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The elucidation of gene regulatory networks (GRNs) is one of the central challenges of systems biology, which is crucial for understanding pathogenesis and curing diseases. Various computational methods have been developed for GRN inference, but identifying redundant regulation remains a fundamental problem. Although considering topological properties and edge importance measures simultaneously can identify and reduce redundant regulations, how to address their respective weaknesses whilst leveraging their strengths is a critical problem faced by researchers. Here, we propose a network structure refinement method for GRN (NSRGRN) that effectively combines the topological properties and edge importance measures during GRN inference. NSRGRN has two major parts. The first part constructs a preliminary ranking list of gene regulations to avoid starting the GRN inference from a directed complete graph. The second part develops a novel network structure refinement (NSR) algorithm to refine the network structure from local and global topology perspectives. Specifically, the Conditional Mutual Information with Directionality and network motifs are applied to optimise the local topology, and the lower and upper networks are used to balance the bilateral relationship between the local topology’s optimisation and the global topology’s maintenance. NSRGRN is compared with six state-of-the-art methods on three datasets (26 networks in total), and it shows the best all-round performance. Furthermore, when acting as a post-processing step, the NSR algorithm can improve the results of other methods in most datasets.

Cytoskeletal reorganization and epithelial-to-mesenchymal transition (EMT) are key processes and typical characteristics of metastatic cancer cells. Rho GTPase‑activating protein 35 (ARHGAP35) is a GTPase-activating protein, which has a significant effect on cell motility. However, the particular function of ARHGAP35 in gastric cancer (GC) remains unknown. In the present study, the role of ARHGAP35 in GC was investigated by

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. In science and engineering, multi-objective optimization problems usually contain multiple complex constraints, which poses a significant challenge in obtaining the optimal solution. This paper aims to solve the challenges brought by multiple complex constraints. First, this paper analyzes the relationship between single constrained Pareto Front (SCPF) and their common Pareto Front sub-constrained Pareto Front (SubCPF). Next, we discussed the SCPF, SubCPF, and Unconstrainti Pareto Front (UPF)’s help to solve constraining Pareto Front (CPF). Then further discusses what kind of cooperation should be used between multiple populations constrained multi-objective optimization algorithm (CMOEA) to better deal with multi-constrained multi-objective optimization problems (mCMOPs). At the same time, based on the discussion in this paper, we propose a new multi-population CMOEA called MCCMO, which uses a new cooperation mechanism. MCCMO uses C+2 (C is the number of constraints) populations to find the UPF, SCPF, and SubCPF at an appropriate time. Furthermore, MCCMO uses the newly proposed Activation Dormancy Detection (ADD) to accelerate the optimization process and uses the proposed Combine Occasion Detection (COD) to find the appropriate time to find the SubCPF. The performance on 32 mCMOPs and real-world mCMOPs shows that our algorithm can obtain competitive solutions on MOPs with multiple constraints.

Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32–79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi’an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi’an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients’ capacity of Xi’an criterion was confirmed in both early and late-stage PBC.ConclusionsXi’an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi’an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Background and aims There is no data regarding the efficacy and safety of fibrates in patients with decompensated liver disease associated with PBC, as published studies have systematically excluded this population. This study aims to evaluate the efficacy and safety of UDCA in combination with fenofibrate in patients with decompensated liver disease related to UDCA-refractory PBC. Methods We conducted a retrospective analysis comparing the clinical results of additional fenofibrate (FF) therapy and continued UDCA monotherapy in decompensated patients refractory to UDCA. Results Total of 63 patients included: 32 cases underwent UDCA monotherapy and 31 cases underwent UDCA combined with FF therapy. Among UDCA-refractory patients with decompensated cirrhosis, FF add-on therapy for 60 months significantly improved the Mayo risk score, the Globe risk score and the alkaline phosphatase (ALP) normalization rate. Parallel changes in liver transplant-free survival, the UK-PBC risk score and surrogate serum indices of liver fibrosis were consistent with this effect. During follow-up, serum ALP, aminotransferase and gamma-glutamyl transpeptidase decreased significantly, while total bilirubin, albumin, serum creatinine, blood urea, estimated glomerular filtration rate, APRI index, FIB-4 index and Forns index remained stable in FF-treated cases. Only the Globe risk score, not ALP normalization, was independently and negatively associated with improved outcomes on multivariable analysis (odds ratio, 2.934; confidence interval, 1.046-8.235; p = 0.041). No significant adverse effects associated with FF-related symptoms or nephrotoxicity were observed in our cohort. However, decompensated cirrhosis with deteriorated cholestasis should be considered as potential limiting factors for FF therapy. Conclusions Additional FF therapy clearly improves the Mayo risk score, the Globe risk score and the ALP normalization rate in patients with decompensated liver disease related to UDCA-refractory PBC. However, the survival rate was not significantly different between the groups. Decompensated cirrhosis with deteriorated cholestasis should be considered as potential limiting factors for FF therapy.

