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The synthesis of green and multifeatured montmorillonite-supported Fe3O4-Cu2+ hybrid adsorbents creates a roadmap for developing adsorbents for a high-abundance proteins.

This paper investigates the extended main-sequence turnoffs (eMSTOs) and stellar populations of three clusters with different ages using Gaia Data Release 2 (DR2) data in detail. The colour–magnitude diagrams (CMDs) of three Galactic clusters show broad main sequences, eMSTOs, blue stragglers, and red giant clumps. We explore the effects of age spread, binaries, and rotating stars on the morphology of the entire CMD, paying particular attention to the effects of binary stars and rotating stars on eMSTOs. Some synthetic CMDs are built on the basis of the advanced stellar population synthesis (ASPS) model to study the observed CMDs and search for the best-fitting stellar population models. The age of the youngest stars, age spread, metallicity, colour excess, distance modulus, binary fraction, and rotating star fraction of clusters are determined. The results show that both binaries and rotating stars are responsible for the eMSTO of intermediate-age cluster LP 585, but binary stars affect more than rotating stars on the eMSTO morphologies of the youngest (M11) and oldest (NGC 6819) clusters in our samples. It suggests that M11 (∼0.3 Gyr) is possibly a composite stellar population of rotating and binary stars, while clusters LP 585 (∼1.1 Gyr) and NGC 6819 (∼2.0 Gyr) are simple stellar populations of rotating and binary stars.

To investigate the role of miR-4301 in rotavirus (RV)-infected Caco-2 cells. In this experiment, RNAs of RV-infected Caco-2 cells were extracted, and the high-throughput second-generation sequencing was performed to detect the expression profiles of host microRNAs (miRNAs). Synthetic miRNA mimics and inhibitors were examined (quantitative polymerase chain reaction [qPCR], crystalline violet, immunofluorescence and electron microscopy) to evaluate the effect on RV replication. Target genes of miR-4301 were predicted by software analysis. The expression of target genes was evaluated by qPCR and Western blot after transfected with miRNA inhibitor/mimic, and crystalline violet and qPCR were used to detect the downregulation effects of target genes on RV replication. By transfecting miRNA inhibitors/mimics and detecting downstream target genes, the mechanism of miRNA affecting RV replication was analyzed. There were 78 known miRNAs with significant differential expression, including 39 upregulated miRNAs and 39 downregulated miRNAs. The results showed that miR-4301 exerted a key role in enhancing RV replication. PPP1R3D protein which can inhibit RV replication was predicted as the target gene of miR-4301 by software analysis. While upregulating miR-4301 by RV, the expression of PPP1R3D and glycogen synthase (GS) is suppressed. For the first time, the effect of miR-4301 on RV infection, and its influence on GS was investigated. Specifically, RV inhibits host cell glycogen synthesis to utilize the host intracellular glucose for promoting its own replication.

The amount of China's sulfur dioxide emission remains significantly large in recent years. To further reduce sulfur dioxide emission, the key is to find out the leading factors affecting sulfur dioxide emission and then take measures to control it accordingly. In order to investigate the influential factors of sulfur dioxide emission of various provinces, the data of sulfur dioxide emission of 30 provinces in China from 2001 to 2020 were collected. We established the symbolic regression model to explore the relationship between the GDP (x

This study presents a combined shape and topology optimization method for designing sound barriers by using the isogeometric boundary element method. The objective function of combined optimization is defined as the sound pressure in reference plane. The sensitivity analysis for the combined optimization is conducted by using either the direct differentiation method or the adjoint variable method. For a shape design, the design variables are the positions of control points in isogeometric analysis, which can control the barrier shape flexibly. In the topology update, the artificial density of an integral element is selected as the design variable to find the optimal distribution of sound absorbing material (SAM) on the barrier surface. In the combined optimization process, the shape and SAM distribution of the sound barrier can be changed in each iteration process to improve the noise reduction. Four different iteration schemes for combined optimization are compared to find an effective one. Numerical tests are provided to demonstrate the validity and efficiency of the proposed methods.

