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Purpose: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method. Methods: The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4–10 ng/ml. Results: In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was −72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively. Conclusion: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4–10 ng/ml for at least 1.72 months. [ABSTRACT FROM AUTHOR]

Background: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. Methods: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. Results: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097–9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). Conclusions: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis. [ABSTRACT FROM AUTHOR]

COVID-19 has caused huge losses to countries around the world, and it will not end in a short time. The lack of motivation for international joint prevention and control is one of the important reasons for the global pandemic of COVID-19. How to improve the efforts and level of international joint prevention and control has become an urgent problem to be solved. Considering the long-term and dynamic nature of international joint prevention and control, the differential game method is used to compare and analyze the optimal decisions of countries in the three scenarios of spontaneous governance, external subsidies and internal cost sharing. The results show that the optimal prevention and control efforts of countries are negatively correlated with discount rates, prevention and control cost coefficients, decay rate and risk factors. It is positively correlated with the impact degree of social benefits, the impact degree of prevention and control efforts on the level of joint prevention and control, the distribution ratio of social benefits, and the impact degree of prevention and control level on social benefits. The prevention and control efforts, joint prevention and control level, social benefits and system benefits under spontaneous governance are the lowest and highest under the internal cost sharing. The internal cost sharing will only be carried out when social benefits distribution ratio obtained reach a certain threshold. This study provides decision-making support for the joint prevention and control of countries to defeat COVID-19 under the normalization of the epidemic. [ABSTRACT FROM AUTHOR]

The binary Ga–Al alloy cathode has been proven to be a prospective candidate for the separation of actinides over lanthanides (Lns) in the dry reprocessing. Therefore, in this work the electrochemical behaviors of U(III) on solid Al, liquid Ga and Ga–Al eutectic alloy cathodes were studied by cyclic voltammetry, and the kinetic properties of U(III)/U on these reactive cathodes were also investigated via electrochemical impedance spectroscopy technique in LiCl–KCl melts. The results showed that the exchange current density (j0) of U(III)/U on the Ga–Al eutectic alloy cathode is the largest, and followed the order: Ga–Al eutectic alloy > Ga > Al. Finally, U was electro-separated on the binary Ga–Al eutectic alloy cathode in a molten salt system containing U and representative Lns (La, Ce, Pr, Nd). The electrolysis products were validated to be Al3U and Ga3U according to XRD and SEM–EDS characterizations. The extraction rate of U was determined to be 88.3% via ICP-OES. This work is of theoretical guidance for high-temperature molten salt electro-separation of An over Ln. [ABSTRACT FROM AUTHOR]

Purpose: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. Methods: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). Result: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80–1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88–1.70, P = 0.238). Conclusion: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection. [ABSTRACT FROM AUTHOR]

The self-excited oscillation effect produces a continuous periodic pulsation without an external excitation source. It is widely used in fluid heat and mass transfer, cavitation and resistance reduction, and other related fields. The self-excited oscillation effect is significantly influenced by the vortex structure created by the jet passing through the specially designed cavity. The flow field in a self-excited oscillation cavity is simulated in this paper using the large eddy simulation (LES) method. The Liutex-Omega ( Ω ~ L ) method is used to analyze the vortex structure's evolution inside the cavity and is contrasted with the Q-criterion, the γ2-criterion, and the Omega (Ω) method. The studies indicate that the Ω ~ L method is less sensitive to threshold selection compared with other methods, while it is more capable of identifying weak vortices. The change in cavity vortex structure can be devided into the four stages of vortex ring priming, growth and development, wall touch separation, and fragmentation. The turbulent energy generated by shear effect can promote the growth and development of the vortex ring structure and has an important influence on the formation of the vortex ring structure. The vortex strength reveals the interaction mechanism between the shear effect and vortex rings. The vortex core area illustrates that the small-scale vortices are mainly distributed inside the collision walls of the cavity and the downstream flow channel. The Liutex-omega method has unique advantages in analyzing the cavity flow field and revealing the mechanism of self-excited oscillations. [ABSTRACT FROM AUTHOR]

It has been established that star polymers with a large number of arms display both the conventional chain relaxation and a slower interchain relaxation due to the formation of hard cores, which is called the local structural relaxation. Here, we demonstrate that this unique relaxation property of multi-arm stars leads to unusual rheological behaviors. We study the response of star polymer melts with various arm numbers to start-up shear flow via nonequilibrium molecular dynamics simulation. Our simulation results indicate that the stress-strain response of multi-arm star polymer melts differs from that of star polymers with a small number of arms in both quantitative and qualitative manners. While the multi-arm star polymer melts exhibit an overshoot peak in the stress-strain curve both at relatively small and sufficiently large shear rates, two overshoot peaks appear when the flow strength is comparable to the relaxation time of the star polymers. This double stress overshoot is absent in linear polymers and star polymers with a small number of arms and is evidently related to the presence of the local structural relaxation in star polymers with a large number of arms. We present a detailed analysis of the conformational and dynamical properties of star polymer melts under start-up shear to gain a molecular understanding of their stress response. [ABSTRACT FROM AUTHOR]