Background: Vagus nerve stimulation (VNS) functions through neuromodulatory mechanisms to provide quality of life improvements to those with drug-resistant epilepsy. Responsive VNS (rVNS) generators are designed to further reduce seizure burden by detecting ictal tachycardia and aborting seizures soon after their onset. Methods: Electronic medical records were accessed from January 2015 to December 2018 to identify patients with epilepsy managed with rVNS generators. Data were collected on seizure burden before and after rVNS implantation. Seizure burden was compared using t-tests, and monthly seizure reductions were gauged with the McHugh scale. Twenty-seven individuals met inclusion criteria; 10 were eliminated due to prior VNS implantation or undocumented seizure frequencies. Results: The average seizure burden prior to rVNS implantation was 24.78 seizures/month. Following generator placement, the mean seizure frequencies at three months, six months, 12 months, and 18 months were 6.81, 16.57, 5.65, and 5.78 seizures/month, respectively. However, despite documented reductions in the average monthly seizure frequency, we found no statistically significant differences in seizure frequency relative to baseline. Conclusion: While many participants showed individual reductions in seizure burden, this study was unable to definitively conclude that rVNS therapy leads to statistically significant reduction in seizure burden.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. It is challenging to solve constrained multi-objective optimization problems (CMOPs). Different from the traditional multi-objective optimization problem, the feasibility, convergence, and diversity of the population must be considered in the optimization process of a CMOP. How these factors are balanced will affect the performance of the constrained multi-objective optimization algorithm. To solve this problem, we propose a dual-population multi-objective optimization evolutionary algorithm. The proposed algorithm can make good use of its secondary population and alternative between evolution and degeneration according to the state of the secondary population to provide better information for the main population. The test results of three benchmark constrained multi-objective optimization problem suites, and four real-world constrained multi-objective optimization problems show that the algorithm is better than existing dual-population multi-objective optimization, especially when there is a distance between the unconstrained PF and the constrained PF.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. There are usually multiple constraints in constrained multi-objective optimization. Those constraints reduce the feasible area of the constrained multi-objective optimization problems (CMOPs) and make it difficult for current multi-objective optimization algorithms (CMOEAs) to obtain satisfactory feasible solutions. In order to solve this problem, this paper studies the relationship between constraints, then obtains the priority between constraints according to the relationship between the Pareto Front (PF) of the single constraint and their common PF. Meanwhile, this paper proposes a multi-stage CMOEA and applies this priority, which can save computing resources while helping the algorithm converge. The proposed algorithm completely abandons the feasibility in the early stage to better explore the objective space, and obtains the priority of constraints according to the relationship; Then the algorithm evaluates a single constraint in the medium stage to further explore the objective space according to this priority, and abandons the evaluation of some less-important constraints according to the relationship to save the evaluation times; At the end stage of the algorithm, the feasibility will be fully considered to improve the quality of the solutions obtained in the first two stages, and finally get the solutions with good convergence, feasibility, and diversity. The results on five CMOP suites and three real-world CMOPs show that the algorithm proposed in this paper can have strong competitiveness in existing constrained multi-objective optimization.