SUMMARYCRISPR-Cas13 systems have been adapted as versatile toolkits for RNA-related applications. Here we systematically evaluate the performance of several popular Cas13 family effectors (Cas13a, Cas13b and Cas13d) under lentiviral vectors and reveal surprisingly differential defects and characteristics of these systems. Using RNA immunoprecipitation sequencing, transcriptome profiling, biochemistry analysis, high-throughput CRISPR-Cas13 screening and machine learning approaches, we determine that each Cas13 system has its intrinsic RNA targets in mammalian cells. Viral process-related host genes can be targeted by Cas13 and affect production of fertile lentiviral particles, thereby restricting the utility of lentiviral Cas13 systems. Multiple RNase activities of Cas13 are involved in endogenous RNA targeting. Unlike target-induced nonspecific collateral effect, intrinsic RNA cleavage can be specific, target-independent and dynamically tuned by varied states of Cas13 nucleases. Our work provides guidance on appropriate use of lentiviral Cas13 systems and further raises cautions about intrinsic RNA targeting during Cas13-based basic and therapeutic applications.

Ethnopharmacological Relevance. Gegen Qinlian decoction (GGQLD) is an effective formula treatment for rotavirus enteritis (RVE), which has been applied for 1900 years. It consists of 4 herbal medicines corresponding to the four roles “monarch, minister, assistant, and guide,” which is the basic rule of prescription composition in traditional Chinese medicine (TCM). However, its active ingredients and therapeutic mechanism on RVE have not been fully investigated. Materials and Methods. In this study, a network pharmacology-based strategy was used to elucidate the mechanism of GGQLD for the treatment of RVE. Oral bioavailability and drug-likeness were taken as the judgment criteria to search the active ingredients of GGQLD in traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). The affinity between protein and ingredients was further determined using the similarity ensemble approach to find the corresponding targets. According to the genes related to enteritis in GeneCards database, the key targets were screened by intersections between drug and disease targets. And the therapeutic mechanism was predicted using the protein-protein interactions (PPIs), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, which was verified by detecting calcium ion concentration with the fluorescent probe. Result. 130 active ingredients were screened from GGQLD, including (R)-canadine, moupinamide, formononetin, and other flavonoids. They act on a total of 366 targets, which is mainly distributed in the biological process of hormone binding or signaling pathways of neuroactive ligand receptor interaction, serotonergic synapse, and calcium signaling pathway. Furthermore, serotonin receptors, adrenergic receptors, cholinergic receptors, and dopamine receptors in the enteric nervous system may be the key targets of RVE treatment by GGQLD. Conclusion. This study demonstrated that the potential mechanism that GGQLD can effectively improve the symptoms of RVE may depend on the regulation of calcium ions, serotonin, and gastrointestinal hormone ion that could mutually affect the intestinal nervous system.

BACKGROUND: To analyze the clinical and infectious characteristics of new coronavirus pneumonia with diagnosed and suspected cases in the Second Hospital of WISCO(Wuhan Iron and Steel Company) of Qingshan District, Wuhan City, and further enhance the understanding of new coronavirus pneumonia. METHODS: According to the fifth and sixth editions of the new coronavirus pneumonia diagnosis and treatment plan issued by the National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine, we carried out the case analysis and infectious disease investigation and research on the confirmed and suspected cases of new coronavirus pneumonia admitted to the second-floor ward of the hospital from January 28th, 2020, to February 26th, 2020. RESULTS: From January 28th, 2020 to February 26th, 2020, 83 patients were admitted, 40 were cured, and 7 died. Before February 13th, 69 patients were admitted, including 22 confirmed patients and 47 suspected patients. After February 13th, the data of newly hospitalized suspected patients decreased to 2 people. The average time from onset to diagnosis was 5.38 days. About 57.1% of the confirmed patients were isolated at home before admission, and 53.2% of the suspected patients were isolated by hospital observation before admission. The proportion of fever and other clinical symptoms was 81.8%, 65.5% of the patients had the fastest heart rate of 90-120 rpm, and 11 of the patients had severe/critical illness, accounting for 20%. The count of leukocytes, neutrophils, and C-reactive proteins (CRPs) in severe patients was higher than those in light patients (P

