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Synergistic bioassay-guided isolation of the extracts of Artemisia rupestris L, which belongs to the family Asteraceae, afforded two acetylenic spiroketal enol ethers, namely rupesdiynes A (1) and B (2). Their structures were determined based on spectroscopic analysis and experimental and calculated ECD investigations. The two compounds exhibited synergistic activity and were able to reduce the minimum inhibitory concentration (MIC) of oxacillin four-fold, with a fractional inhibitory concentration index (FICI) of 0.5 in combination with oxacillin against the oxacillin-resistant EMRSA-16. Biofilm formation inhibitory and Ethidium bromide (EtBr) efflux assay were further employed to verify the possible mechanism of the synergistic antibacterial effect. Additionally, molecular docking studies were conducted to investigate the binding affinities of the two compounds with penicillin-binding protein 2a (PBP2a) of EMRSA-16. Taken together, rupesdiynes A (1) and rupesdiyne B (2) showed moderate synergistic activity against EMRSA-16 with oxacillin via inhibiting biofilm formation and efflux pump activity, respectively.

Linear inverse problems arise in diverse engineering fields especially in signal and image reconstruction. The development of computational methods for linear inverse problems with sparsity tool is one of the recent trends in this area. The so-called optimal $k$-thresholding is a newly introduced method for sparse optimization and linear inverse problems. Compared to other sparsity-aware algorithms, the advantage of optimal $k$-thresholding method lies in that it performs thresholding and error metric reduction simultaneously and thus works stably and robustly for solving medium-sized linear inverse problems. However, the runtime of this method remains high when the problem size is relatively large. The purpose of this paper is to propose an acceleration strategy for this method. Specifically, we propose a heavy-ball-based optimal $k$-thresholding (HBOT) algorithm and its relaxed variants for sparse linear inverse problems. The convergence of these algorithms is shown under the restricted isometry property. In addition, the numerical performance of the heavy-ball-based relaxed optimal $k$-thresholding pursuit (HBROTP) has been studied, and simulations indicate that HBROTP admits robust capability for signal and image reconstruction even in noisy environments.

Additional file 1: Figure 1. The pedigree structures with SUD for WES.

Additional file 3: Table 1. Information of the persons from SUD families for WES.

By a condensation of aliphatic amine containing adamantyl groups (amantadine, memantine, or 3-amino-1-adamantanol) and 5-fluorosalicylaldehyde, three new Schiff base ligands, HL1–3, were synthesized. One Schiff base, zinc(II) chloride, and NaOH were stirred in anhydrous methanol generating three new zinc(II) complexes, C34H38F2N2O2Zn (1), C38H46F2N2O2Zn (2), and C34H38F2N2O4Zn (3), respectively. These complexes were characterized by melting point, elemental analysis, infrared spectrum, ultraviolet–visible spectrum, 1H NMR analysis, thermal analysis, and single-crystal X-ray diffraction analysis. Single-crystal X-ray diffraction analysis shows that 1 and 3 crystallize in the monoclinic system with space group P21/c, but 2 crystallizes in the orthorhombic system with space group Pbca. Each asymmetric unit in 1 is composed of one zinc(II) and two deprotonated ligands; each asymmetric unit in 2 is constituted of one zinc(II), two deprotonated ligands as well as one dichloromethane. Each asymmetric unit in 3 is made up of one zinc(II), two deprotonated ligands, one methanol, and one lattice water. The central zinc(II) in 1–3 is four-coordinate via two nitrogen atoms and two oxygen atoms from the corresponding Schiff base ligands, forming a distorted tetrahedral geometry. The antibacterial activities of the three Schiff base ligands and the corresponding complexes against two gram positive bacteria, Staphylococcus aureus and Bacillus subtilis, and a gram negative bacteria, Escherichia coli, were tested.

We report the radio observations of the eclipsing black widow pulsar J1720-0534, a 3.26 ms pulsar in orbit with a low mass companion of mass 0.029 to 0.034 M$_{\odot}$. We obtain the phase-connected timing ephemeris and polarization profile of this millisecond pulsar (MSP) using the Five-hundred-meter Aperture Spherical Radio Telescope (FAST), the Green Bank Telescope (GBT), and the Parkes Telescope. For the first time from such a system, an oscillatory polarisation angle change was observed from a particular eclipse egress with partial depolarization, indicating 10-milliGauss-level reciprocating magnetic fields oscillating in a length scale of 5000 km (assuming an orbital inclination angle of 90 degrees) outside the companion's magnetosphere. The dispersion measure variation observed during the ingresses and egresses shows the rapid raising of the electron density in the shock boundary between the companion's magnetosphere and the surrounding pulsar wind. We suggest that the observed oscillatory magnetic fields originate from the pulsar wind outside the companion's magnetosphere., Comment: 18 pages, 8 figures, 1 table, accepted by RAA

Additional file 4: Table 2. WES results of susceptible SNVs with a focus on cardiac disease-associated genes in SUD families.

By a condensation of aliphatic amine containing adamantyl groups (amantadine, memantine, or 3-amino-1-adamantanol) and 5-fluorosalicylaldehyde, three new Schiff base ligands, HL1–3, were synthesized. One Schiff base, zinc(II) chloride, and NaOH were stirred in anhydrous methanol generating three new zinc(II) complexes, C34H38F2N2O2Zn (1), C38H46F2N2O2Zn (2), and C34H38F2N2O4Zn (3), respectively. These complexes were characterized by melting point, elemental analysis, infrared spectrum, ultraviolet–visible spectrum, 1H NMR analysis, thermal analysis, and single-crystal X-ray diffraction analysis. Single-crystal X-ray diffraction analysis shows that 1 and 3 crystallize in the monoclinic system with space group P21/c, but 2 crystallizes in the orthorhombic system with space group Pbca. Each asymmetric unit in 1 is composed of one zinc(II) and two deprotonated ligands; each asymmetric unit in 2 is constituted of one zinc(II), two deprotonated ligands as well as one dichloromethane. Each asymmetric unit in 3 is made up of one zinc(II), two deprotonated ligands, one methanol, and one lattice water. The central zinc(II) in 1–3 is four-coordinate via two nitrogen atoms and two oxygen atoms from the corresponding Schiff base ligands, forming a distorted tetrahedral geometry. The antibacterial activities of the three Schiff base ligands and the corresponding complexes against two gram positive bacteria, Staphylococcus aureus and Bacillus subtilis, and a gram negative bacteria, Escherichia coli, were tested.