We report a rare case of ecchordosis physaliphora presenting with headache, nausea, and diplopia. On neurological examination, the patient was found to have left abducens nerve palsy. CT of the head without contrast was unremarkable. Brain MRI demonstrated a non-enhancing retroclival mass with a mass effect upon the ventral pons. The mass had increased signal intensity on T2 and decreased signal intensity on T1-weighted sequences. Lumbar puncture revealed an opening pressure of 37 cm H2O. The patient underwent an endoscopic endonasal approach for retroclival mass resection three weeks later. The tissue analysis of the mass was consistent with ecchordosis physaliphora. This could have been misdiagnosed as idiopathic intracranial hypertension had the MRI of the brain not been performed.

In order to boost the electromechanical coupling factor and decrease the characteristic impedance, a 1-3 piezoelectric composite with a 3-tier polymer structure was designed and fabricated, in which epoxy resin constitutes the middle layer and silicone rubber is used to clamp the epoxy. The effective parameters of the composite, such as resonant frequency, electromechanical coupling factor, and characteristic impedance, were studied by the finite element method and experiment. The experimental results indicate that the electromechanical coupling factor of the composite is enhanced by 8.4% and the characteristic impedance is decreased by 52.8%, compared with the traditional 1-3 ceramic/epoxy composite.

A piezoelectric composite vibrator with a bilaminated structure is designed and fabricated, in this work by applying bending vibration to increase vibration displacement and reduce resonance frequency. The finite element software ANSYS (ANSYS, Inc. USA) is used to simulate the 2-2 and 1-3 piezoelectric composite bilaminated vibrators under free boundary condition and optimize their design. Simulation results show that the vibration displacement of the 2-2 vibrator is higher than that of the 1-3 vibrator, and the resonance frequency of the former is lower than the latter. Five pieces each of the 2-2 and piezoelectric ceramic vibrators are prepared. In addition, simulation and experimental results indicate that the vibration displacement of the 2-2 vibrator increases by 2.3 times, whereas its resonance frequency decreases by nearly 100 Hz, in comparison with those of the piezoelectric ceramic bilaminated vibrator.

To explore the therapeutic efficacy and clinical safety of transcatheter arterial chemoembolization (TACE) combined with Apatinib in patients with advanced hepatocellular carcinoma (HCC).88 patients with advanced HCC admitted to our hospital from March 2015 to March 2016 were randomly assigned into group A (TACE) or B (TACE combined with Apatinib). Therapeutic efficacy and adverse events were recorded by follow-up data every three months after treatment. Disease control rate (DCR) and objective response rate (ORR) in both groups were calculated based on 18-month follow-up records.Nine months after treatment, DCR and ORR in group A were 81.82% and 36.36%, respectively, and 95.45% and 63.64% in group B. Disease-free survival (DFS) in group A and B was 11.15 and 16.5 months, respectively. No significant differences in the adverse event incidence (fever, abdominal pain, nausea and vomiting) after embolization were found between the two groups (p0.05). The incidence of hypertension, hand-foot syndrome, and proteinuria in group B was significantly higher than those in group A (p0.05). Adverse events were all alleviated after symptomatic treatment.The therapeutic efficacy of TACE combined with Apatinib in HCC treatment is higher compared to TACE alone, which may be related to the inhibition of tumor angiogenesis. TACE combined with Apatinib can improve the prognosis and prolong the overall survival (OS) of HCC patients.