This research contributes to the topology optimization of acoustic–structure interaction problems with infinite acoustic domain by focusing on two issues, namely, the variation of the acoustic–structure interface and free-floating elements. To handle the variation of the coupling interface, we divide the analyzed domain into the bounded and unbounded domains by using a virtual surface. For the bounded domain where the coupling interface may appear, we model it with the mixed displacement–pressure (u/p) finite element method (mixed FEM). Then, the boundary element method (BEM) is utilized to model the non-reflecting boundary conditions on the truncated surface. The mixed FEM enables the explicit representation of the acoustic–solid interface in the optimized domain to be circumvented. By spatial variation of the mass density, shear and bulk moduli in the mixed FEM, the topology optimization procedure can be easily implemented similar to standard density approaches. With regard to the free–floating elements, we establish a connected component filter to delete these useless elements. This treatment avoids unreasonable but possibly optimized results. The proposed method is verified by several optimization examples.

In this work, we develop an optimization approach to optimize the distribution of porous material layer inside cavity. The optimization seeks to improve the absorbing effects of the porous material, decreasing the noise level at regions of interest or increasing the sound energy dissipated by the porous material. To achieve the preset optimization aim, two different objective functions are accordingly defined. The acoustic absorption characteristics of porous materials are numerically described using the Delany–Bazley–Miki empirical model and modeled by the admittance boundary conditions in the boundary element analysis. Based on the solid isotropic material with penalization method, an admittance interpolation scheme is established between the element admittance and artificial element density. This transforms the discrete optimization into a continuous optimization problem, which can be solved by a gradient solver with the sensitivity information. As a key treatment in this study, we develop a fast sensitivity analysis approach based on an adjoint variable method and the fast multipole method to calculate the sensitivities of the objective function with respect to a large number of design variables. Finally, we validate the proposed optimization approach through a cabin example.

In this work, two fast multipole boundary element formulations for the linear time-harmonic acoustic analysis of finite periodic structures are presented. Finite periodic structures consist of a bounded number of unit cell replications in one or more directions of periodicity. Such structures can be designed to efficiently control and manipulate sound waves and are referred to as acoustic metamaterials or sonic crystals. Our methods subdivide the geometry into boxes which correspond to the unit cell. A boundary element discretization is applied and interactions between well separated boxes are approximated by a fast multipole expansion. Due to the periodicity of the underlying geometry, certain operators of the expansion become block Toeplitz matrices. This allows to express matrix-vector products as circular convolutions which significantly reduces the computational effort and the overall memory requirements. The efficiency of the presented techniques is shown based on an acoustic scattering problem. In addition, a study on the design of sound barriers is presented where the performance of a wall-like sound barrier is compared to the performance of two sonic crystal sound barriers.

This paper proposes a novel optimization framework in passive control techniques to reduce noise pollution. The geometries of the structures are represented by Catmull-Clark subdivision surfaces, which are able to build gap-free Computer-Aided Design models and meanwhile tackle the extraordinary points that are commonly encountered in geometric modelling. The acoustic fields are simulated using the isogeometric boundary element method, and a density-based topology optimization is conducted to optimize distribution of sound-absorbing materials adhered to structural surfaces. The approach enables one to perform acoustic optimization from Computer-Aided Design models directly without needing meshing and volume parameterization, thereby avoiding the geometric errors and time-consuming preprocessing steps in conventional simulation and optimization methods. The effectiveness of the present method is demonstrated by three dimensional numerical examples.