Coal and oil shale are two common sedimentary energy sources which are often symbiotically developed in Mesozoic–Cenozoic continental fault basins. However, the mechanisms and characteristics of the symbiotic development are not yet clearly known. In this research study, the typical continental fault basins of eastern China were chosen as examples for the purpose of conducting an examination of the coal and oil shale symbiotic assemblage types, genetic environmental differences, and transformation mechanisms, as well as the development and occurrence characteristics of different assemblage types. Through a large number of investigations, systematic experimental testing, and sequence stratigraphy studies, the following conclusions were obtained: (1) There were five types of coal and oil shale symbiotic assemblages observed in the continental fault basins, (2) The development of coal and oil shale deposits requires a warm and humid climate, stable structure, abundant organic matter supply, a certain water depth, and a lower terrestrial source debris supply. The observed differences were that the water depth conditions were diversified in the study area, as well as the sources, types, and content of the organic matter. (3) The rapid transformations of the coal and oil shale genetic environments were mainly controlled by the tectonic settings and climatic conditions, which were determined to control the changes in the water depths, salinity, redox conditions, and lake productivity of the genetic environments. Also, in the symbiotic assemblages, genetic environment changes had induced the development of oil shale deposits, which gradually evolved into coal genetic environments. (4) In the isochronous sequence stratigraphic framework of the coal and oil shale symbiotic assemblages, the lake expansion system tracts (EST) were determined to be the most beneficial to the growth of all the types of assemblages and were characterized by more assemblage development phases and smaller bed thicknesses. From the early to the late stages of the EST, and from the lakesides to lake centers, the thicknesses of the coal seams in the symbiotic assemblages showed trends of thinning, while the thicknesses of the oil shale deposits exhibited increasing trends. The early stages of high stand system tracts were found to be beneficial to the development of the symbiotic assemblages of coal seams overlying the oil shale. This tract type generally presented large bed thicknesses and distribution ranges. The low stand system tract and the late high stand system tract were determined to be unconducive to the development of the symbiotic assemblages. [ABSTRACT FROM AUTHOR]

Plasma electrolytic oxidation (PEO) coatings were fabricated on the aluminum in silicate electrolyte. Microstructures and elemental compositions of these PEO coatings were examined by scanning electron microscopy (SEM) equipped with an energy-dispersive x-ray spectroscopy (EDS). Corrosion resistances of the coated samples were evaluated using the measurements of open-circuit potential (OCP), repetitive polarization and electrochemical impedance spectroscopy (EIS) in 3.5 wt.% NaCl solution. The results indicated that the PEO coatings not only act as a physical shield limiting the penetration of corrosive solution, but also establish an anodic location with high concentration of H+ ions and other product ions as pitting corrosion begins. With the development of pitting corrosion, the accumulation of corrosion products inside the pits and pores of the coatings decreases the corrosion process effectively. [ABSTRACT FROM AUTHOR]

Midazolam is a sedative used by patients with mechanical ventilation. However, the potential clinical value is not fully explored. In this report, we made use of a neuroblastoma-spinal cord hybrid motor neuron-like cell line NSC34, and elucidated the potential role of Midazolam on these cells under the insult of oxidative stress. We found the protective effect of Midazolam on motor neurons against cytotoxicity induced by the combination of oligomycin A and rotenone (O/R) or phenylarsine oxide. The characteristics of apoptosis, such as the ratio of TUNEL+ cells or the expression level of cleaved Caspase-3, was decreased by 22 or 45% in the presence of Midazolam. Furthermore, this effect was correlated with the JNK-ERK signaling pathway. Either phosphorylation of ERK or JNK was positively or negatively modulated with the treatment of Midazolam in NSC34 cells attacked by reactive oxygen species. Meanwhile, inhibition or activation of the JNK-ERK pathway regulated the protective effect of Midazolam on NSC34 cells with oxidative stress insult. Collectively, this study elucidated a previously unidentified clinical effect of Midazolam, and put forward the great promise that Midazolam may be considered as a potential candidate to the treatment of motor neuron disease. [ABSTRACT FROM AUTHOR]