The roles of the Hippo‑Yes‑associated protein (YAP) pathway in lung injury and repair remain elusive. The present study examined the effects of systemic inhibition or stimulation of YAP activity on lung injury, repair and inflammation in a mouse model of lipopolysaccharide (LPS)‑induced lung injury. Mice were treated with or without YAP inhibitor, verteporfin, or with or without YAP stimulator, XMU‑MP‑1, and intraperitoneally injected with LPS (7.5 mg/kg). Lung injury and repair were evaluated by histological analysis and by testing for markers of lung injury. Lung inflammation was assessed by measuring tissue levels of inflammatory mediators. Lung injury was associated with a decreased, whereas lung repair was associated with an increased YAP activity evidenced by nuclear translocation. Lung injury was associated with a high level of lung inflammation and epithelial adherens junction disassembly, but not with cell proliferation or epithelial cell regeneration. The injury phase was defined as 0‑48 h post‑LPS injection, and the 48‑168 h time period was considered the repair phase. Inhibition of YAP activity at the injury phase, using verteporfin, exacerbated, whereas its stimulation, using XMU‑MP‑1, alleviated lung injury, lung inflammation and epithelial adherens junction disassembly. Inhibition or stimulation of YAP activity at the injury phase had no effects on cell proliferation or epithelial regeneration. By contrast, lung repair was associated with inflammation resolution, increased cell proliferation, epithelial regeneration and reassembly of epithelial adherens junctions. Inhibition of YAP activity at the repair phase delayed inflammation resolution, impeded lung recovery, inhibited cell proliferation and epithelial regeneration, and inhibited epithelial adherens junction reassembly. Stimulation of YAP activity at the repair phase reversed all these processes. The results of the current study demonstrated that the Hippo‑YAP activity serves a protective role against endotoxemic lung injury. The Hippo‑YAP activity alleviated lung inflammation and injury at the injury phase and promoted inflammation resolution and lung repair at the repair phase.

Our survey data on migrant workers in the Pearl River Delta region from 2006 to 2010 and recent fieldwork show that the enactment of the Labor Contract Law encouraged both the signing of labor cont...

In-memory computing (IMC) has emerged as a new computing paradigm able to alleviate or suppress the memory bottleneck, which is the major concern for energy efficiency and latency in modern digital computing. While the IMC concept is simple and promising, the details of its implementation cover a broad range of problems and solutions, including various memory technologies, circuit topologies, and programming/processing algorithms. This Perspective aims at providing an orientation map across the wide topic of IMC. First, the memory technologies will be presented, including both conventional complementary metal-oxide-semiconductor-based and emerging resistive/memristive devices. Then, circuit architectures will be considered, describing their aim and application. Circuits include both popular crosspoint arrays and other more advanced structures, such as closed-loop memory arrays and ternary content-addressable memory. The same circuit might serve completely different applications, e.g., a crosspoint array can be used for accelerating matrix-vector multiplication for forward propagation in a neural network and outer product for backpropagation training. The different algorithms and memory properties to enable such diversification of circuit functions will be discussed. Finally, the main challenges and opportunities for IMC will be presented.