This study proposes an optimization approach to maximize the transmission loss (TL) of a muffler by optimizing the thickness of the embedded porous layer. The objective function, i.e. the TL value, is computed by the four-pole parameters based on the boundary element analysis, and the thicknesses assigned to the discretized elements are naturally chosen as the design variables, resulting in a continuous optimization problem. The sound-absorbing property of the porous layer is simulated using the local admittance boundary condition in the boundary element method (BEM) to link the objective function with the design variable. An efficient sensitivity analysis is developed on the basis of the adjoint variable method and the BEM. Finally, the method of moving asymptotes is applied to solve the optimization problem with the assistance of sensitivity information. As the design variable only affects the (local) admittance value, resulting in a diagonal admittance matrix, and the coefficient matrices of the boundary element analysis will not be influenced by the design variables, we can regard the overall optimization as highly efficient. Moreover, the proposed and previously developed (density-based) optimization approaches are compared. Results show high similarities in the optimization results, thus validating the presented optimization approach. The numerical results also indicate the frequency-dependency of the optimized design. The frequency-averaged TL in the frequency band of interest is selected as the objective function to achieve a multi-frequency optimization.

We develop an acoustic topology optimization approach in this work for the surface design of structures covered by porous materials. The fast multipole boundary element method (FMBEM) is employed for the sound scattering analysis. The acoustic absorption characteristics of porous materials are numerically modeled using the Delany–Bazley–Miki empirical model. Based on the solid isotropic material with penalization (SIMP) method, the optimization is performed by setting the artificial element densities of porous material as the design variables, minimizing the sound pressure or the dissipated sound power as the design objective. As a key treatment in this study, we develop a fast sensitivity analysis approach based on an adjoint variable method (AVM) and the fast multipole method (FMM) to calculate the sensitivities of the objective function with respect to a large number of design variables. The FMM is applied to accelerate the vector-matrix product required by the AVM. According to the gradient information, the method of moving asymptotes (MMA) is used for solving the optimization problem to find the optimal solution. We validate the proposed topology optimization approach through numerical examples of acoustic scattering over a single cylinder and multi cylinders, and demonstrate its ability to handle large-scale problems.

Background Normal gastrointestinal motility depends on electrical slow-wave activity generated by interstitial cells of Cajal (ICC) in the tunica muscularis of the gastrointestinal tract. A requirement for HCO3 - in extracellular solutions used to record slow waves indicates a role for HCO3 - transport in ICC pacemaking. The Slc4a4 gene transcript encoding the electrogenic Na+ /HCO3 - cotransporter, NBCe1, is enriched in mouse small intestinal myenteric region ICC (ICC-MY) that generate slow waves. This study aimed to determine how extracellular HCO3 - concentrations affect electrical activity in mouse small intestine and to determine the contribution of NBCe1 activity to these effects. Methods Immunohistochemistry and sharp electrode electrical recordings were used. Key results The NBCe1 immunoreactivity was localized to ICC-MY of the tunica muscularis. In sharp electrode electrical recordings, removal of HCO3 - from extracellular solutions caused significant, reversible, depolarization of the smooth muscle and a reduction in slow-wave amplitude and frequency. In 100 mM HCO3 - , the muscle hyperpolarized and slow wave amplitude and frequency increased. The effects of replacing extracellular Na+ with Li+ , an ion that does not support NBCe1 activity, were similar to, but larger than, the effects of removing HCO3 - . There were no additional changes to electrical activity when HCO3 - was removed from Li+ containing solutions. The Na+ /HCO3 - cotransport inhibitor, S-0859 (30µM) significantly reduced the effect of removing HCO3 - on electrical activity. Conclusions & inferences These studies demonstrate a major role for Na+ /HCO3 - cotransport by NBCe1 in electrical activity of mouse small intestine and indicated that regulation of intracellular acid:base homeostasis contributes to generation of normal pacemaker activity in the gastrointestinal tract.