In our previous study, Human Signal Transduction in Cancer Gene Array was used in 12 fresh tumor samples to detect the gene expression profiles in the esophageal squamous cell carcinoma (ESCC) tissues matched adjacent non-cancerous samples. Among genes up-regulated at least twofold, β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 were found. So subsequently, the aim of this study was to investigate the prognosis and clinicopathologic roles of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC tissue. The mRNA and protein expression levels of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 genes in 70 ESCC and adjacent non-cancerous paraffin-embedded samples were determined by Real-Time Quantitative PCR (RT-PCR) and immunohistochemical staining. The mRNA expression level of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC was significantly higher than that in the adjacent non-cancerous tissues (0.0821 ± 0.0416 vs. 0.0185 ± 0.0201, P = 0.0000; 1.9934 ± 1.9888 vs. 0.8863 ± 0.665, P = 0.0184; 0.0298 ± 0.0215 vs. 0.0189 ± 0.0187, P = 0.0017; 2.098 ± 0.091 vs. 1.016 ± 0.078, P = 0.0000; 2.181 ± 2.158 vs. 0.931 ± 0.894, P = 0.0152; respectively), and the protein expression level of determined genes was also significantly higher than that in the adjacent non-cancerous tissues (0.2835 ± 0.0844 vs. 0.2352 ± 0.0670, P = 0.0003; 0.3830 ± 0.0947 vs. 0.2721 ± 0.1474, P = 0.0000; 0.2637 ± 0.0348 vs. 0.2042 ± 0.0180, P = 0.0000; 0.2058 ± 0.0316 vs. 0.1218 ± 0.0518, P = 0.0000; 0.2736 ± 0.0834 vs. 0.2251 ± 0.0571, P = 0.0001; respectively). Then, the overexpression of mRNA and protein levels of β-catenin, Wnt1 and Bmi-1 was aggressively associated with lymph node metastasis, advanced pathological stage, and prognosis of the patients with ESCC (P < 0.05). The up-expression of Hoxa9 mRNA and protein was also aggressively associated with lymph node metastasis and advanced pathological stage (P < 0.05); however, the overexpression of Hoxa9 protein was not associated with the prognosis (P > 0.05). Meanwhile, the hypo-expression of Smad4 mRNA was aggressively associated with advanced pathological stage and prognosis of the patients with ESCC (P < 0.05); however, the hypo-expression of Smad4 protein was neutral to the prognosis and lymph node metastasis (P > 0.05). β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 protein expression analysis showed that the positive outcomes of the combined detection of Wnt1 and β-catenin expression or Wnt1, β-catenin and Bmi-1 expression were significantly worse than those of a single target protein expression (P < 0.05). Meantime, the prognosis of the combined positive expression of Wnt1, β-catenin, and Bmi-1 was poorer than that in the combined positive expression of Wnt1 and β-catenin (P < 0.05). The prognosis of ESCC patients with the overexpression of Wnt1/β-catenin and Bmi-1 was relatively poor, and the level of Wnt1/β-catenin and Bmi-1 was conversely correlated with advanced pathological stage and lymph node metastasis. The expression level of Smad4 and Hoxa9 mRNA was also associated with the prognosis of the patients with ESCC, pathological stage, and lymph node metastasis; however, they might not be the independent prognostic factor. [ABSTRACT FROM AUTHOR]

Two new myricetin glycosides, myricetin-3- O-(6″- O- E- p-coumaroyl)- α- D-glucocopyranoside ( 1) and 3′,5′-di- O-methylmyricetin-3- O-(6″- O-acetyl)- α-D-glucopyranoside ( 2), and three known flavonoids, myricetin ( 3), cedrin ( 4), and 2 R,3 R-dihydromyricetin ( 5), were isolated from the pine needles of Cedrus deodara. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical evidence. [ABSTRACT FROM AUTHOR]

set of basic deformation modes for hybrid stress finite elements are directly derived from the element displacement field. Subsequently, by employing the so-called united orthogonal conditions, a new orthogonalization method is proposed. The resulting orthogonal basic deformation modes exhibit simple and clear physical meanings. In addition, they do not involve any material parameters, and thus can be efficiently used to examine the element performance and serve as a unified tool to assess different hybrid elements. Thereafter, a convenient approach for the identification of spurious zero-energy modes is presented using the positive definiteness property of a flexibility matrix. Moreover, based on the orthogonality relationship between the given initial stress modes and the orthogonal basic deformation modes, an alternative method of assumed stress modes to formulate a hybrid element free of spurious modes is discussed. It is found that the orthogonality of the basic deformation modes is the sufficient and necessary condition for the suppression of spurious zero-energy modes. Numerical examples of 2D 4-node quadrilateral elements and 3D 8-node hexahedral elements are illustrated in detail to demonstrate the efficiency of the proposed orthogonal basic deformation mode method. [ABSTRACT FROM AUTHOR]