As a country that is poor in petroleum yet rich in coal, it is significant for China to develop direct coal liquefaction (DCL) technology to relieve the pressure from petroleum shortages to guarantee national energy security. To improve the efficiency of the direct coal liquefaction process, scientists and researchers have made great contributions to studying and developing highly efficient hydrogen donor (H-donor) solvents. Nevertheless, the details of hydrogen donation and the transfer pathways of H-donor solvents are still unclear. The present work examined hydrogen donation and transfer pathways using a model H-donor solvent, tetralin, by density functional theory (DFT) calculation. The reaction condition and state of the solvent (gas or liquid) were considered, and the specific elementary reaction routes for hydrogen donation and transfer were calculated. In the DCL process, the dominant hydrogen donation mechanism was the concerted mechanism. The sequence of tetralin donating hydrogen atoms was &alpha, H (C1&ndash, H) &gt, &delta, H (C4&ndash, &beta, H (C2&ndash, &gamma, H (C3&ndash, H). Compared to methyl, it was relatively hard for benzyl to obtain the first hydrogen atom from tetralin, while it was relatively easy to obtain the second and third hydrogen atoms from tetralin. Comparatively, it was easier for coal radicals to capture hydrogen atoms from the H-donor solvent than to obtain hydrogen atoms from hydrogen gas.

This study aimed to investigate the effects of astragaloside IV (AS-IV; 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosylcycloastragenol), which has been reported to have comprehensive pharmacological functions, on sodium taurocholate (NaTc)/L-arginine (L-Arg)-induced acute pancreatitis (AP) in rats in vivo and in rat pancreatic acinar cells in vitro. NaTc-induced experimental AP was induced in rats by injecting 4% NaTc (0.1 ml/100 g) in the retrograde direction of the biliopancreatic duct. L-Arg-induced experimental AP was induced in rats by 2 intraperitoneal injections of 20% L-arg (3 g/kg), with an interval of 1 h between the injections. The rats were pre-treated AS-IV (50 mg/kg) or the vehicle (DMSO) 2 h prior to the induction of AP. Enzyme-linked immunosorbent assay, H&E staining, myeloperoxidase (MPO) activity, reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry were used to evaluate the effects of AS-IV on AP. The results revealed that treatment with AS-IV significantly reduced serum amylase and lipase levels, pancreatic pathological alterations, the secretion of pro-inflammatory cytokines, MPO activity, and the protein expression of nuclear factor-κB (NF-κB) in vivo. Moreover, pre-treatment with AS-IV significantly increased the expression levels of manganese superoxide dismutase and cuprum/zinc superoxide dismutase. In the in vitro experiment, treatment of the cells with AS-IV aslo reduced rat pancreatic acinar cell necrosis and nuclear NF-κB activity, and enhanced the protein expression of superoxide dismutase. In conclusion, this study indicates that the protective effects of AS-IV on experimental AP in rats may be closely related to the inhibition of NF-κB. In addition, our results indicate that AS-IV may exert potential antioxidant effects on AP. Therefore, AS-IV may be an effective therapeutic agent for AP.

Two isomeric forms of the octamolybdate cluster, (NH{sub 4}){sub 2}(Hbpy){sub 2}[Mo{sub 8}O{sub 26}](bpy){sub 3} 1 (bpy=bipydine), and [Cu{sub 2}(imi){sub 4}]{sub 2}[Mo{sub 8}O{sub 26}] 2 (imi=imidazole), were synthesized by hydrothermal method and characterized by X-ray single analysis, one-dimensional (1D) infrared spectroscopy and two-dimensional (2D) correlation infrared spectroscopy under thermal perturbation. In compound 1, the [Mo{sub 8}O{sub 26}] units are {beta}-structure, and octamolybdate anion is {zeta}-structure in compound 2. The 2D IR correlation spectroscopy study indicates that the intensity changes of Mo=O band are more sensitive to the temperature variation than that of the Mo-O bond. The {mu}-Mo-O bond and framework vibrations in compound 1 are more sensitive to the temperature variation than that for compound 2. As the vibrations of {mu}-Mo-O bond accompanied by the transfer of an oxygen atom, the catalysis ability of compound 1 may be higher than that of compound 2. - Graphical abstract: Synchronous and asynchronous correlation spectra of compounds 1 and 2 over a temperature range from 50 to 120 deg. C in the range of 400-1000 cm{sup -1}. Display Omitted.

