiographic indices were combined to derive a three-step echocardiographic diagnostic model. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001).Conclusions The three step approach included the three most useful measurements and the five additional indices with appropriate cut-off values. The algorithm optimizes the diagnosis of fetal CoA and is clinically feasible.Trial registration: retrospectively registered.

Kadsura heteroclita (Roxb) Craib stem (KHS) is a medicinal plant used for the treatment of rheumatism arthritis diseases in Tujia ethnomedicine. Thus far, the complex chemical compositions in KHS are not clear, and the levels of the major compounds in KHS are not well understood. In this study, a novel UHPLC-Q-Orbitrap HRMS method was established for the simultaneous quali-quantitative analysis of KHS. A total of 204 compounds were identified, including triterpenoids, lignans, sesquiterpenes, fatty acids, phenolic acids, and flavonoids, more than 100 of which were first discovered in KHS. Using the same method, 12 representative bioactive components were successfully quantified. The method was fully validated by linearity, LOD, LOQ, precision, stability, recovery, and matrix effects, and it was applied to quantify the 12 representative compounds in 4 batches of KHS. As this method enables retrospective data analysis and has no upper limit to the number of analytes in a single run, it can be applied to quantify more active components of KHS in the future.

Background: Huangqi Guizhi Wuwu decoction (HQGZWW) exhibits good effects when administered to treat multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Understanding the precise mechanism of this decoction is thus important. Based on the findings of our previous study, the aim of the present study was to understand the role of antigen-specific CD8+ T-cells on the pathogenesis of MS/EAE when HQGZWW is administered as treatment. Methods: Myelin oligodendrocyte glycoprotein (MOG) 35-55-induced mice were administered distilled water, prednisone, and high dose or low dose HQGZWW. After purified CD4+ and CD8+ T-cells were stimulated with the MOG35-55 peptide, proliferation and cytokine secretion assays were performed. To establish the adoptive transfer EAE model, naive mice were injected with MOG35-55 -CD8+ or CD4+ T-cells. Results: Significant improvements in EAE score and pathology were observed in the high dose HQGZWW and prednisone groups. Compared to the low dose HQGZWW and distilled water groups, lower antigen-specific responses, lower levels of interferon-gamma, and higher levels of interleukin (IL)-4 and IL-10 from CD8+ and CD4+ T cells were observed in the high dose HQGZWW and prednisone groups. Finally, the EAE score was observed to be similar between the high dose HQGZWW group and prednisone group; however, this finding was not observed in the low dose HQGZWW group. Conclusion: Our findings suggest that high dose HQGZWW has similar effects on cell proliferation, cytokine secretion, and EAE score to prednisone, while low dose HQGZWW does not have such effect. The protective role of HQGZWW against EAE might thus depend on the Th2 cytokine secretion profile induced by either MOG35-55 specific CD8+ or CD4+ T-cells.

Three new coordination complexes [Zn(btec)0.5(L1)0.5(H2O)] n (1), [Ni(H2btec)(L1)(H2O)2] n (2), and {[Ni(btec)0.5(L2)(H2O)3]·2H2O} n (3) [H4btec = 1,2,4,5-benzenetetracarboxylic acid), L1 = N,N′-bis(3-pyridyl)adipamide, L2 = N,N′-bis(3-pyridyl)octanediamide] have been obtained under hydrothermal conditions. Single-crystal X-ray diffraction analysis has revealed that complex 1 has a layer structure based on [Zn(btec)0.5] n ribbons and the μ 2-bridging ligands L 1 . Complex 2 possesses a layered framework constructed by [Ni(H2btec)] n linear chains and [Ni(L1)] n wave-like chains. Complex 3 forms layers based on [Ni(L2)] n helical chains and μ 2-bridging L2 ligands, representing an interesting 4-fold interpenetrating 2D braided framework. The three different 2D frameworks exhibit 3,4-connected {4.62}2{42.62.82} topology for 1, 4-connected {44.62} topology for 2 and 3-connected {63} topology for 3. Their adjacent layers are further linked by hydrogen bonding interactions to generate 3D supramolecular structures. The differences in the nature of both the metal ions and the organic ligands lead to various coordination modes in the final structures. The photocatalytic activities and the fluorescence properties of complexes 1–3 were investigated.