International audience; Comparison of the shape of the Central Sulcus in HominidsOphelie Foubet1, Zhong Yi Sun1, William Hopkins2, Jean-François Mangin1 Institutions:1Université Paris-Saclay, CEA, CNRS, Neurospin, Gif-sur-Yvette, France 2University of Texas MD Anderson Cancer Center, Bastrop, TX Introduction:Gyrification of the neocortex appears during the third trimester of gestation in humans. While the folding pattern is stable and simple in small mammalian brains, it becomes rich and complex in larger brains, reaching a peak of complexity and inter-individual variability in humans [1,2]. However, among this variability some major features are stable within species and even between species. The central sulcus (CS) is one of them, dividing the motor cortex from the somatosensory cortex in primates [3].We examined here the morphological variability of CS in hominids, with a focus on the motor hand region, a significant issue of human evolution.Methods:T2-weighted images scanned at 4.7T or 7T of 30 chimps (Pan troglodytes), 30 gorillas (Gorilla gorilla) and 18 orangutans (Pongo pygmaeus) were acquired under the guidelines of the US Department of Health and Humans Services. CSs were extracted from these MRIs, as well as from T1-weighted images of thirty human HCP subjects, using the "Morphologist 2012" pipeline[4]. All sulci were affinely normalized in Talairach space and a species-specific homothetic transformation was applied before right sulci were flipped to be compared to the left ones. A pairwise comparison of their shape was performed after a rigid alignment [5]. Isomap-based manifold learning was used to capture a one-dimensional approximation of the space spanned by the sulci. To exhibit the variability trait described on the isomap, all sulci were rigidly aligned to the sulcus with the minimum distance to the set and local shape averages were performed at regular intervals along the one-dimensional manifold. We performed different experiments for intra and inter-species comparisons.Results:Beyond their differences in overall CS shape, the 4 species appear to share a common variability trait described on each of their isomap axis. This trait is similar to previous results on large human databases [5,6] and corresponds to a shape variation ranging from a single motor hand knob configuration to a double knob configuration.The axis displaying all sulci reveals a separation of species. While chimp and gorilla populations share the same variation in CS shape (p=0.79), humans and orangutans appear to have their own variability trait and share little with the other species. Interestingly, humans find themselves in the middle, between the shape variability of orangutans and the common one of chimps and gorillas. The axis seems to describe again a variation in shape from a single knob to a double knob, with the addition however of a rotation of the sulcus on the orangutan side. We note the appearance of a shift between the two parts of the SC, dorsal and ventral to the knob, at the level of humans and which develops towards the orangutans. This shift seems to allow for the development of a more ventral somatosensory knob rather than a real second motor knob.Conclusions:The inter-individual variability within all hominid species appears to be characterized primarily by a shape variation ranging from a single to a double knob configuration. When the 4 species are mixed, the single-to-double-knob trait is no longer enough to describe all the variability. The distributions of the different species do not mix, suggesting that differences in overall sulci shape between species prevail. Compared to chimps and gorillas, humans and orangutans appear to have a larger buried gyrus in the central region of the CS, suggesting greater sensory-motor connectivity and integration between their motor and somato-sensory cortices [3]. This common feature could explain the similarity in shape of their hand-knob, as it has to fold over the large buried gyrus. Furthermore, it could explain the appearance of a knob in the somato-sensory cortex of humans and orangutans on the axis common to all 4 species. Their better sensory-motor integration could reflect an increase in hand and digits use for bipedal humans and an increase in hand and foot grasping for tree-dwelling orangutans.Acknowledgement: HBP-SGA2 (785907), FRM (DIC20161236445), ANR(IFOPASUBA), Chaire Blaise Pascal of Region Ile de France to W. Hopkins [1] Fischl B (2008), ‘Cortical folding patterns and predicting cytoarchitecture.’, Cereb Cortex 18:1973-1980. [2] Welker W (1988), ‘Why does cerebral cortex fissure and fold?’, Cereb Cortex 8B:3-135. [3] Hopkins W.D. (2014), ‘Evolution of the Central Sulcus Morphology in Primates’, Brain, behavior and evolution 84.1 (2014): 19-30. [4] Fischer C (2012), ‘Morphologist 2012: the new morphological pipeline of BrainVISA.’, In. HBM. Beijing. [5] Sun Z. Y. (2012), ‘The Effect of Handedness on the Shape of the Central Sulcus’, Neuroimage, 60(1):332-9 [6] Sun Z. Y. (2016), ‘Linking morphological and functional variability in hand movement and silent reading.’, Brain Structure and Function 221(7):3361-71

Matrix computation is ubiquitous in modern scientific and engineering fields. Due to the high computational complexity in conventional digital computers, matrix computation represents a heavy workload in many data-intensive applications, e.g., machine learning, scientific computing, and wireless communications. For fast, efficient matrix computations, analog computing with resistive memory arrays has been proven to be a promising solution. In this Tutorial, we present analog matrix computing (AMC) circuits based on crosspoint resistive memory arrays. AMC circuits are able to carry out basic matrix computations, including matrix multiplication, matrix inversion, pseudoinverse and eigenvector computation, all with one single operation. We describe the main design principles of the AMC circuits, such as local/global or negative/positive feedback configurations, with/without external inputs. Mapping strategies for matrices containing negative values will be presented. The underlying requirements for circuit stability will be described via the transfer function analysis, which also defines time complexity of the circuits towards steady-state results. Lastly, typical applications, challenges, and future trends of AMC circuits will be discussed., Comment: 6 pages, 6 figures, 2 tables, IEEE TCAS-II Tutorial 2022, accepted for publication

Additional file 2: File S1-S2. Multiple alignment of amino acid sequences of CuCBLs and CuCIPKs from ‘Guijing2501’ satsuma mandarin.

The hard thresholding technique plays a vital role in the development of algorithms for sparse signal recovery. By merging this technique and heavy-ball acceleration method which is a multi-step extension of the traditional gradient descent method, we propose the so-called heavy-ball-based hard thresholding (HBHT) and heavy-ball-based hard thresholding pursuit (HBHTP) algorithms for signal recovery. It turns out that the HBHT and HBHTP can successfully recover a $k$-sparse signal if the restricted isometry constant of the measurement matrix satisfies $\delta_{3k}

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that can lead to heart failure and eventually death. MicroRNAs (miRs) play essential roles during PAH progression; however, their exact mechanism of action remains unclear. Apelin is a small bioactive peptide with a key protective function in the pathogenesis of PAH mediated by binding to the APJ gene. The aim of the present study was to investigate the role of miR-335-3p in chronic normobaric hypoxia (CNH)-induced PAH in mice and the potential underlying regulatory mechanism. Adult male C57BL/6 mice were exposed to normoxia (~21% O2) or CNH (~10% O2, 23 h/d) for 5 weeks. MiR-335-3p was significantly increased in lung tissue of CNH-induced PAH mice. Blocking miR-335-3p attenuated CNH-induced PAH and alleviated pulmonary vascular remodeling. Bioinformatics analysis and luciferase reporter assay indicated that nuclear factor-kappa beta (NF-κB) acted as a transcriptional regulator upstream of miR-335-3p. Pyrrolidine dithiocarbamate treatment reversed the CNH-induced increase in miR-335-3p expression and diminished CNH-induced PAH. Moreover, p50-/- mice were resistant to CNH-induced PAH. Finally, APJ was identified as a direct targeting gene downstream of miR-335-3p, and pharmacological activation of APJ by its ligand apelin-13 reduced CNH-induced PAH and improved pulmonary vascular remodeling. Our results indicate that NF-κB-mediated transcriptional upregulation of miR-335-3p contributes to the inhibition of APJ and induction of PAH during hypoxia; hence, miR-335-3p could be a potential therapeutic target for hypoxic PAH.