Two 3D coordination polymers with different structure motifs, [Zn2(PCPA)2(IN)2]n (1) and [Co(PCPA)(IN)]n (2) (PCPA=p-chlorophenoxyacetate, IN=isonicotinate), first constructed from mixed rigid and flexible carboxylate ligands, have been obtained under hydrothermal condition and characterized by elemental analyses, IR spectra, thermogravimetric analysis, fluorescent spectra and single crystal X-ray diffraction analysis. The most intriguing structural feature is that each complex exhibits both infinite helical Zn(μ2-carboxylate) or Co(μ3-carboxylates) chain units with 21 helices and zigzag M2(IN)2 (M=zinc and cobalt) chain units by reason of two different carboxylate ligands coordinating to metal centers. Additionally, compounds 1 and 2 show similar blue fluorescence in the solid state at room temperature.

A novel polyoxometalate (POM) Na2(H2en)2{(VO)10[B14O30(OH)2]2}{Mn4(C2O4) [B2O4(OH)2]2}Mn(H2O)2·(H3O)12(H2O)19 1 (en=ethylenediamine), which is a layer-like transition metal (TM) oxalate templated polyoxovanadium borate, has been synthesized under hydrothermal conditions and characterized by EPR, elemental analysis, thermal analysis, single crystal X-ray diffraction and 2D IR correlation spectroscopy studies, respectively. This compound crystallized in the triclinic space group P 1 ¯ with a = 14.3842 ( 4 ) A , b = 14.6837 ( 3 ) A , c = 15.8681 ( 4 ) A , α = 64.48 ( 1 ) ° , β = 64.68 ( 1 ) ° , γ = 63.93 ( 1 ) ° , V = 2596.80 ( 11 ) A 3 and Z = 2 . The cluster anion with an open central cavity has a central band of ten edge-sharing VO5 square pyramids, which is capped top and bottom by two crown-like polyborate ligands of formula [B14O30(OH)2]20−. There is a fragment of {Mn4(C2O4)[B2O4(OH)2]2}2− fixed in the central cavity as a guest part. The cluster units are connected to form a two-dimensional (2D) framework by octahedral Mn(II) and Na+ sites. In addition, we first introduce the generalized 2D correlation spectroscopy to explore the POMs and obtain the dynamic information about structural changes of POMs.

The asymmetric unit of the title compound, (C2H10N2)2[Ti4O4(C6H6NO6)4], consists of halves of two centrosymmetric tetrameric [Ti4O4{N(CH2COO)3}4]4− anions, two [H3N(CH2)2NH3]2+ cations and a disordered mol­ecule of water of crystallization. In the [Ti4O4{N(CH2COO)3}4]4− tetramer, each Ti atom is coord­inated by one nitrilo­tri­acetate ligand and two μ-oxo ligands, so that four titanium and four μ-O atoms form an eight-membered ring. The tetramers are connected by hydrogen bonds with [H3N(CH2)2NH3]2+ cations and with water mol­ecules, leading to an intricate three-dimensional network.

The title compound, (C2H10N2)[MoO10S2], consists of [MoO2(SO4)2]2− chains linked to [H3NCH2CH2NH3]2+ ions, both of which have twofold symmetry. The MoVI atom is octahedrally surrounded by four sulfate O atoms and two terminal O atoms. The μ2-O atom connects the MoO6 octahedra and the SO4 tetrahedra to form a ring, which extends to form a one-dimensional chain along c.

The title compound, (C2H10N2)2[Mo5O15(HPO4)2], consists of [Mo5O15(HPO4)2]4− clusters with one Mo and one O atom located on a twofold rotation axis linked to [H3N(CH2)2NH3]2+ ions. The [Mo5O15(HPO4)2]4− anion consists of five edge-sharing or corner-sharing MoO6 octahedra, which adopt distorted octahedral geometry, and two corner-sharing PO4 tetrahedra. The anion clusters are connected by hydrogen bonds with [H3N(CH2)2NH3]2+.