BACKGROUND: Mitochondrial transcription elongation factor (TEFM) is an essential molecule that regulates the replication-transcription switch of mitochondrial DNA. TEFM modulates both transcription elongation and RNA processing in mitochondria. The purpose of the present study was to determine the association of TEFM with tumor progression and prognosis in hepatocellular carcinoma (HCC) patients. METHODS: The different protein expression level of TEFM among HCC cell lines was detected by Western blotting. The gene expression profiling interactive analysis (GEPIA) was used to dynamically analyze the mRNA expression of TEFM gene in different stages of HCC. The protein and mRNA expression levels of TEFM were detected by immunohistochemistry, Western blotting and qRT-PCR. The mRNA-SeqV2 expression of TEFM and clinical information of HCC patients were downloaded from the TCGA database by using R3.6.3 software. Next, the relationships between the expression level of TEFM and clinicopathological characteristics and the prognostic value of TEFM were analyzed. A Cox regression model was used for multivariate analysis of the factors that affected the prognosis of HCC. Finally, the association between the expression levels of TEFM and other mitochondrial regulatory genes and HCC biomarker genes was analyzed by GEPIA. RESULTS: TEFM is upregulated in HCC cell lines compared to noncancerous liver cell line. TEFM protein and mRNA expression levels in HCC tissues were significantly upregulated compared with those in noncancerous liver tissues. In addition, the mRNA expression level of TEFM was significantly correlated with sex, serum AFP level, and vascular invasion (P0). CONCLUSIONS: Our findings reveal that TEFM may play an important role in the progression of HCC. More importantly, the elevated expression of TEFM may potentially predict poor overall survival (OS) and disease-free survival (DFS) in patients with HCC.

Non-linear optical chalcogenides with a wide band gap (E

With the rapid development of artificial intelligence, in order to solve the problems of many questions from trainees, poor efficiency of teachers in answering questions and high work intensity in the process of thermal power plant simulation practice, this paper proposes an intelligent training expert guidance system for thermal power plant simulation, and this paper uses Visual C++ software programming to implement an intelligent training expert guidance system with voice interaction and video presentation functions, using the speech development package Microsoft Speech SDK, in-depth study of the SAPI it provides, design and implementation of speech recognition function and speech synthesis function. The XML file is used to define the types of questions and the corresponding Q&A test statements for keyword extraction; the video presentation function is realized with the help of Windows Media Player. The test results show that, based on the successful speech recognition, the system can simulate the way of dialogue between teachers and learners and answer learners’ questions in real time. The system has an open function, users can add questions independently, expand the database in real time, jump out of the traditional limitations of space, time and geography, and increase the interest of learning.

The cytoplasmic polyadenylation element-binding (CPEB) protein family have demonstrated a crucial role for establishing synaptic plasticity and memory in model organisms. In this review, we outline evidence for CPEB3 as a crucial regulator of learning and memory, citing evidence from behavioral, electrophysiological and morphological studies. Subsequently, the regulatory role of CPEB3 is addressed in the context of the plasticity-related proteins, including AMPA and NMDA receptor subunits, actin, and the synaptic scaffolding protein PSD95. Finally, we delve into some of the more well-studied molecular mechanisms that guide the functionality of this dynamic regulator both during synaptic stimulation and in its basal state, including a variety of upstream regulators, post-translational modifications, and important structural domains that confer the unique properties of CPEB3. Collectively, this review offers a comprehensive view of the regulatory layers that allow a pathway for CPEB3’s maintenance of translational control that guides the necessary protein changes required for the establishment and maintenance of lasting synaptic plasticity and ultimately, long term learning and memory.

Three new metal(II)–organic coordination complexes, formula as [Cd3(btc)2(3-dpna)2(H2O)2]·8H2O (1), [Zn3(btc)2(3-dpna)2(H2O)2]·4H2O (2) and [Co3(btc)2(3-dpna)2(H2O)2]·2H2O (3) [3-dpna = N1,N4-di(py...