The containment spray system is of great importance for the nuclear power plant to reduce the pressure and temperature, as well as concentration of radioactive aerosols released from reactor core under the severe accident. The main aim of present study is to develop a simplified model for aerosol removal by spray system, the model is employed to predict the variation of aerosol concentration in containment and reveal the key mechanism influencing aerosol removal. In the present model, the air flow entrained by spraying droplet is considered which is computed by solving simplified one-dimension momentum equations rather than the standard N-S equation. For the validation of the model, a small size sprinkle experiment facility is built. The facility is equipped with non-intrusive instruments such as particle size spectrometer for aerosol spectrum measurement, HELOS/R for measuring the droplet spectrum. The result of aerosol removal of the present model is compared with the result of the full coverage model and the experimental result. In the experiment, polydisperse aerosol is used and the removal rate of aerosols with different sizes is compared against the result of the present model and the full coverage model. The velocity of entrained gas flow and the distribution of droplets are displayed. The computational result reveals the aerosol removal constant distribution along the height.

Pulmonary hypertension (PH), a rare but deadly cardiopulmonary disorder, is characterized by extensive remodeling of pulmonary arteries resulting from enhancement of pulmonary artery smooth muscle cell proliferation and suppressed apoptosis; however, the underlying pathophysiological mechanisms remain largely unknown. Recently, epigenetics has gained increasing prominence in the development of PH. We aimed to investigate the role of vestigial-like family member 4 (VGLL4) in chronic normobaric hypoxia (CNH)-induced PH and to address whether it is associated with epigenetic regulation. The rodent model of PH was established by CNH treatment (10% O2 , 23 hours/day). Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, immunoprecipitation, and adeno-associated virus tests were performed to explore the potential mechanisms involved in CNH-induced PH in mice. VGLL4 expression was upregulated and correlated with CNH in PH mouse lung tissues in a time-dependent manner. VGLL4 colocalized with α-smooth muscle actin in cultured pulmonary arterial smooth muscle cells (PASMCs), and VGLL4 immunoactivity was increased in PASMCs following hypoxia exposure in vitro. VGLL4 knockdown attenuated CNH-induced PH and pulmonary artery remodeling by blunting signal transducer and activator of transcription 3 (STAT3) signaling; conversely, VGLL4 overexpression exacerbated the development of PH. CNH enhanced the acetylation of VGLL4 and increased the interaction of ac-H3K9/VGLL4 and ac-H3K9/STAT3 in the lung tissues, and levels of ac-H3K9, p-STAT3/STAT3, and proliferation-associated protein levels were markedly up-regulated, whereas apoptosis-related protein levels were significantly downregulated, in the lung tissues of mice with CNH-induced PH. Notably, abrogation of VGLL4 acetylation reversed CNH-induced PH and pulmonary artery remodeling and suppressed STAT3 signaling. Finally, STAT3 knockdown alleviated CNH-induced PH. In conclusion, VGLL4 acetylation upregulation could contribute to CNH-induced PH and pulmonary artery remodeling via STAT3 signaling, and abrogation of VGLL4 acetylation reversed CNH-induced PH. Pharmacological or genetic deletion of VGLL4 might be a potential target for therapeutic interventions in CNH-induced PH.

Jia-Ji electro-acupuncture (EA) has been widely applied in clinic to exhibit curative effects on spinal cord injury (SCI). However, its underlying mechanisms leading to improvement of motor function after SCI remain unclear. Allen’s method was made by NYU Impactor M-III equipment to create the SCI rats model. Rats were randomly divided into four groups: Sham (only laminectomy), Model (SCI group), EA (SCI + Jia-Ji EA treatment), EA + CQ (SCI + Jia-Ji EA treatment + inhibitor chloroquine). Basso-Beattie-Bresnahan assessment showed improvement of hind limb motor function after Jia-Ji electro-acupuncture treatment. Histological change of injured spinal cord tissue was alleviated after treatment, observed by hematoxylin-eosin and Nissl staining. The mRNA and protein expression levels of RIPK1, RIPK3 and MLKL were decreased in EA group. Besides, the increased expression of LC3 and reduced expression of P62 after treatment compared with Model group, confirmed that Jia-Ji electro-acupuncture could enhance the autophagy flux. Electron microscopy imaging showed increasing the number of lysosomes, autophagosomes, and autolysosomes after Jia-Ji electro-acupuncture treatment. Furthermore, inhibition of lysosome function with CQ led to partly eliminate the effect of EA on reducing necroptosis. These data make the case that Jia-Ji electro-acupuncture treatment may improve locomotor function by promoting autophagy flux and inhibiting necroptosis.

Additional file 2: Figure S1. Variations in genome size and GC content between species in genus Micrococcus. Figure S2. Heatmap of the distributions of the putative VF genes in M. luteus genomes. Figure S3. Antibiotic resistance gene profiles of M. luteus strains. Figure S4. Comparison of the soft-core, shell and cloud genomes of M. luteus based on COG categories. Figure S5. Hierarchical cluster analysis based on the presence or absence of dispensable genes. Figure S6. Population structure of M. luteus. Figure S7. Ancestral genome content reconstruction using COUNT software

Additional file 2: Figure S1. Variations in genome size and GC content between species in genus Micrococcus. Figure S2. Heatmap of the distributions of the putative VF genes in M. luteus genomes. Figure S3. Antibiotic resistance gene profiles of M. luteus strains. Figure S4. Comparison of the soft-core, shell and cloud genomes of M. luteus based on COG categories. Figure S5. Hierarchical cluster analysis based on the presence or absence of dispensable genes. Figure S6. Population structure of M. luteus. Figure S7. Ancestral genome content reconstruction using COUNT software