A cinnamoyl coenzyme A reductase (CCR, EC 1.2.1.44), one of the key enzyme involved in lignin biosynthesis, was cloned from Populus tomentosa (Chinese white poplar). At the same time, a 4CL1 gene was cloned from P. tomentosa, too. The two genes were subcloned in pQE31 vector and expressed in Escherichia coli M15. Both of them were purified by Ni-NTA. Purified CCR protein was digested by trypsin and analyzed by HPLC-MS; the peptide segments had 27% similarity with the sequence of the CCR protein. 4CL was thought to be a neighbor enzyme of CCR in lignin biosynthesis. In this paper, a 4CL1 from P. tomentosa was cloned, and its enzyme reaction products were extracted for the substrates of CCR. Three 4CL1 enzyme reaction products were monitored by HPLC-MS and then the CCR enzyme reaction was detected by GC-MS. In the CCR reaction, the three corresponding aldehyde ( p-coumaraldehyde, caffealdehyde, and coniferaldehyde) were detected and identified by Frontier3 software. The results showed that the CCR that we cloned from P. tomentosa had affinities with 4CL1 enzyme reaction products and a ptCCR that was cloned from aspen (Li et al., Plant Cell Physiol 46(7):1073–1082, 2005) only had affinity with feruloyl-CoA. The different results maybe depend on the different study method. The method of exacting 4CL enzyme products as the substrates of CCR in the paper was reliable and can be used in lignin biosynthesis network to detect the enzymes in the neighborhood that depended on the polarity of the substrates and products. This CCR gene had eight homology sequence CCR gene when a BLAST was conducted in Populus trichocarpa genome database. The CCR homology genes in Populus suggested that some CCRs may take part in the lignin biosynthesis, too. The gene family would be the hot spot in the future study. [ABSTRACT FROM AUTHOR]

A comprehensive investigation was performed for repairing the different types of cracks appearing on the surface or inside the concrete lining at various depths. The material properties used in grouting and two methods for crack repair were discussed in details, and consequently reliable repair measures were proposed and implemented. It is a better choice to adopt the hole-drilling method for the relatively regular crack. The grouting pressure should not be too high and it is generally between 0.4∼0.6 MPa. For the second time grouting, the pressure maybe increased to 0.8 MPa. Other method is the pasting nozzles method which is more suitable for irregular cracks such as cracks with intensive density and crossing cracks. Its grouting pressure is generally between 0.6∼1.0 MPa. The in-situ tests in Three Gorges Project demonstrate favorably the feasibility and applicability of the proposed methods for crack repair within the lining concrete. [ABSTRACT FROM AUTHOR]

(4E)-5-(3-Chlorophenyl)-N-(4-chlorophenyl)-2-diazo-3-oxopent-4-enoic acid amide (5) was synthesized from p-chloroaniline to N-(4-chlorophenyl)-2-diazo-3-oxo-butyramide (4) with 3-chlorobenzaldehyde. The yielded product 5 was investigated with X-ray crystallographic, NMR, MS, and IR techniques. Compound 5 (C17H11Cl2N3O2, Formula wt = 360.19), crystallizes in the monoclinic space group P21/c with unit cell parameters a = 10.516(2), b = 17.996(4), c = 8.902(2) Å, α = 90.00, β = 105.36(3), γ = 90.00∘. V = 1624.5(6) Å3, Z = 4, Dx = 1.473 Mg m−3. The final R was 0.0511. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The notion of multiband superconductivity with dominant two-gap features has been recently applied to the unconventional superconductor CeCu2Si2 for challenging the previously accepted concept of nodal d-wave pairing. In the proposed study, the realistic multiband Fermi surface topology of CeCu2Si2 was obtained through first-principles calculations, and analysis was conducted with an effective two-band hybridization model including detailed band structure. Within the T-matrix approximation, the obtained calculation results show that different pairing candidates, including fully gapped s-wave, loop-nodal s-wave, and d-wave pairings, could yield qualitatively distinct features characterized by impurity-induced bound states. These features can be verified through high-resolution scanning tunneling microscopy or spectroscopy and provide corroborative justification that would be beneficial for the ongoing research regarding the superconducting gap symmetry of CeCu2Si2 at ambient pressure. [ABSTRACT FROM AUTHOR]

Environment enrichment (EE) has a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) is essential for EE-induced hippocampal neurogenesis and memory enhancement. However, the intracellular pathway downstream of BDNF to modulate EE effects is poorly understood. Here we show that integrin-linked kinase (ILK) levels are elevated upon EE stimuli in a BDNF-dependent manner. Using ILK-shRNA (siILK) lentivirus, we demonstrate that knockdown of ILK impairs EE-promoted hippocampal neurogenesis and memory by increasing glycogen synthase kinase-3β (GSK3β) activity. Finally, overexpressing ILK in the hippocampus could rescue the neurogenesis and memory deficits in BDNF+/− mice. These results indicate that ILK is indispensable for BDNF-mediated hippocampal neurogenesis and memory enhancement upon EE stimuli via regulating GSK3β activity. This is a new insight of the precise mechanism in EE-enhanced memory processes and ILK is a potentially important therapeutic target that merits further study. [ABSTRACT FROM AUTHOR]