This paper presents a boundary element-based scheme for the sensitivity analysis of acoustic eigenfrequencies of both interior and exterior acoustic systems. The nonlinear eigenvalue problem generated by the acoustic boundary element method is first reformulated into a generalized eigenvalue problem of reduced dimension through a contour integral approach. The sensitivity formulations for acoustic eigenfrequencies are then derived based on an adjoint method that uses both the right and left eigenvectors. The adaptive cross approximation in conjunction with the hierarchical matrices is used to reduce the solution burden of the boundary element systems. The Burton-Miller-type combined formulation is applied to shift the spurious eigenfrequencies and their sensitivities, and the strategies to identify the spurious results are suggested. Three numerical examples are used to verify the accuracy and applicability of the developed scheme.

BACKGROUND: Normal gastrointestinal motility depends on electrical slow wave activity generated by interstitial cells of Cajal (ICC) in the tunica muscularis of the gastrointestinal tract. A requirement for HCO(3)(−) in extracellular solutions used to record slow waves indicates a role for HCO(3)(−) transport in ICC pacemaking. The Slc4a4 gene transcript encoding the electrogenic Na(+)/HCO(3)(−) co-transporter, NBCe1, is enriched in mouse small intestinal myenteric region ICC (ICC-MY) that generate slow waves. This study aimed to determine how extracellular HCO(3)(−) concentrations affect electrical activity in mouse small intestine and to determine the contribution of NBCe1 activity to these effects. KEY RESULTS: NBCe1 immunoreactivity was localized to ICC-MY of the tunica muscularis. In sharp electrode electrical recordings, removal of HCO(3)(−) from extracellular solutions caused significant, reversible, depolarization of the smooth muscle and a reduction in slow wave amplitude and frequency. In 100mM HCO(3)(−), the muscle hyperpolarized and slow wave amplitude and frequency increased. The effects of replacing extracellular Na(+) with Li(+), an ion that does not support NBCe1 activity, were similar to, but larger than, the effects of removing HCO(3)(−). There were no additional changes to electrical activity when HCO(3)(−) was removed from Li(+) containing solutions. The Na(+)/HCO(3)(−) co-transport inhibitor, S-0859 (30μM) significantly reduced the effect of removing HCO(3)(−) on electrical activity. CONCLUSIONS: These studies demonstrate a major role for Na(+)/HCO(3)(−) cotransport by NBCe1 in electrical activity of mouse small intestine and indicated that regulation of intracellular acid:base homeostasis contributes to generation of normal pacemaker activity in the gastrointestinal tract.

Viruses have evolved mechanisms to usurp the host's metabolic resources for their own biosynthesis and replication, but host's glucose metabolism change after rotavirus (RV) stress remains unclear. The metabolic profile and differential gluconeogenesis analysis was performed by gas chromatography-mass spectroscopy on RV-infected cells.47 potential differential metabolites were identified to verify glycolytic/gluconeogenesis pathway after RV infection. Glucose consumption and key enzymes of gluconeogenesis (glucose 6-phosphatase (G-6-pase) and phosphoenolpyruvate carboxylase (PEPCK)) were further examined by glucose oxidase-peroxidase method and enzyme linked immunosorbent assay. We found the impairment of glucose consumption, G-6-pase and PEPCK activities which promote gluconeogenesis, were tested in RV infected Caco-2 cells. By Western blot analysis, further studies detected the downregulation expression level of SIK2, which was affected by its upstream proteins of downregulated PDK1, AKT and upregulation p-JNK, and as a consequence influenced the function of gluconeogenesis. In short, RV infection altered the glucose consumption in infectious Caco-2 cells and activated the host cellular gluconeogenesis, which was hijacked through p-JNK-PDK1-AKT-SIK2 signaling pathway for its proliferation and replication with accelerating non-sugar substances conversion into glucose.