Histone H3K27me3 demethylase KDM6B (also known as Jumonji domain-containing protein D3, JMJD3) plays vital roles in the etiology of inflammatory responses; however, little is known about the role of KDM6B in neuroinflammation-induced anxiety-like behavior. The present study aimed to investigate the potential role of KDM6B in lipopolysaccharide (LPS)-induced anxiety-like behavior and to evaluate whether it is associated with the modulation of vestigial-like family member 4 (VGLL4). The elevated plus maze, light-dark box, and open-field test were performed to test the anxiety-like behavior induced by LPS in C57BL/6 J male mice. Levels of relative protein expression in the hippocampus were quantified by western blotting. KDM6B inhibitor GSK-J4 and microglia inhibitor minocycline as well as adeno-associated virus of Vgll4 shRNA were used to explore the underlying mechanisms. We found that KDM6B, VGLL4, interleukin-1β (IL-1β), and ionized calcium-binding adaptor molecule-1 (Iba-1, microglia marker) protein levels were increased in LPS-dose dependent manner in the hippocampus but not in prefrontal cortex. GSK-J4 treatment attenuated LPS-induced VGLL4, the signal transducer and activator of transcription 3 (STAT3), IL-1β and Iba-1 upregulation and anxiety-like behavior. Knockdown VGLL4 with Vgll4 shRNA prevented the increase of anxiety-like behavior and levels of STAT3, IL-1β, and Iba-1 expression in the hippocampus of LPS-treated mice. Moreover, minocycline, an inhibitor of microglia treatment blunted LPS-induced anxiety-like behavior. Collectively, these results demonstrate that the induction of neuroinflammation by LPS promotes KDM6B activation in the hippocampus, and LPS-induced anxiety-like behavior is associated with upregulation of VGLL4 by KDM6B in the hippocampus.

Background: Functional constipation (FC) is a common gastrointestinal disorder characterized by slow bowel movement and defecation difficulties, significantly impacting patients’ quality of life and exerting heavy financial burden to whole society. However, more than 50% FC patients are not completely satisfied with current therapies and alternative therapies are urgently required. Increasing evidences have demonstrated that traditional Chinese medicine has a good therapeutic effect on FC, which is well known for its multitarget and multimode effects on diverse diseases as well as less side effects. Furthermore, studies proved that Qi Di Laxative Decoction was an effective treatment for FC. Its safety and effectiveness should be verified by further studies. Methods: We will search the following electronic databases for randomized controlled trials to evaluate the clinical efficacy of Qi Di Laxative Decoction in treating FC: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to November 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. Results: This proposed study will evaluate the clinical efficacy of Qi Di Laxative Decoction for patients with FC. The outcomes will include changes in FC relief and adverse effect. Conclusion: This proposed systematic review will evaluate the existing evidence on the clinical efficacy of Qi Di Laxative Decoction in treating FC. Dissemination and ethics: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF Registration Number: DOI 10.17605/OSF.IO/M2ESR

Background The most frequent and common form of Krabbe disease (KD) is early‐onset KD in infants, and late‐onset KD has been reported to be a rare disease. In the present study, we reported an adult‐onset KD patient in a consanguineous Chinese family. Methods Clinical and radiological data were collected for a family pedigree. The patient was diagnosed with late‐onset KD through next‐generation sequencing. The result was confirmed by Sanger sequencing. GALC enzyme activity was also examined by the colorimetry method. Both the grey matter volume (GMV) and white matter volume values were examined and compared with the average values from ten age‐matched normal controls. Moreover, we reviewed all the available KD studies on PubMed to understand the correlation between the phenotype and genotype of the identified mutation. Results The main manifestations of the proband were sudden onset seizures and cognitive decline. Mutation analysis of the GALC revealed a homozygous c.1901T>C mutation in exon 16, which resulted in an amino acid change in p.L634S. Sanger sequencing results showed that the homozygous mutation was inherited from the patient's parents, both of whom were revealed to be heterozygous carriers. Moreover, a decrease in GALC enzyme activity was also detected. However, no abnormal signals were found in the brain MRI. Further structural MRI analysis revealed a significantly decreased GMV in the proband compared to the normal controls. Moreover, it is of interest that all patients with the c.1901T>C mutation had late‐onset KD and were selected from Asian countries, especially Japan and China. Conclusions This patient with a homozygous GALC mutation expands the clinical presentation and characteristics of adult‐onset KD, as indicated by grey matter atrophy without abnormal white matter signals., GALC gene analysis revealed a rare homozygous c.1901T>C mutation in exon 16 of the patient.No abnormal signals were found in the brain MRI,but a significantly decreased GMV in the proband compared to the normal controls, which is different from previous cases.It is of interest that all patients with c.1901T>C mutation were late‐onset type and selectively from Asian countries, especially Japan and China.

Poster No: 3524; International audience

Background: Predicting the risk of recurrence during hospitalization in patients with minor ischemic stroke (MIS) is of great significance for clinical and treatment. Compared with early models and prognostic scores, nomogram is a better visualization tool for predicting clinical outcomes. It combines different factors to develop a graphical continuous scoring system, and accurately calculates the risk probability of adverse outcomes based on individual characteristics. Our goal is to develop and validate a nomogram for individualized prediction of hospitalization recurrence in patients with mild ischemic stroke in the Chinese population.Methods: Based on retrospective collection, a single center study was conducted in the first affiliated Hospital of Anhui Medical University from January 2014 to December 2019. The subjects were stroke patients with NIHSS≤5.In order to generate the nomogram, age, systolic blood pressure,previous heart disease, serum total bilirubin, ferritin and smoking were integrated into the model. The predictive accuracy of the nomogram model to predict the probability of unfavorable outcome was assessed by calculation of the area under the receiver operating characteristic curve (AUC–ROC). Calibration of the risk prediction model was assessed by the plot comparing the observed probability of unfavorable outcome against the predicted, and by using the Hosmer–Lemeshow test.Results: Age at admission (OR,0.946; 95% CI,-0.002 to 0.048), SBP (OR,0.012,95%CI,0.000 to 0.024), previous heart disease (OR,0.867,95%CI, 0.084 to 1.651), UA (OR,-0.003,95%CI,-0.006 to 0.001), serum total bilirubin (OR,-0.022,95%CI,-0.036 to -0.008), ferritin (OR,0.004,95%CI, 0.002 to 0.005), smoking (OR,0.494,95%CI,-0.115 to 1.103) are significant predictors of in-hospital recurrence in Chinese patients with minor ischemic stroke.The model shows good discrimination, the AUC-ROC value is 0.737 (95%CI:0.676-0.798), and has perfect calibration performance. Calibration was good (p=0.1457 for the Hosmer-Lemesshow test), which could predict the risk of recurrence of MIS patients during hospitalization.Conclusion: The nomogram developed and validated in this study can provide individualized, intuitive and accurate prediction of recurrence in Chinese patients with minor ischemic stroke during hospitalization.

In recent years, the incidence and mortality of infectious diseases in China are increasing. Infectious diseases, especially new infectious diseases, seriously threaten people's lives. Recent works found that most of the emerging infectious diseases come from wild life. At the same time, the impact of human activities on the environment has further deteriorated the living environment of wildlife. However, with the conducted in-depth research on virus, human beings increase the risk of getting infected. Taking Beta Coronavirus as the example, we analyzed the transmission risks of coronavirus in the prevention and control of the outbreaks of emerging infectious diseases, and recommend the prevention and control strategies before, during and after the viral outbreak. Additional works are urgently needed to better define the biological and epidemiological characteristics of these viruses.

Bacteria were separated from biogas slurry treated by Chlorella vulgaris, and then the interaction between Chlorella vulgaris and bacteria was explored and the effect of algae-bacteria symbiotic system on biogas slurry treatment was discussed. 5 bacteria were separated by flat-plate separation method and were identified by 16S rDNA sequencing technology. They were highly similar to the following bacteria:Pseudomonas alcaliphila, Exiguobacterium, Bacillus amyloliquefaciens, Bacillus subtilis and Bacillus tequilensis. By measuring changes in chlorophyll a of Chlorella vulgaris, it was found that 5 bacteria could promote the growth of chlorella and the effect of Exiguobacterium was most obvious. These single strain were co-cultured with Chlorella vulgaris separately and the purification effect of algae-bacteria symbiotic system on biogas slurry were investigated. The results showed that the consortium of Pseudomonas alcaliphila and Chlorella vulgaris could reduce TP to 0.391 mg·L-1, and its removal rate was the highest(85%). The consortium of Exiguobacterium and Chlorella vulgaris had the best treatment effect on TN and COD, and the removal rate was 64.4% and 72.3% respectively. The removal rates of COD, TN and TP by pure microalgae or pure axenic bacterium were much lower than that of the above two microalgae and bacteria co-culture systems. To summarize, algae-bacteria symbolic system has better effect on sewage treatment than pure culture system and has a good application prospect in sewage treatment.

Aims Endothelial barrier dysfunction is associated with multiple diseases, and barrier repair may be a possible therapeutic target. Yes-associated protein and its pathway have been implicated in organ repair after injury. However, the mechanisms underlying barrier repair and any role YAP plays in the process are unclear. This study aimed to explore the role and mechanism of YAP in the repair of endothelial cell permeability after TNF-α-induced injury. Main methods A trans-endothelial electrical resistance assay was performed to investigate changes in endothelial cell permeability. Lentivirus packaging by calcium phosphate transfection was used to construct endothelial cell lines with knocked down or overexpressed YAP. Western blotting, immunofluorescence, CO-IP, and real-time PCR were used to detect related protein and gene expression. Key findings YAP is involved in the repair process of TNF-α-induced endothelial cell permeability injury; its overexpression promotes repair of endothelial cell permeability, and knockdown weakens repair ability. Moreover, YAP may promote repair by down-regulating STAT3 activity, thereby inhibiting VEGF expression. Significance Elucidating the role of YAP in endothelial cell permeability repair process after injury might reveal mechanisms of endothelial barrier repair and provide therapeutic targets for treatment of vascular hyper-permeability disease.

To investigate the effects of apolipoprotein E (apoE) on the proliferation of pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia.Primary culture of mouse PASMCs was prepared from male C57BL/6 mouse pulmonary artery by the method of tissue block anchorage. PASMCs were divided into four groups: normoxia group, normoxia with apoE administration group, hypoxia group and hypoxia with apoE administration group. The proliferation of PASMCs was observed by EdU incorporation. The protein levels of apoE, proliferating cell nuclear antigen (PCNA), protein kinase C (PKC) and phosphorylated protein kinase C (p-PKC) were analyzed by Western blot.The percentage of PASMCs proliferation of hypoxia group was significantly higher than that of normoxia group by 64.7% (P＜0.05), and the protein expression levels of PCNA and p-PKC of hypoxia group were up-regulated than those of normoxia group by 69.0% and 120.0%, while the protein expression of apoE was down-regulated by 51.0% (P＜0.05), respectively. The percentage of PASMCs proliferation of hypoxia with apoE administration group was significantly lower than that of hypoxia group by 19.6% (P＜0.05), and the protein expression levels of PCNA and p-PKC of hypoxia with apoE administration group were down-regulated than those of hypoxia group by 19.8% and 103.2% (P＜0.05), respectively. There was no significant difference among each group in the protein expression of PKC, nor do there any significant difference between normoxia group and hypoxia group in the protein expression of p-PKC (P＞0.05).ApoE can inhibit the proliferation of PASMCs induced by hypoxia, and the mechanism of its effect may be attributed to blocking PKC pathway.