Objectives Genipin-1-β-d-gentiobioside (GG) is a kind of compound extracted from Gardenia jasminoides Ellis. The chemical structure of GG is similar to that of geniposide and has antidiabetic effects. We aimed to investigate the efficacy of GG on diabetic nephropathy (DN) in vivo and in vitro experiments and explore its potential mechanism. Methods For high-fat diet/streptozotocin-induced DN mice used in our study, the general features of mice were analysed after GG treatment. Oxidative stress parameters and inflammatory factors were also measured by commercial kits. Kidney damage was assessed using hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining, respectively. In vitro, podocyte injury was assessed by TUNEL and flow cytometric analyses. AMP-activated protein kinase/silencing information regulator related enzyme 1 (AMPK/SIRT1)/nuclear factor-κB (NF-κB) pathway-related proteins were detected by AMPK-siRNA intervention and western blotting. Key findings Treatment of GG could increase cell survival and attenuated kidney damage. Despite the presence of inflammatory and oxidative stress, when GG retained the expression of AMPK/SIRT1, it could be observed that the downstream NLRP3 inflammatory-related proteins were inhibited. Conclusions Results showed that the protective efficacy of GG on DN works together with hypoglycemia and suppressing oxidative stress and inflammation, which at least partly involved in APMK/SIRT1/NF-κB-dependent pathway.

Summary RNA viruses are responsible for many zoonotic diseases that post great challenges for public health. Effective therapeutics against these viral infections remain limited. Here, we deployed a computational framework for host-based drug repositioning to predict potential antiviral drugs from 2,352 approved drugs and 1,062 natural compounds embedded in herbs of traditional Chinese medicine. By systematically interrogating public genetic screening data, we comprehensively cataloged host dependency genes (HDGs) that are indispensable for successful viral infection corresponding to 10 families and 29 species of RNA viruses. We then utilized these HDGs as potential drug targets and interrogated extensive drug-target interactions through database retrieval, literature mining, and de novo prediction using artificial intelligence-based algorithms. Repurposed drugs or natural compounds were proposed against many viral pathogens such as coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), flaviviruses, and influenza viruses. This study helps to prioritize promising drug candidates for in-depth evaluation against these virus-related diseases., Graphical abstract, Highlights • Host dependency genes for RNA viruses are systematically cataloged • Repositioned drug candidates target host dependency genes for antiviral purpose • Artificial intelligence-based algorithms help to predict drug-target interactions • Prioritized antiviral drug candidates are proposed against RNA viruses, Molecular Biology; Bioinformatics; Pharmacoinformatics

RNA viruses are responsible for many types of zoonotic diseases that post great challenges for public health system. Effective therapeutics against these viral infections remains limited. Here we deployed a computational framework for host-based drug repositioning to predict potential antiviral drug candidates from 2352 approved drugs and 1062 natural compounds embedded in Traditional Chinese Medicine herbs. By systematically interrogating public genetic screening data, we comprehensively catalogued human-specific host dependency genes that are indispensable for the successful viral infection corresponding to 10 families and 29 species of RNA viruses. In addition, we utilized these host dependency genes as potential drug targets, and interrogated extensive drug-target interactions through multiple ways such as database retrieval, literature mining and de novo prediction using artificial intelligence-based algorithms. Repurposed drugs or natural compounds were proposed for combating many viral pathogens such as coronaviruses (e.g., SARS-CoV-2), flaviviruses (e.g., Zika virus) and influenza viruses. This study helps to prioritize promising drug candidates for further therapeutic evaluation against these viral-related diseases.

We report a study of the color-magnitude diagram (CMD) of globular cluster SL 506, which shows extended main sequence turn-off (eMSTO). The CMD is derived from deep F450W (B) and F555W (V) images of Hubble Space Telescope/Wide Field Planetary Camera 2 (HST/WFPC2). We reproduce the CMD via simple stellar population including the combination of rotational stars and binaries, and composite stellar population of non-rotating single stars. We derive the parameters of the star cluster, including age, age spread, metallicity, color excess, distance modulus, binary fraction, and rotating star fraction, by comparing the observed and synthetic CMDs. The results show that the eMSTO region of the cluster can be reproduced by both age spread and a combination of rotating and binary stars, but the blue stragglers, color and magnitude distributions can not be reproduced well by age spread. This implies that SL 506 is a simple population with rotating, single and binary stars.