Teachers need a lot of teaching design knowledge in daily teaching. By the way, the popularization and development of technologies such as mobile Internet technology, social software and online teaching platform provide an opportunity for the teacher's learning. In order to explore the types of Teaching Design knowledge needs of rural teachers in Mobile environment, and to make recommendations for future organizers, this study will analyze the basic characteristics of rural teachers involved in the Wechat discussion, and use Social network analysis analyze their content in the WeChat group for different topics. the study found that young and middle-aged female teachers with higher education and long-term teaching are more willing to participate in the knowledge interaction of WeChat group in the process of online learning; Rural teachers need to increase training on the application of new technologies, they need more in-depth knowledge guidance on the application of technical resources in teaching and the professional development of teachers, finally, The practical problems of rural teachers in remote mountainous areas require more targeted guidance.

In this paper, we showed the design of an agricultural machinery monitoring system for subsoiling monitoring based on Internet of Things (IoT). The system is designed three-layer framework including the data acquisition layer, the data processing and web service layer, and the data accessing layer. A data processing framework for agricultural telematics data has been developed. First we describe data definition of agricultural machinery trajectory. Then we present crucial data cleaning steps to remove erroneous original measurements. Thereupon we show data processing methods including trajectory segmentation, operation efficiency analysis and operation quality assessment. The practice has proved that the system satisfies higher application requirements for agricultural machinery operation monitoring and intelligent management.

We report the characterization of the compound [K([2.2.2]crypt)]4 [In8 Sb13 ], which proves to contain a 1:1 mixture of [Sb@In8 Sb12 ]3- and [Sb@In8 Sb12 ]5- . The tri-anion displays perfect Th symmetry, the first completely inorganic molecule to do so, and contains eight equivalent In3+ centers in a cube. The gas-phase potential energy surface of the penta-anion has eight equivalent minima where the extra pair of electrons is localized on one In+ center, and these minima are linked by low-lying transition states where the electron pair is delocalized over two adjacent centers. The best fit to the electron density is obtained from a model where the structure of the 5- cluster lies close to the gas-phase transition state.

To observe the changes of apolipoprotein E (apoE) protein expression of pulmonary tissue in mice with pulmonary hypertension induced by hypoxia.The animal model of hypoxic pulmonary hypertension was established by exposing the mice to isobaric hypoxic chamber for 3 weeks (23 h/d, regular chow feed).Twenty male wild type (WT) C57BL/6 mice and twenty apoE gene knockout (apoE-KO) mice were randomly divided into normoxia group and hypoxia group. The plasma concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were detected by ELISA method. The protein expression of apoE in lung and liver, and peroxisome proliferators-activated receptor gamma (PPARγ) in lung were measured by Western blot.①In WT mice, the right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 68% and 59% (Down-regulated expression of apoE in lung tissue participates in the pathological proceeding of pulmonary hypertension induced by hypoxia.

Helmet Mounted Sight (HMS) is an optical aiming and display device installed on the fighter, which plays an important role in modern air combat, but it cost a lot to install a real HMS on ground fighter simulator, so it is a wise choice to design a low-cost simulation HMS instead. In this process, the head posture recognition method is the key point in simulation HMS design. In this paper, a head posture recognition method is proposed for Flight Training Simulation. Firstly, the development process and working principle of Helmet Mounted Sight (HMS) are deeply studied, then the principle of POSIT algorithm is introduced, after that the head posture recognition method based on POSIT is proposed. Finally, the hardware design and software workflow of head posture recognition system are given.

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To observe the changes of lipid levels in mice with pulmonary hypertension induced by hypoxia.The animal model of hypoxic pulmonary hypertension was established by exposing the mice to isobaric hypoxic chamberfor 3 weeks (23 h/d, regular chow feed). Twenty male C57BL/6 mice were randomlydivided into normoxia group and hypoxia group (① The right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group (Abnormal lipid metabolism participates in the pathological proceeding of pulmonary hypertension induced by hypoxia.

To observe the role of apelin in the prevention of pulmonary hypertension induced by hypoxia in mice.Adult male apoE gene knockout (apoE-KO) mice were exposed to isobaric hypoxic chamber (9%~11% O①The right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 87% and 85% (Apelin attenuates hypoxia-induced pulmonary hypertension of mice through regulation of lipid metabolism.

To assess the health-related physical fitness status of students and the attributes of performance in terms of endurance and power.The cross-sectional study was conducted at University of Sindh, Jamshoro, Pakistan, and Tsinghua University, Beijing, China, during academic session of January 2012 to December 2013, and comprised an equal number of male and female students aged 18-23 years. Prior to the assessment, physical activity readiness questionnaire was filled by all the subjects, while standardised health-related physical fitness criterion was used to make comparisons in terms of oxygen consumption. .There were 600 subjects in all; 300(50%) at each of the two centres, and at both centres, there were 150(25%) boys and 150(25%) girls. Both for power and endurance, mean values of Chinese students were significantly better than their Pakistani counterparts (p0.05).Chinese students had better health-related physical fitness levels than Pakistani students of either gender.

G231V and F198S mutations in surfactant protein A2 (SP-A2) are associated with familial pulmonary fibrosis. These mutations cause defects in dimer/trimer assembly, trafficking, and secretion, as well as cause mutant protein aggregation. We investigated the effects and mechanisms of chemical chaperones on the cellular and biochemical properties of mutant SP-A2. Chemical chaperones, including 4-phenyl butyric acid (4-PBA), could enhance secretion and decrease intracellular aggregation of mutant SP-A2 in a dose-dependent manner. Interestingly, increased levels of aggregated mutant SP-A2, resulting from MG-132-mediated proteasome inhibition, could also be alleviated by 4-PBA. 4-PBA treatment reduced the degradation of mutant SP-A2 to chymotrypsin digestion in CHO-K1 cells and up-regulated GRP78 (BiP) expression. Overexpression of GRP78 in SP-A2 G231V- or F198S-expressing cells reduced, whereas shRNA-mediated knockdown of GRP78 enhanced aggregation of mutant SP-A2, suggesting that GRP78 regulates aggregation of mutant SP-A2. Together, these data indicate chemical chaperone 4-PBA and upregulation of GRP78 can alleviate aggregation to stabilize and facilitate secretion of mutant SP-A2. The up-regulation expression of GRP78 might partially contribute to the aggregate-alleviating effect of 4-PBA.

Objective— Disruption of endothelial barrier integrity is a characteristic of many inflammatory conditions. However, the origin and function of endothelial cells (ECs) restoring endothelial barrier function remain unknown. This study defined the roles of resident ECs (RECs) and bone marrow–derived endothelial progenitor cells (BMDEPCs) in endothelial barrier restoration after endotoxemic lung injury. Approach and Results— We generated mice that enable to quantify proliferating RECs or BMDEPCs and also to study the causal link between REC or BMDEPC proliferation and endothelial barrier restoration. Using these mouse models, we showed that endothelial barrier restoration was associated with increased REC and BMDEPC proliferation. RECs and BMDEPCs participate in barrier repair. Immunofluorescence staining demonstrated that RECs proliferate in situ on endothelial layer and that BMDEPCs are engrafted into endothelial layer of lung microvessels at the active barrier repair phase. In lungs, 8 weeks after lipopolysaccharide-induced injury, the number of REC-derived ECs (CD45 − /CD31 + /BrdU + /rtTA + ) or BMDEPC-derived ECs (CD45 − /CD31 + /eNOS + /GFP + ) increased by 22- or 121-fold, respectively. The suppression of REC or BMDEPC proliferation by blocking REC or BMDEPC intrinsic nuclear factor-κB at the barrier repair phase was associated with an augmented endothelial permeability and impeded endothelial barrier recovery. RECs and BMDEPCs contributed differently to endothelial barrier repair. In lungs, 8 weeks after lipopolysaccharide-induced injury, REC-derived ECs constituted 22%, but BMDEPC-derived ECs constituted only 3.7% of the total new ECs. Conclusions— REC is a major and BMDEPC is a complementary source of new ECs in endothelial barrier restoration. RECs and BMDEPCs play important roles in endothelial barrier restoration after inflammatory lung injury.

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Background/aims Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, plays an important anti-tumor role and is involved in various other biological processes, such as, neuroprotection by prevention of aggregation of misfolded proteins generated because of genetic defects. Surfactant protein A2 mutations (G231V and F198S) have been identified to be associated with pulmonary fibrosis and lung cancer, and these mutations cause protein aggregation, instability as well as secretion deficiency. The present study focused on investigating the inhibitory effects of EGCG on aggregation of mutant SP-A2 and elucidating the potential mechanisms underlying this action. Methods Wild-type and mutant SP-A2 were transiently expressed in CHO-K1 cells. The aggregated and soluble proteins were separated into NP-40-insoluble and NP-40-soluble fractions. Protein stability was validated by chymotrypsin limited proteolysis assay. Western blot and RT-PCR were used to determine the protein and mRNA expression level, respectively. Results Mutant SP-A2 alone or wild-type SP-A2 co-expressed with G231V formed NP-40-insoluble aggregates in CHO-K1 cells. EGCG significantly suppressed this aggregation and alleviated mutant SP-A2 accumulation in the ER. When combined with 4-PBA, EGCG treatment completely blocked mutant SP-A2 aggregate formation. Though secretion of mutant protein was not affected, EGCG facilitated protein instability in both wild-type and mutant protein. Importantly, MG132, a proteasome inhibitor, reversed EGCG-induced aggregate reduction. Conclusions EGCG inhibits aggregation of misfolded SP-A2 via induction of protein instability and activation of proteasomal pathway for aggregate degradation.

In this study, a continuous online in situ attenuated total reflection Fourier-transform infrared(ATR-FTIR) spectroscopic technique was used to monitor the behavior of butyl xanthate adsorbed on CuO nanoparticle surfaces. A red-shift phenomenon, i.e., the absorption peak at 1200 cm-1shifted to 1193 cm-1, was observed in the FTIR spectra. However, there was no obvious change in the peak intensity after desorption using ultrapure deionized water, indicating that butyl xanthate was chemisorbed on the CuO surface. We determined the order of the spectral intensity changes in the adsorption process using twodimensional(2D) IR spectroscopy. The 2D asynchronous spectra showed that the spectral intensity of the characteristic peak at 1265 cm-1changed first. This may be attributable to the combined peaks of dixanthogen and xanthate molecular aggregates at the surfaces. The adsorption kinetics was studied by monitoring the intensity changes of the xanthate characteristic peak at 1200 cm-1. The adsorption kinetic data showed that the maximum chemisorption capacity of CuO for butyl xanthate was 529 mg·g-1, and the adsorption kinetics can be described by a pseudo-second-order reaction model.

Steam wetness is an important parameter, which is difficult to measure accurately. A simulation study is performed based on the theories of electrodynamics and hydrodynamics to investigate the characteristics of wetness capacitance sensors with different coaxial cylinders, and an experimental system and two capacitance probes were designed to measure steam wetness. Using a FLUENT user defined function (UDF) code, a program to compute the electric field was compiled which can transmit the data between the electric field and the flow field. The coupling of the steam flow field and the electric field within the sensors is investigated through numerical simulation. The results show that the electric field intensity decreases from the inner electrode plate to the outer electrode plate. The electric field intensity near the inner plate increases with increasing plate thickness while the sensor length has no effect on the electric field intensity distribution in the radial direction, but the peak electric field intensity decreases with increasing sensor length. The peak electric field intensity weakens with increasing electrode separation. Comparison of the numerical simulation results and the experimental results shows that the results of the simulation are similar to those of the experiments, with the output capacitance fluctuating around a fixed value as the steam flow rate changes and increasing linearly with increasing wetness. The maximum difference between the experimental data and the numerical simulation data is 0.78 nF, which is a discrepancy of 19.8%.